NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in NAD+ biosynthesis. Although NAMPT has emerged as a critical regulator of metabolic stress, the underlying mechanisms by which it regulates metabolic stress in cancer cells have not been completely elucidated. In this study, we determined that breast cancer cells expressing a high level of NAMPT were resistant to cell death induced by glucose depletion. Furthermore, NAMPT inhibition suppressed tumor growth in vivo in a xenograft model. Under glucose deprivation conditions, NAMPT inhibition was found to increase the mitochondrial reactive oxygen species (ROS) level, leading to cell death. This cell death was rescued by treatment with antioxidants or NAD+. Finally, we showed that NAMPT increased the pool of NAD+ that could be converted to NADPH through the pentose phosphate pathway and inhibited the depletion of reduced glutathione under glucose deprivation. Collectively, our results suggest a novel mechanism by which tumor cells protect themselves against glucose deprivation-induced oxidative stress by utilizing NAMPT to maintain NADPH levels.

Sensory evaluations of porcine longissimus dorsi muscle: Relationships with postmortem meat quality traits and muscle fiber characteristics.

The objective of this study was to investigate sensory evaluations and their relationships with meat quality measurements and histochemical characteristics in both fresh and cooked pork. Based on the results, postmortem meat quality traits were closely related to almost all the evaluated sensory attributes. With regard to histochemical characteristics, muscle fiber area was related to both fresh- (r=0.18, P<0.05) and cooked-meat color (r=-0.24, P<0.01) as well as abnormal flavor intensity (r=0.25, P<0.01), and muscle fiber composition was associated with fresh pork color and taste acceptability after cooking. There were no significant relationships (P>0.05) between type IIa muscle fiber content and the evaluated sensory attributes; however, good meat sensory quality was partially explained by the percentage of type I fiber.

The relation of blood glucose level to muscle fiber characteristics and pork quality traits.

The purpose of this study was to examine the relationships between blood glucose level, muscle fiber characteristics, and pork quality. Muscle samples were classified into three groups based on blood glucose level measured at slaughter. Pigs with higher area percentages of fiber type IIB showed higher blood glucose levels compared to pigs with lower area percentages of fiber type IIB. The high blood glucose level group presented lower pH values at 45min and 24h postmortem, and also had higher L(∗) values and reduced water holding capacity. In addition, blood glucose level had a negative relationship with pH(45min) and the solubility of sarcoplasmic and myofibrillar proteins, whereas it had a positive relationship with drip loss and filter-paper fluid uptake. In conclusion, blood glucose level was related to muscle fiber area composition and could partially indicate ultimate pork quality.

Upregulation of glial cell line-derived neurotrophic factor (GDNF) in the rat cochlea following noise.

There are endogenous intracellular mechanisms that provide cells with protection from stress, as well as repair from damage. These pathways often involve stress proteins and neurotrophic factors. The present study used Western blot analysis to examine changes in glial cell line-derived neurotrophic factor (GDNF) following noise overstimulation. A noise exposure was utilized which causes a temporary threshold shift and has been previously shown to upregulate heat shock protein 72 in the rat cochlea. This noise exposure also provides protection from a second noise exposure that would otherwise cause a permanent threshold shift. Experimental animals were assessed 2, 4, 8 and 12 h after cessation of noise exposure. Control animals received the same treatment except for the noise exposure and were assessed at the 8 h time point. A moderate expression of GDNF was observed in the normal cochlea. No significant change in GDNF levels was observed at 2 or 4 h following noise overstimulation. However, a significant increase was found at 8 h. At 12 h following noise overstimulation, GDNF levels were no longer significantly elevated from normal. These results suggest that GDNF is involved in the endogenous stress response in the cochlea and are consistent with the protection that exogenously applied GDNF has been shown to provide.

Combination chemotherapy with cyclophosphamide, vincristine, cisplatin and etoposide (COPE) combined with radiotherapy for small cell lung cancer.

OBJECTIVES: Small cell lung cancer is sensitive to chemotherapy and radiotherapy. Nevertheless, responses are still short-lived and apparent cure remains for only limited disease patients. METHODS: We combined cyclophosphamide (750 mg/m2 by intravenous infusion at first day) vincristine (2 mg intravenously at third day), cisplatin (20 mg/m2 intravenously for 3 days), and etoposide (100 mg/m2 intravenously for 3 days) with radiotherapy (total 300cGy over 4 weeks in 17 fractions) and treated 39 patients with small cell lung cancer who had received no prior systemic chemotherapy and radiotherapy. RESULTS: 1) Thirty-nine patients (limited disease: 17 patients, extensive disease 22 patients) were treated and 35 patients were evaluable for response. Overall response rate was 82.8% (complete response 28.6%, partial response 54.2%). 2) The median survival was 52 weeks for all patients and 58 weeks for limited disease and 45 weeks for extensive disease. There was no statically significant survival difference between the two patient groups. The median relapse-free survival time was 48 weeks. 3) Overall, treatment was well tolerated, with granulocytopenia being the most frequent toxicity. CONCLUSIONS: Combination chemotherapy with COPE regimen combined with radiation therapy was effective as a first line therapy for SCLC.