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Tsai SY, Tsai MC, Hsu MS, Tsai LW, Hsu HC, Jhuang JR, Chiang CJ, Lee WC, Chien KL, Hsu HY, Yeh TL. The association of different body weight classes and survival outcomes in patients with cervical cancer. Cancer Epidemiol 2025; 96:102801. [PMID: 40090230 DOI: 10.1016/j.canep.2025.102801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 12/18/2024] [Accepted: 03/06/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND The relationship between different weight class and mortality risk remained uncertain in cervical cancer patients. Thus, we conducted the study to assess the association between different body weight classes and survival outcomes in patients with cervical cancer. METHODS This was a retrospective cohort study including 6908 cervical cancer patients from the Taiwan Cancer Registry database. A COX regression model was used to evaluate the relationship between different weight classes and time-to-event outcomes of overall survival and cancer-specific survival at three years. RESULTS The median follow-up time was 4.64 ± 2.55 years. Our study revealed that the underweight group had a significantly higher risk of overall death [hazard ratio (HR) = 1.65, 95 % confidence interval (CI) = 1.37, 1.99] than the normal-weight group. Overweight patients had a significantly lower risk of overall death (HR = 0.81, 95 % CI = 0.71, 0.93), whereas the obesity group had an insignificant lower risk of overall death (HR = 0.92, 95 % CI = 0.75, 1.13) compared with the reference group. CONCLUSION After controlling for confounding factors, underweight patients with cervical cancer had a higher risk of overall death than normal-weight patients with cervical cancer. Our study indicates that underweight cervical cancer patients had a higher risk of overall death compared with normal-weight cervical cancer patients. Furthermore, the overweight patients had a significantly lower risk of overall death. More strategies are needed to be addressed especially in public health field regarding women's weight class and cancer mortality issues.
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Affiliation(s)
- Szu-Ying Tsai
- Department of Family Medicine, West Garden Hospital, Taiwan
| | - Ming-Chieh Tsai
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Division of Endocrinology, Department of Internal Medicine, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, Taiwan; Department of Medicine, Mackay Medical Collage, New Taipei City, Taiwan
| | - Min-Shu Hsu
- Department of Medical Research, Mackay Memorial Hospital, Taiwan
| | - Li-Wei Tsai
- Department of Surgical Oncology, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Heng-Cheng Hsu
- Department of Surgery, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jing-Rong Jhuang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan
| | - Chun-Ju Chiang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan
| | - Wen-Chung Lee
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan; Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Population Health Research Center, National Taiwan University, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsin-Yin Hsu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Medicine, Mackay Medical Collage, New Taipei City, Taiwan; Department of Family Medicine, Taipei MacKay Memorial Hospital, Taipei, Taiwan.
| | - Tzu-Lin Yeh
- Department of Medicine, Mackay Medical Collage, New Taipei City, Taiwan; Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan.
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Pan X, Li J, Liu P, Li J, Zhao M, Wu Y, Ji S, Ren T, Jiang Q, Zhang S. Global trends in endometrial cancer and metabolic syndrome research: A bibliometric and visualization analysis. Comput Biol Med 2025; 192:110362. [PMID: 40378563 DOI: 10.1016/j.compbiomed.2025.110362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 03/30/2025] [Accepted: 05/06/2025] [Indexed: 05/19/2025]
Abstract
BACKGROUND Currently, many studies have shown that there is a link between metabolic syndrome (MetS) and endometrial cancer (EC). However, there has been no systematic bibliometric analysis of related publications, which limits the comprehensive understanding of research trends and priorities. Our study makes up for this problem. OBJECTIVE Through bibliometric analysis, this study aimed to reveal key research focus areas, developmental trends, and major contributors of EC and MetS. METHODS The literature for this study was obtained from the Web of Science Core Collection (WoSCC) through August 31, 2024. We searched for EC and MetS using subject and free terms. Microsoft Office Excel 2016, CiteSpace, and VOSviewer software packages were used for bibliometric analysis, considering specific characteristics such as year of publication, country, institution, authorship, journal, references, and keywords. RESULTS A total of 367 publications were included. Annual publications exhibited exponential growth (R2 = 0.8282), indicatingsustained interest in the field. The United States (111 publications), China (80), and Italy (38) were the most productive countries. The University of California System led institutional contributions. Keyword co-occurrence and burst analysis revealed that obesity (occurrence: 113; link strength: 630), insulin resistance (112; 587), and polycystic ovary syndrome (83; 386) were the most frequent and interconnected research foci. Emerging trends, identified through keyword time-zone mapping (average citation year: 2015-2019), highlighted weight control and bariatric surgery as novel interventions. Journals with the highest impact included ∗Fertility and Sterility∗ (IF: 6.6) and ∗International Journal of Epidemiology (IF: 6.4). CONCLUSIONS This study conducted a preliminary bibliometric and visual analysis of the EC and MetS research literature, revealing trends, global cooperation models, fundamental knowledge, and emerging frontiers of EC and MetS. For over 30 years, research has mainly focused on the correlation between MetS and EC, disease factors, prognosis, prevention, and other aspects that have guiding significance for public health.
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Affiliation(s)
- Xiaoqiang Pan
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130012, China; Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Jiajia Li
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China; Jilin Provincial Key Laboratory of Female Reproductive Health, Changchun, Jilin, 130012, China.
| | - Panbo Liu
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China
| | - Jin Li
- Department of Blood Transfusion, The First Hospital of Jilin University, Changchun, Jilin, 130012, China
| | - Mingyue Zhao
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China
| | - Yulun Wu
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China
| | - Shuyu Ji
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China
| | - Tong Ren
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Qiuhua Jiang
- Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Songling Zhang
- Department of Gynecologic Oncology, Gynecology and Obstetrics Centre, The First Hospital of Jilin University, Changchun, Jilin, 130012, China; Jilin Provincial Key Laboratory of Female Reproductive Health, Changchun, Jilin, 130012, China.
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3
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Strømland PP, Bertelsen BE, Viste K, Chatziioannou AC, Bellerba F, Robinot N, Trolat A, Flågeng MH, Scalbert A, Keski-Rahkonen P, Sears DD, Bonanni B, Gandini S, Johansson H, Mellgren G. Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial. Sci Rep 2025; 15:16897. [PMID: 40374694 DOI: 10.1038/s41598-025-01705-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 05/07/2025] [Indexed: 05/17/2025] Open
Abstract
Metformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI > 25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1, MT-RNR2, EGFL6 and FDCSP expression to be differentially expressed in breast tissues from metformin-treated postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that postmenopausal breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors.Trial registration: MetBreCs trial is registered at European Union Clinical Trials Register (EudraCT Protocol # 2015-001001-14) on 07/10/2015.
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Affiliation(s)
- Pouda Panahandeh Strømland
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Bjørn-Erik Bertelsen
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | - Kristin Viste
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | | | - Federica Bellerba
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Nivonirina Robinot
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Amarine Trolat
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Marianne Hauglid Flågeng
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
| | - Augustin Scalbert
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Pekka Keski-Rahkonen
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Dorothy D Sears
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Moores Cancer Center, University of California San Diego, La Jolla, San Diego, CA, USA
- Department of Medicine, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Sara Gandini
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Harriet Johansson
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Gunnar Mellgren
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
- Department of Clinical Science, University of Bergen, Bergen, Norway.
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Fasmer KE, Sæterstøl J, Ljunggren MBS, Brun AMK, Pijnenborg JMA, Woie K, Krakstad C, Haldorsen IS. Abdominal fat distribution in endometrial cancer: from diagnosis to follow-up. BMC Cancer 2025; 25:879. [PMID: 40375215 DOI: 10.1186/s12885-025-14155-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 04/14/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND The objective of this study is to quantify abdominal obesity markers from computed tomography (CT) scans at primary diagnosis and follow-up in a large endometrial cancer cohort, and to assess temporal change in obesity markers in relation to surgicopathological patient characteristics and outcome. METHODS Total- (TAV), subcutaneous- (SAV), visceral (VAV) abdominal fat volumes, and visceral-to-total fat percentage (VAV%) were derived from CT scans acquired in an endometrial cancer patient cohort at primary diagnosis (nprimary=293). Temporal (delta, δ) changes in CT obesity markers from primary diagnosis to follow-up were assessed for all patients with a follow-up CT 13 (7, 19) [median (interquartile range)] months after diagnosis (nfollow-up=152/293 patients). The CT obesity markers were assessed in relation to clinicopathological features and progression-free survival (PFS) using Mann-Whitney U-test, and Cox hazard ratios (HRs), respectively. RESULTS At primary diagnosis, VAV% was the only marker significantly associated with high-risk histology (median of 33% for endometrioid endometrial carcinoma (EEC) grade 1-2, 36% for EEC grade 3 and 36% for non-endometrioid EC, p = 0.003), myometrial invasion (MI) (median of 34% for MI < 50% vs. 35% for MI ≥ 50%, p = 0.03) and lymphovascular space invasion (LVSI) (median of 34% for no LVSI vs. 36% for LVSI, p = 0.009). High VAV% (≥ 35%) also predicted poor PFS both in univariable analysis (HR = 1.8, p = 0.02), and when stratified for surgicopathological FIGO stage (HR = 3.1, p = 0.03). At follow-up, median TAV, VAV, SAV, and VAV% were significantly lower than at primary diagnosis (p < 0.001 for all). Furthermore, patients with progression had larger reductions in visceral fat compartments (δVAV=-24%, δVAV% =-3%), than patients with no progression (δVAV=-17%, δVAV%=-2%, p ≤ 0.006 for both). CONCLUSION Visceral abdominal obesity (high VAV%) is associated with high-risk histologic features, myometrial invasion, and poor prognosis. Furthermore, high visceral fat loss during/following therapy is associated with disease progression.
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Affiliation(s)
- Kristine E Fasmer
- Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, Haukeland University Hospital, Bergen, Norway.
- Section for Radiology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Jostein Sæterstøl
- Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, Haukeland University Hospital, Bergen, Norway
- Section for Radiology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Maria B S Ljunggren
- Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, Haukeland University Hospital, Bergen, Norway
| | - Astrid M K Brun
- Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, Haukeland University Hospital, Bergen, Norway
| | - Johanna M A Pijnenborg
- Department of Obstetrics and Gynecology, Radboud university medical center, Nijmegen, The Netherlands
| | - Kathrine Woie
- Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
| | - Camilla Krakstad
- Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
- Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Ingfrid S Haldorsen
- Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, Haukeland University Hospital, Bergen, Norway.
- Section for Radiology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
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5
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Peduzzi G, Archibugi L, Farinella R, de Leon Pisani RP, Vodickova L, Vodicka P, Kraja B, Sainz J, Bars-Cortina D, Daniel N, Silvestri R, Uysal-Onganer P, Landi S, Dulińska-Litewka J, Comandatore A, Campa D, Hughes DJ, Rizzato C. The exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC. Semin Cancer Biol 2025; 113:100-129. [PMID: 40368260 DOI: 10.1016/j.semcancer.2025.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 04/08/2025] [Accepted: 05/04/2025] [Indexed: 05/16/2025]
Abstract
Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a significant global health issue with high mortality rates. PDAC, though only 3 % of cancer diagnoses, causes 7 % of cancer deaths due to its severity and asymptomatic early stages. Risk factors include lifestyle choices, environmental exposures, and genetic predispositions. Conditions like new-onset type 2 diabetes and chronic pancreatitis also contribute significantly. Modifiable risk factors include smoking, alcohol consumption, non-alcoholic fatty pancreatic disease (NAFPD), and obesity. Smoking and heavy alcohol consumption increase PC risk, while NAFPD and obesity, particularly central adiposity, contribute through chronic inflammation and insulin resistance. Refined sugar and sugar-sweetened beverages (SSBs) are also linked to increased PC risk, especially among younger individuals. Hormonal treatments and medications like statins, aspirin, and metformin have mixed results on PC risk, with some showing protective effects. The gut microbiome influences PC through the gut-pancreas axis, with disruptions leading to inflammation and carcinogenesis. Exposure to toxic substances, including heavy metals and chemicals, is associated with increased PC risk. Glycome changes, such as abnormal glycosylation patterns, are significant in PDAC development and offer potential for early diagnosis. Interactions between environmental and genetic factors are crucial in PDAC susceptibility. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) linked to PDAC, but gene-environment interactions remain largely unexplored. Future research should focus on polygenic risk scores (PRS) and large-scale studies to better understand these interactions and their impact on PDAC risk.
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Affiliation(s)
| | - Livia Archibugi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | - Ruggero Ponz de Leon Pisani
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Ludmila Vodickova
- Biomedical Center Martin, Bioinformatic Center, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic
| | - Pavel Vodicka
- Biomedical Center Martin, Bioinformatic Center, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic
| | - Bledar Kraja
- University Clinic of Gastrohepatology, University Hospital Center Mother Teresa, Tirana, Albania
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain; GENYO. Centre for Genomics and Oncological Research. Genomic Oncology department, Granada, Spain; Instituto de Investigación Biosanitaria Ibs.Granada, Granada, Spain
| | - David Bars-Cortina
- Institut Català d'Oncologia (ICO) IDIBELL, Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Institut Català d'Oncologia (ICO) IDIBELL, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Neil Daniel
- Molecular Epidemiology of Cancer Group, UCD Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | | | - Pinar Uysal-Onganer
- Cancer Mechanisms and Biomarkers Research Group, School of Life Sciences, University of Westminster, London, UK
| | - Stefano Landi
- Department of Biology, University of Pisa, Pisa, Italy
| | | | - Annalisa Comandatore
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy
| | - David J Hughes
- Molecular Epidemiology of Cancer Group, UCD Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Wang R, Jia Z, Peng L, Xu J, Zhu Q, Wu Y. Research trends and hotspots of single nucleotide polymorphisms in endometrial cancer: a bibliometric analysis. Discov Oncol 2025; 16:737. [PMID: 40353932 PMCID: PMC12069169 DOI: 10.1007/s12672-025-02583-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence, especially in developed nations. Understanding genetic variations, particularly single nucleotide polymorphisms (SNPs), is crucial for uncovering the disease's pathogenesis, progression, and treatment responses. This study explores the global research landscape of SNPs in EC, focusing on field evolution, key contributors, and emerging trends. METHODS A systematic search of the Web of Science Core Collection (WoSCC) retrieved 838 publications on SNPs in EC from 1991 to 2024. Bibliometric indicators, including publication volume, citation counts, and keyword occurrences, were analyzed using VOSviewer, CiteSpace, and the R package "bibliometrix" for visual mapping and trend analysis. RESULTS The United States (230 publications) and China (182 publications) were leaders in research output. Harvard University and the National Cancer Institute were prominent contributors. Key themes included "microsatellite instability" (a hallmark of DNA mismatch repair deficiency) and "genome-wide association studies" (GWAS), identifying susceptibility loci like HNF1B and CYP19A1. Recent trends, such as "Mendelian randomization," have enhanced causal inference in risk factor studies. SNP research has advanced risk prediction models and personalized therapeutic strategies, such as hormone therapy tailored to genetic profiles. CONCLUSION SNP research has deepened our understanding of EC's genetic basis, with a growing emphasis on Mendelian randomization and GWAS. These advancements have refined risk prediction and opened new avenues for personalized medicine. Integrating SNP data with environmental and hormonal factors remains crucial for advancing prevention, diagnosis, and treatment strategies in EC.
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Affiliation(s)
- Renjie Wang
- Department of Pathology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China
| | - Zhihong Jia
- Department of Pathology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China
| | - Liang Peng
- Department of Gynecology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China
| | - Jinghui Xu
- Department of Pathology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China
| | - Qiying Zhu
- Department of Pathology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China
| | - Yinghong Wu
- Department of Pathology, The Second People's Hospital of Jingdezhen, Jingdezhen, 333000, Jiangxi, China.
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García-Ulloa AC, Pérez-Peralta L, Lugo-Bautista K, Martínez-Sánchez VA, Mehta R, Hernández-Jiménez S. Metabolic Comorbidities Among Relatives of Type 2 Diabetes Patients Stratified by Weight: Implications for Prevention and Care. Diabetes Metab Syndr Obes 2025; 18:1539-1549. [PMID: 40365576 PMCID: PMC12071750 DOI: 10.2147/dmso.s483171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 03/21/2025] [Indexed: 05/15/2025] Open
Abstract
Introduction Diabetes, affecting 18.3% of young adults in Mexico (6), is influenced by both genetic factors and shared unhealthy habits within families. Objective To determine the metabolic abnormalities in relatives of people with T2D, stratified by body mass index. Materials and Methods This observational, descriptive study was conducted at the Center for Comprehensive Care for Patients with Diabetes (CAIPaDi). The study involved relatives of participants with type 2 diabetes mellitus (T2DM), recruited between June 2017 and December 2020. The relatives were people without diabetes, including spouses, siblings, offspring, or close family members aged 18 to 65 who spent over four days a week with the patient. Exclusion criteria included relatives diagnosed with diabetes, smokers, or any individual from a patient-relative pair that was excluded. All participants underwent laboratory tests and body measurements. Relatives were classified into three groups based on body weight: normal weight, overweight, and obesity. The relatives attended four monthly visits and then annual evaluations. Ethical approval was obtained. Results The study enrolled 220 relatives of people with T2DM, 69% women, median age 49±12 years; 19.5% with normal weight, 40.4% overweight, and 40% with obesity. Prediabetes (39.4%), dyslipidemia (67.2%), and abnormal liver function tests (32.2%) were prevalent. Higher levels of triglycerides and LDL cholesterol were associated with increased risk for comorbid conditions. Anxiety and depression showed no significant differences across weight categories. Conclusion These results highlight the importance of overweight and obesity as factors associated with the presence of comorbidities and the metabolic syndrome. It is essential to implement strategies to promote healthy habits among family members of people with diabetes, especially in those who are overweight or obese to reduce the risk of developing future metabolic and cardiovascular diseases.
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Affiliation(s)
- Ana Cristina García-Ulloa
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Liliana Pérez-Peralta
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Karla Lugo-Bautista
- Endocrinology and Lipid Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Víctor A Martínez-Sánchez
- Internal Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Roopa Mehta
- Endocrinology and Lipid Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Sergio Hernández-Jiménez
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - On behalf of CAIPaDi study group
- Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Endocrinology and Lipid Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Internal Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Sander J, Torensma B, Siepe J, Schorp T, Schulte T, Schmeer C, Gögele H, Böckelmann I, Grabenhorst A, Ockert-Belz I, Berends F, Aarts E. Assessment of Preoperative Multivitamin Use on the Impact on Micronutrient Deficiencies in Patients with Obesity Prior to Metabolic Bariatric Surgery. Obes Surg 2025; 35:1818-1826. [PMID: 40199822 PMCID: PMC12065735 DOI: 10.1007/s11695-025-07853-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/18/2025] [Accepted: 04/02/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Most patients achieve successful weight loss following metabolic bariatric surgery (MBS), but they face an increased risk of micronutrient deficiencies due to altered gastrointestinal physiology and dietary restrictions. This study evaluated the impact of a specialized multivitamin on blood serum levels before MBS. METHODS A prospective, within-patient comparison trial was conducted between January and July 2023 at a large bariatric clinic. Differences in serum micronutrient levels between baseline and the 3-month follow-up were assessed, along with changes in the prevalence of micronutrient deficiencies. RESULTS Of 120 patients recruited, 99 (82.5%) completed the 3-month follow-up. Significant changes were observed in 13 of 21 serum parameters (61.9%). Ten parameters, including iron, vitamin K1, zinc, C-reactive protein, hemoglobin, hematocrit, mean corpuscular volume, calcium, folic acid, and vitamin D, showed significant increases (p < 0.001). Conversely, magnesium, phosphate, and albumin levels significantly decreased (p < 0.001). Among 21 parameters, deficiencies were identified in 17 (80.1%), with prevalence rates ranging from 1.0% (copper) to 88.8% (vitamin D). After 3 months, significant reductions in deficiency prevalence were observed for iron, folic acid, and vitamin D. However, phosphate deficiency increased significantly, from 2.1 to 19.8% (p < 0.001). CONCLUSIONS Micronutrient deficiencies are prevalent in patients with obesity. Preoperative specialized multivitamin supplementation effectively reduces key deficiencies, particularly in iron, folic acid, and vitamin D. Future research should address residual deficiencies and evaluate long-term outcomes of prolonged supplementation.
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Affiliation(s)
| | - Bart Torensma
- Erasmus MC, Rotterdam, The Netherlands.
- WeightWorks Clinics, Amersfoort, The Netherlands.
| | | | | | | | | | | | | | | | | | | | - Edo Aarts
- WeightWorks Clinics, Amersfoort, The Netherlands
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9
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Morris DH, Kosmacki A, Tolby L, Marx C, Vanderlan J, Mutch DG, Colditz G, Hagemann AR. Integration of a lifestyle modification intervention for women with overweight and obesity in a gynecologic oncology practice. Gynecol Oncol 2025; 196:168-174. [PMID: 40222070 DOI: 10.1016/j.ygyno.2025.04.516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 03/18/2025] [Accepted: 04/08/2025] [Indexed: 04/15/2025]
Abstract
OBJECTIVE(S) We aimed to assess the feasibility and effectiveness of a remotely delivered, group-based lifestyle modification intervention (LMI) for women with gynecologic cancer and overweight or obesity in a real-world clinic. METHODS A six-month LMI was implemented in an outpatient gynecologic oncologic clinic for women with a body mass index (BMI) >25 kg/m2. Participants were given a weight loss goal of ≥5 % initial body weight. Retrospective data were collected from patients enrolled in the intervention from September 2019 through February 2023. Feasibility of the LMI was assessed by the rate of enrollment and retention in the intervention. De-identified zip code data were collected to assess geographic proximity of participants to the clinic. Repeated measure analysis of variance (ANOVA) was performed to evaluate change in weight across the intervention. RESULTS 164 patients were referred to the LMI with 82 patients being enrolled during the study timeframe. The sample consisted primarily of white (68.3 %) women between the ages of 30 to 73 years old (median age of 57) with an initial median BMI of 41.41 kg/m2. 74 % of enrolled patients completed the entire LMI. The LMI resulted in a mean loss of 4.19 kgs (p < .001), with 40.30 % of patients losing ≥5 % initial body weight. CONCLUSIONS Remotely delivered, group based LMI for gynecologic cancer patients with overweight or obesity is feasible in clinical practice and can transcend rural-urban inequalities. Patients in the LMI achieved statistically and clinically significant weight loss, comparable to that observed in more rigorous clinical trial.
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Affiliation(s)
- David H Morris
- Department of Psychiatry, Alvin J. Siteman Cancer Center, St. Louis, MO, USA.
| | - Alison Kosmacki
- Department of Obstetrics & Gynecology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Leah Tolby
- Department of Obstetrics & Gynecology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Christine Marx
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Jessica Vanderlan
- Department of Psychiatry, Alvin J. Siteman Cancer Center, St. Louis, MO, USA
| | - David G Mutch
- Division of Gynecologic Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Graham Colditz
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - Andrea R Hagemann
- Division of Gynecologic Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
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10
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Hildebrand S, Pfeifer A. The obesity pandemic and its impact on non-communicable disease burden. Pflugers Arch 2025; 477:657-668. [PMID: 39924587 PMCID: PMC12003543 DOI: 10.1007/s00424-025-03066-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 02/11/2025]
Abstract
The rising prevalence of overweight and obesity across the globe is a major threat both to public health and economic development. This is mainly due to the link of obesity with the development and outcomes of non-communicable diseases (NCDs). NCDs are a leading cause of global death and disability, and reducing the burden of NCDs on patients and healthcare systems is of critical importance to improve public health. Obesity is projected to be the number one preventable risk factor for NCDs by 2035, and there is an urgent need to tackle the growing obesity rates in order to reduce NCD incidence and severity. Here, we review the current understanding of the impact of obesity on NCD burden in general, as well as the epidemiological and mechanistic relationship between obesity and some of the most common classes of NCDs. By literature review, we found that over 70% of NCDs have a documented association with obesity, highlighting the importance of a better understanding of the pathophysiologies underlying obesity/overweight as well as the interaction between obesity and NCDs in order to reduce global disease burden.
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Affiliation(s)
- Staffan Hildebrand
- Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127, Bonn, Germany.
| | - Alexander Pfeifer
- Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127, Bonn, Germany.
- PharmaCenter Bonn, University of Bonn, Bonn, Germany.
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11
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Amaeshi LC, Okunade KS, Anorlu RI. Current landscape of cancer genomics research in sub-Saharan Africa - a review of literature. Front Oncol 2025; 15:1512005. [PMID: 40313245 PMCID: PMC12043467 DOI: 10.3389/fonc.2025.1512005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 03/26/2025] [Indexed: 05/03/2025] Open
Abstract
Cancer poses a significant public health challenge in sub-Saharan Africa, a region that has traditionally struggled with infectious diseases. Although communicable diseases remain the leading cause of mortality in sub-Saharan Africa (SSA), there has been a rise in the morbidity and mortality rates associated with non-communicable diseases (NCDs), in recent years. As of 2019, NCDs accounted for 37% of deaths, representing an increase from the 24% recorded in 2000. Cancer is fundamentally a genetic disorder, and genomic research has provided a deeper understanding of its biology leading to identification of biomarkers for early cancer detection and advancement in precision oncology. However, despite Africa's rich genomic diversity and significant cancer burden, the continent remains underrepresented in global genomic research. This underrepresentation is mainly due to challenges such as insufficient funding, inadequate infrastructure, and a limited pool of trained professionals. However, despite these obstacles, initiatives like the H3Africa Consortium, African BioGenome Project, and Prostate Cancer Transatlantic Consortium (CaPTC), amongst others, have made significant strides in funding and developing local capacity and infrastructure for genomic research. In this review, we discuss the unique genomic characteristics of common cancers in Africa, highlight challenges faced in the implementation of genomic research, and explore potential solutions and current initiatives instituted to foster genomic research in the region.
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Affiliation(s)
| | - Kehinde S. Okunade
- Oncology and Pathological Unit, Department of Obstetrics and Gynecology, College of Medicine, University of Lagos, Lagos, Nigeria
- Lagos University Teaching Hospital, Lagos, Nigeria
| | - Rose I. Anorlu
- Oncology and Pathological Unit, Department of Obstetrics and Gynecology, College of Medicine, University of Lagos, Lagos, Nigeria
- Lagos University Teaching Hospital, Lagos, Nigeria
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12
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Abdeen SK, Mastandrea I, Stinchcombe N, Puschhof J, Elinav E. Diet-microbiome interactions in cancer. Cancer Cell 2025; 43:680-707. [PMID: 40185096 DOI: 10.1016/j.ccell.2025.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 02/26/2025] [Accepted: 03/11/2025] [Indexed: 04/07/2025]
Abstract
Diet impacts cancer in diverse manners. Multiple nutritional effects on tumors are mediated by dietary modulation of commensals, residing in mucosal surfaces and possibly also within the tumor microenvironment. Mechanistically understanding such diet-microbiome-host interactions may enable to develop precision nutritional interventions impacting cancer development, dissemination, and treatment responses. However, data-driven nutritional strategies integrating diet-microbiome interactions are infrequently incorporated into cancer prevention and treatment schemes. Herein, we discuss how dietary composition affects cancer-related processes through alterations exerted by specific nutrients and complex foods on the microbiome. We highlight how dietary timing, including time-restricted feeding, impacts microbial function in modulating cancer and its therapy. We review existing and experimental nutritional approaches aimed at enhancing microbiome-mediated cancer treatment responsiveness while minimizing adverse effects, and address challenges and prospects in integrating diet-microbiome interactions into precision oncology. Collectively, mechanistically understanding diet-microbiome-host interactomes may enable to achieve a personalized and microbiome-informed optimization of nutritional cancer interventions.
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Affiliation(s)
- Suhaib K Abdeen
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
| | | | - Nina Stinchcombe
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany
| | - Jens Puschhof
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany.
| | - Eran Elinav
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany.
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13
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García-Saenz JA, Spera G, Pollán M, Bermejo B, Ruiz-Borrego M, Chan A, Martín M, Guerrero-Zotano Á, Calvo L, Rodríguez-Lescure Á, Marín M, Chap L, Crown J, Pienkowski T, Bee V, Casas M, Polonio Ó, Bezares S, Slamon D. Body mass index as a predictive factor for efficacy of adjuvant taxane-based chemotherapy in early-stage breast cancer patients: A pooled analysis from adjuvant GEICAM Spanish Breast Cancer Group and TRIO Translational Research in Oncology Group studies. Int J Cancer 2025. [PMID: 40207789 DOI: 10.1002/ijc.35432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 02/24/2025] [Accepted: 03/17/2025] [Indexed: 04/11/2025]
Abstract
Adjuvant anthracyclines and taxanes reduce recurrence and death in early-stage breast cancer (EBC) patients, but toxicity is a concern. Studies show conflicting results on the correlation between body mass index (BMI) and outcomes. Limited data exist on the efficacy of adjuvant taxanes among BMI categories and the impact of different taxane-based chemotherapies (paclitaxel vs. docetaxel) on disease recurrence. Here, we present a pooled analysis of 13,486 EBC patients treated with adjuvant anthracyclines ± taxanes from seven GEICAM and TRIO trials (1996-2008) conducted. Patients were classified into four BMI categories: normal (<25.0), overweight (25.0-29.9), obese (30.0-34.9), and severely obese (≥35.0). BMI was evaluated as a predictive factor for the efficacy and toxicity of taxane-based chemotherapy. Our results show the following findings: patients' distribution by BMI was 44% normal, 33% overweight, 16% obese, and 8% severely obese. Seventy-nine percent received taxane-based chemotherapy. Ten-year invasive disease-free survival (iDFS) was 71%, 70%, 68%, and 64% for normal, overweight, obese, and severely obese patients, respectively. Obese and severely obese patients had significantly worse outcomes (HR 1.15 and 1.29, respectively). Invasive disease-free survival with docetaxel vs. non-docetaxel was significant in the normal BMI group, while iDFS with paclitaxel was significant in the obese group. Relevant toxicity was observed in 5%, 5.5%, 5.9%, and 9.3% of normal, overweight, obese, and severely obese patients who received docetaxel. In conclusion, heavier EBC patients had a worse prognosis with adjuvant taxane-based chemotherapy. Normal BMI patients benefited more from docetaxel, while obese patients benefited more from paclitaxel.
