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1
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Ließem A, Leimer U, Germann GK, Köllensperger E. Adipokines in Breast Cancer: Decoding Genetic and Proteomic Mechanisms Underlying Migration, Invasion, and Proliferation. BREAST CANCER (DOVE MEDICAL PRESS) 2025; 17:79-102. [PMID: 39882382 PMCID: PMC11776935 DOI: 10.2147/bctt.s491277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 12/04/2024] [Indexed: 01/31/2025]
Abstract
Background Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute to breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of their involvement are not yet completely understood. Methods In this project, varying concentrations of recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, and Resistin) were used to study their effects on four selected breast cancer cell lines (EVSA-T, MCF-7, MDA-MB-231, and SK-Br-3). Over a five-day proliferation phase, linear growth was assessed by calculating doubling times and malignancy-associated changes in gene and protein expression were identified using quantitative TaqMan real-time PCR and multiplex protein analysis. Migration and invasion behaviors were quantified using specialized Boyden chamber assays. Results We found significant, adipokine-mediated genetic and proteomic alterations, with PCR showing an up to 6-fold increase of numerous malignancy-associated genes after adipokine-supplementation. Adipokines further altered protein secretion, such as raising the concentrations of different tumor-associated proteins up to 13-fold. Effects on proliferation varied, however, with most approaches showing significant enhancement in growth kinetics. A concentration-dependent increase in migration and invasion was generally observed, with no significant reductions in any approaches. Conclusion We could show a robust promoting effect of several adipokines on different breast cancer cells in vitro. Understanding the interaction between adipose tissue and breast cancer cells opens potential avenues for innovative breast cancer prevention and therapy strategies. Our findings indicate that antibodies against specific adipokines could become a beneficial component of clinical breast cancer treatment in the future.
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Affiliation(s)
- Anne Ließem
- Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, Germany
| | - Uwe Leimer
- Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, Germany
| | - Günter K Germann
- Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, Germany
| | - Eva Köllensperger
- Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, Germany
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2
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Moar K, Pant A, Saini V, Pandey M, Maurya PK. Potential diagnostic and prognostic biomarkers for breast cancer: A compiled review. Pathol Res Pract 2023; 251:154893. [PMID: 37918101 DOI: 10.1016/j.prp.2023.154893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 11/04/2023]
Abstract
Breast cancer is one of the major reason for death of women worldwide. As per the International Agency for Research on Cancer (IARC) statistics, the number of cases of breast cancer is increasing year by year in many parts of the world. As per the recent global cancer burden figures, in 2020, there were 2.26 million incidences of breast cancer cases and it is one of the main causes of mortality due to cancer in women in the world. Biomarkers of breast cancer would prove to be very beneficial to screen women who are at higher risk and for detection of disease recurrence. Here, studies carried out on biomarkers of breast cancer and susceptibility to the disease have been reviewed. Various databases like Google Scholar, ScienceDirect and PubMed have been used for searching and majorly literature from the last 10 years have been considered. Potential biomarkers of breast cancer including blood based angiogenic factors, glycoprotein-based biomarkers, hormone receptor biomarkers and other biomarkers that were identified from various studies have been summarized.
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Affiliation(s)
- Kareena Moar
- Department of Biochemistry, Central University of Haryana, Mahendergarh 123031, India
| | - Anuja Pant
- Department of Biochemistry, Central University of Haryana, Mahendergarh 123031, India
| | - Vikas Saini
- Department of Vocational Studies & Skill Development, Central University of Haryana, Mahendergarh 123031, India
| | - Manisha Pandey
- Department of Pharmaceutical Sciences, Central University of Haryana, Mahendergarh 123031, India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh 123031, India.
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3
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Hao Y, Xiao J, Fu P, Yan L, Zhao X, Wu X, Zhou M, Zhang X, Xu B, Li X, Liu Z, Yang C, Wang X, Long L, Jiang X, Liao J, Zhang B, Li J. Increases in BMI contribute to worsening inflammatory biomarkers related to breast cancer risk in women: a longitudinal study. Breast Cancer Res Treat 2023; 202:117-127. [PMID: 37541965 DOI: 10.1007/s10549-023-07023-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/26/2023] [Indexed: 08/06/2023]
Abstract
BACKGROUND Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. METHODS A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. RESULTS BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. CONCLUSIONS A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.
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Affiliation(s)
- Yu Hao
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jinyu Xiao
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ping Fu
- Department of Maternal and Child Health, Chengdu Shuangliu District Maternal and Child Health Care Hospital, Chengdu, Sichuan, China
| | - Lanping Yan
- Department of Maternal and Child Health, Chengdu Shuangliu District Maternal and Child Health Care Hospital, Chengdu, Sichuan, China
| | - Xunying Zhao
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xueyao Wu
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Min Zhou
- Department of Maternal and Child Health, Chengdu Shuangliu District Maternal and Child Health Care Hospital, Chengdu, Sichuan, China
| | - Xiaofan Zhang
- Department of Scientific Research & Management, The Second People's Hospital of Guiyang, Guiyang, Guizhou, China
| | - Bin Xu
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xingyue Li
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhenmi Liu
- Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunxia Yang
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xin Wang
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lu Long
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xia Jiang
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiaqiang Liao
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ben Zhang
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiayuan Li
- Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
- West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
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Ajabnoor GMA. The Molecular and Genetic Interactions between Obesity and Breast Cancer Risk. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1338. [PMID: 37512149 PMCID: PMC10384495 DOI: 10.3390/medicina59071338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/14/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023]
Abstract
Breast cancer (BC) is considered the leading cause of death among females worldwide. Various risk factors contribute to BC development, such as age, genetics, reproductive factors, obesity, alcohol intake, and lifestyle. Obesity is considered to be a pandemic health problem globally, affecting millions of people worldwide. Obesity has been associated with a high risk of BC development. Determining the impact of obesity on BC development risk in women by demonstrating the molecular and genetic association in pre- and post-menopause females and risk to BC initiation is crucial in order to improve the diagnosis and prognosis of BC disease. In epidemiological studies, BC in premenopausal women was shown to be protective in a certain pattern. These altered effects between the two phases could be due to various physiological changes, such as estrogen/progesterone fluctuating levels. In addition, the relationship between BC risk and obesity is indicated by different molecular alterations as metabolic pathways and genetic mutation or epigenetic DNA changes supporting a strong connection between obesity and BC risk. However, these molecular and genetic alteration remain incompletely understood. The aim of this review is to highlight and elucidate the different molecular mechanisms and genetic changes occurring in obese women and their association with BC risk and development.
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Affiliation(s)
- Ghada M A Ajabnoor
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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5
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Gonzales Martinez R, van Dongen DM. Deep learning algorithms for the early detection of breast cancer: A comparative study with traditional machine learning. INFORMATICS IN MEDICINE UNLOCKED 2023; 41:101317. [DOI: 10.1016/j.imu.2023.101317] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Liu L, Zhai W, Wang F, Yu L, Zhou F, Xiang Y, Huang S, Zheng C, Yuan Z, He Y, Yu Z, Ji J. Using machine learning to identify gene interaction networks associated with breast cancer. BMC Cancer 2022; 22:1070. [PMID: 36253742 PMCID: PMC9575346 DOI: 10.1186/s12885-022-10170-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 10/10/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Breast cancer (BC) is one of the most prevalent cancers worldwide but its etiology remains unclear. Obesity is recognized as a risk factor for BC, and many obesity-related genes may be involved in its occurrence and development. Research assessing the complex genetic mechanisms of BC should not only consider the effect of a single gene on the disease, but also focus on the interaction between genes. This study sought to construct a gene interaction network to identify potential pathogenic BC genes. METHODS The study included 953 BC patients and 963 control individuals. Chi-square analysis was used to assess the correlation between demographic characteristics and BC. The joint density-based non-parametric differential interaction network analysis and classification (JDINAC) was used to build a BC gene interaction network using single nucleotide polymorphisms (SNP). The odds ratio (OR) and 95% confidence interval (95% CI) of hub gene SNPs were evaluated using a logistic regression model. To assess reliability, the hub genes were quantified by edgeR program using BC RNA-seq data from The Cancer Genome Atlas (TCGA) and identical edges were verified by logistic regression using UK Biobank datasets. Go and KEGG enrichment analysis were used to explore the biological functions of interactive genes. RESULTS Body mass index (BMI) and menopause are important risk factors for BC. After adjusting for potential confounding factors, the BC gene interaction network was identified using JDINAC. LEP, LEPR, XRCC6, and RETN were identified as hub genes and both hub genes and edges were verified. LEPR genetic polymorphisms (rs1137101 and rs4655555) were also significantly associated with BC. Enrichment analysis showed that the identified genes were mainly involved in energy regulation and fat-related signaling pathways. CONCLUSION We explored the interaction network of genes derived from SNP data in BC progression. Gene interaction networks provide new insight into the underlying mechanisms of BC.
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Affiliation(s)
- Liyuan Liu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,School of Mathematics, Shandong University, Jinan, 250100, China
| | - Wenli Zhai
- Institute for Financial Studies, Shandong University, Jinan, 250100, China
| | - Fei Wang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Lixiang Yu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Fei Zhou
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Yujuan Xiang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Shuya Huang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Chao Zheng
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China.,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China
| | - Zhongshang Yuan
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Yong He
- Institute for Financial Studies, Shandong University, Jinan, 250100, China
| | - Zhigang Yu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 250033, Jinan, China. .,Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, 250100, China.
| | - Jiadong Ji
- Institute for Financial Studies, Shandong University, Jinan, 250100, China.
