This study evaluated the capacity of 23 multidrug-resistant (MDR) clinical isolates of Acinetobacter baumannii to adhere to respiratory epithelial cell surfaces and to form biofilm on a polystyrene surface. All 23 A. baumannii isolates were capable of adhering efficiently to respiratory epithelial cells, and biofilm production was positively associated with epithelial cell adhesiveness (r 0.80, p <0.0001). In the presence of the chelating agent EDTA, biofilm formation was markedly reduced. Cell adhesiveness and biofilm formation were significantly higher in isolates carrying the bla(PER-1) gene as compared with isolates without this extended-spectrum beta-lactamase gene (p <0.005 and p <0.001, respectively). Further examination by RT-PCR showed a positive correlation between the level of expression of the bla(PER-1) gene and the level of biofilm formation (r 0.89, p <0.0001) and cell adhesiveness (r 0.74, p <0.006). Overall, the study demonstrated a high capacity of clinical isolates of MDR A. baumannii to form biofilm and to adhere to respiratory epithelial cells. This feature, combined with multidrug resistance, might contribute to the survival of these organisms and their dissemination in the hospital environment.

The expression level of the telomerase catalytic subunit (telomerase reverse transcriptase, TERT) positively correlates with cell survival after exposure to several lethal stresses. However, whether the protective role of TERT is independent of telomerase activity has not yet been clearly explored. Here, we genetically evaluated the protective roles of both TERT and telomerase activity against cell death induced by staurosporine (STS) and N-methyl-Daspartic acid (NMDA). First generation (G1) TERTdeficient mouse embryonic fibroblasts (MEFs) displayed an increased sensitivity to STS, while TERT transgenic MEFs were more resistant to STS-induced apoptosis than wildtype. Deletion of the telomerase RNA component (TERC) failed to alter the sensitivity of TERT transgenic MEFs to STS treatment. Similarly, NMDA-induced excitotoxic cell death of primary neurons was suppressed by TERT, but not by TERC both in vitro and in vivo. Specifically, NMDA accelerated death of TERT-deficient mice, while TERT transgenic mice showed enhanced survival when compared with wild-type littermates after administration of NMDA. In addition, the transgenic expression of TERT protected motor neurons from apoptosis induced by sciatic nerve axotomy. These results indicate that telomerase activity is not essential for the protective function of TERT. This telomerase activity-independent TERT function may contribute to cancer development and aging independently of telomere lengthening.

A few studies reported the association between negative Helicobacter pylori infection and poor clinical outcome in resected gastric cancer patients. We investigated the H. pylori infection status and its association with the clinical outcome in 274 locally advanced gastric cancer patients (American Joint Committee on Cancer stage IB: 25, II: 82, IIIA: 80, IIIB: 39 and IV: 48) who underwent adjuvant chemotherapy after curative resection (≥D2 dissection). H. pylori infection status in hematoxylin and eosin stained corporal and antral mucosa of non‐tumor tissue was graded according to the updated Sydney System and categorized as H. pylori negative (normal or mild infection) and H. pylori positive (moderate or marked infection). Eighty‐one patients received 5‐fluorouracil (5‐FU) and doxorubicin‐based chemotherapy, while 193 patients underwent 5‐FU, mitomycin‐C and polysaccharide‐K chemotherapy. The median follow‐up duration of survivors was 144 (120–184) months. In univariate analysis, patients with H. pylori negative status (108 patients) demonstrated significantly poor 10‐year overall survival (OS) compared to those with H. pylori‐positive status (166 patients; 21.3% vs. 71.1%, p < 0.0001). H. pylori negative status was associated with poor outcome in all stages except stage IIIB. In multivariate analysis, H. pylori‐negative status was the most significant independent prognostic factor of poor OS (hazard ratio: 3.45, 95% confidence interval: 2.43–4.89, p < 0.0001) followed by old age (>54 years, p < 0.0001), advanced stage (stage III or IV, p = 0.001), and Borrmann type IV (p = 0.027). H. pylori infection status seems to have strong prognostic significance in locally advanced gastric cancer. H. pylori‐negative patients may need careful follow‐up after curative resection.

