Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention
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 st...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-06, Vol.105 (24), p.8369-8374 |
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| creator | Ornish, Dean Magbanua, Mark Jesus M Weidner, Gerdi Weinberg, Vivian Kemp, Colleen Green, Christopher Mattie, Michael D Marlin, Ruth Simko, Jeff Shinohara, Katsuto Haqq, Christopher M Carroll, Peter R |
| description | 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. |
| doi_str_mv | 10.1073/pnas.0803080105 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0803080105</identifier><identifier>PMID: 18559852</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Abdominal Fat ; Aged ; Aged, 80 and over ; Biological Sciences ; Biopsies ; Blood Pressure ; Body Weight ; Cardiovascular Diseases - epidemiology ; Diet ; diet therapy ; Down regulation ; gene down-regulation ; Gene expression ; Gene Expression Profiling ; gene expression regulation ; Gene Expression Regulation, Neoplastic ; gene induction ; gene up-regulation ; Genes ; Humans ; Life Style ; Lifestyle ; Male ; messenger RNA ; microarray technology ; Middle Aged ; Molecules ; Nutrition ; nutritional intervention ; obesity ; Obesity - epidemiology ; Pilot Projects ; Prospective Studies ; Prostate ; Prostate - metabolism ; Prostate cancer ; prostate gland ; prostatic neoplasms ; Prostatic Neoplasms - epidemiology ; Prostatic Neoplasms - genetics ; Proteins ; Ribonucleic acid ; Risk Factors ; RNA ; Studies ; Tumors ; Up-Regulation ; weight loss</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-06, Vol.105 (24), p.8369-8374</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 17, 2008</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-538cd41eccd62746c5c65a833b0456204cefa47ddfb43c10cef3ead0ad7f5ebf3</citedby><cites>FETCH-LOGICAL-c552t-538cd41eccd62746c5c65a833b0456204cefa47ddfb43c10cef3ead0ad7f5ebf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25462788$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25462788$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18559852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ornish, Dean</creatorcontrib><creatorcontrib>Magbanua, Mark Jesus M</creatorcontrib><creatorcontrib>Weidner, Gerdi</creatorcontrib><creatorcontrib>Weinberg, Vivian</creatorcontrib><creatorcontrib>Kemp, Colleen</creatorcontrib><creatorcontrib>Green, Christopher</creatorcontrib><creatorcontrib>Mattie, Michael D</creatorcontrib><creatorcontrib>Marlin, Ruth</creatorcontrib><creatorcontrib>Simko, Jeff</creatorcontrib><creatorcontrib>Shinohara, Katsuto</creatorcontrib><creatorcontrib>Haqq, Christopher M</creatorcontrib><creatorcontrib>Carroll, Peter R</creatorcontrib><title>Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Abdominal Fat</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological Sciences</subject><subject>Biopsies</subject><subject>Blood Pressure</subject><subject>Body Weight</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Diet</subject><subject>diet therapy</subject><subject>Down regulation</subject><subject>gene down-regulation</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>gene expression regulation</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>gene induction</subject><subject>gene up-regulation</subject><subject>Genes</subject><subject>Humans</subject><subject>Life Style</subject><subject>Lifestyle</subject><subject>Male</subject><subject>messenger RNA</subject><subject>microarray technology</subject><subject>Middle Aged</subject><subject>Molecules</subject><subject>Nutrition</subject><subject>nutritional intervention</subject><subject>obesity</subject><subject>Obesity - epidemiology</subject><subject>Pilot Projects</subject><subject>Prospective Studies</subject><subject>Prostate</subject><subject>Prostate - metabolism</subject><subject>Prostate cancer</subject><subject>prostate gland</subject><subject>prostatic neoplasms</subject><subject>Prostatic Neoplasms - epidemiology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>Risk Factors</subject><subject>RNA</subject><subject>Studies</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>weight