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Ancona G. Clinical features of acquired lipodystrophy after total body irradiation: a case report and mini review. Curr Med Res Opin 2025:1-11. [PMID: 40340619 DOI: 10.1080/03007995.2025.2475090] [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: 08/06/2024] [Revised: 02/21/2025] [Accepted: 02/28/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Acquired partial lipodystrophy is a late complication of total body irradiation (TBI) performed during hematopoietic stem cell transplantation. Diagnosing this condition remains challenging due to its rarity and limited clinical awareness. Long-term patient observation is essential since this type of lipodystrophy develops more than a decade post-TBI. CASE REPORT We present a unique case of a patient with acquired lipodystrophy who underwent TBI for leukemia treatment in 2003 and was diagnosed with diabetes in 2013, but standard diabetes therapies proved ineffective. By 2018, the patient exhibited distinctive features, i.e. hirsutism, reduced lean mass, cutaneous alterations (including an umbilical psoriatic plaque), barrel chest, hepatomegaly, lipoatrophy of upper and lower limbs, acanthosis nigricans in the axillae and Cushingoid facies. In 2020, she was diagnosed with breast cancer, followed by liver, ovarian and pancreatic metastases in 2021. RESULTS In addition to this case report, we reviewed the literature on acquired lipodystrophy cases following TBI to compare their clinical features and phenotypes with those of our patient. This comparison aims to aid clinical practice by facilitating earlier diagnosis and treatment of lipodystrophy. CONCLUSION TBI can lead to acquired lipodystrophy, which is associated with severe comorbidities. Due to its diagnostic complexity, expert clinicians and a multidisciplinary approach are essential for early identification and appropriate treatment according to etiologic aspects. We hypothesize that this condition may serve as a model for studying metabolic dysfunction in fat-related diseases.
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Affiliation(s)
- Giuseppe Ancona
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
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2
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Luo Y, Liu J, Qu P, Han S, Li X, Wang Y, Su X, Zeng J, Li J, Deng S, Liang Q, Hou L, Cheng P. The crosstalk of breast cancer and ischemic heart disease. Cell Death Discov 2025; 11:185. [PMID: 40251177 PMCID: PMC12008236 DOI: 10.1038/s41420-025-02428-6] [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: 08/06/2024] [Revised: 03/07/2025] [Accepted: 03/21/2025] [Indexed: 04/20/2025] Open
Abstract
In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.
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Affiliation(s)
- Yunbo Luo
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jun Liu
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China
| | - Peng Qu
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Shiqi Han
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xue Li
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Yali Wang
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xiaohan Su
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Jiao Zeng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jinsui Li
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Shishan Deng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Qi Liang
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
| | - Lingmi Hou
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
| | - Panke Cheng
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China.
- Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Chengdu, 610072, P.R. China.
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3
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Pan Z, Tan Z, Xu N, Yao Z, Zheng C, Shang J, Xie L, Xu J, Wang J, Jiang L, Zhu X, Yu D, Li Y, Che Y, Gong Y, Qin Z, Zhang Y, Zou X, Xu T, Guo Z, Jin T, Guo T, Wang W, Chen W, Sun Y, Wang W, Peng X, Yin C, Ding C, Huang P, Ge M. Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers. Nat Commun 2025; 16:3601. [PMID: 40234451 PMCID: PMC12000556 DOI: 10.1038/s41467-025-58910-3] [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: 08/19/2024] [Accepted: 04/03/2025] [Indexed: 04/17/2025] Open
Abstract
Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) present major challenges in treatment owing to extreme aggressiveness and high heterogeneity. In this study, deep-scale analyses spanning genomic, proteomic, and phosphoproteomic data are performed on 348 thyroid-cancer and 119 tumor-adjacent samples. TP53 (48%), TERT promoter (36.5%), and BRAF (23%) are most frequently mutated in PDTC and ATC. Ribosome biogenesis is identified as a common hallmark of ATC, and RRP9 silencing dramatically inhibits tumor growth. Proteomic clustering identified three ATC/PDTC subtypes. Pro-I subtype is characterized with aberrant insulin signaling and low immune cell infiltration, and Pro-II is featured with DNA repair signaling, while Pro-III harbors high frequency of TP53 and BRAF mutation and intensive C5AR1+ myeloid infiltration. Targeting C5AR1 synergistically improves antitumor effect of PD-1 blockade against ATC cell-derived tumors. These findings provide systematic insights into tumor biology and opportunities for drug discovery, accelerating precision therapy for virulent thyroid cancers.
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Affiliation(s)
- Zongfu Pan
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Zhuo Tan
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ning Xu
- Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China
| | - Zhenmei Yao
- Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China
| | - Chuanming Zheng
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Jinbiao Shang
- Department of Thyroid Surgery, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, China
| | - Lei Xie
- Department of Head and Neck Surgery, The Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jiajie Xu
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Jiafeng Wang
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Liehao Jiang
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Xuhang Zhu
- Department of Thyroid Surgery, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, China
| | - Dingyi Yu
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Ying Li
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Yulu Che
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Yingying Gong
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Zhaoyu Qin
- Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China
| | - Yiwen Zhang
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Xiaozhou Zou
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Tong Xu
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Zhenying Guo
- Department of Pathology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Tiefeng Jin
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Tiannan Guo
- School of Medicine, Westlake University, Hangzhou, China
| | - Wei Wang
- Department of Pathology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Wanyuan Chen
- Department of Pathology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
| | - Yaoting Sun
- School of Medicine, Westlake University, Hangzhou, China
| | - Weixin Wang
- Hangzhou Cosmos Wisdom Biotechnology Co. Ltd, Hangzhou, China
| | - Xiaojun Peng
- Hangzhou Cosmos Wisdom Biotechnology Co. Ltd, Hangzhou, China
| | - Changtian Yin
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Chen Ding
- Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
| | - Ping Huang
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China.
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China.
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China.
| | - Minghua Ge
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China.
- Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China.
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Zhejiang Provincial People's Hospital, Hangzhou, China.
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4
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Hong Y, He J, Deng D, Liu Q, Zu X, Shen Y. Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer. J Transl Med 2025; 23:439. [PMID: 40229646 PMCID: PMC11995514 DOI: 10.1186/s12967-025-06367-9] [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: 12/09/2024] [Accepted: 03/08/2025] [Indexed: 04/16/2025] Open
Abstract
Breast cancer is one of the most prevalent malignant tumors among women and ranks as the second leading cause of cancer-related deaths in females, primarily due to delays in diagnosis and shortcomings in treatment strategies. Consequently, there is a pressing need to identify reliable therapeutic targets and strategies. In recent years, the identification of effective biomarkers-particularly novel molecular therapeutic targets-has become a focal point in breast cancer research, aimed at predicting disease aggressiveness and monitoring treatment responses. Simultaneously, advancements in understanding the molecular mechanisms underlying cellular programmed death have opened new avenues for targeting kinase-regulated programmed cell death as a viable therapeutic strategy. This review summarizes the latest research progress regarding kinase-regulated programmed death (including apoptosis, pyroptosis, autophagy, necroptosis, and ferroptosis) in breast cancer treatment. It covers the key kinases involved in this mechanism, their roles in the onset and progression of breast cancer, and strategies for modulating these kinases through pharmacological interventions.
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Affiliation(s)
- Yun Hong
- Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jun He
- Department of Spine Surgery, The Nanhua Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, China
| | - Dan Deng
- Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Qinyue Liu
- Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-Incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xuyu Zu
- Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
- Hunan Provincial Clinical Medical Research Center for Drug Evaluation of major chronic diseases, Hengyang, China.
| | - Yingying Shen
- Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
- Hunan Provincial Clinical Medical Research Center for Drug Evaluation of major chronic diseases, Hengyang, China.
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Palanisamy B, Mandal AKA. Unlocking the potential: Receptor-mediated targeted drug delivery in cancer therapy. Pathol Res Pract 2025; 270:155955. [PMID: 40209568 DOI: 10.1016/j.prp.2025.155955] [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: 11/28/2024] [Revised: 03/29/2025] [Accepted: 04/06/2025] [Indexed: 04/12/2025]
Abstract
Receptor-mediated targeted drug delivery has emerged as a pivotal strategy in cancer therapy, offering precision and specificity in combating malignant diseases while minimizing systemic toxicity. This review explores the multifaceted role of receptors in cancer biology, emphasizing their contributions to cancer progression, metastasis, and their potential as therapeutic targets. Ligand-based targeting approaches highlight the utility of small molecules, peptides, and antibodies, as well as the development of novel targeting ligands. A critical focus is placed on engineering receptor-targeted nanoparticles and advanced drug delivery systems. Innovations in dual-targeting strategies and the targeted delivery to the tumour microenvironment (TME) and metastatic niches are discussed, underscoring their potential to enhance therapeutic efficacy. Additionally, receptor-targeted imaging is reviewed for its dual role in diagnosis and real-time treatment monitoring. To address the challenges of side effects and off-target toxicity, strategies that minimize these risks while targeting overexpressed receptors in solid tumours are explored. Finally, the review outlines future directions in receptor-targeted cancer therapy, emphasizing the need for interdisciplinary research to refine these strategies further. This comprehensive analysis aims to provide a roadmap for advancing receptor-based therapeutic approaches, ultimately improving outcomes for cancer patients.
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Affiliation(s)
- Balaji Palanisamy
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
| | - Abul Kalam Azad Mandal
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
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Mejza M, Bajer A, Wanibuchi S, Małecka-Wojciesko E. Can AI Be Useful in the Early Detection of Pancreatic Cancer in Patients with New-Onset Diabetes? Biomedicines 2025; 13:836. [PMID: 40299428 PMCID: PMC12025102 DOI: 10.3390/biomedicines13040836] [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] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/12/2025] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open
Abstract
Pancreatic cancer is one of the most lethal neoplasms. Despite considerable research conducted in recent decades, not much has been achieved to improve its survival rate. That may stem from the lack of effective screening strategies in increased pancreatic cancer risk groups. One population that may be appropriate for screening is new-onset diabetes (NOD) patients. Such a conclusion stems from the fact that pancreatic cancer can cause diabetes several months before diagnosis. The most widely used screening tool for this population, the ENDPAC (Enriching New-Onset Diabetes for Pancreatic Cancer) model, has not achieved satisfactory results in validation trials. This provoked the first attempts at using artificial intelligence (AI) to create larger, multi-parameter models that could better identify the at-risk population, which would be suitable for screening. The results shown by the authors of these trials seem promising. Nonetheless, the number of publications is limited, and the downfalls of using AI are not well highlighted. This narrative review presents a summary of previous publications, recent advancements and feasible solutions for effective screening of patients with NOD for pancreatic cancer.
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Affiliation(s)
- Maja Mejza
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland; (M.M.); (A.B.)
| | - Anna Bajer
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland; (M.M.); (A.B.)
| | - Sora Wanibuchi
- Aichi Medical University Hospital, Nagakute 480-1195, Japan;
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland; (M.M.); (A.B.)
