Randomized trial of a clinic-based weight loss intervention in cancer survivors.

BACKGROUND: This trial examined the efficacy of a clinic-based weight loss intervention in cancer survivors. METHODS: This single-center phase II trial randomized survivors of solid tumors and hematologic malignancies to a 15-week group-based weight loss intervention that included caloric restriction and physical activity (n = 30) or a wait-list control intervention (n = 30). The primary study outcome was body mass. Secondary study outcomes included body composition using dual-energy X-ray absorptiometry, physical fitness using the 6-min walk test (6MWT), and concentrations of serum biomarkers. RESULTS: Participants in the intervention group lost 5.6 ± 4.4% of baseline weight (4.6 ± 3.9 kg), whereas participants in the control group gained 0.2 ± 2.4% of baseline weight (0.2 ± 2.0 kg); intervention effect - 5.8% (95% CI - 7.8, - 3.8); - 4.8 kg (95% CI - 6.6, - 3.0); P = 0.0001. A larger proportion of participants in the intervention group lost ≥ 5% of baseline weight compared to the control group (43 vs 0%; P < 0.0001). The intervention led to reductions in fat mass (- 3.2 ± 0.7 kg; P < 0.0001), improvements in physical fitness (an increase of 22.6 ± 10.8 m on 6MWT; P = 0.03), and reductions in concentrations of insulin (- 7.7 ± 3.5 µU/mL; P = 0.004) and leptin (- 7.3 ± 4.0 ng/mL; P = 0.04). CONCLUSION: A 15-week clinic-based weight loss intervention resulted in significant weight loss and improvements in body composition, physical fitness, and concentrations of serum biomarkers in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Weight loss programs provide a number of benefits for cancer survivors; survivors should inquire about the availability of lifestyle programs offered at their cancer center and within their local communities.

Effect of the LIVESTRONG at the YMCA exercise program on physical activity, fitness, quality of life, and fatigue in cancer survivors.

BACKGROUND: Physical activity (PA) has been linked to a lower risk of developing and dying of cancer, yet many cancer survivors do not exercise. In the current study, the authors evaluated the impact of the LIVESTRONG at the YMCA exercise program, available at Young Men's Christian Associations (YMCAs) across the United States, on PA, fitness, quality of life, fatigue, body composition, serum biomarkers, and program safety in cancer survivors. METHODS: Cancer survivors were recruited through the Yale Cancer Center and the Dana-Farber Cancer Institute and randomized to a 12-week, twice-weekly LIVESTRONG at the YMCA exercise program at YMCAs in Connecticut or Massachusetts or to a control group. Questionnaires, dual-energy x-ray absorptiometry scans, 6-minute walk tests (6MWTs), and a fasting blood draw were completed at baseline and at 12 weeks. Intervention effects were evaluated using mixed model repeated measures analysis, with changes at 12 weeks in PA and 6MWT as the primary endpoints. RESULTS: A total of 186 participants were randomized (95 to the exercise group and 91 to the control group). The majority of patients were diagnosed with AJCC stage I to II cancer and 53% had breast cancer. Participants randomized to the LIVESTRONG at the YMCA program experienced increases in PA (71% exercising at ≥ 150 minutes/week vs 26% of controls; P<.05) and improvements in the 6MWT (group difference: 28.9 meters [95% confidence interval, 0.3-49.0; P = .004]) and quality of life (group difference: 2.6 [95% confidence interval, 0.1-5.0; P = .04]). No adverse events were reported. CONCLUSIONS: The LIVESTRONG at the YMCA exercise program has the potential to impact thousands of survivors across the YMCA network and could lead to improvements in disease and psychosocial outcomes in the growing population of cancer survivors. Cancer 2017;123:1249-1258. © 2016 American Cancer Society.

Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth.

The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumour formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppressing hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis.