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Azam S, Peng C, Rosner BA, Goncalves MD, Phillips E, Eliassen H, Heine J, Hankinson SE, Tamimi RM. Plasma C-peptide mammographic features and risk of breast cancer. NPJ Breast Cancer 2024; 10:91. [PMID: 39420200 PMCID: PMC11487244 DOI: 10.1038/s41523-024-00702-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
Our study in the Nurses' Health Study (NHS) and NHS2, a nested case-control study with 1260 cases and 2221 controls, investigated the association between C-peptide levels, mammographic density (MD) parameters, V (a measure of gray scale variation), and breast cancer (BC) risk. We also examined how C-peptide and BC risk vary across quartiles of mammographic features. Linear and logistic regressions were used to study the associations between C-peptide and MD parameters, and breast cancer. C-peptide was inversely associated with percent MD and positively with non-dense area, but no associations were found with dense area and V measure. C-peptide was associated with an increased risk of invasive BC risk (top vs. bottom quartile, odds ratio = 1.46, 95% CI: 1.12-1.91). No multiplicative interactions were found between C-peptide, MD parameters, and BC risk. Our results suggest a positive association between C-peptide and BC risk, and MD parameters do not seem to modify this association.
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Affiliation(s)
- Shadi Azam
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
| | - Cheng Peng
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Bernard A Rosner
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | | | - Erica Phillips
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Heather Eliassen
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - John Heine
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Susan E Hankinson
- Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
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2
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Rogers CR, May FP, Petersen E, Brooks E, Lopez JA, Kennedy CD, Thiese MS. Factors Associated with Colorectal Cancer Prevalence Among Long-Haul Truck Drivers in the United States. Am J Health Promot 2022; 36:1142-1151. [PMID: 35410488 DOI: 10.1177/08901171221090500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To determine the age-adjusted association between colorectal cancer (CRC) risk factors and CRC prevalence among long-haul truck drivers (aged 21-85), after adjustment for age. DESIGN Pooled cross-sectional analysis using Commercial Driver Medical Exam (CDME) data. Setting. National survey data from January 1, 2005, to October 31, 2012. PARTICIPANTS 47,786 commercial motor vehicle drivers in 48 states. MEASURES CRC prevalence was the primary outcome; independent variables included demographics, body mass index (BMI), and concomitant medical conditions. ANALYSIS Kruskal-Wallis tests to analyze continuous variables; Fischer's exact tests to analyze categorical variables; univariate and multivariable logistic regression for rare events (Firth method) to quantify the association between the independent variables of interest and CRC prevalence. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, gender, years with current employer, year of exam, and BMI in a multivariate logistic regression. RESULTS Many factors were statistically significant. Obesity (OR = 3.14; 95% CI = 1.03-9.61) and increasing age (OR = 1.10 per year; 95% CI = 1.07-1.13) were significantly associated with CRC prevalence. Truckers with 4 or more concomitant medical conditions were significantly more likely to have CRC (OR = 7.03; 95% CI = 1.83-27.03). CONCLUSIONS Our findings highlight mutable risk factors and represent an opportunity for intervention that may decrease CRC morbidity and mortality among truck drivers, a unique population in the United States estimated to live up to 16 years less than the general population.
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Affiliation(s)
- Charles R Rogers
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Folasade P May
- Department of Medicine, University of California, Los Angeles, CA, USA
| | - Ethan Petersen
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Ellen Brooks
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Jasmine A Lopez
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Carson D Kennedy
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Matthew S Thiese
- Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
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3
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Simões LMFR, Tavares NAR, Ferreira-Pêgo C. Plant-Based Diet and IGF-1 Modulation on HER2-Positive Breast Cancer: A Lifestyle Medicine Nutrition Approach in Oncology. Am J Lifestyle Med 2022; 16:36-45. [PMID: 35185425 PMCID: PMC8848116 DOI: 10.1177/15598276211023048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2023] Open
Abstract
Breast cancer is the second most common type of cancer in women worldwide, where nutritional intervention should be part of a multidisciplinary lifestyle approach in oncology, promoting therapeutic success. Insulin-like growth factor 1 (IGF-1), along with estrogen, can promote the development of neoplastic cells in breast tissue. Cancers that develop under IGF-1 stimulation are often resistant to therapy. This case report describes a 47-year-old woman, body mass index 27.4 kg/m2, with HER2-positive breast cancer, as well as elevated blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Soon after her breast cancer diagnosis, she transitioned from a Western pattern diet (WPD) to a predominantly whole-food, plant-based diet (PWFPBD) for 1035 days, followed by 232 days of PWFPBD plus night fasting for 16 hours per day. IGF-1 decreased 22.38%, glycemia and total cholesterol decreased by -55.06% and -36.00% at the end of the first intervention and went up by 6.25%, and 3.87%, respectively, at the end of the second intervention. A PWFPBD, with or without 16-hour overnight fasting, seems to modulate plasma levels of IGF-1 on a 47-year-old woman diagnosed with breast cancer, type HER2-positive. Future research, should explore the physiologic and pathophysiological mechanisms and clarify whether this dietary strategy, may be clinically useful in preventing HER2-positive breast cancer.
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Affiliation(s)
- Laurinda M. F. R. Simões
- School of Sciences and Health Technologies, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal
| | - Nelson A. R. Tavares
- CBIOS-University Lusófona’s Research Center for Biosciences and Health Technologies, Lisbon, Portugal
| | - Cíntia Ferreira-Pêgo
- CBIOS-University Lusófona’s Research Center for Biosciences and Health Technologies, Lisbon, Portugal
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4
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Dowis K, Banga S. The Potential Health Benefits of the Ketogenic Diet: A Narrative Review. Nutrients 2021; 13:nu13051654. [PMID: 34068325 PMCID: PMC8153354 DOI: 10.3390/nu13051654] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/30/2021] [Accepted: 05/09/2021] [Indexed: 02/07/2023] Open
Abstract
Considering the lack of a comprehensive, multi-faceted overview of the ketogenic diet (KD) in relation to health issues, we compiled the evidence related to the use of the ketogenic diet in relation to its impact on the microbiome, the epigenome, diabetes, weight loss, cardiovascular health, and cancer. The KD diet could potentially increase genetic diversity of the microbiome and increase the ratio of Bacteroidetes to Firmicutes. The epigenome might be positively affected by the KD since it creates a signaling molecule known as β-hydroxybutyrate (BHB). KD has helped patients with diabetes reduce their HbA1c and reduce the need for insulin. There is evidence to suggest that a KD can help with weight loss, visceral adiposity, and appetite control. The evidence also suggests that eating a high-fat diet improves lipid profiles by lowering low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and lowering triglycerides (TG). Due to the Warburg effect, the KD is used as an adjuvant treatment to starve cancer cells, making them more vulnerable to chemotherapy and radiation. The potential positive impacts of a KD on each of these areas warrant further analysis, improved studies, and well-designed randomized controlled trials to further illuminate the therapeutic possibilities provided by this dietary intervention.
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5
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Mansor R, Holly J, Barker R, Biernacka K, Zielinska H, Koupparis A, Rowe E, Oxley J, Sewell A, Martin RM, Lane A, Hackshaw-McGeagh L, Perks C. IGF-1 and hyperglycaemia-induced FOXA1 and IGFBP-2 affect epithelial to mesenchymal transition in prostate epithelial cells. Oncotarget 2020; 11:2543-2559. [PMID: 32655839 PMCID: PMC7335671 DOI: 10.18632/oncotarget.27650] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 06/01/2020] [Indexed: 12/22/2022] Open
Abstract
Localized prostate cancer (PCa) is a manageable disease but for most men with metastatic disease, it is often fatal. A western diet has been linked with PCa progression and hyperglycaemia has been associated with the risk of lethal and fatal prostate cancer. Using PCa cell lines, we examined the impact of IGF-I and glucose on markers of epithelial-to-mesenchymal transition (EMT), migration and invasion. We examined the underlying mechanisms using cell lines and tumour tissue samples. IGF-I had differential effects on the process of EMT: inhibiting in normal and promoting in cancer cells, whereas hyperglycamia alone had a stimulatory effect in both. These effects were independent of IGF and in both cases, hyperglycaemia induced an increase IGFBP-2(tumour promoter) and FOXA1. A positive correlation existed between levels of IGFBP-2 and FOXA1 in benign and cancerous prostate tissue samples and in vitro and in vivo data indicated that FOXA1 strongly interacted with the IGFBP-2 gene in normal prostate epithelial cells that was associated with a negative regulation of IGFBP-2, whereas in cancer cells the level of FOXA1 associating with the IGFBP-2 gene was minimal, suggesting loss of this negative regulation. IGF-I and hyperglycaemia-induced FOXA1/IGFBP-2 play important roles in EMT.