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Affiliation(s)
- José A García-Saenz
- Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
| | - Gonzalo Spera
- Translational Research in Oncology, Medical Affairs, Montevideo, Uruguay
| | - Marina Pollán
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Begoña Bermejo
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Hospital Clínico Universitario de Valencia, INCLIVA Instituto de Investigación Sanitaria, Universidad de Medicina de Valencia, Valencia, Spain
| | - Manuel Ruiz-Borrego
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | - Arlene Chan
- Curtin Medical School, Faculty of Health Sciences, Perth, Australia
| | - Miguel Martín
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
- Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain
| | - Ángel Guerrero-Zotano
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Instituto Valenciano de Oncología, Valencia, Spain
| | - Lourdes Calvo
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain
| | - Álvaro Rodríguez-Lescure
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Hospital General Universitario de Elche, Elche, Spain
| | - María Marín
- GEICAM, Spanish Breast Cancer Group, Madrid, Spain
- Consorci Sanitari de Terrassa, Terrassa, Spain
| | - Linnea Chap
- Beverly Hills Cancer, Beverly Hills, Los Angeles, USA
| | - John Crown
- Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland
| | | | - Valerie Bee
- Translational Research in Oncology, Project Management, Paris, France
| | | | | | | | - Dennis Slamon
- Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, California, Los Angeles, USA
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14
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Motevalli M, Stanford FC. Personalized Lifestyle Interventions for Prevention and Treatment of Obesity-Related Cancers: A Call to Action. Cancers (Basel) 2025; 17:1255. [PMID: 40282431 PMCID: PMC12025719 DOI: 10.3390/cancers17081255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/04/2025] [Accepted: 04/06/2025] [Indexed: 04/29/2025] Open
Abstract
The increasing global burden of cancer necessitates innovative approaches to prevention and treatment. Lifestyle factors such as diet, physical activity, and smoking significantly contribute to cancer. At the same time, current guidelines are based on a one-size-fits-all approach, which limits their effectiveness across diverse populations. Obesity is a well-documented risk factor for cancer, directly affecting 13 types of cancer. The complex interplay of genetic, metabolic, hormonal, and environmental factors in obesity's etiology highlights the need for more tailored approaches to obesity-related cancers. This perspective article advocates for a shift toward an integrative, personalized approach that considers a variety of intrinsic and extrinsic factors associated with the etiology of obesity-related cancers. Lifestyle-based cancer prevention strategies should be tailored to an individual's biological profile, demographic background, behaviors, and environmental exposures. Following a diagnosis, a comprehensive treatment approach should consider how these genetic, physiological, lifestyle, and environmental factors interact in the onset and progression of the disease while also taking cancer type and stage into account. This approach paves the way for more precise and effective strategies in tackling cancer. Fulfilling collaboration across research, healthcare, and policy sectors is essential to achieve these goals.
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Affiliation(s)
- Mohamad Motevalli
- Department of Sport Science, University of Innsbruck, 6020 Innsbruck, Austria
| | - Fatima Cody Stanford
- Harvard Medical School, Boston, MA 02115, USA;
- MGH Weight Center, Massachusetts General Hospital, Boston, MA 02114, USA
- Nutrition Obesity Research Center at Harvard (NORCH), Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Pediatrics, Division of Endocrinology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Medicine, Division of Endocrinology-Neuroendocrine, Massachusetts General Hospital, Boston, MA 02114, USA
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15
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Hergueta-Redondo M, Sánchez-Redondo S, Hurtado B, Santos V, Pérez-Martínez M, Ximénez-Embún P, McDowell SAC, Mazariegos MS, Mata G, Torres-Ruiz R, Rodríguez-Perales S, Martínez L, Graña-Castro O, Megias D, Quail D, Quintela-Fandino M, Peinado H. The impact of a high fat diet and platelet activation on pre-metastatic niche formation. Nat Commun 2025; 16:2897. [PMID: 40175356 PMCID: PMC11965330 DOI: 10.1038/s41467-025-57938-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 03/07/2025] [Indexed: 04/04/2025] Open
Abstract
There is active crosstalk between tumor cells and the tumor microenvironment during metastatic progression, a process that is significantly affected by obesity, particularly in breast cancer. Here we analyze the impact of a high fat diet (HFD) on metastasis, focusing on the role of platelets in the formation of premetastatic niches (PMNs). We find that a HFD provokes pre-activation of platelets and endothelial cells, promoting the formation of PMNs in the lung. These niches are characterized by increased vascular leakiness, platelet activation and overexpression of fibronectin in both platelets and endothelial cells. A HFD promotes interactions between platelets, tumor cells and endothelial cells within PMNs, enhancing tumor cell homing and metastasis. Importantly, therapeutic interventions like anti-platelet antibody administration or a dietary switch reduce metastatic cell homing and outgrowth. Moreover, blocking fibronectin reduces the interaction of tumor cells with endothelial cells. Importantly, when coagulation parameters prior to neoadjuvant treatment are considered, triple negative breast cancer (TNBC) female patients with reduced Partial Thromboplastin time (aPTT) had a significantly shorter time to relapse. These findings highlight how diet and platelet activation in pre-metastatic niches affect tumor cell homing and metastasis, suggesting potential therapeutic interventions and prognostic markers for TNBC patients.
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Affiliation(s)
- Marta Hergueta-Redondo
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Sara Sánchez-Redondo
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Begoña Hurtado
- Cancer Cell Cycle Group, Preclinical & Translational Research Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Vanesa Santos
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Manuel Pérez-Martínez
- Confocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Pilar Ximénez-Embún
- Proteomics Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Sheri A C McDowell
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada
| | - Marina S Mazariegos
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Division of Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden
- Lund Stem Cell Center (SCC), Lund University, Lund, Sweden
| | - Gadea Mata
- Confocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Department of Mathematics and Computer Science, University of La Rioja, La Rioja, Spain
| | - Raúl Torres-Ruiz
- Molecular Cytogenetics Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnologicas (CIEMAT), Madrid, Spain
- Advanced Therapies Unit, Instituto de Investigacion Sanitaria Fundacion Jiménez Díaz, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
| | - Sandra Rodríguez-Perales
- Molecular Cytogenetics Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Lola Martínez
- Flow Cytometry Core Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Osvaldo Graña-Castro
- Bioinformatics Unit, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- Departamento de Ciencias Médicas Básicas, Instituto de Medicina Molecular Aplicada (IMMA-Nemesio Díez), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, 28925, Alcorcón, Spain
| | - Diego Megias
- Confocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Advanced Optical Microscopy - ISCIII Madrid, Madrid, Spain
| | - Daniela Quail
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada
| | - Miguel Quintela-Fandino
- Breast Cancer Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
- Medical Oncology, Hospital de Fuenlabrada, Madrid, Spain
| | - Héctor Peinado
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
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16
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Montalvan L, Bernhard JC, Bensalah K, Paparel P, Bigot P, Doumerc N, Olivier J, Bruyère F, Ingels A, Rouprêt M, Audenet F, Lebacle C, Long JA, Durand X, Waeckel T, Durand M, Lang H, Pignot G, Cussenot O, Charles T, Tambwe R, Xylinas E, Boissier R, Patard JJ, Beauval JB, Mallet R, Rouget B, Nouhaud FX. Effect of obesity on histological type of renal tumor: The Uroccr study 69. THE FRENCH JOURNAL OF UROLOGY 2025; 35:102884. [PMID: 40185313 DOI: 10.1016/j.fjurol.2025.102884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 03/13/2025] [Accepted: 03/31/2025] [Indexed: 04/07/2025]
Abstract
Renal cell carcinomas (RCC) are increasing worldwide and obesity is one of its recognized causal factor. Obesity thus could be differently associated with the different histologic types of renal tumors and also impact prognosis and patient care. PURPOSE The primary objective was to evaluate an association between obesity and histological type of RCC. The secondary objective was to assess if there was an effect of obesity on tumor characteristics. METHODS A multicenter comparative descriptive study was carried out in nearly 30 French hospitals. Histological features of operated RCC of patients included between 2007 and 2020 were compared according to their BMI. Obesity was defined as a BMI≥30kg/m2, with a P<0.05. RESULTS In total, 6749 RCC were analyzed, including 1687 (25%) from obese patients. This population was more frequently diabetic (61% versus 41%, P<0.001) and hypertensive (27% versus 11%, P<0.001). Regarding histological evaluation, the obese group presented clearer cell carcinoma. Other types presented odd ratios below 1 on multivariate analysis, P<0.01 except for type II papillary RCC. Tumor size (pT) and nuclear ISUP grade were both lower when BMI was above 30kg/m2: 72.4% of size pT 1-2 versus 68.5% (P=0.026) and 50% of nuclear ISUP grade 1-2 versus 43.3% for the non-obese group (P<0.0001). There was no difference in survival due to an insufficient number of events. CONCLUSION In this large cohort study, we report novel data on a positive association between obesity and histological type of RCC, in particular clear cell RCC. LEVEL OF EVIDENCE: 3
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17
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Blüher M. An overview of obesity-related complications: The epidemiological evidence linking body weight and other markers of obesity to adverse health outcomes. Diabetes Obes Metab 2025; 27 Suppl 2:3-19. [PMID: 40069923 PMCID: PMC12000860 DOI: 10.1111/dom.16263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/23/2025] [Accepted: 02/02/2025] [Indexed: 04/17/2025]
Abstract
Obesity is a highly prevalent chronic multisystem disease associated with shortened life expectancy due to a number of adverse health outcomes. Epidemiological data link body weight and parameters of central fat distribution to an increasing risk for type 2 diabetes, hypertension, fatty liver diseases, cardiovascular diseases including myocardial infarction, heart failure, atrial fibrillation, stroke, obstructive sleep apnoea, osteoarthritis, mental disorders and some types of cancer. However, the individual risk to develop cardiometabolic and other obesity-related diseases cannot entirely be explained by increased fat mass. Rather than excess fat accumulation, dysfunction of adipose tissue may represent the mechanistic link between obesity and adverse health outcomes. There are people living with obesity who seem to be protected against the premature development of cardiometabolic diseases. On the other hand, people with normal weight may develop typical obesity diseases upon dysfunction of adipose tissue and predominantly visceral fat distribution. The mechanisms linking impaired function of adipose tissue in people with obesity include adipocyte hypertrophy, altered cellular composition, limited expandability of safe subcutaneous fat stores, ectopic fat deposition in visceral depots, the liver and other organs, hypoxia, a variety of stresses, inflammatory processes, and the release of pro-inflammatory, diabetogenic and atherogenic signals. Genetic and environmental factors might contribute either alone or via interaction with intrinsic biological factors to variation in adipose tissue function. There are still many open questions regarding the mechanisms of how increased body weight causes obesity-related disorders and whether these pathologies could be reversed. Evidence-based weight loss interventions using behaviour change, pharmacological or surgical approaches have clarified the beneficial effects of realistic and sustained weight loss on obesity-related complications as hard outcomes. This review focusses on recent advances in understanding epidemiological trends and mechanisms of obesity-related diseases. PLAIN LANGUAGE SUMMARY: Obesity is a chronic complex and progressive disease characterized by excessive fat deposition that may impair health and quality of life. Worldwide, the number of adults living with obesity has more than doubled since 1990. Obesity may lead to reduced life expectancy, because it increases the risk for type 2 diabetes, cardiovascular diseases (e.g., myocardial infarction, high blood pressure, stroke), fatty liver diseases, musculoskeletal diseases, chronic respiratory diseases, depression and certain types of cancer. However, not every person with obesity develops these diseases. For better prevention and treatment, it is important to understand the mechanisms linking high fat mass to obesity related diseases. It has become clear that fat mass alone cannot explain the higher risk of obesity complications. People with obesity can have either high or low risk of developing complications. Compared to people with a low risk for obesity complications those with a high risk to develop obesity related diseases are characterized by higher central fat deposition in the abdominal region, on average bigger fat cells, higher number of immune cells in adipose tissue and altered signals released from adipose tissue that may directly affect the brain, liver, vasculature and other organs. Both inherited and environment factors may cause these abnormalities of adipose tissue function. However, weight loss through behaviour changes (e.g., lower calorie intake, higher physical activity), medications or obesity surgery can improve health, quality of life and reduce the risk for obesity related diseases.
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Affiliation(s)
- Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI‐MAG) of the Helmholtz Zentrum MünchenUniversity of Leipzig and University Hospital LeipzigLeipzigGermany
- Medical Department III—Endocrinology, Nephrology, RheumatologyUniversity of Leipzig Medical CenterLeipzigGermany
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18
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Xiao T, Chen D, Peng L, Li Z, Pan W, Dong Y, Zhang J, Li M. Fluorescence-guided Surgery for Hepatocellular Carcinoma: From Clinical Practice to Laboratories. J Clin Transl Hepatol 2025; 13:216-232. [PMID: 40078203 PMCID: PMC11894393 DOI: 10.14218/jcth.2024.00375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/06/2024] [Accepted: 12/12/2024] [Indexed: 03/14/2025] Open
Abstract
Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.
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Affiliation(s)
- Tian Xiao
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Didi Chen
- Hubei Key Laboratory of Purification and Application of Plant Anti-Cancer Active Ingredients, Hubei University of Education, Wuhan, Hubei, China
| | - Li Peng
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuoxia Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenming Pan
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuping Dong
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Jinxiang Zhang
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Xu S, Liu Z, Tian T, Zhao W, Wang Z, Liu M, Xu M, Zhang F, Zhang Z, Chen M, Yin Y, Su M, Fang W, Pan W, Liu S, Li MD, Little PJ, Kamato D, Zhang S, Wang D, Offermanns S, Speakman JR, Weng J. The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21. SCIENCE ADVANCES 2025; 11:eadt3142. [PMID: 40138418 PMCID: PMC11939056 DOI: 10.1126/sciadv.adt3142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 02/20/2025] [Indexed: 03/29/2025]
Abstract
Obesity is a debilitating global pandemic with a huge cost on health care due to it being a major underlying risk factor for several diseases. Therefore, there is an unmet medical need for pharmacological interventions to curb obesity. Here, we report that halofuginone, a Food and Drug Administration-approved anti-scleroderma and antiprotozoal drug, is a promising anti-obesity agent in preclinical mouse and pig models. Halofuginone suppressed food intake, increased energy expenditure, and resulted in weight loss in diet-induced obese mice while also alleviating insulin resistance and hepatic steatosis. Using molecular and pharmacological tools with transcriptomics, we identified that halofuginone increases fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) levels via activating integrated stress response. Using Gdf15 and Fgf21 knockout mice, we show that both hormones are necessary to elicit anti-obesity changes. Together, our study reports the beneficial metabolic effects of halofuginone and underscores its utility in treating obesity and its associated metabolic complications, which merits clinical assessment.
