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Yin SY, Liu YC, Yang YP, Liang BY, Fu ZY, Fan M, Zhang YC, Xie ZH, Han K, Wang JP, Zhang L, Zhang L, Tong BS, Han YX, Zhang CJ. Exploring genes associated with metabolic dysfunction as therapeutic targets for head and neck cancers: a novel strategy. Int J Surg 2025; 111:3129-3134. [PMID: 39907620 DOI: 10.1097/js9.0000000000002293] [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: 11/08/2024] [Accepted: 01/12/2025] [Indexed: 02/06/2025]
Abstract
Evidence suggests a potential link between metabolic dysfunction and head and neck cancer (HNC). This study investigates the potential causal relationships between metabolic dysfunction and HNC using genetic data. While no significant causal associations were identified between metabolic indicators and HNC risk, the research revealed that inhibition of certain genes could reduce cancer risk. Specifically, inhibiting sodium/glucose cotransporter 2 (SLC5A2) was associated with a decreased risk of HNC and oropharyngeal cancer (OPC), while ATP-sensitive inward rectifier potassium channel 11 inhibition was linked to a reduced risk of oral cavity cancer. Additionally, inhibiting SLC5A1 and voltage-dependent L-type calcium channel subunit beta-2 showed a connection to lower OPC risk. These findings suggest that targeting these genes could offer promising therapeutic strategies for preventing and treating HNC, as well as improving both preoperative and postoperative management in affected patients.
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Affiliation(s)
| | - Yu-Chen Liu
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | | | - Bing-Yu Liang
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zi-Yue Fu
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Min Fan
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yu-Chen Zhang
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zi-Hui Xie
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ke Han
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jian-Peng Wang
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lei Zhang
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Liang Zhang
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Bu-Sheng Tong
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yan-Xun Han
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
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Lin F, Hu W, Yang C, Cheng B, Chen H, Li J, Zhu H, Zhang H, Yuan X, Ren X, Hong X, Tang X. Associations of combined lifestyle and metabolic risks with cancer incidence in the UK biobank study. BMC Cancer 2025; 25:547. [PMID: 40140964 PMCID: PMC11948676 DOI: 10.1186/s12885-025-13955-x] [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: 11/08/2024] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Although metabolic syndrome (MetS) is associated with an increased risk of various cancers, the combined impact of MetS and healthy lifestyle factors (HLF) on cancer risk is unclear. This study aimed to investigate the independent and combined effects of MetS and HLF on the risk of 16 site-specific cancers in a large community-based cohort. METHODS A total of 289,557 participants in the UK Biobank were analyzed. MetS was defined using a combination of metabolic factors, while HLF scores were evaluated based on lifestyle behaviors, such as smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models were used to investigate the relationship between MetS or HLF and cancer risk, adjusting for age, sex, ethnicity, education level, family history of cancer, and the Townsend Deprivation Index (TDI). RESULTS During a median follow-up of 11.69 years, 11,190 individuals developed cancer. MetS was associated with an increased risk of 9 cancers in men and 7 cancers in women. Compared with participants with unfavorable lifestyles, regardless of metabolic status, HLF was significantly associated with decreased risk of overall cancer (without MetS: HR: 0.812; 95% CI: 0.745-0.886 for intermediate lifestyle and HR: 0.757; 95% CI: 0.669-0.855 for favorable lifestyle; with MetS: HR: 0.702; 95% CI: 0.572-0.862 for favorable lifestyle) and oesophagus, stomach, liver, lung, bronchus, trachea cancers in men and of lung, bronchus, trachea cancers in women. Our analysis demonstrated that the protective association between HLF and reduced cancer risk was confined to subgroups without MetS. Specifically, this association was observed for cancers of the lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, bladder, and lymphoid leukemia in men, and for overall cancer in women(HR: 0.917; 95% CI: 0.862-0.975 for intermediate lifestyle and HR: 0.875; 95% CI: 0.817-0.938 for favorable lifestyle). CONCLUSION MetS elevates risks for multiple cancers, while adopting a healthy lifestyle reduces risks of oesophagus, stomach, and lung, bronchus, trachea cancers in men and lung, bronchus, trachea cancer in women, regardless of metabolic status. However, MetS counteracts lifestyle-mediated protection against specific cancers-including lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, and bladder cancers in men, as well as pancreas and breast cancers in women. These findings underscore the necessity to develop metabolic status-stratified management strategies and implement proactive prevention of MetS.
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Affiliation(s)
- Feng Lin
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Wen Hu
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Chenfenglin Yang
- Department of Hepatobiliary Surgery, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Binglin Cheng
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Hongfan Chen
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Jiaxin Li
- Department of Obstetrics & Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hanrui Zhu
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Haixiang Zhang
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Xiang Yuan
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Xianyue Ren
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xiaohong Hong
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China.
| | - Xinran Tang
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China.
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Li C, Yang X, Zhong Y, Wang W, Jin X, Bian L, Wang X. Apolipoprotein B/Apolipoprotein A1 ratio is an independent prognostic factor in pancreatic cancer. Transl Oncol 2025; 51:102208. [PMID: 39591897 PMCID: PMC11629317 DOI: 10.1016/j.tranon.2024.102208] [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: 06/14/2024] [Revised: 10/29/2024] [Accepted: 11/17/2024] [Indexed: 11/28/2024] Open
Abstract
OBJECTIVE The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer. METHODS A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. RESULTS Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA1), high ApoB/ApoA1 level indicated a shorter OS (HR:2.028, 95% CI: 1.174-2.504, P = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076-3.009, P = 0.025). Other serum lipid molecules were not associated with PFS and OS. CONCLUSION ApoB/ApoA1 might be an independent prognostic factor of pancreatic cancer.
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Affiliation(s)
- Chenxi Li
- Senior Department of Oncology, the Fifth Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Xuhui Yang
- Senior Department of Oncology, the Fifth Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Yan Zhong
- Department of Radiology, the Fourth Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Wenying Wang
- Senior Department of Obstetrics & Gynecology, the Seventh Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Xin Jin
- Senior Department of Hepato- Pancreato- Biliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, PR China
| | - Lihua Bian
- Department of Obstetrics and Gynecology, Hainan Hospital of PLA General Hospital, Sanya, PR China
| | - Xiaona Wang
- Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, PR China.
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Cao YY, Lv XJ, Li H, Qian LC, Si HP, Li Y, Guo K, Ren S, Wang ZQ. Serum High-Density Lipoprotein Cholesterol Concentrations in Pancreatic Ductal Adenocarcinoma and Its Association With Histological Grade in a Chinese Population. Cancer Control 2025; 32:10732748251316602. [PMID: 39927839 PMCID: PMC11811967 DOI: 10.1177/10732748251316602] [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: 09/24/2024] [Revised: 12/12/2024] [Accepted: 01/06/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND Serum high-density lipoprotein cholesterol (HDL-c) may influence cancer development. However, its relationship with the histological grade of pancreatic ductal adenocarcinoma (PDAC) is not well understood. This study aims to explore the potential associations between serum HDL-c levels and different histological grades of PDAC. METHODS This retrospective study included 181 patients with pathologically confirmed PDAC who underwent radical surgery. Clinical data, blood biochemical results, imaging features, and pathological details of the patients were collected, such as age, gender, diabetes, hypertension, tumor grade, tumor size and location, high-density lipoprotein (HDL-c), low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). RESULTS Patients with high-grade PDAC had significantly lower HDL-c levels compared to those with low-grade PDAC across both training and validation cohorts (P < 0.05). Significant associations were found between HDL-c levels and high-grade PDAC in the training (P < 0.001) and validation (P = 0.044) groups. Moreover, HDL-c levels were inversely related to lymph node metastasis in the training (P = 0.001) and validation (P = 0.012) sets. CONCLUSIONS Lower HDL-c levels are associated with high-grade PDAC and lymph node metastasis, suggesting that HDL-c may play a protective role in the progression of PDAC.
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Affiliation(s)
- Ying-Ying Cao
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiao-Jing Lv
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hui Li
- Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Li-Chao Qian
- Department of Geratology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Hai-Peng Si
- Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan Li
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Kai Guo
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhong-Qiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Erdoğan Özünal I, Kılıçaslan E, Elibol T, Öztürk E. High-density lipoprotein (HDL) has an impact on myeloma outcome: Lower HDL associates with worse progression-free survival. Wien Klin Wochenschr 2024; 136:398-404. [PMID: 37402933 DOI: 10.1007/s00508-023-02239-8] [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: 11/02/2022] [Accepted: 06/11/2023] [Indexed: 07/06/2023]
Abstract
BACKGROUND Multiple myeloma (MM) staging is based on beta‑2 MG, albumin, LDH levels, and the presence of chromosomal abnormalities. We aimed to evaluate the impact of high-density lipoprotein (HDL) on myeloma outcomes. MATERIALS AND METHODS This study included 148 individuals; 68 patients diagnosed with MM and 80 age, sex, comorbidity-matched controls. The relationship between HDL and myeloma stage and the association between HDL and progression-free survival (PFS) were analyzed. RESULTS Sixty-five percent of patients were male in each group. Mean HDL level was higher in the control group than myeloma group (52.6 ± 15.02 mg/dl versus 33.79 ± 12.71) (p < 0.001). According to ISS, 39 patients (57%) had advanced stage (ISS-III) disease. To assess the optimal cut-point for HDL that makes a difference in PFS, the X‑tile software program was used and in line with the created plots, the myeloma cohort was divided into two groups as HDL < 28 and ≥ 28 mg/dl. Twenty-two patients (32.4%) were in HDL < 28 group. According to the ISS, HDL < 28 group had more advanced disease than the HDL ≥ 28 group (p = 0.008). Twenty-nine patients (42.6%) progressed or died during the follow-up and 15 of these were in the HDL < 28 group. Time to progression was shorter in patients who were in the HDL < 28 group (median, 22 versus 40 months, p = 0.03). There was no statistically significant difference between these groups in terms of overall survival (p = 0.708). CONCLUSION Myeloma patients have lower HDL than controls and HDL < 28 mg/dl associates with advanced-stage disease and shorter PFS. Therefore, HDL can be a surrogate prognostic marker in myeloma.