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7
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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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8
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Tian L, Wang Y, Guan J, Zhang L, Fan J. The Prognostic Value and Immunomodulatory Role of Spsb2, a Novel Immune Checkpoint Molecule, in Hepatocellular Carcinoma. Genes (Basel) 2025; 16:346. [PMID: 40149497 PMCID: PMC11941779 DOI: 10.3390/genes16030346] [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: 02/21/2025] [Revised: 03/13/2025] [Accepted: 03/14/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Liver cancer, specifically hepatocellular carcinoma (LIHC), ranks as the second most common cause of cancer-related fatalities globally. Moreover, the occurrence rate of LIHC is steadily increasing. A recently identified gene, SPSB2, has been implicated in cell signaling, impacting the development and progression of non-small cell lung cancer. Nevertheless, studies on the role of SPSB2 in the pathogenesis of LIHC are lacking. METHODS Using the TCGA, GTEx, and GEO databases, we obtained differentially expressed genes that affect the prognosis of patients with LIHC. We utilized the Kruskal-Wallis test, along with univariate and multivariate COX regression analyses, to determine the correlation between SPSB2 and patient clinical indicators. Potential biological functions of SPSB2 in LIHC were explored by enrichment analysis, ssGSEA, and Spearman correlation analysis. Finally, LIHC cell lines Huh7 and SMMC-7721 were used to validate the biological function of SPSB2. RESULTS The results showed LIHC patients with higher SPSB2 expression had a poorer prognosis, and SPSB2 expression was significantly correlated with LIHC patients' Histologic grade, Pathologic T stage, Prothrombin time, Pathologic stage, BMI, weight, adjacent hepatic tissue inflammation, AFP level, and OS event (p < 0.05). SPSB2 shows notable enrichment in pathways linked to tumorigenesis and the immune system. Moreover, its expression is strongly connected to immune cells and immune checkpoints. Knockdown of SPSB2 expression in Huh7 cells and SMMC-7721 cells inhibits SPSB2's biological functions, including proliferation, invasion, metastasis, and other phenotypes. CONCLUSIONS SPSB2 plays a crucial role in the development of LIHC. It is related to the immune response and unfavorable outcomes. SPSB2 may function as a clinical biomarker for prognosis.
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Affiliation(s)
- Lv Tian
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Yiming Wang
- School of Nursing, Jilin University, Changchun 130021, China
| | - Jiexin Guan
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Lu Zhang
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Jun Fan
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 611731, China
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9
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Shaham SH, Vij P, Tripathi MK. Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions. Biomedicines 2025; 13:642. [PMID: 40149618 PMCID: PMC11940796 DOI: 10.3390/biomedicines13030642] [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: 01/30/2025] [Revised: 02/22/2025] [Accepted: 02/25/2025] [Indexed: 03/29/2025] Open
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, necessitating the continuous evolution of therapeutic approaches. Despite advancements in early detection and localized treatments, metastatic colorectal cancer (mCRC) poses significant challenges due to low survival rates and resistance to conventional therapies. This review highlights the current landscape of CRC treatment, focusing on chemotherapy and targeted therapies. Chemotherapeutic agents, including 5-fluorouracil, irinotecan, and oxaliplatin, have significantly improved survival but face limitations such as systemic toxicity and resistance. Targeted therapies, leveraging mechanisms like VEGF, EGFR, and Hedgehog pathway inhibition, offer promising alternatives, minimizing damage to healthy tissues while enhancing therapeutic precision. Furthermore, future directions in CRC treatment include exploring innovative targets such as Wnt/β-catenin, Notch, and TGF-β pathways, alongside IGF/IGF1R inhibition. These emerging strategies aim to address drug resistance and improve patient outcomes. This review emphasizes the importance of integrating molecular insights into drug development, advocating for a more personalized approach to combat CRC's complexity and heterogeneity.
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Affiliation(s)
- Salique H. Shaham
- Medicine and Oncology ISU, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Puneet Vij
- Department of Pharmaceutical Sciences, St. John’s University, 8000 Utopia Parkway, Queens, New York, NY 11439, USA;
| | - Manish K. Tripathi
- Medicine and Oncology ISU, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA
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10
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Ajadee A, Mahmud S, Sarkar A, Noor T, Ahmmed R, Haque Mollah MN. Screening of common genomic biomarkers to explore common drugs for the treatment of pancreatic and kidney cancers with type-2 diabetes through bioinformatics analysis. Sci Rep 2025; 15:7363. [PMID: 40025145 PMCID: PMC11873208 DOI: 10.1038/s41598-025-91875-3] [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: 08/30/2024] [Accepted: 02/24/2025] [Indexed: 03/04/2025] Open
Abstract
Type 2 diabetes (T2D) is a crucial risk factor for both pancreatic cancer (PC) and kidney cancer (KC). However, effective common drugs for treating PC and/or KC patients who are also suffering from T2D are currently lacking, despite the probability of their co-occurrence. Taking disease-specific multiple drugs during the co-existence of multiple diseases may lead to adverse side effects or toxicity to the patients due to drug-drug interactions. This study aimed to identify T2D-, PC and KC-causing common genomic biomarkers (cGBs) highlighting their pathogenetic mechanisms to explore effective drugs as their common treatment. We analyzed transcriptomic profile datasets, applying weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis approaches to identify T2D-, PC-, and KC-causing cGBs. We then disclosed common pathogenetic mechanisms through gene ontology (GO) terms, KEGG pathways, regulatory networks, and DNA methylation of these cGBs. Initially, we identified 78 common differentially expressed genes (cDEGs) that could distinguish T2D, PC, and KC samples from controls based on their transcriptomic profiles. From these, six top-ranked cDEGs (TOP2A, BIRC5, RRM2, ALB, MUC1, and E2F7) were selected as cGBs and considered targets for exploring common drug molecules for each of three diseases. Functional enrichment analyses, including GO terms, KEGG pathways, and regulatory network analyses involving transcription factors (TFs) and microRNAs, along with DNA methylation and immune infiltration studies, revealed critical common molecular mechanisms linked to PC, KC, and T2D. Finally, we identified six top-ranked drug molecules (NVP.BHG712, Irinotecan, Olaparib, Imatinib, RG-4733, and Linsitinib) as potential common treatments for PC, KC and T2D during their co-existence, supported by the literature reviews. Thus, this bioinformatics study provides valuable insights and resources for developing a genome-guided common treatment strategy for PC and/or KC patients who are also suffering from T2D.
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Affiliation(s)
- Alvira Ajadee
- Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Sabkat Mahmud
- Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Arnob Sarkar
- Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh
- Department of Biochemistry & Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Tasfia Noor
- Department of Computer Science and Engineering, Rajshahi University of Engineering & Technology (RUET), Rajshahi, 6204, Bangladesh
| | - Reaz Ahmmed
- Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh
- Department of Biochemistry & Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Md Nurul Haque Mollah
- Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh.
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11
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Liu Y, Zhang Q, Huang X. Effect of metformin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from real-world studies. Prostate Cancer Prostatic Dis 2025; 28:210-219. [PMID: 39014063 DOI: 10.1038/s41391-024-00871-7] [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: 03/31/2024] [Revised: 06/14/2024] [Accepted: 07/08/2024] [Indexed: 07/18/2024]
Abstract
PURPOSE Metformin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between metformin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of metformin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. METHODS A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of metformin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS The across studies results show that metformin use associated with lower incidence of PCa (RR: 0.82, 95% CI: 0.74-0.91). Metformin use was also found to reduce PCa recurrence, but the results were not statistically significant (RR: 0.97, 95% CI: 0.81-1.15). Metformin use was not associated with PCa mortality (RR: 0.94, 95% CI: 0.81-1.09). The results of subgroup analyses indicated that the type of study was a cohort study and the population came from both Asia and Europe showed that taking metformin reduced the incidence of PCa. A linear correlation was found between the duration of metformin use and its protective effect. CONCLUSIONS This meta-analysis revealed an independent correlation between metformin use and reduced incidence of PCa. Metformin use was not associated with either PCa recurrence rate or mortality. Furthermore, the effect of metformin on PCa incidence was found to be related to duration.
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Affiliation(s)
- Yuchen Liu
- Nanchang University Queen Mary School, Nanchang, Jiangxi, PR China
| | - Qingfang Zhang
- Nanchang University Queen Mary School, Nanchang, Jiangxi, PR China
| | - Xuan Huang
- Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, PR China.
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12
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Li F, Gao T, Li Z, Dou H, Ba Y, Jia S, Luo D, Xiao M. Triglyceride-glucose index and triglyceride-glucose-body mass index as prognostic factors for early stage breast cancer patients receiving neoadjuvant chemotherapy. Transl Oncol 2025; 53:102292. [PMID: 39884219 PMCID: PMC11814653 DOI: 10.1016/j.tranon.2025.102292] [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: 08/07/2024] [Revised: 01/13/2025] [Accepted: 01/21/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Insulin resistance (IR) is closely associated with the risk of breast cancer. The triglyceride-glucose (TyG) index and the triglyceride-glucose-body mass index (TyG-BMI) are considered surrogate indicators of IR; however, their prognostic value in breast cancer patients has not been discussed. The purpose of this study is not only to explore whether the TyG index and the TyG-BMI can predict the chemotherapy response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NACT) but also to investigate the possible mediating mechanism and to analyze the relationship between TyG-related enzyme expression and drug resistance and prognosis. METHODS From November 2011 to December 2018, a total of 335 breast cancer patients referred to Harbin Medical University Cancer Hospital who received NACT and surgery were registered in this retrospective study. The TyG index and TyG-BMI before the first chemotherapy were retrospectively calculated. Tissue samples of breast cancer patients were obtained from the Cancer Genome Atlas database, and the associations between the expression levels of the FBP1 and G6PD enzymes and the clinicopathological features and prognosis of breast cancer were analyzed. RESULTS In receiver operating characteristic analyses, the optimal cutoff values for the TyG and TyG-BMI were determined at 8.01 and 194.91, respectively. Low levels of the TyG and TyG-BMI were not associated with pathological complete response. In multivariate analysis, high TyG was an independent prognostic factor for shorter disease-free survival (DFS; HR = 2.402, P = 0.008) and overall survival (OS; HR = 3.206, P = 0.010). After adjustments for the age group, cT stage group, and cN stage group, the dose-response relationships between TyG, TyG-BMI, and survival outcomes showed a linear correlation by restricted cubic spline analyses. Lg-transformed BMI did not significantly (P > 0.05) mediate the recurrence, metastasis, and deaths associated with TyG. The expressions of two enzymes related to TyG, FBP1 and G6PD, were higher in breast cancer tissues than in the adjacent normal tissues and were associated with the TNM stage. Survival analysis shows that patients with high expressions of FBP1 and G6PD have a shorter OS. CONCLUSION This study suggests that the TyG index level before NACT is an independent prognostic factor for DFS and OS and can serve as a promising biomarker to predict the long-term prognosis of breast cancer patients undergoing NACT. Moreover, the TyG index and TyG-BMI show a linear correlation with DFS and OS. The effect of the TyG index on DFS and OS is not significantly mediated by lg-transformed BMI. Besides, FBP1 and G6PD are prognostic indicators for breast cancer patients and may serve as biomarkers for the clinical diagnosis and treatment of breast cancer.
