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Biomedical subjects

George L Blackburn

Publications and source records attributed to George L Blackburn.

At least 19 recordsLinked to original sources
PubMed2006

Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study.

BACKGROUND: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. METHODS: A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. RESULTS: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. CONCLUSIONS: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.

Adult↗
PubMed2006

Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in mice by alterations of cancer cell proliferation and apoptosis and tumor angiogenesis.

A role of dietary bioactive components in bladder cancer prevention is biologically plausible because most substances or metabolites are excreted through the urinary tract and are consequently in direct contact with the mucosa of the bladder. We first determined antigrowth activity of genistein against poorly differentiated 253J B-V human bladder cancer cells in vitro. Genistein inhibited the cell growth in a time- and dose-dependent manner via G(2)-M arrest, down-regulation of nuclear factor kappaB (NF-kappaB), and induction of apoptosis. We also evaluated both genistin, which is a natural form of genistein, and the isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis of 253J B-V tumors in an orthotopic tumor model. Mice treated with genistin and SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P < 0.01) associated with significant down-regulation of NF-kappaB expression in tumor tissues and reduction of circulating insulin-like growth factor-I levels, suggesting that SPC may contain other bioactive ingredients that have antimetastatic activity. The results from our studies suggest that further clinical investigation should be warranted to apply soy phytochemicals, such as SPC, as a potent prevention regimen for bladder cancer progression. This orthotopic human bladder tumor model also provides a clinically relevant experimental tool for assessing potential preventive activity of other dietary components against bladder tumor growth and metastasis.

Animals↗
PubMed2006

The metabolic syndrome: a call to action.

Metabolic syndrome, a cluster of risk factors that enhances the risk for atherosclerotic cardiovascular disease, has received increasing attention in recent years, especially as the worldwide prevalence of obesity has become better defined. Recent controversy has questioned the scientific basis for metabolic syndrome, but does not negate its value as a description of a common phenotype of patients encountered in clinical practice. Revised and refined diagnostic criteria may be useful for physicians. While more research is needed to understand the pathology of the metabolic syndrome, there is no ambiguity that physicians should treat cardiovascular risk factors in individuals with metabolic syndrome.

Cardiovascular Diseases↗
PubMed2005

Expanding the limits of treatment--new strategic initiatives.

The perception that weight reduction is rarely successful is, in fact, a misperception. Between 1999-2000 and 2001-2002, there were no significant changes among adults in the prevalence of overweight, obesity, or extreme obesity, or among children aged 6 through 19 years in the prevalence of at risk for overweight. The National Heart, Lung, and Blood Institute defines successful long-term weight loss as an intentional reduction of 10% from baseline maintained for 1 year. Modest weight loss is not only beneficial but also achievable for persons with overweight and obesity. Of the Americans who have tried to lose weight, almost 50% have maintained their weight loss successfully for at least 1 year. The remaining half, those who seem unable to prevent or reverse their obesity, challenge dietetics professionals to mobilize resources, confront issues at the heart of the obesity epidemic, and develop new solutions. Work to date has paid off for millions of persons. We have stopped the epidemic of obesity. Now it is time to do more by joining health care practitioners with all other stakeholders in the effort to prevent and reverse it.

Adolescent↗
PubMed2005

Pharmacotherapy to reduce visceral fat.

Cardiovascular disease (CVD) is the leading cause of death of men and women in the United States. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing CVD and metabolic disease. Because visceral adipose tissue uniquely contributes to the pathophysiology of CVD and insulin resistance, waist circumference is now being considered as a more useful marker of potential health risks associated with overweight and obesity than body mass index. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, thereby reducing the risk of developing chronic disease and CVD.

Anti-Obesity Agents↗
PubMed2005

Therapy insight: weight-loss surgery and major cardiovascular risk factors.

Weight-loss surgery is an effective treatment for severe, medically complicated and refractory obesity. It reverses, eliminates or significantly ameliorates major cardiovascular risk factors related to obesity. In a large proportion of patients, the therapy produces significant weight loss, reduces the risk of disability and premature death, and improves quality of life. Surgical treatment by gastric-restrictive and malabsorptive procedures started several decades ago in the US. Since the 1970s, accrued clinical experience and advances in technology, particularly in minimally invasive surgical approaches, have changed this therapy. Some procedures have evolved, whereas others have become obsolete. Today's weight-loss operations are safe, effective and potentially life-saving options for severely obese cardiology patients. This review describes weight-loss surgery procedures and their effects on cardiovascular risk factors.