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Affiliation(s)
- Işıl Erdoğan Özünal
- Division of Hematology, Department of Internal Medicine, Istanbul Medeniyet University, Prof. Dr. Süleyman Yalçın Göztepe City Hospital, Eğitim Mah., Kadıköy, 34722, Istanbul, Turkey.
| | - Emrah Kılıçaslan
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Tayfun Elibol
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Erman Öztürk
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
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Wang X, Gao Y, Wang H, Gong X, Bao P. Tumor markers for lipid metabolism-related genes: Based on small cell lung cancer and bronchial asthma dual analysis. ENVIRONMENTAL TOXICOLOGY 2024; 39:2855-2868. [PMID: 38293814 DOI: 10.1002/tox.24152] [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: 11/06/2023] [Revised: 01/09/2024] [Accepted: 01/17/2024] [Indexed: 02/01/2024]
Abstract
Numerous studies have elucidated the intricate relationship between bronchial asthma and small cell lung cancer (SCLC), as well as the role lipid metabolism genes play in transitioning from bronchial asthma to SCLC. Despite this, the predictive power of single gene biomarkers remains insufficient and necessitates the development of more accurate prognostic models. In our study, we downloaded and preprocessed scRNA-seq of SCLC from the GEO database GSE164404 and severe asthma scRNA-seq from GSE145013 using the Seurat package. Using the MSigDB database and geneCard database, we selected lipid metabolism-related genes and performed scRNA-seq data analysis from the gene expression GEO database, aiming to uncover potential links between immune signaling pathways in bronchial asthma and SCLC. Our investigations yielded differentially expressed genes based on the scRNA-seq dataset related to lipid metabolism. We executed differential gene analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. In-depth GSEA pathway activation analysis, crucial target gene predictions via protein-protein interactions, and key cluster gene evaluations for differential and diagnostic ROC values correlation analysis confirmed that key cluster genes are significant predictors for the progression of bronchial asthma to SCLC. To validate our findings, we performed wet laboratory experiments using real-time quantitative PCR to assess the expression of these relevant genes in SCLC cell lines. In conclusion, this research proposes a novel lipid metabolism-related gene marker that can offer comprehensive insights into the pathogenesis of bronchial asthma leading to SCLC. Although this study does not directly focus on senescence-associated molecular alterations, our findings in the lipid metabolism genes associated with inflammation and cancer progression offer valuable insights for further research targeting senescence-related changes in treating inflammatory diseases.
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Affiliation(s)
- Xiaobin Wang
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Medical University, China
| | - Yang Gao
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Medical University, China
| | - Haiqiang Wang
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Medical University, China
| | - Xiaokang Gong
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Medical University, China
| | - Peilong Bao
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Medical University, China
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Nam SY, Jo J, Cho CM. A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk. Nat Commun 2024; 15:2923. [PMID: 38575589 PMCID: PMC10994902 DOI: 10.1038/s41467-024-47193-9] [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: 05/17/2023] [Accepted: 03/19/2024] [Indexed: 04/06/2024] Open
Abstract
High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.
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Affiliation(s)
- Su Youn Nam
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
- Division of Gastroenterology, Kyungpook National University Chilgok Hospital, Daegu, South Korea.
| | - Junwoo Jo
- Department of Statistics, Kyungpook National University, Daegu, South Korea
| | - Chang-Min Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
- Division of Gastroenterology, Kyungpook National University Chilgok Hospital, Daegu, South Korea
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Allegra A, Murdaca G, Mirabile G, Gangemi S. Protective Effects of High-Density Lipoprotein on Cancer Risk: Focus on Multiple Myeloma. Biomedicines 2024; 12:514. [PMID: 38540127 PMCID: PMC10967848 DOI: 10.3390/biomedicines12030514] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/21/2024] [Accepted: 02/23/2024] [Indexed: 04/03/2025] Open
Abstract
Lipid metabolism is intrinsically linked to tumorigenesis. And one of the most important characteristics of cancer is the modification of lipid metabolism and its correlation with oncogenic signaling pathways within the tumors. Because lipids function as signaling molecules, membrane structures, and energy sources, lipids are essential to the development of cancer. Above all, the proper immune response of tumor cells depends on the control of lipid metabolism. Changes in metabolism can modify systems that regulate carcinogenesis, such as inflammation, oxidative stress, and angiogenesis. The dependence of various malignancies on lipid metabolism varies. This review delves into the modifications to lipid metabolism that take place in cancer, specifically focusing on multiple myeloma. The review illustrates how changes in different lipid pathways impact the growth, survival, and drug-responsiveness of multiple myeloma cells, in addition to their interactions with other cells within the tumor microenvironment. The phenotype of malignant plasma cells can be affected by lipid vulnerabilities, and these findings offer a new avenue for understanding this process. Additionally, they identify novel druggable pathways that have a major bearing on multiple myeloma care.
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Affiliation(s)
- Alessandro Allegra
- Hematology Unit, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (A.A.); (G.M.)
| | - Giuseppe Murdaca
- Department of Internal Medicine, University of Genova, Viale Benedetto XV, 16132 Genova, Italy
- Allergology and Clinical Immunology Unit, San Bartolomeo Hospital, 19038 Sarzana, Italy
| | - Giuseppe Mirabile
- Hematology Unit, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (A.A.); (G.M.)
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
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Li L, Yu Z, Ren J, Niu T. Low cholesterol levels are associated with increasing risk of plasma cell neoplasm: A UK biobank cohort study. Cancer Med 2023; 12:20964-20975. [PMID: 37908181 PMCID: PMC10709719 DOI: 10.1002/cam4.6649] [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: 07/10/2023] [Revised: 09/20/2023] [Accepted: 10/04/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry. METHODS Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms. RESULTS We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all ptrend <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma. CONCLUSION Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
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Affiliation(s)
- Linfeng Li
- Department of Hematology, Institute of Hematology, West China HospitalSichuan UniversityChengduChina
| | - Zhengyu Yu
- Department of Hematology, Institute of Hematology, West China HospitalSichuan UniversityChengduChina
| | - Jianjun Ren
- Department of Otolaryngology‐Head and Neck Surgery, West China Hospital, West China Medical SchoolSichuan UniversityChengduChina
| | - Ting Niu
- Department of Hematology, Institute of Hematology, West China HospitalSichuan UniversityChengduChina
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Scherübl H. [Metabolic syndrome and gastrointestinal cancer screening]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1394-1400. [PMID: 36379464 DOI: 10.1055/a-1959-3829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his cancer risk is. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric and esophageal adenocarcinomas. MetS increases cancer mortality up to 2.4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Preventing and treating the MetS together with GI cancer screening is effective and decreases the burden of GI cancer mortality significantly.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin; Gastroenterol., GI Onkol. u. Infektiol., Vivantes Klinikum Am Urban, Berlin, Germany
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Wang H, Nam SY, Jo J. Effect of chronic viral hepatitis and metabolic factors on renal cancer risk in a large cohort in Republic of Korea. Prev Med 2023; 175:107714. [PMID: 37758123 DOI: 10.1016/j.ypmed.2023.107714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 09/20/2023] [Accepted: 09/23/2023] [Indexed: 10/03/2023]
Abstract
PURPOSE We investigated the association between hepatic and metabolic factors and renal cancer risk. METHODS This population-based cohort study included cancer-free individuals who underwent general health evaluation (January to December 2010) at the Korean National Health Insurance Service and followed-up through 2017. Hazard ratios (HR) and 95% confidence intervals (CI), determined by adjusted Cox regression analysis were used to investigate the effect of variables on renal cancer risk. RESULTS Among 4,518,704 subjects, 6531 patients developed renal cancer. Adjusted analyses of epidemiological factors and BMI (body mass index) (Model I) showed serum high-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL (adjusted HR [aHR] 0.88, 95% CI, 0.81-0.95) reduced renal cancer risk comparing to low HDL-C, whereas hepatitis B virus (HBV) antigen (aHR 1.41, 95% CI 1.19-1.68) and chronic HBV infection (aHR 1.65, 95% CI 1.26-2.17) increased its risk. Higher BMI increased renal cancer risk in dose-dependent manner (P for trend <0.001). This association persisted after adjustment for epidemiological factors and waist circumference (Model II). Sex-specific analyses showed similar effect of HBV antigen and chronic HBV infection in both sexes. Normal (50-59 mg/dL in women) or high (≥60 mg/dL in men) HDL-C reduced renal cancer risk. Alcohol consumption increased kidney cancer risk in age ≥ 60 years, but it had no association with renal cancer in age < 60 years. CONCLUSIONS High serum HDL-C levels reduced and HBV antigen and chronic HBV infection increased renal cancer risk across different adjusted analysis models. This effect of low HDL-C and chronic HBV infection persisted in sex-based subanalysis.
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Affiliation(s)
- Hoyoung Wang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Su Youn Nam
- Department of Internal Medicine, Kyungpook National U-653rsity Hospital, Buk-gu, Daegu, Republic of Korea.
| | - Junwoo Jo
- Department of Statistics, Kyungpook National University, Buk-gu, Daegu, Republic of Korea
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12
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Liu M, Zhang JY. Reduction rate of monoclonal protein as a useful prognostic factor in standard-risk group of newly diagnosed multiple myeloma. World J Clin Cases 2023; 11:5643-5652. [PMID: 37727707 PMCID: PMC10506002 DOI: 10.12998/wjcc.v11.i24.5643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 07/02/2023] [Accepted: 08/01/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Multiple myeloma (MM) is a common hematologic malignancy that originates from a malignant clone of plasma cells. Solitary plasmacytoma, history of diabetes, and platelet count are considered as prognostic factors for MM. But some patients are still associated with much worse outcomes without any prognostic predictors. This study aimed to observe the reduction rate of monoclonal protein (M protein) after the first and fourth chemotherapy cycles, which is considered as a new prognostic factor for progression-free survival (PFS) in standard-risk group of newly diagnosed MM patients. AIM To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor. METHODS A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included. All patients were diagnosed according to the National Comprehensive Cancer Network (NCCN) 2020.V1 diagnostic criteria. The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines. After diagnosis, 164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy. The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria. The following baseline data from the patients were collected: Gender, age at diagnosis, Durie-Salmon stage, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, catabolite activator protein, albumin/globulin ratio, lactate dehydrogenase, translocation (t)(6;14), t(11;14), maintenance regimen, total cholesterol (TC), triglyceride, and phosphorous. All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis. The factors influencing the overall survival and PFS were then assessed by multivariate analysis. We found the first cycle (C1) reduction rate and the fourth cycle (C4) reduction rate as predictors of PFS. Then, PFS was compared between patients with a C1 reduction rate of M protein of ≥ 25% vs < 25% and ≥ 50% vs < 50%, and between patients with a C4 reduction rate of ≥ 25% vs < 25%, ≥ 50% vs < 50%, and ≥ 75% vs < 75%. RESULTS Multivariate analysis revealed age [hazard ratio (HR): 1.059, 95% confidence interval (95%CI): 1.033-1.085, P ≤ 0.001], International Staging System stage (HR: 2.136, 95%CI: 1.500-3.041, P ≤ 0.001), autotransplantion (HR: 0.201, 95%CI: 0.069-0.583, P = 0.019), TC (HR: 0.689, 95%CI: 0.533-0.891, P = 0.019), C1 reduction rate (HR: 0474, 95%CI: 0.293-0.767, P = 0.019), and C4 reduction rate (HR: 0.254, 95%CI: 0.139-0.463, P = 0.019) as predictors of PFS. The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle (≥ 50%) and fourth cycle (≥ 75%) chemotherapy was associated with a longer PFS than the lower one. CONCLUSION Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.
