SUMMARY Objective Maintenance of muscle mass is crucial to improving outcome and quality of life in cancer patients. Stimulating muscle protein synthesis is the metabolic basis for maintaining muscle mass, but in cancer patients normal dietary intake has minimal effects on muscle protein synthesis. Adding leucine to high protein supplements stimulates muscle protein synthesis in healthy older subjects. The objective was to determine if a specially formulated medical food, high in leucine and protein, stimulates muscle protein synthesis acutely in individuals with cancer to a greater extent than a conventional medical food. Design A randomized, controlled, double-blind, parallel-group design was used in 25 patients with radiographic evidence of cancer. Patients were studied before their cancer treatment was started or 4 weeks after their treatment was completed or halted. The fractional rate of muscle protein synthesis (FSR) was measured using the tracer incorporation technique with L-[ring-13C6]-phenylalanine. The experimental group (n = 13) received a medical food containing 40 g protein, based on casein and whey protein and enriched with 10% free leucine and other specific components, while the control group (n = 12) was given a conventionally used medical food based on casein protein alone (24 g). Blood and muscle samples were collected in the basal state and 5h hours after ingestion of the medical foods. Results The cancer patients were in an inflammatory state, as reflected by high levels of C-reactive protein (CRP), IL-1β and TNF-α, but were not insulin resistant (HOMA). After ingestion of the experimental medical food, plasma leucine increased to about 400 μM as compared to the peak value of 200 μM, after the control medical food (p < 0.001). Ingestion of the experimental medical food increased muscle protein FSR from 0.073 (SD: 0.023) to 0.097 (SD: 0.033) %/h (p = 0.0269). In contrast, ingestion of the control medical food did not increase muscle FSR; 0.073 (SD: 0.022) and 0.065 (SD: 0.028) %/h. Conclusions In cancer patients, conventional nutritional supplementation is ineffective in stimulating muscle protein synthesis. This anabolic resistance can be overcome with a specially formulated nutritional supplement.
Purpose: Enhanced prognostication power is becoming more desirable in clinical oncology. In this study, we explored the prognostic potential of multigene hypermethylation profiling in non^small-cell lung cancer. Experimental Design: We evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT, DAPK, ECAD, and RASSF1A) using methylation-specific PCR in 105 archived specimens of non^small-cell lung cancer representing all stages of the illness. We analyzed the effect of gene methylation status on outcome individually in a cumulative manner and in a combinatorial approach using recursive partitioning to identify methylation profiles, which affect overall survival. Results: In this data set, tumors harboring promoter hypermethylation at two or more genes exhibit similar survival trends to others in the cohort. Using recursive partitioning, three genes (APC, ATM, and RASSF1A) emerged as determinants of prognostic groups.This designation retained its statistical significance even when disease stage and age were entered into a multivariate analysis. Using this approach, patients whose tumors were hypermethylated at APC and those hypermethylated at only ATM (not also at APC or RASSF1A) enjoyed substantially longer 1-and 2-year survival than patients in the remaining groups. In 32 adjacent histologically normal lung tissue specimens, we detected similar methylation abnormalities. Conclusion: Assessment of promoter hypermethylation aberrations may facilitate prognostic profiling of lung tumors, but validation in independent data sets is needed to verify these profiles. This system uses material that is abundantly available with linked outcome data and can be used to generate reliable epigenetic determinants.
BackgroundThe effect of moderately elevated blood glucose levels among non-diabetic subjects on cancer prognosis is not well described. The goal of this study was to examine the association of elevated random blood glucose (RBG) levels in non-diabetic breast cancer patients with overall survival (OS) and time to tumor recurrence (TTR).ResultsForty-nine deaths and 32 recurrences occurred among 148 eligible study subjects during 855.44 person-years of follow-up, with median follow-up of 5.97 years. We observed that patients with elevated RBG levels experienced significantly shorter OS (hazard ratio [HR], 3.01; 95 % confidence interval [CI] (1.70–5.33); P < 0.001) and shorter TTR (HR, 2.08; CI (1.04–4.16); P = 0.04) as compared to patients with non-elevated RBG levels. After controlling for tumor grade, tumor stage, race, and BMI, elevated RBG continued to display high and statistically significant association with shorter OS (HR, 3.50; CI (1.87–6.54); P < 0.001). Adjustment for age, race, and BMI strengthened HR of RBG for TTR. The association of RGB with TTR lost its borderline statistical significance upon controlling for both tumor grade and stage.ConclusionsThe data suggest that elevated blood glucose is associated with poor prognosis of breast cancer patients. Given the potential clinical implication, these findings warrant further investigation.
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