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Holm JB, Baggesen E, Cronin-Fenton D, Frystyk J, Bruun JM, Christiansen P, Borgquist S. Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups. Sci Rep 2024; 14:14486. [PMID: 38914635 PMCID: PMC11196728 DOI: 10.1038/s41598-024-64428-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/10/2024] [Indexed: 06/26/2024] Open
Abstract
Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.
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Affiliation(s)
- J B Holm
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - E Baggesen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - D Cronin-Fenton
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - J Frystyk
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - J M Bruun
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - P Christiansen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - S Borgquist
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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曾 莲, 李 双, 岳 鹏, 易 成. [The Value of Clinical Characteristics and Hematological Parameters for Prognostic Assessment of Pancreatic Cancer Patients Undergoing Radical Resection]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2024; 55:708-716. [PMID: 38948268 PMCID: PMC11211788 DOI: 10.12182/20240560604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Indexed: 07/02/2024]
Abstract
Objective To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks. Methods We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package. Results The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977). Conclusion In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.
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Affiliation(s)
- 莲丽 曾
- 四川大学华西医院 腹部肿瘤科 （成都 610041）Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - 双双 李
- 四川大学华西医院 腹部肿瘤科 （成都 610041）Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - 鹏飞 岳
- 四川大学华西医院 腹部肿瘤科 （成都 610041）Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - 成 易
- 四川大学华西医院 腹部肿瘤科 （成都 610041）Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, China
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Peterson LL, Ligibel JA. Dietary and serum advanced glycation end-products and clinical outcomes in breast cancer. Biochim Biophys Acta Rev Cancer 2024; 1879:188995. [PMID: 37806640 DOI: 10.1016/j.bbcan.2023.188995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 08/31/2023] [Accepted: 09/27/2023] [Indexed: 10/10/2023]
Abstract
One in five women with breast cancer will relapse despite ideal treatment. Body weight and physical activity are strongly associated with recurrence risk, thus lifestyle modification is an attractive strategy to improve prognosis. Trials of dietary modification in breast cancer are promising but the role of specific diets is unclear, as is whether high-quality diet without weight loss can impact prognosis. Advanced glycation end-products (AGEs) are compounds produced in the body during sugar metabolism. Exogenous AGEs, such as those found in food, combined with endogenous AGEs, make up the total body AGE load. AGEs deposit in tissues over time impacting cell signaling pathways and altering protein functions. AGEs can be measured or estimated in the diet and measured in blood through their metabolites. Studies demonstrate an association between AGEs and breast cancer risk and prognosis. Here, we review the clinical data on dietary and serum AGEs in breast cancer.
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Affiliation(s)
- Lindsay L Peterson
- Washington University School of Medicine, Division of Medical Oncology, Siteman Cancer Center, 660 S. Euclid Avenue, Campus Box 8056, St. Louis, MO 63110, United States of America.
| | - Jennifer A Ligibel
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Boston, MA, United States of America
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Mohammadbeigy I, Khalilian MS, Najafizadeh N, Moazam E, Hemati S, Zeinalian M. The role of serum lipid profile, fasting blood sugar, and body mass index on recurrence and metastasis in patients with estrogen receptor-positive breast cancer: A case-control study. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2023; 28:83. [PMID: 38292335 PMCID: PMC10826846 DOI: 10.4103/jrms.jrms_163_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/11/2023] [Accepted: 04/27/2023] [Indexed: 02/01/2024]
Abstract
Background Breast cancer (BC) is the leading cause of cancer death in women. The current study is designed to evaluate the association of lipid profiles, FBS, and body mass index (BMI) with BC recurrence and metastasis. Materials and Methods This is a case-control study on estrogen receptor-positive BC patients in Isfahan Province, Central Iran, between 2008 and 2020. The control group was patients who had no evidence of recurrence or metastasis at least 1 year after the end of chemotherapy and hormone therapy. The case group was patients with evidence of metastasis or recurrence within 1 year after the end of chemotherapy and hormone therapy. Fasting blood sugar (FBS), total cholesterol (Chol), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured before treatment, after chemotherapy, and after hormone therapy as well as BMI in the case and control groups. Results There were 108 patients in the case and 119 patients in the control group with a mean age of 50.72 ± 13.26 and 51.91 ± 11.79, respectively. There were no meaningful differences between the case and control groups regarding serum FBS, Chol, TG, HDL, LDL, and BMI. Conclusion We found no association between serum FBS, lipid profile, and BMI at initial diagnosis and BC recurrence or metastasis.
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Affiliation(s)
- Iman Mohammadbeigy
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Sadegh Khalilian
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nadia Najafizadeh
- Department of Radiation Oncology, Seyed Al-Shohada (Omid) Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Moazam
- Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Simin Hemati
- Department of Radiation Oncology, Seyed Al-Shohada (Omid) Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
- Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrdad Zeinalian
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Iranian Cancer Control Center (MACSA), Isfahan, Iran
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Milambo JPM, Nyasulu PS, Akudugu JM, Ndirangu J. Long-term effects of aromatase inhibitors on body mass index among postmenopausal breast cancer survivors in Africa: observational cohort study. BMC Res Notes 2023; 16:37. [PMID: 36915158 PMCID: PMC10012500 DOI: 10.1186/s13104-023-06301-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 02/20/2023] [Indexed: 03/16/2023] Open
Abstract
PURPOSE this study was conducted to assess the impact of AIs on body mass index and high sensitivity as prognostic predictors to be incorporated into point of care technology (POCT) testing in postmenopausal breast cancer women after a 24 month follow up in Africa. An observational cohort study was conducted; including 126 female BC patients with stages ranging from 0-III initially subjected to AIs and subsequently followed up for 24 months. Multiple imputation model was conducted to predict missing data. RESULTS Random effects model was used to monitor the changes over the time. The study revealed stronger statistically association between BMI and homocysteine (p = 0.021, 95%CI: 0.0083 to 0.1029). Weight and total body fat were strongly associated after 24 months follow up. Hs-CRP was associated with BMI (p = 0.0001), and hs-CRP was associated with other biomedical markers such as calcium (p = 0.021, 95% CI: 0.01 to 0.10), phosphate (p = 0.039, 95%CI: 0.01 to 0.10), and ferritin (p = 0.002, 95%CI: 0.02 to 0.08) and calcium. The patients subjected to AIs are likely to develop cardiovascular adverse events. POCT of care strategy which include clinical, biomedical and genetic predictor's measurement is required to improve BC survivorship.