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Affiliation(s)
- Min Liu
- Department of Hematology, Lishui Municipal Central Hospital, Lishui 323000, Zhejiang Province, China
| | - Jun-Yu Zhang
- Department of Hematology, Lishui Municipal Central Hospital, Lishui 323000, Zhejiang Province, China
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13
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Grigor’eva IN, Efimova OV, Tov NL, Suvorova TS, Nepomnyashchikh DL. Metabolic Risk Factors and Their Impact on Quality of Life in Patients with Pancreatic Cancer, Acute or Exacerbated Chronic Pancreatitis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:49-60. [DOI: 10.22416/1382-4376-2023-33-3-49-60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Аim: to evaluate metabolic risk factors and their impact on quality of life in patients with pancreatic cancer (PC) and in patients with acute or exacerbated chronic pancreatitis.Materials and methods. Forty-five patients with PC (group 1) and 141 patients with acute pancreatitis or exacerbated chronic pancreatitis (group 2) in an observational multicenter clinical cross-sectional uncontrolled study were examined. Clinical, laboratory and instrumental examination of patients and assessment of risk factors (lipid profile, blood plasma glucose, obesity, arterial hypertension) were carried out in accordance with clinical recommendations. Patients completed the SF-36 questionnaire once to assess quality of life at hospital admission before treatment.Results. In group 1, indicators of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) in blood serum (3.7 ± 0.2; 2.2 ± 0.2 and 0.8 ± 0.1 mmol/L) were lower than in group 2 (5.1 ± 0.1; 3.1 ± 0.1 and 1.2 ± 0.1 mmol/L; p < 0.05). Arterial hypertension was more common in group 1 (55.6 %) than in group 2 (34.8 %; p = 0.013). The presence of arterial hypertension increases the chance of having PC by 2.7 times (p < 0.05). Body mass index parameters, including obesity, as well as parameters of triglycerides, and fasting plasma glucose, did not differ between the groups. Logistic regression analysis revealed a direct relationship with PC HDL hypocholesterolemia (Exp B = 4.976; p < 0.001) and arterial hypertension (Exp B = 2.742; p = 0.027) and an inverse relationship — with hypercholesterolemia (Exp B = 0.204; p = 0.002). The chance of having PC was not associated with age, fasting plasma glucose ³ 7.0 mmol/L, obesity. Quality of life indicators were higher in group 1 than in group 2 on four SF-36 scales: bodily pain (68.1 ± 5.1 and 36.8 ± 2.0; p < 0.001), general health (51.1 ± 2.5 and 38.0 ± 1.7 points; p < 0.001), social functioning (74.7 ± 3.0 and 64.5 ± 2.2 points; p = 0.007), role emotional functioning (28.2 ± 5.2 and 12.5 ± 3.1 points; p = 0.007) and in the general domain “physical component of health” (40.2 ± 1.0 and 33.6 ± 0.8 points; p < 0.001). In group 1 with HDL hypocholesterolemia compared with its absence, the indicators of role emotional functioning (22.2 ± 5.1 and 51.9 ± 13.7 points; p = 0.020) were lower, with arterial hypertension compared with its absence — role physical functioning (5.0 ± 4.0 and 25.5 ± 7.5 points; p = 0.036) and role emotional functioning (16.0 ± 5.1 and 43.3 ± 8.8 points; p = 0.007) were lower.Conclusions. In patients with PC arterial hypertension was more common and the levels of total cholesterol, LDL-C and HDL-C were lower than in patients with acute or exacerbated chronic pancreatitis. The chance of having PC is directly associated with HDL hypocholesterolemia, with arterial hypertension, inversely — with hypercholesterolemia, and is not associated with age, fasting plasma glucose ³ 7 mmol/L, or obesity. In patients with PC, quality of life indicators were higher on four SF-36 scales and on the general domain “physical component of health” than in the group with acute or exacerbated chronic pancreatitis. In patients with PC metabolic factors significantly worsened self-assessment of quality of life in terms of role functioning; in patients with acute or exacerbated chronic pancreatitis there was no such association.
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Affiliation(s)
- I. N. Grigor’eva
- Research Institute of Therapy and Preventive Medicine — Branch of the Federal Scientific Center “Institute of Cytology and Genetics” of the Siberian Branch of the Russian Academy of Sciences
| | - O. V. Efimova
- Research Institute of Therapy and Preventive Medicine — Branch of the Federal Scientific Center “Institute of Cytology and Genetics” of the Siberian Branch of the Russian Academy of Sciences
| | - N. L. Tov
- Novosibirsk State Medical University
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14
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Zvintzou E, Xepapadaki E, Skroubis G, Mparnia V, Giannatou K, Benabdellah K, Kypreos KE. High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities. Pharmaceuticals (Basel) 2023; 16:855. [PMID: 37375802 DOI: 10.3390/ph16060855] [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: 04/10/2023] [Revised: 05/17/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of "the more the better", ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.
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Affiliation(s)
- Evangelia Zvintzou
- Department of Pharmacology, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
| | - Eva Xepapadaki
- Department of Pharmacology, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
| | - George Skroubis
- Morbid Obesity Unit, Department of Surgery, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
| | - Victoria Mparnia
- Department of Pharmacology, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
| | - Katerina Giannatou
- Department of Pharmacology, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
| | - Karim Benabdellah
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Avda. de la Ilustración 114, 18016 Granada, Spain
| | - Kyriakos E Kypreos
- Department of Pharmacology, School of Medicine, University of Patras, Rio Achaias, 26500 Patras, Greece
- Department of Life Sciences, School of Sciences, European University Cyprus, 2404 Nicosia, Cyprus
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15
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Fessler MB. We need to talk about lung cancer's cholesterol-hoarding problem. Cell Stem Cell 2023; 30:745-747. [PMID: 37267910 DOI: 10.1016/j.stem.2023.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 05/04/2023] [Accepted: 05/05/2023] [Indexed: 06/04/2023]
Abstract
Proliferative cells require excess cholesterol to support rapid membrane biogenesis. Using a mutant KRAS mouse model of non-small cell lung cancer, Guilbaud et al. show that lung cancers accumulate cholesterol by locally and distally reprogramming lipid trafficking and that cholesterol-removing interventions may hold promise as a therapeutic strategy.
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Affiliation(s)
- Michael B Fessler
- Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
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16
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Guilbaud E, Barouillet T, Ilie M, Borowczyk C, Ivanov S, Sarrazy V, Vaillant N, Ayrault M, Castiglione A, Rignol G, Brest P, Bazioti V, Zaitsev K, Lebrigand K, Dussaud S, Magnone V, Bertolotto C, Marchetti S, Irondelle M, Goldberg I, Huby T, Westerterp M, Gautier EL, Mari B, Barbry P, Hofman P, Yvan-Charvet L. Cholesterol efflux pathways hinder KRAS-driven lung tumor progenitor cell expansion. Cell Stem Cell 2023; 30:800-817.e9. [PMID: 37267915 DOI: 10.1016/j.stem.2023.05.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/13/2023] [Accepted: 05/04/2023] [Indexed: 06/04/2023]
Abstract
Cholesterol efflux pathways could be exploited in tumor biology to unravel cancer vulnerabilities. A mouse model of lung-tumor-bearing KRASG12D mutation with specific disruption of cholesterol efflux pathways in epithelial progenitor cells promoted tumor growth. Defective cholesterol efflux in epithelial progenitor cells governed their transcriptional landscape to support their expansion and create a pro-tolerogenic tumor microenvironment (TME). Overexpression of the apolipoprotein A-I, to raise HDL levels, protected these mice from tumor development and dire pathologic consequences. Mechanistically, HDL blunted a positive feedback loop between growth factor signaling pathways and cholesterol efflux pathways that cancer cells hijack to expand. Cholesterol removal therapy with cyclodextrin reduced tumor burden in progressing tumor by suppressing the proliferation and expansion of epithelial progenitor cells of tumor origin. Local and systemic perturbations of cholesterol efflux pathways were confirmed in human lung adenocarcinoma (LUAD). Our results position cholesterol removal therapy as a putative metabolic target in lung cancer progenitor cells.
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Affiliation(s)
- Emma Guilbaud
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
| | - Thibault Barouillet
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Marius Ilie
- Institute of Research on Cancer and Aging of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Université Côte d'Azur, CHU de Nice, University Hospital Federation OncoAge, 06107 Nice, France
| | - Coraline Borowczyk
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Stoyan Ivanov
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Vincent Sarrazy
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Nathalie Vaillant
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Marion Ayrault
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Alexia Castiglione
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Guylène Rignol
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Patrick Brest
- Institute of Research on Cancer and Aging of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Université Côte d'Azur, CHU de Nice, University Hospital Federation OncoAge, 06107 Nice, France
| | - Venetia Bazioti
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Konstantin Zaitsev
- Computer Technologies Department, ITMO University, Saint Petersburg, Russia
| | - Kevin Lebrigand
- Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, FHU-OncoAge, Nice Sophia-Antipolis, France
| | | | - Virginie Magnone
- Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, FHU-OncoAge, Nice Sophia-Antipolis, France
| | - Corine Bertolotto
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Sandrine Marchetti
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Marie Irondelle
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France
| | - Ira Goldberg
- Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, USA
| | - Thierry Huby
- Sorbonne Université, INSERM, UMR_S 1166 ICAN, 75013 Paris, France
| | - Marit Westerterp
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | | | - Bernard Mari
- Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, FHU-OncoAge, Nice Sophia-Antipolis, France
| | - Pascal Barbry
- Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, FHU-OncoAge, Nice Sophia-Antipolis, France
| | - Paul Hofman
- Institute of Research on Cancer and Aging of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Université Côte d'Azur, CHU de Nice, University Hospital Federation OncoAge, 06107 Nice, France
| | - Laurent Yvan-Charvet
- Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) OncoAge, 06204 Nice, France.
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17
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Nishiyama H, Funamizu T, Iwata H, Endo H, Chikata Y, Doi S, Wada H, Naito R, Ogita M, Kato Y, Okai I, Dohi T, Kasai T, Isoda K, Okazaki S, Miyauchi K, Minamino T. Low apolipoprotein A1 was associated with increased risk of cancer mortality in patients following percutaneous coronary intervention: A 10-year follow-up study. Int J Cancer 2022; 151:1482-1490. [PMID: 35796324 PMCID: PMC9540779 DOI: 10.1002/ijc.34164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/12/2022] [Accepted: 05/24/2022] [Indexed: 11/11/2022]
Abstract
Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-C) predicted reduced risk of cardiovascular-related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single-center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow-up period between the index PCI and latest follow-up were 5.9 and 0-17.8 years, respectively. Consequently, Kaplan-Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL-C. Multivariable Cox proportional hazard regression analysis adjusted by cancer-related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.
