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Brassetti A, Cacciatore L, Bove AM, Anceschi U, Proietti F, Misuraca L, Tuderti G, Flammia RS, Mastroianni R, Ferriero MC, Chiacchio G, D’Annunzio S, Pallares-Mendez R, Lombardo R, Leonardo C, De Nunzio C, Simone G. The Impact of Physical Activity on the Outcomes of Active Surveillance in Prostate Cancer Patients: A Scoping Review. Cancers (Basel) 2024; 16:630. [PMID: 38339381 PMCID: PMC10854832 DOI: 10.3390/cancers16030630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
INTRODUCTION Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. EVIDENCE ACQUISITION On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("prostate cancer" OR "prostate tumor") AND ("active surveillance") AND ("physical activity" OR "physical exercise" OR "physical intensive activity" OR "intensive exercise") AND ("lifestyle"). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. EVIDENCE SYNTHESIS We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. CONCLUSION Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.
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Affiliation(s)
- Aldo Brassetti
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Loris Cacciatore
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Alfredo Maria Bove
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Umberto Anceschi
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Flavia Proietti
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Leonardo Misuraca
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Gabriele Tuderti
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Rocco Simone Flammia
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Riccardo Mastroianni
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Maria Consiglia Ferriero
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Giuseppe Chiacchio
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Simone D’Annunzio
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Rigoberto Pallares-Mendez
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Riccardo Lombardo
- “Sapienza” University of Rome, Department of Urology, Via di Grottarossa 1035, 00189 Rome, Italy; (R.L.); (C.D.N.)
| | - Costantino Leonardo
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
| | - Cosimo De Nunzio
- “Sapienza” University of Rome, Department of Urology, Via di Grottarossa 1035, 00189 Rome, Italy; (R.L.); (C.D.N.)
| | - Giuseppe Simone
- IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00144 Rome, Italy; (A.B.); (A.M.B.); (U.A.); (F.P.); (L.M.); (G.T.); (R.S.F.); (R.M.); (M.C.F.); (G.C.); (S.D.); (R.P.-M.); (C.L.); (G.S.)
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Powers-James C, Morse M, Narayanan S, Ramondetta L, Lopez G, Wagner R, Cohen L. Integrative Oncology Approaches to Reduce Recurrence of Disease and Improve Survival. Curr Oncol Rep 2024; 26:147-163. [PMID: 38180690 DOI: 10.1007/s11912-023-01467-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2023] [Indexed: 01/06/2024]
Abstract
PURPOSE OF REVIEW After a cancer diagnosis, patients ask what they can do in addition to the recommended treatments to increase their survival. Many turn to integrative medicine modalities and lifestyle changes to improve their chances of survival. Numerous studies have demonstrated that lifestyle changes can significantly improve survival rates for cancer patients. Less support exists for the use of natural products or supplements to improve cancer survival. In this manuscript, we review key findings and evidence in the areas of healthy eating habits, physical activity, stress management and social support, and sleep quality, as well as natural products and supplements as they relate to the cancer recurrence and survival. RECENT FINDINGS While more research is needed to fully understand the mechanisms underlying the associations between lifestyle changes and cancer survival, findings suggest that lifestyle modifications in the areas of diet, physical activity, stress management and social support, and sleep quality improve clinical cancer outcomes. This is especially true for programs that modify more than one lifestyle habit. To date, outside of supplementing with vitamin D to maintain adequate levels, conflicting conclusion within the research remain regarding the efficacy of using natural products or supplement to improve cancer recurrence of disease or cancer survival. A call for further research is warranted. Lifestyle screening and counseling should be incorporated into cancer treatment plans to help improve patient outcomes. While the scientific community strives for the pursuit of high-quality research on natural products to enhance cancer survival, transparency, dialogue, and psychological safety between patients and clinicians must continue to be emphasized. Proactive inquiry by clinicians regarding patients' supplement use will allow for an informed discussion of the benefits and risks of natural products and supplements, as well as a re-emphasis of the evidence supporting diet and other lifestyle habits to increase survival.
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Affiliation(s)
- Catherine Powers-James
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
| | - Meroë Morse
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Santhosshi Narayanan
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Lois Ramondetta
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Gabriel Lopez
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Richard Wagner
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Lorenzo Cohen
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Unit 1414, 1515 Holcombe Blvd, Houston, TX, 77030, USA
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Lyu DW. Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review. Front Physiol 2024; 14:1292580. [PMID: 38239881 PMCID: PMC10794543 DOI: 10.3389/fphys.2023.1292580] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/11/2023] [Indexed: 01/22/2024] Open
Abstract
Successful application of cancer immunotherapy has rekindled hope in cancer patients. However, a number of patients are unresponsive to immunotherapy and related treatments. This unresponsiveness in cancer patients toward different treatment regimens can be mainly attributed to severe immune dysfunction in such patients. Several reports indicate that physical exercise can significantly lead to improved cancer patient outcomes. Since exercise gets immense response from the immune system, it can be utilized to improve immune function. Leukocytes with enhanced functions are substantially mobilized into the circulation by a single bout of intense physical exercise. Chronic physical exercise results in greater muscle endurance and strength and improved cardiorespiratory function. This exercise regime is also useful in improving T-cell abundance and reducing dysfunctional T cells. The current available data strongly justify for future clinical trials to investigate physical exercise use as an adjuvant in cancer therapy; however, optimal parameters using exercise for a defined outcome are yet to be established. The components of the immune system associate with almost every tumorigenesis step. The inter-relationship between inflammation, cancer, and innate immunity has recently gained acceptance; however, the underlying cellular and molecular mechanisms behind this relationship are yet to be solved. Several studies suggest physical exercise-mediated induction of immune cells to elicit anti-tumorigenic effects. This indicates the potential of exercising in modulating the behavior of immune cells to inhibit tumor progression. However, further mechanistic details behind physical exercise-driven immunomodulation and anticancer effects have to be determined. This review aims to summarize and discuss the association between physical exercise and immune function modulation and the potential of exercise as an adjuvant therapy in cancer prevention and treatment.
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Affiliation(s)
- Da-wei Lyu
- Physical Education and Health School, East China Jiaotong University, Nanchang, Jiangxi, China
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Stokes SD, Lewis CC, Mayberry TG, Wakefield MR, Fang Y. A holistic approach to prostate cancer treatment: natural products as enhancers to a medically minded approach. Med Oncol 2023; 40:343. [PMID: 37906337 DOI: 10.1007/s12032-023-02209-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 10/03/2023] [Indexed: 11/02/2023]
Abstract
Prostate cancer (PC) has historically been the most diagnosed cancer in men. Though treatment for prostate cancer is often effective, it is also often very taxing on the body and commonly has negative quality of life implications. One such example is androgen suppression therapy (AST), which has severe side effects that can be mitigated through physical activity. Natural agents and protocols are increasingly studied for their merit against cancer and for their potential to treat cancer in ways that preserve the quality of life. Many agents and lifestyle choices have been shown to have success against prostate cancer. There is promising evidence that simple treatments such as green tea, pomegranate, and a regular exercise routine can be effective against prostate cancer. These treatments have the potential to enhance current treatment protocols. In this review, we will discuss the viability of many natural agents as treatments for prostate cancer and its complications.
