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Drewa J, Lazar-Juszczak K, Adamowicz J, Juszczak K. May Patients Receiving GLP-1 Agonists Be at Lower Risk of Prostate Cancer Aggressiveness and Progression? Cancers (Basel) 2025; 17:1576. [PMID: 40361502 PMCID: PMC12071316 DOI: 10.3390/cancers17091576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 04/27/2025] [Accepted: 05/03/2025] [Indexed: 05/15/2025] Open
Abstract
INTRODUCTION GLP-1 receptor agonists are valuable therapeutic agents for managing obesity and type 2 diabetes. The link between prostate cancer and obesity was described. The modulation of incretin hormone-dependent pathways may decrease the prostate cancer aggressiveness and progression. OBJECTIVES The purpose of this study was to review and summarize the literature on the role of GLP-1 agonists in prostate cancer. MATERIAL & METHODS We performed a scoping literature review of PubMed from January 2002 to February 2025. Search terms included "glucagon-peptide like 1", "incretin hormone", "GLP-1 receptor agonist", and "prostate cancer". Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included GLP-1 receptor, incretin hormones, GLP-1 receptor agonists, and their role in prostate cancer development. RESULTS 77 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the role of GLP-1 receptor and it's agonists in prostate cancer biology and development. The following review aims to discuss and provide information about the role of incretin hormones in prostate cancer pathogenesis and its clinical implication in patients with prostate cancer. CONCLUSION Incretin hormone-dependent pathways play an important role in prostate cancer pathogenesis. Moreover, GLP-1 receptor agonists seems to be a promising therapeutical agents when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer.
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Affiliation(s)
- Julia Drewa
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
| | - Katarzyna Lazar-Juszczak
- Primary Health Care Clinic of the Ujastek Medical Center, Krakow University of Health Promotion, 31-158 Cracow, Poland
| | - Jan Adamowicz
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
| | - Kajetan Juszczak
- Department of Urology and Andrology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
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Chou OHI, Lu L, Chung CT, Chan JSK, Chan RNC, Lee AYH, Dee EC, Ng K, Pui HHH, Lee S, Cheung BMY, Tse G, Zhou J. Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: A population-based cohort study. DIABETES & METABOLISM 2025; 51:101571. [PMID: 39182669 DOI: 10.1016/j.diabet.2024.101571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 07/29/2024] [Accepted: 08/07/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients. This study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients. DESIGN, SETTING AND PARTICIPANTS This was a retrospective population-based cohort study of prospectively recorded data on male patients with T2DM who were prescribed either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 from Hong Kong. METHODS The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbor search was performed and multivariable Cox regression was applied. A three-arm analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted. RESULTS This study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n = 17,120; DPP4I: n = 25,009). In the propensity score matched cohort, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). Over a follow-up duration of 5.61 years, SGLT2I was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) than DPP4I after adjustments. The subgroup analyses showed that the interactions between SGLT2I and age, hypertension, heart failure, and GLP-1a were not statistically significant. The result remained consistent in the sensitivity analysis. CONCLUSION The study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after propensity score matching and adjustments compared to DPP4I amongst T2DM patients.
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Affiliation(s)
- Oscar Hou In Chou
- Division of Clinical Pharmacology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Lei Lu
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Cheuk To Chung
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | | | | | | | - Edward Christopher Dee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer, New York, United States
| | - Kenrick Ng
- Department of Medical Oncology, University College London Hospital, London, UK; Department of Medical Oncology, St Bartholomew's Hospital, London, UK
| | - Hugo Hok Him Pui
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Sharen Lee
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Bernard Man Yung Cheung
- Division of Clinical Pharmacology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China; School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong, China; Kent and Medway Medical School, Canterbury Christ Church University and University of Kent, Canterbury, United Kingdom.
| | - Jiandong Zhou
- Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
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Sultan DH, Ghebrezadik DG, Smith DS, Ombengi DN, Ayedun L, Luke FE, Demery JL, Scoggins CT, Penn-Marshall M. A Problem in NIH and Federally Funded Prostate Cancer Interventional Clinical Trials. J Racial Ethn Health Disparities 2024; 11:2740-2755. [PMID: 37552424 DOI: 10.1007/s40615-023-01737-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Obesity, diagnosed in 41.1% of African American (AA) men, is a risk factor for prostate cancer (PCa) recurrence, progression, and increased mortality. Obesity is associated with aggressive PCa only in AA men and not White American (WA) men. The overall health of AA PCa patients is also more likely to be adversely affected by comorbid type 2 diabetes (T2D), often an outcome of obesity and a cause of reduced odds of PCa survival. This evidence suggests that preventing and controlling comorbid obesity and T2D in AA men diagnosed with PCa should be a research funding priority. AIM The aim of this study is to determine if federally funded PCa clinical trials controlled T2D and obesity. METHODS Completed interventional PCa clinical trials conducted in the USA, funded by the NIH or other federal agency, which included males aged 18-64 years, and reported study protocols were included in the study. We examined the intervention modalities used in the trials to determine if any attempted to control obesity and T2D. RESULTS Fifty-eight trials met the study inclusion criteria. Of these 11 were excluded from the analysis as they did not report AA men. A total of 5802 men participated in the remaining 47 trials. Of these, 917 (15.8%) were AA and 4885 (84.2%) were WA men. Forty (85.1%) trials used pharmaceutical medication therapies or other clinical procedures. None of the medications or clinical procedures used were indicated for treatment of obesity and T2D. 5 (10.6%) trials addressed treatment preferences, survivorship, coping, function, and incontinence among PCa patients. Only 2 (4.25%) trials examined weight loss and diet. CONCLUSIONS None of the completed federally funded PCa clinical trials that included AA men used methods to control T2D. Only an insignificant number (4.25%) attempted to control obesity. This gap in therapeutic optimization to control these comorbid conditions indicates a critical area in need of federal funding priority.
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Affiliation(s)
- Dawood H Sultan
- Mercer University, College of Health Professions, Atlanta, GA, USA.
| | | | - Desiree S Smith
- Mercer University, College of Health Professions, Atlanta, GA, USA
| | | | - Lolade Ayedun
- Mercer University, College of Pharmacy, Atlanta, GA, USA
| | - Faith E Luke
- Mercer University, College of Health Professions, Atlanta, GA, USA
| | - Janee L Demery
- Mercer University, College of Health Professions, Atlanta, GA, USA
| | - Chris T Scoggins
- Mercer University, College of Health Professions, Atlanta, GA, USA
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Tiruye T, Roder D, FitzGerald LM, O'Callaghan M, Moretti K, Caughey GE, Beckmann K. Impact of comorbidities on prostate cancer-specific mortality: A population-based cohort study. Prostate 2024; 84:1138-1145. [PMID: 38798040 DOI: 10.1002/pros.24750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 03/29/2024] [Accepted: 05/13/2024] [Indexed: 05/29/2024]
Abstract
AIM To assess the impact of comorbidities on prostate cancer mortality. METHODS We studied 15,695 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked data sets. Comorbidity was measured 1-year before prostate cancer diagnosis using Rx-Risk, a medication-based comorbidity index. Flexible parametric competing risk regression was used to estimate the independent association between comorbidities and prostate cancer-specific mortality. Specific common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and pain) were also assessed to determine their association with mortality. All models were adjusted for sociodemographic variables, tumor characteristics, and treatment type. RESULTS Prostate cancer-specific mortality was higher for patients with a Rx-Risk score ≥3 versus 0 (adjusted sub-hazard ratio (sHR) 1.34, 95% CI: 1.15-1.56). Lower comorbidity scores (Rx-Risk score 2 vs. 0 and Rx-Risk score 1 vs. 0) were not significantly associated with prostate cancer-specific mortality. Men who were using medications for cardiac disorders (sHR 1.31, 95% CI: 1.13-1.52), chronic airway disease (sHR 1.20, 95% CI: 1.01-1.44), depression and anxiety (sHR 1.17, 95% CI: 1.02-1.35), and thrombosis (sHR 1.21, 95% CI: 1.04-1.42) were at increased risk of dying from prostate cancer compared with men not on those medications. Use of medications for diabetes and chronic pain were not associated with prostate cancer-specific mortality. All Rx-Risk score categories and the specific comorbidities were also associated with increased risk of all-cause mortality. CONCLUSION The findings showed that ≥3 comorbid conditions and specific comorbidities including cardiac disease, chronic airway disease, depression and anxiety, and thrombosis were associated with poor prostate cancer-specific survival. Appropriate management of these comorbidities may help to improve survival in prostate cancer patients.
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Affiliation(s)
- Tenaw Tiruye
- Cancer Epidemiology and Population Health Research Group, Allied Health and Human Performance, University of South Australia, Adelaide, Australia
- School of Public Health, Debre Markos University, Debre Markos, Ethiopia
| | - David Roder
- Cancer Epidemiology and Population Health Research Group, Allied Health and Human Performance, University of South Australia, Adelaide, Australia
| | - Liesel M FitzGerald
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Michael O'Callaghan
- South Australian Prostate Cancer Clinical Outcomes Collaborative, Adelaide, Australia
- Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
- Flinders Medical Centre, Bedford Park, Australia
| | - Kim Moretti
- Cancer Epidemiology and Population Health Research Group, Allied Health and Human Performance, University of South Australia, Adelaide, Australia
- South Australian Prostate Cancer Clinical Outcomes Collaborative, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Gillian E Caughey
- Registry of Senior Australians, South Australian Health and Medical Research Institute, Adelaide, Australia
- Allied Health and Human Performance, University of South Australia, Adelaide, Australia
| | - Kerri Beckmann
- Cancer Epidemiology and Population Health Research Group, Allied Health and Human Performance, University of South Australia, Adelaide, Australia
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Lee JJ, Kim JK, Oh B, Hong SK, Kim BS. Influence of diabetes on microbiome in prostate tissues of patients with prostate cancer. Front Oncol 2024; 14:1445375. [PMID: 39220653 PMCID: PMC11365045 DOI: 10.3389/fonc.2024.1445375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Background Although microbiota in prostatic tissues of patients with prostate cancer have been studied, results of different studies have been inconsistent. Different ethnicity of study subjects, different study designs, and potential contaminations during sample collection and experiments might have influenced microbiome results of prostatic tissues. In this study, we analyzed microbiota and their potential functions in benign and malignant tissues of prostate cancer considering possible contaminants and host variables. Materials and methods A total of 118 tissue samples (59 benign tissues and 59 malignant tissues) obtained by robot-assisted laparoscopic radical prostatectomy were analyzed and 64 negative controls (from sampling to sequencing processes) were included to reduce potential contaminants. Results Alteration of the microbiome in prostate tissues was detected only in patients with diabetes. Furthermore, the influence of diabetes on microbiome was significant in malignant tissues. The microbiome in malignant tissues of patients with diabetes was influenced by pathologic stages. The relative abundance of Cutibacterium was reduced in the high pathologic group compared to that in the intermediate group. This reduction was related to microbial pathways increased in the high pathologic group. Conclusion Results of this study indicate that diabetes can influence the progression of prostate cancer with microbiome alteration in prostate tissues. Although further studies are necessary to confirm findings of this study, this study can help us understand tissue microbiome in prostate cancer and improve clinical therapy strategies.
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Affiliation(s)
- Jin-Jae Lee
- Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, Republic of Korea
| | - Jung Kwon Kim
- Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Bumjo Oh
- Deparment of Family Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Sung Kyu Hong
- Department of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Bong-Soo Kim
- Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, Republic of Korea
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Pliszka M, Szablewski L. Associations between Diabetes Mellitus and Selected Cancers. Int J Mol Sci 2024; 25:7476. [PMID: 39000583 PMCID: PMC11242587 DOI: 10.3390/ijms25137476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/15/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.