Adult↗
PubMed2005

Science-based solutions to obesity: what are the roles of academia, government, industry, and health care?

The complexity of the obesity epidemic requires the cooperation of key stakeholders in this effort. No one sector, academia, government, industry, or health care, has been successful in combating this disease to date. On March 10-11, 2004, The Harvard Medical School Division of Nutrition hosted the symposium "Science-Based Solutions to Obesity: What is the Role of Academia, Government, Industry, and Health care?" as a platform to address the role of these stakeholders, both individually and collectively, in combating the nation's epidemic of obesity. The proceedings from the symposium, included in this supplement, discuss the following: the science of obesity-related topics such as genetics, protein and weight loss, portion size, energy density, and behavior; the need for more aggressive government policies; industry's role in using research and development capabilities to promote healthier, portion-controlled products; and how to translate nutrition information from medical doctors to patients.

Academic Medical Centers↗
PubMed2005

Teaching, learning, doing: best practices in education.

As many as 90 million Americans lack basic skills needed to access, understand, and use health information and services to make healthy dietary choices. Effective teaching by physicians can bridge the learning gap and arrest the epidemic of obesity. The Academy at Harvard Medical School is developing best practices in teaching that will equip future doctors to reduce health illiteracy and promote positive changes in thinking and behavior in their patients. Models of how people learn can help physicians select tasks, questions, and prompts that advance teaching and learning. To keep and use new information, adults need to integrate new ideas into existing frameworks of understanding and participate in the learning process by linking new information to what is already known. By teaching patients how to read a single food label, starting with calories, physicians can set the stage for future learning. The process of change is challenging, particularly in adults. Best practices in teaching and learning can help physicians be more effective agents of change.

Academic Medical Centers↗
PubMed2005

Solutions in weight control: lessons from gastric surgery.

Surgical therapy is currently the only proven way to achieve significant long-term weight loss, improve obesity-related comorbidities, reduce the risk of premature death, and improve quality of life in a large proportion of treated individuals. Roux-en-Y gastric bypass, the most widely performed procedure in the United States, is known to achieve permanent (>14 y of follow-up) and significant (>50% of excess body weight) weight loss in >90% of patients who undergo the operation. Gastric bypass procedures induce physiologic and neuroendocrine changes that appear to affect the weight regulatory centers in the brain. Researchers have begun to explore the molecular pathways responsible for these outcomes. Identifying the differences between surgical and nonsurgical treatments will eventually lead to new therapeutic options.

Gastric Bypass↗
PubMed2004

Progression to androgen-independent LNCaP human prostate tumors: cellular and molecular alterations.

Lethal phenotypes of human prostate cancer are characterized by progression to androgen-independence and metastasis. For want of a clinically relevant animal model, mechanisms behind this progression remain unclear. Our study used an in vivo model of androgen-sensitive LNCaP human prostate cancer cell xenografts in male SCID mice to study the cellular and molecular biology of tumor progression. Primary tumors were established orthotopically, and the mice were then surgically castrated to withdraw androgens. Five generations of androgen-independent tumors were developed using castrated host mice. Tumor samples were used to determine expressions of cellular and molecular markers. Androgen-independent tumors had increased proliferation and decreased apoptosis compared to androgen-sensitive tumors, outcomes associated with elevated expression of p53, p21/waf1, bcl-2, bax and the bcl-2/bax ratio. Blood vessel growth in androgen-independent tumor was associated with increased expression of vascular endothelial growth factor. Overexpression of androgen receptor mRNA and reduced expression of androgen receptor protein in androgen-independent tumors suggest that the androgen receptor signaling pathway may play an important role in the progression of human prostate cancer to androgen-independence. The in vivo orthotopic LNCaP tumor model described in our study mimics the clinical course of human prostate cancer progression. As such, it can be used as a model for defining the molecular mechanisms of prostate cancer progression to androgen-independence and for evaluating the effect of preventive or therapeutic regimens for androgen-independent human prostate cancer.

Androgens↗
PubMed2004

Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice.