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Affiliation(s)
- Jean Paul Muambangu Milambo
- Department of Health Sciences, Division of Public Health, University of Free state, 205 Nelson Mandela Dr, Bloenfontein , 9301, South Africa.
| | - Peter S Nyasulu
- Department of Global Health, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - John M Akudugu
- Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - James Ndirangu
- Department of Health Sciences, Division of Public Health, University of Free State, Bloenfontein , South Africa
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Cho HJ, Song S, Kim Z, Youn HJ, Cho J, Min JW, Kim YS, Choi SW, Lee JE. Associations of body mass index and weight change with circulating levels of high-sensitivity C-reactive protein, proinflammatory cytokines, and adiponectin among breast cancer survivors. Asia Pac J Clin Oncol 2023; 19:113-125. [PMID: 35590398 DOI: 10.1111/ajco.13779] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 03/15/2022] [Accepted: 03/17/2022] [Indexed: 01/20/2023]
Abstract
AIM This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea. METHODS A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high-sensitivity C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and adiponectin. A summary z-score was calculated by summing up the z-scores of each biomarker. The least-square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model. RESULTS Participants with a BMI ≥27.5 kg/m2 at the study enrollment and at diagnosis were significantly associated with elevated summary z-scores compared to those with a BMI < 23 kg/m2 ; the ORs (95% CIs) were 5.42 (2.15-13.71) for current BMI and 3.66 (1.68-7.98) for BMI at diagnosis, respectively. Additionally, a weight loss > 5% since diagnosis was associated with a lower prevalence of high summary z-scores; the OR (95% CI) was .20 (.08-.52) compared to a stable weight. CONCLUSIONS A high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers.
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Affiliation(s)
- Hyun Jeong Cho
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea
| | - Sihan Song
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea
| | - Zisun Kim
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Hyun Jo Youn
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Jihyoung Cho
- Department of Surgery, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Jun Won Min
- Department of Surgery, College of Medicine, Dankook University, Cheonan, Republic of Korea
| | - Yoo Seok Kim
- Department of Surgery, College of Medicine, Chosun University, Gwangju, Republic of Korea
| | - Sang-Woon Choi
- Chaum Life Center, CHA University, Seoul, Republic of Korea.,Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, Massachusetts, USA
| | - Jung Eun Lee
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea.,Research Institute of Human Ecology, Seoul National University, Seoul, Republic of Korea
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Hejazi K, Wong A. Effects of exercise training on inflammatory and cardiometabolic health markers in overweight and obese adults: a systematic review and meta-analysis of randomized controlled trials. J Sports Med Phys Fitness 2023; 63:345-359. [PMID: 35816146 DOI: 10.23736/s0022-4707.22.14103-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The improvements in inflammation and cardiometabolic health play an important role in the prevention and treatment of obesity. However, the interactions between different exercise training (ET) modalities with inflammatory and cardiometabolic biomarkers are not completely understood. This systematic review and meta-analysis investigated the effects of ET on inflammatory and cardiometabolic health markers in overweight and obese adults. EVIDENCE ACQUISITION A systematic search was conducted in PubMed, CINAHL, MEDLINE, Cochrane, Google Scholar, Scopus and Web of Science up to December 15, 2021. Thirty-five studies including 2752 participants were included and analyzed using a random-effects model to estimate weighted mean differences (MD) with 95% confidence intervals (CI). EVIDENCE SYNTHESIS The meta-analysis found that ET significantly (P<0.05) increased adiponectin (WMD: 0.72 µg/mL; 95% CI: 0.60 to 0.84; SMD=0.65) and maximal oxygen consumption levels (WMD: 5.26 mL.kg.min; 95% CI: 3.84, 6.69; SMD=1.21). Moreover, ET significantly (P<0.05) reduced fasting insulin (WMD: -2.40 μIU/mL; 95% CI: -3.43 to -1.37; SMD=-0.87), fasting blood glucose (WMD: -5.41 mg/dL; 95% CI: -7.91, -2.91; SMD=-0.66), insulin resistance (WMD: -0.66; 95% CI: -1.08, -0.24; SMD=-0.66) and triglyceride levels (WMD: -10.88 mg/dL; 95% CI: -17.61, -4.15; SMD=-0.91). No significant changes were observed in interleukin-6, tumor necrosis factor-α, leptin, C-reactive protein and cholesterol concentrations. Subgroup analysis by type of training indicated that aerobic and resistance exercise had the most consistent beneficial effects as compared to other modalities. CONCLUSIONS Our findings suggest that ET may improve inflammation and cardiometabolic health in overweight and obese adults. Aerobic and resistance training appear to be more beneficial for improving adiponectin, fasting insulin, fasting blood glucose, insulin resistance index and triglyceride levels as compared to other exercise modalities. Further long-term studies are required to confirm and expand on these findings.
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Affiliation(s)
- Keyvan Hejazi
- Department of Physical Education and Sport Sciences, Hakim Sabzevari University, Sabzevar, Iran -
| | - Alexei Wong
- Department of Health and Human Performance, Marymount University, Arlington, VA, USA
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A. Abd M, A. Abbas S, G. Shareef L. Impact of serum leptin and adiponectin levels on breast cancer in postmenopausal Iraqi women: an observational Study. F1000Res 2022; 11:1572. [DOI: 10.12688/f1000research.127528.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/01/2023] Open
Abstract
Background: Breast cancer is the most common malignant tumor and the second most significant cause of death for women in Iraq, behind cardiovascular diseases. Obesity has been linked to a substantial increase in the risk of breast cancer. Adipose tissue functions as an endocrine gland, controlling the body's metabolism by secreting adipokines, which play a significant role in metabolism and inflammatory reactions. Methods: Overall, 90 postmenopausal women participated in this research. Of these, 60 patients with breast cancer were recruited at Baghdad's Oncology Teaching Hospital between October 2021 and February 2022: 30 were obese with a body mass index (BMI) of > 30 kg/m2 (group 1), and 30 were not obese (group 2). The third group consisted of 30 participants without breast cancer or obesity (group 3). Each person donated five milliliters of venous blood. The blood levels of adiponectin and leptin are determined using enzyme-linked immunosorbent assay (ELISA) kits. Results: Control individuals who were not obese (group 3) had greater blood adiponectin levels than patients with cancer who were both obese and non-obese (groups 1 and 2), with no significant difference in serum adiponectin levels seen between groups 1 and 2. The findings also showed that group 1 (patients with breast cancer and obesity) had greater serum leptin levels than both group 2 (patients with breast cancer without obesity) and the control group (group 3), with no significant difference in serum leptin levels between groups 2 and 3. Conclusions: Adiponectin levels in the blood of women with breast cancer and obesity were low which may be due to high BMI, which reduces adiponectin's protective effects. Conversely, Leptin levels were more significant in the blood of women with breast cancer and obesity than in the control group, which may be due to its pro-inflammatory effects in obesity, among other variables.
