Pulmonary diffusion at rest predicts (VO2peak), although a relation exists for obese subjects only when DLNO is used, and the magnitude of the relation depends on gender when either DLCO or Vc is used. We recommend DLNO as a measure of pulmonary diffusion, both for its ease of collection as well as its tighter relation with (VO2peak).

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Pancreatic cancer is one of the most devastating human malignancies with an estimate yearly death of 280,000 and an overall median 5-year survival rate of less than 5%. The development of relevant preclinical models of the disease to evaluate novel therapeutic strategies can accelerate basic research findings into the much needed clinical application. We used our recently established three-dimensional (3D) in vitro culture assay system that resembles in-vivo tumor growth to screen small molecule libraries. We identified CEP1430, a sonic hedgehog (hh) pathway inhibitor as a potential drug lead molecule. We selected this molecule for further evaluation because the hh pathway is important for the maintenance of cancer stem cells. The CEP1430 treatment markedly inhibited in-vitro growth of human pancreatic CSC (IC50 value of ∼10 nM). In-vitro, CEP1430 induced apoptotic cell death of CSC and reduced pro-angiogenic but increased anti-angiogenic marker expression at the doses tested. In-vivo efficacy of CEP 1430 was evaluated in female SCID mice bearing human pancreatic CSC. The once daily administration (ip) of CEP1430 (doses:10, 15, and 20 mg/kg) for 30 days resulted in 80%, 89% and 90% tumor growth inhibition. The tumor growth inhibitory effect of CEP1430 in all treatment groups was statistically significant in comparison to vehicle treated control (P<0.001). The administration of CEP1430 for a period of 30 days was well tolerated without significant changes in body weight or toxicity by histological examination of tissues and organs. We are using proteomic and miRNA platforms to monitor biomarkers of response, mode of action and selectivity of CEP1430. Further pre-clinical in-vivo studies are ongoing to project human dose and schedule as monotherapy and in combination with therapeutic vaccination to advance CEP1430 for clinical investigation. Citation Format: Jitesh Jani, Mandana Amiri, Cristian Sharma, Joshua Harris, Shruthi Satish, Michael Sharma, Robert Rodriguez, Miriam Navel, Natalee Amezcua, Shaleekha Sharma, Arun Sharma, Dhimant Desai, Shantu Amin, Satya Narayan, Rubio Punzalan, Jay P. Sharma. A novel pharmacological inhibitor CEP1430 for human pancreatic cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4225. doi:10.1158/1538-7445.AM2015-4225

Elevation training masks (ETM) have become popular in active/training populations to enhance performance via purported adaptations associated with altitude and respiratory muscle training. PURPOSE: To compare the effect of training with (TM) to without (CON) wearing the ETM. METHODS: 22 heathy adults (TM: ♂5, ♀6; 27.64±0.86 yr; 23.17±0.88 kg•m 2 | CON: ♂5, ♀6; 29.91±1.63 yr; 24.75±1.03 kg•m 2) provided informed consent for this study. VO2max and time to exhaustion were assessed (Bruce protocol GXT, w/ & w/o ETM). Anaerobic endurance was assessed using two consecutive 300-yrd shuttle sprints (5min rest). Pulmonary function was assessed using a metabolic cart. Following group assignment (TM and CON), subjects trained 3d/wk for 12 wks alternating between steady state running (Progression: 65->85% VO2max, 30->45min) and sprint conditioning every other session with VO2max reassessment following wk 6. The TM group performed all sessions wearing the ETM at manufacturer reported simulated altitude of 9,000 ft. A (2)group x (2)time ANCOVA followed by a Tukey's post-hoc test was used to detect within and between group differences following training. Type I error set at α=0.05. RESULTS (Table): The TM group was found to have a lower improvements in aerobic as well as anaerobic capacity compared to the CON group (p<0.05) with reduced reductions in % body fat (p<0.05). No between group differences were observed for pulmonary function measures. CONCLUSION: Training w/ the ETM does not enhance, and may inhibit, improvements in aerobic or anaerobic endurance compared to standard training. However, further study is required to determine if there may be adaptive benefits to ETM training for those who typically perform under restricted breathing conditions.