Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma.

Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulation of genes relevant to quinolinate phosphoribosyltransferase-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also report that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but nicotinamide riboside kinase 1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations is synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.

[Successful Conservative Management of Bronchopleural Fistula after Intraoperative Bronchial Injury].

A 64-year-old woman diagnosed as primary lung cancer was admitted for surgery. Right lower lobectomy and ND2a-1 nodal dissection was performed under video-assisted thoracic surgery( VATS). The membranous portion of intermediate bronchus was injured about length of 5 mm while dissecting subcarinal lymph nodes. The fistula was closed by knotted suture using 4-0 polydioxanone (PDS) and covered with pericardial fat pad. Although the postoperative course was uneventful and discharged at postoperative day (POD) nine, bloody sputum appeared and right pneumothorax developed at POD 11. Bronchoscopy revealed a slit-like bronchopleural fistula at intermediate bronchus. By continuous thoracic drainage, the fistula successfully closed at POD 13.

Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy.

Recent advances in cancer biology reveal the importance of metabolic changes in cancer; however, less is known about how metabolic pathways in tumors are regulated in vivo. Here, we report analysis of the lung cancer metabolism based on different surgical procedures, namely lobectomy and partial resection. In lobectomy, but not in partial resection, pulmonary arteries and veins are ligated prior to removal of tissues, rendering tissues ischemic. We show that tumors indeed undergo ischemia upon lobectomy and that the tumor metabolome differs markedly from that of tumors removed by partial resection. Comparison of the responses to ischemia in tumor and normal lung tissues revealed that lung cancer tissue exhibits greater TCA cycle and autophagic activity than do normal lung tissues in vivo in patients. Finally, we report that deleting ATG7, which encodes a protein essential for autophagy, antagonizes growth of tumors derived from lung cancer cell lines, suggesting that autophagy confers metabolic advantages to lung cancer. Our findings shed light on divergent metabolic responses to ischemia seen in tumors and normal tissues.

Preoperative bronchoscopic cancer confirmation does not increase risk of recurrence in stage1A non-small cell lung cancer.

OBJECTIVE: This study was conducted to evaluate the risk of recurrence possibly caused by preoperative bronchoscopic cancer confirmation in stage1A non-small cell lung cancer. METHODS: One hundred and seventy-nine cases of peripheral non-small cell lung cancer (including 151 adenocarcinoma) with no more than 3 cm in their tumor longer diameter were selected. All patients underwent preoperative diagnostic bronchoscopy followed by lobectomy, and were demonstrated to have pathologically free of lymph node involvement and pleural involvement. Radiological and pathological low-grade adenocarcinomas were excluded. Of 179 cases, 95 were confirmed lung cancer by bronchoscope (Group 1) and rest 84 had failed cancer confirmation by bronchoscope before surgery (Group 2). Forty-eight pairs for non-small cell lung cancer and 41 pairs for adenocarcinoma were identified from each group by propensity caliper matching. Kaplan-Meier method and log-rank test were performed on matched groups, and Cox proportional hazard model analysis was performed on whole matched cases. RESULTS: Log-rank test revealed no significant inferiority of recurrence-free survival of Group 1 in both all-NSCLC and adenocarcinoma subset. Cox proportional hazard model analysis also revealed that the 'presence of preoperative bronchoscopic cancer confirmation' dose not increase risk of recurrence in both NSCLC and adenocarcinoma subset. CONCLUSIONS: It is unlikely that preoperative bronchoscopic cancer confirmation would increase recurrence risk in stage1A non-small cell lung cancer; however, a future prospective study with larger cohorts would be warranted to validate the results.