sulindac and Obesity

Chemoprevention with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) + sulindac markedly reduces risk of recurrent adenoma in colorectal adenoma patients. Obesity is associated with risk of colorectal adenoma and colorectal cancer. This study investigates how obesity influences risk of recurrent adenoma after prolonged treatment with DFMO + sulindac versus placebo.. Our analysis included subjects enrolled in the phase III colorectal adenoma prevention clinical trial investigating DFMO + sulindac versus placebo. Patients were classified by obesity (body mass index, BMI ≥ 30 kg/m(2)) status at baseline. Pearson χ(2) statistic and Mann-Whitney U test were used to compare baseline characteristics, including rectal tissue polyamine levels. Log-binomial regression analysis was used to determine the risk ratio (RR) of recurrent adenomas, adjusted for covariates and an interaction term for obesity and treatment.. The final analytic cohort was comprised of 267 patients. In separate regression models, the risk of adenoma recurrence after treatment compared to placebo was similar for obese (RR = 0.32, 95 % CI 15-71) and non-obese patients (RR = 0.27, 95 % CI 15-49). No significant interaction was detected between obesity, treatment, and risk of colorectal adenoma in the full regression model (p (interaction) = 0.91).. Obesity does not substantially modify the colorectal adenoma risk reduction ascribed to DFMO + sulindac versus placebo.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Double-Blind Method; Eflornithine; Female; Humans; Male; Middle Aged; Obesity; Placebo Effect; Polyamines; Regression Analysis; Sulindac; Treatment Outcome

The effects of sulindac and indomethacin on the blood pressure response to labetalol were determined in well-controlled predominantly obese hypertensive patients (n = 26). A stabilized dose of labetalol alone was administered on weeks 1 and 3, and either indomethacin or sulindac was administered with labetalol on week 2, with cross-over to the other drug on week 4. Indomethacin and sulindac increased the sitting and standing systolic blood pressure (BP) to a statistically significant extent compared with placebo. The effects of indomethacin on systolic BP, diastolic BP, and weight were not significantly different from those with sulindac. Indomethacin but not sulindac produced minor increases in diastolic BP and weight compared with placebo.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure; Body Weight; Chlorides; Drug Interactions; Humans; Hypertension; Indomethacin; Labetalol; Middle Aged; Obesity; Random Allocation; Sodium; Sulindac

Obesity is associated with an increased risk of colon cancer. Our current study examines whether weight loss and/or treatment with the NSAID sulindac suppresses the protumor effects of obesity in a mouse model of colon cancer. Azoxymethane-treated male FVB/N mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 15 weeks, then HFD mice were randomized to remain on HFD (obese) or switch to LFD [formerly obese (FOb-LFD)]. Within the control (LFD), obese, and FOb-LFD groups, half the mice started sulindac treatment (140 ppm in the diet). All mice were euthanized 7 weeks later. FOb-LFD mice had intermediate body weight levels, lower than obese but higher than control (P < 0.05). Sulindac did not affect body weight. Obese mice had greater tumor multiplicity and burden than all other groups (P < 0.05). Transcriptomic profiling indicated that weight loss and sulindac each modulate the expression of tumor genes related to invasion and may promote a more antitumor immune landscape. Furthermore, the fecal microbes Coprobacillus, Prevotella, and Akkermansia muciniphila were positively correlated with tumor multiplicity and reduced by sulindac in obese mice. Coprobacillus abundance was also decreased in FOb-LFD mice. In sum, weight loss and sulindac treatment, alone and in combination, reversed the effects of chronic obesity on colon tumor multiplicity and burden. Our findings suggest that an investigation regarding the effects of NSAID treatment on colon cancer risk and/or progression in obese individuals is warranted, particularly for those unable to achieve moderate weight loss.. Obesity is a colon cancer risk and/or progression factor, but the underlying mechanisms are incompletely understood. Herein we demonstrate that obesity enhances murine colon carcinogenesis and expression of numerous tumoral procancer and immunosuppressive pathways. Moreover, we establish that weight loss via LFD and/or the NSAID sulindac mitigate procancer effects of obesity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Colonic Neoplasms; Diet, High-Fat; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Microbiota; Obesity; Sulindac; Transcriptome; Weight Loss

The nutritional composition of diets and prevalence of obesity in 77 osteoarthritis patients were assessed biweekly for 12 weeks as part of a multidisciplinary approach to the management of osteoarthritis. Height was measured at the first visit, and weight was measured at each of the seven biweekly follow-up visits. A body mass index was calculated, based on height and weight, to determine obesity. Nutrient information was obtained by use of a 24-hour dietary recall and a food frequency questionnaire. Seventy-nine percent of the patients were obese. Obesity was positively related to pain from osteoarthritis and was more prevalent among these osteoarthritis patients than it is among the general geriatric population. Dietary intakes of vitamin D, folacin, vitamin B6, zinc, and pantothenic acid were below 80% of the recommended dietary allowance. Osteoarthritis patients may benefit from weight loss if they are obese and from eating more foods that supply the nutrients in which they are deficient. In addition to providing nutritional recommendations to avoid dietary deficiencies, a registered dietitian can assist in the multidisciplinary treatment of osteoarthritis by providing weight-control counseling and follow-up.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Diet; Diet, Reducing; Energy Intake; Female; Humans; Male; Middle Aged; Obesity; Osteoarthritis; Patient Care Team; Sulindac; Time Factors