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7
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Wang YY, Hung AC, Wu YC, Lo S, Chen HD, Chen YK, Hsieh YC, Hu SCS, Hou MF, Yuan SSF. ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model. Sci Rep 2022; 12:15437. [PMID: 36104403 PMCID: PMC9475041 DOI: 10.1038/s41598-022-19290-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022] Open
Abstract
The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.
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Affiliation(s)
- Yen-Yun Wang
- School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Amos C Hung
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Chia Wu
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Steven Lo
- College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Huan-Da Chen
- Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yuk-Kwan Chen
- School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Oral Pathology and Maxillofacial Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Oral and Maxillofacial Imaging Center, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ya-Ching Hsieh
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Stephen Chu-Sung Hu
- Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Feng Hou
- Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shyng-Shiou F Yuan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
- Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
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8
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Aziz MA, Akter T, Sarwar MS, Islam MS. The first combined meta‐analytic approach for elucidating the relationship of circulating resistin levels and RETN gene polymorphisms with colorectal and breast cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00240-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Evidence suggests that circulating resistin levels are altered in colorectal cancer (CRC) and breast cancer (BC). Again, polymorphisms in resistin-encoding gene RETN have been evaluated in CRC and BC. However, there is a scarcity of data establishing the relationship of resistin and RETN polymorphisms (rs1862513 and rs3745367) with these cancers. This study aimed to analyze the relationship of resistin levels and RETN polymorphisms with CRC and BC in a combined meta-analytic approach.
Main body of the abstract
After a comprehensive online literature search, screening and eligibility check, 41 articles (31 with resistin level and 10 with RETN polymorphisms) were retrieved for meta-analyses. The mean difference (MD) of resistin was calculated and pooled to investigate the effect sizes with a 95% confidence interval (CI), and the connection of genetic polymorphisms was analyzed with an odds ratio (OR) and 95% CI. The analysis showed that resistin level is significantly higher in CRC (MD = 3.39) and BC (MD = 3.91) patients. Subgroup analysis in CRC showed significantly higher resistin in serum (MD = 4.61) and plasma (MD = 0.34), and in BC, a significantly elevated resistin level was reported in premenopausal (MD = 7.82) and postmenopausal (MD = 0.37) patients. Again, RETN rs1862513 showed a significantly strong association with CRC (codominant 1—OR 1.24, codominant 2—OR 1.31, dominant model—OR 1.25, and allele model—OR 1.16) and with BC (codominant 2—OR 1.51, codominant 3—OR 1.51, recessive model—OR 1.51, and allele model—OR 1.21). RETN rs3745367 did not show any association with these cancers.
Short conclusion
Overall, our analysis indicates that higher circulating resistin levels are associated with an elevated risk of CRC and premenopausal and postmenopausal BC. Besides, rs1862513 in RETN gene is significantly connected with both CRC and BC.
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Crafts TD, Tonneson JE, Wolfe BM, Stroud AM. Obesity and breast cancer: Preventive and therapeutic possibilities for bariatric surgery. Obesity (Silver Spring) 2022; 30:587-598. [PMID: 35195366 DOI: 10.1002/oby.23369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 11/10/2021] [Accepted: 11/29/2021] [Indexed: 11/07/2022]
Abstract
Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.
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Affiliation(s)
- Trevor D Crafts
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Jennifer E Tonneson
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Bruce M Wolfe
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Andrea M Stroud
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
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10
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Obi N, Jung AY, Maurer T, Huebner M, Johnson T, Behrens S, Jaskulski S, Becher H, Chang-Claude J. Association of circulating leptin, adiponectin, and resistin concentrations with long-term breast cancer prognosis in a German patient cohort. Sci Rep 2021; 11:23526. [PMID: 34876619 PMCID: PMC8651788 DOI: 10.1038/s41598-021-02958-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/19/2021] [Indexed: 12/23/2022] Open
Abstract
Adipokines including leptin, adiponectin and resistin have been linked to risk of obesity-related cancers potentially through low-grade chronic inflammation pathways. We aimed to assess the role of post-diagnosis circulating adipokines on long-term prognosis in a prospective breast cancer cohort. Adipokines were measured in blood collected at baseline shortly after diagnosis (2002-2005) and at follow-up (2009) from 3112 breast cancer patients enrolled in the population-based MARIE study. Half of the patients had measurements at both time-points. All-cause mortality, breast cancer specific mortality and recurrences were ascertained up to June 2015 (11 years median follow-up). Associations with time-varying adipokine concentrations overall and stratified by estrogen and progesterone receptor (ERPR) were evaluated using adjusted proportional hazard regression. At baseline (n = 2700) and follow-up (n = 2027), median concentrations for leptin, adiponectin and resistin were 4.6 and 2.7 ng/ml, 24.4 and 30.0 mg/l, 15.4 and 26.2 ng/ml, respectively. After adjustment, there was no evidence for associations between adipokines and any outcome overall. In ERPR negative tumors, highest vs. lowest quintile of adiponectin was significantly associated with increased breast cancer specific mortality (HR 2.51, 95%CI 1.07-5.92). Overall, post-diagnosis adipokines were not associated with long-term outcomes after breast cancer. In patients with ERPR negative tumors, higher concentrations of adiponectin may be associated with increased breast cancer specific mortality and warrant further investigation.
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Affiliation(s)
- Nadia Obi
- Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Audrey Y Jung
- Division of Cancer Epidemiology/Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
| | - Tabea Maurer
- Cancer Epidemiology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marianne Huebner
- Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
- Department of Statistics and Probability, Michigan State University, East Lansing, MI, 48824, USA
| | - Theron Johnson
- Division of Cancer Epidemiology/Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
| | - Sabine Behrens
- Division of Cancer Epidemiology/Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
| | - Stefanie Jaskulski
- Division of Cancer Epidemiology/Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University Medical Center, University of Freiburg, Freiburg, Germany
| | - Heiko Becher
- Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology/Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
- Cancer Epidemiology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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11
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Christodoulatos GS, Antonakos G, Karampela I, Psallida S, Stratigou T, Vallianou N, Lekka A, Marinou I, Vogiatzakis E, Kokoris S, Papavassiliou AG, Dalamaga M. Circulating Omentin-1 as a Biomarker at the Intersection of Postmenopausal Breast Cancer Occurrence and Cardiometabolic Risk: An Observational Cross-Sectional Study. Biomolecules 2021; 11:1609. [PMID: 34827610 PMCID: PMC8615461 DOI: 10.3390/biom11111609] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/10/2021] [Accepted: 10/28/2021] [Indexed: 12/11/2022] Open
Abstract
Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL (p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes (p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79-0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.
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Affiliation(s)
- Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece; (G.S.C.); (S.P.); (A.G.P.)
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry & Laboratory of Hematology and Blood Bank Unit, Medical School, National and Kapodistrian University of Athens, Attikon General University Hospital, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (G.A.); (S.K.)
| | - Irene Karampela
- 2nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini Street, Chaidari, 12462 Athens, Greece;
| | - Sotiria Psallida
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece; (G.S.C.); (S.P.); (A.G.P.)
| | - Theodora Stratigou
- Department of Internal Medicine and Endocrinology, Evaggelismos General Hospital, 45-47 Ypsilantou Street, 10676 Athens, Greece; (T.S.); (N.V.)
| | - Natalia Vallianou
- Department of Internal Medicine and Endocrinology, Evaggelismos General Hospital, 45-47 Ypsilantou Street, 10676 Athens, Greece; (T.S.); (N.V.)
| | - Antigoni Lekka
- Laboratory Department, NIMTS-Army Share Fund General Hospital, 12 Monis Petraki and Vasilissis Sofias Avenue, 11528 Athens, Greece;
| | - Ioanna Marinou
- Laboratory Department, Sotiria Athens General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece; (I.M.); (E.V.)
| | - Evaggelos Vogiatzakis
- Laboratory Department, Sotiria Athens General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece; (I.M.); (E.V.)
| | - Styliani Kokoris
- Laboratory of Clinical Biochemistry & Laboratory of Hematology and Blood Bank Unit, Medical School, National and Kapodistrian University of Athens, Attikon General University Hospital, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (G.A.); (S.K.)
| | - Athanasios G. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece; (G.S.C.); (S.P.); (A.G.P.)
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, Greece; (G.S.C.); (S.P.); (A.G.P.)
