Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Department of Urology, The Helen Diller Family Comprehensive Cancer Center, University of California, 2340 Sutter Street, San Francisco, CA 94115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2008; 105(24):8369-74. DOI: 10.1073/pnas.0803080105
Source: PubMed


Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.

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    • "Assuming a 10% dropout rate (including patients who are treated before progression), we are enrolling a total of 464 patients. We based the expected 10% dropout rate on our pilot study, in which the observed dropout rate was 2%; for this trial, we conservatively assigned an expected 5-fold increase in the dropout rate compared to the pilot [21]. We are stratifying randomization by age (b 70 years versus ≥70 years), race (African American versus other) and—to account for any additional prostate biopsies performed after the diagnostic baseline prostate biopsy but prior to study entry—time since baseline prostate biopsy (≤12 months prior to registration versus N 12 months prior to registration). "
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    ABSTRACT: Background: Diet may substantially alter prostate cancer initiation and progression. However, large-scale clinical trials of diet modification have yet to be performed for prostate cancer. The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) is investigating the effect of increased vegetable consumption on clinical progression in men with localized prostate cancer. Study design: MEAL is a randomized, phase III clinical trial designed to test whether an intervention that increases vegetable intake will decrease the incidence of clinical progression in men with clinically localized prostate cancer on active surveillance. We are randomizing 464 patients to either a validated telephone-based diet counseling intervention or a control condition in which patients receive a published diet guideline. The intervention will continue for two years. The primary outcome variable is clinical progression defined by serum prostate-specific antigen (PSA) and pathological findings on follow-up prostate biopsy. Secondary outcome variables include incidence of surgical and non-surgical treatments for prostate cancer, prostate-cancer related patient anxiety and health-related quality of life. Conclusion: The MEAL Study is assessing the effectiveness of a high-vegetable diet intervention for preventing clinical progression in men with localized prostate cancer on active surveillance.
    Contemporary Clinical Trials 05/2014; 38(2). DOI:10.1016/j.cct.2014.05.002 · 1.94 Impact Factor
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    • "Social influences on gene expression can also penetrate surprisingly deeply into the body to remodel basal transcriptomes within several bodily tissues including the breast (Williams et al., 2009), lymph nodes (Sloan et al., 2007), and brain (Berton et al., 2006; Drnevich et al., 2012; Karssen et al., 2007; Weaver, Meaney, & Szyf, 2006). Similar effects have also been observed for diseased tissues, such as ovarian cancers (Lutgendorf et al., 2009), prostate cancers (Ornish et al., 2008), breast cancers (Sloan et al., 2010), and ischemic brain injuries (Karelina et al., 2009; see Cole, in press). Although additional research is needed to evaluate how widespread and deep the effects of social adversity on gene expression are, the fact that social influences can remodel transcriptional activity in the brain (and not just in the periphery of the body) is particularly important because it provides a biologically plausible explanation for how social adversity may elicit the wide range of neural, psychological, and behavioral alterations that characterize mental and physical health problems that have been associated with adverse social-environmental circumstances. "
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    ABSTRACT: Although we generally experience our bodies as being biologically stable across time and situations, an emerging field of research is demonstrating that external social conditions, especially our subjective perceptions of those conditions, can influence our most basic internal biological processes-namely, the expression of our genes. This research on human social genomics has begun to identify the types of genes that are subject to social-environmental regulation, the neural and molecular mechanisms that mediate the effects of social processes on gene expression, and the genetic polymorphisms that moderate individual differences in genomic sensitivity to social context. The molecular models resulting from this research provide new opportunities for understanding how social and genetic factors interact to shape complex behavioral phenotypes and susceptibility to disease. This research also sheds new light on the evolution of the human genome and challenges the fundamental belief that our molecular makeup is relatively stable and impermeable to social-environmental influence.
    07/2013; 1(3):331-348. DOI:10.1177/2167702613478594
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    • "Adhering to a broader " evidence house " [23], there are some compelling trends of emerging CAM research that may hint at promising directions of how to strategically synthesize evidence and contribute to evidence-based integrative health care development and reform. Examples may range from evidence derived from small clinical trials on the advantageous effects of intense lifestyle changes and even mindfulness-based meditation on gene expression, where disease-promoting genes are down regulated and disease-preventing genes are up regulated and where telomerase mediated genomic integrity improves [24] [25] [26], to large health economic registry studies, indicating that patients whose general practitioner knows CAM, tend to have lower costs and live longer [27]. Findings from our own extensive mixed methods clinical research in primary and emergency care suggest that IC services are feasible and effective [28] [29] [30] [31] with the results from primary care described in more detail in Box 2. On-going health registry studies in Sweden add to these trends by showing that chronically ill patients with pain or stress disorders seem to increase their quality of life and self-rated health after intensive periods of anthroposophic integrative care in a cost-effective manner at economic threshold levels likely to be compatible with implementing new health technologies in Sweden [32]. "
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    ABSTRACT: Introduction The concept of integrative medicine/care – often referred to as the new medicine – typically signifies a sound combination of safe and effective ancient traditional medicine or complementary and alternative medicine, and state-of-the-art conventional medicine. In this opinion article, we draw on a decade of research and development including our own experiences in low-, middle- and high-income countries, by means of qualitative and quantitative research approaches, and explore trends vital to the development of evidence-informed integrative care and communication systems. Discussion Proponents suggest that an integrative health care system with a diversity of therapeutic options – and no particular differentiation between any evidence-informed health care paradigms – might be the best way to revitalize health care and reduce societal health care costs. Opponents argue – based on reasoning common to followers of scientism – that such developments constitute pseudoscience and will effectively overburden the healthcare system. Integrating insights from medicine, the humanities, ethics and philosophy in a health care model, which combines high-tech conventional health care with ancient health care systems and therapies, with the aim to achieve a pluralistic, accessible, affordable, safe and effective health system is clearly a challenge, but one which in fact has been recommended by the Director General of the WHO. Conclusion To maintain a polarized situation in the light of the growing demand for person-centred health care services, is unhelpful to nations and patients alike, detrimental to therapeutic relationships and may even occasionally be dangerous.
    European Journal of Integrative Medicine 01/2013; 6(1). DOI:10.1016/j.eujim.2013.09.005 · 0.78 Impact Factor
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