Breast cancer is significantly less prevalent among Asian women, whose diets contain high intake of soy products and tea. The objective of our present study was to identify the combined effects of dietary soy phytochemicals and tea components on breast tumor progression in a clinically relevant in vivo model of MCF-7 androgen-dependent human breast tumor in female SCID mice. MCF-7 tumor growth, tumor cell proliferation and apoptosis, microvessel density, and expressions of tumor estrogen receptors were compared in mice treated with genistin-rich soy isoflavones (GSI), soy phytochemical concentrate (SPC), black tea (BT), green tea (GT), SPC/BT combination and SPC/GT combination. GSI and SPC led to dose-dependent inhibition of MCF-7 tumor growth via inhibition of cancer cell proliferation in vivo. GT showed more potent anti-breast tumor activity than BT. GT infusion at 1.5 g tealeaf/100 mL water produced significant (p < 0.05) reductions of 56% in final tumor weight. GT plus SPC at 0.1% of the diet further reduced final tumor weight by 72% (p < 0.005). Analysis of serum and tumor biomarkers showed that the combined effects of SPC and GT inhibited tumor angiogenesis, and reduced estrogen receptor (ER)-alpha and serum levels of insulin-like growth factor (IGF)-I. Our study suggests that dietary SPC plus GT may be used as a potential effective dietary regimen for inhibiting progression of estrogen-dependent breast cancer.

Animals↗
PubMed2004

Dietary patterns in women treated for breast cancer who successfully reduce fat intake: the Women's Intervention Nutrition Study (WINS).

OBJECTIVE: The objectives of this study were to assess the types of dietary changes made by women who successfully reduced their fat intake in response to low-fat diet instruction and to evaluate the effects of these changes on nutrient intake. DESIGN: Two hundred women enrolled in the low-fat intervention arm of the Women's Intervention Nutrition Study (WINS) were randomly selected. Woman whose baseline fat intake was less than 20% energy from fat were excluded from the study, resulting in a total population of 163. These women were categorized into either the strictly adherent (SA) (those who met their fat gram goal and reported less than 20 % calories from fat, n=50) or the not strictly adherent (NSA) (those who exceeded their fat gram goal and reported 20% or greater calories from fat, n=113) group. The food choices made by SA and NSA subjects were analyzed to identify those that promoted greater adherence. SUBJECTS/SETTING: The participants were free-living women who had been instructed to follow a diet that would meet a specific fat gram goal calculated to provide 15% of calories from fat. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were used to describe food groups and subgroups. t tests were used to determine statistical significance between and within groups. chi(2) analysis was used to assess differences in demographic variables. RESULTS: There were no marked differences in food patterns of the SA and NSA subjects when compared with the Food Guide Pyramid (FGP) recommendations. Both met FGP serving recommendations at baseline. At 12 months, both showed reductions in the number of servings from fats and oils; SA subjects showed a greater reduction (from 4.18+/-3.6 to 3.0+/-2.4) as well as a reduction in servings from the bread group intake (5.7+/-2.2 to 4.8+/-2.1). Evaluation of food subgroups from within FGP groups showed strategies that promoted fat reduction, such as reducing portion sizes of high-fat foods. The use of these strategies was greater in the SA subjects. The reduction in fat intake had little impact on nutrient adequacy. SA and NSA subjects reduced energy intake from baseline to follow-up, with SA subjects reporting lower intakes. There were few differences in nutrient intakes between the SA and NSA subjects at either time period. CONCLUSIONS: The results from this study suggest specific strategies that promote successful reduction in fat intake without compromising nutrient intake. This information can be used to guide others in making dietary changes.

Adult↗
PubMed2004

Effects of weight loss surgeries on liver disease.

Obesity is the single most significant risk factor for the development of nonalcoholic fatty liver disease (NAFLD) in children and adults. NALFD is estimated to occur in 30 to 100% of obese adults, and in approximately 53% of obese children. The majority of obese patients have ultrasonographic evidence of fatty liver; 30% have histologically documented nonalcoholic steatohepatitis (NASH). Up to 25% of patients with NASH may progress to cirrhosis. In the United States, an estimated 65% of adults are overweight and 31% are obese. Between 2001 and 2002, the number of people with severe obesity, who are more than 100 pounds overweight, rose to nearly 11 million. Since 1970, levels of childhood and teen overweight have climbed to approximately 16% in those aged 6 to 19 years. Recent findings indicate that key features of NAFLD and NASH improve or resolve dramatically with weight loss. This article discusses weight loss surgeries and their effects on liver disease.

Adipose Tissue↗