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Affiliation(s)
- Fucheng Li
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Tian Gao
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Zhaoting Li
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - He Dou
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Yuling Ba
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Siyuan Jia
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Danli Luo
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Min Xiao
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang 150081, China.
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13
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Hashimoto H, Nojiri S, Takeda T, Urasaki W, Nishizaki Y, Nagahara A, Aoki S. Examining associations of digestive system cancer with hypertension and diabetes using network analysis in older patients. Sci Rep 2025; 15:6458. [PMID: 39987328 PMCID: PMC11846871 DOI: 10.1038/s41598-025-90734-5] [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: 09/21/2024] [Accepted: 02/14/2025] [Indexed: 02/24/2025] Open
Abstract
Hypertension and diabetes are prevalent among older people and may be associated with cancer. Although several network analyses have been conducted to visualize the associations between diseases and relevant factors, to the best of our knowledge, none have focused on visualizing the associations between cancer and other diseases. We conducted a network analysis to explore the associations between cancer, hypertension, and diabetes. This study used a large-scale clinical dataset of 1,026,305 hospitalized patients aged ≥ 65 years, collected between April 2008 and December 2020. Diseases were categorized using the International Classification of Diseases-10 (2019 version) codes. The analysis focused on diseases with a prevalence of ≥ 1%. A multimorbidity network was constructed for the entire patient cohort, and the same analysis was applied specifically to cancer patients. Hypertension (degree centrality: 58/61) and diabetes (degree centrality: 56/61) were connected to several diseases, indicating significant multimorbidity in the cohort. The associations (observed-to-expected ratio) between digestive system cancers and hypertension and diabetes were relatively stronger than those between the diseases and other cancers. Type 2 diabetes and essential hypertension may be risk factors of cancers at multiple digestive system sites. Early treatment of these conditions could prevent or delay the progression of digestive system cancers.
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Affiliation(s)
- Hidenori Hashimoto
- Data Science, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Shuko Nojiri
- Medical Technology Innovation Center, Juntendo University, Tokyo, Japan
- Clinical Research and Trial Center, Juntendo University School of Medicine, Juntendo Hospital, Tokyo, Japan
| | - Tsutomu Takeda
- Department of Gastroenterology, Faculty of Medicine, Juntendo University, Tokyo, Japan
| | - Wataru Urasaki
- Clinical Research and Trial Center, Juntendo University School of Medicine, Juntendo Hospital, Tokyo, Japan
- Department of Information Sciences, Tokyo University of Science, Chiba, Japan
| | - Yuji Nishizaki
- Data Science, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
- Division of Medical Education, Faculty of Medicine, Juntendo University, Tokyo, Japan.
- Clinical Translational Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Akihito Nagahara
- Department of Gastroenterology, Faculty of Medicine, Juntendo University, Tokyo, Japan
- Department of Pathophysiological Research and Therapeutics for Gastrointestinal Diseases, Juntendo University, Tokyo, Japan
| | - Shigeki Aoki
- Data Science, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Faculty of Health Data Science, Juntendo University, Tokyo, Japan
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14
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Park MN, Choi J, Maharub Hossain Fahim M, Asevedo EA, Nurkolis F, Ribeiro RIMA, Kang HN, Kang S, Syahputra RA, Kim B. Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy. Front Pharmacol 2025; 16:1504618. [PMID: 40034825 PMCID: PMC11872924 DOI: 10.3389/fphar.2025.1504618] [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: 10/01/2024] [Accepted: 01/20/2025] [Indexed: 03/05/2025] Open
Abstract
Achyranthes japonica (Miq.) Nakai (AJN) and Melandrium firmum (Siebold and Zucc.) Rohrb. (MFR) are medicinal plants recognized for their bioactive phytochemicals, including ecdysteroids, anthraquinones, and flavonoids. This study investigates the anticancer properties of key constituents of these plants, focusing on the BK002 formulation, a novel combination of AJN and MFR. Specifically, the research employs advanced molecular docking and in silico analyses to assess the interactions of bioactive compounds ecdysterone, inokosterone, and 20-hydroxyecdysone (20-HE) with key prostate cancer-related network proteins, including 5α-reductase, CYP17, DNMT1, Dicer, PD-1, and PD-L1. Molecular docking techniques were applied to evaluate the binding affinities contributions of the bioactive compounds in BK002 against prostate cancer-hub network targets. The primary focus was on enzymes like 5α-reductase and CYP17, which are central to androgen biosynthesis, as well as on cancer-related proteins such as DNA methyltransferase 1 (DNMT1), Dicer, programmed death-1 (PD-1), and programmed death ligand-1 (PD-L1). Based on data from prostate cancer patients, key target networks were identified, followed by in silico analysis of the primary bioactive components of BK002.In silico assessments were conducted to evaluate the safety profiles of these compounds, providing insights into their therapeutic potential. The docking studies revealed that ecdysterone, inokosterone, and 20-hydroxyecdysonec demonstrated strong binding affinities to the critical prostate cancer-related enzymes 5α-reductase and CYP17, contributing to a potential reduction in androgenic activity. These compounds also exhibited significant inhibitory interactions with DNMT1, Dicer, PD-1, and PD-L1, suggesting a capacity to interfere with key oncogenic and immune evasion pathways. Ecdysterone, inokosterone, and 20-hydroxyecdysone have demonstrated the ability to target key oncogenic pathways, and their favorable binding affinity profiles further underscore their potential as novel therapeutic agents for prostate cancer. These findings provide a strong rationale for further preclinical and clinical investigations, supporting the integration of BK002 into therapeutic regimens aimed at modulating tumor progression and immune responses.
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Affiliation(s)
- Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Jinwon Choi
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | | | - Estéfani Alves Asevedo
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
- Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
| | - Fahrul Nurkolis
- Department of Biological Sciences, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, Indonesia
| | | | - Han Na Kang
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Sojin Kang
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Rony Abdi Syahputra
- Department of Biological Sciences, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, Indonesia
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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15
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Liu K, Wang W, Liu Y, Li J, Ma C, Tian Y, Dong Z, Zhu L, Wei W, Ren M, Wu S, Liu S. Correlation of cumulative fasting blood glucose exposure with gastrointestinal cancers: A prospective cohort study. Medicine (Baltimore) 2025; 104:e41529. [PMID: 39960953 PMCID: PMC11835132 DOI: 10.1097/md.0000000000041529] [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: 08/03/2024] [Accepted: 01/27/2025] [Indexed: 02/20/2025] Open
Abstract
At present, there is a lack of research on the correlation between cumFPG and digestive malignancies, and previous cohort studies have not considered the competitive risk between death and digestive malignancies, which may overestimate the impact of related risk factors. To explore the correlation between cumFPG and malignant tumors of the digestive system. In this study, 53,747 participants who had undergone 3 consecutive physical examinations since 2006 were collected. Finally, a total of 53,747 participants were included in this study. According to the grouping method of previous studies, cumFPG was divided into 4 groups according to the quartile. Cox regression model and competitive risk model were used to assess the risk of new digestive system malignancy. In sensitivity analyses, participants with cancer within 5 years of follow-up were excluded to eliminate the possibility of reverse causation. Subjects taking hypoglycemic drugs were excluded to eliminate the effect of the drug on blood glucose. Restricted cubic splineregresion (RCS) was then used to calculate the relationship between cumFPG and GI cancers. The mean age of participants was 49.02 ± 11.78 years. During a mean follow-up of 10.58 years, 817 new Gastrointestinal cases were identified, and the Cox proportional hazards model suggested that the risk of incidence in the Q2 to Q4 group increased sequentially compared with the lowest Q1 group, even after excluding the diagnosis of digestive malignancy within 5 years, the participants taking hypoglycemic drugs, and the death competition risk model analysis. In site-specific analysis, we observed that this risk was more pronounced in colorectal cancer, liver cancer, and pancreatic cancer, while gastric cancer, small bowel cancer, and bile duct cancer all had a similar trend to the main model but were not statistically significant, while esophageal cancer was U-shaped but not statistically significant. RCS results showed that cumFPG was associated with a similar risk of digestive system tumors, showing an inverted "√" type relationship. High levels of cumFPG are an independent factor in malignancy of the digestive system. cumFPG can provide a new idea for the prevention of Gastrointestinal cancers.
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Affiliation(s)
- Kuan Liu
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Wanchao Wang
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Ye Liu
- Affiliated Hospital of North China University of Science and Technology, Breast Disease Treatment Center, Tangshan, Hebei, China
| | - Jiaxing Li
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Chao Ma
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Yuan Tian
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Zhigang Dong
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Lichao Zhu
- Affiliated Hospital of North China University of Science and Technology, GastrointestinalOncology Treatment Center, Tangshan, Hebei, China
| | - Wenqiang Wei
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Minqiang Ren
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
| | - Shouling Wu
- Kailuan Employee Health Examination Center, Tangshan, Hebei, China
| | - Siqing Liu
- Affiliated Hospital of North China University of Science and Technology, Department of Hepatobiliary and Pancreatic Surgery, Tangshan, Hebei, China
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Bora Yildiz C, Du J, Mohan KN, Zimmer-Bensch G, Abdolahi S. The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma. Epigenomics 2025; 17:125-140. [PMID: 39829063 PMCID: PMC11792803 DOI: 10.1080/17501911.2024.2442297] [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: 05/13/2024] [Accepted: 12/10/2024] [Indexed: 01/22/2025] Open
Abstract
Gliomas, highly aggressive tumors of the central nervous system, present overwhelming challenges due to their heterogeneity and therapeutic resistance. Glioblastoma multiforme (GBM), the most malignant form, underscores this clinical urgency due to dismal prognosis despite aggressive treatment regimens. Recent advances in cancer research revealed signaling pathways and epigenetic mechanisms that intricately govern glioma progression, offering multifaceted targets for therapeutic intervention. This review explores the dynamic interplay between signaling events and epigenetic regulation in the context of glioma, with a particular focus on the crucial roles played by non-coding RNAs (ncRNAs). Through direct and indirect epigenetic targeting, ncRNAs emerge as key regulators shaping the molecular landscape of glioblastoma across its various stages. By dissecting these intricate regulatory networks, novel and patient-tailored therapeutic strategies could be devised to improve patient outcomes with this devastating disease.