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Affiliation(s)
- Sydney D Stokes
- Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, 50312, USA
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA
| | - Cade C Lewis
- Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, 50312, USA
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA
| | - Trenton G Mayberry
- Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, 50312, USA
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA
| | - Mark R Wakefield
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA
- Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO, 65212, USA
| | - Yujiang Fang
- Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, 50312, USA.
- Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
- Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
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Exercise Improves Redox Homeostasis and Mitochondrial Function in White Adipose Tissue. Antioxidants (Basel) 2022; 11:antiox11091689. [PMID: 36139762 PMCID: PMC9495527 DOI: 10.3390/antiox11091689] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 12/02/2022] Open
Abstract
Exercise has beneficial effects on energy balance and also improves metabolic health independently of weight loss. Adipose tissue function is a critical denominator of a healthy metabolism but the adaptation of adipocytes in response to exercise is insufficiently well understood. We have previously shown that one aerobic exercise session was associated with increased expression of antioxidant and cytoprotective genes in white adipose tissue (WAT). In the present study, we evaluate the chronic effects of physical exercise on WAT redox homeostasis and mitochondrial function. Adult male Wistar rats were separated into two groups: a control group that did not exercise and a group that performed running exercise sessions on a treadmill for 30 min, 5 days per week for 9 weeks. Reactive oxygen species (ROS) generation, antioxidant enzyme activities, mitochondrial function, markers of oxidative stress and inflammation, and proteins related to DNA damage response were analyzed. In WAT from the exercise group, we found higher mitochondrial respiration in states I, II, and III of Complex I and Complex II, followed by an increase in ATP production, and the ROS/ATP ratio when compared to tissues from control rats. Regarding redox homeostasis, NADPH oxidase activity, protein carbonylation, and lipid peroxidation levels were lower in WAT from the exercise group when compared to control tissues. Moreover, antioxidant enzymatic activity, reduced glutathione/oxidized glutathione ratio, and total nuclear factor erythroid-2, like-2 (NFE2L2/NRF2) protein levels were higher in the exercise group compared to control. Finally, we found that exercise reduced the phosphorylation levels of H2AX histone (γH2AX), a central protein that contributes to genome stability through the signaling of DNA damage. In conclusion, our results show that chronic exercise modulates redox homeostasis in WAT, improving antioxidant capacity, and mitochondrial function. This hormetic remodeling of adipocyte redox balance points to improved adipocyte health and seems to be directly associated with the beneficial effects of exercise.
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Mandal S. Round up. Indian J Urol 2022; 38:85-90. [PMID: 35400875 PMCID: PMC8992724 DOI: 10.4103/iju.iju_84_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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The Relationship Between Preoperative Physical Activity With American Society of Anesthesiologists Score and Postoperative Length of Stay in Patients Undergoing Radical Prostatectomy. J Phys Act Health 2021; 19:29-36. [PMID: 34740993 DOI: 10.1123/jpah.2021-0314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/15/2021] [Accepted: 09/08/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND The relationship between preoperative physical activity (PA) and hospital length of stay (LOS) following radical prostatectomy (RP) is poorly understood. In addition, the relationship between PA and the American Society of Anesthesiologists Physical Status score (ASA PS), an established prognosticator of surgical risk, has not been studied. The authors assessed the relationship between leisure-time PA (LTPA), ASA PS, and LOS in individuals undergoing RP. METHODS This retrospective cohort study was conducted using data from an institutional database. Ordinal logistic regression was used to assess the relationship between preoperative LTPA and physical status as indicated by the ASA PS. Binary logistic regression was used to assess the relationship between preoperative LTPA and LOS. RESULTS A sample of 1064 participants were included in the analyses. The participants in the highest preoperative LTPA quartile had 45% reduced odds (P = .015) of a worse ASA PS classification compared with participants in the lowest quartile. The participants engaging in vigorous LTPA preoperatively had 35% lower odds (P = .014) of a >2-day LOS following RP compared with participants who were not engaging in preoperative vigorous LTPA. CONCLUSIONS Our findings suggest that total and vigorous preoperative LTPA is associated with improved preoperative American Society of Anesthesiologists scores and LOS following RP, respectively.
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Thomas R, Kenfield SA, Yanagisawa Y, Newton RU. Why exercise has a crucial role in cancer prevention, risk reduction and improved outcomes. Br Med Bull 2021; 139:100-119. [PMID: 34426823 PMCID: PMC8431973 DOI: 10.1093/bmb/ldab019] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/30/2021] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Exercise is one of several factors known to lower the risk of developing cancer, as well as improve outcomes in patients already diagnosed. People who exercise after cancer have lower rates of cancer complications, treatment toxicities, relapse and improved survival. This review highlights the supportive data and biochemical processes, which explain these potential benefits. SOURCES OF DATA PubMed, Embase, Medline and Cochrane libraries were searched for papers which addressed the effects of exercise and physical activity on cancer for this review. The search terms used were physical activity, exercise and cancer up to February 2021. We also referred to the background research required for international exercise intervention study involving men with prostate cancer (INTERVAL-GAP4) and scrutinized references within the robust papers published on this subject to ensure we did not miss any clinically studies. One hundred and eighty eight papers were included. AREAS OF AGREEMENT Exercise programmes mitigate many of the complications and risks associated with cancer, particularly thromboembolism, fatigue, weight gain, arthralgia, cognitive impairment and depression. AREAS OF CONTROVERSY Molecular and biomarker changes, resulting from exercise, suggest that exercise elicits beneficial changes in insulin-related pathways, down-regulates inflammation and serum oestrogen levels, and enhances oxidative, immune and cellular repair pathways. Nonetheless, the evidence remains preliminary. GROWING POINTS The timing, intensity and challenges of prehabilitation, adjunct and rehabilitation exercise programmes are being increasingly understood but their implementation remains sporadic. AREAS FOR DEVELOPING RESEARCH More robust clinical trial data are needed to substantiate a causal effect of exercise on overall and cancer-specific survival. These studies are ongoing. Research evaluating the most cost-efficient ways of incorporating prehabilitation, adjunct and rehabilitation programmes into routine practice would be helpful to funding bodies and health care strategists.
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Affiliation(s)
- Robert Thomas
- Department of Oncology, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
| | - Stacey A Kenfield
- Departments of Urology and Epidemiology and Biostatistics, University of California at San Francisco, Mission Hall, Box 1695-550, 16th Street, 6th Floor, San Francisco, CA 9414, USA
| | - Yuuki Yanagisawa
- Department of Medicine, Bedford Hospital, Kempston road, Bedford MK42 9DJ, UK
| | - Robert U Newton
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Perth, WA 6027, Australia
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Wu J, Fang X, Xia X. Identification of Key Genes and Pathways associated with Endometriosis by Weighted Gene Co-expression Network Analysis. Int J Med Sci 2021; 18:3425-3436. [PMID: 34522169 PMCID: PMC8436105 DOI: 10.7150/ijms.63541] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/26/2021] [Indexed: 12/22/2022] Open
Abstract
Background: Endometriosis is a common gynecological disorder with high rates of infertility and pelvic pain. However, its pathogenesis and diagnostic biomarkers remain unclear. This study aimed to elucidate potential hub genes and key pathways associated with endometriosis in ectopic endometrium (EC) and eutopic endometrium (EU). Material and Method: EC and EU-associated microarray datasets were obtained from the gene expression omnibus (GEO) database. Gene set enrichment analysis was performed to obtain further biological insight into the EU and EC-associated genes. Weighted gene co-expression network analysis (WGCNA) was performed to find clinically significant modules of highly-correlated genes. The hub genes that belong to both the weighted gene co-expression network and protein-protein interaction (PPI) network were identified using a Venn diagram. Results: We obtained EC and EU-associated microarray datasets GSE7305 and GSE120103. Genes in the EC were mainly enriched in the immune response and immune cell trafficking, and genes in the EU were mainly enriched in stress response and steroid hormone biosynthesis. PPI networks and weighted gene co-expression networks were constructed. An EC-associated blue module and an EU-associated magenta module were identified, and their function annotations revealed that hormone receptor signaling or inflammatory microenvironments may promote EU passing through the oviducts and migrating to the ovarian surfaces, and adhesion and immune correlated genes may induce the successful ectopic implantation of the endometrium (EC). Twelve hub genes in the EC and sixteen hub genes in the EU were recognized and further validated in independent datasets. Conclusion: Our study identified, for the first time, the hub genes and enrichment pathways in the EC and EU using WGCNA, which may provide a comprehensive understanding of the pathogenesis of endometriosis and have important clinical implications for the treatment and diagnosis of endometriosis.
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Affiliation(s)
- Jingni Wu
- Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, United States
| | - Xiaoling Fang
- Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Xiaomeng Xia
- Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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Brassetti A, Ferriero M, Napodano G, Sanseverino R, Badenchini F, Tuderti G, Anceschi U, Bove A, Misuraca L, Mastroianni R, Proietti F, Gallucci M, Simone G. Physical activity decreases the risk of cancer reclassification in patients on active surveillance: a multicenter retrospective study. Prostate Cancer Prostatic Dis 2021; 24:1151-1157. [PMID: 34007014 DOI: 10.1038/s41391-021-00375-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 04/13/2021] [Accepted: 04/23/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Physical activity (PA) is associated with favorable outcomes in prostate cancer (PCa) patients. We assessed its effect on the risk of PCa reclassification (PCaR) during active surveillance. METHODS Anthropometric, demographic, and clinical data concerning men diagnosed with a low-risk PCa and initially managed with active surveillance at the two participating institutions were retrospectively collected. The Physical Activity Scale for the Elderly (PASE) was used for patients' self-assessment of their daily exercise and their consequent stratification into three groups: sedentary (PASE ≤ 65), moderately active (65 < PASE < 125), active (PASE ≥ 125). Kaplan-Meier model was used to evaluate the predictive role of PA on PCaR, computed at 2, 5, 10 years after diagnosis; differences between lifestyle groups were assessed using the log-rank and uni-/multivariable Cox analyses applied to identify predictors of reclassification. RESULTS Eighty-five patients were included in the analysis, with a median age of 66 years (IQR: 59-70); 16% were active, 45% were former smokers, and 3 presented with metabolic syndrome (MetS). Prostate-specific antigen (PSA) density was 0.12 (IQR: 0.07-0.15); 34 men showed a PSA doubling time <10 years. The Median PASE score was 86 (IQR: 61.5-115.8): 24 patients were sedentary, 46 moderately active, and 15 active. At a median follow-up of 37 months (IQR: 14-53), 25% of patients experienced PCaR. These were less physically active (PASE score 69.3 vs 87.8; p = 0.056) and presented with significantly smaller prostates (46 ml vs 50.7 ml; p = 0.001) and a higher PSAD (0.14 vs 0.10; p = 0.019). At 2 years, the risk of reclassification was 25 ± 5%, while it was 38 ± 7% at both 5 and 10 years. The risk was significantly different in the three PA groups (Log Rank p = 0.033). PASE score was the only independent predictor of PCaR (HR: 0.987; 95%CI: 0.977-0.998; p = 0.016). CONCLUSIONS PA influences PCa evolution, as increasing levels are associated with a significantly reduced risk of tumor reclassification among patients undergoing active surveillance.
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Affiliation(s)
- Aldo Brassetti
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy.
| | | | - Giorgio Napodano
- Department of Urology, "Umberto I" Hospital, Nocera Inferiore, Italy
| | | | - Fabio Badenchini
- Department of Urology, Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Gabriele Tuderti
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
| | - Umberto Anceschi
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
| | - Alfredo Bove
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
| | - Leonardo Misuraca
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
| | | | - Flavia Proietti
- Department of Urology, "Sapienza" University of Rome, Rome, Italy
| | - Michele Gallucci
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy.,Department of Urology, "Sapienza" University of Rome, Rome, Italy
| | - Giuseppe Simone
- Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy
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11
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Matta L, Fonseca TS, Faria CC, Lima-Junior NC, De Oliveira DF, Maciel L, Boa LF, Pierucci APTR, Ferreira ACF, Nascimento JHM, Carvalho DP, Fortunato RS. The Effect of Acute Aerobic Exercise on Redox Homeostasis and Mitochondrial Function of Rat White Adipose Tissue. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:4593496. [PMID: 33603946 PMCID: PMC7868166 DOI: 10.1155/2021/4593496] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 12/01/2020] [Accepted: 01/16/2021] [Indexed: 12/21/2022]
Abstract
Physical exercise is characterized by an increase in physical and metabolic demand in face of physical stress. It is reported that a single exercise session induces physiological responses through redox signaling to increase cellular function and energy support in diverse organs. However, little is known about the effect of a single bout of exercise on the redox homeostasis and cytoprotective gene expression of white adipose tissue (WAT). Thus, we aimed at evaluating the effects of acute aerobic exercise on WAT redox homeostasis, mitochondrial metabolism, and cytoprotective genic response. Male Wistar rats were submitted to a single moderate-high running session (treadmill) and were divided into five groups: control (CTRL, without exercise), and euthanized immediately (0 h), 30 min, 1 hour, or 2 hours after the end of the exercise session. NADPH oxidase activity was higher in 0 h and 30 min groups when compared to CTRL group. Extramitochondrial ROS production was higher in 0 h group in comparison to CTRL and 2 h groups. Mitochondrial respiration in phosphorylative state increased in 0 h group when compared to CTRL, 30 min, 1, and 2 h groups. On the other hand, mitochondrial ATP production was lower in 0 h in comparison to 30 min group, increasing in 1 and 2 h groups when compared to CTRL and 0 h groups. CAT activity was lower in all exercised groups when compared to CTRL. Regarding oxidative stress biomarkers, we observed a decrease in reduced thiol content in 0 h group compared to CTRL and 2 h groups, and higher levels of protein carbonylation in 0 and 30 min groups in comparison to the other groups. The levels returned to basal condition in 2 h group. Furthermore, aerobic exercise increased NRF2, GPX2, HMOX1, SOD1, and CAT mRNA levels. Taken together, our results suggest that one session of aerobic exercise can induce a transient prooxidative state in WAT, followed by an increase in antioxidant and cytoprotective gene expression.
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Affiliation(s)
- Leonardo Matta
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Túlio S. Fonseca
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Caroline C. Faria
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | | | - Dahienne F. De Oliveira
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Leonardo Maciel
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Luiz F. Boa
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | | | - Andrea C. F. Ferreira
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
- NUMPEX, Duque de Caxias Campus, Federal University of Rio de Janeiro, Brazil
| | - José H. M. Nascimento
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Denise P. Carvalho
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
| | - Rodrigo S. Fortunato
- Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-590, Brazil
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12
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Pernar CH, Parmigiani G, Giovannucci EL, Rimm EB, Tyekucheva S, Loda M, Finn SP, Heiden MGV, Fiorentino M, Ebot EM, Mucci LA. Gene Expression Pathways in Prostate Tissue Associated with Vigorous Physical Activity in Prostate Cancer. Cancer Epidemiol Biomarkers Prev 2021; 30:751-756. [PMID: 33500320 DOI: 10.1158/1055-9965.epi-20-1461] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/10/2020] [Accepted: 01/08/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Men engaged in high physical activity have lower risks of advanced and fatal prostate cancer. Mechanisms underlying this association are not well understood but may include systemic and tumor-specific effects. We investigated potential mechanisms linking physical activity and gene expression in prostate tissue from men with prostate cancer. METHODS We included a subset of 118 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 1986 and 2005 with whole-transcriptome gene expression profiling on tumor and adjacent normal prostate tissue and physical activity data. Long-term vigorous physical activity was self-reported as the average time spent engaged in various forms of recreational physical activity at baseline and biennially until prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and Hallmark gene sets to identify pathways with differential expression based on vigorous physical activity. RESULTS In adjacent normal tissue, we identified 25 KEGG gene sets enriched (downregulated) in the highest compared with lowest quintile of vigorous physical activity at an FDR <0.10, including a number of cancer- and immune-related pathways. Although no gene sets reached statistical significance in tumor tissue, top gene sets differentially expressed included TGF beta, apoptosis, and p53 signaling pathways. CONCLUSIONS These findings suggest that physical activity may influence the tumor microenvironment. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to lethal prostate cancer. IMPACT Identification of gene expression alterations in the prostate associated with physical activity can improve our understanding of prostate cancer etiology.
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Affiliation(s)
- Claire H Pernar
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
| | - Giovanni Parmigiani
- Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Eric B Rimm
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Svitlana Tyekucheva
- Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Massimo Loda
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York
| | - Stephen P Finn
- Department of Histopathology, Trinity College, Dublin, Ireland.,Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Matthew G Vander Heiden
- Koch Institute for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Michelangelo Fiorentino
- Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.,Pathology Unit, Addarii Institute, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Ericka M Ebot
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Lorelei A Mucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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13
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Bellezza I, Riuzzi F, Chiappalupi S, Arcuri C, Giambanco I, Sorci G, Donato R. Reductive stress in striated muscle cells. Cell Mol Life Sci 2020; 77:3547-3565. [PMID: 32072237 PMCID: PMC11105111 DOI: 10.1007/s00018-020-03476-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 01/17/2020] [Accepted: 02/03/2020] [Indexed: 12/11/2022]
Abstract
Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/NAD+ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2-the master regulator of the antioxidant response-, consequent in most cases to defective autophagy, can lead to reductive stress. In addition, hyperglycemia-induced activation of the polyol pathway can lead to increased NADH/NAD+ ratio, which might translate into increased levels of hydrogen sulfide-via enhanced activity of cystathionine β-synthase-that would fuel reductive stress through inhibition of mitochondrial complex I. Reductive stress may be either a potential weapon against cancer priming tumor cells to apoptosis or a cancer's ally promoting tumor cell proliferation and making tumor cells resistant to reactive oxygen species-inducing drugs. In non-cancer pathological states reductive stress is definitely harmful paradoxically leading to reactive oxygen species overproduction via excess NADPH oxidase 4 activity. In face of the documented occurrence of reductive stress in several heart diseases, there is much less information about the occurrence and effects of reductive stress in skeletal muscle tissue. In the present review we describe relevant results emerged from studies of reductive stress in the heart and review skeletal muscle conditions in which reductive stress has been experimentally documented and those in which reductive stress might have an as yet unrecognized pathophysiological role. Establishing whether reductive stress has a (patho)physiological role in skeletal muscle will hopefully contribute to answer the question whether antioxidant supplementation to the general population, athletes, and a large cohort of patients (e.g. heart, sarcopenic, dystrophic, myopathic, cancer, and bronco-pulmonary patients) is harmless or detrimental.
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Affiliation(s)
- Ilaria Bellezza
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Francesca Riuzzi
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
| | - Sara Chiappalupi
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
| | - Cataldo Arcuri
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Ileana Giambanco
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
| | - Guglielmo Sorci
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy
- Centro Universitario Di Ricerca Sulla Genomica Funzionale, University of Perugia, 06132, Perugia, Italy
| | - Rosario Donato
- Department of Experimental Medicine, Medical School, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, Italy.
- Interuniversity Institute of Myology (IIM), University of Perugia, 06132, Perugia, Italy.
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14
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Perfil de força de preensão manual em pacientes idosos com câncer de próstata. SCIENTIA MEDICA 2020. [DOI: 10.15448/1980-6108.2020.1.35399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Objetivo: analisar o perfil de Força de Preensão Manual em pacientes idosos com câncer de próstata, atendidos em instituição hospitalar filantrópica do Recife.Métodos: estudo transversal com análise de dados secundários, coletados no Ambulatório de Oncogeriatria do Instituto de Medicina Integral Professor Fernando Figueira, utilizando uma amostra por conveniência com uma amostragem de 72 idosos. A análise estatística foi realizada utilizando o programa estatístico STATA 12. O teste de Kolmogorov-Smirnov foi aplicado a variáveis numéricas para se determinar a normalidade da amostra. Em caso de não normalidade, foi utilizado o teste de Mann-Whitney. Adotou-se o nível de significância de 0,05%.Resultados: observou-se uma Força de Preensão Manual reduzida nos pacientes com estadiamento de uma doença mais avançada quando comparado a outros estágios mais localizados ou clinicamente melhores (estadiamento I: 27,78 vs. estadiamento IV: 27,20 no braço dominante (p=0, 340)/ estadiamento I: 27,33 vs. estadiamento IV: 24,13 no braço não dominante) sendo esse resultado melhor reproduzido na mão não dominante (p=0,090). Por meio da análise das comorbidades (hipertensão, diabetes, cardiomiopatia e osteoartrite) em relação à mão dominante e não dominante, não foram verificadas diferenças significativas na Força de Preensão Manual na presença ou ausência das comorbidades analisadas tanto na mão dominante quanto da não dominante (p=0,189 vs.p=0,437).Conclusões: o estudo trouxe subsídios relevantes sobre a importância da Força de Preensão Manual como um importante parâmetro geral para força e um indicativo de saúde, principalmente quando analisados em idosos com câncer, onde afeta significativamente sua função física e neuromuscular, incluindo atrofia muscular, diminuição da força muscular e diminuição do desempenho funcional em atividades diárias, comprometendo significativamente a qualidade de vida e seu prognóstico.