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Affiliation(s)
- Hiroki Nishiyama
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Takehiro Funamizu
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Hiroshi Iwata
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Hirohisa Endo
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Yuichi Chikata
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Shinichiro Doi
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Hideki Wada
- Department of CardiologyJuntendo University Shizuoka HospitalShizuokaJapan
| | - Ryo Naito
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Manabu Ogita
- Department of CardiologyJuntendo University Shizuoka HospitalShizuokaJapan
| | - Yoshiteru Kato
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Iwao Okai
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Tomotaka Dohi
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Takatoshi Kasai
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Kikuo Isoda
- Department of CardiologyJuntendo University Nerima HospitalTokyoJapan
| | - Shinya Okazaki
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Katsumi Miyauchi
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Tohru Minamino
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
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18
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Oberle R, Kührer K, Österreicher T, Weber F, Steinbauer S, Udonta F, Wroblewski M, Ben-Batalla I, Hassl I, Körbelin J, Unseld M, Jauhiainen M, Plochberger B, Röhrl C, Hengstschläger M, Loges S, Stangl H. The HDL particle composition determines its antitumor activity in pancreatic cancer. Life Sci Alliance 2022; 5:e202101317. [PMID: 35577388 PMCID: PMC9112193 DOI: 10.26508/lsa.202101317] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 12/03/2022] Open
Abstract
Despite enormous efforts to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis promotes growth advantage to and chemotherapy resistance for PDAC tumor cells. Here, we demonstrate that high-density lipoprotein (HDL)-mediated efficient cholesterol removal from cancer cells results in PDAC cell growth reduction and induction of apoptosis in vitro. This effect is driven by an HDL particle composition-dependent interaction with SR-B1 and ABCA1 on cancer cells. AAV-mediated overexpression of APOA1 and rHDL injections decreased PDAC tumor development in vivo. Interestingly, plasma samples from pancreatic-cancer patients displayed a significantly reduced APOA1-to-SAA1 ratio and a reduced cholesterol efflux capacity compared with healthy donors. We conclude that efficient, HDL-mediated cholesterol depletion represents an interesting strategy to interfere with the aggressive growth characteristics of PDAC.
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Affiliation(s)
- Raimund Oberle
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
| | - Kristina Kührer
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
| | - Tamina Österreicher
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
| | - Florian Weber
- School of Medical Engineering and Applied Social Sciences, University of Applied Sciences Upper Austria, Linz, Austria
| | - Stefanie Steinbauer
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria
| | - Florian Udonta
- Department of Oncology, Hematology and Bone Marrow Transplantation, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Mark Wroblewski
- Department of Oncology, Hematology and Bone Marrow Transplantation, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Isabel Ben-Batalla
- Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ingrid Hassl
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
| | - Jakob Körbelin
- ENDomics Lab, Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Matthias Unseld
- Department of Medicine I, Division of Palliative Medicine, Medical University of Vienna, Vienna, Austria
| | - Matti Jauhiainen
- Minerva Foundation Institute for Medical Research and Finnish Institute for Health and Welfare, Genomics and Biobank Unit, Biomedicum 2U, Helsinki, Finland
| | - Birgit Plochberger
- School of Medical Engineering and Applied Social Sciences, University of Applied Sciences Upper Austria, Linz, Austria
| | - Clemens Röhrl
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria
| | - Markus Hengstschläger
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
| | - Sonja Loges
- Department of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Herbert Stangl
- Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria
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Abstract
Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his risk of cancer. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric, esophageal, thyroid, breast, endometrial and renal cell cancers. MetS increases cancer mortality up to 2,4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Both a low-risk lifestyle and cancer screening are effective and decrease the burden of cancer.
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Kim J, Kim MK, Baek KH, Song KH, Han K, Kwon HS. Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea. Endocrinol Metab (Seoul) 2022; 37:303-311. [PMID: 35381688 PMCID: PMC9081313 DOI: 10.3803/enm.2021.1332] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/11/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer. METHODS The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models. RESULTS A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126). CONCLUSION Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.
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Affiliation(s)
- Jinyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki-Hyun Baek
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
- Corresponding authors: Kyungdo Han Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul 06978, Korea Tel: +82-2-820-7025, Fax: +82-2-823-1746, E-mail:
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Hyuk-Sang Kwon Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea Tel: +82-2-3779-1039, Fax: +82-2-786-1479, E-mail:
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21
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Karahan I, Arslan F, Yalçin S. The prediction of lung cancer prognosis with blood lipid levels and ratios at the time of diagnosis. BIOMEDICAL AND BIOTECHNOLOGY RESEARCH JOURNAL (BBRJ) 2022. [DOI: 10.4103/bbrj.bbrj_311_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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22
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Loosen SH, Kostev K, Luedde M, Luedde T, Roderburg C. Low blood levels of high-density lipoprotein (HDL) cholesterol are positively associated with cancer. J Cancer Res Clin Oncol 2021; 148:3039-3046. [PMID: 34897572 PMCID: PMC9508001 DOI: 10.1007/s00432-021-03867-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/06/2021] [Indexed: 12/01/2022]
Abstract
Purpose There is a growing body of evidence suggesting a decisive involvement of the human lipid metabolism in cancer development. However, clinical data on the association between blood triglyceride or cholesterol levels including the cholesterol transporters high-density and low-density lipoproteins (LDL, HDL) and cancer incidence have remained inconclusive. Here, we investigated the association between blood triglyceride as well as total, LDL and HDL cholesterol levels and cancer among outpatients from Germany. Methods 61,936 patients with available blood lipid values were identified from the IQVIA Disease Analyzer database and followed up between 2005 and 2019. Multivariable logistic regression models were used to study the association between lipid values and cancer. Results The probability of cancer was significantly lower among patients with elevated total cholesterol concentrations and higher in patients with decreased HDL serum levels. In contrast, serum concentrations of LDL and triglycerides had no impact on cancer risk. In cancer site-stratified analyses, we observed a trend towards higher rates of cancers from digestive organs, breast, skin cancer, urinary tract and cancers from lymphoid and hematopoietic tissue in patients with HDL values < 35 mg/dl, while a negative association between total cholesterol > 250 mg/dl and respiratory organ as well as urinary tract cancers was observed. Conclusion Our data strongly support the hypothesis that serum-specific lipid profiles are positively associated with cancer.
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Affiliation(s)
- Sven H Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | | | | | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
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He T, Wang Z, Wu Y, Zhang X, Li X, Li J, Du L, Chen J, Lv Q. Lipid changes during the perioperative period in patients with early breast cancer: a real-world retrospective analysis. BMC Surg 2021; 21:396. [PMID: 34772381 PMCID: PMC8588613 DOI: 10.1186/s12893-021-01396-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 11/04/2021] [Indexed: 02/08/2023] Open
Abstract
Background Surgery remains the major treatment for early breast cancer (BC), but surgery itself is also a trauma which might induce alterations in lipid metabolism. The aim of this study was to investigate the changes in lipid profiles and to explore factors associated with lipid changes pre- and postoperation. Methods We retrospectively analyzed the pre- and postoperative serum lipid profiles of 1934 BC patients. Results The levels of triglycerides (TG) (p < 0.001) and low-density lipoprotein cholesterol (LDL) (p < 0.001) were significantly elevated after surgery, while the levels of high-density lipoprotein cholesterol (HDL) (p < 0.001) were significantly decreased. After surgery, 27.76% of patients with preoperative ortholiposis developed dyslipidemia. Postmenopausal BC patients had a higher incidence of dyslipidemia (32.31%) after surgery than premenopausal BC patients (26.07%; p = 0.041). Additionally, patients with BMI > 24 (34.92%) had a higher incidence of dyslipidemia than patients with BMI ≤ 24 (24.84%; p = 0.001). Moreover, the magnitudes of the TG increase (p < 0.001), cholesterol (TC) increase (p = 0.013) and LDL increase (p = 0.015) in the premenopausal group were all greater than those in the postmenopausal group. After adjusting for multiple baseline covariates, preoperative hyperlipidemia and progesterone receptor (PR)-positive status were significantly associated with elevated TG, TC and LDL levels after surgery. Conclusions Serum lipid profiles of BC patients may increase after surgery, especially premenopausal patients. Additionally, postmenopausal and overweight patients may have a higher risk of being diagnosed with dyslipidemia after surgery. Therefore, lipid monitoring, dyslipidemia prevention and corresponding interventions should be taken into consideration during the perioperative period.
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Affiliation(s)
- Tao He
- Department of Breast Surgery, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zhu Wang
- Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yunhao Wu
- West China School of Medicine/West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xinyi Zhang
- West China School of Medicine/West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xu Li
- Center of Biostatistics, Design, Measurement and Evaluation (CBDME), Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jiayuan Li
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Liang Du
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jie Chen
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Qing Lv
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
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Fragkoulis C, Glykas I, Tzelves L, Stasinopoulos K, Lazarou L, Kaoukis A, Dellis A, Stathouros G, Papadopoulos G, Ntoumas K. Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy. Arch Ital Urol Androl 2021; 93:291-295. [PMID: 34839634 DOI: 10.4081/aiua.2021.3.291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/10/2021] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION AND OBJECTIVE Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.
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Affiliation(s)
| | - Ioannis Glykas
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Lazaros Tzelves
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | | | - Lazaros Lazarou
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | - Andreas Kaoukis
- Department of Cardiology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Athanasios Dellis
- 2nd Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens.
| | - Georgios Stathouros
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
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Cao J, Yan W, Ma X, Huang H, Yan H. Insulin-like Growth Factor 2 mRNA-Binding Protein 2-a Potential Link Between Type 2 Diabetes Mellitus and Cancer. J Clin Endocrinol Metab 2021; 106:2807-2818. [PMID: 34061963 PMCID: PMC8475209 DOI: 10.1210/clinem/dgab391] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Indexed: 12/12/2022]
Abstract
CONTEXT Type 2 diabetes mellitus (T2DM) and cancer share a variety of risk factors and pathophysiological features. It is becoming increasingly accepted that the 2 diseases are related, and that T2DM increases the risk of certain malignancies. OBJECTIVE This review summarizes recent advancements in the elucidation of functions of insulin-like growth factor 2 (IGF-2) messenger RNA (mRNA)-binding protein 2 (IGF2BP2) in T2DM and cancer. METHODS A PubMed review of the literature was conducted, and search terms included IGF2BP2, IMP2, or p62 in combination with cancer or T2DM. Additional sources were identified through manual searches of reference lists. The increased risk of multiple malignancies and cancer-associated mortality in patients with T2DM is believed to be driven by insulin resistance, hyperinsulinemia, hyperglycemia, chronic inflammation, and dysregulation of adipokines and sex hormones. Furthermore, IGF-2 is oncogenic, and its loss-of-function splice variant is protective against T2DM, which highlights the pivotal role of this growth factor in the pathogenesis of these 2 diseases. IGF-2 mRNA-binding proteins, particularly IGF2BP2, are also involved in T2DM and cancer, and single-nucleotide variations (formerly single-nucleotide polymorphisms) of IGF2BP2 are associated with both diseases. Deletion of the IGF2BP2 gene in mice improves their glucose tolerance and insulin sensitivity, and mice with transgenic p62, a splice variant of IGF2BP2, are prone to diet-induced fatty liver disease and hepatocellular carcinoma, suggesting the biological significance of IGF2BP2 in T2DM and cancer. CONCLUSION Accumulating evidence has revealed that IGF2BP2 mediates the pathogenesis of T2DM and cancer by regulating glucose metabolism, insulin sensitivity, and tumorigenesis. This review provides insight into the potential involvement of this RNA binding protein in the link between T2DM and cancer.
