Signals from the Adipose Microenvironment and the Obesity-Cancer Link-A Systematic Review.
01 Sep 2017-Cancer Prevention Research (American Association for Cancer Research Inc.)-Vol. 10, Iss: 9, pp 494-506
TL;DR: Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL6, TNFα, and other mechanisms may lead to new targets and strategies for decreasing the burden of obesity-related cancers.
Abstract: Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiologic, clinical, and preclinical data suggest that within the growth-promoting, proinflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct "crosstalk" between adipose tissue and carcinomas in humans. We identified 4,641 articles with n = 20 human clinical studies, which are summarized as: (i) breast (n = 7); (ii) colorectal (n = 4); (iii) esophageal (n = 2); (iv) esophageal/colorectal (n = 1); (v) endometrial (n = 1); (vi) prostate (n = 4); and (vii) ear-nose-throat (ENT) cancer (n = 1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL6, TNFα, and other mechanisms. Moreover, visceral white adipose tissue plays a more central role, as it is more bioenergetically active and is associated with a more procancer secretome than subcutaneous adipose tissue. Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers. Cancer Prev Res; 10(9); 494-506. ©2017 AACR.
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Lawrence Berkeley National Laboratory1, Buck Institute for Research on Aging2, Lund University3, University of California, San Francisco4, National Institutes of Health5, University College London6, Harvard University7, Columbia University Medical Center8, Emory University9, University of Milan10, Humanitas University11, Queen Mary University of London12, Stanford University13, Albert Einstein College of Medicine14, Veterans Health Administration15, University of California, Los Angeles16, European University of Madrid17
TL;DR: The multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress are described.
Abstract: Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.
1,708 citations
Icahn School of Medicine at Mount Sinai1, Boston University2, Ohio State University3, University of Alabama at Birmingham4, Harborview Medical Center5, Harvard University6, Northwestern University7, Providence Health & Services8, University of Texas Health Science Center at San Antonio9, Brigham and Women's Hospital10, American Association of Clinical Endocrinologists11, University of Arizona12, Mayo Clinic13, Gundersen Health System14, University of Texas Health Science Center at Houston15, Geisinger Health System16
TL;DR: These updated clinical practice guidelines for bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity and clinical decision-making should be evidence-based within the context of a chronic disease.
302 citations
Icahn School of Medicine at Mount Sinai1, Mount Sinai Hospital2, Boston University3, Ohio State University4, University of Alabama at Birmingham5, Veterans Health Administration6, Harborview Medical Center7, Harvard University8, Northwestern University9, Providence Health & Services10, University of Texas Health Science Center at San Antonio11, Brigham and Women's Hospital12, American Association of Clinical Endocrinologists13, University of Arizona14, Mayo Clinic15, Gundersen Health System16, University of Texas Health Science Center at Houston17, Geisinger Health System18
TL;DR: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity and clinical decision-making should be evidence-based within the context of a chronic disease.
245 citations
TL;DR: This review summarizes recent evidence, documenting many alterations in the content and composition of fatty acids, polar lipids, oxylipins and triacylglycerols in CRC patients’ sera, tumor tissues and adipose tissue.
Abstract: Altered metabolism of lipids is currently considered a hallmark characteristic of many malignancies, including colorectal cancer (CRC). Lipids are a large group of metabolites that differ in terms of their fatty acid composition. This review summarizes recent evidence, documenting many alterations in the content and composition of fatty acids, polar lipids, oxylipins and triacylglycerols in CRC patients’ sera, tumor tissues and adipose tissue. Some of altered lipid molecules may be potential biomarkers of CRC risk, development and progression. Owing to a significant role of many lipids in cancer cell metabolism, some of lipid metabolism pathways may also constitute specific targets for anti-CRC therapy.
192 citations
Icahn School of Medicine at Mount Sinai1, Boston University2, Ohio State University3, University of Alabama at Birmingham4, Harborview Medical Center5, Harvard University6, Northwestern University7, Providence Health & Services8, University of Texas Health Science Center at San Antonio9, Brigham and Women's Hospital10, University of Arizona11, Mayo Clinic12, Gundersen Health System13, University of Texas Health Science Center at Houston14, Geisinger Health System15
TL;DR: The updated clinical practice guidelines (CPGs) were developed by the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), American Society for Metabolic and Bariatric Surgery (ASMBS), Obesity Medicine Association (OMA), and American Society of Anesthesiologists (ASA) Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists as mentioned in this paper.
Abstract: Objective The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), American Society for Metabolic and Bariatric Surgery (ASMBS), Obesity Medicine Association (OMA), and American Society of Anesthesiologists (ASA) Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists. Methods Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts. Results New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest). Conclusions Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues.
128 citations
References
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
"Signals from the Adipose Microenvir..." refers background in this paper
...Adipose tissue–induced inflammation Inflammation, a hallmark of cancer (4), has been linked to obesity and cancer in both epidemiologic and preclinical research (15)....
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...The interactions between an evolving tumor and its microenvironment are known to involve a complex interplay among multiple cells, local and systemic secreted mediators, and other components (4, 5)....
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TL;DR: A reporting guideline is described, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015), which consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review.
Abstract: Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
14,708 citations
"Signals from the Adipose Microenvir..." refers methods in this paper
...Preferred Reporting Items for Systematic Reviews and Meta Analyses Protocols (PRISMA) flow diagram (63)....
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TL;DR: Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults.
Abstract: Importance More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. Objective To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Design, Setting, and Participants Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. Main Outcomes and Measures In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). Results In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children ( P = .03) and women ( P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Conclusions and Relevance Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
7,532 citations
TL;DR: Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults.
Abstract: Importance More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. Objective To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Design, Setting, and Participants Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. Main Outcomes and Measures In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). Results In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children ( P = .03) and women ( P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Conclusions and Relevance Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
3,351 citations
"Signals from the Adipose Microenvir..." refers background in this paper
...In the United States, 38% of adults are obese, defined as having a body mass index (BMI) >30 kg/m(2), and nearly 8% are extremely obese, with a BMI > 40 kg/m(2) (2)....
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