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Affiliation(s)
- Monika Pliszka
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
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Ko EJ, Lee SJ. Comparative Study of Diabetes Knowledge, Attitudes, Family Support, Self-efficacy, and Self-management Behaviors Between Cancer Survivors With Diabetes and Diabetes Patients Without Cancer. Cancer Nurs 2024:00002820-990000000-00244. [PMID: 38625752 DOI: 10.1097/ncc.0000000000001351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2024]
Abstract
BACKGROUND Studies have compared diabetes management quality indicators, focusing on physiological markers such as hemoglobin A1c, between cancer survivors with diabetes and general diabetes patients. However, research comparing differences in diabetes self-management behaviors and the factors influencing them between these groups is lacking. OBJECTIVES This study aimed to compare self-management behaviors, guided by the information-motivation-behavior model, between cancer survivors with diabetes and general diabetes patients. In addition, we aimed to identify differences in factors such as diabetes knowledge, attitudes, family support, and self-efficacy that may influence diabetes self-management behaviors in both groups. METHODS A total of 125 cancer survivors with diabetes and 126 general diabetes patients participated in this cross-sectional study. A structured questionnaire assessed demographics, diabetes knowledge, attitudes, self-efficacy, and self-management behaviors. RESULTS Regarding diabetes education, 47.0% of cancer survivors and 61.6% of general diabetes patients received education. The cancer survivors had lower diabetes knowledge scores (10.30 ± 4.15, P < .001), a lower perceived value of strict blood glucose control (4.10 ± 0.56, P < .001), and less family support (15.50 ± 7.50, P = .019) than the patients without cancer (13.51 ± 3.84, 4.25 ± 0.65, and 17.57 ± 6.40, respectively). CONCLUSION This study reveals significant differences in diabetes self-management between cancer survivors and general diabetes patients. Cancer survivors showed lower diabetes knowledge, glucose control perception, and family support. These findings highlight the need for tailored self-management programs for cancer survivors. IMPLICATIONS FOR PRACTICE This study offers insights for developing tailored diabetes self-management programs and educational interventions for cancer survivors.
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Affiliation(s)
- Eun Jeong Ko
- Authors' Affiliation: School of Nursing, Research Institute of Nursing Science, Hallym University, Gangwon-do, Republic of Korea
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Harborg S, Kjærgaard KA, Thomsen RW, Borgquist S, Cronin-Fenton D, Hjorth CF. New Horizons: Epidemiology of Obesity, Diabetes Mellitus, and Cancer Prognosis. J Clin Endocrinol Metab 2024; 109:924-935. [PMID: 37552777 DOI: 10.1210/clinem/dgad450] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 06/30/2023] [Accepted: 07/31/2023] [Indexed: 08/10/2023]
Abstract
The global prevalence of obesity and diabetes mellitus has increased in parallel with increasing cancer incidence, due to environmental and lifestyle factors and population aging. Metabolic diseases are associated with increased cancer risk, so a growing number of patients with cancer have coexistent obesity and/or diabetes mellitus. In this narrative review, we highlight recent evidence on the clinical impact of obesity and diabetes mellitus on the prognosis of prostate, breast, and colorectal cancer, and provide an overview of the underlying mechanisms. There is evidence that obesity is associated with increased risk of recurrence, and all-cause and cancer-specific mortality among adults with prostate, breast, and colorectal cancer. Diabetes mellitus is associated with increased all-cause and cancer-specific mortality for these 3 cancers, beyond any impact of obesity. Evidence also suggests increased risk of colorectal cancer recurrence in patients with diabetes mellitus. The underlying mechanisms are multifactorial and likely include hormonal imbalances and chronic inflammation that promote cancer cell growth. Obesity and diabetes mellitus are associated with increased risk of complications and side effects of cancer treatment. Associated comorbidities such as impaired kidney function, cardiovascular disease, and neuropathies may preclude the use of guideline cancer treatment and are competing causes of death. Cancer patients with metabolic diseases require a designated clinical program and a multidisciplinary approach involving oncologists, endocrinologists, surgeons, nutritionists, and physiotherapists, to ensure coordinated and optimized patient care.
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Affiliation(s)
- Sixten Harborg
- Department of Oncology, Aarhus University Hospital, 8200 Aarhus N, Denmark
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, 8200 Aarhus N, Denmark
| | - Kasper A Kjærgaard
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, 8200 Aarhus N, Denmark
| | - Reimar Wernich Thomsen
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, 8200 Aarhus N, Denmark
| | - Signe Borgquist
- Department of Oncology, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Deirdre Cronin-Fenton
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, 8200 Aarhus N, Denmark
| | - Cathrine F Hjorth
- Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, 8200 Aarhus N, Denmark
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Alzahrani MA, Alkhani KO, Alassaf AM, Alorainy JI, Binsaleh S, Almannie R. Updates in the pathophysiology of COVID-19 infection in male reproductive and sexual health: a literature review. Front Endocrinol (Lausanne) 2024; 14:1226858. [PMID: 38468633 PMCID: PMC10925715 DOI: 10.3389/fendo.2023.1226858] [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: 05/23/2023] [Accepted: 12/26/2023] [Indexed: 03/13/2024] Open
Abstract
This extensive comprehensive review explores the impact of the Coronavirus disease 2019 (COVID-19) pandemic on men's sexual and reproductive health. We conducted a literature review focusing on the possible pathophysiology by which severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) affects men's sexual and reproductive systems. We reviewed most of the studies that reported the impact of SARS-CoV-2 infection on the Testicular, Epididymal, Prostatic, and Penile tissue. Also, we focused on evaluating the SARS-CoV-2 infection on semen parameters and male reproductive hormones. Finally, we reviewed the COVID-19 vaccine's effect on male reproductive and sexual health. Findings revealed the adverse consequences of SARS-CoV-2 at cellular and organ levels on the male genital tract. However, the reported data are still controversial. The initial data regarding COVID-19 vaccination was promising promoted safety for men's reproductive and sexual health. We conclude this paper by offering recommendations to address these adverse consequences and potentially improve sexual and reproductive health among men in the post-COVID-19 pandemic era.
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Affiliation(s)
- Meshari A. Alzahrani
- Department of Urology, College of Medicine, Majmaah University, Al-Majmaah, Saudi Arabia
| | | | | | | | - Saleh Binsaleh
- Department of Surgery, Urology Division, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Raed Almannie
- Department of Surgery, Urology Division, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Hori S, Imamura Y, Kanie Y, Okamura A, Kanamori J, Watanabe M. Early postoperative hyperglycemia as a predictor of postoperative infectious complications and overall survival in non-diabetic patients with esophageal cancer. J Gastrointest Surg 2023; 27:2743-2751. [PMID: 37940808 DOI: 10.1007/s11605-023-05869-5] [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: 07/23/2023] [Accepted: 10/14/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND Diabetes mellitus (DM) is known to be a risk factor for postoperative infectious complications (PICs). However, the significance of postoperative hyperglycemia in non-DM cases has not been well investigated. We sought to establish whether postoperative hyperglycemia is associated with PICs and survival among patients with esophageal cancer, with a focus on non-DM cases. METHODS A total of 430 patients who underwent subtotal esophagectomy for esophageal cancer between 2014 and 2018 were enrolled. Postoperative blood glucose was measured by arterial blood gas test every 8 h from postoperative day (POD) 1 to POD4. The association between hyperglycemia (mean ≥ 200 mg/dl) and PICs or long-term outcomes on each POD was investigated. RESULTS There were 53 DM and 377 non-DM cases. PICs occurred in 127 patients. In the multivariate analysis of all cases, PICs were associated with hyperglycemia on POD1 or -2 (odds ratio [OR] = 1.69, 95% CI, 1.05-2.73, P = 0.031 for POD1; OR = 2.55, 95% CI, 1.10-5.93, P = 0.029 for POD 2). Among non-DM cases, the association was more evident, and persisted until POD4 (OR = 1.94, 95% CI, 1.16-3.24, P = 0.012 for POD1; OR = 3.68, 95% CI, 1.28-10.6, P = 0.016 for POD2; OR = 3.07, 95% CI, 1.11-8.51, P = 0.031 for POD4). Survival analyses limited to R0 cases revealed hyperglycemia on POD2 as an independent prognostic factor in all cases (N = 412) [hazard ratio (HR) = 2.61, 95%CI, 1.21-5.63, P = 0.014], with the prognostic impact more evident among non-DM cases (N = 360) (HR = 4.38, 95% CI, 1.82-10.57, P = 0.0010). CONCLUSION Postoperative hyperglycemia is associated with PICs and worse survival after esophagectomy, particularly in patients without DM.
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Affiliation(s)
- Soshi Hori
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan.
| | - Yasukazu Kanie
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
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Timofte AD, Caruntu ID, Covic AC, Hancianu M, Girlescu N, Chifu MB, Giusca SE. Renal Function Parameters in Distinctive Molecular Subtypes of Prostate Cancer. Cancers (Basel) 2023; 15:5013. [PMID: 37894380 PMCID: PMC10605320 DOI: 10.3390/cancers15205013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 10/01/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023] Open
Abstract
Prostate cancer is a prevalent malignancy in male patients, having diverse clinical outcomes. The follow-up of patients diagnosed with prostate cancer involves the evaluation of renal function, because its impairment reduces patient survival rates and adds complexity to their treatment and clinical care. This study aimed to investigate the relationship between renal function parameters and distinctive molecular subtypes of prostate adenocarcinomas, defined by the immunoexpression of the SPINK1, ERG, HOXB13, and TFF3 markers. The study group comprised 72 patients with prostate cancer and associated chronic kidney disease (CKD) who underwent radical prostatectomy. Histopathological, molecular, and renal parameters were analyzed. Patients were categorized based on ERG/SPINK1 and HOXB13/TFF3 status, and correlations with renal function and prognostic grade groups were assessed. The ERG+/SPINK1+ subgroup exhibited significantly higher postoperative CKD stages and serum creatinine levels compared to the ERG+/SPINK1- subgroup. This suggests an intricate relationship between SPINK1 overexpression and renal function dynamics. The HOXB13-/TFF3+ subgroup displayed higher preoperative serum creatinine levels and CKD stages than the HOXB13-/TFF3- subgroup, aligning with TFF3's potential role in renal function. Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis.
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Affiliation(s)
- Andrei Daniel Timofte
- Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (N.G.); (M.B.C.); (S.E.G.)
| | - Irina-Draga Caruntu
- Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (N.G.); (M.B.C.); (S.E.G.)
- Department of Pathology, “Dr. C. I. Parhon” University Hospital, 700503 Iasi, Romania
- Romanian Medical Science Academy, 030171 Bucharest, Romania;
| | - Adrian C. Covic
- Romanian Medical Science Academy, 030171 Bucharest, Romania;
- Romanian Academy of Scientists, 50044 Bucharest, Romania
- Department Medical II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Department of Nephrology, Dialysis and Renal Transplant Center, “Dr. C. I. Parhon” University Hospital, 700503 Iasi, Romania
| | - Monica Hancianu
- Department of Pharmaceutical Sciences II, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Nona Girlescu
- Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (N.G.); (M.B.C.); (S.E.G.)
| | - Mariana Bianca Chifu
- Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (N.G.); (M.B.C.); (S.E.G.)
| | - Simona Eliza Giusca
- Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (N.G.); (M.B.C.); (S.E.G.)
- Department of Pathology, “Dr. C. I. Parhon” University Hospital, 700503 Iasi, Romania
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12
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Sergeyev A, Gu L, De Hoedt AM, Amling CL, Aronson WJ, Cooperberg MR, Kane CJ, Klaassen Z, Terris MK, Guerrios-Rivera L, Freedland SJ, Csizmadi I. Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort. Cancer Epidemiol Biomarkers Prev 2023; 32:1208-1216. [PMID: 37294698 PMCID: PMC10529387 DOI: 10.1158/1055-9965.epi-22-1324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 03/27/2023] [Accepted: 06/07/2023] [Indexed: 06/11/2023] Open
Abstract
BACKGROUND The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). METHODS Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined]. RESULTS Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS In men with late-stage prostate cancer, ICD-9/10 'code-identified' diabetes is associated with better overall survival than 'undiagnosed' diabetes identified by high HbA1c values only. IMPACT Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.