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15
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Feng Y, Powell L, Vassallo AJ, Hamer M, Stamatakis E. Does adequate physical activity attenuate the associations of alcohol and alcohol‐related cancer mortality? A pooled study of 54 686 British adults. Int J Cancer 2020; 147:2754-2763. [DOI: 10.1002/ijc.33052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 04/16/2020] [Accepted: 04/24/2020] [Indexed: 12/22/2022]
Affiliation(s)
- Yingyu Feng
- Kolling Institute, Northern Clinical School University of Sydney Sydney New South Wales Australia
| | - Lauren Powell
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Amy Jo Vassallo
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Mark Hamer
- UCL Faculty Medical Sciences Institute Sport Exercise & Health London UK
| | - Emmanuel Stamatakis
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
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16
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Arefin S, Buchanan S, Hobson S, Steinmetz J, Alsalhi S, Shiels PG, Kublickiene K, Stenvinkel P. Nrf2 in early vascular ageing: Calcification, senescence and therapy. Clin Chim Acta 2020; 505:108-118. [PMID: 32097628 DOI: 10.1016/j.cca.2020.02.026] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 02/19/2020] [Accepted: 02/20/2020] [Indexed: 12/15/2022]
Abstract
Under normal physiological conditions, free radical generation and antioxidant defences are balanced, and reactive oxygen species (ROS) usually act as secondary messengers in a plethora of biological processes. However, when this balance is impaired, oxidative stress develops due to imbalanced redox homeostasis resulting in cellular damage. Oxidative stress is now recognized as a trigger of cellular senescence, which is associated with multiple chronic 'burden of lifestyle' diseases, including atherosclerosis, type-2 diabetes, chronic kidney disease and vascular calcification; all of which possess signs of early vascular ageing. Nuclear factor erythroid 2-related factor 2 (Nrf2), termed the master regulator of antioxidant responses, is a transcription factor found to be frequently dysregulated in conditions characterized by oxidative stress and inflammation. Recent evidence suggests that activation of Nrf2 may be beneficial in protecting against vascular senescence and calcification. Both natural and synthetic Nrf2 agonists have been introduced as promising drug classes in different phases of clinical trials. However, overexpression of the Nrf2 pathway has also been linked to tumorigenesis, which highlights the requirement for further understanding of pathways involving Nrf2 activity, especially in the context of cellular senescence and vascular calcification. Therefore, comprehensive translational pre-clinical and clinical studies addressing the targeting capabilities of Nrf2 agonists are urgently required. The present review discusses the impact of Nrf2 in senescence and calcification in early vascular ageing, with focus on the potential clinical implications of Nrf2 agonists and non-pharmacological Nrf2 therapeutics.
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Affiliation(s)
- Samsul Arefin
- Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital, 14186 Stockholm, Sweden
| | - Sarah Buchanan
- Institute of Cancer Sciences, Wolfson Wohl CRC, ICS, MVLS, University of Glasgow, Glasgow, UK
| | - Sam Hobson
- Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital, 14186 Stockholm, Sweden
| | - Julia Steinmetz
- Rheumatology Unit, Dep. of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
| | - Shno Alsalhi
- Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital, 14186 Stockholm, Sweden; Research Center, Salahaddin University-Erbil, 44001 Erbil, Kurdistan-Region, Iraq
| | - Paul G Shiels
- Institute of Cancer Sciences, Wolfson Wohl CRC, ICS, MVLS, University of Glasgow, Glasgow, UK
| | - Karolina Kublickiene
- Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital, 14186 Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital, 14186 Stockholm, Sweden.
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17
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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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18
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Tu W, Wang H, Li S, Liu Q, Sha H. The Anti-Inflammatory and Anti-Oxidant Mechanisms of the Keap1/Nrf2/ARE Signaling Pathway in Chronic Diseases. Aging Dis 2019; 10:637-651. [PMID: 31165007 PMCID: PMC6538222 DOI: 10.14336/ad.2018.0513] [Citation(s) in RCA: 439] [Impact Index Per Article: 73.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 05/12/2018] [Indexed: 12/22/2022] Open
Abstract
Oxidative stress is defined as an imbalance between production of free radicals and reactive metabolites or [reactive oxygen species (ROS)] and their elimination by through protective mechanisms, including (antioxidants). This Such imbalance leads to damage of cells and important biomolecules and cells, with hence posing a potential adverse impact on the whole organism. At the center of the day-to-day biological response to oxidative stress is the Kelch-like ECH-associated protein 1 (Keap1) - nuclear factor erythroid 2-related factor 2 (Nrf2)- antioxidant response elements (ARE) pathway, which regulates the transcription of many several antioxidant genes that preserve cellular homeostasis and detoxification genes that process and eliminate carcinogens and toxins before they can cause damage. The redox-sensitive signaling system Keap1/Nrf2/ARE plays a key role in the maintenance of cellular homeostasis under stress, inflammatory, carcinogenic, and pro-apoptotic conditions, which allows us to consider it as a pharmacological target. Herein, we review and discuss the recent advancements in the regulation of the Keap1/Nrf2/ARE system, and its role under physiological and pathophysiological conditions, e.g. such as in exercise, diabetes, cardiovascular diseases, cancer, neurodegenerative disorders, stroke, liver and kidney system, etc. and such.
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Affiliation(s)
- Wenjun Tu
- Institute of Radiation Medicine, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
- Department of Neurosurgery, Beijing Tiantan Hospital of Capital Medical University, Beijing, China
- Center for Translational Medicine, Institutes of Stroke, Weifang Medical University, Weifang, China
| | - Hong Wang
- Institute of Biomedical Engineering, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Song Li
- Institute of Radiation Medicine, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Qiang Liu
- Institute of Radiation Medicine, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Hong Sha
- Institute of Biomedical Engineering, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
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19
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Gómez-Martín A, Martinez-Gonzalez LJ, Puche-Sanz I, Cozar JM, Lorente JA, Hernández AF, Alvarez-Cubero MJ. GSTM1 gene expression and copy number variation in prostate cancer patients-Effect of chemical exposures and physical activity. Urol Oncol 2018; 37:290.e9-290.e15. [PMID: 30595465 DOI: 10.1016/j.urolonc.2018.12.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 12/12/2018] [Accepted: 12/16/2018] [Indexed: 11/28/2022]
Abstract
BACKGROUND Many etiological factors have been related to prostate cancer (CaP) development, progression, and survival, such as age, population origin, geographic area, occupational exposures, and nutrition and lifestyle factors. However, physical activity affords health benefits to cancer patients, including those with CaP. Glutathione S-Transferases enzymes have been linked to CaP because of their role in the detoxification of a wide variety of potential carcinogens, steroid hormones and xenobiotics. Among the different glutathione S-transferases isoforms, null genotype for GSTM1 has been associated with an increased risk of CaP, although data are controversial. As the relationship between copy number variation and gene expression of GSTM1 in CaP remains unexplored, this study analyzed GSTM1 gene expression and/or dosage effect on CaP risk and aggressiveness. The potential protective role of physical activity was also explored. METHODS Three hundred and seventeen patients (159 non-CaP and 158 CaP) were recruited from the Service of Urology (Hospital Virgen de las Nieves, Granada, Spain) over the period 2012 to 2014 and were followed-up until January 2018 to ensure a correct classification of control and patients. Individuals were classified in each group based on histological analysis of tissue biopsy, along with data on PSA level, Gleason score and T stage in patients with biopsies positive for CaP. Individuals with a negative biopsy were considered as controls. All controls underwent a systematic 20-core ultrasound guided biopsy in order to limit the false negative rate. Genomic DNA was extracted from peripheral blood to determine the exact copy numbers of GSTM1, and RNA was extracted from prostate tissue samples to determine GSTM1 gene expression. Both analyses were performed using the qPCR method. A questionnaire was administered to all patients to assess environmental exposures, lifestyle, and physical activity. The association of GSTM1 copy number variation and expression with the rest of variables was assessed by chi-square test and the Mann-Whitney test. Multiple logistic regression was used to assess which factors were associated with the risk of CaP. RESULTS The presence of 1 or 2 copies of the GSTM1 gene was not less prevalent in CaP compared to non-CaP patients; however, a significant decreased GSTM1 gene expression was observed in CaP tissue relative to non-CaP tissue (P = 0.003). CaP patients with environmental exposure to dust and smoke, and smoking habit had a significantly decreased GSTM1 gene expression (and near-significantly decreased for living in urban areas) as compared to non-CaP patients with the same exposures. In addition, physical activity was significantly associated with a lower risk of CaP (P = 0.006) and with increased GSTM1 gene expression (P = 0.002). CONCLUSIONS A reduced GSTM1 gene expression in prostate tissue was observed in CaP patients with some environmental chemical exposures. Intriguingly, physical activity might play a protective role against CaP development, possibly as a result of increasing GSTM1 gene expression in prostate tissue. However, this observation warrants further confirmation.