The purpose of this study was to investigate whether the minimum absolute lymphocyte count during radiotherapy (min ALC) and the absolute lymphocyte count 1 month after radiotherapy (post ALC) could predict clinical outcome in limited-stage small cell lung cancer (LS-SCLC) patients. We analyzed 73 LS-SCLC patients treated with chemotherapy and radiotherapy; we collected data on the min ALC from 62 patients and on the post ALC from 60 patients. Both min ALC and post ALC were statistically significant predictors of overall survival in multivariate analysis (hazard ratio [95 % confidence interval] 2.67 [1.06-6.75], P = 0.038 and 2.62 [1.19-5.74], P = 0.016, respectively). The median overall survival of the patients with min ALC ≤297 and >297 cells/μL was 12.2 and 35.3 months, respectively (P < 0.001). Patients with post ALC ≤698 and >698 cells/μL had an overall survival of 19.3 and 46.9 months, respectively (P = 0.001). The median overall survival of the lymphopenia (min ALC ≤ 297 cells/μL or post ALC ≤ 698 cells/μL) and the non-lymphopenia group (min ALC > 297 cells/μL and post ALC > 698 cells/μL) was 19.0 and 131.7 months, respectively, while the median progression survival was 8.1 and 16.6 months, respectively (P < 0.001 and P = 0.001). Radiation-related lymphopenia could predict poor survival in LS-SCLC. Its prognostic role should be evaluated in further prospective studies.

The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.

No abstract

CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6 in non-small cell lung cancer (NSCLC) and its association with PD-L1 has not been confirmed. The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles for anti-PD-1 therapy in non-small cell lung cancer. CMTM6 and PD-L1 immunohistochemical expressions were evaluated in 35 advanced, treatment-refractory NSCLC patients who received PD-1 inhibitor therapy. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (Pearson's r = 0.342 and p = .044). A positive correlation was also identified in the mRNA expression data. Using receiver operating characteristic curves, the levels of CMTM6 and PD-L1 expression which provided the best distinguishing point between responder versus non-responder to PD-1 inhibitors were 70 and 75 H-scores, respectively. The patients in the PD-1 inhibitor responder group had higher CMTM6 expressions in univariate logistic regression analysis (odds ratio (OR) = 5.333, p = .037). However, PD-L1 expression was not associated with response to PD-1 inhibitor (p = .288). In multivariate analysis, CMTM6 was also found to be an independent predictor of the response to PD-1 inhibitors (OR = 6.226, p = .032). CMTM6 expression can be a promising predictor useful for therapeutic decision-making regarding PD-1 inhibitors.

Recent studies have indicated that the C-reactive protein (CRP)/albumin (CRP/Alb) ratio is associated with clinical outcomes in patients with various carcinomas. However, no studies have explored the association between the ratio of CRP/Alb and clinical outcome of inoperable patients with nonsmall cell lung cancers (NSCLCs). We examined the prognostic impact of CRP/Alb ratio on 165 stage IV NSCLC receiving palliative chemotherapy. The optimal cutoff level of CRP/Alb ratio was set at 0.195. The median follow-up time was 9 months (range, 1–74 months). On univariate analysis, high CRP/Alb ratio (≥0.195) was correlated (P < .001) with poorer overall survival (OS). Subgroup analysis of adenocarcinoma showed that CRP/Alb ratio was significantly (P < .001) associated with OS. Multivariate analysis showed that CRP/Alb ratio was an independent prognostic factor for OS (hazard ratio: 2.227, P = .001). Subgroup analysis revealed that the CRP/Alb ratio had a significant (P = .001) prognostic impact on adenocarcinoma patients receiving platinum chemotherapy. Elevated CRP/Alb ratio was significantly associated with male gender (P = .002) and smoking history (P = .009). The results of this study suggest that the CRP/Alb ratio might be used as a simple, inexpensive, and independent prognostic factor for OS of patients with advanced lung adenocarcinomas receiving platinum chemotherapy.