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Affiliation(s)
- Andrei Sergeyev
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | - Lin Gu
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | | | | | | | - Matthew R. Cooperberg
- University of California San Francisco Medical Center, San Francisco, California, USA
| | - Christopher J. Kane
- University of California San Diego Health System, San Diego, California, USA
| | | | | | | | - Stephen J. Freedland
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
- Cedars-Sinai Medical Center, Los Angeles, California, USA
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13
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Ng CT, Bonilla HMG, Bryce AH, Singh P, Herrmann J. Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer. Curr Cardiol Rep 2023; 25:889-899. [PMID: 37490155 PMCID: PMC10894683 DOI: 10.1007/s11886-023-01909-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2023] [Indexed: 07/26/2023]
Abstract
PURPOSE OF REVIEW Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy. RECENT FINDINGS While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.
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Affiliation(s)
- Choon Ta Ng
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
- Department of Cardiology, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore.
| | | | - Alan H Bryce
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Parminder Singh
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Joerg Herrmann
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
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14
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Mapanga W, Norris SA, Craig A, Pumpalova Y, Ayeni OA, Chen WC, Jacobson JS, Neugut AI, Muchengeti M, Pentz A, Doherty S, Minkowitz S, Haffejee M, Rebbeck T, Joffe M. Prevalence of multimorbidity in men of African descent with and without prostate cancer in Soweto, South Africa. PLoS One 2022; 17:e0276050. [PMID: 36256648 PMCID: PMC9578630 DOI: 10.1371/journal.pone.0276050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 09/27/2022] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE With increases in chronic disease, men with prostate cancer are likely to have at least one other chronic health condition. The burden and complexity of each additional chronic disease may complicate prostate cancer treatment and reduce survival. In this paper, we describe the frequency of multimorbid chronic diseases, HIV and depression among men in Soweto, South Africa (SA) with and without prostate cancer and determine whether the presence of multimorbid diseases is associated with metastatic and high-risk, non-metastatic prostate cancer. METHODS A population-based case-control study on prostate cancer was conducted among black men in Soweto. All participants completed a baseline survey on sociodemographics, lifestyle, and comorbid medical conditions. All participants completed a depression screening survey and HIV testing at enrolment. Blood pressure measurements and blood testing for fasting glucose, total cholesterol, and high-density lipoprotein were performed on a subset of randomly selected cases and controls. For men with prostate cancer, clinical T staging was assessed with the digital rectal examination, the diagnosis was confirmed with a biopsy and PSA levels were assessed at presentation. The metastatic staging was assessed by bone scans, and this was confirmed with PSMA PET scans, CT scans and X-rays, standard for our resource-constrained setting. Normal PSA scores were used as an inclusion criterion for controls. RESULTS Of the 2136 men (1095 with prostate cancer and 1041 controls) included in the analysis, 43.0% reported at least one chronic metabolic disease; 24.1% reported two metabolic diseases; 5.3% reported three metabolic diseases; and 0.3% reported four metabolic diseases. Men with prostate cancer were more likely to report a multimorbid chronic metabolic disease compared to controls (p<0.001) and more likely to test positive for HIV (p = 0.05). The majority of men (66.2%) reported at least one metabolic disease, tested negative for HIV and had a negative depression screen. The clinical characteristics of men with prostate cancer, were as follows: 396 (36.2%) had a Gleason score of 8 and above; 552 (51.3%) had a PSA score of >20ng/ml; 233 (21.7%) had confirmed metastatic prostate cancer at diagnosis. Older age was associated with metastatic prostate cancer (OR = 1.043 95% CI:1.02-1.07) and NCCN defined high-risk non-metastatic prostate cancer (OR = 1.03 95% CI:1.01-1.05), whilst being hypertensive was protective (OR = 0.63 95% CI:0.47-0.84 and OR = 0.55 95% CI:0.37-0.83) respectively for metastatic and high-risk, non-metastatic prostate cancer. CONCLUSION The high prevalence of multimorbid metabolic diseases and HIV among men with prostate cancer represents a public health concern in South Africa. There is a need to effectively address multiple chronic diseases among men with prostate cancer by incorporating coordinated care models.
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Affiliation(s)
- Witness Mapanga
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
- SAMRC/Wits Developmental Pathways to Health Research Unit, Department of Paediatrics, Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- SAMRC Common Epithelial Cancer Research Centre, Cape Town, South Africa
- Division of Medical Oncology, Department of Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- * E-mail: ,
| | - Shane A. Norris
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
- SAMRC/Wits Developmental Pathways to Health Research Unit, Department of Paediatrics, Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- SAMRC Common Epithelial Cancer Research Centre, Cape Town, South Africa
- Global Health Research Institute, School of Human Development and Health, University of Southampton, Southampton, United Kingdom
| | - Ashleigh Craig
- Division of Medical Oncology, Department of Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Yoanna Pumpalova
- Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
| | - Oluwatosin A. Ayeni
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
- Division of Medical Oncology, Department of Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Wenlong Carl Chen
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
- National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Judith S. Jacobson
- Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America
| | - Alfred I. Neugut
- Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
- Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America
| | - Mazvita Muchengeti
- National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
| | - Audrey Pentz
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
| | - Sean Doherty
- Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Shauli Minkowitz
- Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mohammed Haffejee
- Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tim Rebbeck
- Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
- Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - Maureen Joffe
- Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
- SAMRC/Wits Developmental Pathways to Health Research Unit, Department of Paediatrics, Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- SAMRC Common Epithelial Cancer Research Centre, Cape Town, South Africa
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15
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Metabolic changes during prostate cancer development and progression. J Cancer Res Clin Oncol 2022; 149:2259-2270. [PMID: 36151426 PMCID: PMC10097763 DOI: 10.1007/s00432-022-04371-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 09/18/2022] [Indexed: 10/14/2022]
Abstract
Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour's bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic and biochemical changes in 1927. In prostate cancer (PCa) epithelial cells, the tumour metabolism also changes during development and progress. These alterations are partly driven by the androgen receptor, the key regulator in PCa development, progress, and survival. In contrast to other epithelial cells of different entities, glycolytic metabolism in prostate cells sustains physiological citrate secretion in the normal prostatic epithelium. In the early stages of PCa, citrate is utilised to power oxidative phosphorylation and fuel lipogenesis, enabling tumour growth and progression. In advanced and incurable castration-resistant PCa, a metabolic shift towards choline, amino acid, and glycolytic metabolism fueling tumour growth and progression has been described. Therefore, even if the metabolic changes are not fully understood, the altered metabolism during tumour progression may provide opportunities for novel therapeutic strategies, especially in advanced PCa stages. This review focuses on the main differences in PCa's metabolism during tumourigenesis and progression highlighting glutamine's role in PCa.
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16
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Chatterjee A, Sakallioglu IT, Murthy D, Kosmacek EA, Singh PK, McDonald JT, Powers R, Oberley-Deegan RE. MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure. Redox Biol 2022; 52:102301. [PMID: 35358851 PMCID: PMC8967707 DOI: 10.1016/j.redox.2022.102301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/04/2022] [Accepted: 03/21/2022] [Indexed: 11/20/2022] Open
Abstract
Radiation is a common anticancer therapy for prostate cancer, which transforms tumor-associated normal fibroblasts to myofibroblasts, resulting in fibrosis. Oxidative stress caused by radiation-mediated mitochondrial damage is one of the major contributors to fibrosis. As diabetics are oxidatively stressed, radiation-mediated reactive oxygen species cause severe treatment failure, treatment-related side effects, and significantly reduced survival for diabetic prostate cancer patients as compared to non-diabetic prostate cancer patients. Hyperglycemia and enhanced mitochondrial damage significantly contribute to oxidative damage and disease progression after radiation therapy among diabetic prostate cancer patients. Therefore, reduction of mitochondrial damage in normal prostate fibroblasts after radiation should improve the overall clinical state of diabetic prostate cancer patients. We previously reported that MnTE-2-PyP, a manganese porphyrin, reduces oxidative damage in irradiated hyperglycemic prostate fibroblasts by scavenging superoxide and activating NRF2. In the current study, we have investigated the potential role of MnTE-2-PyP to protect mitochondrial health in irradiated hyperglycemic prostate fibroblasts. This study revealed that hyperglycemia and radiation increased mitochondrial ROS via blocking the mitochondrial electron transport chain, altered mitochondrial dynamics, and reduced mitochondrial biogenesis. Increased mitochondrial damage preceeded an increase in myofibroblast differentiation. MnTE-2-PyP reduced myofibroblast differentiation, improved mitochondrial health by releasing the block on the mitochondrial electron transport chain, enhanced ATP production efficiency, and restored mitochondrial dynamics and metabolism in the irradiated-hyperglycemic prostate fibroblasts. Therefore, we are proposing that one of the mechanisms that MnTE-2-PyP protects prostate fibroblasts from irradiation and hyperglycemia-mediated damage is by protecting the mitochondrial health in diabetic prostate cancer patients.
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Affiliation(s)
- Arpita Chatterjee
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Isin T Sakallioglu
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA
| | - Divya Murthy
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Elizabeth A Kosmacek
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Pankaj K Singh
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - J Tyson McDonald
- Department of Physics & Cancer Research Center, Hampton University, Hampton, VA, 23668, USA
| | - Robert Powers
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA; Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA
| | - Rebecca E Oberley-Deegan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
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17
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Lin CC, Wu MF, Chang YL, Sheu WHH, Liou WS. Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer. J Chin Med Assoc 2022; 85:331-340. [PMID: 34561410 DOI: 10.1097/jcma.0000000000000623] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. METHODS All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. RESULTS A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. CONCLUSION Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.
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Affiliation(s)
- Chih-Chung Lin
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Ming-Fen Wu
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Yen-Lin Chang
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Wayne Huey-Herng Sheu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
- Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
- College of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC
- Institute of Medical Technology, National Chung Hsing University, Taichung, Taiwan, ROC
- College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Wen-Shyong Liou
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
- School of Pharmacy, China Medical University, Taichung, Taiwan, ROC
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18
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Mao D, Lau ESH, Wu H, Yang A, Shi M, Fan B, Tam CHT, Chow E, Kong APS, Ma RCW, Luk A, Chan JCN. Risk associations of long-term HbA1c variability and obesity on cancer events and cancer-specific death in 15,286 patients with diabetes - A prospective cohort study. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2022; 18:100315. [PMID: 35024653 PMCID: PMC8669375 DOI: 10.1016/j.lanwpc.2021.100315] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/05/2021] [Accepted: 10/11/2021] [Indexed: 02/07/2023]
Abstract
Background Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes. Methods In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit. Findings We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m2, all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m2), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death. Interpretation Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D. Funding The Chinese University of Hong Kong Diabetes Research Fund
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Key Words
- ALT, alanine aminotransferase
- BMI, body mass index
- BP, blood pressure
- CI, confidence interval
- CVD, cardiovascular disease
- EMR, electronic medical record
- GV, glycaemic variability
- HA, Hospital Authority
- HDLC, high-density lipoprotein cholesterol
- HKDR, Hong Kong Diabetes Register
- HR, hazard ratio
- HVS, HbA1c variability score
- IQR, inter‐quartile range
- LDLC, low-density lipoprotein cholesterol
- LLD, lipid lowering drug
- MD, median
- Mn, mean
- OGLDs, oral glucose lowering drugs
- RAS, renin angiotensin system
- SD, standard deviation
- SDIM, SD independent of mean
- T2D, type 2 diabetes
- TC, total cholesterol
- TG, triglyceride
- aHR, adjusted hazard ratio
- cancer and all cause death
- diabetes
- glycaemic variability
- obesity
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Affiliation(s)
- Dandan Mao
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Claudia H T Tam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Andrea Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.,Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
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19
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Alharbi SS. Diabetes Mellitus as a Risk Factor for Different Types of Cancers: A Systematic Review. CLINICAL CANCER INVESTIGATION JOURNAL 2022. [DOI: 10.51847/trrtsjqjys] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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20
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Kotwal A, Cheung YMM, Cromwell G, Drincic A, Leblebjian H, Quandt Z, Rushakoff RJ, McDonnell ME. Patient-Centered Diabetes Care of Cancer Patients. Curr Diab Rep 2021; 21:62. [PMID: 34902069 DOI: 10.1007/s11892-021-01435-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/02/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW There is a bidirectional relationship between cancer and diabetes, with one condition influencing the prognosis of the other. Multiple cancer therapies cause diabetes including well-established medications such as glucocorticoids and novel cancer therapies such as immune checkpoint inhibitors (CPIs) and phosphoinositide 3-kinase (PI3K) inhibitors. RECENT FINDINGS The nature and severity of diabetes caused by each therapy differ, with some predominantly mediated by insulin resistance, such as PI3K inhibitors and glucocorticoids, while others by insulin deficiency, such as CPIs. Studies have demonstrated diabetes from CPIs to be more rapidly progressing than conventional type 1 diabetes. There remains a scarcity of published guidance for the screening, diagnosis, and management of hyperglycemia and diabetes from these therapies. The need for such guidance is critical because diabetes management in the cancer patient is complex, individualized, and requires inter-disciplinary care. In the present narrative review, we synthesize and summarize the most relevant literature pertaining to diabetes and hyperglycemia in the setting of these cancer therapies and provide an updated patient-centered framework for their evaluation and management.