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Affiliation(s)
- Can Bora Yildiz
- Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, Aachen, Germany
- Research Training Group 2416 Multi Senses – Multi Scales, RWTH Aachen University, Aachen, Germany
| | - Jian Du
- Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, Aachen, Germany
| | - K. Naga Mohan
- Molecular Biology and Genetics Laboratory, Department of Biological Sciences, Hyderabad, India
| | - Geraldine Zimmer-Bensch
- Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, Aachen, Germany
- Research Training Group 2416 Multi Senses – Multi Scales, RWTH Aachen University, Aachen, Germany
| | - Sara Abdolahi
- Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University, Aachen, Germany
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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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Mackawy AMH, Alharbi M, Badawy MEH, Alharbi HOA. Knowledge and Awareness of Obesity-Related Breast Cancer Risk Among Women in the Qassim Region, Saudi Arabia: A Cross-Sectional Study. Healthcare (Basel) 2025; 13:278. [PMID: 39942467 PMCID: PMC11816457 DOI: 10.3390/healthcare13030278] [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: 11/25/2024] [Revised: 01/21/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Breast cancer (BC) is a major health concern globally and the second leading cause of cancer-related mortality in women in Saudi Arabia. Although peoples' awareness of BC risk factors has been previously examined, studies on obesity-related BC awareness in the Qassim region are inconclusive. We aimed to evaluate knowledge and awareness of obesity-related BC risk among Saudi women in the Qassim region. Methods: This is a cross-sectional study with a stratified random sampling technique of 400 Saudi women randomly selected from the Qassim region through an online platform and community health centers. An online closed-ended pretested validated structured questionnaire was completed by the participants using a Google Forms link. The categorical variables were frequency and percentage. The chi-square test was used to study the relationship between the dependent and independent variables. Results: There is moderate to poor knowledge regarding breast cancer risk factors. The results showed poor knowledge about obesity after menopause as a risk factor for BC (49%). Over half of the participants (51.0%) did not consider obesity a BC risk factor. The need for self-examinations and mammogram screenings showed moderate (59.6%) and poor awareness levels (4.75%). Conclusions: The findings highlight a noticeable gap in knowledge and awareness about obesity-related BC risks, as well as a limited awareness of the need for breast self-examinations and mammogram screenings. These results underscore the urgent need for targeted awareness campaigns and educational programs in the Qassim region to address this critical health issue. Promoting breast self-examination practices, weight management, and regular mammogram screenings could significantly enhance early detection, improve prognosis, and reduce BC-related mortality among Saudi women in the Qassim region.
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Affiliation(s)
- Amal Mohamad Husein Mackawy
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Almulaida 52571, Saudi Arabia
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig City 7120730, Egypt
| | - Manal Alharbi
- Medical Laboratory Specialist, Medical Laboratory, Applied Medical Sciences College, Qassim University, Almulaida 52571, Saudi Arabia;
| | | | - Hajed Obaid Abdullah Alharbi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Almulaida 52571, Saudi Arabia
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Kurexi A, Peng J, Yao J, Wang L, Wang Q. Association of "a body shape index" with the risk of developing colorectal cancer in U.S. patients with metabolic syndrome: evidence from the NHANES 1999-2018. BMC Gastroenterol 2024; 24:447. [PMID: 39627686 PMCID: PMC11613469 DOI: 10.1186/s12876-024-03537-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/22/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide and presents a significant challenge to public health. Metabolic syndrome (MetS) is a condition that is predominantly characterized by abdominal obesity and metabolic abnormalities such as hypertension, hyperglycemia, and hyperlipidemia, and it is one of the critical risk factors for CRC. Traditional anthropometric measures have limitations in accurately assessing the risk associated with abdominal obesity. This study aimed to investigate the association between "A Body Shape Index" (ABSI) and the risk of developing CRC among individuals with MetS utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS This cross-sectional study conducted a statistical analysis of all adult participants who met the diagnostic criteria for MetS in the NHANES data from 1999 to 2018. The ABSI was calculated to quantify abdominal obesity. ABSI is derived from a formula that incorporates waist circumference (WC), body mass index (BMI), and height, and is calculated as ABSI = WC / (BMI^(2/3) × Height^(1/2)). Multivariate logistic regression modeling was used to examine the independent association between ABSI and CRC incidence. Receiver Operating Characteristic (ROC) curves were employed to analyze the ability of ABSI compared to traditional metrics in identifying CRC risk. RESULTS This study involved 16,018 MetS patients with a mean age of 51.8 years, of whom 50.3% were male and 49.7% were female. Logistic regression adjusted for confounders revealed a significant association between an elevated ABSI and an increased risk of developing CRC (odds ratio (OR): 1.433, 95% confidence interval (CI): 1.116 to 1.841; P = 0.005). ROC analyses confirmed that the predictive accuracy of the ABSI for the risk of developing CRC area under the curve (AUC): (0.668, 95% CI: 0.624 to 0.713) surpassed that of traditional measurement methods. CONCLUSION Among individuals with MetS, the ABSI is linked to an elevated risk of developing CRC. Compared with traditional anthropometric indices, the ABSI is a superior predictive marker for the risk of developing CRC.
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Affiliation(s)
- Airepati Kurexi
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Jingqi Peng
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Juyi Yao
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Lin Wang
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Qisan Wang
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China.
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20
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Park JS, Moon SJ, Park HS, Cho SH. Survival benefit of metformin use according to cancer diagnosis in diabetic patients with metabolic syndrome. Prev Med Rep 2024; 48:102928. [PMID: 39634282 PMCID: PMC11616528 DOI: 10.1016/j.pmedr.2024.102928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 12/07/2024] Open
Abstract
Background Metabolic syndrome (MetSyn) is a disease cluster causing cardiovascular disease, cancer, and high mortality. Metformin is the most common antidiabetic agent inhibiting the tumorigenesis and insulin resistance of MetSyn. We describe the association between metformin intake and survival of patients with type 2 diabetes mellitus (T2DM) and MetSyn, according to the presence of cancer. Methods We analyzed the clinical characteristics and all-cause mortality of patients with T2DM and MetSyn using a 5-year dataset between January 1, 2009 and December 31, 2013 derived from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Cox proportional hazards regression models were used to investigate metformin effects adjusted for other potential confounding variables. Results Among a total of 43,043 patients with both MetSyn and T2DM, 24,725 patients (57.4 %) received metformin regularly. Female sex, high income, regular exercise, and metformin use were good prognostic factors, whereas hypertension, current smoking, cancer, and diabetes medication (except metformin) were poor prognostic factors. After adjustment for possible confounding variables, metformin showed a significant effect on patient survival (hazard ratio [HR], 0.68; 95 % confidence interval [CI], 0.63-0.75; p < 0.001). The effect of metformin was pronounced on the group of patients with liver, lung, colorectal, or prostate cancers (HR, 0.57; CI, 0.46-0.70). Conclusions Metformin intake may be related to favorable survival among patients with T2DM and MetSyn. The efficacy might be more remarkable in those with liver, lung, colorectal, and prostate cancers. The potential benefit of metformin in patients with these risk factors should be further investigated.
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Affiliation(s)
- Ji Soo Park
- Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
- Division of Medical Oncology, Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soo Jin Moon
- Department of Statistics and Actuarial Science, Soongsil University, South Korea
| | - Hyung Seok Park
- Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang-Hoon Cho
- Department of Statistics and Actuarial Science, Soongsil University, South Korea
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21
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Almeida-Nunes DL, Silva JPN, Nunes M, Silva PMA, Silvestre R, Dinis-Oliveira RJ, Bousbaa H, Ricardo S. Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines. Int J Mol Sci 2024; 25:11935. [PMID: 39596005 PMCID: PMC11594113 DOI: 10.3390/ijms252211935] [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: 10/16/2024] [Revised: 10/30/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Targeting the insulin-like growth factor 1 (IGF-1) signaling pathway has emerged as a promising therapeutic strategy. Linsitinib, an IGF-1 receptor (IGF-1R) inhibitor, has shown potential in disrupting this pathway. Additionally, metformin, commonly used in the treatment of type 2 diabetes, has been studied for its anti-cancer properties due to its ability to inhibit metabolic pathways that intersect with IGF-1 signaling, making it a candidate for combination therapy in cancer treatments. This study explores the anti-cancer effects of linsitinib and metformin on OVCAR3 cells by the suppression of the IGF-1 signaling pathway by siRNA-mediated IGF-1 gene silencing. The goal is to evaluate their efficacy as therapeutic agents and to emphasize the critical role of this pathway in OC cell proliferation. Cellular viability was evaluated by resazurin-based assay, and apoptosis was assessed by flux cytometry. The results of this study indicate that the combination of linsitinib and metformin exhibits an antagonistic effect (obtained by SynergyFinder 2.0 Software), reducing their anti-neoplastic efficacy in OC cell lines. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey's or Šídák's multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).
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Affiliation(s)
- Diana Luísa Almeida-Nunes
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal; (D.L.A.-N.); (P.M.A.S.); (R.J.D.-O.)
- UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
- Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal;
| | - João P. N. Silva
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (H.B.)
| | - Mariana Nunes
- Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal;
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal
| | - Patrícia M. A. Silva
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal; (D.L.A.-N.); (P.M.A.S.); (R.J.D.-O.)
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (H.B.)
- UCIBIO—Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
| | - Ricardo Silvestre
- Life and Health Sciences Research Institute (ICVS), School of Medicine from University of Minho, 4710-057 Braga, Portugal;
- ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal
| | - Ricardo Jorge Dinis-Oliveira
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal; (D.L.A.-N.); (P.M.A.S.); (R.J.D.-O.)
- UCIBIO—Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine from University of Porto (FMUP), 4050-319 Porto, Portugal
- FOREN—Forensic Science Experts, 1400-136 Lisboa, Portugal
| | - Hassan Bousbaa
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (H.B.)
| | - Sara Ricardo
- Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal; (D.L.A.-N.); (P.M.A.S.); (R.J.D.-O.)
- UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
- Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal;
- UNIPRO—Oral Pathology and Rehabilitation Research Unit, Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra 1317, 4585-116 Gandra, Portugal; (J.P.N.S.); (H.B.)
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22
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Zhu L, Yang L, Liang Z, Shi W, Ma M, Chen J, Abdula Z, Gong X. Association between dietary calcium intake and constipation in a metabolic syndrome population: evidence from NHANES 2005-2010. Front Nutr 2024; 11:1422564. [PMID: 39539369 PMCID: PMC11557474 DOI: 10.3389/fnut.2024.1422564] [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: 07/08/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Background The global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS. Methods This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships. Results The study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704). Conclusion The findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.