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Affiliation(s)
- Rehanna Mansor
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
- Faculty of Medicine, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, MY
| | - Jeff Holly
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Rachel Barker
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Kalina Biernacka
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Hanna Zielinska
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
| | - Anthony Koupparis
- Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, UK
| | - Edward Rowe
- Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, UK
| | - Jon Oxley
- Department of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK
| | - Alex Sewell
- Department of Cellular Pathology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK
| | - Richard M. Martin
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Athene Lane
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Lucy Hackshaw-McGeagh
- NIHR Biomedical Research Centre, Level 3, University Hospitals Bristol Education Centre, Bristol, UK
| | - Claire Perks
- IGFs and Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Southmead Hospital, Bristol, UK
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6
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Kompella P, Vasquez KM. Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Mol Carcinog 2019; 58:1531-1550. [PMID: 31168912 PMCID: PMC6692207 DOI: 10.1002/mc.23048] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 05/08/2019] [Accepted: 05/10/2019] [Indexed: 12/16/2022]
Abstract
Obesity, defined as a state of positive energy balance with a body mass index exceeding 30 kg/m2 in adults and 95th percentile in children, is an increasing global concern. Approximately one-third of the world's population is overweight or obese, and in the United States alone, obesity affects one in six children. Meta-analysis studies suggest that obesity increases the likelihood of developing several types of cancer, and with poorer outcomes, especially in children. The contribution of obesity to cancer risk requires a better understanding of the association between obesity-induced metabolic changes and its impact on genomic instability, which is a major driving force of tumorigenesis. In this review, we discuss how molecular changes during adipose tissue dysregulation can result in oxidative stress and subsequent DNA damage. This represents one of the many critical steps connecting obesity and cancer since oxidative DNA lesions can result in cancer-associated genetic instability. In addition, the by-products of the oxidative degradation of lipids (e.g., malondialdehyde, 4-hydroxynonenal, and acrolein), and gut microbiota-mediated secondary bile acid metabolites (e.g., deoxycholic acid and lithocholic acid), can function as genotoxic agents and tumor promoters. We also discuss how obesity can impact DNA repair efficiency, potentially contributing to cancer initiation and progression. Finally, we outline obesity-related epigenetic changes and identify the gaps in knowledge to be addressed for the development of better therapeutic strategies for the prevention and treatment of obesity-related cancers.
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Affiliation(s)
- Pallavi Kompella
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Boulevard, Austin, TX 78723, USA
| | - Karen M. Vasquez
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Boulevard, Austin, TX 78723, USA
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7
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Cohen CW, Fontaine KR, Arend RC, Gower BA. A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial. Nutr Cancer 2019; 72:584-594. [PMID: 31352797 DOI: 10.1080/01635581.2019.1645864] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Ketogenic diets (KDs) are emerging as effective therapies for several chronic diseases, including cancer. However, concerns regarding safety and adherence may prevent clinicians from prescribing KDs. We hypothesized that a KD does not negatively affect blood lipid profile compared to a lower-fat diet in ovarian and endometrial cancer patients, and that KD subjects would demonstrate acceptable adherence. Subjects were randomized to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (ACS; high-fiber and lower-fat). Blood lipids and ketones were measured at baseline and after 12 weeks of the assigned intervention. Adherence measures included urinary ketones in the KD and 4 days' diet records. Diet records were also examined to identify general patterns of consumption. Differences between the diets on blood lipids and dietary intake were assessed with Analysis of covariance and independent t-tests. Correlation analyses were used to estimate associations between dietary intake and serum analytes. At 12 weeks, there were no significant differences between diet groups in blood lipids, after adjusting for baseline values and weight loss. Adherence among KD subjects ranged from 57% to 80%. These findings suggest that KDs may be a safe and achievable component of treatment for some cancer patients.
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Affiliation(s)
- Caroline W Cohen
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kevin R Fontaine
- Department of Health Behavior, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rebecca C Arend
- Department of Obstetrics and Gynecology, University of Alabama at Birmingham, AL, USA.,Division of Gynecologic Oncology, University of Alabama at Birmingham, AL, USA
| | - Barbara A Gower
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
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8
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Sadeghi A, Sadeghi O, Khodadost M, Pirouzi A, Hosseini B, Saedisomeolia A. Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose-Response Meta-Analysis. Nutr Cancer 2019; 72:5-14. [PMID: 31184513 DOI: 10.1080/01635581.2019.1621356] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A meta-analysis in 2015 revealed no significant association between glycemic index (GI), glycemic load (GL), and prostate cancer. Moreover, until now, no study has examined the dose-response association of GI, GL, and prostate cancer yet. The online databases were searched by two independent researchers for relevant publications up to Jan. 2019, using relevant keywords. Nine studies including five prospective and four case-control studies were included in the current systematic review and meta-analysis. These studies have included 290,911 individuals. We found a significant positive dose-response association between dietary GI and prostate cancer (Pnonlinearity = 0.03). Comparing individuals in the highest category of GI with those in the lowest category, no significant association was found between GI and prostate cancer (combined effect size: 1.08, 95% CI: 0.97-1.19, P = 0.17). Furthermore, no significant association was seen between dietary GL and prostate cancer in both dose-response analysis and when comparing the highest versus lowest categories of GL (combined effect size: 1.03, 95% CI: 0.91-1.16, P = 0.65). In conclusion, we found a significant positive dose-response association between dietary GI and prostate cancer. However, significant association was not seen for dietary GL.
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Affiliation(s)
- Alireza Sadeghi
- Gerash University of Medical Sciences, Gerash, Iran.,Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Omid Sadeghi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Khodadost
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Banafsheh Hosseini
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
| | - Ahmad Saedisomeolia
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Discipline of Pharmacology, School of Medicine, Western Sydney University, Sydney, NSW, Australia
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9
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Galle SA, van der Spek A, Drent ML, Brugts MP, Scherder EJA, Janssen JAMJL, Ikram MA, van Duijn CM. Revisiting the Role of Insulin-Like Growth Factor-I Receptor Stimulating Activity and the Apolipoprotein E in Alzheimer's Disease. Front Aging Neurosci 2019; 11:20. [PMID: 30809143 PMCID: PMC6380107 DOI: 10.3389/fnagi.2019.00020] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 01/24/2019] [Indexed: 12/18/2022] Open
Abstract
Background: Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia. Objective: In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE). Methods: At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models. Results: During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odds ratio 1.11; 95% confidence interval (CI) 0.97-1.28]. Interestingly, we found evidence of an interaction between ApoE-ε4 and tertiles of IGF-I receptor stimulating activity. IGF-I receptor stimulating activity in the median and top tertiles was related to increased dementia incidence in hetero- and homozygotes of the ApoE-ε4 allele, but did not show any association with dementia risk in people without the ApoE-ε4 allele (adjusted odds ratio medium vs. low IGF-I receptor stimulating activity in ApoE-ε4 carriers: 1.45; 95% CI 1.00-2.12). These findings suggest a threshold effect in ApoE-ε4 carriers. In line with the hypothesis that downregulation of IGF-I signaling is associated with increased dementia risk, ApoE-ε4 homozygotes without prevalent dementia displayed lower levels of IGF-I receptor stimulating activity than heterozygotes and non-carriers. Conclusion: The findings shed new light on the association between IGF-I signaling and the neuropathology of dementia and ask for replication in other cohorts, using measures of IGF-I receptor stimulating activity rather than total serum levels as putative markers of dementia risk.