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Affiliation(s)
- Antonio Gómez-Martín
- GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain
| | - Luis J Martinez-Gonzalez
- GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.
| | - Ignacio Puche-Sanz
- Service of Urology, University Hospital Virgen de las Nieves, Granada, Spain
| | - Jose M Cozar
- Service of Urology, University Hospital Virgen de las Nieves, Granada, Spain
| | - Jose A Lorente
- GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain; University of Granada, Legal Medicine and Toxicology Department, Faculty of Medicine, PTS, Granada, Spain
| | - Antonio F Hernández
- University of Granada, Legal Medicine and Toxicology Department, Faculty of Medicine, PTS, Granada, Spain
| | - Maria J Alvarez-Cubero
- GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain; University of Granada, Department of Biochemistry and Molecular Biology III, Faculty of Medicine, PTS, Granada, Spain
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Dai JY, Wang B, Wang X, Cheng A, Kolb S, Stanford JL, Wright JL. Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene. Cancer Epidemiol Biomarkers Prev 2018; 28:258-264. [PMID: 30464020 DOI: 10.1158/1055-9965.epi-18-0622] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 09/13/2018] [Accepted: 11/06/2018] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND There is preliminary evidence linking physical activity to better prostate cancer outcomes, though the molecular mechanisms underlying this association are not clear. METHODS In a Seattle-based cohort of patients diagnosed with clinically localized prostate cancer and prospective follow-up for outcomes (n = 1,354), we studied the association between self-reported vigorous physical activity and prostate cancer progression to a metastatic-lethal phenotype. A subset of patients had prostate cancer tissue samples available for investigating DNA methylation (Infinium HumanMethylation450 BeadChip array) and exercise (n = 524). RESULTS Patients who had vigorous physical activity at least once per week during the year before diagnosis (∼79% of the cohort) were significantly less likely to progress to metastatic-lethal prostate cancer compared with those who had vigorous physical activity less frequently (adjusted hazard ratio = 0.63; P = 0.029). Among the subset of men who had radical prostatectomy as primary treatment and tumor tissue available, a differentially methylated region (DMR) was identified (family-wise error rate = 0.03, hypomethylated in the weekly exercise group), with 9 methylation probes located in the promoter region of CRACR2A. This gene encodes a calcium binding protein involved in innate immune response. The methylation level of the nine CpGs was inversely correlated with CRACR2A gene expression (average correlation coefficient = -0.35). CONCLUSIONS Vigorous physical activity before diagnosis is associated with epigenetic alterations of CRACR2A and prostate cancer metastatic-lethal progression. IMPACT This analysis provides strong evidence for the association between vigorous physical activity and a less likelihood to develop metastatic-lethal progression, and a suggestive link between exercise and DNA methylation in the CRACRA2A gene.
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Affiliation(s)
- James Y Dai
- Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.
- Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington
| | - Bo Wang
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyu Wang
- Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington
| | - Anqi Cheng
- Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington
| | - Suzanne Kolb
- Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington
| | - Janet L Stanford
- Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington
| | - Jonathan L Wright
- Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington
- Department of Urology, University of Washington School of Medicine, Seattle, Washington
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Nrf2-Keap1 signaling in oxidative and reductive stress. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2018; 1865:721-733. [PMID: 29499228 DOI: 10.1016/j.bbamcr.2018.02.010] [Citation(s) in RCA: 1209] [Impact Index Per Article: 172.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 01/25/2018] [Accepted: 02/22/2018] [Indexed: 02/07/2023]
Abstract
Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocates to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription. In the present review we briefly introduce the Nrf2-Keap1 system and describe Nrf2 functions, illustrate the Nrf2-NF-κB cross-talk, and highlight the effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress.
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22
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Al Qadire M, Alkhalaileh M, ALBashtawy M. Lifestyle and Dietary Factors and Prostate Cancer Risk: A Multicentre Case-Control Study. Clin Nurs Res 2018; 28:992-1008. [PMID: 29426230 DOI: 10.1177/1054773818757311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This study aims to explore the association between fruit and vegetable intake, high fat, body mass index (BMI) score, physical activity, and the occurrence of prostate cancer among Jordanian men. A case-control study was conducted in three large referral hospitals. The sample included 165 prostate cancer patients in the case group and 177 healthy participants in the control group. The results showed that smoking (odds ratio [OR] = 0.32; 95% confidence interval [CI] = [0.18, 0.57]), a history of prostate infection (OR = 0.21; 95% CI = [0.11, 0.38]), high-fat intake (OR = 0.44; 95% CI = [0.23, 0.85]), and increased mean of BMI (OR = 1.08; 95% CI = [1.02, 1.13]) increased the likelihood of developing prostate cancer. Healthy diet and giving up smoking are recommended, as they may contribute to a reduction in the incidence of prostate cancer. More randomized clinical trials in this area are needed to strengthen the available evidence and reduce the effects of confounding variables.
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Seemann T, Pozzobom F, Vieira MDCS, Boing L, Machado Z, Guimarães ACDA. Influence of symptoms of depression on the quality of life of men diagnosed with prostate cancer. REVISTA BRASILEIRA DE GERIATRIA E GERONTOLOGIA 2018. [DOI: 10.1590/1981-22562018021.170114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Abstract Objective: to evaluate the prevalence of symptoms of depression among men diagnosed with prostate cancer and their association with quality of life and treatment-related factors. Methods: a cross-sectional study of 85 men with a mean age of 66±8 years who were diagnosed with prostate cancer was performed. The survey was based on a questionnaire with previously validated instruments which investigated social, demographic and economic characteristics, the history of the disease, quality of life (European Organization for Research and Treatment of Cancer Questionnaire C30 - EORTC QLQ-C30 / QLQ-PR25) and symptoms of depression (Beck Depression Inventory). The presence of symptoms of depression was considered an outcome, and statistical analyzes were performed using the Chi-square test, Fisher's exact test, Mann Whitney U test and Poisson regression (p<0.05). Results: significant results were found for quality of life in relation to symptoms of depression in the functional, global and symptomatic health scale (p<0.001). This demonstrates that the presence of symptoms of depression is related to a negative quality of life. Conclusions: for a greater understanding of prostate cancer and its consequences on the quality of life of patients it is important to consider possible disorders in psychological aspects caused by the illness, as symptoms of depression are frequent in patients undergoing treatment for prostate cancer.
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Recreational Physical Activity in Relation to Prostate Cancer–specific Mortality Among Men with Nonmetastatic Prostate Cancer. Eur Urol 2017; 72:931-939. [DOI: 10.1016/j.eururo.2017.06.037] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 06/24/2017] [Indexed: 11/20/2022]
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25
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Kerr J, Anderson C, Lippman SM. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol 2017; 18:e457-e471. [PMID: 28759385 PMCID: PMC10441558 DOI: 10.1016/s1470-2045(17)30411-4] [Citation(s) in RCA: 400] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 04/21/2017] [Accepted: 04/27/2017] [Indexed: 12/11/2022]
Abstract
The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels. Epidemiological studies show that the inclusion of wholegrain, fibre, fruits, and vegetables within diets are associated with reduced cancer risk, with diet during early life (age <8 years) having the strongest apparent association with cancer incidence. However, randomised controlled trials of diet-related factors have not yet shown any conclusive associations between diet and cancer incidence. Obesity is a key contributory factor associated with cancer risk and mortality, including in dose-response associations in endometrial and post-menopausal breast cancer, and in degree and duration of fatty liver disease-related hepatocellular carcinoma. Obesity produces an inflammatory state, characterised by macrophages clustered around enlarged hypertrophied, dead, and dying adipocytes, forming crown-like structures. Increased concentrations of aromatase and interleukin 6 in inflamed breast tissue and an increased number of macrophages, compared with healthy tissue, are also observed in women with normal body mass index, suggesting a metabolic obesity state. Emerging randomised controlled trials of physical activity and dietary factors and mechanistic studies of immunity, inflammation, extracellular matrix mechanics, epigenetic or transcriptional regulation, protein translation, circadian disruption, and interactions of the multibiome with lifestyle factors will be crucial to advance this field.
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Affiliation(s)
- Jacqueline Kerr
- Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA; Department of Family Medicine and Public Health, University of California, La Jolla, San Diego, CA, USA
| | - Cheryl Anderson
- Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA; Department of Family Medicine and Public Health, University of California, La Jolla, San Diego, CA, USA
| | - Scott M Lippman
- Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA; Department of Medicine, University of California, La Jolla, San Diego, CA, USA.
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26
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Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med 2017; 51:640-644. [PMID: 27993842 PMCID: PMC5466928 DOI: 10.1136/bjsports-2016-096343] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2016] [Indexed: 12/20/2022]
Abstract
AIM To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways. METHODS The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance. RESULTS 168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance. SUMMARY Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits.
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Affiliation(s)
| | - Stacey A Kenfield
- Department of Urology, University of California, San Francisco, California, USA
| | - Alfonso Jimenez
- Centre for Applied Biological and Exercise Sciences, Faculty of Health and Life Sciences, Coventry University, Coventry, UK
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27
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Galvão DA, Taaffe DR, Spry N, Gardiner RA, Taylor R, Risbridger GP, Frydenberg M, Hill M, Chambers SK, Stricker P, Shannon T, Hayne D, Zopf E, Newton RU. Enhancing active surveillance of prostate cancer: the potential of exercise medicine. Nat Rev Urol 2016; 13:258-65. [PMID: 26954333 DOI: 10.1038/nrurol.2016.46] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Active surveillance (AS) is a strategy for the management of patients with low-risk, localized prostate cancer, in which men undergo regular monitoring of serum PSA levels and tumour characteristics, using multiparametric MRI and repeat biopsy sampling, to identify signs of disease progression. This strategy reduces overtreatment of clinically insignificant disease while also preserving opportunities for curative therapy in patients whose disease progresses. Preliminary studies of lifestyle interventions involving basic exercise advice have indicated that exercise reduces the numbers of patients undergoing active treatment, as well as modulating the biological processes involved in tumour progression. Therefore, preliminary evidence suggests that lifestyle and/or exercise interventions might have therapeutic potential in this growing population of men with prostate cancer. However, several important issues remain unclear: the exact value of different types of lifestyle and exercise medicine interventions during AS; the biological mechanisms of exercise in delaying disease progression; and the influence of the anxieties and distress created by having a diagnosis of cancer without then receiving active treatment. Future studies are required to confirm and expand these findings and determine the relative contributions of each lifestyle component to specific end points and patient outcomes during AS.
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Affiliation(s)
- Daniel A Galvão
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia
| | - Dennis R Taaffe
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,School of Medicine, University of Wollongong, Wollongong, New South Wales 2522, Australia
| | - Nigel Spry
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia
| | - Robert A Gardiner
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,University of Queensland Medical School, 288 Herston Road, Herston, Brisbane, Queensland 4006, Australia.,Department of Urology, Royal Brisbane and Women's Hospital, Herston, Brisbane, Queensland 4029, Australia
| | - Renea Taylor
- Cancer Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia
| | - Gail P Risbridger
- Cancer Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia
| | - Mark Frydenberg
- Department of Surgery, Monash University, Melbourne, Victoria 3800, Australia
| | - Michelle Hill
- The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Suzanne K Chambers
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,Menzies Health Institute of Queensland, Griffith University, Brisbane, Queensland 4222, Australia
| | - Phillip Stricker
- Suite 1001, St Vincent's Prostate Cancer Centre, 438 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia
| | - Tom Shannon
- Suite 32, Hollywood Specialist Centre, 95 Monash Avenue, Nedlands Western Australia 6009, Australia
| | - Dickon Hayne
- Department of Surgery, University of Western Australia (M704), 35 Stirling Highway, Crawley, Western Australia 6009, Australia
| | - Eva Zopf
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,Institute of Cardiovascular Research and Sport Medicine, German Sport University, Graditzer Strasse 87D, Köln 50735, Germany
| | - Robert U Newton
- Exercise Medicine Research Institute, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia 6027, Australia.,University of Queensland Medical School, 288 Herston Road, Herston, Brisbane, Queensland 4006, Australia
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Maru GB, Hudlikar RR, Kumar G, Gandhi K, Mahimkar MB. Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials. World J Biol Chem 2016; 7:88-99. [PMID: 26981198 PMCID: PMC4768127 DOI: 10.4331/wjbc.v7.i1.88] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/04/2015] [Accepted: 11/25/2015] [Indexed: 02/05/2023] Open
Abstract
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our: (1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and (2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.
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29
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Houghton CA, Fassett RG, Coombes JS. Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality? OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:7857186. [PMID: 26881038 PMCID: PMC4736808 DOI: 10.1155/2016/7857186] [Citation(s) in RCA: 175] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 12/06/2015] [Indexed: 12/14/2022]
Abstract
The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements.