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Affiliation(s)
- Junguo Cao
- Shaanxi Eye Hospital (Xi’an People’s Hospital), Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 71004, Shaanxi Province, China
- Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Heidelberg 69120, Germany
| | - Weijia Yan
- Shaanxi Eye Hospital (Xi’an People’s Hospital), Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 71004, Shaanxi Province, China
- Department of Ophthalmology, University of Heidelberg, Heidelberg 69120, Germany
| | - Xiujian Ma
- Division of Molecular Neurogenetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Haiyan Huang
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130000, China
| | - Hong Yan
- Shaanxi Eye Hospital (Xi’an People’s Hospital), Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 71004, Shaanxi Province, China
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Luo F, Zeng KM, Cao JX, Zhou T, Lin SX, Ma WJ, Yang YP, Zhang ZH, Lu FT, Huang Y, Zhao HY, Zhang L. Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study. Lipids Health Dis 2021; 20:109. [PMID: 34544437 PMCID: PMC8454045 DOI: 10.1186/s12944-021-01538-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/25/2022] Open
Abstract
Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.
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Affiliation(s)
- Fan Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Kang-Mei Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
| | - Jia-Xin Cao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Ting Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Su-Xia Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Pathology, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Wen-Juan Ma
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Yun-Peng Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Zhong-Han Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Fei-Teng Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Yan Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Hong-Yun Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Clinical Research, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
| | - Li Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
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Gu JN, Yao S, Cao YH, Deng SH, Mao FW, Jiang HY, He YT, Li XY, Ke SQ, Li HL, Li H, Liu XH, Liu HL, Wang JL, Wu K, Liu L, Cai KL. Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients. World J Gastrointest Surg 2021; 13:689-701. [PMID: 34354802 PMCID: PMC8316850 DOI: 10.4240/wjgs.v13.i7.689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/11/2021] [Accepted: 06/28/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.
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Affiliation(s)
- Jun-Nan Gu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Shuang Yao
- Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Ying-Hao Cao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Sheng-He Deng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Fu-Wei Mao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hong-Yu Jiang
- Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yang-Ting He
- Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xin-Ying Li
- Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Song-Qing Ke
- Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hui-Li Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hang Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xing-Hua Liu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hong-Li Liu
- Cancer Center, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Ji-Liang Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Ke Wu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Li Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Kai-Lin Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Connecting Cholesterol Efflux Factors to Lung Cancer Biology and Therapeutics. Int J Mol Sci 2021; 22:ijms22137209. [PMID: 34281263 PMCID: PMC8268178 DOI: 10.3390/ijms22137209] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/28/2021] [Accepted: 06/30/2021] [Indexed: 12/17/2022] Open
Abstract
Cholesterol is a foundational molecule of biology. There is a long-standing interest in understanding how cholesterol metabolism is intertwined with cancer biology. In this review, we focus on the known connections between lung cancer and molecules mediating cholesterol efflux. A major take-home lesson is that the roles of many cholesterol efflux factors remain underexplored. It is our hope that this article would motivate others to investigate how cholesterol efflux factors contribute to lung cancer biology.
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Wei Y, Huang Y, Yang W, Huang Q, Chen Y, Zeng K, Chen J, Chen J. The significances and clinical implications of cholesterol components in human breast cancer. Sci Prog 2021; 104:368504211028395. [PMID: 34510991 PMCID: PMC10450717 DOI: 10.1177/00368504211028395] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Breast cancer is one the most common malignancies and leading cause of cancer-related mortality in women. Recent studies suggested that hypercholesterolemia may be the potential modifiable risk factors for breast cancer. Cholesterol was well-known for its strong association with cardiovascular disease for long. Moreover, solid evidence has been provided by different studies to illustrate the correlation between lipid and incidence in multiple cancers. Although the conclusion remains controversial or sometimes contrary, which may be due to the multifactorial nature of the disease and the disparity of ethnic population, it is critical to elucidate the relationship between specific cholesterol components in certain population and the exact underlying mechanism of the lipid-associated signaling pathway in breast cancer. The implications of dysregulated lipoproteins as therapeutic targets or options for breast cancer provide novel strategies for us in combating with this malignant disease, which may be achieved by manipulating lipid levels with pharmacological compounds.
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Affiliation(s)
- Yanghui Wei
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Yao Huang
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Weiqin Yang
- School of Biomedical Sciences, The Chinese, University of Hong Kong, Hong Kong, China
| | - Qingnan Huang
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Yong Chen
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Kai Zeng
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Juan Chen
- Department of Medicine & Rehabilitation, Tung Wah Eastern Hospital, Hong Kong, China
| | - Jiawei Chen
- Department of Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
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Zhao TJ, Zhu N, Shi YN, Wang YX, Zhang CJ, Deng CF, Liao DF, Qin L. Targeting HDL in tumor microenvironment: New hope for cancer therapy. J Cell Physiol 2021; 236:7853-7873. [PMID: 34018609 DOI: 10.1002/jcp.30412] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/16/2021] [Accepted: 04/24/2021] [Indexed: 12/12/2022]
Abstract
Epidemiological studies have shown that plasma HDL-C levels are closely related to the risk of prostate cancer, breast cancer, and other malignancies. As one of the key carriers of cholesterol regulation, high-density lipoprotein (HDL) plays an important role in tumorigenesis and cancer development through anti-inflammation, antioxidation, immune-modulation, and mediating cholesterol transportation in cancer cells and noncancer cells. In addition, the occurrence and progression of cancer are closely related to the alteration of the tumor microenvironment (TME). Cancer cells synthesize and secrete a variety of cytokines and other factors to promote the reprogramming of surrounding cells and shape the microenvironment suitable for cancer survival. By analyzing the effect of HDL on the infiltrating immune cells in the TME, as well as the relationship between HDL and tumor-associated angiogenesis, it is suggested that a moderate increase in the level of HDL in vivo with consequent improvement of the function of HDL in the TME and induction of intracellular cholesterol efflux may be a promising strategy for cancer therapy.
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Affiliation(s)
- Tan-Jun Zhao
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Neng Zhu
- Department of Urology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Ya-Ning Shi
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Yu-Xiang Wang
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Chan-Juan Zhang
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Chang-Feng Deng
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Duan-Fang Liao
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Li Qin
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
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Nakazawa A, Fujioka S, Notsumata K, Shima T, Yangita K, Kawaguchi M, Tahara T, Oomoto M, Ishikawa T, Kawana I, Tsukada N, Funakoshi S, Itoh H, Nagano T, Horie Y, Tatemichi M, Yamamoto K, Okanoue T. Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study. WORLD ACADEMY OF SCIENCES JOURNAL 2021; 3:27. [DOI: 10.3892/wasj.2021.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Affiliation(s)
- Atsushi Nakazawa
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Shinichi Fujioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700‑8511, Japan
| | - Kazuo Notsumata
- Department of Internal Medicine, Fukui‑ken Saiseikai Hospital, Fukui 918‑8503, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Suita Hospital, Osaka 564‑0013, Japan
| | - Kimihiko Yangita
- Department of Internal Medicine, Saiseikai Karatsu Hospital, Karatsu, Saga 847‑0852, Japan
| | - Masanori Kawaguchi
- Department of Gastroenterology, Saiseikai Wakayama Hospital, Wakayama 640‑8158, Japan
| | - Toshiyuki Tahara
- Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi 321‑0974, Japan
| | - Masaki Oomoto
- Department of Internal Medicine and Gastroenterology, Saiseikai Imabari Hospital, Imabari, Ehime 799‑1502, Japan
| | - Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950‑1104, Japan
| | - Ichiro Kawana
- Department of Gastroenterology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa 234‑0054, Japan
| | - Nobuhiro Tsukada
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Shinsuke Funakoshi
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Hiroyuki Itoh
- Department of Internal Medicine, Saiseikai Kure Hospital, Kure, Hiroshima 737‑0821, Japan
| | - Tomoo Nagano
- Department of Internal Medicine, Kamisu Saisekai Hospital, Kamisu, Ibaraki 314‑0112, Japan
| | - Yutaka Horie
- Department of Gastroenterology, Shimaneken Saiseikai Gotsu General Hospital, Gotsu, Shimane 695‑0011, Japan
| | - Masayuki Tatemichi
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259‑1193, Japan
| | - Kazuhide Yamamoto
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700‑8511, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Suita Hospital, Osaka 564‑0013, Japan
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Revealing the Role of High-Density Lipoprotein in Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22073352. [PMID: 33805921 PMCID: PMC8037642 DOI: 10.3390/ijms22073352] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/11/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.
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Viaud M, Abdel-Wahab O, Gall J, Ivanov S, Guinamard R, Sore S, Merlin J, Ayrault M, Guilbaud E, Jacquel A, Auberger P, Wang N, Levine RL, Tall AR, Yvan-Charvet L. ABCA1 Exerts Tumor-Suppressor Function in Myeloproliferative Neoplasms. Cell Rep 2021; 30:3397-3410.e5. [PMID: 32160545 PMCID: PMC7473128 DOI: 10.1016/j.celrep.2020.02.056] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 11/23/2019] [Accepted: 02/12/2020] [Indexed: 12/13/2022] Open
Abstract
Defective cholesterol efflux pathways in mice promote the expansion of hematopoietic stem and progenitor cells and a bias toward the myeloid lineage, as observed in chronic myelomonocytic leukemia (CMML). Here, we identify 5 somatic missense mutations in ABCA1 in 26 patients with CMML. These mutations confer a proliferative advantage to monocytic leukemia cell lines in vitro. In vivo inactivation of ABCA1 or expression of ABCA1 mutants in hematopoietic cells in the setting of Tet2 loss demonstrates a myelosuppressive function of ABCA1. Mechanistically, ABCA1 mutations impair the tumor-suppressor functions of WT ABCA1 in myeloproliferative neoplasms by increasing the IL-3Rβ signaling via MAPK and JAK2 and subsequent metabolic reprogramming. Overexpression of a human apolipoprotein A-1 transgene dampens myeloproliferation. These findings identify somatic mutations in ABCA1 that subvert its anti-proliferative and cholesterol efflux functions and permit the progression of myeloid neoplasms. Therapeutic increases in HDL bypass these defects and restore normal hematopoiesis. Viaud et al. show that ABCA1 mutants identified in CMML patients diminish the tumor-suppressor functions of ABCA1 and cooperate with Tet2 loss to confer the hypersensitivity of myeloid progenitors to IL-3 receptor β canonical signaling, which can be prevented by raising HDL levels.