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12
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Rahman M, Ghasemi Y, Suley E, Zhou Y, Wang S, Rogers J. Machine Learning Based Computer Aided Diagnosis of Breast Cancer Utilizing Anthropometric and Clinical Features. Ing Rech Biomed 2021. [DOI: 10.1016/j.irbm.2020.05.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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13
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Deb A, Deshmukh B, Ramteke P, Bhati FK, Bhat MK. Resistin: A journey from metabolism to cancer. Transl Oncol 2021; 14:101178. [PMID: 34293684 PMCID: PMC8319804 DOI: 10.1016/j.tranon.2021.101178] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 06/23/2021] [Accepted: 07/09/2021] [Indexed: 12/11/2022] Open
Abstract
Resistin levels have been associated with several pathological disorders such as metabolic disorders, cancers etc. Resistin exists in three isoforms namely RELM-α, β and γ. High resistin level activates inflammatory pathways, promotes metabolic disorders and is associated with carcinogenesis. Increase in the resistin level impairs the therapeutic response by inducing stemness or resistance, in cancer cells. Conventional drugs which alter resistin level could have therapeutic implications in several pathological disorders. Resistin, a small secretory molecule, has been implicated to play an important role in the development of insulin resistance under obese condition. For the past few decades, it has been linked to various cellular and metabolic functions. It has been associated with diseases like metabolic disorders, cardiovascular diseases and cancers. Numerous clinical studies have indicated an increased serum resistin level in pathological disorders which have been reported to increase mortality rate in comparison to low resistin expressing subjects. Various molecular studies suggest resistin plays a pivotal role in proliferation, metastasis, angiogenesis, inflammation as well as in regulating metabolism in cancer cells. Therefore, understanding the role of resistin and elucidating its’ associated molecular mechanism will give a better insight into the management of these disorders. In this article, we summarize the diverse roles of resistin in pathological disorders based on the available literature, clinicopathological data, and a compiled study from various databases. The article mainly provides comprehensive information of its role as a target in different treatment modalities in pre as well as post-clinical studies.
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Affiliation(s)
- Ankita Deb
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Bhavana Deshmukh
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Pranay Ramteke
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Firoz Khan Bhati
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Manoj Kumar Bhat
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India.
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14
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ZARE MOAIEDI M, AHMADPOOR F, RASHIDI M, AHMADZADEH A, SALMASI AA, MOHAMMADZADEH G. The association between mRNA expression of resistin, TNF- α, IL-6, IL-8, and ER-α in peripheral blood mononuclear cells and breast cancer. Turk J Med Sci 2021; 51:1345-1353. [PMID: 33517609 PMCID: PMC8283432 DOI: 10.3906/sag-2008-292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 01/30/2021] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Adipocytokines, adipose tissue-derived proteins, were demonstrated to be involved in the pathogenesis of breast cancer. We assessed the mRNA expression of resistin, tumor necrosis factor-alpha (TNF-α), interleukins 6 and 8 (IL-6, and IL-8), and estrogen receptor alpha (ER-α) in peripheral blood mononuclear cells (PBMCs) of women with and without breast cancer. METHODS The PBMCs were isolated from the whole blood of 32 women with breast cancer and 18 women without breast cancer using density gradient centrifugation. The mRNA expression of the target genes was measured by reverse-transcription polymerase chain reaction (RT-PCR). Body mass index was calculated, additionally, clinicopathological characteristics of the breast cancer patients were determined by histopathological examination. RESULTS The mRNA expression of resistin (3.5-fold) and IL-6 (15-fold) in PBMCs of breast cancer patients significantly increased in comparison to healthy controls. Resistin expression was significantly associated with inflammatory markers including TNF-α, IL-6, IL-8, but not with anthropometric indices. Logistic regression analysis revealed the studied adipokines were not associated with breast cancer. Based on the ROC curve analysis the diagnostic performance of IL-6 was significant (0.825, 95% CI: 0.549-0.94, p = 0.030), thus, it might be considered as a breast cancer biomarker that reflecting an early and inflammatory stage of the disease. DISCUSSION Breast cancer is not associated with increased expression of inflammatory cytokines in PBMCs. Our results suggested that a PBMC-based gene expression test may be developed to detect breast cancer early.
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Affiliation(s)
- Maasoumeh ZARE MOAIEDI
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, AhvazIran
| | - Fatemeh AHMADPOOR
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, AhvazIran
| | - Mojtaba RASHIDI
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, AhvazIran
| | - Ahmad AHMADZADEH
- Department of Hematology-Oncology, Faculty of Medicine, Firoozgar Clinical Research Development Center, Iran University of Medical Sciences, TehranIran
| | - Amir Ahmad SALMASI
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, AhvazIran
- Department of Surgery, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, AhvazIran
| | - Ghorban MOHAMMADZADEH
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Science, Hyperlipidemia Research center, AhvazIran
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15
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Bergqvist M, Elebro K, Borgquist S, Rosendahl AH. Adipocytes Under Obese-Like Conditions Change Cell Cycle Distribution and Phosphorylation Profiles of Breast Cancer Cells: The Adipokine Receptor CAP1 Matters. Front Oncol 2021; 11:628653. [PMID: 33738261 PMCID: PMC7962603 DOI: 10.3389/fonc.2021.628653] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 01/22/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Obesity and associated metabolic conditions impact adipocyte functionality with potential consequences for breast cancer risk and prognosis, but contributing mechanisms remain to be understood. The adipokine receptor adenylyl cyclase-associated protein-1 (CAP1) has been implicated in the progression of breast cancer, but results are conflicting and the underlying molecular mechanisms are still unknown. In this study, molecular and cellular effects in breast cancer cells by stimulation of adipocytes under normal or obese-like conditions, and potential involvement of CAP1, were assessed. MATERIAL AND METHODS Estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cells were exposed to adipocyte-secretome from adipocytes placed under pressures mimicking normal and obese-like metabolic conditions. Changes in phosphorylated kinase proteins and related biological pathways were assessed by phospho-antibody array and PANTHER analysis, cell proliferation were investigated through sulforhodamine B, cell cycle distribution by flow cytometry. Functional effects of CAP1 were subsequently examined following small interfering (si)RNA-mediated knockdown. RESULTS Protein phosphorylations involved in important biological processes were enriched in T47D breast cancer cells in response to adipocyte secretome from obese-like compared with normal conditions. The obesity-associated adipocyte secretome further stimulated cell proliferation and a shift from cell cycle G1-phase to S- and G2/M-phase was observed. Silencing of CAP1 decreased cell proliferation in both T47D and MDA-MB-231 cells, and reduced the obesity-associated secretome-induction of phosphoproteins involved in cell proliferation pathways. CONCLUSIONS These results indicate that the adipocyte secretome and CAP1 are mechanistically important for the proliferation of both ER-positive and ER-negative breast cancer cells, and potential signaling mediators were identified. These studies provide biological insight into how obesity-associated factors could affect breast cancer.
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Affiliation(s)
- Malin Bergqvist
- Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Karin Elebro
- Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences Malmö, Surgery, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Signe Borgquist
- Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Ann H. Rosendahl
- Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden
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16
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Soni S, Torvund M, Mandal CC. Molecular insights into the interplay between adiposity, breast cancer and bone metastasis. Clin Exp Metastasis 2021; 38:119-138. [PMID: 33591548 DOI: 10.1007/s10585-021-10076-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 02/03/2021] [Indexed: 01/20/2023]
Abstract
Cancer is a complex disease, with various pre-existing health ailments enhancing its pathology. In cancer, the extracellular environment contains various intrinsic physiological factors whose levels are altered with aging and pre-existing conditions. In obesity, the tumor microenvironment and metastases are enriched with factors that are both derived locally, and from other physiological compartments. Similarly, in obesity, the cancer cell environment both at the site of origin and at the secondary site i.e., metastatic niche, contains significantly more phenotypically-altered adipocytes than that of un-obese cancer patients. Indeed, obesity has been linked with cancer progression, metastasis, and therapy resistance. Adipocytes not only interact with tumor cells, but also with adjacent stromal cells at primary and metastatic sites. This review emphasizes the importance of bidirectional interactions between adipocytes and breast tumor cells in breast cancer progression and its bone metastases. This paper not only chronicles the role of various adipocyte-derived factors in tumor growth, but also describes the significance of adipocyte-derived bone metastatic factors in the development of bone metastasis of breast cancer. It provides a molecular view of the interplay between the adipocytes and tumor cells involved in breast cancer bone metastasis. However, more research is needed to determine if targeting cancer-associated adipocytes holds promise as a potential therapeutic approach for breast cancer bone metastasis treatment. Interplay between adipocytes and breast cancer cells at primary cancer site and metastatic bone microenvironment. AMSC Adipose-derived mesenchymal stem cell, CAA Cancer associated adipocytes, CAF Cancer associated fibroblast, BMSC Bone marrow derived mesenchymal stem cell, BMA Bone marrow adipocyte.
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Affiliation(s)
- Sneha Soni
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Meaghan Torvund
- Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA
| | - Chandi C Mandal
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India.
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17
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Adipocytokines visfatin and resistin in breast cancer: Clinical relevance, biological mechanisms, and therapeutic potential. Cancer Lett 2020; 498:229-239. [PMID: 33152400 DOI: 10.1016/j.canlet.2020.10.045] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/11/2020] [Accepted: 10/26/2020] [Indexed: 12/17/2022]
Abstract
Obesity is one of the major modifiable risk factors in breast cancer, with obese adipose tissue showing a pathological role in breast cancer development and malignancy via the release of secretory factors, such as proinflammatory cytokines and adipocytokines. The current article focuses on visfatin and resistin, two such adipocytokines that have emerged over the last two decades as leading breast cancer promoting factors in obesity. The clinical association of circulating visfatin and resistin with breast cancer and their biological mechanisms are reviewed, in addition to their role in the context of tumor-stromal interactions in the breast cancer microenvironment. Recent findings have unraveled several mediators of visfatin and resistin that are involved in the crosstalk between breast cancer cells and adipose tissue in the breast tumor microenvironment, including growth differentiation factor 15 (GDF15), interleukin 6 (IL-6), and toll-like receptor 4 (TLR4). Finally, current therapeutics targeting visfatin and resistin and their respective pathways are discussed, including future therapeutic strategies such as new drug design or neutralizing peptides that target extracellular visfatin or resistin. These hold promise in the development of novel breast cancer therapies and are of increasing relevance as the prevalence of obesity-related breast cancer increases worldwide.