loss</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EotuFMycg4oC4pB1_Jc4FCa3Kh1SJA_RseZ1J6lXWWWxn1f57HHbVBQ5wsCx7nnlnxq8JeUHhgkLNL3fexAtQwPOiIB-RBYWGlpVo4DFZALC6VIKJM3Ie4wYAGqngKTmjSspGSbYg_erW-B5j4XyxC2NMJmHRo8cC73YBY3Sjn2Nb9MXkWwz96HxfmPkyoY9uj4WfUnBpBo1vi8F1GNP9gL-IsEc_h56RJ50ZIj4_7kty8_Hq--pzef3105fVh-vSSslSKbmyraBobVuxWlRW2koaxfkahKwYCIudEXXbdmvBLYV85GhaMG3dSVx3fEneH3R303qLrc3Vgxn0LritCfd6NE7_GfHuVvfjXjPBgVUyC7w9CoTxx5Qn0VsXLQ6D8ThOUVcN48Ar-C9ImxoaoCqDb_4CN-MUfH4FzYDymkN2ckkuD5DNJsSA3UPLFPRstZ6t1ierc8ar3yc98UdvM_D6CMyZJzmZZ9WKV00m3v2b0N00DAnvUkZfHtBNTGN4YJkU2SelTsU6M2rTBxf1zbd5vPzn5oY5_wm3xtNU</recordid><startdate>20080617</startdate><enddate>20080617</enddate><creator>Ornish, Dean</creator><creator>Magbanua, Mark Jesus M</creator><creator>Weidner, Gerdi</creator><creator>Weinberg, Vivian</creator><creator>Kemp, Colleen</creator><creator>Green, Christopher</creator><creator>Mattie, Michael D</creator><creator>Marlin, Ruth</creator><creator>Simko, Jeff</creator><creator>Shinohara, Katsuto</creator><creator>Haqq, Christopher M</creator><creator>Carroll, Peter R</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080617</creationdate><title>Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention</title><author>Ornish, Dean ; Magbanua, Mark Jesus M ; Weidner, Gerdi ; Weinberg, Vivian ; Kemp, Colleen ; Green, Christopher ; Mattie, Michael D ; Marlin, Ruth ; Simko, Jeff ; Shinohara, Katsuto ; Haqq, Christopher M ; Carroll, Peter R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-538cd41eccd62746c5c65a833b0456204cefa47ddfb43c10cef3ead0ad7f5ebf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Abdominal Fat</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological Sciences</topic><topic>Biopsies</topic><topic>Blood Pressure</topic><topic>Body Weight</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Diet</topic><topic>diet therapy</topic><topic>Down regulation</topic><topic>gene down-regulation</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>gene expression regulation</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>gene induction</topic><topic>gene up-regulation</topic><topic>Genes</topic><topic>Humans</topic><topic>Life Style</topic><topic>Lifestyle</topic><topic>Male</topic><topic>messenger RNA</topic><topic>microarray technology</topic><topic>Middle Aged</topic><topic>Molecules</topic><topic>Nutrition</topic><topic>nutritional intervention</topic><topic>obesity</topic><topic>Obesity - epidemiology</topic><topic>Pilot Projects</topic><topic>Prospective Studies</topic><topic>Prostate</topic><topic>Prostate - metabolism</topic><topic>Prostate cancer</topic><topic>prostate gland</topic><topic>prostatic neoplasms</topic><topic>Prostatic Neoplasms - epidemiology</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>Risk Factors</topic><topic>RNA</topic><topic>Studies</topic><topic>Tumors</topic><topic>Up-Regulation</topic><topic>weight loss</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ornish, Dean</creatorcontrib><creatorcontrib>Magbanua, Mark Jesus M</creatorcontrib><creatorcontrib>Weidner, Gerdi</creatorcontrib><creatorcontrib>Weinberg, Vivian</creatorcontrib><creatorcontrib>Kemp, Colleen</creatorcontrib><creatorcontrib>Green, Christopher</creatorcontrib><creatorcontrib>Mattie, Michael D</creatorcontrib><creatorcontrib>Marlin, Ruth</creatorcontrib><creatorcontrib>Simko, Jeff</creatorcontrib><creatorcontrib>Shinohara, Katsuto</creatorcontrib><creatorcontrib>Haqq, Christopher M</creatorcontrib><creatorcontrib>Carroll, Peter R</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18559852</pmid><doi>10.1073/pnas.0803080105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Abdominal Fat Aged Aged, 80 and over Biological Sciences Biopsies Blood Pressure Body Weight Cardiovascular Diseases - epidemiology Diet diet therapy Down regulation gene down-regulation Gene expression Gene Expression Profiling gene expression regulation Gene Expression Regulation, Neoplastic gene induction gene up-regulation Genes Humans Life Style Lifestyle Male messenger RNA microarray technology Middle Aged Molecules Nutrition nutritional intervention obesity Obesity - epidemiology Pilot Projects Prospective Studies Prostate Prostate - metabolism Prostate cancer prostate gland prostatic neoplasms Prostatic Neoplasms - epidemiology Prostatic Neoplasms - genetics Proteins Ribonucleic acid Risk Factors RNA Studies Tumors Up-Regulation weight loss |
| title | Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention |
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