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Affiliation(s)
- Manon Viaud
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Omar Abdel-Wahab
- Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Julie Gall
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Stoyan Ivanov
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Rodolphe Guinamard
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Sophie Sore
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Johanna Merlin
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Marion Ayrault
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Emma Guilbaud
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Arnaud Jacquel
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Patrick Auberger
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France
| | - Nan Wang
- Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Ross L Levine
- Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Alan R Tall
- Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Laurent Yvan-Charvet
- Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, 06204 Nice, France.
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Gong IY, Cheung MC, Read S, Na Y, Lega IC, Lipscombe LL. Association between diabetes and haematological malignancies: a population-based study. Diabetologia 2021; 64:540-551. [PMID: 33409570 DOI: 10.1007/s00125-020-05338-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 10/16/2020] [Indexed: 12/16/2022]
Abstract
AIMS/HYPOTHESIS Contemporary data for the association of diabetes with haematological malignancies are lacking. We evaluated the risk of developing haematological malignancies and subsequent mortality in individuals with diabetes compared with those without diabetes. METHODS We conducted a population-based observational study using healthcare databases from Ontario, Canada. All Ontario residents 30 years of age or older free of cancer and diabetes between 1 January 1996 and 31 December 2015 were eligible for inclusion. Using Cox regression analyses, we explored the association between diabetes and the risk and mortality of haematological malignancies (leukaemia, lymphoma, multiple myeloma). The impact of timing on associations was evaluated with analyses stratified by time since diabetes diagnosis (<3 months, 3 months to 1 year, ≥1 year). RESULTS We identified 1,003,276 individuals with diabetes and age and sex matched these to 2,006,552 individuals without diabetes. Compared with individuals without diabetes, those with diabetes had a modest but significantly higher risk of a haematological malignancy (adjusted HR 1.10 [95% CI 1.08, 1.12] p < 0.0001). This association persisted across all time periods since diabetes diagnosis. Among those with haematological malignancies, diabetes was associated with a higher all-cause mortality (HR 1.36 [95% CI 1.31, 1.41] p < 0.0001) compared with no diabetes, as well as cause-specific mortality. CONCLUSIONS/INTERPRETATION Diabetes is associated with a higher risk of haematological malignancies and is an independent risk factor of all-cause and cause-specific mortality. Greater efforts for lifestyle modification may not only reduce diabetes burden and its complications but may also potentially lower risk of malignancy and mortality. Graphical abstract.
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Affiliation(s)
- Inna Y Gong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Matthew C Cheung
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, Ontario, Canada
- Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, ON, Canada
| | - Stephanie Read
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
| | - Yingbo Na
- ICES, Toronto, Ontario, Canada
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
| | - Iliana C Lega
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, Ontario, Canada
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
| | - Lorraine L Lipscombe
- Department of Medicine, University of Toronto, Toronto, ON, Canada.
- ICES, Toronto, Ontario, Canada.
- Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
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Cochran BJ, Ong KL, Manandhar B, Rye KA. APOA1: a Protein with Multiple Therapeutic Functions. Curr Atheroscler Rep 2021; 23:11. [PMID: 33591433 DOI: 10.1007/s11883-021-00906-7] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2021] [Indexed: 01/11/2023]
Abstract
PURPOSE OF THE REVIEW Apolipoprotein (APO) A1, the main apolipoprotein of plasma high-density lipoproteins (HDLs), has several well documented cardioprotective functions. A number of additional potentially beneficial functions of APOA1 have recently been identified. This review is concerned with the therapeutic potential of all of these functions in multiple disease states. RECENT FINDINGS Knowledge of the beneficial functions of APOA1 in atherosclerosis, thrombosis, diabetes, cancer, and neurological disorders is increasing exponentially. These insights have led to the development of clinically relevant peptides and APOA1-containing, synthetic reconstituted HDL (rHDL) preparations that mimic the functions of full-length APOA1. APOA1 is a multifunctional apolipoprotein that has therapeutic potential in several diseases. Translation of this knowledge into the clinic is likely to be dependent on the efficacy and bioavailability of small peptides and synthetic rHDL preparations that are currently under investigation, or in development.
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Affiliation(s)
- Blake J Cochran
- Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, Level 4E Wallace Wurth Building, Kensington, New South Wales, 2052, Australia
| | - Kwok-Leung Ong
- Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, Level 4E Wallace Wurth Building, Kensington, New South Wales, 2052, Australia
| | - Bikash Manandhar
- Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, Level 4E Wallace Wurth Building, Kensington, New South Wales, 2052, Australia
| | - Kerry-Anne Rye
- Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, Level 4E Wallace Wurth Building, Kensington, New South Wales, 2052, Australia.
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Lp-PLA2, a potential protector of lung cancer patients complicated with pleural effusion from lung diseases, proves effective for the diagnosis and pathological classification of lung cancer. Transl Oncol 2021; 14:101030. [PMID: 33550206 PMCID: PMC7868612 DOI: 10.1016/j.tranon.2021.101030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/25/2021] [Accepted: 01/25/2021] [Indexed: 11/24/2022] Open
Abstract
Abnormal lipid metabolism plays a crucial role in cancers, but few studies have investigated the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and lung cancer. In this study, 58 benign lung disease (LB) and 57 lung cancer (LC) patients complicated with pleural effusion (PE) were included, and their fasting serum and PE samples were collected. Results showed that serum Lp-PLA2 in the LC group was lower than that in the LB group, and other serum lipids were higher (P < 0.05). Tumor markers from serum and the PE samples of LC patients were higher than those in the LB group (P < 0.05). Serum prealbumin (PA) in LC patients was higher than that in the LB group, and serum C-reactive protein (CRP) and procalcitonin (PCT) were lower (P < 0.05). In the LC group, serum Lp-PLA2 concentration was positively correlated with serum triglyceride (TG), Lp (a), carbohydrate antigen 199 (CA199), nutritional markers, and Lp-PLA2 in PE and negatively correlated with serum high-density lipoprotein cholesterol (HDLC), Apolipoprotein A1 (APOA1), CRP, PCT, and alpha fetoprotein (AFP) and LDH in PE. The ROC curve showed that the cutoff level of serum Lp-PLA2 for diagnosing LC was 226.685 (U/L) (sensitivity: 0.632, specificity: 0.793), while the C-index of the nomogram model combined with serum Lp-PLA2, age, and gender was 0.750. In LC patients, the higher serum Lp-PLA2 indicated higher probability of adenocarcinoma and lower probability of squamous cell carcinoma (SCC). In conclusion, Lp-PLA2 may be a protective factor of lung cancer among lung disease patients complicated with pleural effusion, and it would facilitate the diagnosis and pathological classification of lung cancer.
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Jacobo-Albavera L, Domínguez-Pérez M, Medina-Leyte DJ, González-Garrido A, Villarreal-Molina T. The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease. Int J Mol Sci 2021; 22:ijms22041593. [PMID: 33562440 PMCID: PMC7915494 DOI: 10.3390/ijms22041593] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 02/06/2023] Open
Abstract
Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.
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Affiliation(s)
- Leonor Jacobo-Albavera
- Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; (L.J.-A.); (M.D.-P.); (D.J.M.-L.); (A.G.-G.)
| | - Mayra Domínguez-Pérez
- Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; (L.J.-A.); (M.D.-P.); (D.J.M.-L.); (A.G.-G.)
| | - Diana Jhoseline Medina-Leyte
- Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; (L.J.-A.); (M.D.-P.); (D.J.M.-L.); (A.G.-G.)
- Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM), Coyoacán, Mexico City CP04510, Mexico
| | - Antonia González-Garrido
- Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; (L.J.-A.); (M.D.-P.); (D.J.M.-L.); (A.G.-G.)
| | - Teresa Villarreal-Molina
- Laboratorio de Genómica de Enfermedades Cardiovasculares, Dirección de Investigación, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City CP14610, Mexico; (L.J.-A.); (M.D.-P.); (D.J.M.-L.); (A.G.-G.)
- Correspondence:
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Deng Z, Xuan Y, Li X, Crawford WJ, Yuan Z, Chen Z, Brooks A, Song Y, Wang H, Liang X, Chen T. Effect of metabolic syndrome components on the risk of malignancy in patients with gallbladder lesions. J Cancer 2021; 12:1531-1537. [PMID: 33531998 PMCID: PMC7847661 DOI: 10.7150/jca.54617] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Gallbladder lesions have become more common nowadays. But there is limited evidence-based guidance on surveillance of these patients for malignancy. Predicting malignancy could help clinicians better manage this condition and improve the prognosis. We evaluated the independent and joint effects of metabolic syndrome components on the risk of malignancy among patients with gallbladder lesions. Methods: Using a multicenter database, consecutive patients with pathologically confirmed gallbladder lesions between 2012 and 2019 were identified. Univariate and multivariate logistic regression analyses were used to evaluate the effects of metabolic syndrome components (diabetes, hypertension, dyslipidemia and obesity) as additive or combined indicators for the risk of malignancy. Unadjusted and adjusted odds ratios were calculated. Results: Of the 625 patients, 567 patients were identified with benign gallbladder lesions and 58 patients with gallbladder cancer (GBC). GBC group had less obesity but more dyslipidemia. Among all metabolic syndrome components, only dyslipidemia was significantly associated with GBC (odds ratio 2.674, 95% confidence interval 1.173-6.094). Dyslipidemia was an independent risk factor for malignancy (adjusted odds ratio 2.164, 95% confidence interval 1.165-4.021), regardless of whether the other risk factors and metabolic syndrome components were combined. Patients with decreased high-density lipoprotein had 3.035-fold higher risk of malignancy (adjusted odds ratio 3.035, 95% confidence interval 1.645-5.600). Conclusions: Dyslipidemia is associated with a 2.674-fold increase in the risk of malignancy in patients with gallbladder lesions. Dyslipidemia is an independent risk factor for malignancy, regardless of the presence of the other risk factors and metabolic syndrome components.