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18
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Motawi TM, Zakhary NI, Darwish HA, Abdullah H, Tadros SA. Significance of Some Non-Invasive Biomarkers in the Early Diagnosis and Staging of Egyptian Breast Cancer Patients. Asian Pac J Cancer Prev 2020; 21:3279-3284. [PMID: 33247685 PMCID: PMC8033118 DOI: 10.31557/apjcp.2020.21.11.3279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction: Breast cancer is one of the most relevant malignancies among women. Early diagnosis and accurate staging of breast cancer is important for the selection of an appropriate therapeutic strategy and achieving a better outcome. Aim: This study aimed to explore the significance of some non-invasive biomarkers in the early diagnosis and staging of Egyptian breast cancer patients. Subjects and Methods: A total of 135 female patients with physically and pathologically confirmed breast cancer and 40 unrelated controls as well as 40 patients with benign breast mass were enrolled in this study. The malignant breast cancer group was further divided into four groups according to tumor size. Serum levels of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), resistin and visfatin were determined by enzyme immunoassay. Results: Elevated levels of CEACAM1, resistin and visfatin were observed in breast cancer patients when compared with normal control and benign groups. The cutoff values, sensitivities and specificities of these biomarkers were appropriate for the discrimination of breast cancer from controls. Additionally, the serum levels of visfatin increased positively with tumor size and consequently with breast cancer stages. Conclusion: CEACAM1, resistin and visfatin are valuable in early diagnosis of breast cancer, with visfatin being preferentially used in staging.
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Affiliation(s)
- Tarek Mk Motawi
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nadia I Zakhary
- Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Hebatallah A Darwish
- Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt
| | - Hassan Abdullah
- Department of Surgical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Samer A Tadros
- Department of Biochemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), October, Egypt
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Nicchio BO, Barrouin-Melo SM, Machado MC, Vieira-Filho CH, Santos FL, Martins-Filho EF, Barbosa VF, Barral TD, Portela RW, Damasceno KA, Estrela-Lima A. Hyperresistinemia in Obese Female Dogs With Mammary Carcinoma in Benign-Mixed Tumors and Its Correlation With Tumor Aggressiveness and Survival. Front Vet Sci 2020; 7:509. [PMID: 32903534 PMCID: PMC7438446 DOI: 10.3389/fvets.2020.00509] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 07/03/2020] [Indexed: 12/16/2022] Open
Abstract
Resistin is associated with metabolic, inflammatory, and neoplastic disorders, and is also considered a prognostic marker in human oncology. Canine mammary tumors have epidemiological, clinical, biological, and genetic characteristics similar to those of women and are proposed as a comparative study model. Here, we evaluate the serum levels of resistin in female dogs with or without mammary carcinoma in mixed tumors (CBMT) and its correlation with the proliferative potential of the tumor, obesity, and survival. Eighty dogs grouped according to the presence (50) or absence (30) of CBMT, reproductive status and body condition were assessed for weight, fat percentage, and canine body mass index. The characteristic of the proliferative potential of the tumor (Ki-67) was evaluated. Ki-67 levels (p = 0.024), staging (p = 0.004), and grade (p = 0.016) influenced the survival of the female dogs. Through a multifactorial analysis, it could be seen that the parameters proliferation index (Ki-67) (p = 0.044) and staging (p = 0.036) influenced the survival of the animals. Neutered and overweight dogs from the control and CBMT groups showed hyperresistinemia. Ki-67 expression and resistin levels in dogs with CBMT were higher in overweight dogs than in dogs with normal weight (p = 0.0001). The survival rate of dogs with CBMT, obese and with high levels of resistin (8,400 μg L−1) was lower when compared to those with lower levels of resistin. These results showed an important relationship between hyperresistinemia, tumor proliferative potential and excessive body fat, suggesting that resistin levels may act as an interesting prognostic marker in patients with CBMT.
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Affiliation(s)
- Bianca Oliveira Nicchio
- School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil.,Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil
| | | | - Marilia Carneiro Machado
- School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil.,Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil
| | - Carlos Humberto Vieira-Filho
- School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil.,Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil
| | - Ferlando Lima Santos
- Health Science Center, Federal University of the Recôncavo of Bahia, Santo Antônio de Jesus, Brazil
| | - Emanoel Ferreira Martins-Filho
- School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil.,Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil
| | | | - Thiago Doria Barral
- Laboratory of Immunology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil
| | - Ricardo Wagner Portela
- Laboratory of Immunology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil
| | - Karine Araújo Damasceno
- Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil.,Laboratory of Experimental Pathology, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil
| | - Alessandra Estrela-Lima
- School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil.,Research Center on Mammary Oncology NPqOM/HOSPMEV/UFBA, Salvador, Brazil
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The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis. Int J Mol Sci 2020; 21:ijms21144967. [PMID: 32674405 PMCID: PMC7404398 DOI: 10.3390/ijms21144967] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023] Open
Abstract
The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted by both, are expected to play the most important role. Bone marrow adipocyte (BMA) is one of the cell types comprising the bone, and adipokine is one of the cytokines secreted by both breast cancer cells and BMAs. These BMAs and adipokines are known to be responsible for cancer progression, and this review is focused on how BMAs and adipokines work in the process of breast cancer bone metastasis. Their potential as suppressive targets for bone metastasis is also explored in this review.
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21
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Kolb R, Zhang W. Obesity and Breast Cancer: A Case of Inflamed Adipose Tissue. Cancers (Basel) 2020; 12:E1686. [PMID: 32630445 PMCID: PMC7352736 DOI: 10.3390/cancers12061686] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/09/2020] [Accepted: 06/22/2020] [Indexed: 02/07/2023] Open
Abstract
Obesity is associated with an increased risk of estrogen receptor-positive breast cancer in postmenopausal women and a worse prognosis for all major breast cancer subtypes regardless of menopausal status. While the link between obesity and the pathogenesis of breast cancer is clear, the molecular mechanism of this association is not completely understood due to the complexity of both obesity and breast cancer. The aim of this review is to highlight the association between obesity and breast cancer and discuss the literature, which indicates that this association is due to chronic adipose tissue inflammation. We will discuss the epidemiological data for the association between breast cancer incidence and progression as well as the potential molecular mechanisms for this association. We will focus on the role of inflammation within the adipose tissue during the pathogenesis of breast cancer. A better understanding of how obesity and adipose tissue inflammation affects the pathogenesis of breast cancer will lead to new strategies to reduce breast cancer risk and improve patient outcomes for obese patients.
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Affiliation(s)
- Ryan Kolb
- Department of Pathology, Immunology and Laboratory Medicine, Gainesville, FL 32610, USA;
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
| | - Weizhou Zhang
- Department of Pathology, Immunology and Laboratory Medicine, Gainesville, FL 32610, USA;
- University of Florida Health Cancer Center, Gainesville, FL 32610, USA
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22
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Sundaram S, Yan L. Adipose monocyte chemotactic protein-1 deficiency reduces high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. J Nutr Biochem 2020; 77:108313. [PMID: 31837540 DOI: 10.1016/j.jnutbio.2019.108313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 10/16/2019] [Accepted: 11/25/2019] [Indexed: 01/24/2023]
Abstract
Monocyte chemotactic protein-1 (MCP-1) is an adipokine with demonstrated carcinogenic potential. However, there is a lack of evidence whether adipose-produced MCP-1 contributes to breast cancer. We tested the hypothesis that adipose-produced MCP-1 contributes to mammary tumorigenesis in this study. In a breast cancer model of mouse mammary tumor virus-polyomavirus middle T-antigen (MMTV-PyMT), mice with or without adipose MCP-1 knockout [designated as Mcp-1-/- or wild-type (WT)] were fed the standard AIN93G diet (16% of energy from soybean oil) or a high-fat diet (HFD, 45% of energy from soybean oil). Adipose MCP-1 knockout reduced Mcp-1 expression in adipose tissue and concentrations of MCP-1 in plasma. Mcp-1-/- mice fed the HFD had less body fat than their WT counterparts. Adipose MCP-1 knockout attenuated HFD-enhanced mammary tumorigenesis, evidenced by lower mammary tumor volume. Furthermore, Mcp-1-/- mice, regardless of diet, had a longer tumor latency and less tumor weight than WT mice. When fed the HFD, Mcp-1-/- mice, compared to WT mice, exhibited lower concentrations of insulin, leptin, resistin, vascular endothelial growth factor and hepatic growth factor in plasma. In summary, adipose MCP-1 deficiency attenuated HFD-enhanced MMTV-PyMT mammary tumorigenesis. This attenuation can be attributed to less body adiposity, improvement in insulin sensitivity and down-regulation in protumorigenic inflammation cytokines and angiogenic factors in Mcp-1-/- mice. It concludes that adipose-produced MCP-1 contributes to mammary tumorigenesis in the MMTV-PyMT mouse model.