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Affiliation(s)
- Li Zhu
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Long Yang
- Pediatric Cardiothoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Zonghua Liang
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Wen Shi
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Ming Ma
- Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Jingbo Chen
- Department of Traditional Chinese Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Zulipikaer Abdula
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xuchen Gong
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
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Zemer A, Samaei S, Yoel U, Biderman A, Pincu Y. Ketogenic diet in clinical populations-a narrative review. Front Med (Lausanne) 2024; 11:1432717. [PMID: 39534224 PMCID: PMC11554467 DOI: 10.3389/fmed.2024.1432717] [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: 05/14/2024] [Accepted: 10/14/2024] [Indexed: 11/16/2024] Open
Abstract
Ketogenic diet (KD) is a high-fat, low-carbohydrate (CHO) diet, designed to induce a metabolic state of ketosis in which the body metabolizes primarily lipids for energy production. Various forms of KD are being promoted as promising treatments for numerous health conditions from chronic headaches to weight-loss and even different forms of cancer and are becoming increasingly more popular. KD appears to be an efficacious approach for weight-loss, and maintenance, improved glycemia, cognitive function and cancer prognosis. However, there is a controversy regarding the safety of KD, and the potential health risks that might be associated with long-term exposure to KD. There is a gap between the acceptance and utilization of KD in individuals with health conditions and the criticism and negative attitudes toward KD by some clinicians. Many individuals choose to follow KD and are encouraged by the positive results they experience. Although the medical establishment does not endorse KD as a first line of treatment, clinicians need to be informed about KD, and offer support and medical supervision for patients who self-select to follow KD. This can ensure that within the boundaries of KD, patients will make good and healthy dietary choices and prevent clinical disengagement in extreme cases. To that end, there is an urgent need for good quality research to address the issues of long-term safety of KD in different clinical populations and for standardization of KD both in research and in the clinic.
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Affiliation(s)
- Alon Zemer
- Department of Pharmacology and Clinical Biochemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Shabnam Samaei
- Department of Health and Exercise Science, University of Oklahoma, Norman, OK, United States
| | - Uri Yoel
- Endocrinology Unit, Soroka University Medical Center, Beer Sheva, Israel
| | - Aya Biderman
- Department of Family Medicine, Goldman Medical School, Ben-Gurion University of the Negev and Clalit Health Services, Beer Sheva, Israel
| | - Yair Pincu
- Department of Pharmacology and Clinical Biochemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Department of Health and Exercise Science, University of Oklahoma, Norman, OK, United States
- Harold Hamm Diabetes Center, Oklahoma City, OK, United States
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Fan S, Liu H, Hou J, Zheng G, Gu P, Liu X. Characterizing adipocytokine-related signatures for prognosis prediction in prostate cancer. Front Cell Dev Biol 2024; 12:1475980. [PMID: 39524226 PMCID: PMC11544632 DOI: 10.3389/fcell.2024.1475980] [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: 08/04/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
Background Prostate cancer (PCa) is a prevalent malignant tumor in males, with a significant incidence of biochemical recurrence (BCR) despite advancements in treatment. Adipose tissue surrounding the prostate, known as periprostatic adipose tissue (PPAT), contributes to PCa invasion through adipocytokine production. However, the relationship between adipocytokine-related genes and PCa prognosis remains understudied. This study was conducted to provide a theoretical basis and serve as a reference for the use of adipocytokine-related genes as prognostic markers in PCa. Methods Transcriptome and survival data of PCa patients from The Cancer Genome Atlas (TCGA) database were analyzed. Differential gene expression analysis was conducted using the DESeq2 and limma packages. Prognostic genes were identified through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A prognostic model was developed and validated utilizing receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves. Assessments of immune cell infiltration and drug sensitivity were also carried out. Subsequently, the function of BNIP3L gene in PCa was verified. Results A total of 47 adipocytokine-related differentially expressed genes (DEGs) were identified. Five genes (PPARGC1A, APOE, BNIP3L, STEAP4, and C1QTNF3) were selected as prognostic markers. The prognostic model demonstrated significant predictive accuracy in both training and validation cohorts. Patients with higher risk scores exhibited poorer survival outcomes. Immune cell infiltration analysis revealed that the high-risk group had increased immune and ESTIMATE scores, while the low-risk group had higher tumor purity. In vitro experiments confirmed the suppressive effects of BNIP3L on PCa cell proliferation, migration, and invasion. Conclusion The prognostic model independently predicts the survival of patients with PCa, aiding in prognostic prediction and therapeutic efficacy. It expands the study of adipocytokine-related genes in PCa, presenting novel targets for treatment.
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Affiliation(s)
- Shicheng Fan
- Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Haolin Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian Hou
- Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Guiying Zheng
- Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Peng Gu
- Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Xiaodong Liu
- Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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25
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Wang X, Jiang R, Shen J, Chen S, Wu S, Hu H, Cai H. Transitions in metabolic syndrome and metabolic obesity status over time and risk of urologic cancer: A prospective cohort study. PLoS One 2024; 19:e0311492. [PMID: 39432545 PMCID: PMC11493304 DOI: 10.1371/journal.pone.0311492] [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: 07/03/2024] [Accepted: 09/18/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND AND AIMS The effects of metabolic obesity (MO) phenotypes status and their dynamic changes on urologic cancer (UC) is ignored. We aimed to investigate the association between metabolic syndrome (MetS) and MO status at baseline, their dynamic changes and UC risk. METHODS This paper studied 97,897 subjects who were free of cancers at baseline (2006-2007). Individuals were classified into four MO phenotypes by MetS and obesity at baseline. Transitions in MetS and MO status from 2006-2007 to 2008-2009 were considered. The hazard ratios (HRs) and 95% confidence intervals (CIs) for UC were assessed by multifactorial Cox proportional risk regression models. The main limitations of this study are as follows: the ratio of men to women in the cohort is unbalanced; the impacts of MetS and MO on each cancer type (kidney cancer, prostate cancer, bladder cancer) have not been analyzed separately; the transition intervals of MetS and MO phenotypes are relatively short. RESULTS From baseline (2006-2007) survey to December 31, 2020, during a median follow-up of 14.02 years, 554 cases of UC were diagnosed. Participants with MetS [HRs (95% CI) = 1.26 (1.06-1.49)] and metabolically unhealthy obesity (MUO) [HRs (95% CI) = 1.49 (1.17-1.89)] had significantly higher risk of UC than those with non-MetS and metabolically healthy normal weight (MHN). Transitions in MetS and MO phenotypes over time were studied. Compared with non-MetS to non-MetS, the risks for UC in MetS to MetS [HRs (95% CI) = 1.45 (1.11-1.88)] was increased. Compared with MHN to MHN, both MUO to metabolically healthy obesity (MHO) [HRs (95% CI) = 2.65 (1.43-4.92)] and MUO to MUO [HRs (95% CI) = 1.60 (1.06-2.42)] had significantly higher UC risk. CONCLUSIONS MetS and MUO increased the UC risk at baseline. Transitions of MetS to MetS, MUO to MUO and even MUO to MHO over time significantly increased the risk of UC development.
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Affiliation(s)
- Xia Wang
- Department of Gynaecology, Tangshan Hongci Hospital, Tangshan, Hebei, China
| | - Runxue Jiang
- Department of Oncology Surgery, Tangshan People’s Hospital, Tangshan, Hebei, China
- Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Jianglun Shen
- Department of Oncology Surgery, Tangshan People’s Hospital, Tangshan, Hebei, China
| | - Shuohua Chen
- Health Department of Kailuan(Group), Tangshan, Hebei, China
| | - Shouling Wu
- Health Department of Kailuan(Group), Tangshan, Hebei, China
| | - Hailong Hu
- Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Haifeng Cai
- Department of Oncology Surgery, Tangshan People’s Hospital, Tangshan, Hebei, China
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26
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Wang Q, Yang HS. The Impact of Pdcd4, a Translation Inhibitor, on Drug Resistance. Pharmaceuticals (Basel) 2024; 17:1396. [PMID: 39459035 PMCID: PMC11510623 DOI: 10.3390/ph17101396] [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: 09/19/2024] [Revised: 10/10/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024] Open
Abstract
Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.
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Affiliation(s)
- Qing Wang
- Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA;
| | - Hsin-Sheng Yang
- Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA;
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
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Azam S, Peng C, Rosner BA, Goncalves MD, Phillips E, Eliassen H, Heine J, Hankinson SE, Tamimi RM. Plasma C-peptide mammographic features and risk of breast cancer. NPJ Breast Cancer 2024; 10:91. [PMID: 39420200 PMCID: PMC11487244 DOI: 10.1038/s41523-024-00702-x] [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: 09/25/2023] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
Our study in the Nurses' Health Study (NHS) and NHS2, a nested case-control study with 1260 cases and 2221 controls, investigated the association between C-peptide levels, mammographic density (MD) parameters, V (a measure of gray scale variation), and breast cancer (BC) risk. We also examined how C-peptide and BC risk vary across quartiles of mammographic features. Linear and logistic regressions were used to study the associations between C-peptide and MD parameters, and breast cancer. C-peptide was inversely associated with percent MD and positively with non-dense area, but no associations were found with dense area and V measure. C-peptide was associated with an increased risk of invasive BC risk (top vs. bottom quartile, odds ratio = 1.46, 95% CI: 1.12-1.91). No multiplicative interactions were found between C-peptide, MD parameters, and BC risk. Our results suggest a positive association between C-peptide and BC risk, and MD parameters do not seem to modify this association.
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Affiliation(s)
- Shadi Azam
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
| | - Cheng Peng
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Bernard A Rosner
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | | | - Erica Phillips
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Heather Eliassen
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - John Heine
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Susan E Hankinson
- Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
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Zheng X, Wang Y, Chen Y, Liu T, Liu C, Lin S, Xie H, Ma X, Wang Z, Shi J, Zhang H, Yang M, Liu X, Deng L, Zhang Q, Shi H. Metabolic obesity phenotypes and the risk of cancer: a prospective study of the Kailuan cohort. Front Endocrinol (Lausanne) 2024; 15:1333488. [PMID: 39479267 PMCID: PMC11521940 DOI: 10.3389/fendo.2024.1333488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 09/30/2024] [Indexed: 11/02/2024] Open
Abstract
Background Obesity is as an important risk factor for chronic diseases. Metabolically healthy obesity (MHO) is considered a benign state. The association between metabolic health and obesity categories and cancer risk remains unclear. This study aimed to investigate the relationship between metabolic health status combined with obesity phenotypes and the risk of cancer. Methods Data from 91,834 participants in the Kailuan cohort were analyzed, excluding individuals with a body mass index (BMI) < 18.5 kg/m² and those with a history of cancer. Obesity phenotypes were classified based on BMI and waist circumference (WC) combined with metabolic health status, resulting in six phenotypes. Cox proportional hazard regression models were used to assess the association between metabolic health and obesity phenotypes with cancer risk and all-cause mortality. Results The prevalence of metabolically healthy obesity and metabolically unhealthy obesity defined by BMI was 6.86% and 12.18%, while that defined by WC was 20.79% and 25.76%, respectively. Compared to metabolically healthy participants, individuals with an unhealthy metabolic status had a significantly higher risk of cancer (HR, 1.09; 95% CI, 1.03-1.15; p=0.004). The hazard ratios for cancer were 1.19, 1.23, 1.20, and 1.55 for individuals with one, two, three, and four metabolic disorders, respectively. Among those classified as metabolically unhealthy, both overweight and obesity were associated with a protective effect on cancer risk (HR, 0.88; 95% CI, 0.80-0.96; p=0.006 for overweight; HR, 0.87; 95% CI, 0.78-0.97; p=0.010 for obesity). However, abdominal obesity significantly increased cancer risk in both metabolically healthy and unhealthy participants. In subgroup analysis, simple obesity showed a protective trend against cancer in those with respiratory cancers, while abdominal obesity consistently posed a risk for various cancer types. Conclusion Metabolically unhealthy status and abdominal obesity are risk factors for cancer and all-cause mortality, whereas simple obesity offers protective effects against cancer and all-cause mortality in metabolically unhealthy individuals. These findings suggest that maintaining metabolic health and reducing the metabolic risks associated with abdominal obesity should be key targets for cancer prevention.