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Affiliation(s)
- Zheng Deng
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201112, China
| | - Yan Xuan
- Department of Endocrinology, Luwan Branch, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, China
| | - Xinxing Li
- Department of Gastroenterological Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.,Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China
| | - William J Crawford
- Department of Medical Sciences, University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Zhiqing Yuan
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201112, China
| | - Zhoukan Chen
- Department of General Surgery, Luwan Branch, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, China
| | - Anastasia Brooks
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, 4102, Australia.,Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, 4120, Australia
| | - Yanyan Song
- Department of biostatistics, clinical research institute, School of Medine, Shanghai Jiaotong University, Shanghai, 200025, China
| | - Haolu Wang
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, 4102, Australia.,Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, 4120, Australia
| | - Xiaowen Liang
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, 4102, Australia.,Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, 4120, Australia
| | - Tao Chen
- Department of General Surgery, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201112, China.,Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
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Nowicki GJ, Ślusarska B, Naylor K, Prystupa A, Rudnicka-Drożak E, Halyuk U, Pokotylo P. The Relationship Between the Metabolic Syndrome and the Place of Residence in the Local Community on the Example of the Janów Lubelski District in Eastern Poland: A Population-Based Study. Diabetes Metab Syndr Obes 2021; 14:2041-2056. [PMID: 33986605 PMCID: PMC8110259 DOI: 10.2147/dmso.s301639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 03/20/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The aim of this study was to estimate the incidence concerning metabolic syndrome (MetS) in a local community with a low socioeconomic status and a medium and high cardiovascular risk on the example of residents of Janów Lubelski district, eastern Poland. The second goal of the research was to analyze the relationship between residence and the occurrence of MetS. METHODS We conducted a cross-sectional study of 4040 people living in eastern Poland. A group of 3046 people with medium and high cardiovascular risk was selected among the respondents and included in further analyzes. The research adopted the definition criteria proposed by the National Cholesterol Education Program - Third Adult Treatment Panel (NCEP ATP III) to implement diagnostic evaluation of MetS. RESULTS It was observed that metabolic syndrome was significantly more frequent among the inhabitants of rural areas (40.56%; n=810) compared to those living in the city (35.27%; n=370) p=0.005. Among the inhabitants of rural areas, the percentage of people with elevated glucose levels was significantly higher, fasting blood glucose (FGB) p<0.001, elevated blood pressure (HBP) p<0.001, elevated serum triglycerides (TGs) p=0.01, and abnormal waist circumference (WC) p=0.003 compared to urban inhabitants. After adjusting for potential confounding variables (age, education, smoking, marital status, and level of physical activity), in both women and men, the odds of developing metabolic syndrome were approximately 30% higher in rural areas compared to urban residents (women: odds ratio (OR)=1.25, 95% confidence intervals (CI)=1.01-1.56; men: OR=1.30, 95% CI=1.01-1.67). CONCLUSION AND RECOMMENDATIONS A higher incidence of metabolic syndrome was observed among respondents living in rural areas than those living in cities. Similarly, across the gender strata, metabolic syndrome is more commonly diagnosed among men and women living in rural areas. Healthcare workers, especially in rural areas, should engage in education, prevention, and the promotion of a healthy lifestyle.
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Affiliation(s)
- Grzegorz Józef Nowicki
- Department of Family Medicine and Community Nursing, Medical University of Lublin, Lublin, Poland
- Correspondence: Grzegorz Józef Nowicki Department of Family Medicine and Community Nursing, Medical University of Lublin, Staszica 6 Street, PL-20-081, Lublin, PolandTel +48 81448 6810Fax +48 81448 6811 Email
| | - Barbara Ślusarska
- Department of Family Medicine and Community Nursing, Medical University of Lublin, Lublin, Poland
| | - Katarzyna Naylor
- Department of Didactics and Medical Simulation, Medical University of Lublin, Lublin, Poland
| | - Andrzej Prystupa
- Department of Internal Medicine, Medical University of Lublin, Lublin, Poland
| | | | - Ulyana Halyuk
- Department of Normal Anatomy, Lviv National Medical University, Lviv, Ukraine
| | - Petro Pokotylo
- Department of Normal Anatomy, Lviv National Medical University, Lviv, Ukraine
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BEDİR F, KOCATÜRK H, ALTAY MS, ŞEBİN E, BEDİR B. Serum paraoxonase 1 and 3 activities in benign and malignant diseases of the prostate and changes in levels following robotic-assisted laparoscopic radical prostatectomy. Turk J Med Sci 2020; 50:1872-1878. [PMID: 32549522 PMCID: PMC7775696 DOI: 10.3906/sag-2004-353] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 06/15/2020] [Indexed: 12/28/2022] Open
Abstract
Background/aim This study aimed to examine serum paraoxonase 1 and 3 (PON1 and PON3) activities in benign and malignant diseases of the prostate, to determine lipid profile and malondialdehyde (MDA) levels, and to investigate changes in levels following robotic-assisted laparoscopic radical prostatectomy (RALRP). Materials and methods A total of 137 patients, including a control group, were enrolled in the study and assigned into four groups. Group 1 (n = 33) consisted of patients previously undergoing RALRP with no recurrence, group 2 (n = 36) consisted of patients diagnosed with prostate cancer (PCa) and undergoing RALRP, and group 3 (n = 34) consisted of patients diagnosed with benign prostatic hyperplasia. The control group (n = 34) consisted of healthy individuals. Serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol, prostate-specific antigen (PSA), PON1, PON3, and MDA values were measured. In addition, group 2 MDA, PON1, PON3, and PON1/HDL levels were investigated preoperatively and at the first month postoperatively. Results Significant changes were found in PON1, PON3, and MDA levels. PON1 and PON3 levels decreased significantly in patients with PCa, while MDA levels increased. PON1 and PON3 increased postoperatively in the PCa group, while MDA decreased. BPH group PON1, PON3, and MDA levels were higher than those of the control group. Conclusion An increase in free oxygen radicals in the body or a decrease in endogenous antioxidant enzyme levels can result in malignant and benign diseases of the prostate. Surgical excision of malignant tissue in PCa causes a decrease in oxidative stress.
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Affiliation(s)
- Fevzi BEDİR
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, ErzurumTurkey
| | - Hüseyin KOCATÜRK
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, ErzurumTurkey
| | - Mehmet Sefa ALTAY
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, ErzurumTurkey
| | - Engin ŞEBİN
- Department of Biochemistry, Health Sciences University, Erzurum Regional Training and Research Hospital, ErzurumTurkey
| | - Banu BEDİR
- Department of Public Health, Aziziye District Health Directorate, ErzurumTurkey
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Lee Y, Joo J, Lee YJ, Lee EK, Park S, Kim TS, Lee SH, Kim SY, Wie GA, Park M, Kim MJ, Lee JS, Han JY. Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer. Lung Cancer 2020; 151:8-15. [PMID: 33278671 DOI: 10.1016/j.lungcan.2020.11.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/30/2020] [Accepted: 11/04/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients. MATERIALS AND METHODS This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m2) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes. RESULTS Metformin group showed no significant difference in the risk of progression and death compared to control group (progression: hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 - 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67-1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose (FDG) uptake on baseline PET image than non-SqCC NSCLC (P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12-0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18-0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatment in metformin group compared to control group (P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment. CONCLUSIONS Addition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.
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Affiliation(s)
- Youngjoo Lee
- Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea
| | - Jungnam Joo
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
| | - You Jin Lee
- Division of Endocrinology, Department of Internal Medicine, National Cancer Center Korea, Goyang, Republic of Korea
| | - Eun Kyung Lee
- Division of Endocrinology, Department of Internal Medicine, National Cancer Center Korea, Goyang, Republic of Korea
| | - Sohyun Park
- Department of Nuclear Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Tae-Sung Kim
- Department of Nuclear Medicine, National Cancer Center Korea, Goyang, Republic of Korea
| | - Soo-Hyun Lee
- Department of Radiology, National Cancer Center Korea, Goyang, Republic of Korea
| | - So Young Kim
- Department of Clinical Nutrition, National Cancer Center Korea, Goyang, Republic of Korea
| | - Gyung-Ah Wie
- Department of Clinical Nutrition, National Cancer Center Korea, Goyang, Republic of Korea
| | - Minjoung Park
- Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea
| | - Mi-Jung Kim
- Division of Medical Oncology, Department of Internal Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Jin Soo Lee
- Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea
| | - Ji-Youn Han
- Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea.
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Low high-density lipoprotein and increased risk of several cancers: 2 population-based cohort studies including 116,728 individuals. J Hematol Oncol 2020; 13:129. [PMID: 32998735 PMCID: PMC7528381 DOI: 10.1186/s13045-020-00963-6] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 09/09/2020] [Indexed: 12/22/2022] Open
Abstract
Background Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. Methods Individuals from two population-based cohorts, the Copenhagen General Population Study (2003–2015, N = 107 341), and the Copenhagen City Heart Study (1991–1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. Results During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04–1.22) for individuals with HDL cholesterol of 1.5–1.99 mmol/L (58–77 mg/dL), 1.18 (1.08–1.30) for HDL cholesterol of 1.0–1.49 mmol/L (39–58 mg/dL), and 1.29 (1.12–1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96–1.17) for individuals with apolipoprotein A1 of 160–189 mg/dL, 1.18 (1.07–1.30) for apolipoprotein A1 of 130–159 mg/dL, and 1.28 (1.13–1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. Conclusions Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.
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Zieliński K, Kalińczuk Ł, Chmielak Z, Mintz GS, Dąbrowski M, Pręgowski J, Świerczewski M, Kowalik I, Demkow M, Hryniewiecki T, Michałowska I, Witkowski A. Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation. Am J Cardiol 2020; 126:66-72. [PMID: 32340714 DOI: 10.1016/j.amjcard.2020.03.037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/27/2020] [Accepted: 03/27/2020] [Indexed: 12/13/2022]
Abstract
Available prediction models are inaccurate in elderly who underwent transcatheter aortic valve implantation (TAVI). The aim of present study was to analyze the separate and combined prognostic values of baseline HDL-C and C-reactive protein (CRP) levels in patients treated successfully with TAVI who had complete 2-year follow-up. We analyzed 334 patients treated with TAVI from 01/2010 to 07/2017 who had measurements of HDL-C and CRP on admission or during qualification for the procedure. Baseline HDL-C ≤46 mg/dl (areas under the curve [AUC] = 0.657) and CRP ≥0.20 mg/dl (AUC = 0.634) were predictive of 2-year mortality. After stratification with both cutoffs, patients with low HDL-C and concomitant high CRP most often had LVEF ≤50% and were high risk as per EuroSCORE II. Those with isolated CRP elevation had the lowest frequency of LVEF ≤50%, but more sarcopenia (based on psoas muscle area). After adjustment in the multivariate analysis for other identified predictors including EuroSCORE II and statin therapy, isolated HDL-C ≤46 mg/dl (identified in 40 patients) and isolated CRP ≥0.20 mg/dl (n = 109) were both independent predictors of 2-year mortality (hazard ratio [HR] = 2.92 and HR = 2.42, respectively) compared with patients with both markers within established cutoffs (n = 105) who had the lowest 2-year mortality (9.5%). Patients with both markers exceeding cutoffs (n = 80) had the highest risk (HR = 4.53) with 2-year mortality of 42.5%. High CRP was associated with increased mortality within the first year of follow-up, whereas low HDL-C increased mortality in the second year. The combination of both markers with EuroSCORE II enhanced mortality prediction (AUC = 0.697). In conclusion, low baseline HDL-C and high CRP jointly contribute to the prediction of increased all-cause mortality after TAVI.