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Affiliation(s)
- Sneha Sundaram
- U.S. Department of Agriculture Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA.
| | - Lin Yan
- U.S. Department of Agriculture Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA.
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23
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Oktay K, Santaliz-Casiano A, Patel M, Marino N, Storniolo AMV, Torun H, Acar B, Madak Erdogan Z. A Computational Statistics Approach to Evaluate Blood Biomarkers for Breast Cancer Risk Stratification. Discov Oncol 2019; 11:17-33. [PMID: 31858384 DOI: 10.1007/s12672-019-00372-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 11/25/2019] [Indexed: 02/07/2023] Open
Abstract
Breast cancer is the second leading cause of cancer mortality among women. Mammography and tumor biopsy followed by histopathological analysis are the current methods to diagnose breast cancer. Mammography does not detect all breast tumor subtypes, especially those that arise in younger women or women with dense breast tissue, and are more aggressive. There is an urgent need to find circulating prognostic molecules and liquid biopsy methods for breast cancer diagnosis and reducing the mortality rate. In this study, we systematically evaluated metabolites and proteins in blood to develop a pipeline to identify potential circulating biomarkers for breast cancer risk. Our aim is to identify a group of molecules to be used in the design of portable and low-cost biomarker detection devices. We obtained plasma samples from women who are cancer free (healthy) and women who were cancer free at the time of blood collection but developed breast cancer later (susceptible). We extracted potential prognostic biomarkers for breast cancer risk from plasma metabolomics and proteomics data using statistical and discriminative power analyses. We pre-processed the data to ensure the quality of subsequent analyses, and used two main feature selection methods to determine the importance of each molecule. After further feature elimination based on pairwise dependencies, we measured the performance of logistic regression classifier on the remaining molecules and compared their biological relevance. We identified six signatures that predicted breast cancer risk with different specificity and selectivity. The best performing signature had 13 factors. We validated the difference in level of one of the biomarkers, SCF/KITLG, in plasma from healthy and susceptible individuals. These biomarkers will be used to develop low-cost liquid biopsy methods toward early identification of breast cancer risk and hence decreased mortality. Our findings provide the knowledge basis needed to proceed in this direction.
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Affiliation(s)
- Kaan Oktay
- VAVlab, Electrical & Electronics Engineering Department, Bogazici University, Istanbul, Turkey
| | | | - Meera Patel
- Susan G. Komen Tissue Bank at the IU Simon Cancer Center, Indianapolis, IN, USA
| | - Natascia Marino
- Susan G. Komen Tissue Bank at the IU Simon Cancer Center, Indianapolis, IN, USA.,Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Anna Maria V Storniolo
- Susan G. Komen Tissue Bank at the IU Simon Cancer Center, Indianapolis, IN, USA.,Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Hamdi Torun
- Faculty of Engineering and Environment, University of Northumbria, Newcastle upon Tyne, UK
| | - Burak Acar
- VAVlab, Electrical & Electronics Engineering Department, Bogazici University, Istanbul, Turkey
| | - Zeynep Madak Erdogan
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA. .,Department of Food Sciences and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL, USA. .,National Center for Supercomputing Applications, University of Illinois Urbana-Champaign, Urbana, IL, USA. .,Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA. .,Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA. .,Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
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24
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Christodoulatos GS, Spyrou N, Kadillari J, Psallida S, Dalamaga M. The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives. Curr Obes Rep 2019; 8:413-433. [PMID: 31637624 DOI: 10.1007/s13679-019-00364-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The current review shows evidence for the role of adipokines in breast cancer (BC) pathogenesis summarizing the mechanisms underlying the association between adipokines and breast malignancy. Special emphasis is given also on intriguing insights into the relationship between obesity and BC as well as on the role of novel adipokines in BC development. RECENT FINDINGS Recent evidence has underscored the role of the triad of obesity, insulin resistance, and adipokines in postmenopausal BC. Adipokines exert independent and joint effects on activation of major intracellular signal networks implicated in BC cell proliferation, growth, survival, invasion, and metastasis, particularly in the context of obesity, considered a systemic endocrine dysfunction characterized by chronic inflammation. To date, more than 10 adipokines have been linked to BC, and this catalog is continuously increasing. The majority of circulating adipokines, such as leptin, resistin, visfatin, apelin, lipocalin 2, osteopontin, and oncostatin M, is elevated in BC, while some adipokines such as adiponectin and irisin (adipo-myokine) are generally decreased in BC and considered protective against breast carcinogenesis. Further evidence from basic and translational research is necessary to delineate the ontological role of adipokines and their interplay in BC pathogenesis. More large-scale clinical and longitudinal studies are awaited to assess their clinical utility in BC prognosis and follow-up. Finally, novel more effective and safer adipokine-centered therapeutic strategies could pave the way for targeted oncotherapy.
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Affiliation(s)
- Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece
- Laboratory of Microbiology, KAT Hospital, 2 Nikis, Kifisia, 14561, Athens, Greece
| | - Nikolaos Spyrou
- 251 Airforce General Hospital, 3 Kanellopoulou, 11525, Athens, Greece
| | - Jona Kadillari
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece
| | - Sotiria Psallida
- Laboratory of Microbiology, KAT Hospital, 2 Nikis, Kifisia, 14561, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece.
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25
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Karampela I, Christodoulatos GS, Dalamaga M. The Role of Adipose Tissue and Adipokines in Sepsis: Inflammatory and Metabolic Considerations, and the Obesity Paradox. Curr Obes Rep 2019; 8:434-457. [PMID: 31637623 DOI: 10.1007/s13679-019-00360-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE Sepsis has become a global health problem with rising incidence and high mortality, creating a substantial social and economic burden. Early diagnosis and treatment can improve outcome, but reliable sepsis biomarkers are lacking. This review summarizes current evidence of the pathophysiological mechanisms linking adipose tissue to sepsis and presents experimental and clinical data on adipokines and sepsis along with important insights into the obesity paradox in sepsis survival. RECENT FINDINGS Sepsis is characterized by significant alterations in circulating cytokines and adipokines, biologically active molecules produced by the adipose tissue, being implicated in metabolic and inflammatory processes. Although data are inconclusive regarding classic adipokines such as leptin and adiponectin, recent evidence have highlighted the striking elevation of resistin and visfatin in critical illness and sepsis as well as their association with sepsis severity and outcomes. Given that inflammatory and metabolic pathways are involved in sepsis, studying adipokines presents an attractive, innovative, and promising research field that may provide more powerful diagnostic and prognostic biomarkers as well as novel therapeutic targets, empowering the therapeutic armamentarium for sepsis management in order to improve survival.
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Affiliation(s)
- Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462, Athens, Greece.
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece.
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece
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26
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Ghani MU, Alam TM, Jaskani FH. Comparison of Classification Models for Early Prediction of Breast Cancer. 2019 INTERNATIONAL CONFERENCE ON INNOVATIVE COMPUTING (ICIC) 2019. [DOI: 10.1109/icic48496.2019.8966691] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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27
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Chu DT, Phuong TNT, Tien NLB, Tran DK, Nguyen TT, Thanh VV, Quang TL, Minh LB, Pham VH, Ngoc VTN, Kushekhar K, Chu-Dinh T. The Effects of Adipocytes on the Regulation of Breast Cancer in the Tumor Microenvironment: An Update. Cells 2019; 8:E857. [PMID: 31398937 PMCID: PMC6721665 DOI: 10.3390/cells8080857] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 07/27/2019] [Accepted: 08/06/2019] [Indexed: 12/24/2022] Open
Abstract
Obesity is a global pandemic and it is well evident that obesity is associated with the development of many disorders including many cancer types. Breast cancer is one of that associated with a high mortality rate. Adipocytes, a major cellular component in adipose tissue, are dysfunctional during obesity and also known to promote breast cancer development both in vitro and in vivo. Dysfunctional adipocytes can release metabolic substrates, adipokines, and cytokines, which promote proliferation, progression, invasion, and migration of breast cancer cells. The secretion of adipocytes can alter gene expression profile, induce inflammation and hypoxia, as well as inhibit apoptosis. It is known that excessive free fatty acids, cholesterol, triglycerides, hormones, leptin, interleukins, and chemokines upregulate breast cancer development. Interestingly, adiponectin is the only adipokine that has anti-tumor properties. Moreover, adipocytes are also related to chemotherapeutic resistance, resulting in the poorer outcome of treatment and advanced stages in breast cancer. Evaluation of the adipocyte secretion levels in the circulation can be useful for prognosis and evaluation of the effectiveness of cancer therapy in the patients. Therefore, understanding about functions of adipocytes as well as obesity in breast cancer may reveal novel targets that support the development of new anti-tumor therapy. In this systemic review, we summarize and update the effects of secreted factors by adipocytes on the regulation of breast cancer in the tumor microenvironment.
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Affiliation(s)
- Dinh-Toi Chu
- Faculty of Biology, Hanoi National University of Education, Hanoi 100000, Vietnam.
- School of Odonto Stomatology, Hanoi Medical University, Hanoi 100000, Vietnam.