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Affiliation(s)
- Sara A Galle
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.,Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Ashley van der Spek
- Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Madeleine L Drent
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.,Section of Endocrinology, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Michael P Brugts
- Department of Internal Medicine, Ikazia Ziekenhuis, Rotterdam, Netherlands
| | - Erik J A Scherder
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | | | - M Arfan Ikram
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.,Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands.,Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Cornelia M van Duijn
- Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.,Nuffield Department of Population Health, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
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10
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Zhou X, Zhao X, Li X, Ping G, Pei S, Chen M, Wang Z, Zhou W, Jin B. PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation and migration of glioma cells. J Chemother 2017; 28:44-9. [PMID: 25971682 DOI: 10.1179/1973947815y.0000000026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Growth factor signalling pathways transduce extra-cellular physiological cues to guide cells to maintain critical cellular functions, including cell proliferation, survival and metabolism. Dysregulation of certain growth factor signalling pathways has been shown as a major route to promote tumourigenesis. Glioma is a type of aggressive malignant tumour with no effective systematic therapy so far. Overexpression or hyperactivation of IGF-1R has been observed to be tightly associated with glioma progression and poor prognosis. Here, we examined the biological effects of a specific IGF-1R inhibitor, PQ401, on suppressing U87MG glioma cell growth and migration. Specifically, we observed that PQ401 not only induced cellular apoptosis in U87MG cells and subsequently reduced cell viability and proliferation but also attenuated cell mobility in vitro. More importantly, through a mouse xenograft model, we observed that administration of PQ401 on mice led to suppression of glioma tumour growth in vivo. In summary, our study suggests that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling.
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Affiliation(s)
- Xiang Zhou
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Xinli Zhao
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Xiangsheng Li
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Guanfang Ping
- b Department of Pharmacy , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Sujuan Pei
- b Department of Pharmacy , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Ming Chen
- b Department of Pharmacy , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Zhongwei Wang
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Wenke Zhou
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
| | - Baozhe Jin
- a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China
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11
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Insulin growth factor (IGF) 1, IGF-binding proteins and ovarian cancer risk: A systematic review and meta-analysis. Maturitas 2016; 94:22-29. [DOI: 10.1016/j.maturitas.2016.08.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 08/17/2016] [Accepted: 08/19/2016] [Indexed: 11/20/2022]
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12
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Uzick M. Naturopathic Approaches. Integr Cancer Ther 2016. [DOI: 10.1177/1534735405279633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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13
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Olsen CM, Wilson LF, Nagle CM, Kendall BJ, Bain CJ, Pandeya N, Webb PM, Whiteman DC. Cancers in Australia in 2010 attributable to insufficient physical activity. Aust N Z J Public Health 2016; 39:458-63. [PMID: 26437732 PMCID: PMC4606781 DOI: 10.1111/1753-6405.12469] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 07/01/2015] [Accepted: 07/01/2015] [Indexed: 12/20/2022] Open
Abstract
Objectives To estimate the proportion and numbers of cancers occurring in Australia in 2010 attributable to insufficient levels of physical activity. Methods We estimated the population attributable fraction (PAF) of cancers causally associated with insufficient physical activity (colon, post-menopausal breast and endometrium) using standard formulae incorporating prevalence of insufficient physical activity (<60 minutes at least 5 days/week), relative risks associated with physical activity and cancer incidence. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that everyone with insufficient activity levels increased their exercise by 30 minutes/week. Results An estimated 1,814 cases of colon, post-menopausal breast and endometrial cancer were attributable to insufficient levels of physical activity: 707 (6.5%) colon; 971 (7.8%) post-menopausal breast; and 136 (6.0%) endometrial cancers. If those exercising below the recommended level had increased their activity level by 30 minutes/week, we estimate 314 fewer cancers (17% of those attributable to insufficient physical activity) would have occurred in 2010. Conclusions More than 1,500 cancers were attributable to insufficient levels of physical activity in the Australian population. Implications Increasing the proportion of Australians who exercise could reduce the incidence of several common cancers.
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Affiliation(s)
- Catherine M Olsen
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | | | - Christina M Nagle
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - Bradley J Kendall
- QIMR Berghofer Medical Research Institute, Queensland.,School of Medicine, The University of Queensland
| | - Christopher J Bain
- QIMR Berghofer Medical Research Institute, Queensland.,National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Australian Capital Territory
| | - Nirmala Pandeya
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - Penelope M Webb
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - David C Whiteman
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
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14
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Malkani N, Biggar K, Shehab MA, Li SSC, Jansson T, Gupta MB. Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC. Mol Cell Endocrinol 2016; 425:48-60. [PMID: 26733150 PMCID: PMC4811673 DOI: 10.1016/j.mce.2015.12.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 12/01/2015] [Accepted: 12/07/2015] [Indexed: 01/11/2023]
Abstract
Insulin-like growth factor binding protein-1 (IGFBP-1), secreted by fetal liver, is a key regulator of IGF-I bioavailability and fetal growth. IGFBP-1 phosphorylation decreases IGF-I bioavailability and diminishes its growth-promoting effects. Growth-restricted fetuses have decreased levels of circulating essential amino acids. We recently showed that IGFBP-1 hyperphosphorylation (pSer101/119/169) in response to leucine deprivation is regulated via activation of the amino acid response (AAR) in HepG2 cells. Here we investigated nutrient-sensitive protein kinases CK2/PKC/PKA in mediating IGFBP-1 phosphorylation in leucine deprivation. We demonstrated that leucine deprivation stimulated CK2 activity (enzymatic assay) and induced IGFBP-1 phosphorylation (immunoblotting/MRM-MS). Inhibition (pharmacological/siRNA) of CK2/PKC, but not PKA, prevented IGFBP-1 hyperphosphorylation in leucine deprivation. PKC inhibition also prevented leucine deprivation-stimulated CK2 activity. Functionally, leucine deprivation decreased IGF-I-induced-IGF-1R autophosphorylation when CK2/PKC were not inhibited. Our data strongly support that PKC promotes leucine deprivation-induced IGFBP-1 hyperphosphorylation via CK2 activation, mechanistically linking decreased amino acid availability and reduced fetal growth.
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Affiliation(s)
- Niyati Malkani
- Dept of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
| | - Kyle Biggar
- Dept of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
| | - Majida Abu Shehab
- Children's Health Research Institute, University of Western Ontario, London, ON, Canada
| | - Shawn Shun-Cheng Li
- Dept of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
| | - Thomas Jansson
- Dept of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Madhulika B Gupta
- Dept of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada; Children's Health Research Institute, University of Western Ontario, London, ON, Canada; Dept of Pediatrics, University of Western Ontario, London, Canada.
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15
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Dietary Carbohydrate, Glycemic Index, Glycemic Load, and Breast Cancer Risk Among Mexican Women. Epidemiology 2015; 26:917-24. [DOI: 10.1097/ede.0000000000000374] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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16
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Gordon-Dseagu VLZ, Mindell JS, Steptoe A, Moody A, Wardle J, Demakakos P, Shelton NJ. Impaired glucose metabolism among those with and without diagnosed diabetes and mortality: a cohort study using Health Survey for England data. PLoS One 2015; 10:e0119882. [PMID: 25785731 PMCID: PMC4365017 DOI: 10.1371/journal.pone.0119882] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Accepted: 02/03/2015] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND The extent that controlled diabetes impacts upon mortality, compared with uncontrolled diabetes, and how pre-diabetes alters mortality risk remain issues requiring clarification. METHODS We carried out a cohort study of 22,106 Health Survey for England participants with a HbA1C measurement linked with UK mortality records. We estimated hazard ratios (HRs) of all-cause, cancer and cardiovascular disease (CVD) mortality and 95% confidence intervals (CI) using Cox regression. RESULTS Average follow-up time was seven years and there were 1,509 deaths within the sample. Compared with the non-diabetic and normoglycaemic group (HbA1C <5.7% [<39 mmol/mol] and did not indicate diabetes), undiagnosed diabetes (HbA1C ≥6.5% [≥48 mmol/mol] and did not indicate diabetes) inferred an increased risk of mortality for all-causes (HR 1.40, 1.09-1.80) and CVD (1.99, 1.35-2.94), as did uncontrolled diabetes (diagnosed diabetes and HbA1C ≥6.5% [≥48 mmol/mol]) and diabetes with moderately raised HbA1C (diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol]). Those with controlled diabetes (diagnosed diabetes and HbA<5.7% [<39 mmol/mol]) had an increased HR in relation to mortality from CVD only. Pre-diabetes (those who did not indicate diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol]) was not associated with increased mortality, and raised HbA1C did not appear to have a statistically significant impact upon cancer mortality. Adjustment for BMI and socioeconomic status had a limited impact upon our results. We also found women had a higher all-cause and CVD mortality risk compared with men. CONCLUSIONS We found higher rates of all-cause and CVD mortality among those with raised HbA1C, but not for those with pre-diabetes, compared with those without diabetes. This excess differed by sex and diabetes status. The large number of deaths from cancer and CVD globally suggests that controlling blood glucose levels and policies to prevent hyperglycaemia should be considered public health priorities.