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Traughber CA, Opoku E, Brubaker G, Major J, Lu H, Lorkowski SW, Neumann C, Hardaway A, Chung YM, Gulshan K, Sharifi N, Brown JM, Smith JD. Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice. J Biol Chem 2020; 295:8252-8261. [PMID: 32358065 PMCID: PMC7294086 DOI: 10.1074/jbc.ra120.013694] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 04/28/2020] [Indexed: 12/30/2022] Open
Abstract
High-density lipoprotein (HDL) metabolism is facilitated in part by scavenger receptor class B, type 1 (SR-B1) that mediates HDL uptake into cells. Higher levels of HDL have been associated with protection in other diseases, however, its role in prostate cancer is not definitive. SR-B1 is up-regulated in prostate cancer tissue, suggesting a possible role of this receptor in tumor progression. Here, we report that knockout (KO) of SR-B1 in both human and mouse prostate cancer cell lines through CRISPR/Cas9-mediated genome editing reduces HDL uptake into the prostate cancer cells and reduces their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 WT (SR-B1+/+) and SR-B1 KO (SR-B1-/-) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice revealed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1-/- prostate cancer cells formed smaller tumors in WT hosts than SR-B1+/+ cells in the same host model. Increased tumor volume was overall associated with reduced survival. We conclude that knocking out SR-B1 in prostate cancer tumors reduces HDL-associated increases in prostate cancer cell proliferation and disease progression.
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Affiliation(s)
- C Alicia Traughber
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Emmanuel Opoku
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Gregory Brubaker
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Jennifer Major
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Hanxu Lu
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Shuhui Wang Lorkowski
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Chase Neumann
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Aimalie Hardaway
- Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Yoon-Mi Chung
- Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Kailash Gulshan
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - Nima Sharifi
- Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
| | - J Mark Brown
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA
- Center for Microbiome and Human Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Jonathan D Smith
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
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The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets. Cancers (Basel) 2020; 12:cancers12061410. [PMID: 32486083 DOI: 10.3390/cancers12061410] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/23/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022] Open
Abstract
Cholesterol plays an important role in cellular homeostasis by maintaining the rigidity of cell membranes, providing a medium for signaling transduction, and being converted into other vital macromolecules, such as sterol hormones and bile acids. Epidemiological studies have shown the correlation between cholesterol content and cancer incidence worldwide. Accumulating evidence has shown the emerging roles of the dysregulation of cholesterol metabolism in cancer development. More specifically, recent reports have shown the distinct role of cholesterol in the suppression of immune cells, regulation of cell survival, and modulation of cancer stem cells in cancer. Here, we provide a comprehensive review of the epidemiological analysis, functional roles, and mechanistic action of cholesterol homeostasis in regard to its contribution to cancer development. Based on the existing data, cholesterol homeostasis is identified to be a new key player in cancer pathogenesis. Lastly, we also discuss the therapeutic implications of natural compounds and cholesterol-lowering drugs in cancer prevention and treatment. In conclusion, intervention in cholesterol metabolism may offer a new therapeutic avenue for cancer treatment.
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Zamanian-Daryoush M, Lindner DJ, Buffa J, Gopalan B, Na J, Hazen SL, DiDonato JA. Apolipoprotein A-I anti-tumor activity targets cancer cell metabolism. Oncotarget 2020; 11:1777-1796. [PMID: 32477466 PMCID: PMC7233810 DOI: 10.18632/oncotarget.27590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 04/10/2020] [Indexed: 02/07/2023] Open
Abstract
Previously, we reported apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), has potent anti-melanoma activity. We used DNA microarray and bioinformatics to interrogate gene expression profiles of tumors from apoA-I expressing (A-I Tg+/-) versus apoA-I-null (A-I KO) animals to gain insights into mechanisms of apoA-I tumor protection. Differential expression analyses of 11 distinct tumors per group with > 1.2-fold cut-off and a false discovery rate adjusted p < 0.05, identified 176 significant transcripts (71 upregulated and 105 downregulated in A-I Tg+/- versus A-I KO group). Bioinformatic analyses identified the mevalonate and de novo serine/glycine synthesis pathways as potential targets for apoA-I anti-tumor activity. Relative to A-I KO, day 7 B16F10L melanoma tumor homografts from A-I Tg+/- exhibited reduced expression of mevalonate-5-pyrophosphate decarboxylase (Mvd), a key enzyme targeted in cancer therapy, along with a number of key genes in the sterol synthesis arm of the mevalonate pathway. Phosphoglycerate dehydrogenase (Phgdh), the first enzyme branching off glycolysis into the de novo serine synthesis pathway, was the most repressed transcript in tumors from A-I Tg+/-. We validated our mouse tumor studies by comparing the significant transcripts with adverse tumor markers previously identified in human melanoma and found 45% concordance. Our findings suggest apoA-I targets the mevalonate and serine synthesis pathways in melanoma cells in vivo, thus providing anti-tumor metabolic effects by inhibiting the flux of biomolecular building blocks for macromolecule synthesis that drive rapid tumor growth.
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Affiliation(s)
- Maryam Zamanian-Daryoush
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Daniel J. Lindner
- Taussig Cancer Institute, Cleveland Clinic, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Jennifer Buffa
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | | | - Jie Na
- Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA
| | - Stanley L. Hazen
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Joseph A. DiDonato
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
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Kluck GEG, Durham KK, Yoo JA, Trigatti BL. High Density Lipoprotein and Its Precursor Protein Apolipoprotein A1 as Potential Therapeutics to Prevent Anthracycline Associated Cardiotoxicity. Front Cardiovasc Med 2020; 7:65. [PMID: 32411725 PMCID: PMC7198830 DOI: 10.3389/fcvm.2020.00065] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 04/06/2020] [Indexed: 01/01/2023] Open
Abstract
Cardiovascular disease and cancer are the leading causes of death in developed societies. Despite their effectiveness, many cancer therapies exhibit deleterious cardiovascular side effects such as cardiotoxicity and heart failure. The cardiotoxic effects of anthracyclines such as doxorubicin are the most well-characterized of cardiotoxic anti-cancer therapies. While other anti-neoplastic drugs also induce cardiotoxicity, often leading to heart failure, they are beyond the scope of this review. This review first summarizes the mechanisms of doxorubicin-induced cardiotoxicity. It then reviews emerging preclinical evidence that high density lipoprotein and its precursor protein apolipoprotein A1, which are known for their protective effects against ischemic cardiovascular disease, may also protect against doxorubicin-induced cardiotoxicity both directly and indirectly, when used therapeutically.
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Affiliation(s)
- George E. G. Kluck
- Department of Biochemistry and Biomedical Sciences, Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
| | - Kristina K. Durham
- Faculty of Health Sciences, Institute of Applied Health Sciences, School of Rehabilitation Sciences, McMaster University, Hamilton, ON, Canada
| | - Jeong-Ah Yoo
- Department of Biochemistry and Biomedical Sciences, Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
| | - Bernardo L. Trigatti
- Department of Biochemistry and Biomedical Sciences, Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
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Srougi V, Reis ST, Viana N, Gallucci FP, Leite KR, Srougi M, Nahas WC. Prospective evaluation of a urinary biomarker panel to detect and predict recurrence of non-muscle-invasive bladder cancer. World J Urol 2020; 39:453-459. [PMID: 32253580 DOI: 10.1007/s00345-020-03188-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 03/27/2020] [Indexed: 01/10/2023] Open
Abstract
PURPOSE To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up. METHODS We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers. RESULTS Median follow-up time was 47 months (interquartile range 39-50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5-47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4-11.4). Previous use of intravesical BCG did not affect biomarker levels. CONCLUSION In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.
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Affiliation(s)
- Victor Srougi
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil.
| | - Sabrina T Reis
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil.,Faculdade Atenas, Campos Passos, Rua Oscar Cândido Monteiro, 1000, Passos, MG, 37900-380, Brazil
| | - Nayara Viana
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil
| | - Fabio P Gallucci
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil
| | - Katia R Leite
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil
| | - Miguel Srougi
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil
| | - William C Nahas
- Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil
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49
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Kim NH, Kim SG. Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction. Diabetes Metab J 2020; 44:213-221. [PMID: 32347023 PMCID: PMC7188966 DOI: 10.4093/dmj.2020.0001] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 02/05/2020] [Indexed: 12/18/2022] Open
Abstract
Fibrates, peroxisome proliferator-activated receptor-α agonists, are potent lipid-modifying drugs. Their main effects are reduction of triglycerides and increase in high-density lipoprotein levels. Several randomized controlled trials have not demonstrated their benefits on cardiovascular risk reduction, especially as an "add on" to statin therapy. However, subsequent analyses by major clinical trials, meta-analyses, and real-world evidence have proposed their potential in specific patient populations with atherogenic dyslipidemia and metabolic syndrome. Here, we have reviewed and discussed the accumulated data on fibrates to understand their current status in cardiovascular risk management.
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Affiliation(s)
- Nam Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sin Gon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
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50
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Park SK, Oh C, Kim M, Ha E, Choi Y, Ryoo J. Metabolic syndrome, metabolic components, and their relation to the risk of pancreatic cancer. Cancer 2020; 126:1979-1986. [DOI: 10.1002/cncr.32737] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 12/09/2019] [Accepted: 01/14/2020] [Indexed: 12/21/2022]
Affiliation(s)
- Sung Keun Park
- Total Healthcare Center Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine Seoul Korea
| | - Chang‐Mo Oh
- Department of Preventive Medicine School of Medicine Kyung Hee University Seoul Korea
| | - Min‐Ho Kim
- Ewha Institute of Convergence Medicine Ewha Womans UniversityMokdong Hospital Seoul Korea
| | - Eunhee Ha
- Department of Occupational and Environment Medicine College of Medicine Ewha Womans University Seoul Korea
| | - Yong‐Sung Choi
- Department of Pediatrics School of Medicine Kyung Hee University Seoul Korea
| | - Jae‐Hong Ryoo
- Department of Occupational and Environmental Medicine, School of Medicine Kyung Hee University Seoul Korea
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