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Greaney SK, Amin N, Prudner BC, Compernolle M, Sandell LJ, Tebb SC, Weilbaecher KN, Abeln P, Luo J, Tao Y, Hirbe AC, Peterson LL. Yoga Therapy During Chemotherapy for Early-Stage and Locally Advanced Breast Cancer. Integr Cancer Ther 2022; 21:15347354221137285. [PMID: 36412916 PMCID: PMC9706042 DOI: 10.1177/15347354221137285] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background: Chemotherapy is associated with decreased quality of life (QOL), fatigue, depression, and weight gain in patients with breast cancer. Weight gain is associated with poorer prognosis. Yoga improves QOL, fatigue, and mood in women with breast cancer but its effect on treatment-related weight gain has not been studied. The aim of this trial was to determine the feasibility of personalized yoga therapy in women receiving treatment for early-stage or locally advanced breast cancer and assess its impact on weight gain. Methods: Thirty women were randomized 1:1 to receive yoga therapy by a certified yoga therapist during treatment or a control group. Participants in the yoga arm were asked to complete three 30 minute yoga sessions weekly (which included movement, breath work, mindfulness, and relaxation) throughout adjuvant or neoadjuvant chemotherapy (N = 29) or endocrine (N = 1); the control arm received breast cancer treatment without yoga. For comparability between participants randomized to yoga therapy, the single patient treated with endocrine therapy was excluded from the analysis. Primary outcomes were feasibility and weight change. Additional outcomes were mood, fatigue, QOL, serum tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) as immune mediator biomarkers. Results: Mean age was 51.6 years, 75.9% were white and 24.1% were people of color, reflecting the cancer center population. 80% had stage II-III disease. Enrollment was completed in 9 months. Compliance was lower than predicted; however, participants participated in on average 1.7 yoga sessions/week for a mean 15.6 weeks duration. There were no adverse events. Control arm participants gained on average 2.63% body weight during treatment while yoga participants lost 0.14% body weight (weight change = −0.36 in yoga arm vs. 2.89 in standard of care arm, Wilcoxon rank sum test P = .024). Control participants reported increased fatigue and decreased QOL, while yoga participants reported no change in QOL. No significant change in TNF-alpha or CRP was noted in either arm. Conclusion: This feasibility study suggests that personalized yoga therapy is beneficial for QOL and weight maintenance among women undergoing chemotherapy for early-stage or locally advanced breast cancer. Weight maintenance associated with yoga therapy may be of clinical significance in this population given the poorer prognosis associated with weight gain in breast cancer survivors. Trial Registration: NIH Clinicaltrials.gov #NCT03262831; August 25, 2017. https://clinicaltrials.gov/ct2/show/NCT03262831
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Affiliation(s)
| | - Neha Amin
- Washington University School of Medicine, Saint Louis, MO, USA
| | | | | | | | | | | | - Peri Abeln
- Washington University School of Medicine, Saint Louis, MO, USA
| | - Jingqin Luo
- Washington University School of Medicine, Saint Louis, MO, USA
| | - Yu Tao
- Washington University School of Medicine, Saint Louis, MO, USA
| | - Angela C. Hirbe
- Washington University School of Medicine, Saint Louis, MO, USA
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Moslemi D, Babaei Z, Parsian H, Korani B, Mostafazadeh A. Body composition and serum levels of matrix metalloproteinase-9, adiponectin and AMP-activated protein kinase in breast cancer survivors. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2022; 27:48. [PMID: 35968203 PMCID: PMC9374150 DOI: 10.4103/jrms.jrms_453_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 08/10/2020] [Accepted: 10/06/2020] [Indexed: 11/16/2022]
Abstract
Background: Available data suggest that obesity is related to changes in the several adipocyte-derived proteins levels, which are involved in cancer recurrence. The purpose of this work was to investigate the correlation between obesity with metalloproteinase-9 (MMP-9), adiponectin and adiponectin and AMP-activated protein kinase (AMPK) levels by comparing serum levels of MMP-9, AMPK in normal weight and obese breast cancer survivors. Materials and Methods: In this cross-sectional study, 30 normal weight breast cancer survivors (body mass index [BMI] 18.5-25 kg/m2) and 30 obese breast cancer survivors (BMI ≥30 kg/m2) were investigated. Anthropometric parameters and serum levels of MMP-9, adiponectin, and AMPK were compared between the two groups. Results: No differences were detected in the serum levels of MMP-9, adiponectin, and AMPK in obese patients and normal weight patients (P > 0.05). There were no correlations between MMP-9, adiponectin, and AMPK levels with anthropometric measurements in two groups (P > 0.05). Conclusion: We found that there was a lack of correlation between obesity measures and serum levels of MMP-9, adiponectin, and AMPK. In breast cancer survivors, it seems that circulating levels of adiponectin, AMPK, and MMP-9 do not change in obesity state.
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Lambert M, Sabiston CM, Wrosch C, Brunet J. Behavioural, physical, and psychological predictors of cortisol and C-reactive protein in breast cancer survivors: A longitudinal study. Brain Behav Immun Health 2021; 10:100180. [PMID: 34589720 PMCID: PMC8474539 DOI: 10.1016/j.bbih.2020.100180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/26/2020] [Accepted: 11/28/2020] [Indexed: 12/05/2022] Open
Abstract
Background Breast cancer survivors (BCS) can exhibit a dysregulation of cortisol and elevated C-reactive protein (CRP) levels post-treatment, which increase the risk of diverse health outcomes. Certain behavioural, physical, and psychological variables may help to predict cortisol and CRP levels post-treatment. The aims of this study were to: (1) describe naturally occurring changes in absolute diurnal cortisol and CRP levels over a period of 1.5 years post-treatment among BCS, (2) assess if absolute diurnal cortisol and CRP levels change in tandem, and (3) assess behavioural, physical, and psychological variables as predictors of absolute diurnal cortisol levels and CRP levels. Methods Capillary blood and saliva samples were collected from 201 BCS, on average, 3.5 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2−T5). At each time point, five saliva samples were collected on two nonconsecutive days: at awakening, 30 min after awakening, 2:00 p.m., 4:00 p.m., and at bedtime. At each time point, participants also completed self-report questionnaires and wore an accelerometer for seven consecutive days. Data were analyzed using multilevel modeling. Results Absolute diurnal cortisol levels did not change significantly over time. CRP levels decreased across time points (Blinear = −0.31, p = .01), though the rate of decrease slowed over time (Bquadratic = 0.05, p = .03). Generally, greater sedentary time predicted higher overall absolute diurnal cortisol levels (B < 0.01, p = .01); whereas higher physical activity (B = −0.004, p < .01), lower body mass index (B = 0.10, p < .01), and lower health- and cancer-related stress (B = 0.24, p = .04) predicted lower overall CRP levels. Also, lower absolute diurnal cortisol levels were evident when participants engaged in more sedentary time, as compared to their own average sedentary time (B = −0.01, p < .01). Conclusions Results offer insight into the nature of change in diurnal cortisol and CRP levels among BCS from treatment completion onwards and offer clinical implications. Helping BCS manage their weight, reduce stress, increase physical activity participation, and decrease sedentary time as soon as possible after treatment may help to reduce physiological dysregulations, thereby lowering the risk of adverse health outcomes in this population. Further research investigating specific intervention parameters such as type, context, frequency, and intensity are warranted for the development of the most optimal interventions.