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Affiliation(s)
- Xin Zheng
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Yiming Wang
- Department of Hepatological Surgery, Kailuan General Hospital, Tangshan, China
| | - Yue Chen
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
- The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
| | - Tong Liu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Chenan Liu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Shiqi Lin
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
- The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hailun Xie
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Xiangming Ma
- The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ziwen Wang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Jinyu Shi
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Heyang Zhang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Ming Yang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Xiaoyue Liu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Li Deng
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
| | - Qingsong Zhang
- Department of General Surgery, Kailuan General Hospital, Tangshan, China
| | - Hanping Shi
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China
- Key Laboratory of Cancer Food for Special Medical Purposes (FSMP) for State Market Regulation, Beijing, China
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Ding B, Mai B, Liu T, Liu C, Bao H, Hu J, Qian X, Wang S, Ou Q, Dong X, Lei Z, Yan G. Anlotinib treatment for rapidly progressing pediatric embryonal rhabdomyosarcoma in the maxillary gingiva: a case report. Diagn Pathol 2024; 19:135. [PMID: 39379998 PMCID: PMC11460102 DOI: 10.1186/s13000-024-01555-5] [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: 07/03/2024] [Accepted: 09/22/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Embryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies. CASE PRESENTATION In this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU. CONCLUSIONS Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.
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Affiliation(s)
- Bo Ding
- Department of Pediatric Intensive Care Unit, Hainan Women and Children's Medical Center, Children's Hospital of Fudan University at Hainan, Children's Hospital of Hainan Medical University, Haikou, 570100, China
| | - Biwei Mai
- Department of Pediatric Intensive Care Unit, Hainan Women and Children's Medical Center, Children's Hospital of Fudan University at Hainan, Children's Hospital of Hainan Medical University, Haikou, 570100, China
| | - Tingyan Liu
- Department of Pediatric Intensive Care Unit, National Center for Children's Health, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China
| | - Cuicui Liu
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, 210032, China
| | - Hairong Bao
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, 210032, China
| | - Jingzhou Hu
- Department of Oral and Maxillofacial Surgery, ZhangZhiyuan Academician Workstation, Hainan Western Central Hospital, Shanghai Ninth People's Hospital, Danzhou, 571700, Hainan, China
| | - Xiaowen Qian
- Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Song Wang
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, 210032, China
| | - Qiuxiang Ou
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, 210032, China
| | - Xiujuan Dong
- Department of Hematology and Oncology, Hainan Women and Children's Medical Center, Children's Hospital of Fudan University at Hainan, Children's Hospital of Hainan Medical University, Haikou, 570100, China
| | - Zhixian Lei
- Department of Pediatric Intensive Care Unit, Hainan Women and Children's Medical Center, Children's Hospital of Fudan University at Hainan, Children's Hospital of Hainan Medical University, Haikou, 570100, China.
| | - Gangfeng Yan
- Department of Pediatric Intensive Care Unit, National Center for Children's Health, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
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30
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Yeşildağ A, Kızıloğlu HT, Dirican E, Erbaş E, Gelen V, Kara A. Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells. Biol Trace Elem Res 2024; 202:4494-4507. [PMID: 38358644 PMCID: PMC11339093 DOI: 10.1007/s12011-024-04090-y] [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: 12/08/2023] [Accepted: 01/29/2024] [Indexed: 02/16/2024]
Abstract
Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.
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Affiliation(s)
- Ali Yeşildağ
- Department of Bioengineering, Faculty of Engineering and Architecture, Kafkas University, Kars, Turkey.
| | - Halime Topal Kızıloğlu
- Department of Molecular Biology and Genetic, Faculty of Science, Erzurum Technical University, Erzurum, Turkey
| | - Ebubekir Dirican
- Department of Medical Biology, Faculty of Medicine, Bilecik Şeyh Edabali University, Bilecik, Turkey
| | - Elif Erbaş
- Department of Histology and Embryology Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Volkan Gelen
- Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey
| | - Adem Kara
- Department of Molecular Biology and Genetic, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.
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31
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Meng X, Zhang S, Zhou S, Ma Y, Yu X, Guan L. Putative Risk Biomarkers of Bipolar Disorder in At-risk Youth. Neurosci Bull 2024; 40:1557-1572. [PMID: 38710851 PMCID: PMC11422403 DOI: 10.1007/s12264-024-01219-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: 11/23/2023] [Accepted: 03/08/2024] [Indexed: 05/08/2024] Open
Abstract
Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies.
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Affiliation(s)
- Xinyu Meng
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
| | - Shengmin Zhang
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
| | - Shuzhe Zhou
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
| | - Yantao Ma
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
| | - Xin Yu
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
| | - Lili Guan
- Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China.
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32
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Pîrvu BF, Clenciu D, Beldie LA, Dica CC, Burticală MA, Ţenea-Cojan TŞ, Mitrea A, Amzolini AM, Efrem IC, Mogoş GFR, Vladu IM. The burden of cancer in metabolic dysfunction-associated steatotic liver disease. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2024; 65:627-635. [PMID: 39957024 PMCID: PMC11924906 DOI: 10.47162/rjme.65.4.09] [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: 11/21/2024] [Accepted: 01/08/2025] [Indexed: 02/18/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and has become a major public health problem. MASLD frequently progresses to cirrhosis and hepatocellular carcinoma, but recent studies also show a frequent association with extrahepatic cancers. One of the mechanisms involved in both locations is insulin resistance and hyperinsulinemia. The aim of this narrative review was to present the main etiopathogenic mechanisms involved in cancer development in patients with MASLD.
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Affiliation(s)
- Bianca Florentina Pîrvu
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Clinical Hospital, Craiova, Romania
| | - Diana Clenciu
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Luiza Andreea Beldie
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Clinical Hospital, Craiova, Romania
| | - Cristina Camelia Dica
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Clinical Hospital, Craiova, Romania
| | | | | | - Adina Mitrea
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Anca Maria Amzolini
- Department of Medical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
| | - Ion Cristian Efrem
- Department of Medical Semiology, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Romania
| | | | - Ionela Mihaela Vladu
- Department of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania
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33
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Maier JA, Castiglioni S, Petrelli A, Cannatelli R, Ferretti F, Pellegrino G, Sarzi Puttini P, Fiorina P, Ardizzone S. Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison. Front Immunol 2024; 15:1436581. [PMID: 39359726 PMCID: PMC11445042 DOI: 10.3389/fimmu.2024.1436581] [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: 05/22/2024] [Accepted: 08/29/2024] [Indexed: 10/04/2024] Open
Abstract
Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management.
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Affiliation(s)
- Jeanette A Maier
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Sara Castiglioni
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Alessandra Petrelli
- Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy
| | | | | | | | - Piercarlo Sarzi Puttini
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milano, Italy
| | - Paolo Fiorina
- Department of Biomedical and Clinical Sciences, Università di Milano, Milano, Italy
| | - Sandro Ardizzone
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Milano, Italy
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34
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Kristensson FM, Andersson-Assarsson JC, Peltonen M, Jacobson P, Ahlin S, Svensson PA, Sjöholm K, Carlsson LMS, Taube M. Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial. JAMA Surg 2024; 159:856-863. [PMID: 38748431 PMCID: PMC11097101 DOI: 10.1001/jamasurg.2024.1169] [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: 10/17/2023] [Accepted: 03/08/2024] [Indexed: 05/18/2024]
Abstract
Importance Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. Objective To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). Intervention In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Main Outcome and Measures Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. Results The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). Conclusions and Relevance This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. Trial Registration ClinicalTrials.gov Identifier: NCT01479452.
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Affiliation(s)
- Felipe M. Kristensson
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Surgery, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
| | - Johanna C. Andersson-Assarsson
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | | | - Peter Jacobson
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Sofie Ahlin
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Physiology, Region Västra Götaland, NU Hospital Group, Trollhättan, Sweden
| | - Per-Arne Svensson
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Institute of Health and Care Sciences, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Kajsa Sjöholm
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Lena M. S. Carlsson
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Magdalena Taube
- Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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Kanehara R, Park SY, Okada Y, Iwasaki M, Tsugane S, Sawada N, Inoue M, Haiman CA, Wilkens LR, Le Marchand L. Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study. J Nutr 2024; 154:2481-2492. [PMID: 38795743 PMCID: PMC11375464 DOI: 10.1016/j.tjnut.2024.05.016] [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: 01/04/2024] [Revised: 05/10/2024] [Accepted: 05/18/2024] [Indexed: 05/28/2024] Open
Abstract
BACKGROUND The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial, and there is a need to investigate the heterogeneity of effects among racial and ethnic groups. OBJECTIVES To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 y. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS As of December 2017, 4403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4, and Q5 compared with Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (95% CI: 0.96, 1.16), 1.12 (95% CI: 1.01, 1.24), and 1.13 (95% CI: 1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 y at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among racial and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSIONS In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC, and the association was strongest for colon cancer, younger participants, and Latinos.
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Affiliation(s)
- Rieko Kanehara
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States; Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
| | - Song-Yi Park
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States
| | - Yuito Okada
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan; International University of Health and Welfare Graduate School of Public Health, Tokyo, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Manami Inoue
- National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Christopher A Haiman
- Department of Population and Public Health Sciences, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States
| | - Lynne R Wilkens
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States
| | - Loïc Le Marchand
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States
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Xiong JL, Wang YX, Luo JY, Wang SM, Sun JJ, Xi QY, Chen T, Zhang YL. Pituitary-derived small extracellular vesicles promote liver repair by its cargo miR-143-3p. Sci Rep 2024; 14:16635. [PMID: 39025906 PMCID: PMC11258314 DOI: 10.1038/s41598-024-67434-7] [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: 03/04/2024] [Accepted: 07/11/2024] [Indexed: 07/20/2024] Open
Abstract
The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.