- Former address: Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, 0349 Oslo, Norway.
| | - Thuy Nguyen Thi Phuong
- Department of Animal Science, College of Agriculture and Life Science, Chonnam National University, Gwangju 61186, Korea
| | - Nguyen Le Bao Tien
- Institute of Orthopaedics and Trauma Surgery, Viet Duc Hospital, Hanoi 100000, Vietnam
| | - Dang-Khoa Tran
- Department of Anatomy, University of Medicine Pham Ngoc Thach, Ho Chi Minh City 700000, Vietnam
| | - Tran-Thuy Nguyen
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Center, E Hospital, Hanoi 100000, Vietnam
- School of Medicine and Pharmacy, Vietnam National University, Hanoi 100000, Vietnam
| | - Vo Van Thanh
- Institute of Orthopaedics and Trauma Surgery, Viet Duc Hospital, Hanoi 100000, Vietnam
- Department of Surgery, Hanoi Medical University, Hanoi 100000, Vietnam
| | - Thuy Luu Quang
- Center for Anesthesia and Surgical Intensive Care, Viet Duc Hospital, Hanoi 100000, Vietnam
| | - Le Bui Minh
- NTT Hi-tech Institute, Nguyen Tat Thanh University, 300A Nguyen Tat Thanh St., Ward 13, District 4, Ho Chi Minh City 700000, Vietnam
| | - Van Huy Pham
- AI Lab, Faculty of Information Technology, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam.
| | - Vo Truong Nhu Ngoc
- School of Odonto Stomatology, Hanoi Medical University, Hanoi 100000, Vietnam
| | - Kushi Kushekhar
- Institute of Cancer Research, Oslo University Hospital, 0310 Oslo, Norway
| | - Thien Chu-Dinh
- Institute for Research and Development, Duy Tan University, Danang 550000, Vietnam.
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Avtanski D, Garcia A, Caraballo B, Thangeswaran P, Marin S, Bianco J, Lavi A, Poretsky L. Resistin induces breast cancer cells epithelial to mesenchymal transition (EMT) and stemness through both adenylyl cyclase-associated protein 1 (CAP1)-dependent and CAP1-independent mechanisms. Cytokine 2019; 120:155-164. [PMID: 31085453 DOI: 10.1016/j.cyto.2019.04.016] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/21/2019] [Accepted: 04/22/2019] [Indexed: 01/08/2023]
Abstract
Breast cancer incidence and metastasis in postmenopausal women are known to associate with obesity, but the molecular mechanisms behind this association are largely unknown. We investigated the effect of adipokine resistin on epithelial to mesenchymal transition (EMT) and stemness in breast cancer cells in vitro. Previous reports demonstrated that the inflammatory actions of resistin are mediated by the adenylyl cyclase-associated protein 1 (CAP1), which serves as its receptor. As a model for our study, we used MCF-7 and MDA-MB-231 breast cancer and MCF-10A breast epithelial cells. We showed that in MCF-7 cells resistin increases the migration of MCF-7 and MDA-MB-231 cells and induces the formation of cellular protrusions through reorganization of F-actin filaments. Resistin upregulated the expression of mesenchymal markers involved in EMT (SNAIL, SLUG, ZEB1, TWIST1, fibronectin, and vimentin), and downregulated those of epithelial markers (E-cadherin and claudin-1). Resistin also potentiated the nuclear translocation of SNAIL protein, indicating initiation of EMT reprogramming. We further induced EMT in non-carcinogenic breast epithelial MCF-10A cells demonstrating that the effects of resistin on EMT were not breast cancer cell specific. In order to assess whether resistin-induced EMT depends on CAP1, we used siRNA approach to silence CAP1 gene in MCF-7 cells. Results demonstrated that when CAP1 was silenced, the induction of SNAIL, ZEB1 and vimentin expression by resistin as well as SNAIL and ZEB1 nuclear translocation, were abolished. Additionally, CAP1 silencing resulted in a suppression of MCF-7 cells migration. We performed quantitative PCR array profiling the expression of 84 genes related to cancer stem cells (CSC), pluripotency and metastasis and selected a set of genes (ALDH1A1, ITGA4, LIN28B, SMO, KLF17, PTPRC, PROM1, SIRT1, and PECAM1) that were modulated by resistin. Further experiments demonstrated that the effect of resistin on the expression of some of these genes (PROM1, PTPRC, KLF17, SIRT1, and PECAM1) was also dependent on CAP1. Our results demonstrate that resistin promotes the metastatic potential of breast cancer cells by inducing EMT and stemness and some of these effects are mediated by CAP1.
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Affiliation(s)
- Dimiter Avtanski
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
| | - Anabel Garcia
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Beatriz Caraballo
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | | | - Sela Marin
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Julianna Bianco
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Aaron Lavi
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Leonid Poretsky
- Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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Determining relevant biomarkers for prediction of breast cancer using anthropometric and clinical features: A comparative investigation in machine learning paradigm. Biocybern Biomed Eng 2019. [DOI: 10.1016/j.bbe.2019.03.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Karampela I, Christodoulatos GS, Kandri E, Antonakos G, Vogiatzakis E, Dimopoulos G, Armaganidis A, Dalamaga M. Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: A prospective observational study. Cytokine 2019; 119:62-70. [PMID: 30884428 DOI: 10.1016/j.cyto.2019.03.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 03/06/2019] [Accepted: 03/07/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND The adipocytokines eNampt and resistin are involved in the regulation of inflammation exerting pro-inflammatory actions. Our aim was to jointly investigate whether circulating eNampt and resistin, and their kinetics predict 28-day mortality of sepsis. METHODS In a prospective study, serum eNampt and resistin were determined in 102 critically ill patients fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after, and in 102 healthy controls matched on age, gender and month of diagnosis. RESULTS Serum eNampt and resistin were significantly higher in septic patients than controls (p < 0.001), and higher in septic shock compared to sepsis (p < 0.001). Both eNampt and resistin decreased significantly during the first week of sepsis (p < 0.001). However, patients with septic shock presented a sustained elevation of eNampt and resistin compared to patients with sepsis. Both adipocytokines were positively correlated with sepsis severity scores and lactate. Baseline eNampt was a better discriminator of sepsis and septic shock compared to C-reactive protein and procalcitonin. Serum eNampt and resistin were higher in nonsurvivors than in survivors during the first week of sepsis. Prolonged and sustained elevation of both eNampt and resistin, as reflected by a lower percentage change from their baseline values, was independently associated with 28-day mortality (HR: 0.05, 95% C.I. 0.01-0.28, p = 0.001; HR: 0.19, 95% C.I. 0.07-0.50, p = 0.001, respectively), after adjustment for significant clinical and laboratory biomarkers. CONCLUSION Circulating eNampt and resistin, and their kinetics may represent useful diagnostic and prognostic biomarkers in critically ill septic patients. More prospective studies are needed to elucidate their ontological and pathophysiological role in sepsis.
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Affiliation(s)
- Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Evangelia Kandri
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | | | - George Dimopoulos
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Apostolos Armaganidis
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
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31
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Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism 2019; 92:121-135. [PMID: 30445141 DOI: 10.1016/j.metabol.2018.11.001] [Citation(s) in RCA: 841] [Impact Index Per Article: 140.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/02/2018] [Accepted: 11/03/2018] [Indexed: 02/07/2023]
Abstract
Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.
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Affiliation(s)
| | - Nikolaos Spyrou
- 251 Airforce General Hospital, Kanellopoulou 3, 11525, Athens, Greece
| | - Christos S Mantzoros
- Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece.
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32
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Acquarone E, Monacelli F, Borghi R, Nencioni A, Odetti P. Resistin: A reappraisal. Mech Ageing Dev 2019; 178:46-63. [DOI: 10.1016/j.mad.2019.01.004] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 12/28/2018] [Accepted: 01/11/2019] [Indexed: 02/07/2023]
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33
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Spyrou N, Avgerinos KI, Mantzoros CS, Dalamaga M. Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies. Curr Obes Rep 2018; 7:260-275. [PMID: 30145771 DOI: 10.1007/s13679-018-0318-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development. RECENT FINDINGS Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis. Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.
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Affiliation(s)
- Nikolaos Spyrou
- 251 Airforce General Hospital, Kanellopoulou 3, 11525, Athens, Greece
| | | | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA
- Section of Endocrinology, VA Boston Healthcare System, Boston, MA, USA
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece.
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Kang C, LeRoith D, Gallagher EJ. Diabetes, Obesity, and Breast Cancer. Endocrinology 2018; 159:3801-3812. [PMID: 30215698 PMCID: PMC6202853 DOI: 10.1210/en.2018-00574] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 09/05/2018] [Indexed: 12/13/2022]
Abstract
The rates of obesity and diabetes are increasing worldwide, whereas the age of onset for both obesity and diabetes are decreasing steadily. Obesity and diabetes are associated with multiple factors that contribute to the increased risk of a number of different cancers, including breast cancer. These factors are hyperinsulinemia, elevated IGFs, hyperglycemia, dyslipidemia, adipokines, inflammatory cytokines, and the gut microbiome. In this review, we discuss the current understanding of the complex signaling pathways underlying these multiple factors involved in the obesity/diabetes-breast cancer link, with a focus particularly on the roles of the insulin/IGF system and dyslipidemia in preclinical breast cancer models. We review some of the therapeutic strategies to target these metabolic derangements in cancer. Future research directions and potential therapeutic strategies are also discussed.