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Affiliation(s)
- Anupam Kotwal
- Division of Diabetes, Endocrinology and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA
| | - Yee-Ming M Cheung
- Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA
| | - Grace Cromwell
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA
| | - Andjela Drincic
- Division of Diabetes, Endocrinology and Metabolism, University of Nebraska Medical Center, Omaha, NE, USA
| | - Houry Leblebjian
- Department of Pharmacy, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Zoe Quandt
- Division of Endocrinology and Metabolism, University of California, San Francisco, CA, USA
| | - Robert J Rushakoff
- Division of Endocrinology and Metabolism, University of California, San Francisco, CA, USA
| | - Marie E McDonnell
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA.
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21
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Del Bosque-Plata L, Hernández-Cortés EP, Gragnoli C. The broad pathogenetic role of TCF7L2 in human diseases beyond type 2 diabetes. J Cell Physiol 2021; 237:301-312. [PMID: 34612510 PMCID: PMC9292842 DOI: 10.1002/jcp.30581] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 12/20/2022]
Abstract
The TCF7L2 protein is a key transcriptional effector of the Wnt/β‐catenin signaling pathway, regulating gene expression. It was initially identified in cancer research and embryologic developmental studies. Later, the TCF7L2 gene was linked to type 2 diabetes (T2D), implicating TCF7L2 and Wnt‐signaling in metabolic disorders and homeostasis. In fact, TCF7L2‐T2D variants confer the greatest relative risk for T2D, unquestionably predicting conversion to T2D in individuals with impaired glucose tolerance. We aim to describe the relevance of TCF7L2 in other human disorders. The TCF7L2‐single nucleotide polymorphisms (SNPs) and T2D‐risk association have been replicated in numerous follow‐up studies, and research has now been performed in several other diseases. In this article, we discuss common TCF7L2‐T2D variants within the framework of their association with human diseases. The TCF7L2 functional regions need to be further investigated because the molecular and cellular mechanisms through which TCF7L2 contributes to risk associations with different diseases are still not fully elucidated. In this review, we show the association of common TCF7L2‐T2D variants with many types of diseases. However, the role of rare genetic variations in the TCF7L2 gene in distinct diseases and ethnic groups has not been explored, and understanding their impact on specific phenotypes will be of clinical relevance. This offers an excellent opportunity to gain a clearer picture of the role that the TCF7L2 gene plays in the pathophysiology of human diseases. The potential pleiotropic role of TCF7L2 may underlie a possible pathway for comorbidity in human disorders.
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Affiliation(s)
- Laura Del Bosque-Plata
- Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | | | - Claudia Gragnoli
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolic Disease, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.,Division of Endocrinology, Creighton University School of Medicine, Omaha, Nebraska, USA.,Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA.,Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, Rome, Italy
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22
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Population-wide impacts of aspirin, statins, and metformin use on prostate cancer incidence and mortality. Sci Rep 2021; 11:16171. [PMID: 34373584 PMCID: PMC8352896 DOI: 10.1038/s41598-021-95764-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 07/29/2021] [Indexed: 12/24/2022] Open
Abstract
We evaluated the association between aspirin, statins, and metformin use and prostate cancer (PC) incidence and mortality using a large population-based dataset. 388,760 men who participated in national health screening program in Korea during 2002–2003 were observed from 2004 to 2013. Hazard ratios of aspirin, statins, and metformin use for PC incidence and PC mortality were calculated with adjustment for simultaneous drug use. Cumulative use of each drug was inserted as time-dependent variable with 2-year time windows. Aspirin use ≥ 1.5 year (per 2-year) was associated with borderline decrease in PC mortality when compared to non-users (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.50–1.02). Statins use was not associated with either PC incidence or PC mortality. Metformin ever-use was associated with decreased PC incidence compared with non-diabetics (aHR 0.86, 95% CI 0.77–0.96). Diabetics who were not using metformin or using low cumulative doses had higher PC mortality than non-diabetics (aHR 2.01, 95% CI 1.44–2.81, and aHR 1.70, 95% CI 1.07–2.69, respectively). However, subjects with higher cumulative doses of metformin did not show increased PC mortality. In conclusion, metformin use was associated with lower PC incidence. Use of aspirin and that of metformin among diabetic patients were associated with lower PC mortality.
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23
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Lee H, Byun SS, Lee SE, Hong SK. Impact of poor glycemic control upon clinical outcomes after radical prostatectomy in localized prostate cancer. Sci Rep 2021; 11:12002. [PMID: 34099748 PMCID: PMC8184888 DOI: 10.1038/s41598-021-91310-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/20/2021] [Indexed: 12/29/2022] Open
Abstract
To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000–1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012–1.674, p = 0.040) in multi-variate regression tests. Kaplan–Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016–1.267, p = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group (p = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879–0.981, p = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.
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Affiliation(s)
- Hakmin Lee
- Department of Urology, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 463-707, Gyeonggi-do, Korea.,Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Seok-Soo Byun
- Department of Urology, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 463-707, Gyeonggi-do, Korea.,Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Eun Lee
- Department of Urology, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 463-707, Gyeonggi-do, Korea.,Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Kyu Hong
- Department of Urology, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 463-707, Gyeonggi-do, Korea. .,Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
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24
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Knura M, Garczorz W, Borek A, Drzymała F, Rachwał K, George K, Francuz T. The Influence of Anti-Diabetic Drugs on Prostate Cancer. Cancers (Basel) 2021; 13:cancers13081827. [PMID: 33921222 PMCID: PMC8068793 DOI: 10.3390/cancers13081827] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/27/2021] [Accepted: 04/08/2021] [Indexed: 12/13/2022] Open
Abstract
The incidences of prostate cancer (PC) and diabetes are increasing, with a sustained trend. The occurrence of PC and type 2 diabetes mellitus (T2DM) is growing with aging. The correlation between PC occurrence and diabetes is noteworthy, as T2DM is correlated with a reduced risk of incidence of prostate cancer. Despite this reduction, diabetes mellitus increases the mortality in many cancer types, including prostate cancer. The treatment of T2DM is based on lifestyle changes and pharmacological management. Current available drugs, except insulin, are aimed at increasing insulin secretion (sulfonylureas, incretin drugs), improving insulin sensitivity (biguanides, thiazolidinediones), or increasing urinary glucose excretion (gliflozin). Comorbidities should be taken into consideration during the treatment of T2DM. This review describes currently known information about the mechanism and impact of commonly used antidiabetic drugs on the incidence and progression of PC. Outcomes of pre-clinical studies are briefly presented and their correlations with available clinical trials have also been observed. Available reports and meta-analyses demonstrate that most anti-diabetic drugs do not increase the risk during the treatment of patients with PC. However, some reports show a potential advantage of treatment of T2DM with specific drugs. Based on clinical reports, use of metformin should be considered as a therapeutic option. Moreover, anticancer properties of metformin were augmented while combined with GLP-1 analogs.
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25
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Kelkar S, Oyekunle T, Eisenberg A, Howard L, Aronson WJ, Kane CJ, Amling CL, Cooperberg MR, Klaassen Z, Terris MK, Freedland SJ, Csizmadi I. Diabetes and Prostate Cancer Outcomes in Obese and Nonobese Men After Radical Prostatectomy. JNCI Cancer Spectr 2021; 5:pkab023. [PMID: 34169227 PMCID: PMC8220304 DOI: 10.1093/jncics/pkab023] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/29/2021] [Accepted: 03/05/2021] [Indexed: 12/31/2022] Open
Abstract
Background The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP). Methods We included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese <30 kg/m2; obese ≥30 kg/m2). All statistical tests were 2-sided. Results Diabetes was not associated with PCSM (adj-HR = 1.38, 95% CI = 0.86 to 2.24), CRPC (adj-HR = 1.05, 95% CI = 0.67 to 1.64), or metastases (adj-HR = 1.01, 95% CI = 0.70 to 1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC, and metastases (P ≤ .04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR = 3.06, 95% CI = 1.40 to 6.69), CRPC (adj-HR = 2.14, 95% CI = 1.11 to 4.15), and metastases (adj-HR = 1.57, 95% CI = 0.88 to 2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance. Conclusions Diabetes was associated with increased risks of prostate cancer progression and mortality among obese men but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.
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Affiliation(s)
- Sonia Kelkar
- Urology Section, Veterans Affairs Medical Center, Durham, NC, USA
| | - Taofik Oyekunle
- Duke Cancer Institute Biostatistics Shared Resource, Duke University School of Medicine, Durham, NC, USA
| | - Adva Eisenberg
- Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, USA
| | - Lauren Howard
- Duke Cancer Institute Biostatistics Shared Resource, Duke University School of Medicine, Durham, NC, USA
| | - William J Aronson
- Department of Urology, University of California Los Angeles Medical Center, Los Angeles, CA, USA.,Urology Section, Wadsworth VA Medical Center, Los Angeles, CA, USA
| | - Christopher J Kane
- Department of Urology, University of California San Diego Health System, San Diego, CA, USA
| | | | - Matthew R Cooperberg
- Department of Urology, University of California San Francisco Medical Center, San Francisco, CA, USA
| | - Zachary Klaassen
- Department of Surgery, Section of Urology, Augusta University, Augusta, GA, USA
| | - Martha K Terris
- Department of Surgery, Section of Urology, Augusta University, Augusta, GA, USA
| | - Stephen J Freedland
- Urology Section, Veterans Affairs Medical Center, Durham, NC, USA.,Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ilona Csizmadi
- Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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26
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Vihervuori VJ, Talala K, Taari K, Lahtela J, Tammela TLJ, Auvinen A, Raittinen P, Murtola TJ. Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Population-Based Cohort. Cancer Epidemiol Biomarkers Prev 2021; 30:982-989. [PMID: 33653815 DOI: 10.1158/1055-9965.epi-19-0580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 11/01/2020] [Accepted: 02/22/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs. METHODS The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009. Use of medication was attained from the nationwide prescription database of the Social Insurance Institution of Finland. Median follow-up was 9.2 years postdiagnosis. A total of 1,603 (24,5%) men had used antidiabetic medication. A total of 771 men died of prostate cancer during the follow-up. We used multivariable-adjusted Cox regression to evaluate the risk of prostate cancer death and onset of androgen deprivation therapy (ADT) with adjustment for prostate cancer clinical characteristics, comorbidities and use of other drugs. Separate analyses were further adjusted for blood glucose. RESULTS Risk of prostate cancer death was higher among antidiabetic drug users overall (HR = 1.42; 95% CI, 1.18-1.70) compared with nonusers, separately among insulin and metformin users. Adjustment for blood glucose level abolished the risk increase. Risk of ADT initiation was increased among the medication users (HR = 1.26; 95% CI, 1.05-1.49). CONCLUSIONS Men with prostate cancer using antidiabetic medication are generally at increased risk of dying from prostate cancer compared with nonusers. The risk association is driven by underlying diabetes, as adjustment for blood glucose level ameliorates the risk increase. IMPACT Type 2 diabetes should be considered as a risk factor when considering prostate cancer prognosis.