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Affiliation(s)
- Jia-Li Xiong
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
- College of Medicine, Jiaxing University, Jiaxing, 314000, Zhejiang, China
| | - Yu-Xuan Wang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
| | - Jun-Yi Luo
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
| | - Shu-Meng Wang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
| | - Jia-Jie Sun
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
| | - Qian-Yun Xi
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China
| | - Ting Chen
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China.
| | - Yong-Liang Zhang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, 510642, Guangdong, China.
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He Y, Han S, Li H, Wu Y, Jia W, Chen Z, Pan Y, Cai N, Wen J, Li G, Liang J, Zhao J, Liu Q, Liang H, Ding Z, Huang Z, Zhang B. CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA-binding motif protein 38. MedComm (Beijing) 2024; 5:e633. [PMID: 38952575 PMCID: PMC11215284 DOI: 10.1002/mco2.633] [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: 07/26/2023] [Revised: 05/29/2024] [Accepted: 05/30/2024] [Indexed: 07/03/2024] Open
Abstract
cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA-binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.
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Affiliation(s)
- Yi He
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Department of Pediatric SurgeryTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Shenqi Han
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Han Li
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Yu Wu
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Wenlong Jia
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Zeyu Chen
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Yonglong Pan
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Department of Pediatric SurgeryTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Ning Cai
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Jingyuan Wen
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Ganxun Li
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Junnan Liang
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Jianping Zhao
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Qiumeng Liu
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Huifang Liang
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Zeyang Ding
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Zhao Huang
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Bixiang Zhang
- Hepatic Surgery CenterTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Clinical Medical Research Center of Hepatic Surgery at Hubei ProvinceWuhanChina
- Hubei Key Laboratory of Hepato‐Pancreatic‐Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
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Dhanalakshmi B, Anil Kumar BM, Srinivasa Murthy V, Srinivasa SM, Vivek HK, Sennappan M, Rangappa S. Design, synthesis and docking studies of novel 4-aminophenol-1,2,4-oxadiazole hybrids as apoptosis inducers against triple negative breast cancer cells targeting MAP kinase. J Biomol Struct Dyn 2024; 42:5841-5857. [PMID: 37529915 DOI: 10.1080/07391102.2023.2239912] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/17/2023] [Indexed: 08/03/2023]
Abstract
In our study, a series of novel 4-aminophenol benzamide-1,2,4-oxadiazole hybrid analogues have been designed and synthesized by condensing 4-hydroxyphenyl arylamides (3a-c) and 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (6a-d). The structure of the synthesised compounds was verified by various spectroscopic techniques (1H NMR, 13C NMR, IR and LC-MS). All the prepared compounds were subjected to in silico and in vitro antiproliferative study against TNBC cell lines MDA-MB-468 and MDA-MB-231. The investigations revealed that compound 7k significantly promoted apoptosis against MDA-MB-468 and MDA-MB-231 cells with IC50 values of 22.31 µM and 26.27 µM, respectively. Compound 7k interacted with crucial active sites of MAPK and exhibited the highest docking score of -7.06 kcal/mol. Docking was validated with molecular dynamic studies with simulation for 100 ns, depicting various stable interactions with MAPK. Consequently, 7k forms stable H-Bonds and π-π stacking with amino acid residues along with π-cation. Our investigations reveal that the in vitro antiproliferative study of 7k was in good correlation with the in silico studies. Hence, 7k serves as a potential novel lead for the inhibition of TNBCs by downregulating MAPK P38.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Boregowda Dhanalakshmi
- Department of Chemistry, School of Engineering, Dayananda Sagar University, Bengaluru, Karnataka, India
- Department of Chemistry, Rajeev Institute of Technology, Visvesvaraya Technological University, Hassan, Karnataka, India
| | - Belagal Motatis Anil Kumar
- Department of Molecular Biology, Adichunchanagiri School of Natural Sciences, ACU-CRI, Adichunchanagiri University, BGSIT, B.G Nagara, Karnataka, India
- Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, B.G Nagara, Karnataka, India
| | | | - Sudhanva Muddenahalli Srinivasa
- Department of Molecular Biology, Adichunchanagiri School of Natural Sciences, ACU-CRI, Adichunchanagiri University, BGSIT, B.G Nagara, Karnataka, India
- Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, B.G Nagara, Karnataka, India
| | - Hamse Kameshwar Vivek
- Department of Biochemistry, Adichunchanagiri School of Natural Sciences, ACU-CRI, Adichunchanagiri University, BGSIT, B.G Nagara, Karnataka, India
- Department of Biochemistry, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, B.G Nagara, Karnataka, India
| | - Madhappan Sennappan
- Department of Chemistry, Dayananda Sagar College of Engineering, Bangalore, Karnataka, India
| | - Shobith Rangappa
- Department of Molecular Biology, Adichunchanagiri School of Natural Sciences, ACU-CRI, Adichunchanagiri University, BGSIT, B.G Nagara, Karnataka, India
- Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, B.G Nagara, Karnataka, India
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Miyauchi J. The hematopoietic microenvironment of the fetal liver and transient abnormal myelopoiesis associated with Down syndrome: A review. Crit Rev Oncol Hematol 2024; 199:104382. [PMID: 38723838 DOI: 10.1016/j.critrevonc.2024.104382] [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: 11/02/2023] [Revised: 04/21/2024] [Accepted: 05/02/2024] [Indexed: 05/23/2024] Open
Abstract
Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome is a distinct form of leukemia or preleukemia that mirrors the hematological features of acute megakaryoblastic leukemia. However, it typically resolves spontaneously in the early stages. TAM originates from fetal liver (FL) hematopoietic precursor cells and emerges due to somatic mutations in GATA1 in utero. In TAM, progenitor cells proliferate and differentiate into mature megakaryocytes and granulocytes. This process occurs both in vitro, aided by hematopoietic growth factors (HGFs) produced in the FL, and in vivo, particularly in specific anatomical sites like the FL and blood vessels. The FL's hematopoietic microenvironment plays a crucial role in TAM's pathogenesis and may contribute to its spontaneous regression. This review presents an overview of current knowledge regarding the unique features of TAM in relation to the FL hematopoietic microenvironment, focusing on the functions of HGFs and the pathological features of TAM.
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Affiliation(s)
- Jun Miyauchi
- Department of Diagnostic Pathology, Saitama City Hospital, Saitama, Saitama-ken, Japan.
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Boysen ML, Troelsen FS, Sørensen HT, Erichsen R. Type 2 diabetes mellitus and post-colonoscopy colorectal cancer: clinical and molecular characteristics and survival. Cancer Causes Control 2024; 35:1043-1052. [PMID: 38483686 PMCID: PMC11217032 DOI: 10.1007/s10552-024-01861-9] [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: 06/29/2023] [Accepted: 02/05/2024] [Indexed: 07/02/2024]
Abstract
PURPOSE Studies suggest that patients with type two diabetes mellitus (T2D) may be at increased risk of post-colonoscopy colorectal cancer (PCCRC). We investigated clinical and molecular characteristics and survival of T2D patients with PCCRC to elucidate how T2D-related PCCRC may arise. METHODS We identified T2D patients with colorectal cancer (CRC) from 1995 to 2015 and computed prevalence ratios (PRs) comparing clinical and molecular characteristics of CRC in T2D patients with PCCRC vs. in T2D patients with colonoscopy-detected CRC (dCRC). We also followed T2D patients from the diagnosis of PCCRC/dCRC until death, emigration, or study end and compared mortality using Cox-proportional hazards regression models adjusted for sex, age, year of CRC diagnosis, and CRC stage. RESULTS Compared with dCRC, PCCRC was associated with a higher prevalence of proximal CRCs (54% vs. 40%; PR: 1.43, 95% confidence interval [CI] 1.27-1.62) in T2D patients. We found no difference between PCCRC vs. dCRC for CRC stage, histology, and mismatch repair status. The proportion of CRCs that could be categorized as PCCRC decreased over time. Within one year after CRC, 63% of PCCRC vs. 78% of dCRC patients were alive (hazard ratio [HR] 1.85 [95% CI 1.47-2.31]). Within five years after CRC, 44% of PCCRC vs. 54% of dCRC patients were still alive (HR 1.44 [95% CI 1.11-1.87]). CONCLUSION The increased prevalence of proximally located PCCRCs and the poorer survival may suggest overlooked colorectal lesions as a predominant explanation for T2D-related PCCRC, although altered tumor progression cannot be ruled out.
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Affiliation(s)
- Mette L Boysen
- Department of Surgery, Gødstrup Regional Hospital, 7400, Herning, Denmark
- Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark
| | - Frederikke S Troelsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
- Department of Surgery, Randers Regional Hospital, 8930, Randers, Denmark.
| | - Henrik T Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark
| | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark
- Department of Surgery, Randers Regional Hospital, 8930, Randers, Denmark
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Wright JL, Schenk JM, Gulati R, Beatty SJ, VanDoren M, Lin DW, Porter MP, Morrissey C, Dash A, Gore JL, Etzioni R, Plymate SR, Neuhouser ML. The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance. Cancer 2024; 130:2108-2119. [PMID: 38353455 PMCID: PMC11527460 DOI: 10.1002/cncr.35241] [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: 07/29/2023] [Revised: 01/11/2024] [Accepted: 01/16/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. METHODS Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.
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Affiliation(s)
- Jonathan L Wright
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
- Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | | | - Roman Gulati
- Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | | | | | - Daniel W Lin
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
- Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Michael P Porter
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | - Colm Morrissey
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
| | - Atreya Dash
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | - John L Gore
- Department of Urology, University of Washington School of Medicine, Seattle, Washington, USA
- Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Ruth Etzioni
- Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Stephen R Plymate
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
- Geriatric Research Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
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An N, Zhang Y, Sha Z, Xu Z, Liu X. T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis. Front Oncol 2024; 14:1327154. [PMID: 38947888 PMCID: PMC11211363 DOI: 10.3389/fonc.2024.1327154] [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: 11/13/2023] [Accepted: 05/29/2024] [Indexed: 07/02/2024] Open
Abstract
Introduction Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included. Methods Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively. Results T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044). Conclusion T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.
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Affiliation(s)
- Ni An
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yu Zhang
- No.91126 Military Hospital of Chinese PLA, Dalian, China
| | - Zhilin Sha
- Department I of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Zhen Xu
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiuzhen Liu
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
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Chmielewski PP, Data K, Strzelec B, Farzaneh M, Anbiyaiee A, Zaheer U, Uddin S, Sheykhi-Sabzehpoush M, Mozdziak P, Zabel M, Dzięgiel P, Kempisty B. Human Aging and Age-Related Diseases: From Underlying Mechanisms to Pro-Longevity Interventions. Aging Dis 2024:AD.2024.0280. [PMID: 38913049 DOI: 10.14336/ad.2024.0280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/02/2024] [Indexed: 06/25/2024] Open
Abstract
As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with age-related diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.