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Affiliation(s)
- Vanessa L. Z. Gordon-Dseagu
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
- * E-mail:
| | - Jennifer S. Mindell
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
| | - Andrew Steptoe
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
| | - Alison Moody
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
| | - Jane Wardle
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
| | - Panayotes Demakakos
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
| | - Nicola J. Shelton
- Department of Epidemiology and Public Health, UCL (University College London), 1–19 Torrington Place, London, WC1E 6BT, United Kingdom
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17
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Mourouti N, Kontogianni MD, Papavagelis C, Panagiotakos DB. Diet and breast cancer: a systematic review. Int J Food Sci Nutr 2014; 66:1-42. [DOI: 10.3109/09637486.2014.950207] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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18
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He XD, Wu Q, Liu W, Hong T, Li JJ, Miao RY, Zhao HT. Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China. World J Gastroenterol 2014; 20:9541-9548. [PMID: 25071350 PMCID: PMC4110587 DOI: 10.3748/wjg.v20.i28.9541] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 02/22/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the risk factors for ampullary adenoma and ampullary cancer.
METHODS: This case-control study included ampullary tumor patients referred to Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of the same hospital. Data on metabolic syndromes, medical conditions, and family history were collected by retrospective review of the patients’ records and health examination reports, or by interview.
RESULTS: A total of 181 patients and 905 age- and sex-matched controls were enrolled. We found that a history of diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were significantly related to ampullary adenomas. Diabetes, cholecystolithiasis, chronic pancreatitis, total cholesterol, high-density lipoprotein, and apolipoprotein A were also significantly related to ampullary cancer.
CONCLUSION: Some metabolic syndrome components and medical conditions are potential risk factors for the development of ampullary tumors. Cholelithiasis, diabetes, and apolipoprotein A may contribute to the malignant transformation of benign ampullary adenomas into ampullary cancer.
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19
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Ilich JZ, Kelly OJ, Inglis JE, Panton LB, Duque G, Ormsbee MJ. Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res Rev 2014; 15:51-60. [PMID: 24632496 DOI: 10.1016/j.arr.2014.02.007] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 01/25/2014] [Accepted: 02/28/2014] [Indexed: 12/24/2022]
Abstract
While sarcopenia and sarcopenic obesity have been recognized in the last decade, a combined concept to include decreased muscle mass and strength, as well as decreased bone mass with coexistence of adiposity is discussed here. We introduce a new term, osteopenic obesity, and operationalize its meaning within the context of osteopenia and obesity. Next, we consolidate osteopenic obesity with the already existing and more familiar term, sarcopenic obesity, and delineate the resulting combined condition assigning it the term osteosarcopenic obesity. Identification and possible diagnosis of each condition are discussed, as well as the interactions of muscle, fat and bone tissues on cellular level, considering their endocrine features. Special emphasis is placed on the mesenchymal stem cell commitment into osteoblastogenic, adipogenic and myogenic lineages and causes of its deregulation. Based on the presented evidence and as expounded within the text, it is reasonable to say that under certain conditions, osteoporosis and sarcopenia could be the obesity of bone and muscle, respectively, with the term osteosarcopenic obesity as an encompassment for all.
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20
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Dotto GP. Multifocal epithelial tumors and field cancerization: stroma as a primary determinant. J Clin Invest 2014; 124:1446-53. [PMID: 24691479 DOI: 10.1172/jci72589] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
It is increasingly evident that cancer results from altered organ homeostasis rather than from deregulated control of single cells or groups of cells. This applies especially to epithelial cancer, the most common form of human solid tumors and a major cause of cancer lethality. In the vast majority of cases, in situ epithelial cancer lesions do not progress into malignancy, even if they harbor many of the genetic changes found in invasive and metastatic tumors. While changes in tumor stroma are frequently viewed as secondary to changes in the epithelium, recent evidence indicates that they can play a primary role in both cancer progression and initiation. These processes may explain the phenomenon of field cancerization, i.e., the occurrence of multifocal and recurrent epithelial tumors that are preceded by and associated with widespread changes of surrounding tissue or organ "fields."
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21
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Choi YJ, Kim YH, Cho CH, Kim SH, Lee JE. Circulating concentrations of C-Peptide and colorectal adenoma. Clin Nutr Res 2014; 3:17-23. [PMID: 24527416 PMCID: PMC3921291 DOI: 10.7762/cnr.2014.3.1.17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 01/15/2014] [Accepted: 01/16/2014] [Indexed: 12/30/2022] Open
Abstract
Hyperinsulinemia may increase the risk of colorectal neoplasia because of its mitogenic and antiapoptotic properties, which have a growth-promoting effect. We examined the association between circulating concentrations of C-peptide, a biomarker of insulin secretion, and colorectal adenoma prevalence in a case-control study of Korean adults. A total of 364 participants (112 cases and 252 controls) were included. Participants who underwent a colonoscopy completed questionnaires and provided blood samples. We used multivariate logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal adenoma. Circulating concentrations of C-peptide were not associated with colorectal adenoma; the multivariate OR (95% CI) was 0.95 (0.51-1.75) comparing the highest tertile with the lowest tertile (p for trend = 0.91). When we used a conditional logistic regression model by fasting status and sex matching, there was still no association (OR = 0.92; 95% CI = 0.43-1.99) when comparing the highest tertile with the lowest tertile. We observed no association between circulating concentrations of C-peptide and colorectal adenoma prevalence in Korean adults.
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Affiliation(s)
- Yoon Ji Choi
- Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, South Korea
| | - Young Ha Kim
- Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, South Korea
| | - Chang Ho Cho
- Department of Pathology, Daegu Catholic University Medical Center, Daegu 705-718, South Korea
| | - Sung Hi Kim
- Department of Family Medicine, Daegu Catholic University Medical Center, Daegu 705-718, South Korea
| | - Jung Eun Lee
- Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, South Korea
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22
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A multicountry ecological study of cancer incidence rates in 2008 with respect to various risk-modifying factors. Nutrients 2013; 6:163-89. [PMID: 24379012 PMCID: PMC3916854 DOI: 10.3390/nu6010163] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Revised: 12/12/2013] [Accepted: 12/14/2013] [Indexed: 02/06/2023] Open
Abstract
Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.
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23
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King B, Jiang Y, Su X, Xu J, Xie L, Standard J, Wang W. Weight control, endocrine hormones and cancer prevention. Exp Biol Med (Maywood) 2013; 238:502-8. [PMID: 23856901 DOI: 10.1177/1535370213480695] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.
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Affiliation(s)
- Brenee King
- Department of Human Nutrition, Kansas State University, Manhattan, KS 66506, USA
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24
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Jackson M, Tulloch-Reid M, Walker S, McFarlane-Anderson N, Bennett F, Francis D, Coard K. Dietary patterns as predictors of prostate cancer in Jamaican men. Nutr Cancer 2013; 65:367-74. [PMID: 23530635 DOI: 10.1080/01635581.2013.757631] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Studies of diet and prostate cancer have focused primarily on food and nutrients; however, dietary patterns examine the overall diet, particularly foods eaten in combination, and risk of disease. We evaluated the association of dietary patterns and prostate cancer and low- and high-grade subgroups in Jamaican men. In a case-control study, we enrolled 243 incident cases and 273 urology controls in Jamaican clinics, March 2005-July 2007. Dietary patterns were identified using principal component analysis. Four food patterns were identified: a "vegetable and legume" pattern, a "fast food" pattern, a "meat" pattern, and a "refined carbohydrate" pattern. Men in the highest tertile for the refined carbohydrate pattern, characterized by high intakes of rice, pasta, sugar sweetened beverages, and sweet baked foods were at increased risk of total prostate cancer [odds ratio (OR) = 2.02; 95% confidence interval (CI) = 1.05-3.87 (Ptrend = 0.029)] and low-grade disease [OR = 2.91; 95% CI = 1.18-7.13 (Ptrend = 0.019)] compared with men in the lowest tertile. The vegetable and legumes pattern (healthy), meat pattern, or fast food pattern were not associated with prostate cancer risk. These data suggest a carbohydrate dietary pattern high in refined carbohydrates may be a risk factor for prostate cancer in Jamaican men.
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Affiliation(s)
- Maria Jackson
- Faculty of Medical Sciences, University of West Indies, Kingston, Jamaica.