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Affiliation(s)
- Ville J Vihervuori
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
| | | | - Kimmo Taari
- Department of Urology, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Jorma Lahtela
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Teuvo L J Tammela
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Urology, Tampere University Hospital, Tampere, Finland
| | - Anssi Auvinen
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | | | - Teemu J Murtola
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Urology, Tampere University Hospital, Tampere, Finland.,Department of Surgery, Seinäjoki Central Hospital, Seinäjoki, Finland
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27
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Neuzillet Y, Rouanne M, Dreyfus JF, Raynaud JP, Schneider M, Roupret M, Drouin S, Galiano M, Cathelinau X, Lebret T, Botto H. Metabolic syndrome, levels of androgens, and changes of erectile dysfunction and quality of life impairment 1 year after radical prostatectomy. Asian J Androl 2021; 23:370-375. [PMID: 33565427 PMCID: PMC8269836 DOI: 10.4103/aja.aja_88_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Robust data evaluating the association of preoperative parameters of the patients with quality of life after radical prostatectomy are lacking. We investigated whether clinical and biological preoperative characteristics of the patients were associated with impaired patient-reported quality of life (QoL) and sexual outcomes 1 year after radical prostatectomy. We evaluated patient-reported outcomes among the 1343 men participating in the AndroCan trial (NCT02235142). QoL and erectile dysfunction (ED) were assessed before and 1 year after radical prostatectomy using validated self-assessment questionnaires (Aging Male's Symptoms [AMS] and the 5-item abridged version of the International Index of Erectile Function [IIEF5]). At baseline, 1194 patients (88.9%) accepted to participate. A total of 750 (55.8%) patients answered the 1-year postoperative questionnaires. Out of them, only 378 (50.4% of responders) provided answers that could be used for calculations. One year after prostatectomy, ED had worsened by 8.0 (95% confidence interval [CI]: 7.3–8.7; P < 0.0001) out of a maximum of 20. The global AMS score has worsened by 2.8 (95% CI: 1.7–3.8; P < 0.0001). ED scores 1 year postsurgery were positively correlated with preoperative age and percentage of fat mass, and negatively correlated with total cholesterol, dehydroepiandrosterone (DHEA), and androstenediol (D5); AMS were poorly correlated with preoperative parameters. QoL and sexual symptoms significantly worsened after radical prostatectomy. Baseline bioavailable testosterone levels were significantly correlated with smaller changes on AMS somatic subscores postprostatectomy. These findings may be used to inform patients with newly diagnosed prostate cancer.
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Affiliation(s)
- Yann Neuzillet
- Department of Urology, Hospital Foch, UVSQ-Paris-Saclay University, Suresnes 92150, France
| | - Mathieu Rouanne
- Department of Urology, Hospital Foch, UVSQ-Paris-Saclay University, Suresnes 92150, France
| | - Jean-François Dreyfus
- Department of Clinical Research and Innovation, Hospital Foch, UVSQ-Paris-Saclay University, Suresnes 92150, France
| | | | - Marc Schneider
- Department of Urology, Hospital Louis Pasteur, Colmar 68000, France
| | - Morgan Roupret
- Department of Urology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris 75013, France
| | - Sarah Drouin
- Department of Urology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris 75013, France
| | - Marc Galiano
- Department of Urology, Montsouris Institute, Paris-Descartes University, Paris 75014, France
| | - Xavier Cathelinau
- Department of Urology, Montsouris Institute, Paris-Descartes University, Paris 75014, France
| | - Thierry Lebret
- Department of Urology, Hospital Foch, UVSQ-Paris-Saclay University, Suresnes 92150, France
| | - Henry Botto
- Department of Urology, Hospital Foch, UVSQ-Paris-Saclay University, Suresnes 92150, France
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28
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Crigna AT, Samec M, Koklesova L, Liskova A, Giordano FA, Kubatka P, Golubnitschaja O. Cell-free nucleic acid patterns in disease prediction and monitoring-hype or hope? EPMA J 2020; 11:603-627. [PMID: 33144898 PMCID: PMC7594983 DOI: 10.1007/s13167-020-00226-x] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023]
Abstract
Interest in the use of cell-free nucleic acids (CFNAs) as clinical non-invasive biomarker panels for prediction and prevention of multiple diseases has greatly increased over the last decade. Indeed, circulating CFNAs are attributable to many physiological and pathological processes such as imbalanced stress conditions, physical activities, extensive apoptosis of different origin, systemic hypoxic-ischemic events and tumour progression, amongst others. This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Presented considerations conform with principles of 3P medicine and serve for improving individual outcomes and cost efficacy of medical services provided to the population.
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Affiliation(s)
- Adriana Torres Crigna
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Marek Samec
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Lenka Koklesova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Alena Liskova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Frank A. Giordano
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Olga Golubnitschaja
- Predictive, Preventive, Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
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29
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Delgado-Balderas JR, Gallardo-Blanco HL, Yee-De León JF, Rivas-Estilla AM, Soto-García B, Aráiz-Hernández D, Garza-Guajardo R, Náñez-Marín M, Hernández-Barajas D, García-Bailón AM, Vízcarra-Mata G, Ocaña-Munguía MA, Gómez-Guerra LS, Sánchez-Domínguez CN. Steroid 5 alpha-reductase 2 enzyme variants, biomass exposure and tobacco use in Mexican patients with prostate cancer. Oncol Lett 2020; 20:261. [PMID: 32989395 PMCID: PMC7517572 DOI: 10.3892/ol.2020.12124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 07/31/2020] [Indexed: 11/25/2022] Open
Abstract
The presence of the genetic variants of the steroid 5-alpha reductase 2 enzyme, which is encoded by the SRD5A2 gene, has been associated with an increased risk of developing prostate cancer among certain ethnic groups. However, these molecular studies have not been conducted on the Mexican population. The analysis of the genetic variants, rs9282858 and rs523349, was performed in 101 males with prostate cancer and 100 healthy controls classified as males without prostate abnormalities (n=60) and males with benign prostatic hyperplasia (n=40), to identify a probable association with this cancer type in the Northeast Mexican population. An association was identified between prostate cancer and biomass exposure [P=0.012; odds ratio (OR), 2.89; confidence interval (CI)=1.21-6.88] and tobacco use (P=0.028; OR=1.88; CI=1.07-3.31), while no association was observed between cancer development and the rs9282858 variant, or between a protective effect and the rs523349 variant. Notably, an association was identified between rs523349 and biomass exposure (P=0.013, OR=3.17; CI=1.23-8.17 for the G risk allele, and OR=0.32, CI=0.12-0.81 for the C protective allele) using the dominant genetic model. To the best of our knowledge, the present study was the first of its type to investigate the Mexican population with prostate cancer.
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Affiliation(s)
- Jesus Rolando Delgado-Balderas
- Department of Biochemistry and Molecular Medicine, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | | | | | - Ana Maria Rivas-Estilla
- Department of Biochemistry and Molecular Medicine, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | | | | | - Raquel Garza-Guajardo
- Pathological Anatomy and Cytopathology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Melissa Náñez-Marín
- Pathological Anatomy and Cytopathology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - David Hernández-Barajas
- Oncology Service, University Center Against Cancer, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Aldo Missael García-Bailón
- Urology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Guillermo Vízcarra-Mata
- Urology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Marco Alberto Ocaña-Munguía
- Urology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Lauro Salvador Gómez-Guerra
- Urology Service, 'Dr. José Eleuterio González' University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
| | - Celia Nohemí Sánchez-Domínguez
- Department of Biochemistry and Molecular Medicine, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
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30
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Sharma U, Jagannathan NR. Metabolism of prostate cancer by magnetic resonance spectroscopy (MRS). Biophys Rev 2020; 12:1163-1173. [PMID: 32918707 DOI: 10.1007/s12551-020-00758-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/04/2020] [Indexed: 12/11/2022] Open
Abstract
Understanding the metabolism of prostate cancer (PCa) is important for developing better diagnostic approaches and also for exploring new therapeutic targets. Magnetic resonance spectroscopy (MRS) techniques have been shown to be useful in the detection and quantification of metabolites. PCa illustrates metabolic phenotype, showing lower levels of citrate (Cit), a key metabolite of oxidative phosphorylation and alteration in several metabolic pathways to sustain tumor growth. Recently, dynamic nuclear polarization (DNP) studies have documented high rates of glycolysis (Warburg phenomenon) in PCa. High-throughput metabolic profiling strategies using MRS on variety of samples including intact tissues, biofluids like prostatic fluid, seminal fluid, blood plasma/sera, and urine have also played a vital role in understanding the abnormal metabolic activity of PCa patients. The enhanced analytical potential of these techniques in the detection and quantification of a large number of metabolites provides an in-depth understanding of metabolic rewiring associated with the tumorigenesis. Metabolomics analysis offers dual advantages of identification of diagnostic and predictive biomarkers as well as in understanding the altered metabolic pathways which can be targeted for inhibiting the cancer progression. This review briefly describes the potential applications of in vivo 1H MRS, high-resolution magic angle spinning spectroscopy (HRMAS) and in vitro MRS methods in understanding the metabolic changes of PCa and its usefulness in the management of PCa patients.
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Affiliation(s)
- Uma Sharma
- Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Naranamangalam R Jagannathan
- Department of Radiology, Chettinad Hospital & Research Institute, Chettinad Academy of Research & Education, Kelambakkam, TN, 603103, India.
- Department of Radiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, 600116, India.
- Department of Electrical Engineering, Indian Institute Technology Madras, Chennai, 600 036, India.
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31
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Linkeviciute-Ulinskiene D, Patasius A, Kincius M, Zabuliene L, Smailyte G. Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer. Scand J Urol 2020; 54:401-407. [PMID: 32748714 DOI: 10.1080/21681805.2020.1798502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To assess prostate cancer-specific and overall survival in prostate cancer patients with or without preexisting type 2 diabetes mellitus (T2DM) with regards to metformin use. METHODS Patients diagnosed with prostate cancer in the Lithuanian population between 2001 and 2005 were identified through the Lithuanian Cancer Registry and followed until 2016, date of death, loss to follow-up or whichever came first. Information regarding the diagnosis of T2DM and antihyperglycemic medications were obtained from the National Health Insurance Fund database. Prostate cancer-specific and overall survival outcomes were analysed using univariate and multivariate Cox proportional hazard models. RESULTS Out of 6689 men included, 254 (3.8%) had preexisting T2DM. There were 4807 deaths during follow-up, including 2084 from prostate cancer. No differences were found in prostate cancer-specific survival between men with or without T2DM. The risk of overall mortality was higher (HR = 1.24, 95% CI = 1.07-1.43) in diabetic men. Univariate analysis showed cancer stage at diagnosis and age to be significant predictors of survival. After adjustment for age and stage at diagnosis, there was no difference in prostate-specific survival between non-diabetic patients compared to metformin users or metformin non-users. However, overall survival was lower in T2DM patients, with a higher mortality risk for metformin non-users (HR = 1.63, 95% CI = 1.27-2.10). Prostate cancer-specific mortality risk was insignificantly lower in diabetic men on metformin (HR = 0.74, 95% CI = 0.54-1.02). CONCLUSION There was no difference in long-term prostate cancer-specific survival in patients with or without T2DM. Overall survival was lower in T2DM patients not treated with metformin.