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Affiliation(s)
- Suowen Xu
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Provincial Key Laboratory of Metabolic Health and Panvascular Diseases, Hefei 230001, China
- Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany
- Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei 230001, China
| | - Zhenghong Liu
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Tian Tian
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Wenqi Zhao
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Zhihua Wang
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Monan Liu
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Mengyun Xu
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Fanshun Zhang
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Zhidan Zhang
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Meijie Chen
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Yanjun Yin
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Meiming Su
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Wenxiang Fang
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Wenhao Pan
- Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Shiyong Liu
- Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Min-dian Li
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, MOE Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease, Southwest Hospital, Army Medical University, Chongqing, China
| | - Peter J. Little
- Department of Pharmacy, Guangzhou Xinhua University, No. 721, Guangshan Road 1, Guangzhou 510520, China
| | - Danielle Kamato
- Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland 4111, Australia
| | - Songyang Zhang
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Dongdong Wang
- Centre for Metabolism, Obesity, and Diabetes Research, McMaster University, Hamilton, Ontario, Canada
| | - Stefan Offermanns
- Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany
| | - John R. Speakman
- Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- School of Biological Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK
| | - Jianping Weng
- Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Provincial Key Laboratory of Metabolic Health and Panvascular Diseases, Hefei 230001, China
- Institute of Endocrine and Metabolic Diseases, University of Science and Technology of China, Hefei 230001, China
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
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20
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Xie W, Wang Z, Liu X, Tan S. Robotic single site versus robotic multiport hysterectomy in endometrial cancer: a systematic review and meta-analysis. BMC Cancer 2025; 25:554. [PMID: 40148895 PMCID: PMC11951834 DOI: 10.1186/s12885-025-13968-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/19/2025] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVE This meta-analysis aims to compare the safety and efficacy of robotic single-site hysterectomy (RSSH) with robotic multiport hysterectomy (RMPH) in treating endometrial cancer. METHODS We conducted a comprehensive literature search across several databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the Chinese National Knowledge Infrastructure (CNKI), Wan Fang, and the Chinese Science and Technology Journal Full Text Database (VIP). The search covered literature from inception until October 17, 2024. The primary outcomes included intraoperative complications, postoperative complications, postoperative pain scores, and satisfaction with cosmetic outcomes. The secondary outcomes included operative time (min), estimated blood loss (ml), hemoglobin drop, blood transfusion, conversion, postoperative hospital stay, lymph nodes harvested, sentinel lymph node identification, recurrence, and mortality during follow-up. Data analysis was performed using random-effects or fixed-effects models, calculating combined risk ratios (RR), weighted mean difference (WMD), and 95% confidence intervals (95% CI). RESULTS Five studies describing a total of 448 patients were retained and included for this meta-analysis. No significant differences were found between RSSH and RMPH regarding intraoperative complications, postoperative complications, and postoperative pain scores. There were also no differences in terms of operation time, estimated blood loss, hemoglobin drop, blood transfusion, conversion, postoperative hospital stay, lymph nodes harvested, and sentinel lymph node identification. CONCLUSION This systematic review and meta-analysis provides evidence that RSSH is effective and safe for the treatment of endometrial cancer, as it is generally equivalent to RMPH regarding perioperative outcomes.
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Affiliation(s)
- Weimin Xie
- Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hunan Province, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, 421000, China
| | - Zhangyi Wang
- Nursing Department, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hunan Province, Hengyang, 421000, China
| | - Xiaohang Liu
- Department of Gynecology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikouaq , Hainan, 570100, China
| | - Songhong Tan
- Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hunan Province, No. 31 Guanghui Road, Zhengxiang District, Hengyang City, 421000, China.
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21
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Che PY, Zuo CJ, Tian J. Global trends in esophageal cancer and metabolic syndrome research: bibliometric analysis and visualization from 1995 to 2024. Discov Oncol 2025; 16:398. [PMID: 40138022 PMCID: PMC11947393 DOI: 10.1007/s12672-025-02181-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/18/2025] [Indexed: 03/29/2025] Open
Abstract
PURPOSE Metabolic syndrome (MetS) plays a key role in the progression of esophageal cancer (EC), yet few studies have comprehensively explored research trends on this topic. To fill this gap, this study analyzes global research developments, hotspots, and collaborations related to MetS and EC. METHODS A total of 1008 publications from 1995 to 2024 were analyzed using bibliometric tools like VOSviewer, CiteSpace, and the R package 'bibliometrix', drawing from the Web of Science Core Collection. RESULTS The analysis includes contributions from 5,183 researchers at 1500 institutions across 85 countries, with publications appearing in 411 journals. The United States, China, and the United Kingdom are leading in both publication volume and research impact. Karolinska Institutet emerged as a prominent contributor to this body of work. Key journals include the Diseases of the Esophagus and Gastroenterology. Main areas cover metabolic factors, metabolic surgery, adipokines, lifestyle risk factors, cirrhosis & portal hypertension. Emerging trends focus on "metabolic syndrome and EC risk", "inflammation and adipokines", "bariatric surgery and EC prevention", "post-surgical outcomes", "early detection strategies". CONCLUSION As the first comprehensive bibliometric study on MetS and EC, this research highlights metabolism-related factors driving EC progression. Future research should focus on clarifying MetS-EC mechanisms and developing prevention and treatment strategies.
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Affiliation(s)
- Peng-Yu Che
- Department of Cardiothoracic Surgery, The People's Hospital of Chongqing Hechuan, Chongqing, 401520, China.
| | - Chun-Jian Zuo
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Jie Tian
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, China.
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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22
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Sawai Y, Hayakawa M, Yasuda H, Nakao R, Ogata T, Nakamura A, Mochizuki K, Takata T, Miyake H, Sogame Y, Morimura R, Kurahashi T, Dai P, Konishi E, Itoh Y, Tanaka H, Harada Y. Oleic acid enhances the proliferation of gallbladder cancer cells via the GPR120/ERK pathway. Biochem Biophys Res Commun 2025; 754:151530. [PMID: 40023990 DOI: 10.1016/j.bbrc.2025.151530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/17/2025] [Accepted: 02/22/2025] [Indexed: 03/04/2025]
Abstract
Gallbladder cancer (GBC) is a highly aggressive malignancy exhibiting a correlation between increased body mass index and increased risk of developing GBC. In obese individuals, the release of free fatty acids from the adipose tissue into the circulating blood is augmented. However, the role of oleic acid (OA), one of the most abundant monounsaturated fatty acids in the plasma, in GBC cell proliferation has not been determined. In this study, we investigated the effects of OA on the proliferation of GBC cells. We focused on the role of G protein-coupled receptor 120/free fatty acid receptor 4 (GPR120/FFAR4) and G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which have a high affinity for long-chain fatty acids. OA significantly promoted the proliferation of human GBC cell lines (G-415 and GBC-SD) in vitro, with the highest increase observed at 200 μM OA. In vivo, OA-treated nude mice bearing G-415 xenografts exhibited enhanced tumor growth compared to controls. Immunohistochemical analysis revealed the expression of GPR120 and GPR40 in cultured GBC cells and patient tissues. OA-induced proliferation was mediated by GPR120, as evident from significantly reduced cell proliferation upon GPR120 silencing or inhibition, and no effect of GPR40 inhibition. Furthermore, OA-induced GPR120 activation enhanced ERK phosphorylation, implicating the GPR120/ERK signaling pathway in GBC cell growth. To our knowledge, this is the first study to elucidate the role of OA in GBC cell proliferation via GPR120, suggesting its potential as a therapeutic target for GBC treatment.
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Affiliation(s)
- Yuki Sawai
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan; Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michiyo Hayakawa
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Hiroaki Yasuda
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryuta Nakao
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Takehiro Ogata
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Akihiro Nakamura
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Kentaro Mochizuki
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Tomoki Takata
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan; Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hayato Miyake
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshio Sogame
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Toshihiro Kurahashi
- Department of Cellular Regenerative Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Ping Dai
- Department of Cellular Regenerative Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eiichi Konishi
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideo Tanaka
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan; Faculty of Health and Medical Sciences, Kyoto University of Advanced Science, 18 Yamanouchi Gotanda-cho, Ukyo-ku, Kyoto, 615-8577, Japan
| | - Yoshinori Harada
- Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho Kamigyo-Ku, Kyoto, 602-8566, Japan.
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Walsh RM, Ambrose J, Jack JL, Eades AE, Bye BA, Tannus Ruckert M, Messaggio F, Olou AA, Chalise P, Pei D, VanSaun MN. Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer. J Immunother Cancer 2025; 13:e010057. [PMID: 40121029 PMCID: PMC11931939 DOI: 10.1136/jitc-2024-010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 03/10/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands are a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and even adipocytes, they are also secreted by immune-evasive cancer cells. CXC-ligand release is known to occur in response to inflammatory stimuli. Adipose tissue is an endocrine organ and a source of inflammatory signaling peptides. Importantly, adipose-derived cytokines and chemokines are implicated as potential drivers of tumor cell immune evasion; cumulatively, these findings suggest that targeting CXC-ligands may be beneficial in the context of obesity. METHODS RNA-sequencing of human PDAC cell lines was used to assess influences of adipose conditioned media on the cancer cell transcriptome. The adipose-induced secretome of PDAC cells was validated with ELISA for induction of CXCL5 secretion. Human tissue data from CPTAC was used to correlate IL-1β and TNF expression with both CXCL5 mRNA and protein levels. CRISPR-Cas9 was used to knockout CXCL5 from a murine PDAC KPC cell line to assess orthotopic tumor studies in syngeneic, diet-induced obese mice. Flow cytometry and immunohistochemistry were used to compare the immune profiles between tumors with or without CXCL5. Mice-bearing CXCL5 competent or deficient tumors were monitored for differential tumor size in response to anti-PD-1 immune checkpoint blockade therapy. RESULTS Human adipose tissue conditioned media stimulates CXCL5 secretion from PDAC cells via either IL-1β or TNF; neutralization of both is required to significantly block the release of CXCL5 from tumor cells. Ablation of CXCL5 from tumors promoted an enriched immune phenotype with an unanticipatedly increased number of exhausted CD8 T cells. Application of anti-PD-1 treatment to control tumors failed to alter tumor growth, yet treatment of CXCL5-deficient tumors showed response by significantly diminished tumor mass. CONCLUSIONS In summary, our findings show that both TNF and IL-1β can stimulate CXCL5 release from PDAC cells in vitro, which correlates with expression in patient data. CXCL5 depletion in vivo alone is sufficient to promote T cell infiltration into tumors, increasing efficacy and requiring checkpoint blockade inhibition to alleviate tumor burden.
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Affiliation(s)
| | | | | | | | | | | | - Fanuel Messaggio
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | - Prabhakar Chalise
- Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas, USA
- The University of Kansas Cancer Center, Kansas City, Kansas, USA
| | - Dong Pei
- Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas, USA
- The University of Kansas Cancer Center, Kansas City, Kansas, USA
| | - Michael N VanSaun
- Cancer Biology, KUMC, Kansas City, Kansas, USA
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
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24
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Luo Q, Bai X, Li X, Liu C. The role and mechanism of selenium in the prevention and progression of hepatocellular carcinoma. Front Oncol 2025; 15:1557233. [PMID: 40182029 PMCID: PMC11965637 DOI: 10.3389/fonc.2025.1557233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/05/2025] [Indexed: 04/05/2025] Open
Abstract
Hepatocellular carcinoma (HCC) represents the most prevalent form of liver cancer. Despite notable advancements in therapeutic strategies, HCC continues to pose significant public health challenges due to its rising incidence and high mortality rates worldwide. Selenium is an essential trace element that playing a critical role in human health. Recent studies have highlighted its potential preventive and therapeutic benefits in the context of HCC. However, some in vitro and in vivo investigations have yielded inconsistent results, and the mechanisms by which selenium influences HCC are still not completely clear. This review begins by providing an extensive evaluation of the effects and mechanisms of selenium on the primary risk factors associated with HCC, including viral infections, metabolic abnormalities, and lifestyle factors. Subsequently, we outline the roles and mechanisms by which selenium influences the proliferation, metastasis, and immune microenvironment of HCC. Finally, we emphasize the imperative for further investigation into the optimal dosage and forms of selenium, as well as its effects on the HCC microenvironment, to inform the development of effective clinical strategies. This review thus provides a foundational framework for the potential clinical application of selenium in the treatment of HCC.
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Affiliation(s)
- Qinying Luo
- BioBank, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaofang Bai
- Department of Ultrasonography, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Xiaojiao Li
- BioBank, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chang Liu
- Department of Clinical Laboratory, Gongli Hospital of Shanghai Pudong, Shanghai, China
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Ntim EA, Nyamekye S, Yeboah KO, Safianu R, Djankpa FT, Ainooson GK, Appiah KAA. Associations between green tea drinking and body mass index, serum lipid profile and prostate-specific antigen in a Ghanaian population: a cross-sectional study. BMC Nutr 2025; 11:55. [PMID: 40087803 PMCID: PMC11908008 DOI: 10.1186/s40795-025-01039-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 03/05/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Prostate cancer (PCa) is a major malignancy that affects men worldwide. Obesity, dyslipidemia and elevated serum PSA are common risk factors. Green tea is a popular beverage in some West African communities with a relatively low incidence of PCa. However, the associations of green tea consumption with these PCa risk factors in that population remain unknown. This study therefore aimed at investigating the associations between green tea intake and the serum lipid profile, body mass index (BMI), and serum PSA. METHODS An analytical cross-sectional survey was conducted to compare the serum lipid profile, BMI and serum PSA between green tea drinkers (GTD) and non-tea drinkers (NTD). A total of 415 men, 40 years or older, who gave their consent were assigned to four groups on the basis of age: 40-49 years, 50-59 years, 60-69 years, and 70 + years. BMI, serum lipid profile (total cholesterol, HDL-c, LDL-c, and triglycerides), and serum PSA level were determined and compared between GTD and NTD. RESULTS Compared with the NTD group, the GTD with normal BMI were significantly greater across all age groups, and the odds of being overweight (obese) were significantly lower in the GTD group than in the NTD group. Compared with those in the NTD, significantly fewer atherogenic lipids in the GTD were observed across all age categories. Furthermore, the odds of dyslipidemia in GTD groups were lower than those in NTD groups across all age groups. A significantly lower mean serum PSA level was observed in the older GTD age groups (60-69 and 70+) than in the NTD group, and significantly lower odds of elevated serum PSA were detected in the GTD group than in the NTD group. However, there were no differences in the mean PSA between the GTD and NTD groups in the younger age groups. Weak positive correlations between serum PSA and BMI were observed in the NTD group regardless of the age category. However, a significantly strong negative correlation between the serum PSA concentration and BMI was observed in the older age GTD group compared with the NTD group. CONCLUSIONS Consumption of green tea was associated with reduced atherogenic serum lipids and improved BMI independent of age. Furthermore, GTD was significantly associated with reduced serum PSA in older men but not in younger adults.
