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Choline is an essential human nutrient that is particular important for proliferating cells, and altered choline metabolism has been associated with cancer transformation. Yet, the various metabolic fates of choline in proliferating cells have not been investigated systematically.

This study aims to map the metabolic products of choline in normal and cancerous proliferating cells.

We performed

C-choline tracing followed by liquid chromatography-high resolutionmass spectrometry (LC-HRMS) analysis of metabolic products in normal and in vitro-transformed (tumor-forming) epithelial cells, and also in tumor-derived cancer cell lines. Selected metabolites were quantified by internal standards.

Untargeted analysis revealed 121 LCMS peaks that were

C-labeled from choline, including various phospholipid species, but also previously unknown products such as monomethyl- and dimethyl-ethanolamines. Interestingly, we observed formation of betaine from choline specifically in tumor-derived cells. Expression of choline dehydrogenase (CHDH), which catalyzes the first step of betaine synthesis, correlated with betaine synthesis across the cell lines studied. RNAi silencing of CHDH did not affect cell proliferation, although we observed an increased fraction of G

M phase cells with some RNAi sequences, suggesting that CHDH and its product betaine may play a role in cell cycle progression. Betaine cell concentration was around 10µM, arguing against an osmotic function, and was not used as a methyl donor. The function of betaine in these tumor-derived cells is presently unknown.

This study identifies novel metabolites of choline in cancer and normal cell lines, and reveals altered choline metabolism in cancer cells.

This study identifies novel metabolites of choline in cancer and normal cell lines, and reveals altered choline metabolism in cancer cells.

The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined.

Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (< 50% area), or extensive (≥ 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed.

Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis n = 552, 60.1% vs < 50% necrosis n = 256, 27.9% vs ≥ 50% necrosis n = 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS no necrosis, 84.0months vs < 50% necrosis, 73.6months vs ≥ 50% necrosis 59.3months; p < 0.001) and RFS (median RFS no necrosis, 49.6months vs < 50% necrosis, 38.3months vs ≥ 50% necrosis 26.5months; p < 0.05). Patients with T1 tumors with extensive ≥ 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8months; p = 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4months; p = 0.713).

Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.

Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.

The bilateral recurrent laryngeal nerve (RLN) lymph nodes are the most common metastatic site for esophageal squamous cell carcinoma (ESCC); however, the RLNs are susceptible to injury during dissection. Clinically, there is an urgent need to determine an effective diagnostic method for RLN nodes to help achieve selective nodal dissection and avoid potential serious complications by performing more conservative surgery for those with nonmetastatic nodes. Here, we innovatively applied endobronchial ultrasonography (EBUS) and investigated its diagnostic performance for preoperative evaluation of RLN nodes in ESCC patients.

All 81 enrolled ESCC patients underwent preoperative EBUS and CT examinations. The ability of EBUS and CT to detect RLN node metastasis was evaluated based on the resulting sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).

The diagnostic performance of EBUS was superior to that of CT; in particular, EBUS of the left RLN (L-RLN) nodes presented the best sensitivity, specificity, PPV, NPV, and accuracy compared with EBUS evaluations of the right RLN (R-RLN) nodes, CT of the L-RLN and R-RLN nodes. Moreover, EBUS combined with CT increased the NPV relative to that of EBUS or CT alone, promoting the ability to identify true-negative RLN nodes. In particular, the NPVs of the combined modality were 100% for both the L- and R-RLN nodes in early-T-stage (T1-T2) ESCC.

EBUS is an efficient tool for RLN node evaluation, and the combination with CT may provide better guidance for selective RLN node dissection in ESCC patients.

EBUS is an efficient tool for RLN node evaluation, and the combination with CT may provide better guidance for selective RLN node dissection in ESCC patients.

This study aimed to construct a nomogram to effectively predict the overall survival (OS) of patients with stage IB non-small-cell lung cancer (NSCLC).

In total, 5513 patients with stage IB NSCLC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and used as the training cohort. We enrolled 440 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, for the external validation cohort. A nomogram was constructed based on the risk factors affecting prognosis using a Cox proportional hazards regression model. NADPH tetrasodium salt in vitro The discrimination and calibration of the nomogram were evaluated by C-indexes and calibration curves.

Six independent risk factors for OS were identified and integrated into the nomogram. The discrimination of the nomogram revealed good prognostic accuracy and clinical applicability as indicated by C-index values of 0.637 (95% CI 0.634-0.641) and 0.667 (95% CI 0.656-0.678) for the training cohort and the external validation cohort, respectively. Additionally, the patients were divided into two groups according to risk (sum-score>185), and significant differences in OS were observed between the high-risk and low-risk groups in the training and external validation cohorts (P<0.