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Affiliation(s)
- Donata Linkeviciute-Ulinskiene
- Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Ausvydas Patasius
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius, Lithuania.,Department of Public Health, Institute of Health Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Marius Kincius
- Department of Oncourology, National Cancer Institute, Vilnius, Lithuania
| | - Lina Zabuliene
- Clinic of Rheumatology, Orthopaedics, Traumatology and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Giedre Smailyte
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius, Lithuania.,Department of Public Health, Institute of Health Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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Chakravarty D, Nair SS, Hammouda N, Ratnani P, Gharib Y, Wagaskar V, Mohamed N, Lundon D, Dovey Z, Kyprianou N, Tewari AK. Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer. Commun Biol 2020; 3:374. [PMID: 32641750 PMCID: PMC7343823 DOI: 10.1038/s42003-020-1088-9] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 06/17/2020] [Indexed: 01/08/2023] Open
Abstract
The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.
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Affiliation(s)
- Dimple Chakravarty
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
| | - Sujit S Nair
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
| | - Nada Hammouda
- Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Parita Ratnani
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Yasmine Gharib
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Vinayak Wagaskar
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Nihal Mohamed
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Dara Lundon
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Zachary Dovey
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Natasha Kyprianou
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Ashutosh K Tewari
- Department of Urology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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Mansor R, Holly J, Barker R, Biernacka K, Zielinska H, Koupparis A, Rowe E, Oxley J, Sewell A, Martin RM, Lane A, Hackshaw-McGeagh L, Perks C. IGF-1 and hyperglycaemia-induced FOXA1 and IGFBP-2 affect epithelial to mesenchymal transition in prostate epithelial cells. Oncotarget 2020; 11:2543-2559. [PMID: 32655839 PMCID: PMC7335671 DOI: 10.18632/oncotarget.27650] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 06/01/2020] [Indexed: 12/22/2022] Open
Abstract
Localized prostate cancer (PCa) is a manageable disease but for most men with metastatic disease, it is often fatal. A western diet has been linked with PCa progression and hyperglycaemia has been associated with the risk of lethal and fatal prostate cancer. Using PCa cell lines, we examined the impact of IGF-I and glucose on markers of epithelial-to-mesenchymal transition (EMT), migration and invasion. We examined the underlying mechanisms using cell lines and tumour tissue samples. IGF-I had differential effects on the process of EMT: inhibiting in normal and promoting in cancer cells, whereas hyperglycamia alone had a stimulatory effect in both. These effects were independent of IGF and in both cases, hyperglycaemia induced an increase IGFBP-2(tumour promoter) and FOXA1. A positive correlation existed between levels of IGFBP-2 and FOXA1 in benign and cancerous prostate tissue samples and in vitro and in vivo data indicated that FOXA1 strongly interacted with the IGFBP-2 gene in normal prostate epithelial cells that was associated with a negative regulation of IGFBP-2, whereas in cancer cells the level of FOXA1 associating with the IGFBP-2 gene was minimal, suggesting loss of this negative regulation. IGF-I and hyperglycaemia-induced FOXA1/IGFBP-2 play important roles in EMT.
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Affiliation(s)
- Rehanna Mansor
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
- Faculty of Medicine, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, MY
| | - Jeff Holly
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Rachel Barker
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Kalina Biernacka
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Hanna Zielinska
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Anthony Koupparis
- Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, UK
| | - Edward Rowe
- Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, UK
| | - Jon Oxley
- Department of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK
| | - Alex Sewell
- Department of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK
| | - Richard M. Martin
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Athene Lane
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Lucy Hackshaw-McGeagh
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
| | - Claire Perks
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
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Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11:227-238. [PMID: 32547697 PMCID: PMC7284016 DOI: 10.4239/wjd.v11.i6.227] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 04/24/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of diabetes and cancer has increased significantly in recent years. Furthermore, there are many common risk factors for both diabetes and cancer, such as obesity, sedentary lifestyle, smoking, and ageing. A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death. The incidence and mortality of various types of cancer, such as pancreas, liver, colorectal, breast, endometrial, and bladder cancers, have a modest growth in diabetics. However, diabetes may work as a protective factor for prostate cancer. Although the underlying biological mechanisms have not been totally understood, studies have validated that insulin/insulin-like growth factor (IGF) axis (including insulin resistance, hyperinsulinemia, and IGF), hyperglycemia, inflammatory cytokines, and sex hormones provide good circumstances for cancer cell proliferation and metastasis. Insulin/IGF axis activates several metabolic and mitogenic signaling pathways; hyperglycemia provides energy for cancer cell growth; inflammatory cytokines influence cancer cell apoptosis. Thus, these three factors affect all types of cancer, while sex hormones only play important roles in breast cancer, endometrial cancer, and prostate cancer. This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.
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Affiliation(s)
- Mina Wang
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yingying Yang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17177, Sweden
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna 17177, Sweden
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The association of diabetes with risk of prostate cancer defined by clinical and molecular features. Br J Cancer 2020; 123:657-665. [PMID: 32467600 PMCID: PMC7435261 DOI: 10.1038/s41416-020-0910-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 04/23/2020] [Accepted: 05/06/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical and molecular features. METHODS A total of 49,392 men from the Health Professionals Follow-up Study (HPFS) were followed from 1986 to 2014. Data on self-reported diabetes were collected at baseline and updated biennially. Clinical features of prostate cancer included localised, advanced, lethal, low-grade, intermediate-grade, and high-grade. Molecular features included TMPRSS2: ERG and PTEN subtypes. Cox proportional hazards regression models were used to evaluate the association between diabetes and incidence of subtype-specific prostate cancer. RESULTS During 28 years of follow-up, we documented 6733 incident prostate cancer cases. Relative to men free from diabetes, men with diabetes had lower risks of total (HR: 0.82, 95% CI: 0.75-0.90), localised (HR: 0.82, 95% CI: 0.74-0.92), low-and intermediate-grade prostate cancer (HR: 0.77, 95% CI: 0.66-0.90; HR: 0.77, 95% CI: 0.65-0.91, respectively). For molecular subtypes, the HRs for ERG-negative and ERG-positive cases were 0.63 (0.42-0.95) and 0.72 (0.46-1.12); and for PTEN-intact and PTEN-loss cases were 0.69 (0.48-0.98) and 0.52 (0.19-1.41), respectively. CONCLUSION Besides providing advanced evidence for the inverse association between diabetes and prostate cancer, this study is the first to report associations between diabetes and ERG/PTEN defined prostate cancers.
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Wang M, Wasserman E, Geyer N, Carroll RM, Zhao S, Zhang L, Hohl R, Lengerich EJ, McDonald AC. Spatial patterns in prostate Cancer-specific mortality in Pennsylvania using Pennsylvania Cancer registry data, 2004-2014. BMC Cancer 2020; 20:394. [PMID: 32375682 PMCID: PMC7203834 DOI: 10.1186/s12885-020-06902-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/26/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual- and county-level risk factors. METHODS Prostate cancer cases, aged ≥40 years, were identified in the 2004-2014 Pennsylvania Cancer Registry. The 2018 County Health Rankings data and the 2014 U.S. Environmental Protection Agency's Environmental Quality Index were used to extract county-level data. The accelerated failure time models with spatial frailties for geographical correlations were used to assess prostate cancer-specific mortality rates for Pennsylvania and by the Penn State Cancer Institute (PSCI) 28-county catchment area. Secondary assessment based on estimated spatial frailties was conducted to identify potential health and environmental risk factors for mortality. RESULTS There were 94,274 cases included. The 5-year survival rate in PA was 82% (95% confidence interval, CI: 81.1-82.8%), with the catchment area having a lower survival rate 81% (95% CI: 79.5-82.6%) compared to the non-catchment area rate of 82.3% (95% CI: 81.4-83.2%). Black men, uninsured, more aggressive prostate cancer, rural and urban Appalachia, positive lymph nodes, and no definitive treatment were associated with lower survival. Several county-level health (i.e., poor physical activity) and environmental factors in air and land (i.e., defoliate chemical applied) were associated with higher mortality rates. CONCLUSIONS Spatial variations in prostate cancer-specific mortality rates exist in Pennsylvania with a higher risk in the PSCI's catchment area, in particular, rural-Appalachia. County-level health and environmental factors may contribute to spatial heterogeneity in prostate cancer-specific mortality.
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Affiliation(s)
- Ming Wang
- Department of Public Health Sciences, Penn State College of Medicine and Cancer Institute, 90 Hope Drive, Hershey, PA, 17033, USA.
- Penn State Cancer Institute, Hershey, PA, USA.
| | - Emily Wasserman
- Department of Public Health Sciences, Penn State College of Medicine and Cancer Institute, 90 Hope Drive, Hershey, PA, 17033, USA
| | - Nathaniel Geyer
- Department of Public Health Sciences, Penn State College of Medicine and Cancer Institute, 90 Hope Drive, Hershey, PA, 17033, USA
| | - Rachel M Carroll
- Department of Mathematics and Statistics, the University of North Carolina at Wilmington, Wilmington, NC, USA
| | - Shanshan Zhao
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Lijun Zhang
- Penn State Cancer Institute, Hershey, PA, USA
- Penn State Institute of Personalized Medicine, Hershey, PA, USA
| | - Raymond Hohl
- Penn State Cancer Institute, Hershey, PA, USA
- Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
- Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
| | - Eugene J Lengerich
- Department of Public Health Sciences, Penn State College of Medicine and Cancer Institute, 90 Hope Drive, Hershey, PA, 17033, USA
- Penn State Cancer Institute, Hershey, PA, USA
- Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Alicia C McDonald
- Department of Public Health Sciences, Penn State College of Medicine and Cancer Institute, 90 Hope Drive, Hershey, PA, 17033, USA
- Penn State Cancer Institute, Hershey, PA, USA
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Chatterjee A, Kosmacek EA, Shrishrimal S, McDonald JT, Oberley-Deegan RE. MnTE-2-PyP, a manganese porphyrin, reduces cytotoxicity caused by irradiation in a diabetic environment through the induction of endogenous antioxidant defenses. Redox Biol 2020; 34:101542. [PMID: 32361681 PMCID: PMC7200317 DOI: 10.1016/j.redox.2020.101542] [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: 03/04/2020] [Revised: 04/03/2020] [Accepted: 04/13/2020] [Indexed: 01/01/2023] Open
Abstract
Radiation is a common anticancer therapy for many cancer patients, including prostate cancer. Diabetic prostate cancer patients suffer from increased lymph node metastasis, tumor recurrence and decreased survival as compared to non-diabetic prostate cancer patients. These patients are also at increased risk for enhanced radiation-induced normal tissue damage such as proctitis. Diabetics are oxidatively stressed and radiation causes additional oxidative damage. We and others have reported that, MnTE-2-PyP, a manganese porphyrin, protects normal prostate tissue from radiation damage. We have also reported that, in an in vivo mouse model of prostate cancer, MnTE-2-PyP decreases tumor volume and increases survival of the mice. In addition, MnTE-2-PyP has also been shown to reduce blood glucose and inhibits pro-fibrotic signaling in a diabetic model. Therefore, to investigate the role of MnTE-2-PyP in normal tissue protection in an irradiated diabetic environment, we have treated human prostate fibroblast cells with MnTE-2-PyP in an irradiated hyperglycemic environment. This study revealed that hyperglycemia causes increased cell death after radiation as compared to normo-glycemia. MnTE-2-PyP protects against hyperglycemia-induced cell death after radiation. MnTE-2-PyP decreases expression of NOX4 and α-SMA, one of the major oxidative enzymes and pro-fibrotic molecules respectively. MnTE-2-PyP obstructs NF-κB activity by decreasing DNA binding of the p50-p50 homodimer in the irradiated hyperglycemic environment. MnTE-2-PyP increases NRF2 mediated cytoprotection by increasing NRF2 protein expression and DNA binding. Therefore, we are proposing that, MnTE-2-PyP protects fibroblasts from irradiation and hyperglycemia damage by enhancing the NRF2- mediated pathway in diabetic prostate cancer patients, undergoing radiotherapy.