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Affiliation(s)
- M Lambert
- School of Psychology, University of Ottawa, ON, Canada
| | - C M Sabiston
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Canada
| | - C Wrosch
- Department of Psychology, Concordia University, Montreal, Canada
| | - J Brunet
- School of Human Kinetics, University of Ottawa, Montpetit Hall, Room 339, Ottawa, ON K1N 6N5, Canada
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12
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Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis. Eur J Clin Pharmacol 2021; 77:1825-1834. [PMID: 34218304 DOI: 10.1007/s00228-021-03181-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 06/24/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.
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13
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Wang C, Han W, Gu Y. Changes in the levels of T lymphocytes and inflammatory factors in the peripheral blood of breast cancer patients during postoperative chemotherapy. Gland Surg 2020; 9:2155-2161. [PMID: 33447566 DOI: 10.21037/gs-20-818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background As one of the main malignant tumors affecting women, the incidence of breast cancer increases year by year. This study aims to analyze the risk factors of infection in breast cancer patients during postoperative chemotherapy by measuring the changes in the levels of T lymphocytes and inflammatory factors in peripheral blood. Methods The clinical data of 156 patients who underwent radical mastectomy and postoperative chemotherapy [docetaxel, epirubicin, cyclophosphamide (TEC)] in our hospital from May 2014 to April 2018 were retrospectively analyzed. According to the presence or absence of infection after chemotherapy, patients were divided into the infection group and the normal group. The risk factors of infection during chemotherapy were analyzed by univariate and multiple logistic regression analyses. Serum before surgery, and before and after chemotherapy, was collected to detect the levels of T lymphocytes and inflammatory factors. Results A total of 36 patients developed an infection during chemotherapy, with an infection rate of 23.08%. The main infection site was the respiratory tract. The main pathogens detected were Gram-negative bacteria and Gram-positive bacteria. The results of univariate analysis showed that there were significant differences in age, diabetes mellitus, clinical TNM staging, white blood cell count (WBC), T lymphocyte subsets CD4+/CD8+, C-reactive protein (CRP) levels, and tumor necrosis factor-α (TNF-α) levels between the 2 groups (P<0.05). Results of logistic regression analysis showed that age ≥60 years old, diabetes mellitus, clinical TNM staging ≥ stage III, WBC <3.5×109/L, CD4+/CD8+ <1.33, TNF-α ≥70 ng/L and CRP ≥60 mg/L were all independent risk factors of postoperative infection (P<0.05). Both before and after chemotherapy, levels of CD3+, CD3+CD4+ and CD4+/CD8+ cells in the infection group were significantly lower than those in the normal group, while levels of CRP, TNF-α and IL-6 were significantly higher than those in the normal group (P<0.05). Conclusions Dynamic monitoring of changes in the levels of T lymphocytes and inflammatory factors during chemotherapy may be of clinical value for predicting the risk of infection. Implementing targeted intervention measures for these risk factors may therefore be beneficial for controlling infection.
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Affiliation(s)
- Cunliang Wang
- Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Medical Service, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Han
- Quality Control Division, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuanting Gu
- Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Spielmann J, Mattheis L, Jung JS, Rauße H, Glaß M, Bähr I, Quandt D, Oswald J, Kielstein H. Effects of obesity on NK cells in a mouse model of postmenopausal breast cancer. Sci Rep 2020; 10:20606. [PMID: 33244094 PMCID: PMC7692502 DOI: 10.1038/s41598-020-76906-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 11/03/2020] [Indexed: 02/07/2023] Open
Abstract
Obesity is a widely spread disease and a crucial risk factor for malign disorders, including breast cancer of women in the postmenopause. Studies demonstrated that in case of obesity crucial natural killer (NK) cell functions like combating tumor cells are affected. This study aims to analyze NK cells and NK cell receptor expression of obese mice in a model for postmenopausal breast cancer. Therefore, female BALB/c mice were fed either a high fat or a standard diet. Thereafter, ovaries were ectomized and a syngeneic and orthotopical injection of 4T1-luc2 mouse mammary tumor cells into the mammary adipose tissue pad was performed. Obese mice showed increased body weights and visceral fat mass as well as increased levels of leptin and IL-6 in plasma. Moreover, compared to the lean littermates, tumor growth was increased and the NKp46-expression on circulating NK cells was decreased. Furthermore, the activating NK cell receptor NKG2D ligand (MULT1) expression was enhanced in adipose tissue of obese tumor bearing mice. The present study gives novel insights into gene expression of NK cell receptors in obesity and aims to promote possible links of the obesity-impaired NK cell physiology and the elevated breast cancer risk in obese women.
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Affiliation(s)
- Julia Spielmann
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany.
| | - Laura Mattheis
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
- Deptartment of Internal Medicine I, Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Juliane-Susanne Jung
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
| | - Henrik Rauße
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
- Clinic for Psychosomatics and Psychotherapy, Landschaftsverband Westfalen-Lippe Clinic, Lengerich, Germany
| | - Markus Glaß
- Institute of Molecular Medicine, Charles Tanford Protein Center, Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Ina Bähr
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
| | - Dagmar Quandt
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland
| | - Jana Oswald
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
| | - Heike Kielstein
- Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle (Saale), Germany
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Lambert M, Sabiston CM, Wrosch C, Brunet J. An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study. Breast Cancer 2020; 27:1096-1106. [PMID: 32488733 DOI: 10.1007/s12282-020-01113-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 05/16/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Breast cancer survivors (BCS) may exhibit dysregulated patterns of cortisol and C-reactive protein (CRP). The aims of this study were to describe BCS' cortisol and CRP levels over a 1-year period after treatment, and assess how levels relate to socio-demographic- (age, education level, marital status), health- (body mass index [BMI] category, menopausal status), and cancer-related factors (cancer stage, chemotherapy exposure, time since diagnosis). METHODS Participants (N = 201) provided data at 3 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2-T5). At T1, participants completed self-report questionnaires and had their weight and height measured by a trained technician. At T1-T5, they provided five saliva samples at awakening, 30 min after awakening, 2:00 pm, 4:00 pm, and before bedtime on two nonconsecutive days to measure diurnal cortisol, and provided capillary whole blood to measure CRP. Data were analyzed using repeated-measure analyses of variance (ANOVAs) and mixed-design ANOVAs. RESULTS Diurnal cortisol and CRP levels fluctuated over time. In univariate models, older age and post-menopausal status were associated with higher cortisol and CRP levels, higher cancer stage and chemotherapy were associated with lower cortisol levels, and higher BMI category was associated with higher CRP levels. In adjusted models, age was no longer associated with CRP levels and shorter time since diagnosis was significantly associated with higher CRP levels. CONCLUSIONS Socio-demographic-, health-, and cancer-related factors may help identify BCS at risk of physiological dysregulation who need intervention. Identifying modifiable factors associated with cortisol and CRP will inform cancer care interventions.