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Affiliation(s)
- Emmanuel Amankwah Ntim
- Department of Physiology, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Samuel Nyamekye
- Department of Physiology, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kofi Oduro Yeboah
- Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Rufai Safianu
- Department of Basic Medical Sciences, School of Medicine, University of Health and Allied Sciences, Ho, Ghana
| | - Francis Tanam Djankpa
- Department of Physiology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - George Kwaw Ainooson
- Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kwaku Addai Arhin Appiah
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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Marathe SJ, Grey EW, Bohm MS, Joseph SC, Ramesh AV, Cottam MA, Idrees K, Wellen KE, Hasty AH, Rathmell JC, Makowski L. Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression. NPJ METABOLIC HEALTH AND DISEASE 2025; 3:10. [PMID: 40094000 PMCID: PMC11908972 DOI: 10.1038/s44324-025-00054-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/12/2025] [Indexed: 03/19/2025]
Abstract
Medical therapeutics for weight loss are changing the landscape of obesity but impacts on obesity-associated cancer remain unclear. We report that in pre-clinical models with significant retatrutide (RETA, LY3437943)-induced weight loss, pancreatic cancer engraftment was reduced, tumor onset was delayed, and progression was attenuated resulting in a 14-fold reduction in tumor volume compared to only 4-fold reduction in single agonist semaglutide-treated mice. Despite weight re-gain after RETA withdrawal, the anti-tumor benefits of RETA persisted. Remarkably, RETA-induced protection extends to a lung cancer model with 50% reduced tumor engraftment, significantly delayed tumor onset, and mitigated tumor progression, with a 17-fold reduction in tumor volume compared to controls. RETA induced immune reprogramming systemically and in the tumor microenvironment with durable anti-tumor immunity evidenced by elevated circulating IL-6, increased antigen presenting cells, reduced immunosuppressive cells, and activation of pro-inflammatory pathways. In sum, our findings suggest that patients with RETA-mediated weight loss may also benefit from reduced cancer risk and improved outcomes.
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Affiliation(s)
- Sandesh J. Marathe
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
- UTHSC Center for Cancer Research, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
| | - Emily W. Grey
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
| | - Margaret S. Bohm
- Department of Microbiology, Immunology, and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
| | - Sydney C. Joseph
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
| | - Arvind V. Ramesh
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
| | - Matthew A. Cottam
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN USA
| | - Kathryn E. Wellen
- Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Alyssa H. Hasty
- Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern, Dallas, TX USA
| | - Jeffrey C. Rathmell
- Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN USA
| | - Liza Makowski
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
- UTHSC Center for Cancer Research, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
- Department of Microbiology, Immunology, and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN USA
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Prete A, Gambale C, Bottici V, Cappagli V, Aringhieri G, Puccini M, Landi S, Torregrossa L, Santini F, Matrone A, Elisei R. Body Mass Index and Sporadic Medullary Thyroid Cancer: Insights from a Large Series. Cancers (Basel) 2025; 17:950. [PMID: 40149286 PMCID: PMC11940153 DOI: 10.3390/cancers17060950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/28/2025] [Accepted: 03/08/2025] [Indexed: 03/29/2025] Open
Abstract
Background: Excess adipose tissue has been associated with the increased prevalence and aggressiveness of many human cancers. While its role in differentiated thyroid cancer is well established, in medullary thyroid cancer (MTC), data are conflicting. We aimed to evaluate the impact of excess adipose tissue on MTC prevalence, aggressiveness at diagnosis, and outcome in a large series of patients. Methods: We evaluated 529 patients with sporadic MTC from a prospectively maintained database. Weight and height were measured in all patients at the time of surgery, and body mass index (BMI) was calculated. Therefore, patients were classified according to BMI categories suggested by the WHO for Caucasian patients. Data about somatic mutations were available in 254/529 patients (48.0%). Results: The prevalence of subjects with obesity was higher than that in the Italian general population (20.2 vs. 12.0%). Patients with obesity presented smaller tumors, lower T and N stage, and lower AJCC 8th edition stage, as well as lower preoperative calcitonin values compared to under/normal and overweight ones. The prevalence of somatic RET and RAS mutations did not differ significantly across the WHO BMI categories. At the end of follow-up, structural disease was less common in patients with obesity (15.4%) compared to under/normal (25.6%, p < 0.05) and overweight (24.1%, p = 0.079). Further surgeries for local recurrence were less common in patients with obesity (3.8%) compared to overweight ones (11.0%, p < 0.05). Survival was superimposable in the different categories of BMI. Conclusions: Among patients with sporadic MTC, there is a higher prevalence of patients with obesity compared to the general population. A higher BMI was associated with less aggressive clinical presentation and better clinical outcomes.
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Affiliation(s)
- Alessandro Prete
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Carla Gambale
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Valeria Bottici
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Virginia Cappagli
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Giacomo Aringhieri
- Academic Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy;
| | - Marco Puccini
- Endocrine Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy;
| | - Stefano Landi
- Department of Biology, University of Pisa, 56124 Pisa, Italy;
| | - Liborio Torregrossa
- Pathology Unit 3, Department of Surgical, Medical and Molecular Pathology, University of Pisa, 56124 Pisa, Italy;
| | - Ferruccio Santini
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Antonio Matrone
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
| | - Rossella Elisei
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy; (A.P.); (C.G.); (V.B.); (V.C.); (F.S.); (R.E.)
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Hontecillas-Prieto L, García-Domínguez DJ, Jiménez-Cortegana C, Nogales-Fernández E, Palazón-Carrión N, García-Sancho AM, Ríos-Herranz E, Gumà-Padrò J, Provencio-Pulla M, Rueda-Domínguez A, de la Cruz-Merino L, Sánchez-Margalet V. Obesity and overweight in R/R DLBCL patients is associated with a better response to treatment of R2-GDP-GOTEL trial. Potential role of NK CD8 + cells and vitamin D. Cancer Metab 2025; 13:12. [PMID: 40038834 DOI: 10.1186/s40170-025-00381-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/23/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide and is characterized by its heterogeneity. Although first-line therapy improves survival outcomes for DLBCL patients, approximately one third will relapse, often with a poor prognosis. Among the factors influencing prognosis and response to treatment in cancer patients, including those with lymphoma, overweight and obesity have emerged as significant considerations. However, the role of excess weight in DLBCL remains controversial, with studies reporting both negative and positive effects on cancer outcomes. In this translational substudy of the R2-GDP-GOTEL trial, we have evaluated the impact of excess weight as a predictor of treatment response and survival in patients with relapsed/refractory (R/R) DLBCL, and examining its relationship with immune cell dynamics. METHODS Of the 79 patients who received the R2-GDP scheme in the phase II trial, weight and height parameters were obtained in 75 patients before starting treatment. Blood samples were analyzed by flow cytometry. Statistical analyses were performed to determine the prognostic value of overweight and obesity at baseline in R/R DLBCL patients. RESULTS Our results indicate that overweight (including obese) patients exhibit longer survival compared to patients of ideal weight. This group also demonstrated a reduction of regulatory T cells with supposedly protumor activity and an increase of Natural Killer (NK)-like T cells with supposedly antitumor activity. Additionally, we have found that excess weight correlates with better treatment response, associated with elevated levels of vitamin D and CD8 + NK cells. CONCLUSIONS Our findings suggest that excess weight does not exacerbate the progression of DLBCL. Instead, it appears to confer a survival advantage and improve treatment response, with the immune system playing a possible pivotal role in mediating these effects. TRIAL REGISTRATION EudraCT, ID:2014-001620-29.
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Affiliation(s)
- Lourdes Hontecillas-Prieto
- Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, Spain
- Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain
- Clinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain
| | - Daniel J García-Domínguez
- Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain
- Institute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, Spain
| | - Carlos Jiménez-Cortegana
- Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain
| | - Esteban Nogales-Fernández
- Clinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain
- Department of Medicine, University of Seville, Seville, Spain
| | - Natalia Palazón-Carrión
- Clinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain
- Department of Medicine, University of Seville, Seville, Spain
| | - Alejandro Martín García-Sancho
- Department of Hematology, Hospital Universitario de Salamanca, IBSAL, CIBERONC, University of Salamanca, Salamanca, Spain
| | | | - Josep Gumà-Padrò
- Department of Clinical Oncology, Hospital Universitari Sant Joan de Reus URV, IISPV, Reus, Spain
| | - Mariano Provencio-Pulla
- Department of Medical Oncology, Facultad de Medicina, Hospital Universitario Puerta de Hierro-Majadahonda, Universidad Autónoma de Madrid, IDIPHISA, Madrid, Spain
| | | | - Luis de la Cruz-Merino
- Clinical Oncology Service, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain.
- Institute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, Spain.
- Department of Medicine, University of Seville, Seville, Spain.
| | - Víctor Sánchez-Margalet
- Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, Spain.
- Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain.
- Institute of Biomedicine of Seville, Virgen Macarena University Hospital, CSIC, University of Seville, Seville, Spain.
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Machado RD, Faria EF, Júnior AAR, Stirpari F, Feres RN, Spiess PE, Shariat SF, Reis LO, Dos Reis RB. Is body mass index a risk factor for lymphnode metastasis in penile cancer? BMC Cancer 2025; 25:394. [PMID: 40038702 PMCID: PMC11881301 DOI: 10.1186/s12885-025-13763-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/18/2025] [Indexed: 03/06/2025] Open
Abstract
INTRODUCTION Obese patients with penile cancer may have more advanced disease. This study evaluated the association of obesity with penile cancer and the risk of lymph node metastases in patients who underwent inguinal lymphadenectomy. METHODS We retrospectively reviewed the charts of 197 penile cancer (PC) patients from January 2000 to December 2011. Seventy underwent inguinal lymphadenectomy. For this subgroup, chi-square analysis evaluated the correlations of sociodemographic, clinical, and pathological variables with the presence of positive inguinal lymph nodes. Patients were divided into normal weight, overweight, and obese categories according to body mass index (BMI). The mean numbers of positive and resected lymph nodes were compared for each BMI category. RESULTS The percentage of overweight men in the Brazilian population and among patients with PC was 52.6% and 42.8%, respectively. For patients who underwent lymphadenectomy, the mean BMIs were 25.9 ± 6. Most patients were white, married, had a lower education level, and had no history of smoking. Partial penectomy was the most frequently performed surgery; lymphovascular invasion occurred in 45.7%, and lymph node metastasis occurred in 52.9% of cases. The mean numbers of resected and positive lymph nodes for normal weight, overweight, and obesity were 21.1 and 2.2, 23.3 and 2.2, and 16.8 and 1.5, respectively. CONCLUSION Overweight and obesity were less frequently seen in patients with PC than in the Brazilian population. BMI was not a risk factor for developing lymph node metastasis; the only predictive factor for lymph node metastasis was the presence of lymphovascular invasion.
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Affiliation(s)
| | | | | | - Filipe Stirpari
- Medicine School of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil
| | | | - Philippe E Spiess
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Urology, Weill Cornell Medical College, New York, NY, USA
| | - Leonardo Oliveira Reis
- UroScience, State University of Campinas, Unicamp, and ImmunOncology, Pontifical Catholic University of Campinas, São Paulo, SP, Brazil.
| | - Rodolfo Borges Dos Reis
- Medicine School of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil.
- UroScience, State University of Campinas, Unicamp, and ImmunOncology, Pontifical Catholic University of Campinas, São Paulo, SP, Brazil.
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Cui X, Zhu Y, Zeng L, Zhang M, Uddin A, Gillespie TW, McCullough LE, Zhao S, Torres MA, Wan Y. Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2407494. [PMID: 39868848 PMCID: PMC11923992 DOI: 10.1002/advs.202407494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 01/13/2025] [Indexed: 01/28/2025]
Abstract
Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC. Mechanistically, cancer-associated adipocytes drive metabolic reprogramming resulting in an upregulated hexosamine biosynthetic pathway (HBP). This aberrant upregulation of HBP promotes YAP O-GlcNAcylation and the subsequent recruitment of EIF3H deubiquitinase, which stabilizes YAP, thus promoting tumor growth and chemotherapy resistance. It is found that Retatrutide, an anti-obesity agent, inhibits HBP and YAP O-GlcNAcylation leading to increased YAP degradation through the deprivation of EIF3H-mediated deubiquitylation of YAP. In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors. Overall, these findings reveal a critical interplay between adipocyte-mediated metabolic reprogramming and EIF3H-mediated YAP proteolytic control, offering promising therapeutic strategies to mitigate the adverse effects of obesity on TNBC progression.