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25
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Abstract
Insulin-like growth factor 1 (IGF-1) is a pleiotropic polypeptide. Its expression is tightly regulated and it plays significant roles during early development, maturation, and adulthood. This article discusses the roles of IGF-1 in determination of body size, skeletal acquisition, muscle growth, carbohydrate metabolism, and longevity, as learned from mouse models.
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Affiliation(s)
- Shoshana Yakar
- Department of Basic Science and Craniofacial Biology, David B. Kriser Dental Center, New York University College of Dentistry, New York, NY 10010-4086, USA.
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26
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Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling. Mol Cell Endocrinol 2012; 351:269-78. [PMID: 22233684 DOI: 10.1016/j.mce.2011.12.017] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Accepted: 12/22/2011] [Indexed: 01/28/2023]
Abstract
For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer--often considered guilty more by association, than actual cause--with little attention paid to the important role of increased intracellular oestrogen, in the pathogenesis of these chronic diseases. In the final stage of the steroidogenic cascade, testosterone is metabolised to oestradiol by P450 aromatase, in the cytoplasm of adipocytes, breast cells, endothelial cells and prostate cells, to increase intracellular oestradiol concentration at the expense of testosterone. It follows therefore, that any compound that up-regulates aromatase, or any molecule that mimics oestrogen, will not only increase the activation of the mainly proliferative, classic ER-α, oestrogen receptors to induce adipogenesis and growth disorders in oestrogen-sensitive tissues, but also activate the recently identified transmembrane G protein-coupled oestrogen receptors (GPER), and deleteriously alter important intracellular signalling sequences, that promote mitogenic growth and endothelial damage. This paper simplifies how stress, xeno-oestrogens, poor dietary choices and reactive toxins up-regulate aromatase to increase intracellular oestradiol production; how oestradiol in combination with leptin and insulin cause insulin resistance and leptin resistance through aberrant serine phosphorylation; how the increased oestradiol, insulin and leptin stimulate rapid, non-genomic G protein-coupled phosphorylation cascades, to increase fat deposition and create the vasoconstrictive, dyslipidemic features of metabolic syndrome; how aberrant GPER signalling induces benign prostatic hypertrophy; and how increased intracellular oestradiol stimulates mitogenic change and tumour-cell activators, to cause prostate cancer. In essence, the up-regulation of aromatase produces increased intracellular oestradiol, increases ER-α activation and increases GPER activation, in combination with insulin, to cause aberrant downstream transduction signaling, and thus induce metabolic syndrome and mitogenic prostate growth. To understand this fact, that raised intracellular oestradiol levels in men, induce and promote obesity, gynecomastia, metabolic syndrome, type two diabetes, benign prostatic hypertrophy and prostate cancer, rather than low testosterone, represents a shift in medical thinking, a new awareness, that will reduce the rising incidence of obesity, metabolic syndrome and prostate disease, and significantly improve the health of men worldwide.
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Affiliation(s)
- Graeme Williams
- Metabolic Endocrinology and Clinical Research, P.O. Box 1574, Noosa Heads, Qld. 4567, Australia.
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27
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Physiologische und molekulare Mechanismen der Wirkung von körperlicher Aktivität auf das Krebsrisiko und den Verlauf einer Krebserkrankung. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2011; 55:3-9. [DOI: 10.1007/s00103-011-1400-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Abstract
The authors conducted a cross-sectional study to investigate the associations of fat, fiber, and carbohydrate intake with endogenous estrogen, androgen, and insulin-like growth factor (IGF) levels among 595 premenopausal women. Overall, no significant associations were found between dietary intake of these macronutrients and plasma sex steroid hormone levels. Dietary fat intake was inversely associated with IGF-I and IGF-binding protein 3 (IGFBP-3) levels. When substituting 5% of energy from total fat for the equivalent amount of energy from carbohydrate or protein intake, the plasma levels of IGF-I and IGFBP-3 were 2.8% (95% confidence interval [CI] 0.3, 5.3) and 1.6% (95% CI 0.4, 2.8) lower, respectively. Animal fat, saturated fat, and monounsaturated fat intakes also were inversely associated with IGFBP-3 levels (P<0.05). Carbohydrates were positively associated with plasma IGF-I level. When substituting 5% of energy from carbohydrates for the equivalent amount of energy from fat or protein intake, the plasma IGF-I level was 2.0% (95% CI 0.1, 3.9%) higher. No independent associations between fiber intake and hormone levels were observed. The results suggest that a low-fat/high-fiber or carbohydrate diet is not associated with endogenous levels of sex steroid hormones, but it may modestly increase IGF-I and IGFBP-3 levels among premenopausal women.
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29
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Abstract
Weight control via dietary caloric restriction and/or physical activity has been demonstrated in animal models for cancer prevention. However, the underlying mechanisms are not fully understood. Body weight loss due to negative energy balance significantly reduces some metabolic growth factors and endocrinal hormones such as IGF-1, leptin, and adiponectin, but enhances glucocorticoids, that may be associated with anti-cancer mechanisms. In this review, we summarized the recent studies related to weight control and growth factors. The potential molecular targets focused on those growth factors- and hormones-dependent cellular signaling pathways are further discussed. It appears that multiple factors and multiple signaling cascades, especially for Ras-MAPK-proliferation and PI3K-Akt-anti-apoptosis, could be involved in response to weight change by dietary calorie restriction and/or exercise training. Considering prevalence of obesity or overweight that becomes apparent over the world, understanding the underlying mechanisms among weight control, endocrine change and cancer risk is critically important. Future studies using "-omics" technologies will be warrant for a broader and deeper mechanistic information regarding cancer prevention by weight control.
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Affiliation(s)
- YU JIANG
- Department of Human Nutrition, Kansas State University, Manhattan, KS 66506, USA
| | - WEIQUN WANG
- Department of Human Nutrition, Kansas State University, Manhattan, KS 66506, USA
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30
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Lifetime physical activity and the incidence of proliferative benign breast disease. Cancer Causes Control 2011; 22:1297-305. [PMID: 21748307 DOI: 10.1007/s10552-011-9803-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2010] [Accepted: 06/15/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND Exercise is a modifiable factor that is inversely related to risk for breast cancer. To determine if physical activity has a preventative effect on development of premalignant breast lesions, we examined the association between exercise and the incidence of proliferative benign breast disease. METHODS In 1997, the Nurses' Health Study II cohort reported levels of physical activity during adolescence and adulthood using a validated recall instrument. We followed 40,318 participants free from benign breast disease (BBD) or cancer prospectively for four years and confirmed 232 proliferative benign breast lesions by centralized pathology review. Cox proportional hazards models estimated the age-adjusted and multivariable-adjusted relative risks for physical activity and proliferative benign breast disease. RESULTS We observed a significant inverse association for walking and incidence of BBD, risk was reduced by 9% per hour of walking (95% CI 0% to 17%), (p trend = 0.05). Despite a small number of cases, risk of columnar cell lesions also suggested an inverse association with strenuous activity (RR for 4 or more hours of strenuous activity per week = 0.62; 0.31-1.22 compared to < 1 h per week). CONCLUSIONS This study suggests that exercise may be inversely associated with the risk of developing proliferative benign breast disease, one of the earliest steps in the development of breast cancer.
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Bao B, Wang Z, Li Y, Kong D, Ali S, Banerjee S, Ahmad A, Sarkar FH. The complexities of obesity and diabetes with the development and progression of pancreatic cancer. BIOCHIMICA ET BIOPHYSICA ACTA 2011; 1815:135-46. [PMID: 21129444 PMCID: PMC3056906 DOI: 10.1016/j.bbcan.2010.11.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 11/19/2010] [Accepted: 11/20/2010] [Indexed: 12/12/2022]
Abstract
Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes, and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese, and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and PC.