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Affiliation(s)
- M Lambert
- School of Psychology, University of Ottawa, Ontario, Canada
| | - C M Sabiston
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Canada
| | - C Wrosch
- Department of Psychology, Concordia University, Montreal, Canada
| | - J Brunet
- School of Human Kinetics, University of Ottawa, Montpetit Hall, Room 339, Ottawa, ON, K1N 6N5, Canada.
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16
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Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer. Mol Biol Rep 2020; 47:3807-3820. [PMID: 32279213 DOI: 10.1007/s11033-020-05436-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 04/03/2020] [Indexed: 12/18/2022]
Abstract
The leptin is discharged from breast adipose tissue and is overexpressed in breast cancer (BC). Conflicting relation of leptin with BC was reported. We investigated this association and its impact on leptin level and disease characteristics. The study included 70 females (40 women with pathological proof of invasive BC patients and 30 controls). LEP and LEPR polymorphisms were evaluated by real-time PCR. Serum leptin was estimated by ELISA. Both LEPR and LEP disturbances increase the danger of BC where GG genotype and G allele frequencies of LEPR were higher in patients vs. control. GG genotype increases BC risk with OR (9.1) while G allele predisposes to disease with OR (3.8). Furthermore, LEP A allele was uniquely elevated in patients than healthy ones with OR (2.06). Precise relation of circulating leptin and its polymorphisms with predicting BC may authorize its utilization in early screening.
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17
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Christensen MA, Smoak P, Lisano JK, Hayward R, Coronado C, Kage K, Shackelford D, Stewart LK. Cardiorespiratory fitness, visceral fat, and body fat, but not dietary inflammatory index, are related to C-reactive protein in cancer survivors. Nutr Health 2019; 25:195-202. [PMID: 30991889 DOI: 10.1177/0260106019841840] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
BACKGROUND The control of chronic inflammation has emerged as a target for improving the health of cancer survivors (CS). AIM To examine differences in fitness and dietary characteristics of CS when grouped by low vs. moderate to high serum C-reactive protein (CRP). METHODS CS (N = 26, mean age = 68 ± 12 years) were evaluated for body mass index (BMI), body composition, cardiorespiratory fitness, dietary intake, dietary inflammatory index (DII), and serum CRP. Participants were assigned to one of two groups based on serum CRP concentrations: low CRP (≤1 mg/L) (LWC; n = 13) or moderate to high (CRP > 1 mg/L) (MHC; n = 13) and t-tests compared them. Data are presented as mean ± SD. RESULTS LWC had higher VO2peak values (mL/kg/min) (p = 0.0003), and lower visceral fat area (cm2) (p = 0.02) and body fat mass (kg) (p = 0.04). Secondary analysis using Pearson's correlation coefficients, including all current study participant data, found significant negative relationships between CRP and total dietary fat intake (p = 0.02), saturated fat (p = 0.03), and polyunsaturated fat (p = 0.03). CONCLUSION CS with moderate to high serum CRP concentrations had higher fat mass, visceral fat mass, and lower cardiorespiratory fitness. There was a significant negative relationship between dietary, fat, polyunsaturated and saturated fat, and CRP. However, these dietary fat related findings warrant further investigation. To summarize, improving cardiorespiratory fitness, maintaining lower body fat, may be helpful in altering chronic inflammation in CS.
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Affiliation(s)
- Matthew A Christensen
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
| | - Peter Smoak
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
| | - Jonathon K Lisano
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
| | - Reid Hayward
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
- University of Northern Colorado Cancer Rehabilitation Institute, Greeley, CO, USA
| | - Craig Coronado
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
| | - Katie Kage
- School of Nutrition and Dietetics, University of Northern Colorado, Greeley, CO, USA
| | - Daniel Shackelford
- University of Northern Colorado Cancer Rehabilitation Institute, Greeley, CO, USA
| | - Laura K Stewart
- School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA
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18
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Moghbeli M. Genetic and molecular biology of breast cancer among Iranian patients. J Transl Med 2019; 17:218. [PMID: 31286981 PMCID: PMC6615213 DOI: 10.1186/s12967-019-1968-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 07/04/2019] [Indexed: 02/07/2023] Open
Abstract
Abstract Background, Breast cancer (BC) is one of the leading causes of cancer related deaths in Iran. This high ratio of mortality had a rising trend during the recent years which is probably associated with late diagnosis. Main body Therefore it is critical to define a unique panel of genetic markers for the early detection among our population. In present review we summarized all of the reported significant genetic markers among Iranian BC patients for the first time, which are categorized based on their cellular functions. Conclusions This review paves the way of introducing a unique ethnic specific panel of diagnostic markers among Iranian BC patients. Indeed, this review can also clarify the genetic and molecular bases of BC progression among Iranians.
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Affiliation(s)
- Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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19
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Shimura T, Shibata M, Gonda K, Murakami Y, Noda M, Tachibana K, Abe N, Ohtake T. Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer. Oncol Lett 2019; 17:5139-5146. [PMID: 31186728 DOI: 10.3892/ol.2019.10183] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 02/27/2019] [Indexed: 12/13/2022] Open
Abstract
The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 <10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP <0.12 mg/dl (P<0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.
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Affiliation(s)
- Tatsuo Shimura
- Department of Progressive DOHaD Research, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Masahiko Shibata
- Department of Advanced Cancer Immunotherapy, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Kenji Gonda
- Clinical Oncology Center, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Yuko Murakami
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Masaru Noda
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Kazunoshin Tachibana
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Noriko Abe
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Tohru Ohtake
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
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20
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Olea-Flores M, Juárez-Cruz JC, Mendoza-Catalán MA, Padilla-Benavides T, Navarro-Tito N. Signaling Pathways Induced by Leptin during Epithelial⁻Mesenchymal Transition in Breast Cancer. Int J Mol Sci 2018; 19:E3493. [PMID: 30404206 PMCID: PMC6275018 DOI: 10.3390/ijms19113493] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 10/27/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022] Open
Abstract
Leptin is an adipokine that is overexpressed in obese and overweight people. Interestingly, women with breast cancer present high levels of leptin and of its receptor ObR. Leptin plays an important role in breast cancer progression due to the biological processes it participates in, such as epithelial⁻mesenchymal transition (EMT). EMT consists of a series of orchestrated events in which cell⁻cell and cell⁻extracellular matrix interactions are altered and lead to the release of epithelial cells from the surrounding tissue. The cytoskeleton is also re-arranged, allowing the three-dimensional movement of epithelial cells into the extracellular matrix. This transition provides cells with the ability to migrate and invade adjacent or distal tissues, which is a classic feature of invasive or metastatic carcinoma cells. In recent years, the number of cases of breast cancer has increased, making this disease a public health problem worldwide and the leading cause of death due to cancer in women. In this review, we focus on recent advances that establish: (1) leptin as a risk factor for the development of breast cancer, and (2) leptin as an inducer of EMT, an event that promotes tumor progression.