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Affiliation(s)
- Christine A. Houghton
- School of Human Movement and Nutrition Science, The University of Queensland, Brisbane, Australia
| | - Robert G. Fassett
- School of Human Movement and Nutrition Science, The University of Queensland, Brisbane, Australia
| | - Jeff S. Coombes
- School of Human Movement and Nutrition Science, The University of Queensland, Brisbane, Australia
- *Jeff S. Coombes:
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Abstract
Integrative oncology, the diagnosis-specific field of integrative medicine, addresses symptom control with nonpharmacologic therapies. Known commonly as "complementary therapies" these are evidence-based adjuncts to mainstream care that effectively control physical and emotional symptoms, enhance physical and emotional strength, and provide patients with skills enabling them to help themselves throughout and following mainstream cancer treatment. Integrative or complementary therapies are rational and noninvasive. They have been subjected to study to determine their value, to document the problems they ameliorate, and to define the circumstances under which such therapies are beneficial. Conversely, "alternative" therapies typically are promoted literally as such; as actual antitumor treatments. They lack biologic plausibility and scientific evidence of safety and efficacy. Many are outright fraudulent. Conflating these two very different categories by use of the convenient acronym "CAM," for "complementary and alternative therapies," confuses the issue and does a substantial disservice to patients and medical professionals. Complementary and integrative modalities have demonstrated safety value and benefits. If the same were true for "alternatives," they would not be "alternatives." Rather, they would become part of mainstream cancer care. This manuscript explores the medical and sociocultural context of interest in integrative oncology as well as in "alternative" therapies, reviews commonly-asked patient questions, summarizes research results in both categories, and offers recommendations to help guide patients and family members through what is often a difficult maze. Combining complementary therapies with mainstream oncology care to address patients' physical, psychologic and spiritual needs constitutes the practice of integrative oncology. By recommending nonpharmacologic modalities that reduce symptom burden and improve quality of life, physicians also enable patients to play a role in their care. Critical for most patients, this also improves the physician-patient relationship, the quality of cancer care, and the well-being of patients and their families.
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Affiliation(s)
- Gary Deng
- From the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Barrie Cassileth
- From the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY
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31
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Pettapiece-Phillips R, Kotlyar M, Chehade R, Salmena L, Narod SA, Akbari M, Jurisica I, Kotsopoulos J. Uninterrupted Sedentary Behavior Downregulates BRCA1 Gene Expression. Cancer Prev Res (Phila) 2015; 9:83-8. [DOI: 10.1158/1940-6207.capr-15-0291] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 10/21/2015] [Indexed: 11/16/2022]
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32
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Wekesa A, Harrison M, Watson RW. Physical activity and its mechanistic effects on prostate cancer. Prostate Cancer Prostatic Dis 2015; 18:197-207. [PMID: 25800589 DOI: 10.1038/pcan.2015.9] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 02/04/2015] [Accepted: 02/06/2015] [Indexed: 12/22/2022]
Abstract
Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes.
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Affiliation(s)
- A Wekesa
- UCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - M Harrison
- Department of Health, Sport and Exercise Science, Waterford Institute of Technology, Waterford, Ireland
| | - R W Watson
- UCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
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33
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Pettapiece-Phillips R, Narod SA, Kotsopoulos J. The role of body size and physical activity on the risk of breast cancer in BRCA mutation carriers. Cancer Causes Control 2015; 26:333-44. [PMID: 25579073 DOI: 10.1007/s10552-014-0521-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 12/23/2014] [Indexed: 01/18/2023]
Abstract
Women who inherit a BRCA mutation face a high lifetime risk of developing breast cancer. Given the high penetrance of these mutations, prevention is of extreme importance. Here, we review the literature regarding the role of body size and of physical activity in the context of BRCA-associated breast cancer. There is some evidence to support a protective role of a healthy body size and of regular physical activity among mutation carriers, particularly during adolescence or early adulthood. Factors which increase the physiologic expression of the normal copy of the BRCA1 or BRCA2 gene and thereby normalize protein levels, contribute to stem cell homeostasis, and/or affect hormone levels, might mitigate the effects of an inherited BRCA mutation. Preliminary evidence from one in vivo study and from one epidemiologic report suggests that an increase in BRCA1 mRNA expression occurs with increasing levels of physical activity. The prospect of changing lifestyle for the purpose of preventing breast cancer in high-risk women, complemented by mechanistic evidence, warrants evaluation in large-scale prospective studies.
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Affiliation(s)
- Rachael Pettapiece-Phillips
- Women's College Research Institute, Women's College Hospital, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, Canada
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34
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Gueritat J, Lefeuvre-Orfila L, Vincent S, Cretual A, Ravanat JL, Gratas-Delamarche A, Rannou-Bekono F, Rebillard A. Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of their single treatment in prostate cancer through inhibition of redox adaptation. Free Radic Biol Med 2014; 77:95-105. [PMID: 25236740 DOI: 10.1016/j.freeradbiomed.2014.09.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 09/02/2014] [Accepted: 09/03/2014] [Indexed: 12/14/2022]
Abstract
In preclinical models, exercise training (ET) or pomegranate juice (PJ) prevents prostate cancer progression. Here, we hypothesized that physical exercise combined with antioxidants could induce synergistic effects through oxidative stress modulation. Forty male Copenhagen rats with prostate tumors were divided into four groups: control, PJ, ET, and PJ+ET. Rats from the PJ group consumed 750 µl of PJ daily, rats from the ET group ran on a treadmill 5 days per week, and PJ+ET rats received the combined treatment. Each week, tumor growth was evaluated. After 4 weeks of treatment, the rats were euthanized and blood, muscles, and tumors were collected. Tumor Ki67, extracellular signal-regulated kinase (ERK) activation, Bcl-2 expression, and enzymatic and nonenzymatic antioxidant defenses, as well as oxidative stress markers (oxidized base, lipid peroxidation, protein carbonylation), were measured. PJ or ET significantly decreased prostate tumor proliferation (Ki67 staining, p<0.05) through the modulation of ERK phosphorylation, whereas the combination of treatments did not limit cancer progression. PJ significantly reduced Bcl-2 expression in tumors (p<0.05) and the combination of PJ and ET prevented this effect. PJ or ET increased enzymatic antioxidant defenses in muscle, PJ increased nonenzymatic antioxidant defenses in plasma and whole blood. In addition, PJ reduced TBARS and 8-oxodGuo levels in tumors as well as ET (p<0.05), whereas protein carbonyl levels were not affected by these two strategies. Paradoxically, association of PJ+ET did not increase antioxidant defenses and no reduction in oxidative stress markers was induced. Loading cancer cells with antioxidants blunts the positive effects of ET and interferes with important reactive oxygen species-mediated physiological processes such as antioxidant adaptations.
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Affiliation(s)
- Jordan Gueritat
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Luz Lefeuvre-Orfila
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Sophie Vincent
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Armel Cretual
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Jean-Luc Ravanat
- Laboratoire "Lésions des Acides Nucléiques," Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France
| | - Arlette Gratas-Delamarche
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Françoise Rannou-Bekono
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France
| | - Amélie Rebillard
- EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
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Abstract
For men with prostate cancer (PC), patient care and treatment recommendations should not focus solely on the disease but should also take into account the views of the patient. The diagnosis and consequences of monitoring or treatment should be fully explained. Recommending Active Surveillance (AS) for the monitoring of a proven low-risk, low-volume prostate cancer should ensure that the psychological impact of AS is taken into account and included in a holistic approach to patient and disease management. This article is a rapid literature search relating to AS, and how the psychological impact of a cancer diagnosis may influence patient choice.
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Affiliation(s)
- Paula Simpson
- Uro-Oncology Specialist Nurse at East Kent Hospitals University NHS Foundation Trust, Kent and Canterbury Hospital
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