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Affiliation(s)
- Bin Bao
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Zhiwei Wang
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Yiwei Li
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Dejuan Kong
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Shadan Ali
- Division of Hematology/Oncology Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Sanjeev Banerjee
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Aamir Ahmad
- Department of Pathology, Wayne State University, Detroit, Michigan
| | - Fazlul H. Sarkar
- Department of Pathology, Wayne State University, Detroit, Michigan
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Sampey BP, Lewis TD, Barbier CS, Makowski L, Kaufman DG. Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures. Exp Mol Pathol 2011; 90:257-63. [PMID: 21281625 DOI: 10.1016/j.yexmp.2011.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 01/20/2011] [Indexed: 11/18/2022]
Abstract
BACKGROUND Estrogen is the leading etiologic factor for endometrial cancer. Estrogen-induced proliferation of endometrial epithelial cells normally requires paracrine growth factors produced by stromal cells. Epidemiologic evidence indicates that dietary soy prevents endometrial cancer, and implicates the phytoestrogen genistein in this effect. However, results from previous studies are conflicting regarding the effects of genistein on hormone responsive cancers. METHODS The effects of estrogen and genistein on proliferation of Ishikawa (IK) endometrial adenocarcinoma cells were examined in co-cultures of IK cells with endometrial stromal cells, recapitulating the heterotypic cell-to-cell interactions observed in vivo. The roles of estrogen receptor (ER)α and ERβ were evaluated using ERα and ERβ specific agonists. ER activation and cell proliferation in the IK epithelial cells were determined by alkaline phosphatase assay and Coulter counter enumeration, respectively. RESULTS Both estrogen and genistein increased estrogen receptor-induced gene activity in IK cells over a range of concentrations. Estrogen alone but not genistein increased IK proliferation in co-cultures. When primed by estrogen treatment, increasing concentrations of genistein produced a biphasic effect on IK proliferation: nM concentrations inhibited estrogen-induced proliferation while μM concentrations increased proliferation. Studies with an ERβ-specific agonist produced similar results. Genistein did not influence the effects of estrogen on IK proliferation in monoculture. CONCLUSIONS Our study indicates that nutritionally relevant concentrations (nM) of genistein inhibit the proliferative effects of estrogen on endometrial adenocarcinoma cells presumably through activation of stromal cell ERβ. We believe that sub-micromolar concentrations of genistein may represent a novel adjuvant for endometrial cancer treatment and prevention.
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Affiliation(s)
- Brante P Sampey
- Department of Pathology and Laboratory Medicine, 620 Brinkhous-Bullitt Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA
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Nimptsch K, Kenfield S, Jensen MK, Stampfer MJ, Franz M, Sampson L, Brand-Miller JC, Willett WC, Giovannucci E. Dietary glycemic index, glycemic load, insulin index, fiber and whole-grain intake in relation to risk of prostate cancer. Cancer Causes Control 2011; 22:51-61. [PMID: 21069447 PMCID: PMC3117232 DOI: 10.1007/s10552-010-9671-x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2010] [Accepted: 10/14/2010] [Indexed: 10/18/2022]
Abstract
OBJECTIVE Insulin may play a role in prostate cancer tumorigenesis. Postprandial blood glucose and insulin responses of foods depend importantly on the carbohydrate quality and quantity, represented by glycemic index (GI), glycemic load (GL), fiber and whole-grain content, but are also influenced by intake of protein and other characteristics. The recently developed insulin index (II) quantifies the postprandial insulin secretion, also taking into account these additional characteristics. METHODS We investigated the association between dietary GI, GL, II, fiber, and whole grains and risk of total prostate cancer (n = 5,112) and subgroups of prostate cancer as defined by stage or grade in 49,934 male participants of the Health Professionals Follow-up Study. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS Dietary GI, GL, II, or fiber was not associated with risk of total or subgroups of prostate cancer. We observed a positive association between dietary intake of whole grains and total prostate cancer (HR highest versus lowest quintile 1.13, 95% CI 1.03-1.24), which was attenuated after restriction to PSA-screened participants (HR 1.03, 95% CI 0.91-1.17). CONCLUSIONS These results suggest that long-term exposure to a diet with a high insulin response does not affect prostate cancer incidence.
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Affiliation(s)
- K Nimptsch
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
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Dogan S, Rogozina OP, Lokshin AE, Grande JP, Cleary MP. Effects of chronic vs. intermittent calorie restriction on mammary tumor incidence and serum adiponectin and leptin levels in MMTV-TGF-α mice at different ages. Oncol Lett 2010; 1:167-176. [PMID: 22966277 DOI: 10.3892/ol_00000031] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2009] [Accepted: 07/31/2009] [Indexed: 02/07/2023] Open
Abstract
Calorie restriction prevents mammary tumor (MT) development in rodents. Usually, chronic calorie restriction (CCR) has been implemented. In contrast, intermittent calorie restriction (ICR) has been less frequently used. Recent studies indicate that when a direct comparison of the same degree of CCR vs. ICR was made using MMTV-TGF-α mice which develop MTs in the second year of life, ICR provided greater protection than CCR in delaying MT detection and reducing tumor incidence. Adiponectin and leptin are two adipocytokines secreted from adipose tissue which have opposite effects on many physiological functions, including proliferation of human breast cancer cells. A recent study indicated that a low adiponectin/leptin ratio was associated with breast cancer. We evaluated the relationship of adiponectin and leptin to MT development in MMTV-TGF-α calorie-restricted mice at several ages. Mice were enrolled at 10 weeks of age and subjected to 25% caloric reduction implemented either chronically or intermittently. Mice were euthanized at designated time points up to 74 weeks of age. Serum samples were collected to measure adiponectin and leptin concentrations. Both CCR and ICR mice had significantly reduced MT incidence. For the groups studied, serum leptin increased over time, while there was a trend for an increase in serum adiponectin levels in ad libitum and ICR mice, with no change in CCR mice between 10 and 74 weeks of age. The adiponectin/leptin ratio was significantly reduced as mice aged, but this ratio in ICR mice was significantly higher than that for ad libitum and CCR mice. No correlation was noted between serum adiponectin and leptin. These findings demonstrate that intermittent calorie restriction delays the early development of MTs. This delay was associated with reduced serum leptin levels following the restriction phases of the protocol. Additionally, serum leptin levels correlated with body weight and body fat in the groups studied.
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Affiliation(s)
- Soner Dogan
- Hormel Institute, University of Minnesota, Austin, MN 55912
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Finstad SE, Emaus A, Tretli S, Jasienska G, Ellison PT, Furberg AS, Wist EA, Thune I. Adult height, insulin, and 17beta-estradiol in young women. Cancer Epidemiol Biomarkers Prev 2009; 18:1477-83. [PMID: 19423524 DOI: 10.1158/1055-9965.epi-08-0972] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Adult height and insulin are thought to modify the development of breast cancer. However, little is known about the association between height and 17beta-estradiol, a key factor in breast carcinogenesis, and whether insulin modifies such an association. METHODS Among 204 healthy women, ages 25 to 35 years, who participated in the Energy Balance and Breast Cancer Aspect I study, adult height (in centimeters) and fasting serum concentrations of insulin (pmol/L) were measured. 17beta-Estradiol concentrations were measured in daily saliva samples throughout an entire menstrual cycle through RIA. Age and multivariate linear regression models were used to study the association between adult height and 17beta-estradiol levels throughout an entire menstrual cycle and whether serum levels of fasting insulin may modify such an association. RESULTS The women had a mean age of 30.7 years, adult height of 166.9 cm, and serum insulin of 85.7 pmol/L. For each increase of one SD in insulin levels in the upper tertile of adult height, the adjusted level of 17beta-estradiol increased by 3.1 pmol/L (95% confidence interval, 1.1-5.2), equivalent to a 17.3% higher mean average concentration of 17beta-estradiol. Women with an adult height > or =170 cm (upper tertile) and insulin levels >101 pmol/L (upper quartile) experienced, on average, 41% higher 17beta-estradiol levels throughout the entire menstrual cycle compared with women with the same adult height and insulin levels <101 pmol/L. CONCLUSION Our findings support that premenopausal levels of 17beta-estradiol vary in response to adult height and insulin levels, of possible importance for breast cancer risk.
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Kruk J. Intensity of lifetime physical activity and breast cancer risk among Polish women. J Sports Sci 2009; 27:437-45. [DOI: 10.1080/02640410802668510] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses 2009; 72:125-8. [DOI: 10.1016/j.mehy.2008.07.044] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2006] [Revised: 07/30/2008] [Accepted: 07/30/2008] [Indexed: 01/08/2023]
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Olsen CM, Bain CJ, Jordan SJ, Nagle CM, Green AC, Whiteman DC, Webb PM. Recreational physical activity and epithelial ovarian cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2008; 16:2321-30. [PMID: 18006921 DOI: 10.1158/1055-9965.epi-07-0566] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n=1,269) or borderline (n=311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n=1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and the risk of ovarian cancer.
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Affiliation(s)
- Catherine M Olsen
- Cancer and Population Studies Group, Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Herston 4029, Queensland, Australia.