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Affiliation(s)
- Monserrat Olea-Flores
- Laboratorio de Biología Celular del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo, GRO 39090, México.
| | - Juan Carlos Juárez-Cruz
- Laboratorio de Biología Celular del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo, GRO 39090, México.
| | - Miguel A Mendoza-Catalán
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo, GRO 39090, México.
| | - Teresita Padilla-Benavides
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
| | - Napoleón Navarro-Tito
- Laboratorio de Biología Celular del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo, GRO 39090, México.
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Lim B, Woodward WA, Wang X, Reuben JM, Ueno NT. Inflammatory breast cancer biology: the tumour microenvironment is key. Nat Rev Cancer 2018; 18:485-499. [PMID: 29703913 DOI: 10.1038/s41568-018-0010-y] [Citation(s) in RCA: 221] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.
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Affiliation(s)
- Bora Lim
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Wendy A Woodward
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaoping Wang
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - James M Reuben
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naoto T Ueno
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Heydari N, Nikbakhsh N, Sadeghi F, Farnoush N, Khafri S, Bastami M, Parsian H. Overexpression of serum MicroRNA-140-3p in premenopausal women with newly diagnosed breast cancer. Gene 2018; 655:25-29. [PMID: 29474861 DOI: 10.1016/j.gene.2018.02.032] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 01/16/2018] [Accepted: 02/12/2018] [Indexed: 12/21/2022]
Abstract
AIMS The purpose of the present study was to evaluate microRNA-140-3p expression level in breast cancer patients in comparison to healthy controls. PATIENTS & METHODS Serum microRNA-140-3p level was quantified by realtime quantitative reverse transcription PCR in 40 women with breast cancer and 40 healthy subjects. RESULTS Serum microRNA-140-3p level in patients compared to healthy subjects was significantly up-regulated (P = 0.01). MicroRNA-140-3p had a good diagnostic accuracy for discrimination of the two groups (AUC = 0.667; sensitivity = 70%; specificity = 50%). Serum microRNA-140-3p level was overexpressed in premenopausal patients who were ≤48 years old. ROC curve showed a similar pattern again (AUC = 0.690; sensitivity = 73%; specificity = 50%). CONCLUSIONS microRNA-140-3p has the potential for detection of breast cancer, especially in premenopausal and in ≤48 years old women.
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Affiliation(s)
- Nadia Heydari
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Novin Nikbakhsh
- Cancer Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Nazila Farnoush
- Department of Surgery, Babol University of Medical Sciences, Babol, Iran
| | - Soraya Khafri
- Department of Epidemiology, Babol University of Medical Sciences, Babol, Iran
| | - Milad Bastami
- Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Parsian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Randell EW, Twells LK, Gregory DM, Lester KK, Daneshtalab N, Dillon C, Pace D, Smith C, Boone D. Pre-operative and post-operative changes in CRP and other biomarkers sensitive to inflammatory status in patients with severe obesity undergoing laparoscopic sleeve gastrectomy. Clin Biochem 2018; 52:13-19. [DOI: 10.1016/j.clinbiochem.2017.10.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 10/15/2017] [Indexed: 01/09/2023]
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24
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Haque I, Ghosh A, Acup S, Banerjee S, Dhar K, Ray A, Sarkar S, Kambhampati S, Banerjee SK. Leptin-induced ER-α-positive breast cancer cell viability and migration is mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway. BMC Cancer 2018; 18:99. [PMID: 29370782 PMCID: PMC5785848 DOI: 10.1186/s12885-018-3993-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 01/16/2018] [Indexed: 12/15/2022] Open
Abstract
Background In menopausal women, one of the critical risk factors for breast cancer is obesity/adiposity. It is evident from various studies that leptin, a 16 kDa protein hormone overproduced in obese people, plays the critical role in neovascularization and tumorigenesis in breast and other organs. However, the mechanisms by which obesity influences the breast carcinogenesis remained unclear. In this study, by analyzing different estrogen receptor-α (ER-α)-positive and ER-α-negative BC cell lines, we defined the role of CCN5 in the leptin-mediated regulation of growth and invasive capacity. Methods We analyzed the effect of leptin on cell viability of ER-α-positive MCF-7 and ZR-75-1 cell lines and ER-α-negative MDA-MB-231 cell line. Additionally, we also determined the effect of leptin on the epithelial-mesenchymal transition (EMT) bio-markers, in vitro invasion and sphere-formation of MCF-7 and ZR-75-1 cell lines. To understand the mechanism, we determined the impact of leptin on CCN5 expression and the functional role of CCN5 in these cells by the treatment of human recombinant CCN5 protein(hrCCN5). Moreover, we also determined the role of JAK-STAT and AKT in the regulation of leptin-induced suppression of CCN5 in BC cells. Results Present studies demonstrate that leptin can induce cell viability, EMT, sphere-forming ability and migration of MCF-7 and ZR-75-1 cell lines. Furthermore, these studies found that leptin suppresses the expression of CCN5 at the transcriptional level. Although the CCN5 suppression has no impact on the constitutive proliferation of MCF-7 and ZR-75-1 cells, it is critical for leptin-induced viability and necessary for EMT, induction of in vitro migration and sphere formation, as the hrCCN5 treatment significantly inhibits the leptin-induced viability, EMT, migration and sphere-forming ability of these cells. Mechanistically, CCN5-suppression by leptin is mediated via activating JAK/AKT/STAT-signaling pathways. Conclusions These studies suggest that CCN5 serves as a gatekeeper for leptin-dependent growth and progression of luminal-type (ER-positive) BC cells. Leptin may thus need to destroy the CCN5-barrier to promote BC growth and progression via activating JAK/AKT/STAT signaling. Therefore, these observations suggest a therapeutic potency of CCN5 by restoration or treatment in obese-related luminal-type BC growth and progression.
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Affiliation(s)
- Inamul Haque
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.,Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Arnab Ghosh
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.,Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Seth Acup
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA
| | - Snigdha Banerjee
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA. .,Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA. .,Cancer Research Unit, Research Division 151, VA Medical Center, 4801 Linwood Boulevard, Kansas City, MO, 64128, USA.
| | - Kakali Dhar
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.,Present Address: Syngene International Ltd, Clinical Development, Tower 1, Semicon Park, Phase II, Electronics City, Hosur Road, Bangalore, Karnataka, 560100, India.,Present Address: Saint James School of Medicine, Anguilla, British West Indies, USA
| | - Amitabha Ray
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.,Present Address: Syngene International Ltd, Clinical Development, Tower 1, Semicon Park, Phase II, Electronics City, Hosur Road, Bangalore, Karnataka, 560100, India.,Present Address: Saint James School of Medicine, Anguilla, British West Indies, USA
| | - Sandipto Sarkar
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA.,Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | | | - Sushanta K Banerjee
- Cancer Research Unit, VA Medical Center, Kansas City, MO, USA. .,Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA. .,Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA. .,Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA. .,Cancer Research Unit, Research Division 151, VA Medical Center, 4801 Linwood Boulevard, Kansas City, MO, 64128, USA.