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Affiliation(s)
- Xin Cui
- Department of Pharmacology and Chemical BiologyEmory University School of MedicineAtlantaGA30322USA
| | - Yueming Zhu
- Department of Pharmacology and Chemical BiologyEmory University School of MedicineAtlantaGA30322USA
- Winship Cancer InstituteEmory University School of MedicineAtlantaGA30322USA
| | - Lidan Zeng
- Department of Pharmacology and Chemical BiologyEmory University School of MedicineAtlantaGA30322USA
| | - Mengyuan Zhang
- Department of Biochemistry and Molecular BiologyInstitute of BioinformaticsUniversity of GeorgiaAthensGA30602USA
| | - Amad Uddin
- Department of Pharmacology and Chemical BiologyEmory University School of MedicineAtlantaGA30322USA
| | - Theresa W. Gillespie
- Winship Cancer InstituteEmory University School of MedicineAtlantaGA30322USA
- Department of SurgeryEmory University School of MedicineAtlantaGA30322USA
- Department of Hematology and Medical OncologyEmory University School of MedicineAtlantaGA30322USA
| | - Lauren E. McCullough
- Winship Cancer InstituteEmory University School of MedicineAtlantaGA30322USA
- Department of EpidemiologyEmory University Rollins School of Public HealthAtlantaGA30322USA
| | - Shaying Zhao
- Department of Biochemistry and Molecular BiologyInstitute of BioinformaticsUniversity of GeorgiaAthensGA30602USA
| | - Mylin A. Torres
- Winship Cancer InstituteEmory University School of MedicineAtlantaGA30322USA
- Department of Radiation OncologyEmory University School of MedicineAtlantaGA30322USA
| | - Yong Wan
- Department of Pharmacology and Chemical BiologyEmory University School of MedicineAtlantaGA30322USA
- Winship Cancer InstituteEmory University School of MedicineAtlantaGA30322USA
- Department of Hematology and Medical OncologyEmory University School of MedicineAtlantaGA30322USA
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Francoeur AA, Liao CI, Chang J, Johnson CR, Clair K, Tewari KS, Kapp DS, Chan JK, Bristow RE. Associated Trends in Obesity and Endometrioid Endometrial Cancer in the United States. Obstet Gynecol 2025; 145:e107-e116. [PMID: 39746203 DOI: 10.1097/aog.0000000000005814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/07/2024] [Indexed: 01/04/2025]
Abstract
OBJECTIVE To evaluate the correlation in temporal trends in obesity and endometrioid endometrial cancer incidence in the United States using two comprehensive national databases. METHODS This is a cohort study in which data on endometrioid endometrial cancer were obtained from the U.S. Cancer Statistics from 2001 to 2018 and corrected for hysterectomy and pregnancy. Data on obesity were collected from the NHANES (National Health and Nutrition Examination Survey) database from 1988 to 2018. Average annual percentage changes (AAPCs) were used to describe trends. Pearson correlation coefficients ( r ) were calculated to examine the relationship between trends. SEER*Stat 8.3.9.2 and joinpoint regression program 5.2.0 were used for statistical analysis. RESULTS From U.S. Cancer Statistics data, 586,742 cases of endometrioid cancer were identified from 2001 to 2018. The average annual increase in endometrioid cancer was as follows: Hispanic 1.37% (95% CI, 1.14-1.60, P <.001), Black 1.30% (95% CI, 1.04-1.57, P <.001), and White -0.17 (95% CI, -0.91 to 0.58, P =.656). Women aged 20-29 years had a 4.48% annual increase (95% CI, 3.72-5.25, P <.001) and women aged 30-39 years had a 3.00% annual increase in rates (95% CI, 2.65-3.36, P <.001). According to the NHANES data, the prevalence of obesity in 2018 in adult women was as follows: Black 56.80%, Hispanic 44.10%, and White 40.90%. An examination of trends by age showed that women aged 20-29 years had the highest annual rise in obesity compared with other age groups (AAPC 7.36%, 95% CI, 4.0-10.8, P <.05). Strong and statistically significant correlations between endometrioid cancer and obesity trends were noted for Black ( r =0.78, P =.01) and Hispanic ( r =0.91, P <.001) women, as well as women aged 20-29 years ( r =0.72, P =.03) and 30-39 years ( r =0.88, P =.001). CONCLUSION The current data demonstrate a temporal association between the increasing incidence of obesity and endometrioid endometrial cancer, and this effect disproportionately affects younger women and Black and Hispanic women.
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Affiliation(s)
- Alex A Francoeur
- Department of Obstetrics and Gynecology and the Department of Medicine, University of California, Irvine, Orange, the Division of Gynecologic Oncology, California Pacific/Palo Alto/Sutter Health Research Institute, San Francisco, and the Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; and the Department of Obstetrics and Gynecology, Pingtung Veterans Hospital, Pingtung City, Taiwan
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Ardila V, Li H, Brunstein C, Kalaycio M, Sobecks R, Sauter CS, Hamilton BK. Impact of Obesity on GVHD in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies. Transplant Cell Ther 2025; 31:178.e1-178.e9. [PMID: 39824502 DOI: 10.1016/j.jtct.2025.01.881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/04/2025] [Accepted: 01/11/2025] [Indexed: 01/20/2025]
Abstract
BACKGROUND The relationship between obesity and graft-versus-host disease (GVHD) has been studied in both preclinical and clinical studies with varying results. OBJECTIVES We aimed to investigate the impact of obesity, as measured by body mass index (BMI), on the incidence, severity, and response to therapy of GVHD in a contemporary cohort. STUDY DESIGN We conducted a retrospective study of patients undergoing allogeneic hematopoietic cell transplant (HCT) for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 at the Cleveland Clinic. Incidence, grade, organ involvement, and response to therapy of acute and chronic GVHD were compared between patients with obesity (BMI ≥30) and without obesity. Secondary outcomes included relapse, nonrelapse mortality (NRM), and overall survival (OS). RESULTS 531 patients were identified, with a median follow-up of 19 months (range, 7-49). Mean (SD) BMI at time of HCT was 29.1 (6.3) kg/m2. There was no significant difference in demographic and HCT characteristics between patients with obesity (N = 199) and without obesity (N = 332). Development of any acute (42% versus 43%) or chronic (29% versus 30%) GVHD was similar in patients with and without obesity. Patients with obesity were less likely to have gastrointestinal involvement from chronic GVHD (28% versus 48%, P = .01). Skin (64% versus 56%), mouth (45% versus 35%) and eye (35% versus 27%) involvements were higher in patients with obesity, although statistically not significant. There were no significant differences in OS, NRM, or relapse. CONCLUSION There were no significant differences in incidence of GVHD among patients with and without obesity. Additional studies are needed to further understand potential differences in organ involvement.
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Affiliation(s)
- Valentina Ardila
- Internal Medicine Residency Program, Cleveland Clinic, Cleveland, Ohio
| | - Hong Li
- Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Claudio Brunstein
- Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Matt Kalaycio
- Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ronald Sobecks
- Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Craig S Sauter
- Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Betty K Hamilton
- Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
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Liu C, Du S, Liu X, Niu W, Song K, Yu J. Global, regional, and national burden of gallbladder and biliary tract cancer, 1990 to 2021 and predictions to 2045: an analysis of the Global Burden of Disease study 2021. J Gastrointest Surg 2025; 29:101968. [PMID: 39848314 DOI: 10.1016/j.gassur.2025.101968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/13/2025] [Accepted: 01/18/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Identifying past, present, and future temporal trends in gallbladder and biliary tract cancer (GBTC) can increase public awareness and promote changes in prevention and treatment strategies. METHODS The incidence and death rates of GBTC between 1990 and 2021 were extracted from the Global Burden of Disease study 2021 and assessed according to country, region, year, age, and sex. Time trends were measured using the average annual percentage change (AAPC) and projections of the burden of disease for 2022 to 2045 were made using the Bayesian age-period-cohort model. RESULTS In 2021, there were 216,768.3 new cases (95% uncertainty interval [UI], 181,888.0-245,237.6) and 171,961.2 deaths (95% UI, 142,351.8-194,238.4) in GBTC globally. The increases in incidence and deaths were 101.09% and 74.26%, respectively, compared with 1990. The GBTC burden was higher in females and older adults. However, age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) trended downward from 1990 to 2021, with AAPC at -0.39 (95% CI, -0.52 to -0.26) and -0.88 (95% CI, -0.96 to -0.79), respectively. Although the ASIR and ASDR for both sexes are projected to decline gradually from 2022 to 2045, the incidence and deaths are expected to increase steadily. In addition, the global proportion of GBTC deaths owing to high body mass index in 2021 was 12.66% for females and 10.48% for males, which did not change significantly from 1990. CONCLUSION GBTC is becoming a major global health burden, especially among females and older adults. Given the increasing burden of an aging population, there is a need to reduce the incidence of this disease by adopting effective strategies and measures targeting risk factors.
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Affiliation(s)
- Chunlong Liu
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital, Fuyang, China
| | - Sen Du
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital of Bengbu Medical University, Fuyang, China
| | - Xue Liu
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital of Bengbu Medical University, Fuyang, China
| | - Wang Niu
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital of Bengbu Medical University, Fuyang, China
| | - Kun Song
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital of Bengbu Medical University, Fuyang, China
| | - Jiangtao Yu
- Department of Hepatobiliary and Pancreatic Surgery, Fuyang People's Hospital, Fuyang, China.
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Yang YM, Kim J, Wang Z, Kim J, Kim SY, Cho GJ, Lee JH, Kim SM, Tsuchiya T, Matsuda M, Pandyarajan V, Pandol SJ, Lewis MS, Gangi A, Noble PW, Jiang D, Merchant A, Posadas EM, Bhowmick NA, Lu SC, You S, Xu AM, Seki E. Metastatic tumor growth in steatotic liver is promoted by HAS2-mediated fibrotic tumor microenvironment. J Clin Invest 2025; 135:e180802. [PMID: 39946200 PMCID: PMC11957696 DOI: 10.1172/jci180802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 02/07/2025] [Indexed: 02/20/2025] Open
Abstract
Steatotic liver enhances liver metastasis of colorectal cancer (CRC), but this process is not fully understood. Steatotic liver induced by a high-fat diet increases cancer-associated fibroblast (CAF) infiltration and collagen and hyaluronic acid (HA) production. We investigated the role of HA synthase 2 (HAS2) in the fibrotic tumor microenvironment in steatotic liver using Has2ΔHSC mice, in which Has2 is deleted from hepatic stellate cells. Has2ΔHSC mice had reduced steatotic liver-associated metastatic tumor growth of MC38 CRC cells, collagen and HA deposition, and CAF and M2 macrophage infiltration. We found that low-molecular weight HA activates Yes-associated protein (YAP) in cancer cells, which then releases connective tissue growth factor to further activate CAFs for HAS2 expression. Single-cell analyses revealed a link between CAF-derived HAS2 and M2 macrophages and CRC cells through CD44; these cells were associated with exhausted CD8+ T cells via programmed death-ligand 1 and programmed cell death protein 1 (PD-1). HA synthesis inhibitors reduced steatotic liver-associated metastasis of CRC, YAP expression, and CAF and M2 macrophage infiltration, and improved response to anti-PD-1 antibody. In conclusion, steatotic liver modulates a fibrotic tumor microenvironment to enhance metastatic cancer activity through a bidirectional regulation between CAFs and metastatic tumors, enhancing the metastatic potential of CRC in the liver.
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Affiliation(s)
- Yoon Mee Yang
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Pharmacy
- Multidimensional Genomics Research Center, and
- Innovative Drug Development Research Team for Intractable Diseases (BK21 plus), Kangwon National University, Chuncheon, South Korea
| | - Jieun Kim
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Zhijun Wang
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jina Kim
- Samuel Oschin Comprehensive Cancer Institute
- Department of Urology
- Department of Computational Biomedicine, and
| | - So Yeon Kim
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Gyu Jeong Cho
- Department of Pharmacy
- Innovative Drug Development Research Team for Intractable Diseases (BK21 plus), Kangwon National University, Chuncheon, South Korea
| | | | - Sun Myoung Kim
- Department of Pharmacy
- Innovative Drug Development Research Team for Intractable Diseases (BK21 plus), Kangwon National University, Chuncheon, South Korea
| | - Takashi Tsuchiya
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michitaka Matsuda
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vijay Pandyarajan
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Stephen J. Pandol
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michael S. Lewis
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Pathology, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California, USA
| | | | - Paul W. Noble
- Department of Medicine and Women’s Guild Lung Institute
| | - Dianhua Jiang
- Department of Medicine and Women’s Guild Lung Institute
| | - Akil Merchant
- Samuel Oschin Comprehensive Cancer Institute
- Division of Hematology and Cellular Therapy, Department of Medicine
| | - Edwin M. Posadas
- Samuel Oschin Comprehensive Cancer Institute
- Division of Medical Oncology, Department of Medicine, and
| | - Neil A. Bhowmick
- Samuel Oschin Comprehensive Cancer Institute
- Division of Medical Oncology, Department of Medicine, and
| | - Shelly C. Lu
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Sungyong You
- Samuel Oschin Comprehensive Cancer Institute
- Department of Urology
- Department of Computational Biomedicine, and
| | - Alexander M. Xu
- Samuel Oschin Comprehensive Cancer Institute
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, Maryland, USA
| | - Ekihiro Seki
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Samuel Oschin Comprehensive Cancer Institute
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Forder BH, Ardasheva A, Atha K, Nentwich H, Abhari R, Kartsonaki C. Models for predicting risk of endometrial cancer: a systematic review. Diagn Progn Res 2025; 9:3. [PMID: 39901248 PMCID: PMC11792366 DOI: 10.1186/s41512-024-00178-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 09/30/2024] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Endometrial cancer (EC) is the most prevalent gynaecological cancer in the UK with a rising incidence. Various models exist to predict the risk of developing EC, for different settings and prediction timeframes. This systematic review aims to provide a summary of models and assess their characteristics and performance. METHODS A systematic search of the MEDLINE and Embase (OVID) databases was used to identify risk prediction models related to EC and studies validating these models. Papers relating to predicting the risk of a future diagnosis of EC were selected for inclusion. Study characteristics, variables included in the model, methods used, and model performance, were extracted. The Prediction model Risk-of-Bias Assessment Tool was used to assess model quality. RESULTS Twenty studies describing 19 models were included. Ten were designed for the general population and nine for high-risk populations. Three models were developed for premenopausal women and two for postmenopausal women. Logistic regression was the most used development method. Three models, all in the general population, had a low risk of bias and all models had high applicability. Most models had moderate (area under the receiver operating characteristic curve (AUC) 0.60-0.80) or high predictive ability (AUC > 0.80) with AUCs ranging from 0.56 to 0.92. Calibration was assessed for five models. Two of these, the Hippisley-Cox and Coupland QCancer models, had high predictive ability and were well calibrated; these models also received a low risk of bias rating. CONCLUSIONS Several models of moderate-high predictive ability exist for predicting the risk of EC, but study quality varies, with most models at high risk of bias. External validation of well-performing models in large, diverse cohorts is needed to assess their utility. REGISTRATION The protocol for this review is available on PROSPERO (CRD42022303085).
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Affiliation(s)
| | | | - Karyna Atha
- Medical Sciences Division, University of Oxford, Oxford, UK
| | | | - Roxanna Abhari
- Medical Sciences Division, University of Oxford, Oxford, UK
| | - Christiana Kartsonaki
- Clinical Trials Service Unit and Epidemiological Studies Unit (CTSU), Nuffield, Department of Population Health (NDPH), Big Data Institute Building , University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.