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Maruti SS, Willett WC, Feskanich D, Rosner B, Colditz GA. A prospective study of age-specific physical activity and premenopausal breast cancer. J Natl Cancer Inst 2008; 100:728-37. [PMID: 18477801 DOI: 10.1093/jnci/djn135] [Citation(s) in RCA: 116] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Physical activity has been consistently associated with lower risk of postmenopausal breast cancer, but its relationship with premenopausal breast cancer is unclear. We investigated whether physical activity is associated with reduced incidence of premenopausal breast cancer, and, if so, what age period and intensity of activity are critical. METHODS A total of 64,777 premenopausal women in the Nurses' Health Study II reported, starting on the 1997 questionnaire, their leisure-time physical activity from age 12 to current age. Cox regression models were used to examine the relationship between physical activity, categorized by age period (adolescence, adulthood, and lifetime) and intensity (strenuous, moderate, walking, and total), and risk of invasive premenopausal breast cancer. RESULTS During 6 years of follow-up, 550 premenopausal women developed breast cancer. The strongest associations were for total leisure-time activity during participants' lifetimes rather than for any one intensity or age period. Active women engaging in 39 or more metabolic equivalent hours per week (MET-h/wk) of total activity on average during their lifetime had a 23% lower risk of premenopausal breast cancer (relative risk = 0.77; 95% confidence interval = 0.64 to 0.93) than women reporting less activity. This level of total activity is equivalent to 3.25 h/wk of running or 13 h/wk of walking. The age-adjusted incidence rates of breast cancer for the highest (> or = 54 MET-h/wk) and lowest (< 21 MET-h/wk) total lifetime physical activity categories were 136 and 194 per 100 000 person-years, respectively. High levels of physical activity during ages 12-22 years contributed most strongly to the association. CONCLUSIONS Leisure-time physical activity was associated with a reduced risk for premenopausal breast cancer in this cohort. Premenopausal women regularly engaging in high amounts of physical activity during both adolescence and adulthood may derive the most benefit.
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Affiliation(s)
- Sonia S Maruti
- Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., M4-B402, Seattle, WA 98109-1024, USA.
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Dogan S, Hu X, Zhang Y, Maihle NJ, Grande JP, Cleary MP. Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice. Breast Cancer Res 2008; 9:R91. [PMID: 18162139 PMCID: PMC2246166 DOI: 10.1186/bcr1840] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2007] [Revised: 11/12/2007] [Accepted: 12/27/2007] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-alpha mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins. METHODS MMTV-TGF-alpha mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT. RESULTS Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb (leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice. CONCLUSION These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight.
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Affiliation(s)
- Soner Dogan
- Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
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Cao J, Luo SM, Liang L, Lai J. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis. JPEN J Parenter Enteral Nutr 2008; 31:496-501. [PMID: 17947606 DOI: 10.1177/0148607107031006496] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Complex alterations in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis are thought to play an important role in the protein catabolism that complicates major surgical procedures. The aim of this study was to evaluate the potential roles of recombinant human growth hormone (rhGH) therapy after hepatectomy in hepatocellular carcinoma (HCC) with liver cirrhosis, and to investigate whether postoperative administration of rhGH increases the risk of tumor recurrences. METHODS Twenty-four patients with HCC in the setting of cirrhosis who underwent hepatectomy were randomly divided into 2 groups: parenteral nutrition (PN) group (n = 12) and rhGH + parenteral nutrition group (n = 12). Liver function, serum GH, IGF-1, and IGF binding protein-3 (IGFBP-3) were measured before operation, at postoperative days (POD) 1 and 6. IGF-1 and IGFBP-3 mRNA in liver tissue was measured by reverse transcriptase polymerase chain reaction. Liver Ki67 immunohistochemistry staining was studied. At the same time, 12 patients with cholelithiasis or liver hemangioma who underwent operation were segregated as a normal control. RESULTS On POD 6, compared with the PN group, serum prealbumin, GH, IGF-1, IGFBP-3, hepatic IGF-1 mRNA, IGFBP-3 mRNA, and liver Ki67 LI were higher in rhGH + PN group. The 6- and 12-month tumor-free survival rates, a median tumor-free survival time, were not different between the PN and rhGH + PN group. CONCLUSIONS rhGH + PN can ameliorate changes in the GH/IGF-1 axis after hepatectomy for HCC in the setting of cirrhosis.
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Affiliation(s)
- Jie Cao
- Department of General Surgery, Affiliated Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, China.
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Cao J, Luo S, Liang L, Lai J, Chen S. Effects of parenteral nutrition with and without GH on the GH/IGF-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis. FRONTIERS OF MEDICINE IN CHINA 2007; 1:287-293. [PMID: 24573868 DOI: 10.1007/s11684-007-0055-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2007] [Accepted: 04/20/2007] [Indexed: 06/03/2023]
Abstract
Postoperative hepatic insulin-like growth factor-1 (IGF-1) production may be severely disturbed in patients with liver cirrhosis. Complex alterations in the GH/IGF-1 axis are thought to play an important role in the protein catabolism that complicates major surgical procedures. The aim of this study was to explore the effects of parenteral nutrition (PN) with and without growth hormone (GH) on the GH/IGF-1 axis after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis and evaluate the potential roles of recombinant human GH (rhGH) therapy. Twenty-four patients with HCC with cirrhosis who underwent hepatectomy were randomly divided into two groups: a PN group (n = 12) and an rhGH + PN group (n = 12). Liver function, serum GH, IGF-1 and IGFBP-3 were measured before the operation and at post-operative days (POD) 1 and 6. Insulin-like growth factor-1 and IGFBP-3 mRNA in the liver tissue was detected by RT-PCR. The liver Ki67 immunohistochemistry staining was studied. At the same time, 12 patients with cholelithiasis or liver hemangioma who underwent operation served as normal control group. On POD 6, serum prealbumin, GH, IGF-1, IGFBP-3, hepatic IGF-1 mRNA, IGFBP-3 mRNA and liver Ki67 LI were higher in the rhGH + PN group than in the PN group. There was no significant difference in the 6-and 12-month tumor-free survival rate and the median tumor-free survival time between the PN group and the rhGH + PN group (P>0.05). These data indicate that rhGH + PN could ameliorate the changes in the GH/IGF-1 axis after hepatectomy for HCC in the setting of cirrhosis.
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Affiliation(s)
- Jie Cao
- Department of General Surgery, Affiliated Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, 510180, China,
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Pavelić J, Radaković B, Pavelić K. Insulin-like growth factor 2 and its receptors (IGF 1R and IGF 2R/mannose 6-phosphate) in endometrial adenocarcinoma. Gynecol Oncol 2007; 105:727-35. [PMID: 17399767 DOI: 10.1016/j.ygyno.2007.02.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2006] [Revised: 01/30/2007] [Accepted: 02/06/2007] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To investigate the consequences of IGF proteins dysfunction in development of endometrial adenocarcinomas. METHODS The expression of IGF 2 and IGF 1R was correlated with the expression of IGF 2R and apoptosis rate in 59 human endometrial adenocarcinomas, 10 endometrial hyperplasias and 7 normal tissues. The presence of mutations in the IGF 2R gene was followed in 46 adenocarcinomas. We also examined the effect of IGF 1 receptor blockage on cancer cell proliferation. In groups of either IGF 2-positive or IGF 2-negative tumors (stages III and IV) the expression of IGF 1 and IGF 1R was correlated with cell proliferation index and telomerase activity. RESULTS The expression of IGF 2 and IGF 1R was much higher in malignant tissue of stages III and IV than in tumors of stages I and II and normal or hyperplastic endometrium. This correlated with a decreased apoptosis rate and IGF 2R expression. Eight adenocarcinomas expressed biallelic mutation of the IGF 2R gene. The specific inhibition of IGF 1R and IGF 2 decreased tumor cell proliferation in IGF 2/IGF 1R-positive tumors. Furthermore, the positive correlation between increased expression of IGF 1 and IGF 1R proteins and increased telomerase activity and cell proliferation index was found in both IGF 2-negative and IGF 2-positive tumors. CONCLUSION Our data suggest that IGF 1, IGF 2 and their receptors are involved in the progression of endometrial adenocarcinomas. As cancer cell proliferation can be abrogated by blocking mRNA or protein products of these genes, tumors with extensive involvement of the IGF 2 pathway would be candidates for the therapeutics strategies aimed at interference with this pathway.
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Affiliation(s)
- Jasminka Pavelić
- Division of Molecular Medicine, Laboratory of Molecular Oncology, Rudjer Bosković Institute, Bijenicka 54, HR-10002 Zagreb, Croatia.