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25
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Sahoo AK, Das JK, Nayak S. Isolation, culture, characterization, and osteogenic differentiation of canine endometrial mesenchymal stem cell. Vet World 2017; 10:1533-1541. [PMID: 29391698 PMCID: PMC5771182 DOI: 10.14202/vetworld.2017.1533-1541] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 12/04/2017] [Indexed: 01/09/2023] Open
Abstract
Aim In this study, the canine endometrium tissue is characterized for its stem cell properties such as adherence to tissue culture plate (plasticity), short population doubling time, serial clonal passaging, long-term culturing properties, stem cell marker expression, and multilineage differentiation potential. Materials and Methods The present work describes a novel isolation protocol for obtaining mesenchymal stem cells from the uterine endometrium and is compared with cells derived from umbilical cord matrix as a positive control. These cells are clonogenic, can undergo several population doublings in vitro, and can be differentiated to the osteocytes in mature mesenchymal tissues when grown in osteogenic differentiation media as detected by Alizarin Red-S staining. Results It is reported for the first time that the cells derived from the canine endometrium (e-multipotent stem cells [MSCs]) were able to differentiate into a heterologous cell type: Osteocytes, thus demonstrating the presence of MSCs. Thus, the endometrium may be told as a potential source of MSCs which can be used for various therapeutic purposes. Conclusion The endometrium can be used as a potential source of MSCs, which can be used for various therapeutic purposes.
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Affiliation(s)
- A K Sahoo
- Department of Veterinary Surgery and Radiology, College of Veterinary Science and Animal Husbandry, OUAT, Bhubaneswar - 751 003, Odisha, India
| | - J K Das
- Department of Veterinary Surgery and Radiology, College of Veterinary Science and Animal Husbandry, OUAT, Bhubaneswar - 751 003, Odisha, India
| | - S Nayak
- Department of Veterinary Surgery and Radiology, College of Veterinary Science and Animal Husbandry, OUAT, Bhubaneswar - 751 003, Odisha, India
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26
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Vaidya HB, Gangadaran S, Cheema SK. A high fat-high sucrose diet enriched in blue mussels protects against systemic inflammation, metabolic dysregulation and weight gain in C57BL/6 mice. Food Res Int 2017; 100:78-85. [PMID: 28888461 DOI: 10.1016/j.foodres.2017.08.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 08/11/2017] [Accepted: 08/13/2017] [Indexed: 01/09/2023]
Abstract
High fat-high sucrose (HF-HS) diet, known as the western diet, has been shown to induce the onset of obesity via increasing metabolic inflammation, insulin resistance and adipose tissue dysfunction. Hyperleptinemia, hyperglycemia and dyslipidemia are also the primary observations of obesogenic diet induced obesity. We have previously reported anti-adipogenic and insulin sensitizing effects of blue mussels (BM) using 3T3-L1 cells. BM is a rich source of omega-3 polyunsaturated fatty acids, phytosterols and other micronutrients that has been shown to elicit benefits under obese conditions using in-vitro cell culture models. However, no studies to date have established the anti-obesity effects, safety and efficacy of BM in an in-vivo animal model. In the present study, we fed a HF-HS diet supplemented with different concentrations of BM freeze-dried powder (1.25, 2.5 and 5% w/w) to C57BL/6 mice for 12weeks. A HF-HS diet caused rapid weight gain, hyperglycemia, dyslipidemia, hyperleptinemia, and increased plasma levels of inflammatory cytokines; interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Incorporating 2.5% BM in the HF-HS diet prevented weight gain, dyslipidemia, hyperglycemia and reduced the levels of inflammatory cytokines and leptin mRNA expression. Furthermore, plasma from 2.5% BM increased cholesterol efflux capacity of J774 macrophage cells, compared to plasma from HF-HS diet. There was no effect of 1.25% BM on any tested parameters, while 5% BM was not palatable after four weeks. In conclusion, our findings have established the efficacy and safety of BM using C57BL/6 mice, demonstrating that BM has the potential to target obesity and related complications.
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Affiliation(s)
- Hitesh B Vaidya
- Department of Biochemistry, Memorial University, St. John's, NL A1B 3X9, Canada
| | | | - Sukhinder K Cheema
- Department of Biochemistry, Memorial University, St. John's, NL A1B 3X9, Canada.
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27
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Tchio Mantho CI, Harbuzariu A, Gonzalez-Perez RR. Histone deacetylases, microRNA and leptin crosstalk in pancreatic cancer. World J Clin Oncol 2017; 8:178-189. [PMID: 28638788 PMCID: PMC5465008 DOI: 10.5306/wjco.v8.i3.178] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/06/2017] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
Because pancreatic cancer (PC) historically has had poor prognosis and five year survival rates, it has been intensely investigated. Analysis of PC incidence and biology has shown a link between different risk factors such as smoking, alcoholism, and obesity and disease progression. Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation, and actions of microRNA inducing oncogenic or tumor suppressor effects. Studies have identified markers whose dysregulation seem to play important roles in PC progression. PC markers involve classical histone deacetylases (HDAC), PC stem cell (PCSC), and leptin. In this review, we discuss the role of several PC biomarkers, and the potential crosstalk between HDAC, microRNA, and leptin in PC progression. Dysregulated expression of these molecules can increase proliferation, survival, PCSC, resistance to chemotherapy and tumor angiogenesis. The potential relationships between these molecules are further analyzed using data from The Cancer Genome Atlas and crosstalk pathways generated by the Pathway Studio Platform (Ariadne Genomics, Inc.). Oncogenic miRNA21 and tumor suppressor miRNA200 have been previously linked to leptin signaling. Preliminary analysis of PC biopsies and signaling crosstalk suggests that the main adipokine leptin could affect the expression of microRNA and HDAC in PC. Data analysis suggests that HDAC-microRNA-leptin signaling crosstalk may be a new target for PC therapy.