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Affiliation(s)
- Arpita Chatterjee
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Elizabeth A Kosmacek
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shashank Shrishrimal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - J Tyson McDonald
- Department of Physics & Cancer Research Center, Hampton University, Hampton, VA, 23668, USA
| | - Rebecca E Oberley-Deegan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
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Lam T, Birzniece V, McLean M, Gurney H, Hayden A, Cheema BS. The Adverse Effects of Androgen Deprivation Therapy in Prostate Cancer and the Benefits and Potential Anti-oncogenic Mechanisms of Progressive Resistance Training. SPORTS MEDICINE-OPEN 2020; 6:13. [PMID: 32056047 PMCID: PMC7018888 DOI: 10.1186/s40798-020-0242-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/05/2020] [Indexed: 12/25/2022]
Abstract
Prostate cancer has the second highest incidence of all cancers amongst men worldwide. Androgen deprivation therapy (ADT) remains a common form of treatment. However, in reducing serum testosterone to castrate levels and rendering men hypogonadal, ADT contributes to a myriad of adverse effects which can affect prostate cancer prognosis. Physical activity is currently recommended as synergistic medicine in prostate cancer patients to alleviate the adverse effects of treatment. Progressive resistance training (PRT) is an anabolic exercise modality which may be of benefit in prostate cancer patients given its potency in maintaining and positively adapting skeletal muscle. However, currently, there is a scarcity of RCTs which have evaluated the use of isolated PRT in counteracting the adverse effects of prostate cancer treatment. Moreover, although physical activity in general has been found to reduce relapse rates and improve survival in prostate cancer, the precise anti-oncogenic effects of specific exercise modalities, including PRT, have not been fully established. Thus, the overall objective of this article is to provide a rationale for the in-depth investigation of PRT and its biological effects in men with prostate cancer on ADT. This will be achieved by (1) summarising the metabolic effects of ADT in patients with prostate cancer and its effect on prostate cancer progression and prognosis, (2) reviewing the existing evidence regarding the metabolic benefits of PRT in this cohort, (3) exploring the possible oncological pathways by which PRT can affect prostate cancer prognosis and progression and (4) outlining avenues for future research.
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Affiliation(s)
- Teresa Lam
- School of Medicine, Western Sydney University, Penrith, NSW, Australia. .,Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia. .,Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, NSW, Australia.
| | - Vita Birzniece
- School of Medicine, Western Sydney University, Penrith, NSW, Australia.,Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, NSW, Australia.,School of Medicine, UNSW Sydney, Sydney, NSW, Australia.,Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.,Translational Health Research Institute, Penrith, NSW, Australia
| | - Mark McLean
- School of Medicine, Western Sydney University, Penrith, NSW, Australia.,Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, NSW, Australia
| | - Howard Gurney
- Crown Princess Mary Cancer Centre, Westmead, NSW, Australia
| | - Amy Hayden
- Crown Princess Mary Cancer Centre, Westmead, NSW, Australia.,Department of Radiation Oncology, Blacktown Hospital, Blacktown, NSW, Australia
| | - Birinder S Cheema
- School of Science and Health, Western Sydney University, Penrith, NSW, Australia
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Kensler KH, Rebbeck TR. Cancer Progress and Priorities: Prostate Cancer. Cancer Epidemiol Biomarkers Prev 2020; 29:267-277. [PMID: 32024765 PMCID: PMC7006991 DOI: 10.1158/1055-9965.epi-19-0412] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/10/2019] [Accepted: 12/03/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Kevin H Kensler
- Division of Population Sciences, Dana-Farber Cancer Institute and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Timothy R Rebbeck
- Division of Population Sciences, Dana-Farber Cancer Institute and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Lopez DS, Huang D, Tsilidis KK, Khera M, Williams SB, Urban RJ, Panagiotou OA, Kuo YF, Baillargeon J, Farias A, Krause T. Association of the extent of therapy with prostate cancer in those receiving testosterone therapy in a US commercial insurance claims database. Clin Endocrinol (Oxf) 2019; 91:885-891. [PMID: 31498469 PMCID: PMC7294776 DOI: 10.1111/cen.14093] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 09/03/2019] [Accepted: 09/04/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Conflicting evidence remains in the association of testosterone therapy (TTh) with prostate cancer (PCa). This inconsistency maybe due, in part, to the small sample sizes from previous studies and an incomplete assessment of comorbidities, particularly diabetes. OBJECTIVE We investigated the association of PCa with TTh (injection or gel) and different TTh doses and determined whether this association varies by the presence of diabetes at baseline in a large, nationally representative, commercially insured cohort. DESIGN We conducted a retrospective cohort study of 189 491 men aged 40-60 years old in the IBM MarketScan® Commercial Database, which included 1424 PCa cases diagnosed from 2011 to 2014. TTh was defined using CPT codes from inpatient and outpatient, and NDC codes from pharmacy claims. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident PCa. RESULTS We found a 33% reduced association of PCa after comparing the highest category (>12) of TTh injections with the lowest (1-2 injections) category (HR = 0.67, 95% CI: 0.54-0.82). Similar statistical significant inverse association for PCa was observed for men who received TTh topical gels (>330 vs 1- to 60-days supply). Among nondiabetics, we found significant inverse association between TTh (injection and gel) and PCa, but a weak interaction between TTh injections and diabetes (P = .05). CONCLUSION Overall, increased use of TTh is inversely associated with PCa and this remained significant only among nondiabetics. These findings warrant further investigation in large randomized placebo-controlled trials to infer any health benefit by TTh.
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Affiliation(s)
- David S. Lopez
- Deparment of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA
| | - Danmeng Huang
- Deparment of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA
| | - Konstantinos K. Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Mohit Khera
- Scott Department of Urology at Baylor College of Medicine, Houston, TX, USA
| | - Stephen B. Williams
- Division of Urology, Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA
| | - Randall J. Urban
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Orestis A. Panagiotou
- Department of Policy and Practice, School of Public Health, Brown University, Providence, RI, USA
| | - Yong-fang Kuo
- Deparment of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA
| | - Jacques Baillargeon
- Deparment of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA
| | - Albert Farias
- Department of Preventive Medicine, Norris Comprehensive Cancer Center, Gehr Family Center for Health Systems Science, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Trudy Krause
- UTHealth School of Public Health, Houston, TX, USA
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41
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Huynh LM, Ahlering TE. Challenging beliefs of testosterone therapy and prostate cancer. Nat Rev Urol 2019; 16:699-701. [PMID: 31659332 DOI: 10.1038/s41585-019-0253-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Linda My Huynh
- University of California, Irvine Health, Orange, CA, USA
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42
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Abudawood M. Diabetes and cancer: A comprehensive review. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2019; 24:94. [PMID: 31741666 PMCID: PMC6856544 DOI: 10.4103/jrms.jrms_242_19] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/30/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus (DM) is a common worldwide endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. A number of clinical studies have investigated diabetes and its causal relation with neoplasm. Several epidemiological studies have found that diabetic patients have an increased risk of different types of cancers, for example liver, pancreas, gastric (stomach), colorectum, kidney, and breast, and it is predicted that hyperglycemic state observed in diabetic milieu enhances the cancer risk in prediabetic and diabetic individuals. To explore the strength of evidence and biases in the claimed associations between type 2 DM (T2DM) and risk of developing cancer, an umbrella review of the evidence across published meta-analyses or systematic reviews is performed. The concurrence of T2DM with the growing burden of cancer globally has generated interest in defining the epidemiological and biological relationships between these medical conditions. Through this review, it was found that diabetes could be related to cancer. Yet, the results from most of the studies are obscure and conflicting and need a robust research so that the link between diabetes and cancer could be firmly and impeccably documented.
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Affiliation(s)
- Manal Abudawood
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, KSA
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43
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Iwase M, Fujii H, Idewaki Y, Nakamura U, Ohkuma T, Ide H, Komorita Y, Jodai-Kitamura T, Yoshinari M, Kitazono T. Prospective study of cancer in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry. Diabetol Int 2019; 10:260-267. [PMID: 31592402 DOI: 10.1007/s13340-019-00390-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 02/13/2019] [Indexed: 10/27/2022]
Abstract
Background Although the association between type 2 diabetes and cancer has been reported, few epidemiological studies have been conducted in Japanese patients whose leading cause of death is cancer. We prospectively studied the incidence of site-specific cancer, risk factors for developing cancer, cancer death, and survival in Japanese patients with type 2 diabetes. Methods We followed 4923 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 99.0%). Results During the follow-up period, cancer occurred in 450 participants (incidence rate, 22.3/1000 person-years in men and 12.2/1000 person-years in women). In men, prostate cancer was the most common cancer (4.3/1000 person-years), colorectal cancer was the second (3.6/1000 person-years), and gastric cancer was the third (3.3/1000 person-years). In women, colorectal cancer was the most common cancer (2.6/1000 person-years), gastric cancer was the second (2.0/1000 person-years), and breast cancer was the third (1.4/1000 person-years). Smoking, male sex, low-density lipoprotein cholesterol, family history of cancer, and reduced intake of isoflavone daidzein were significant risk factors for developing cancer using multivariable Cox proportional hazards models. The leading cancer death was lung cancer in men and pancreatic cancer in women. The survival was the best for prostate cancer and the worst for pancreatic cancer (2-year cancer-specific survival 95.4%, 30.0%, respectively). Conclusions Since the leading cause of death in patients with type 2 diabetes is cancer in Japan, clinicians should be aware of epidemiological data regarding cancer besides diabetic complications.
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Affiliation(s)
- Masanori Iwase
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan.,Diabetes Center and Clinical Research Center, Hakujyuji Hospital, Fukuoka, Japan
| | - Hiroki Fujii
- 3Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Idewaki
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan.,Diabetes Center and Clinical Research Center, Hakujyuji Hospital, Fukuoka, Japan
| | - Udai Nakamura
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Toshiaki Ohkuma
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Hitoshi Ide
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Yuji Komorita
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Tamaki Jodai-Kitamura
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Masahito Yoshinari
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
| | - Takanari Kitazono
- 1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan
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44
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Mandal S, Arabi Belaghi R, Mahmoudi A, Aminnejad M. Stein-type shrinkage estimators in gamma regression model with application to prostate cancer data. Stat Med 2019; 38:4310-4322. [PMID: 31317564 DOI: 10.1002/sim.8297] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 06/06/2019] [Indexed: 11/08/2022]
Abstract
Gamma regression is applied in several areas such as life testing, forecasting cancer incidences, genomics, rainfall prediction, experimental designs, and quality control. Gamma regression models allow for a monotone and no constant hazard in survival models. Owing to the broad applicability of gamma regression, we propose some novel and improved methods to estimate the coefficients of gamma regression model. We combine the unrestricted maximum likelihood (ML) estimators and the estimators that are restricted by linear hypothesis, and we present Stein-type shrinkage estimators (SEs). We then develop an asymptotic theory for SEs and obtain their asymptotic quadratic risks. In addition, we conduct Monte Carlo simulations to study the performance of the estimators in terms of their simulated relative efficiencies. It is evident from our studies that the proposed SEs outperform the usual ML estimators. Furthermore, some tabular and graphical representations are given as proofs of our assertions. This study is finally ended by appraising the performance of our estimators for a real prostate cancer data.