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Tamimi RM, Cox DG, Kraft P, Pollak MN, Haiman CA, Cheng I, Freedman ML, Hankinson SE, Hunter DJ, Colditz GA. Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study. Breast Cancer Res 2007; 9:R18. [PMID: 17300730 PMCID: PMC1851377 DOI: 10.1186/bcr1655] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2006] [Revised: 02/02/2007] [Accepted: 02/14/2007] [Indexed: 12/12/2022] Open
Abstract
Introduction Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, we examined the association between common genetic variation in this pathway and mammographic density. Methods We conducted a cross-sectional analysis among controls (n = 1,121) who were between the ages of 42 and 78 years at mammography, from a breast cancer case-control study nested within the Nurses' Health Study cohort. At the time of mammography, 204 women were premenopausal and 917 were postmenopausal. We genotyped 29 haplotype-tagging SNPs demonstrated to capture common genetic variation in IGF1, IGF binding protein (IGFBP)-1, and IGFBP-3. Results Common haplotype patterns in three of the four haplotype blocks spanning the gene encoding IGF1 were associated with mammographic density. Haplotype patterns in block 1 (p = 0.03), block 3 (p = 0.009), and block 4 (p = 0.007) were associated with mammographic density, whereas those in block 2 were not. None of the common haplotypes in the three haplotype blocks spanning the genes encoding IGFBP-1/IGFBP-3 were significantly associated with mammographic density. Two haplotype-tagging SNPs in IGF1, rs1520220 and rs2946834, showed a strong association with mammographic density. Those with the homozygous variant genotype for rs1520220 had a mean percentage mammographic density of 19.6% compared with those with the homozygous wild-type genotype, who had a mean percentage mammographic density of 27.9% (p for trend < 0.0001). Those that were homozygous variant for rs2946834 had a mean percentage mammographic density of 23.2% compared with those who were homozygous wild-type with a mean percentage mammographic density of 28.2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). Conclusion Common genetic variation in IGF1 is strongly associated with percentage mammographic density.
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Affiliation(s)
- Rulla M Tamimi
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
| | - David G Cox
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
| | - Peter Kraft
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
- Department of Biostatics, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
| | - Michael N Pollak
- Department of Medicine and Oncology, McGill University, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2, Canada
| | - Christopher A Haiman
- Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
| | - Iona Cheng
- Department of Epidemiology and Biostatistics, University of California, 513 Parnassus Avenue S966B, San Francisco, CA 94143, USA
| | - Matthew L Freedman
- Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, 7 Cambridge Center, Cambridge MA 02142, USA
| | - Susan E Hankinson
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
| | - David J Hunter
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
- Department of Surgery, Washington University School of Medicine, Campus Box 8100 660, S. Euclid Avenue, St. Louis, MO 63110 USA
| | - Graham A Colditz
- Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
- Department of Surgery, Washington University School of Medicine, Campus Box 8100 660, S. Euclid Avenue, St. Louis, MO 63110 USA
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Ray A, Nkhata KJ, Grande JP, Cleary MP. Diet-induced obesity and mammary tumor development in relation to estrogen receptor status. Cancer Lett 2007; 253:291-300. [PMID: 17399892 DOI: 10.1016/j.canlet.2007.02.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2006] [Revised: 02/02/2007] [Accepted: 02/05/2007] [Indexed: 11/22/2022]
Abstract
Leptin enhances proliferation of estrogen receptor (ER)-positive breast cancer cells in vitro. Here, we compared mammary tumor (MT) formation from ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cells in athymic mice fed a High-Fat diet to elevate serum leptin. Neither body weight, diet or serum leptin levels impacted MT latency, burden or tumor grade. However, protein expression in mammary fat pads exhibited elevated PCNA and Cyclin D1 while in MTs, Ob-Rb, IGF-IR, Bcl-2, and Bax were lower in Low-Fat versus High-Fat mice. In conclusion, diet rather than serum leptin impacted breast cancer cell tumor metabolism.
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Affiliation(s)
- Amitabha Ray
- Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
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Abstract
As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroombeta-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, beta-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and beta-hydroxy-beta-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-B activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.
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Affiliation(s)
- Mark F McCarty
- Block Center for Integrative Cancer Care, Evanston, IL 60201, USA.
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Abstract
Multifocal angiostatic therapy (MAT) is a strategy that seeks to impede cancer-induced angiogenesis by addressing multiple targets that regulate the angiogenic capacity of a cancer and/or the angiogenic responsiveness of endothelial cells, using measures that are preferentially, but not exclusively, nutraceutical. A prototype of such a regimen has been proposed previously, composed of green tea polyphenols, fish oil, selenium, and high-dose glycine, complementing a low-fat vegan diet, exercise training, and the copper-sequestering drug tetrathiomolybdate (TM). A review of more recent evidence suggests additional agents that could appropriately be included in this regimen and clarifies to some extent the mechanisms of action of its constituents. Diindolylmethane, a widely available crucifera-derived nutraceutical, has inhibited cancer growth in several mouse xenograft models; this effect may be largely attributable to an angiostatic action, as concentrations as low as 5 to 10 muM inhibit proliferation, migration, and tube-forming capacity of human endothelial cells in vitro, and a parenteral dose of 5 mg/kg markedly impairs matrigel angiogenesis in mice. Silymarin/silbinin, which has slowed the growth of human xenografts in a number of studies, suppresses the proliferation, migration, and tube-forming capacity of endothelial cells and inhibits vascular endothelial growth factor (VEGF) secretion by a range of human cancer cell lines, in concentrations that should be clinically feasible. The angiostatic activity of orally administered green tea now appears likely to reflect inhibition of the kinase activity of VEGFR-2. Glycine's angiostatic activity may be attributable to a hyperpolarizing effect on endothelial cells that decreases the activity of NADPH oxidase, now known to promote tyrosine kinase signaling in endothelial cells. The ability of TM to suppress cancer cell production of a range of angiogenic factors results at least in part from a down regulation of NF-kappaB activation. Dual-purpose molecular targets, whose inhibition could be expected to decrease the aggressiveness and chemoresistance of cancer cells while simultaneously impeding angiogenesis, include NF-kappaB, cox-2, c-Src, Stat3, and hsp90; drugs that can address these targets are now in development, and salicylates are notable for the fact that they can simultaneously inhibit NF-kappaB and cox-2. The potential complementary of the components of MAT should be assessed in nude mouse xenograft models.
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Affiliation(s)
- Mark F McCarty
- Block Center for Integrative Cancer Care, Evanston, Illinois 60201, USA.
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Diorio C, Pollak M, Byrne C, Mâsse B, Hébert-Croteau N, Yaffe M, Coté G, Bérubé S, Brisson J. Levels of C-peptide and mammographic breast density. Cancer Epidemiol Biomarkers Prev 2006; 14:2661-4. [PMID: 16284393 DOI: 10.1158/1055-9965.epi-05-0466] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Members of the insulin-like growth factor family have been associated with breast cancer risk and mammographic breast density, one of the strongest known breast cancer risk indicators. The aim of this cross-sectional study was to examine the association of levels of C-peptide (a marker of insulin secretion) with mammographic breast density among 1,499 healthy women recruited during screening mammography examinations. At time of mammography, blood samples and time since last meal were collected. Plasma C-peptide levels were measured by ELISA method, and mammographic breast density by a computer-assisted method. Spearman's partial correlation coefficients, adjusting for age and time since last meal (when necessary), were used to evaluate the associations. High body mass index and waist-to-hip ratio measurements were independently correlated with high levels of C-peptide (r(s) = 0.173 and r(s) = 0.252, respectively; P < 0.0001) or low breast density (r(s) = -0.389 and r(s) = -0.142, respectively; P < 0.0001). High levels of C-peptide were correlated with low breast density (r(s) = -0.210, P < 0.0001). However, the strength of the negative correlation was substantially reduced and was no longer significant after further adjustment for body mass index and waist-to-hip ratio (r(s) = -0.022, P = 0.41). These results suggest that C-peptide levels are not associated with breast density after complete adjustment for adiposity. Thus, the insulin/C-peptide-breast density relation does not seem to mirror the insulin/C-peptide-breast cancer association.
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Affiliation(s)
- Caroline Diorio
- Unité de recherche en santé des populations Centre hospitalier affilié universitaire de Québec, Hôpital Saint-Sacrement, 1050 Chemin Sainte-Foy, Quebec, Canada G1S 4L8
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