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Rodrigo C, Tennekoon KH, Karunanayake EH, De Silva K, Amarasinghe I, Wijayasiri A. Circulating leptin, soluble leptin receptor, free leptin index, visfatin and selected leptin and leptin receptor gene polymorphisms in sporadic breast cancer. Endocr J 2017; 64:393-401. [PMID: 28190851 DOI: 10.1507/endocrj.ej16-0448] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Leptin and visfatin are implicated in breast cancer risk but studies accounting for bioavailability of leptin are sparse. Reports on the association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with breast cancer are also inconsistent. Only a very few studies have examined biochemical and genetic variables concomitantly in the same cohort. A matched pairs study was carried out to ascertain whether plasma leptin, soluble leptin receptor, free leptin index (leptin/soluble leptin receptor), serum visfatin and selected LEP and LEPR polymorphisms are risk factors for sporadic breast cancer. Newly diagnosed sporadic breast cancer patients (N=80) were matched for age, body mass index (BMI) and menopausal status with healthy controls. Plasma leptin, soluble leptin receptor and serum visfatin were measured by enzyme-immunoassay. LEP -2548 A/G and LEPR K109R, LEPR Q223R polymorphisms were determined by genotyping. Leptin (p=0.0234), leptin/BMI (p=0.0468), free leptin index (p<0.0001) and visfatin (p=0.0002) were significantly higher and soluble leptin receptor (p<0.0001) was significantly lower in patients. LEPR gene K109R A/G polymorphism increased breast cancer risk (odds ratio: 4.125). Multivariate analysis confirmed that leptin, soluble leptin receptor, free leptin index and G109 (R109) allele of the LEPR gene K109R polymorphism are risk factors for breast cancer. When stratified by menopausal status free leptin index and soluble leptin receptor remained as risk factors irrespective of menopausal status while LEPR gene K109R A/G polymorphism remained as a risk factor only in the postmenopausal group.
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Affiliation(s)
- Chrishani Rodrigo
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka
| | - Kamani Hemamala Tennekoon
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka
| | - Eric Hamilton Karunanayake
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka
| | | | | | - Ananda Wijayasiri
- Department of Community Medicine, Faculty of Medical Sciences, University of Sri Jayawardenapura, Nugegoda 10250, Sri Lanka
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Madej P, Franik G, Kurpas P, Owczarek A, Chudek J, Olszanecka-Glinianowicz M. Evaluation of Adipokines, Inflammatory Markers, and Sex Hormones in Simple and Complex Breast Cysts' Fluid. DISEASE MARKERS 2016; 2016:5174929. [PMID: 27293305 PMCID: PMC4880712 DOI: 10.1155/2016/5174929] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 04/02/2016] [Accepted: 04/13/2016] [Indexed: 11/18/2022]
Abstract
Objective. The aim of the study was to analyze the association between levels of adipokines in the breast cyst fluid and in the circulation in relation to the type of cysts. Material and Measurements. A cross-sectional study involved 86 women with breast cysts (42 with simple cysts and 44 with complex cysts). Plasma and breast cyst fluid leptin, adiponectin, visfatin/NAMPT, resistin, TNF-α, and IL-6 levels, in addition to serum levels of estradiol, progesterone and prolactin, and anthropometric parameters and body composition (by bioimpedance method), were measured. Results. The levels of leptin, adiponectin, and resistin were significantly lower in breast cyst fluid than in plasma regardless of the cyst type. Contrarily, the levels of visfatin/NAMPT and TNF-α were significantly increased, and IL-6 levels were similar in the breast cyst fluid and plasma in both study groups. There was no correlation between corresponding levels of leptin, adiponectin, resistin, visfatin/NAMPT, TNF-α, and IL-6 in breast cyst fluid and plasma. Conclusions. Higher levels of visfatin/NAMPT and TNF-α in the fluid from simple and complex breast cysts than in plasma suggest that their local production is related to inflammation.
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Affiliation(s)
- Paweł Madej
- Department of Endocrinological Gynecology, Medical Faculty in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Grzegorz Franik
- Department of Endocrinological Gynecology, Medical Faculty in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Piotr Kurpas
- Department of Endocrinological Gynecology, Medical Faculty in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Aleksander Owczarek
- Department of Statistics in Sosnowiec, Medical University of Silesia, 40-752 Katowice, Poland
| | - Jerzy Chudek
- Pathophysiology Unit, Department of Pathophysiology, Medical Faculty in Katowice, Medical University of Silesia, 20-093 Katowice, Poland
| | - Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical Faculty in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
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30
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Khalil Arjmandi M, Moslemi D, Sadati Zarrini A, Ebrahimnezhad Gorji M, Mosapour A, Haghhaghighi A, Halalkhor S, Bijani A, Parsian H. Pre and post radiotherapy serum oxidant/antioxidant status in breast cancer patients: Impact of age, BMI and clinical stage of the disease. Rep Pract Oncol Radiother 2016; 21:141-8. [PMID: 27601942 DOI: 10.1016/j.rpor.2015.12.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 11/04/2015] [Accepted: 12/23/2015] [Indexed: 01/15/2023] Open
Abstract
AIM In this study the effects of radiation therapy (RT) on serum oxidant/antioxidant status in breast cancer patients and the impact of age, BMI and clinical stage of the disease on the aforementioned variables were investigated. BACKGROUND RT that is used for cancer treatment is dependent on the production of reactive oxygen species. MATERIALS AND METHODS Eighty patients with breast cancer participated in this study and received RT at a dose of 50 Gy for 5 weeks. Blood samples were obtained in one day before and after the end of RT. Serum status of malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analyzed by spectrophotometry or ELISA and selenium (Se) level were analyzed by atomic absorption spectrometry. Paired t-test was used for comparing pre and post radiotherapy data. RESULTS Before and after the radiotherapy, a significant increase in MDA level was observed, while a significant decrease in GPx activity, SOD, TAS and Se levels were found (p < 0.05). The level of the CAT enzyme had no significant changes (p = 0.568). The results showed some changes in the status of TAS, SOD and GPx which are associated with age, BMI and clinical stage of the disease. CONCLUSION It seems that RT would have the potential to cause variations in the status of antioxidant/oxidant system. Although, some changes in variables were observed by sub-classification of the age, BMI and the disease stage, but it seems that these changes are not necessarily dependent to them.
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Affiliation(s)
| | - Dariush Moslemi
- Department of Radiation Oncology, Babol University of Medical Sciences, Babol, Iran
| | - Azadeh Sadati Zarrini
- Department of Biology, Science and Research Branch, Islamic Azad University, Fars, Iran
| | | | - Abbas Mosapour
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Asefeh Haghhaghighi
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Sohrab Halalkhor
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Ali Bijani
- Social Determinant of Health Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Hadi Parsian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
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Shouman S, Wagih M, Kamel M. Leptin influences estrogen metabolism and increases DNA adduct formation in breast cancer cells. Cancer Biol Med 2016; 13:505-513. [PMID: 28154783 PMCID: PMC5250609 DOI: 10.20892/j.issn.2095-3941.2016.0079] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells. Methods: High performance liquid chromatography (HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction (real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-450 1B1 (CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1 (NQO1), and Catechol-O-methyl transferase (COMT). Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and mRNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT. Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.
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Affiliation(s)
- Samia Shouman
- Department of Cancer Biology, Unit of Pharmacology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
| | - Mohamed Wagih
- Department of Pathology, Faculty of Medicine, Beni-Suef University, Benisuef 62511, Egypt
| | - Marwa Kamel
- Department of Cancer Biology, Unit of Pharmacology, National Cancer Institute, Cairo University, Cairo 11796, Egypt
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