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Affiliation(s)
- Chifei Kang
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Derek LeRoith
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Emily J Gallagher
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York
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Hashemi M, Bahari G, Tabasi F, Moazeni-Roodi A, Ghavami S. Association between rs1862513 and rs3745367 Genetic Polymorphisms of Resistin and Risk of Cancer: A Meta-Analysis. Asian Pac J Cancer Prev 2018; 19:2709-2716. [PMID: 30360595 PMCID: PMC6291049 DOI: 10.22034/apjcp.2018.19.10.2709] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The present study aimed to assess any associations between resistin gene (RETN) polymorphisms and cancer
susceptibility by conducting a meta-analysis. A comprehensive literature search was performed with PubMed, Web of
Science, Scopus and Google Scholar for relevant studies published before April 2018. For the rs1862513 polymorphism,
data from 9 studies covering 1,951 cancer patients and 2,295 healthy controls were included in this meta-analysis. Pooled
odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Our meta-analysis revealed that this RETN
polymorphism significantly increased the risk of cancer in codominant (OR=1.23, 95% CI= 1.01-1.50, p=0.04, CG vs CC;
and OR=1.25, 95% CI= 1.03-1.53, p=0.03, GG vs CC), dominant (OR=1.19, 95% CI= 1.05-1.35, p=0.006, CG+GG vs CC),
and allele (OR=1.14, 95% CI= 1.00-1.30, p=0.04, G vs C) inheritance genetic models. Stratification analysis by cancer
type revealed that the rs1862513 variant significantly increased the risk of colorectal and breast cancer, and that cancer
overall in Caucasians (OR=1.22, 95% CI= 1.04-1.43, p=0.02, CG+GG vs CC; OR=1.18, 95% CI= 1.04-1.34, p=0.01,
G vs C). The data revealed no correlation between the rs3745367 polymorphism and cancer risk. Further well-designed
studies with larger sample sizes and different ethnicities are warranted to validate the present findings.
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Affiliation(s)
- Mohammad Hashemi
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
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Sotiropoulos GP, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Kotopouli M, Karampela I, Christodoulatos GS, Lekka A, Papavassiliou AG. Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer. Lung Cancer 2018; 125:291-299. [PMID: 30429035 DOI: 10.1016/j.lungcan.2018.10.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 10/05/2018] [Accepted: 10/08/2018] [Indexed: 01/29/2023]
Abstract
OBJECTIVES Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). RESULTS NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. CONCLUSION Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.
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Affiliation(s)
- George P Sotiropoulos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece; Department of Thoracic Surgery, 'Sotiria' General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece.
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462 Athens, Greece
| | - Ioanna Marinou
- Laboratory of Microbiology, 'Sotiria'General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece
| | - Evaggelos Vogiatzakis
- Laboratory of Microbiology, 'Sotiria'General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece
| | - Marianna Kotopouli
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece
| | - Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462 Athens, Greece
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece
| | - Antigoni Lekka
- Department of Laboratory Hematology, NIMTS General Hospital, Monis Petraki 10-12, 11521 Athens, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece
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Bassaro L, Russell SJ, Pastwa E, Somiari SA, Somiari RI. Screening for Multiple Autoantibodies in Plasma of Patients with Breast Cancer. Cancer Genomics Proteomics 2018; 14:427-435. [PMID: 29109092 DOI: 10.21873/cgp.20052] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 09/20/2017] [Accepted: 09/22/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIM Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an Autoantibody Profiling System (APS) and quantify the levels in plasma of donors with/without breast cancer. MATERIALS AND METHODS Plasma from nine female donors diagnosed with breast cancer (test group) and nine matched donors with no personal history of cancer (reference group) were screened with an APS containing probes for 30 autoantibodies. Autoantibody levels ≥1.5 times the mean concentration of the group were considered elevated, and test/reference ratios ≥1.3 were considered higher in the test group compared to the reference group. RESULTS Twenty percent of the probes detected elevated levels of autoantibodies against proteins involved in different cancer mechanisms. Amongst these, the levels of autoantibodies against interleukin 29 (IL29), osteoprotegerin (OPG), survivin (SUR), growth hormone (GRH) and resistin (RES) were significantly higher in the cancer group compared to the reference group (p<0.05), whereas the level of autoantibody against cytotoxic T-lymphocyte associated antigen-4 (CTLA4) was not significantly different between the two groups (p=0.38). CONCLUSION Disease-relevant autoantibodies were detected in the plasma of patients with breast cancer and donors without breast cancer. This means that identifying the type and level of autoantibodies in samples will be important in determining their significance in the disease process. A microtiter plate-based array system could be a fast and inexpensive screening method for identifying and quantifying autoantibodies in human plasma.
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Affiliation(s)
- Lauren Bassaro
- Functional Genomics & Proteomics Unit, ITSI-Biosciences, Johnstown, PA, U.S.A
| | - Stephen J Russell
- Functional Genomics & Proteomics Unit, ITSI-Biosciences, Johnstown, PA, U.S.A
| | - Elzbieta Pastwa
- Functional Genomics & Proteomics Unit, ITSI-Biosciences, Johnstown, PA, U.S.A
| | - Stella A Somiari
- Biobanking & Biospecimen Science Research Unit, Windber Research Institute, Windber, PA, U.S.A
| | - Richard I Somiari
- Functional Genomics & Proteomics Unit, ITSI-Biosciences, Johnstown, PA, U.S.A.
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Stratigou T, Dalamaga M, Antonakos G, Marinou I, Vogiatzakis E, Christodoulatos GS, Karampela I, Papavassiliou AG. Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors. Endocrine 2018; 61:83-93. [PMID: 29455364 DOI: 10.1007/s12020-018-1550-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 01/29/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. METHODS In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. RESULTS SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09). CONCLUSIONS Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.
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Affiliation(s)
- Theodora Stratigou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527, Athens, Greece
- Department of Endocrinology, 'Evangelismos' General Hospital of Athens, 45-47 Ypsilantou street, 10676, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527, Athens, Greece.
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462, Athens, Greece
| | - Ioanna Marinou
- Laboratory of Microbiology, 'Sotiria' General Hospital, 152 Mesogeion Avenue, 11527, Athens, Greece
| | - Evaggelos Vogiatzakis
- Laboratory of Microbiology, 'Sotiria' General Hospital, 152 Mesogeion Avenue, 11527, Athens, Greece
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527, Athens, Greece
| | - Irene Karampela
- Department of Internal Medicine, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462, Athens, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527, Athens, Greece
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Tang H, Bai Y, Shen W, Wei Y, Xu M, Zhou X, Zhao J. Clinical significance of combined detection of interleukin-6 and tumour markers in lung cancer. Autoimmunity 2018; 51:191-198. [PMID: 29869537 DOI: 10.1080/08916934.2018.1477133] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Hexiao Tang
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yuquan Bai
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Wulin Shen
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yanhong Wei
- Department of Nephrology, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ming Xu
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xuefeng Zhou
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jinping Zhao
- Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
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Dalamaga M, Christodoulatos GS, Mantzoros CS. The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges. Metabolism 2018; 82:72-87. [PMID: 29330025 DOI: 10.1016/j.metabol.2018.01.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 12/23/2017] [Accepted: 01/04/2018] [Indexed: 02/07/2023]
Abstract
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.
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Affiliation(s)
- Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece.
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece; Department of Microbiology, KAT Hospital, Nikis 2, Kifisia, 14561 Athens, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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Evaluation of serum resistin levels in patients with hepatocellular carcinoma before and after treatment. EGYPTIAN LIVER JOURNAL 2018. [DOI: 10.1097/01.elx.0000546516.15821.c2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Li J, Han X. Adipocytokines and breast cancer. Curr Probl Cancer 2018; 42:208-214. [PMID: 29433827 DOI: 10.1016/j.currproblcancer.2018.01.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 12/26/2017] [Accepted: 01/04/2018] [Indexed: 12/11/2022]
Abstract
A substantial number of studies have revealed that a growing list of cancers might be influenced by obesity. In this regard, one of the most prominent and well-characterized cancers is breast cancer, the leading cause of cancer death among women. Obesity is associated with an increased risk for the occurrence and development of breast cancer particular in postmenopausal women. Moreover, the relationship between adiposity and breast cancer risk is complex, with associations that differ depending on when body size is assessed (eg, premenopausal vs postmenopausal obesity) and when breast cancer is diagnosed (ie, premenopausal vs postmenopausal disease). Obesity is mainly due to excessive fat accumulation in the regional tissue. Adipocytes in obese individuals produce endocrine, inflammatory, and angiogenic factors to affect adjacent breast cancer cells. Adipocytokines, are biologically active polypeptides that are produced either exclusively or substantially by adipocytes, play a critical and complex role, and act by endocrine, paracrine, and autocrine pathways in the malignant progression of breast cancer. Furthermore, the increased levels of leptin, resistin, and decreased adiponectin secretion are directly associated with breast cancer development. And there are also many studies indicating that adipocytokines could mediate the survival, growth, invasion, and metastasis of breast cancer cells by different cellular and molecular mechanisms to reduce the survival time and prompt the malignancy. In present review, we discuss the correlations between several adipocytokines and breast cancer cells in obesity as well as the underlying signaling pathways to provide the novel ideas for the prevention and treatment of breast cancer.