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Affiliation(s)
- Saumen Mandal
- Department of Statistics, University of Manitoba, Winnipeg, Canada
| | | | - Akram Mahmoudi
- Department of Statistics, University of Tabriz, Tabriz, Iran
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45
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Roos JF, Qudsi M, Samara A, Rahim MM, Al-Bayedh SA, Ahmed H. Metformin for lung cancer prevention and improved survival: a novel approach. Eur J Cancer Prev 2019; 28:311-315. [PMID: 29481337 DOI: 10.1097/cej.0000000000000442] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus has been associated with increased risk for the development of many types of cancer. Metformin, an oral medication and first-line treatment for type 2 diabetes mellitus, has been suggested to reduce cancer risk and mortality in various types of cancer. This study focuses on assessing metformin association with lung cancer as reported in the literature. Recent studies and reviews investigating metformin effects on lung cancer incidence and patient survival are critically and systematically discussed.
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Affiliation(s)
- Juliana F Roos
- Department of Clinical Pharmacy and Pharmacy Practice, Dubai Pharmacy College
| | - Mariam Qudsi
- Department of Clinical Pharmacy and Pharmacy Practice, Dubai Pharmacy College
| | - Arwa Samara
- Department of Clinical Pharmacy and Pharmacy Practice, Dubai Pharmacy College
| | - Madina M Rahim
- Department of Clinical Pharmacy and Pharmacy Practice, Dubai Pharmacy College
| | - Samar A Al-Bayedh
- Department of Clinical Pharmacy and Pharmacy Practice, Dubai Pharmacy College
| | - Hafez Ahmed
- Department of Biochemistry, Dubai Medical College, Dubai, United Arab Emirates
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46
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Li S, Wang J, Zhang B, Li X, Liu Y. Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study. Diabetes Metab J 2019; 43:319-341. [PMID: 31210036 PMCID: PMC6581547 DOI: 10.4093/dmj.2018.0060] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 11/09/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND To investigate whether diabetes contributes to mortality for major types of diseases. METHODS Six National Health and Nutrition Examination Survey data cycles (1999 to 2000, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010) and their linked mortality files were used. A population of 15,513 participants was included according to the availability of diabetes and mortality status. RESULTS Participants with diabetes tended to have higher all-cause mortality and mortality due to cardiovascular disease, cancer, chronic lower respiratory diseases, cerebrovascular disease, influenza and pneumonia, and kidney disease. Confounder-adjusted Cox proportional hazard models showed that both diagnosed diabetes category (yes or no) and diabetes status (diabetes, prediabetes, or no diabetes) were associated with all-cause mortality and with mortality due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease. No associations were found for cancer-, accidents-, or Alzheimer's disease-related mortality. CONCLUSION The current study's findings provide epidemiological evidence that diagnosed diabetes at the baseline is associated with increased mortality risk due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease, but not with cancer or Alzheimer's disease.
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Affiliation(s)
- Sen Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Department of Physiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong.
| | - Jiaxin Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Biao Zhang
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Xinyi Li
- School of Management, Beijing University of Chinese Medicine, Beijing, China
| | - Yuan Liu
- Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA
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47
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Akhavan S, Ghahghaei-Nezamabadi A, Modaresgilani M, Mousavi AS, Sepidarkish M, Tehranian A, Rezayof E. Impact of diabetes mellitus on epithelial ovarian cancer survival. BMC Cancer 2018; 18:1246. [PMID: 30541490 PMCID: PMC6291925 DOI: 10.1186/s12885-018-5162-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 11/29/2018] [Indexed: 12/31/2022] Open
Abstract
Background Diabetes mellitus (DM) is associated with poorer outcomes in some cancers. Its effect on ovarian cancer is less clear. We consider the effect of DM on overall survival (OS) and progression free survival (PFS) in patients with epithelial ovarian cancer (EOC). Methods A retrospective cohort study of 215 patients with EOC diagnosed between 2009 and 2016 was performed. Records were reviewed for standard demographic, pathologic and DM diagnosis data. Cox regression was used to evaluate the relationship between disease status and survival after adjustment for age, body mass index (BMI), parity, stage, grade, histology, debulking status, hypertension (HTN), menopause status and neoadjuant chemotherapy. Results Patients with DM (27.97, 95%CI: 23.63 to 32.30) had a significantly shorter OS rates compared to patients without DM (41.01, 95%CI: 38.84 to 43.17). The unadjusted hazard ratio (HR) for the association between OS time and DM was 4.76 (95%CI: 2.99 to 7.59, P < 0.001). Following adjustment for demographic and pathologic variables, the HR was 3.93 (95% CI: 2.01 to 7.68; P < 0.001). The PFS in patients with DM (14.10, 95%CI: 11.76 to 16.44) was significantly shorter compared to patients without DM (28.83, 95%CI: 26.13 to 31.54). The unadjusted HR for PFS and DM was 5.69 (95% CI: 3.05 to 10.61; P < 0.001). After adjustment for demographic and pathologic variables, the HR was 2.73 (95% CI, 1.18 to 6.95; P < 0.001). Conclusions DM can negatively effect on PFS and OS in EOC patients independent of the effect of other variables.
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Affiliation(s)
- Setareh Akhavan
- Gynecology Oncology Department, Vali-Asr Hospital, Tehran University of Medical Sciences, P.O. Box: 16635148, Tehran, Iran
| | - Akram Ghahghaei-Nezamabadi
- Gynecology Oncology Department, Vali-Asr Hospital, Tehran University of Medical Sciences, P.O. Box: 16635148, Tehran, Iran.
| | - Mitra Modaresgilani
- Gynecology Oncology Department, Vali-Asr Hospital, Tehran University of Medical Sciences, P.O. Box: 16635148, Tehran, Iran
| | - Azam Sadat Mousavi
- Gynecology Oncology Department, Vali-Asr Hospital, Tehran University of Medical Sciences, P.O. Box: 16635148, Tehran, Iran
| | - Mahdi Sepidarkish
- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Afsaneh Tehranian
- Department of Obstetrics and Gynecology, Roointan-Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Elahe Rezayof
- Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran
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48
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Shah RR, Stonier PD. Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead. J Clin Pharm Ther 2018; 44:6-22. [PMID: 30218625 DOI: 10.1111/jcpt.12759] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 08/08/2018] [Accepted: 08/19/2018] [Indexed: 12/11/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE In order to expedite the availability of drugs to treat cancers in a cost-effective manner, repurposing of old drugs for oncological indications is gathering momentum. Revolutionary advances in pharmacology and genomics have demonstrated many old drugs to have activity at novel antioncogenic pharmacological targets. We decided to investigate whether prospective studies support the promises of nonclinical and retrospective clinical studies on repurposing three old drugs, namely metformin, valproate and astemizole. METHODS We conducted an extensive literature search through PubMed to gather representative nonclinical and retrospective clinical studies that investigated the potential repurposing of these three drugs for oncological indications. We then searched for prospective studies aimed at confirming the promises of retrospective data. RESULTS AND DISCUSSION While evidence from nonclinical and retrospective clinical studies with these drugs appears highly promising, large scale prospective studies are either lacking or have failed to substantiate this promise. We provide a brief discussion of some of the challenges in repurposing. Principal challenges and obstacles relate to heterogeneity of cancers studied without considering their molecular signatures, trials with small sample size and short duration, failure consider issues of ethnicity of study population and effective antioncogenic doses of the drug studied. WHAT IS NEW AND CONCLUSION Well-designed prospective studies demonstrating efficacy are required for repurposing old drugs for oncology indications, just as they are for new chemical entities for any indication. Early and ongoing interactions with regulatory authorities are invaluable. We outline a tentative framework for a structured approach to repurposing old drugs for novel indications in oncology.
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Affiliation(s)
- Rashmi R Shah
- Pharmaceutical Consultant, Gerrards Cross, Buckinghamshire, UK
| | - Peter D Stonier
- Department of Pharmaceutical Medicine, School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College, London, UK
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Giunchi F, Fiorentino M, Loda M. The Metabolic Landscape of Prostate Cancer. Eur Urol Oncol 2018; 2:28-36. [PMID: 30929843 DOI: 10.1016/j.euo.2018.06.010] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 05/30/2018] [Accepted: 06/22/2018] [Indexed: 12/28/2022]
Abstract
CONTEXT Neoplastic cells are characterized by metabolic alterations that sustain tumor growth. Interventions aimed at modifying metabolic rewiring of cancer cells are currently being investigated in several tumor types, including prostate cancer (PC). OBJECTIVE To review relevant metabolic alterations reported for PC and potential diagnostic and therapeutic opportunities that could be exploited on the basis of these discoveries. EVIDENCE ACQUISITION We performed a review of PubMed/Medline in March 2018 for PC in association with each of the following search terms: metabolomics; lipid, cholesterol, one-carbon, amino acid, and glucose metabolism. Fifty publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS The reports included were grouped according to fatty acid and cholesterol metabolism (28 studies); one-carbon metabolism (9 studies); amino acid metabolism (6 studies); and glucose metabolism (7 studies). We report on multiple metabolic pathways that are dysregulated in prostate cancer. Metabolic alterations can result in at least one of the following changes: protein lipidation, oncogene activation, DNA methylation, cellular signaling, and protein-protein interactions. CONCLUSIONS Metabolic alterations play a crucial role in PC development, progression, and resistance to therapy. Increasing knowledge of metabolic rewiring is revealing novel metabolic signatures in PC. These signatures could be utilized for PC diagnosis, as well as for the discovery of novel therapeutic interventions to overcome castration resistance. PATIENT SUMMARY Metabolic alterations play a crucial role in the development and progression of prostate cancer and its resistance to therapy. Our knowledge of metabolic rewiring is increasing and revealing novel metabolic signatures in prostate cancer. These signatures could be used for diagnosis and for the discovery of novel therapeutic interventions aimed at overcoming castration resistance.
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Affiliation(s)
- Francesca Giunchi
- Division of Genito-Urinary Pathology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy
| | - Michelangelo Fiorentino
- Division of Genito-Urinary Pathology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy.
| | - Massimo Loda
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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50
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Okamura A, Watanabe M, Imamura Y, Hayami M, Yamashita K, Kurogochi T, Mine S. Glycemic Status and Prognosis of Patients with Squamous Cell Carcinoma of the Esophagus. World J Surg 2018; 41:2591-2597. [PMID: 28447164 DOI: 10.1007/s00268-017-4036-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of glycemic status on esophageal squamous cell carcinoma (ESCC) prognosis is unclear. METHODS A total of 623 patients who underwent curative subtotal esophagectomy for ESCC were evaluated. Diabetes was defined as a prior diagnosis of diabetes under treatment or newly diagnosed diabetes based on preoperative glycosylated hemoglobin (HbA1c) levels. Poor glycemic control was defined as HbA1c ≥ 7.0%, whereas good glycemic control was defined as HbA1c < 7.0%. The impact of glycemic status on long-term survival after esophagectomy was evaluated. RESULTS Among the 623 patients, 64 (10.3%) had diabetes including 30 (4.8%) with poor glycemic control. Although diabetes did not influence patient survival, patients with poor glycemic control had worse overall and disease-specific survival compared with those with good glycemic control (P = 0.011 and 0.039, respectively). Comparing poor glycemic control with good glycemic control, the hazard ratios (HRs) for overall and disease-specific mortality were 1.91 (1.15-3.18) and 1.89 (1.02-3.49) in univariate analysis. After multivariate adjustment, poor glycemic control also had increased risk of overall and disease-specific mortality [HR 1.72 (95% CI 1.02-2.88) and 1.65 (95% CI 0.89-3.08), respectively]. Poor glycemic control did not increase the risk of overall or disease-specific mortality in patients with stages 0-II disease but significantly increased this risk in those with stages III-IV disease [HR 2.05 (1.14-3.69) and 1.95 (1.01-3.80), respectively]. CONCLUSIONS Poor glycemic control is an independent risk factor for overall and disease-specific mortality after esophagectomy for advanced-stage ESCC.
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Affiliation(s)
- Akihiko Okamura
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Yu Imamura
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Masaru Hayami
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Takanori Kurogochi
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Shinji Mine
- Department of Gastroenterological Surgery, Gastroenterology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
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