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Affiliation(s)
- Piotr Pawel Chmielewski
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Data
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Bartłomiej Strzelec
- 2nd Department of General Surgery and Surgical Oncology, Medical University Hospital, Wroclaw, Poland
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Amir Anbiyaiee
- Department of Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Uzma Zaheer
- School of Biosciences, Faculty of Health Sciences and Medicine, The University of Surrey, United Kingdom
| | - Shahab Uddin
- Translational Institute and Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India
| | | | - Paul Mozdziak
- Graduate Physiology Program, North Carolina State University, Raleigh, NC 27695, USA
| | - Maciej Zabel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
- Division of Anatomy and Histology, The University of Zielona Góra, Poland
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
| | - Bartosz Kempisty
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun, Poland
- Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA
- Center of Assisted Reproduction, Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic
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Cheung KS. Big data approach in the field of gastric and colorectal cancer research. J Gastroenterol Hepatol 2024; 39:1027-1032. [PMID: 38413187 DOI: 10.1111/jgh.16527] [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: 01/28/2024] [Accepted: 02/07/2024] [Indexed: 02/29/2024]
Abstract
Big data is characterized by three attributes: volume, variety,, and velocity. In healthcare setting, big data refers to vast dataset that is electronically stored and managed in an automated manner and has the potential to enhance human health and healthcare system. In this review, gastric cancer (GC) and postcolonoscopy colorectal cancer (PCCRC) will be used to illustrate application of big data approach in the field of gastrointestinal cancer research. Helicobacter pylori (HP) eradication only reduces GC risk by 46% due to preexisting precancerous lesions. Apart from endoscopy surveillance, identifying medications that modify GC risk is another strategy. Population-based cohort studies showed that long-term use of proton pump inhibitors (PPIs) associated with higher GC risk after HP eradication, while aspirin and statins associated with lower risk. While diabetes mellitus conferred 73% higher GC risk, metformin use associated with 51% lower risk, effect of which was independent of glycemic control. Nonetheless, nonsteroidal anti-inflammatory drugs (NA-NSAIDs) are not associated with lower GC risk. CRC can still occur after initial colonoscopy in which no cancer was detected (i.e. PCCRC). Between 2005 and 2013, the rate of interval-type PCCRC-3y (defined as CRC diagnosed between 6 and 36 months of index colonoscopy which was negative for CRC) was 7.9% in Hong Kong, with >80% being distal cancers and higher cancer-specific mortality compared with detected CRC. Certain clinical and endoscopy-related factors were associated with PCCRC-3 risk. Medications shown to have chemopreventive effects on PCCRC include statins, NA-NSAIDs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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45
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de Cavanagh EMV, Inserra F, Ferder L. Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging? Physiol Rep 2024; 12:e16094. [PMID: 38924381 PMCID: PMC11200104 DOI: 10.14814/phy2.16094] [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: 02/22/2024] [Revised: 05/18/2024] [Accepted: 05/18/2024] [Indexed: 06/28/2024] Open
Abstract
The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.
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Affiliation(s)
| | - Felipe Inserra
- Department of MedicineMaimonides UniversityBuenos AiresArgentina
- Master of Vascular Mechanics and Arterial Hypertension, Postgraduate DepartmentAustral UniversityPilarArgentina
| | - León Ferder
- Department of MedicineMaimonides UniversityBuenos AiresArgentina
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Elemam NM, Hotait HY, Saleh MA, El-Huneidi W, Talaat IM. Insulin-like growth factor family and prostate cancer: new insights and emerging opportunities. Front Endocrinol (Lausanne) 2024; 15:1396192. [PMID: 38872970 PMCID: PMC11169579 DOI: 10.3389/fendo.2024.1396192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 05/14/2024] [Indexed: 06/15/2024] Open
Abstract
Prostate cancer is the second most commonly diagnosed cancer in men. The mammalian insulin-like growth factor (IGF) family is made up of three ligands (IGF-I, IGF-II, and insulin), three receptors (IGF-I receptor (IGF-1R), insulin receptor (IR), and IGF-II receptor (IGF-2R)), and six IGF-binding proteins (IGFBPs). IGF-I and IGF-II were identified as potent mitogens and were previously associated with an increased risk of cancer development including prostate cancer. Several reports showed controversy about the expression of the IGF family and their connection to prostate cancer risk due to the high degree of heterogeneity among prostate tumors, sampling bias, and evaluation techniques. Despite that, it is clear that several IGF family members play a role in prostate cancer development, metastasis, and androgen-independent progression. In this review, we aim to expand our understanding of prostate tumorigenesis and regulation through the IGF system. Further understanding of the role of IGF signaling in PCa shows promise and needs to be considered in the context of a comprehensive treatment strategy.
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Affiliation(s)
- Noha M. Elemam
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | | | - Mohamed A. Saleh
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Waseem El-Huneidi
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Iman M. Talaat
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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47
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Ji Y, Xu Q, Wang W. Single-cell transcriptome reveals the heterogeneity of malignant ductal cells and the prognostic value of REG4 and SPINK1 in primary pancreatic ductal adenocarcinoma. PeerJ 2024; 12:e17350. [PMID: 38827297 PMCID: PMC11141562 DOI: 10.7717/peerj.17350] [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: 12/12/2023] [Accepted: 04/17/2024] [Indexed: 06/04/2024] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths, with very limited therapeutic options available. This study aims to comprehensively depict the heterogeneity and identify prognostic targets for PDAC with single-cell RNA sequencing (scRNA-seq) analysis. Methods ScRNA-seq analysis was performed on 16 primary PDAC and three adjacent lesions. A series of analytical methods were applied for analysis in cell clustering, gene profiling, lineage trajectory analysis and cell-to-cell interactions. In vitro experiments including colony formation, wound healing and sphere formation assay were performed to assess the role of makers. Results A total of 32,480 cells were clustered into six major populations, among which the ductal cell cluster expressing high copy number variants (CNVs) was defined as malignant cells. Malignant cells were further subtyped into five subgroups which exhibited specific features in immunologic and metabolic activities. Pseudotime trajectory analysis indicated that components of various oncogenic pathways were differentially expressed along tumor progression. Furthermore, intensive substantial crosstalk between ductal cells and stromal cells was identified. Finally, genes (REG4 and SPINK1) screened out of differentially expressed genes (DEGs) were upregulated in PDAC cell lines. Silencing either of them significantly impaired proliferation, invasion, migration and stemness of PDAC cells. Conclusions Our findings offer a valuable resource for deciphering the heterogeneity of malignant ductal cells in PDAC. REG4 and SPINK1 are expected to be promising targets for PDAC therapy.
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MESH Headings
- Female
- Humans
- Male
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/pathology
- Cell Line, Tumor
- Gene Expression Regulation, Neoplastic
- Lectins, C-Type/genetics
- Lectins, C-Type/metabolism
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Pancreatitis-Associated Proteins
- Prognosis
- Single-Cell Analysis
- Transcriptome
- Trypsin Inhibitor, Kazal Pancreatic/genetics
- Trypsin Inhibitor, Kazal Pancreatic/metabolism
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Affiliation(s)
- Yutian Ji
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | | | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
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48
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Ahn BY, Kim B, Park S, Kim SG, Han K, Cho SJ. Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study. Cancer 2024; 130:1807-1815. [PMID: 38198291 DOI: 10.1002/cncr.35197] [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: 08/10/2023] [Revised: 11/20/2023] [Accepted: 12/12/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.
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Affiliation(s)
- Byeong Yun Ahn
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Bokyung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sanghyun Park
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Soo-Jeong Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Orešković D, Madero Pohlen A, Cvitković I, Alen JF, Raguž M, Álvarez-Sala de la Cuadra A, Bazarra Castro GJ, Bušić Z, Konstantinović I, Ledenko V, Martínez Macho C, Müller D, Žarak M, Jovanov-Milosevic N, Chudy D, Marinović T. Chronic hyperglycemia and intracranial meningiomas. BMC Cancer 2024; 24:488. [PMID: 38632533 PMCID: PMC11022447 DOI: 10.1186/s12885-024-12243-4] [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: 12/27/2023] [Accepted: 04/09/2024] [Indexed: 04/19/2024] Open
Abstract
Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.
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Affiliation(s)
- D Orešković
- Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia.
| | - A Madero Pohlen
- Department of Neurosurgery, University Hospital de la Princesa, Madrid, Spain
| | - I Cvitković
- Department of Neurosurgery, University Hospital Center Split, Split, Croatia
| | - J F Alen
- Department of Neurosurgery, University Hospital de la Princesa, Madrid, Spain
| | - M Raguž
- Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia
| | | | - G J Bazarra Castro
- Department of Neurosurgery, University Hospital de la Princesa, Madrid, Spain
| | - Z Bušić
- Department of Neurosurgery, University Hospital Center Split, Split, Croatia
| | - I Konstantinović
- Department of Neurosurgery, University Hospital Center Split, Split, Croatia
| | - V Ledenko
- Department of Neurosurgery, University Hospital Center Split, Split, Croatia
| | - C Martínez Macho
- Department of Neurosurgery, University Hospital de la Princesa, Madrid, Spain
| | - D Müller
- Department of Pathology, Clinical Hospital Dubrava, Zagreb, Croatia
| | - M Žarak
- Clinical Department of Laboratory Diagnostics, Clinical Hospital Dubrava, Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
| | - N Jovanov-Milosevic
- Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia
| | - D Chudy
- Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia
- Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia
| | - T Marinović
- Department of Neurosurgery, Clinical Hospital Dubrava, Zagreb, Croatia
- Department of Neurology and Neurosurgery, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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Galal MA, Al-Rimawi M, Hajeer A, Dahman H, Alouch S, Aljada A. Metformin: A Dual-Role Player in Cancer Treatment and Prevention. Int J Mol Sci 2024; 25:4083. [PMID: 38612893 PMCID: PMC11012626 DOI: 10.3390/ijms25074083] [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: 03/06/2024] [Revised: 03/30/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.
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Affiliation(s)
- Mariam Ahmed Galal
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia; (M.A.G.); (M.A.-R.); (H.D.); (S.A.)
- Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK
| | - Mohammed Al-Rimawi
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia; (M.A.G.); (M.A.-R.); (H.D.); (S.A.)
| | | | - Huda Dahman
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia; (M.A.G.); (M.A.-R.); (H.D.); (S.A.)
| | - Samhar Alouch
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia; (M.A.G.); (M.A.-R.); (H.D.); (S.A.)
| | - Ahmad Aljada
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia; (M.A.G.); (M.A.-R.); (H.D.); (S.A.)
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