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Affiliation(s)
- Jiajia Li
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xianghui Han
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Patrício M, Pereira J, Crisóstomo J, Matafome P, Gomes M, Seiça R, Caramelo F. Using Resistin, glucose, age and BMI to predict the presence of breast cancer. BMC Cancer 2018; 18:29. [PMID: 29301500 PMCID: PMC5755302 DOI: 10.1186/s12885-017-3877-1] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 12/05/2017] [Indexed: 12/11/2022] Open
Abstract
Background The goal of this exploratory study was to develop and assess a prediction model which can potentially be used as a biomarker of breast cancer, based on anthropometric data and parameters which can be gathered in routine blood analysis. Methods For each of the 166 participants several clinical features were observed or measured, including age, BMI, Glucose, Insulin, HOMA, Leptin, Adiponectin, Resistin and MCP-1. Machine learning algorithms (logistic regression, random forests, support vector machines) were implemented taking in as predictors different numbers of variables. The resulting models were assessed with a Monte Carlo Cross-Validation approach to determine 95% confidence intervals for the sensitivity, specificity and AUC of the models. Results Support vector machines models using Glucose, Resistin, Age and BMI as predictors allowed predicting the presence of breast cancer in women with sensitivity ranging between 82 and 88% and specificity ranging between 85 and 90%. The 95% confidence interval for the AUC was [0.87, 0.91]. Conclusions These findings provide promising evidence that models combining age, BMI and metabolic parameters may be a powerful tool for a cheap and effective biomarker of breast cancer. Electronic supplementary material The online version of this article (10.1186/s12885-017-3877-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Miguel Patrício
- Laboratory of Biostatistics and Medical Informatics and IBILI - Faculty of Medicine, University of Coimbra, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal.
| | - José Pereira
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Joana Crisóstomo
- Laboratory of Physiology, IBILI - Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Paulo Matafome
- Laboratory of Physiology, IBILI - Faculty of Medicine of University of Coimbra, Coimbra, Portugal.,Department of Complementary Sciences, Coimbra Health School - Instituto Politécnico de Coimbra, Coimbra, Portugal
| | - Manuel Gomes
- Department of Internal Medicine, University Hospital Centre of Coimbra, Coimbra, Portugal
| | - Raquel Seiça
- Laboratory of Physiology, IBILI - Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Francisco Caramelo
- Laboratory of Biostatistics and Medical Informatics and IBILI - Faculty of Medicine, University of Coimbra, Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal
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Circulating resistin levels and risk of multiple myeloma in three prospective cohorts. Br J Cancer 2017; 117:1241-1245. [PMID: 28829767 PMCID: PMC5674102 DOI: 10.1038/bjc.2017.282] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 07/11/2017] [Accepted: 07/21/2017] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men.
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Singh S, Chouhan S, Mohammad N, Bhat MK. Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3. FEBS Lett 2017; 591:1371-1382. [PMID: 28417458 DOI: 10.1002/1873-3468.12655] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 03/17/2017] [Accepted: 04/10/2017] [Indexed: 12/18/2022]
Abstract
Resistin, a proinflammatory cytokine, is elevated in a number of pathological disorders, including cancer. The serum resistin level in colon cancer patients is elevated and correlates with tumor grade. However, the implications of increased resistin on colon cancer cells remain unclear. In the present study, we find that resistin binds to TLR4 on colon cancer cell membrane and initiates TLR4-MyD88-dependent activation of ERK. In addition, the upregulation of SOCS3 by ERK downregulates the JAK2/TAT3 pathway and causes the arrest of cells in G1 phase. Interestingly, we observe that resistin-exposed cells survive 5-fluorouracil treatment because of a decrease in drug uptake due to the arrest of cells in G1 phase.
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Karampela I, Kandri E, Antonakos G, Vogiatzakis E, Christodoulatos GS, Nikolaidou A, Dimopoulos G, Armaganidis A, Dalamaga M. Kinetics of circulating fetuin-A may predict mortality independently from adiponectin, high molecular weight adiponectin and prognostic factors in critically ill patients with sepsis: A prospective study. J Crit Care 2017; 41:78-85. [PMID: 28500919 DOI: 10.1016/j.jcrc.2017.05.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 04/20/2017] [Accepted: 05/03/2017] [Indexed: 12/29/2022]
Abstract
PURPOSE Fetuin-A and adiponectin, major hepatokine and adipokine respectively, have been implicated in systematic inflammation. Our aim was to jointly investigate whether kinetics of circulating fetuin-A, adiponectin and its isoform HMWA predict 28-day mortality in sepsis. MATERIALS AND METHODS In a prospective study, serum fetuin-A, adiponectin and HMWA were determined in 102 ICU patients fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after, and in 102 healthy controls matched on age and gender. RESULTS Serum fetuin-A was significantly lower in septic patients than controls (p<0.001). Among septic patients, those with septic shock and nonsurvivors presented lower fetuin-A, but higher adiponectin and HMWA compared to patients with sepsis and survivors respectively, both at baseline and day 7 (p<0.001). Fetuin-A exhibited negative correlations with APACHE II, CRP, procalcitonin, adiponectin and IL-6 but a positive one with albumin. Reduced fetuin-A as well as lower serum kinetics of fetuin-A (HR: 0.55, 95% C.I. 0.34-0.91, p=0.02), adiponectin but not HMWA were independently associated with 28-day mortality adjusting for age, gender, BMI, APACHE II, septic shock and laboratory biomarkers. CONCLUSIONS Circulating fetuin-A kinetics may be a prognostic biomarker in septic patients. More research is essential to elucidate fetuin-A's ontological role in sepsis pathophysiology.
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Affiliation(s)
- Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelia Kandri
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | | | | | - Athina Nikolaidou
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - George Dimopoulos
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Apostolos Armaganidis
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece.
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Dalamaga M, Christodoulatos GS. Visfatin, Obesity, and Cancer. ADIPOCYTOKINES, ENERGY BALANCE, AND CANCER 2017. [DOI: 10.1007/978-3-319-41677-9_6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Zhang HP, Zou J, Xu ZQ, Ruan J, Yang SD, Yin Y, Mu HJ. Association of leptin, visfatin, apelin, resistin and adiponectin with clear cell renal cell carcinoma. Oncol Lett 2016; 13:463-468. [PMID: 28123583 DOI: 10.3892/ol.2016.5408] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 11/03/2016] [Indexed: 12/11/2022] Open
Abstract
Although an association between obesity and the occurrence of renal cell carcinoma (RCC) has been identified, the mechanism by which obesity functions to increase this risk of cancer remains unclear. Leptin, visfatin, apelin, resistin and adiponectin are peptide hormones secreted by adipocytes; it is considered that these may affect RCC development by exerting effects on proliferation, cell growth and inflammation. The aim of the present study was to investigate the association between the aforementioned adipokine genes and clear cell RCC (CC-RCC). The GSE6344 dataset was downloaded from the Gene Expression Omnibus database, and the relative expression levels of the adipokine genes were analyzed. To verify the results of the mRNA microarray, 77 paired samples of CC-RCC and corresponding adjacent normal tissue were allocated into two groups. The extraction of total RNA was conducted, and the mRNA expression of adipokine genes was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The data from the GSE6344 dataset indicated that the expression of visfatin and apelin was upregulated (P<0.0001 and P<0.01, respectively), and adiponectin was downregulated (P<0.001) in the CC-RCC tissues compared with the adjacent normal tissues. The data from RT-qPCR demonstrated that visfatin and resistin gene expression was increased (P<0.01 and P<0.05, respectively) in the CC-RCC tissues. Furthermore, the mRNA expression level of leptin and adiponectin in the adjacent normal tissue was higher than those in the cancer tissue (P<0.01). The current study verifies that visfatin and adiponectin are associated with an increased risk of CC-RCC, which presents further insights into the molecular mechanisms of CC-RCC tumorigenesis.
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Affiliation(s)
- Hai-Ping Zhang
- Department of Derma Science Laboratory, Wuxi No. 2 People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Jian Zou
- Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
| | - Zhuo-Qun Xu
- Department of Urinary Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
| | - Jun Ruan
- Department of Urinary Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
| | - Shu-Dong Yang
- Department of Pathology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
| | - Ying Yin
- Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
| | - Hui-Jun Mu
- Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
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Georgiou GP, Provatopoulou X, Kalogera E, Siasos G, Menenakos E, Zografos GC, Gounaris A. Serum resistin is inversely related to breast cancer risk in premenopausal women. Breast 2016; 29:163-9. [DOI: 10.1016/j.breast.2016.07.025] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 07/22/2016] [Accepted: 07/22/2016] [Indexed: 02/07/2023] Open
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Elsayed EY, Mosalam NA, Mohamed NR. Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis. Asian Pac J Cancer Prev 2016; 16:7139-42. [PMID: 26514502 DOI: 10.7314/apjcp.2015.16.16.7139] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. MATERIALS AND METHODS This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. RESULTS HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA >4 being 1.6 times more likely to have HCC. CONCLUSIONS HOMA and serum resistin allow for early identification of patients with cirrhosis who are at substantially increased risk of HCC. RECOMMENDATION HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.
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Affiliation(s)
- Engy Yousry Elsayed
- Internal Medicine, Oncology and Clinical Pathology Departments, Faculty of Medicine, Ain Shams University, Cairo, Egypt E-mail :
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