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Granel N, Iserte G, Bartres C, Llarch N, Pla A, Sapena V, Mariño Z, Lens S, Vilana R, Nuñez I, Darnell A, Belmonte E, García-Criado Á, Díaz A, Sanduzzi-Zamparelli M, Fuster C, Muñoz-Martínez S, Ayuso C, Rimola J, Forner A, Soler A, Torres F, Ríos J, Bruix J, Moon AM, Forns X, Reig M. Liver cancer risk and changes in lifestyle habits after successful hepatitis C virus therapy post-DAA HCV therapy: lifestyle changes and liver cancer risk. BMC Gastroenterol 2025; 25:51. [PMID: 39901067 PMCID: PMC11792182 DOI: 10.1186/s12876-025-03611-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/14/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND The eradication of the Hepatitis C Virus (HCV) reduce the risk of liver cancer (LC), but lifestyle changes after cure may counterbalance its benefit. Our study investigates lifestyle changes that occur in HCV patients with Sustained Virological Response (SVR) after direct-acting antiviral (DAA) treatment. METHODS In this prospective, single-center study, HCV patients with advanced liver disease (F3/F4) treated and cured with DAA were invited to fill a lifestyle habits questionnaire in and perform abdominal ultrasound (US), blood extraction and anthropometric measurements within the 1st month after SVR and every 6 months thereafter until 48 months of follow-up, LC development, death, or loss to follow-up. RESULTS This prospective cohort included 182 patients with SVR after DAA in this first analysis through the 4 years of follow-up. At the time of SVR, 65.9% had cirrhosis, median BMI was 27.1 kg/m2, 74.2% were overweight or obese and 6.6% had an US with hepatic steatosis. Within a year of SVR, 9% of males and 4% of females progressed from normal weight to overweight/obesity and 19.4% increased alcohol consumption. At 48 months, there were statistically significant increases in BMI (0.75, p = 0.001) and alcohol consumption (6.4% p = 0.007). CONCLUSIONS In this prospective cohort, successful HCV therapy was followed by significant changes in lifestyle habits translating into increases in BMI and alcohol consumption. These post-SVR changes raise concerns that the chemopreventive benefits of HCV cure may be counterbalanced by increased risks of liver disease progression and LC development from metabolic risk factors and alcohol use. Post-SVR, patients may benefit from intensive counseling and pharmacotherapy to address obesity and alcohol use. TRIAL REGISTRATION/ CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Núria Granel
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Gemma Iserte
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Neus Llarch
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Anna Pla
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Víctor Sapena
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Department of Clinical Farmacology Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Ramón Vilana
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Isabel Nuñez
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Anna Darnell
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Ernest Belmonte
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Ángeles García-Criado
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Alba Díaz
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Pathology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Carla Fuster
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Pathology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Sergio Muñoz-Martínez
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Carmen Ayuso
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Alexandre Soler
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Oncology Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - José Ríos
- Department of Clinical Farmacology Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA
| | - Xavier Forns
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain.
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) group. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
- Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain.
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Karin M, Kim JY. MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives. Mol Oncol 2025; 19:275-294. [PMID: 38874196 PMCID: PMC11793012 DOI: 10.1002/1878-0261.13685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 04/15/2024] [Accepted: 06/04/2024] [Indexed: 06/15/2024] Open
Abstract
Hepatocellular carcinoma is one of the deadliest and fastest-growing cancers. Among HCC etiologies, metabolic dysfunction-associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD-driven HCC development. Thus, suitable preclinical models that recapitulate human etiologies are essentially required. Numerous preclinical models have been created but not many mimicked anthropometric measures and the course of disease progression shown in the patients. Here we review the literature on adipose tissues, liver-related HCC etiologies and recently discovered genetic mutation signatures found in MAFLD-driven HCC patients. We also critically review current rodent models suggested for MAFLD-driven HCC study.
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Affiliation(s)
- Michael Karin
- Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of MedicineUniversity of California San DiegoLa JollaCAUSA
| | - Ju Youn Kim
- Department of Molecular and Life ScienceHanyang University ERICAAnsanKorea
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38
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Chen C, Zhang D, Ye M, You Y, Song Y, Chen X. Effects of various exercise types on inflammatory response in individuals with overweight and obesity: a systematic review and network meta-analysis of randomized controlled trials. Int J Obes (Lond) 2025; 49:214-225. [PMID: 39420086 DOI: 10.1038/s41366-024-01649-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 09/25/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024]
Abstract
OBJECTIVE To explore effective exercise types for reducing chronic inflammation in individuals with overweight and obesity (IOO) while accounting for confounders. METHODS A systematic search for RCTs in English between January 2000 and August 2023 was conducted to evaluating exercise effects on inflammatory biomarkers in IOO. A network meta-analysis conducted. RESULTS A total of 123 RCTs were analyzed. Different exercise type yielded distinct effects on various inflammatory biomarkers. Specifically, aerobic exercise combined with resistance training (COM) and aerobic exercise (AE) were the most effective for improving leptin levels. AE exhibited the greatest effectiveness in reducing CRP and increasing adiponectin. High-intensity interval training (HIIT) was identified as the most effective exercise modality for ameliorating IL-6, TNF-α, and IL-10. Resistance training (RT) had the least effect compared to other exercise types. Meta regression and subgroup analyses revealed that high-intensity AE demonstrated a greater effect size compared to moderate-intensity AE. The impact of AE on IL-10 was positively associated with both the training period and the age of participants. Positive correlations were observed between reductions in body fat and the effect sizes of CRP, TNF-α, and IL-10. Gender influenced AE effects on IL-6 and TNF-α, with females responding better. CONCLUSION This study highlights the potential of exercise in alleviating the inflammatory status in IOO, with different exercise types showing various effects on specific inflammatory biomarkers. The intensity and duration of exercise had a dose-response relationship with intervention effectiveness. Changes in body composition correlated with the effectiveness of the intervention. COM, AE, and HIIT are recommended exercise approaches.
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Affiliation(s)
- Chaofan Chen
- Department of Physical Education, Tsinghua University, 100084, Beijing, China
| | - Dong Zhang
- Institute of Sports Artificial Intelligence, Capital University of Physical Education and Sports, 100084, Beijing, China
| | - Mingyi Ye
- Department of Kinesiology and Community Health, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
| | - Yanwei You
- Department of Physical Education, Tsinghua University, 100084, Beijing, China
| | - Yiling Song
- Department of Physical Education, Tsinghua University, 100084, Beijing, China
| | - Xiaoke Chen
- Department of Physical Education, Tsinghua University, 100084, Beijing, China.
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Abdulla A, Sadida HQ, Jerobin J, Elfaki I, Mir R, Mirza S, Singh M, Macha MA, Uddin S, Fakhro K, Bhat AA, Akil ASAS. Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link. JOURNAL OF THE NATIONAL CANCER CENTER 2025; 5:8-27. [PMID: 40040878 PMCID: PMC11873641 DOI: 10.1016/j.jncc.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/16/2024] [Accepted: 11/11/2024] [Indexed: 03/06/2025] Open
Abstract
Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8+ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.
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Affiliation(s)
- Alanoud Abdulla
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar
| | - Hana Q. Sadida
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar
| | - Jayakumar Jerobin
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Imadeldin Elfaki
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Rashid Mir
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Sameer Mirza
- Department of Chemistry, College of Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Mayank Singh
- Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Muzafar A. Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Pulwama, Jammu and Kashmir, India
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Laboratory of Animal Research Center, Qatar University, Doha, Qatar
| | - Khalid Fakhro
- Department of Human Genetics, Sidra Medicine, Doha, Qatar
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar
| | - Ajaz A. Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar
| | - Ammira S. Al-Shabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar
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Ouyang J, Yang Y, Xu Y, Wang Z, Zhou Y, Zhao H, Zhao H, Cai J, Ye F, Zhou J. How different body compositions affect the prognosis of HCC undergoing immunotherapy: the paradoxical phenomenon of BMI. LA RADIOLOGIA MEDICA 2025; 130:258-270. [PMID: 39671053 DOI: 10.1007/s11547-024-01933-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 11/12/2024] [Indexed: 12/14/2024]
Abstract
PURPOSE Body mass index (BMI) is associated with the prognosis of hepatocellular carcinoma (HCC) receiving immunotherapy. Body compositions are considered to account for this association, but this hypothesis has yet to be verified conclusively. MATERIAL AND METHODS Our study included 305 patients received immunotherapy at 3 centers between August 2018 and February 2022. We calculated skeletal muscle index (SMI), mean skeletal muscle density (SMD), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and visceral to subcutaneous adipose tissue area ratio (VSR) at lumbar 3 level. The influences of BMI and body compositions on overall survival (OS) were comprehensively described. RESULTS Sarcopenia (Low SMI, HR = 2.203, 95% CI:1.425-3.405, P < 0.001), myosteatosis (low SMD, HR = 2.013, 95% CI:1.246-3.252, P = 0.004) and visceral adipose deposition (high VATI, HR = 0.658, 95% CI:0.453-0.957, P = 0.028) were independent predictors of OS, while BMI was not. The prognosis of underweight (BMI < 20.0 kg/m2, P = 0.009) and obesity (BMI ≥ 25.0 kg/m2, P = 0.003) were significantly worse than normal weight (20.0 ≤ BMI ≤ 24.9 kg/m2), which might attribute to the differences in body compositions. High VATI had significantly improved OS than low VATI (P = 0.002), and the difference remained significant after propensity score matching (P = 0.017). CONCLUSION In HCC receiving immunotherapy, sarcopenia, myosteatosis, and visceral adipose deposition independently predicted OS, and visceral adipose was protective in OS. The effects of BMI on OS depended on body compositions.
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Affiliation(s)
- Jingzhong Ouyang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, China
| | - Yi Yang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ying Xu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhengzheng Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, China
| | - Yanzhao Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Feng Ye
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, China.
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Lin A, Pearl N, Flynn J, Devlin S, Dahi P, Perales MA, Scordo M, Shah GL. Influence of Obesity on the Efficacy and Toxicity of Patients Undergoing Autologous Hematopoietic Cell Transplantation for Lymphoma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025; 25:e90-e95. [PMID: 39343716 DOI: 10.1016/j.clml.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/05/2024] [Accepted: 09/06/2024] [Indexed: 10/01/2024]
Abstract
Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes. BACKGROUND Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking. PATIENTS AND METHODS We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78). RESULTS In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities. CONCLUSION In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.
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Affiliation(s)
- Andrew Lin
- Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY.
| | - Nicole Pearl
- Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Jessica Flynn
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sean Devlin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Parastoo Dahi
- Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Miguel-Angel Perales
- Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Michael Scordo
- Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Gunjan L Shah
- Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY
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Taunk K, Jajula S, Bhavsar PP, Choudhari M, Bhanuse S, Tamhankar A, Naiya T, Kalita B, Rapole S. The prowess of metabolomics in cancer research: current trends, challenges and future perspectives. Mol Cell Biochem 2025; 480:693-720. [PMID: 38814423 DOI: 10.1007/s11010-024-05041-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 05/18/2024] [Indexed: 05/31/2024]
Abstract
Cancer due to its heterogeneous nature and large prevalence has tremendous socioeconomic impacts on populations across the world. Therefore, it is crucial to discover effective panels of biomarkers for diagnosing cancer at an early stage. Cancer leads to alterations in cell growth and differentiation at the molecular level, some of which are very unique. Therefore, comprehending these alterations can aid in a better understanding of the disease pathology and identification of the biomolecules that can serve as effective biomarkers for cancer diagnosis. Metabolites, among other biomolecules of interest, play a key role in the pathophysiology of cancer whose levels are significantly altered while 'reprogramming the energy metabolism', a cellular condition favored in cancer cells which is one of the hallmarks of cancer. Metabolomics, an emerging omics technology has tremendous potential to contribute towards the goal of investigating cancer metabolites or the metabolic alterations during the development of cancer. Diverse metabolites can be screened in a variety of biofluids, and tumor tissues sampled from cancer patients against healthy controls to capture the altered metabolism. In this review, we provide an overview of different metabolomics approaches employed in cancer research and the potential of metabolites as biomarkers for cancer diagnosis. In addition, we discuss the challenges associated with metabolomics-driven cancer research and gaze upon the prospects of this emerging field.
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Affiliation(s)
- Khushman Taunk
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India
- Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, West Bengal, NH12 Simhat, Haringhata, Nadia, West Bengal, 741249, India
| | - Saikiran Jajula
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India
| | - Praneeta Pradip Bhavsar
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India
| | - Mahima Choudhari
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India
| | - Sadanand Bhanuse
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India
| | - Anup Tamhankar
- Department of Surgical Oncology, Deenanath Mangeshkar Hospital and Research Centre, Erandawne, Pune, Maharashtra, 411004, India
| | - Tufan Naiya
- Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, West Bengal, NH12 Simhat, Haringhata, Nadia, West Bengal, 741249, India
| | - Bhargab Kalita
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India.
- Amrita School of Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala, 682041, India.
| | - Srikanth Rapole
- Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, 411007, India.
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Goddard E, Pace D, Twells L, Neveu J. Laparoscopic bariatric surgery with hysterectomy for endometrial cancer to improve long-term outcomes: A review article. Int J Gynecol Cancer 2025; 35:100033. [PMID: 39971420 DOI: 10.1016/j.ijgc.2024.100033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Indexed: 02/21/2025] Open
Abstract
Endometrial cancer is the most common gynecologic malignant disease in Canada, and women with an elevated body mass index carry an increased lifetime risk of developing this disease. As rates of obesity have risen, the rates of endometrial cancer have seen a similar rise. Given this association, women diagnosed with endometrial cancer often suffer from several obesity-related co-morbidities, including type 2 diabetes, hypertension, and cardiovascular disease. Studies have suggested that women with early-stage endometrial cancer have a higher potential to die of obesity-related complications than recurrence and that weight reduction would be beneficial for these patients to improve quality-of-life and long-term obesity-related morbidity and mortality. Bariatric surgery is currently the only treatment modality to result in sustained long-term weight loss for this cohort of patients. Early evidence has suggested that combining bariatric surgery with total laparoscopic hysterectomy may improve the underlying metabolic disease, the patients' quality of life, and the long-term obesity-related morbidity and mortality. Additionally, the inclusion of bariatric surgery in treatment of patients with obesity and endometrial cancer may decrease the projected lifetime health care cost when compared to hysterectomy alone. This narrative review aims to examine the evidence surrounding endometrial cancer and its link to obesity. Further, we hope to explore current treatments for the aforementioned conditions and the possible benefits and feasibility of a combined intervention of vertical sleeve gastrectomy and total laparoscopic hysterectomy for patients with obesity and endometrial cancer.
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Affiliation(s)
- Emma Goddard
- Memorial University of Newfoundland Discipline of Obstetrics & Gynecology, St. John's, Canada.
| | - David Pace
- Memorial University of Newfoundland, Faculty of Medicine, Discipline of General Surgery (Bariatric Surgery), St. John's, Canada
| | - Laurie Twells
- Memorial University of Newfoundland, Faculty of Medicine, Division of Population Health and Applied Health Sciences, St. John's, Canada
| | - Joannie Neveu
- Memorial University of Newfoundland, Faculty of Medicine, Discipline of Obstetrics & Gynecology, Department of Gynecologic Oncology, St. John's, Canada
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Mao J, Qiu X, Zhang Y, Wang C, Yang X, Li Q. A systematic review and meta-analysis of randomized controlled trials for physical activity among colorectal cancer survivors: directions for future research. PeerJ 2025; 13:e18892. [PMID: 39902324 PMCID: PMC11789654 DOI: 10.7717/peerj.18892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 01/02/2025] [Indexed: 02/05/2025] Open
Abstract
Background Physical activity (PA) is critically important to cancer rehabilitation. However, PA levels are generally lower in colorectal cancer (CRC) survivors compared to other cancer survivors. The purpose of this study was to examine the effectiveness of PA interventions in increasing PA levels and to provide recommendations for developing PA interventions in CRC survivors. Methods A systematic literature search was conducted in Cochrane Library, Embase, PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, and Wan Fang Data from January 2010 to March 1, 2024. The Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of eligible studies, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method was used to evaluate the certainty of evidence. The random-effects model was used in meta-analysis, and data were analyzed using standardized mean differences and 95% confidence intervals. Results A total of 22 studies were included in this review, all of which were rated as having good methodological quality based on the PEDro scale. In the meta-analysis, nine of these studies involving 684 participants were included, and results showed that PA interventions have a positive effect on increasing total PA levels in CRC survivors (Z = 2.79, p = 0.005). Results of subgroup analysis revealed that supervised PA interventions (Z = 2.82, p = 0.005) and PA interventions with multiple intervention components (Z = 3.06, p = 0.002) effectively increased total PA levels for CRC survivors. In addition, research evidence suggests that daily as the frequency (Z = 4.28, p < 0.001), Moderate-to-vigorous physical activity (MVPA) as the intensity (Z = 2.29, p = 0.022), aerobic combined with resistance exercise as the type of PA (Z = 4.19, p < 0.001) is appropriate for increasing total PA levels in CRC survivors. Conclusions The findings of this review provide strong evidence supporting the positive role of PA interventions in improving total PA levels among CRC survivors. This study offers preliminary insights into the appropriate patterns of PA interventions (e.g., frequency, intensity, type) for enhancing total PA levels in CRC survivors. However, further high-quality clinical trials are needed to determine the optimal timing, duration, and delivery methods of PA interventions to maximize their effectiveness in this population.
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Affiliation(s)
- Jiayu Mao
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China
| | - Xiaoke Qiu
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China
| | - Yi Zhang
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China
| | - Can Wang
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China
| | - Xueli Yang
- Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
| | - Qiuping Li
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, China
- Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
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Shi S, Ou X, Liu C, Li R, Zheng Q, Hu L. NF-κB signaling and the tumor microenvironment in osteosarcoma: implications for immune evasion and therapeutic resistance. Front Immunol 2025; 16:1518664. [PMID: 39949765 PMCID: PMC11821961 DOI: 10.3389/fimmu.2025.1518664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/10/2025] [Indexed: 02/16/2025] Open
Abstract
Osteosarcoma, a highly aggressive malignancy with a generally poor prognosis, is characterized by tumor cells' ability to evade immune responses and resist treatment. The nuclear transcription factor NF-κB signaling pathway is crucial in regulating inflammatory and immune reactions. It occupies a central position in the development of the osteosarcoma tumor microenvironment. This research aimed to explore how NF-κB influences the recruitment and polarization of tumor-associated macrophages and myeloid-derived suppressor cells, both of which contribute to immunosuppression. Furthermore, NF-κB facilitates immune surveillance evasion in osteosarcoma cells by altering the expression of immune checkpoint molecules, such as PD-L1. It also enhances tumor cell resistance to chemotherapy and radiotherapy by activating anti-apoptotic signaling pathways and exacerbating treatment-induced inflammation. Potential therapeutic approaches include using NF-κB inhibitors, possibly in combination with immune checkpoint inhibitors, to overcome tumor cell resistance mechanisms and reshape antitumor immune responses. A thorough examination of NF-κB's role in osteosarcoma development is expected to yield novel clinical treatment strategies, and significantly improve patient prognosis by targeting this key signaling pathway.
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Affiliation(s)
| | | | | | | | | | - Leiming Hu
- Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, XI’an, China
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Nôga DA, Meth EMS, Pacheco AP, Cedernaes J, Xue P, Benedict C. Habitual sleep duration, healthy eating, and digestive system cancer mortality. BMC Med 2025; 23:44. [PMID: 39865237 PMCID: PMC11770963 DOI: 10.1186/s12916-025-03882-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 01/16/2025] [Indexed: 01/28/2025] Open
Abstract
BACKGROUND Lifestyle choices, such as dietary patterns and sleep duration, significantly impact the health of the digestive system and may influence the risk of mortality from digestive system cancer. METHODS This study aimed to examine the associations between sleep duration, dietary habits, and mortality from digestive system cancers. The analysis included 406,584 participants from the UK Biobank cohort (54.1% women; age range: 38-73 years), with sleep duration classified as short (≤ 6 h, 24.2%), normal (7-8 h, 68.4%), and long (≥ 9 h, 7.4%). Healthy eating habits were defined as a daily intake of at least 25 g of fibre, seven portions of fruits and vegetables, and fewer than four servings of meat per week. These dietary factors were combined into a score ranging from 0 (least healthy) to 3 (healthiest). Cox proportional hazards regression analyses were conducted, with a median follow-up period of 12.6 years, ending on September 30, 2021. RESULTS 3949 participants died from cancer of the digestive system. Both short and long sleep duration were associated with an increased risk of mortality from cancer of the digestive system (1.09 (1.01-1.18) and 1.14 (1.03-1.27), respectively). Additionally, a diet score ≥ 1 was linked to a lower cancer risk (0.72-0.91 (0.59-0.96)). Adjusting for smoking, type 2 diabetes, and body mass index (BMI) status eliminated the association between sleep duration and digestive cancer mortality. The association between healthy dietary patterns and the risk of digestive system cancer mortality did not vary by sleep duration. CONCLUSIONS Aberrant sleep durations may increase the risk of mortality from digestive system cancer, potentially through smoking, higher BMI, and type 2 diabetes. However, aberrant sleep durations do not seem to reduce the protective effects of a healthy dietary pattern.
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Affiliation(s)
- Diana A Nôga
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden.
| | - Elisa M S Meth
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
| | - André P Pacheco
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
- Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University Hospital, Sognsvannsveien 21, Oslo, 0372, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postboks 1039 Blindern, 0315, Oslo, Norway
| | - Jonathan Cedernaes
- Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Ing. 40, 5 Tr, Uppsala, 751 85, Sweden
- Department of Medical Cell Biology, Uppsala University, Box 571, Husargatan 3, Uppsala, 751 24, Sweden
| | - Pei Xue
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
| | - Christian Benedict
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
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Drewa J, Lazar-Juszczak K, Adamowicz J, Juszczak K. Periprostatic Adipose Tissue as a Contributor to Prostate Cancer Pathogenesis: A Narrative Review. Cancers (Basel) 2025; 17:372. [PMID: 39941741 PMCID: PMC11816168 DOI: 10.3390/cancers17030372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/03/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Periprostatic adipose tissue (PPAT) contributes to the pathogenesis of prostate cancer. The purpose of this study was to review and summarize the literature on the role of PPAT in prostate cancer pathogenesis. Moreover, we evaluated the clinical implication of PPAT in patients with prostate cancer. We performed a scoping literature review of PubMed from January 2002 to November 2024. Search terms included "periprostatic adipose tissue", "adipokines", and "prostate cancer". Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included PPAT, adipokines, and their role in prostate cancer biology and clinical features. In total 225 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the pathogenesis of PPAT as a contributor to prostate cancer biology and its aggressiveness. The review also presents new research directions for PPAT as a new target for the treatment of prostate cancer. Based on the current review, it can be stated that PPAT plays an important role in prostate cancer pathogenesis. Moreover, PPAT seems to be a promising target point when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer.
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Affiliation(s)
- Julia Drewa
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
| | - Katarzyna Lazar-Juszczak
- Primary Health Care Clinic of the Ujastek Medical Center, 31-752 Cracow, Poland
- Krakow University of Health Promotion, 31-158 Cracow, Poland
| | - Jan Adamowicz
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
- Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
| | - Kajetan Juszczak
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
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Qu G, Lyu SC, Zhang Y, Gao K, Zhou C. CT-based skeletal muscle loss predicts long term prognosis in patients with distal cholangiocarcinoma undergone pancreaticoduodenectomy. Sci Rep 2025; 15:2885. [PMID: 39843804 PMCID: PMC11754836 DOI: 10.1038/s41598-025-87458-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 01/20/2025] [Indexed: 01/24/2025] Open
Abstract
Skeletal muscle index (SMI), as an effective indicator of nutritional status, plays an important role in the prognosis of malignancy. However, the impact of skeletal muscle changes on tumor prognosis has not been systematically elaborated. We aimed to explore the value of skeletal muscle changes in the prognosis of distal cholangiocarcinoma (DCC) patients undergone pancreaticoduodenectomy (PD). Patients who underwent PD for DCC between 2015 and 2023 were included in this study. Demographic, laboratory and follow-up information was obtained. The cross-sectional images of skeletal muscle area at the level of the third lumbar spine was obtained based on computed tomography (CT), and the SMI was calculated by skeletal muscle mass through height squared normalization. Skeletal muscle index and skeletal muscle loss (SML) were obtained before PD and three to six months after surgery. Patients were classified into two groups (High-SML and Low-SML) based on the optimal SML cut-off value. The univariate and multivariate Cox proportional hazards analysis was conducted to evaluate the influence of SML in predicting over survival (OS) and recurrence free survival (RFS) of DCC. Of the 112 patients with distal cholangiocarcinoma, 55 (49%) were diagnosed with low SMI preoperatively. The best cut-off values of SML were - 4.01% and - 5.99% for OS and RFS. In multivariate analysis, tumor size > 2.0 cm (hazard ratio (HR) = 1.90, P = 0.017), poor differentiation (hazard ratio (HR) = 2.80, P > 0.001), higher SML (SML ≤ - 4.01%) (hazard ratio (HR) = 3.60, P < 0.001), lymph metastasis (hazard ratio (HR) = 4.00, P < 0.001) and vascular invasion (hazard ratio (HR) = 2.10, P = 0.013) were independent risk factors forOS. Meanwhile, poor differentiation (hazard ratio (HR) = 1.90, P = 0.043), higher SML (SML ≤ -5.99%) (hazard ratio (HR) = 3.80, P < 0.001) and lymph metastasis (hazard ratio (HR) = 2.60, P = 0.003) was an independent risk factor forRFS. The models combining SML and clinical characteristics had excellent predictive performance for OS and RFS. The nutritional status marker SML are effective and convenient indicators for predicting the long-term prognosis of DCC after PD, and the SMLafter PD is notable. The combination of CT quantified SML and clinical features can help clinicians predict the long-term survival of DCC patients after PD.
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Affiliation(s)
- Guangzhen Qu
- Department of Interventional Radiology, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China
| | - Yong Zhang
- Department of Interventional Radiology, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China
| | - Kun Gao
- Department of Interventional Radiology, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China
| | - Chuanguo Zhou
- Department of Interventional Radiology, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China.
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Gaber M, Quentel A, Holmes J, Lepetit C, Triki H, Wilson A, Payne V, Tenvooren I, Dehours C, Peoples A, Duet ML, Katz AJ, Pécot T, Bougras-Cartron G, Cartron PF, Cook KL, Vidi PA. Obesity increases DNA damage in the breast epithelium. Breast Cancer Res 2025; 27:11. [PMID: 39838489 PMCID: PMC11753040 DOI: 10.1186/s13058-025-01961-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 01/10/2025] [Indexed: 01/23/2025] Open
Abstract
Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue. In a mouse model of diet-induced obesity, weight gain was associated with elevated levels of DNA double-strand breaks in the mammary gland. We also found a positive correlation between BMI and DNA breaks in the breast epithelium of premenopausal women (but not postmenopausal women). High BMI was associated with elevated systemic and tissue-level oxidative DNA damage across the lifespan, and we propose that the breast epithelium undergoing menstruous proliferation waves is particularly prone to the generation of DNA breaks from oxidative lesions. Ancestry was an important modulator of the obesity-DNA break connection. Compared to non-Hispanic Whites, women identifying as African Americans had higher levels of DNA breaks, as well as elevated leptin and IGF-1. In 3D cultures of breast acini, both leptin and IGF-1 caused an accumulation of DNA damage. The results highlight a connection between premalignant genomic alterations in the breast epithelium and metabolic health modulated by obesity and ancestry. They call for attention on biological determinants of breast cancer risk disparities.
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Affiliation(s)
- Mohamed Gaber
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Arnaud Quentel
- Institut de Cancérologie de l'Ouest, Angers, F-49055, France
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France
| | - Julia Holmes
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | | | - Hana Triki
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France
- Institut de Cancérologie de l'Ouest, Saint Herblain, F-44805, France
- Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, Nantes, France
| | - Adam Wilson
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Valerie Payne
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Iliana Tenvooren
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Cloé Dehours
- Institut de Cancérologie de l'Ouest, Angers, F-49055, France
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France
| | - Abigail Peoples
- Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Mary L Duet
- Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Adam J Katz
- Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Thierry Pécot
- Biosit, UAR 3480 CNRS - US 18 Inserm, Rennes University, Rennes, F-35042, France
| | - Gwenola Bougras-Cartron
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France
- Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, Nantes, France
| | - Pierre-François Cartron
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France
- Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, Nantes, France
| | - Katherine L Cook
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Pierre-Alexandre Vidi
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
- Institut de Cancérologie de l'Ouest, Angers, F-49055, France.
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICAT, Angers, France.
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50
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Shou S, Liu R, He J, Jiang X, Liu F, Li Y, Zhang X, En G, Pu Z, Hua B, Pang B, Zhang X. Current and projected incidence rates of pancreatic cancer in 43 countries: an analysis of the Cancer Incidence in Five Continents database. BMJ Open Gastroenterol 2025; 12:e001544. [PMID: 39837792 PMCID: PMC11784423 DOI: 10.1136/bmjgast-2024-001544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 11/20/2024] [Indexed: 01/23/2025] Open
Abstract
OBJECTIVE The aetiology of pancreatic cancer is complex, and there is limited research on its incidence. We aimed to investigate the incidence trends of pancreatic cancer in 43 countries and predict trends up to 2030. METHODS The annual incidence of pancreatic cancer was obtained from the Cancer Incidence in Five Continents database, which comprises 108 cancer registries from 43 countries. Based on available data, we calculated age-standardized incidence rates (ASRs) per 100 000 people for 1988-2012. A Bayesian age-period-cohort model was used to predict the number of new cases and incidence rates up to 2030. RESULTS From 1988 to 2012, the global incidence rate of pancreatic cancer showed a continuously increasing trend, with the ASR increasing from 5.89 in 1988 to 6.78 in 2012, representing an overall average annual percentage change of 8.45%. This increasing trend is expected to persist in most selected countries, whereas a few countries are projected to exhibit a declining trend by 2030. CONCLUSION It appears that the future global incidence of pancreatic cancer is on the rise, but the rate of increase varies among different countries, with some showing a declining trend.
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Affiliation(s)
- Songting Shou
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Rui Liu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie He
- Department of Health Management, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Xiaochen Jiang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fudong Liu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi Li
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiyuan Zhang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Geer En
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhiqing Pu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Baojin Hua
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bo Pang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xing Zhang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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