Impact of Somatic Mutations in Non-Small-Cell Lung Cancer: A Retrospective Study of a Chinese Cohort.

BACKGROUND: Somatic mutations are important biomarkers for selecting an optimal targeted therapy and predicting outcomes for non-small-cell lung cancer (NSCLC) patients that are often detected from tissue samples. However, tissue samples are not always readily available from these patients. The exploration of using circulating tumor DNA (ctDNA) to identify somatic mutations offers an alternative source that should be explored. METHODS: In this retrospective study, we included 280 patients diagnosed with adenocarcinoma between 2017 and 2018 in a hospital in eastern China. Tissue or ctDNA was collected, and a wide spectrum of somatic mutations was analyzed by targeted next-generation sequencing platforms. Associations among the mutation status, biomarkers, screening methods, disease stages, and interaction with treatment with overall survival (OS) were investigated. RESULTS: We found that the EGFR L858R mutation was the most frequently identified mutation in adenocarcinoma in this population by both methods, followed by KRAS (p=3.7e-09), PIK3CA (p=5e-04), and HER2 mutations (p=6.3e-03). We observed that EGFR mutations were significantly mutually exclusive with KRAS, HER2, and MET. FGFR1 mutations were significantly more abundantly detected in the ctDNA group. We found an interaction effect between EGFR mutation and target therapies. The ability of the targeted therapy to improve OS in patients with a single EGFR mutation (HR=0.069, p=0.07) approached significance, but this was not the case for the patients with more than one EGFR mutation or without an EGFR mutation (HR=0.813, p=0.725). Furthermore, the effect of chemotherapy was more predominant in the EGFR group in comparison to the control group. CONCLUSION: These findings provide useful information on the distribution of somatic mutations via different screening methods and how this related to the optimal treatment selection in Chinese patients with NSCLC.

Role of long non-coding RNA MALAT1 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a pathological inflammatory condition of the lungs that is associated with high rates of mortality. Although long non-coding RNAs (lncRNAs) serve a role in lung diseases, their functions in COPD pathogenesis are relatively unknown. The present study aimed to assess the role of differentially expressed lncRNAs in COPD. Expression profile analysis of six lncRNAs in age-matched COPD and non-COPD tissues were conducted. Among the six tested lncRNAs, metastasis-associated in lung adenocarcinoma transcript 1 (MALAT1) was the most consistently overexpressed in COPD lung tissue specimens. To model COPD in vitro, human lung fibroblasts were treated with transforming growth factor-ß (TGF-ß) and MALAT1 was knocked down by small interfering RNA. This promoted cell viability and concurrently inhibited the expression of mesenchymal proteins, fibronectin and α-smooth muscle actin. In COPD, cell senescence is linked to the activation of mammalian target of rapamycin complex 1 (mTORC1). Upon gene silencing of MALAT1 in non-TGF-ß-treated cells, cells demonstrated constitutive activation of mTORC1, which was assessed by the protein expression levels of mTORC1 substrate S6 kinase (S6K1). By contrast, upon MALAT1 silencing in the TGF-ß-treated cells, mTORC1 activation was not suppressed, despite the mesenchymal cell markers protein expression levels being downregulated. Thus, lncRNA MALAT1 may represent a potent biomarker in COPD patients and may act as a target for both diagnostic and therapeutic purposes.

The association between body mass index and testosterone deficiency in aging Chinese men with benign prostatic hyperplasia: results from a cross-sectional study.

BACKGROUND AND OBJECTIVES: Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH) and hypogonadism. In this paper, we performed a retrospective study and discussed the prevalence of testosterone deficiency (TD) and its relationship to body mass index (BMI) in aging Chinese men with BPH who have surgical intervention. MATERIAL AND METHODS: We reviewed the clinical data by age, BMI, medical history, serum prostate-specific antigen (PSA) levels, serum total testosterone (TT) levels, biochemical analysis, and transrectal ultrasound. BMI and other variables were considered to be independent variables in an effort to evaluate any potential associations between these factors and TD status using non-adjusted and multivariate-adjusted regression models. RESULTS: Of the 795 BPH participants, 27.2% (216) patients had TD. After adjusting for all potential covariates, there was a similar J-shaped relationship between BMI and TD, with an inflection point of 19.2 kg/m2. The effect sizes and the confidence intervals on the left and right sides of this inflection point were 0.6 (0.4-1.0) (p = .043) and 1.2 (1.1-1.3) (p < .001), respectively. CONCLUSION: Nearly one-third of the aging Chinese BPH patients had TD in this study. The association between BMI and TD is not simple. A J-shaped curve correlation was detected. BMI was positively correlated with TD when it was over 19.2 kg/m2 and inversely correlated with TD when it was below 19.2 kg/m2. Long-term prospective studies are needed to confirm these findings.

An integrated aerobic-anaerobic strategy for performance enhancement of Pseudomonas aeruginosa-inoculated microbial fuel cell.

Microbial fuel cell (MFC) is a promising device for energy generation and organic waste treatment simultaneously by electrochemically active bacteria (EAB). In this study, an integrated aerobic-anaerobic strategy was developed to improve the performance of P. aeruginosa-inoculated MFC. With an aerobic start-up and following an anaerobic discharge process, the current density of MFC reached a maximum of 99.80µA/cm2, which was 91.6% higher than the MFC with conventional constant-anaerobic operation. Cyclic voltammetry and HPLC analysis showed that aerobic start-up significantly increased electron shuttle (pyocyanin) production (76% higher than the constant-anaerobic MFC). Additionally, enhanced anode biofilm formation was also observed in the integrated aerobic-anaerobic MFC. The increased pyocyanin production and biofilm formation promoted extracellular electron transfer from EAB to the anode and were the underlying mechanism for the MFC performance enhancement. This work demonstrated the integrated aerobic-anaerobic strategy would be a practical strategy to enhance the electricity generation of MFC.

TRPM2 mediates histone deacetylase inhibition-induced apoptosis in bladder cancer cells.

PURPOSE: Inhibition of histone deacetylase (HDAC) activity results in growth arrest and apoptosis in multiple types of cancer cells. It has been well established that p21 is responsible for HDAC inhibitor (HDACi)-induced growth inhibition, while the mechanism underlying HDACi-elicited apoptosis in bladder cancer cells remains largely unknown. METHODS: In this study, the apoptotic response to HDACi (trichostatin A and sodium butyrate) with different concentrations was determined by flow cytometry analysis and real-time polymerase chain reaction was conducted to examine the TRPM2 (Transient receptor potential cation channel, subfamily M, member 2) expression change on HDACi treatment. TRPM2 knockdown and overexpression were performed to investigate the role of TRPM2 in HDACi-induced apoptosis. The mechanism of HDACi-elicited upregulation of TRPM2 was studied by chromatin-immunoprecipitation. RESULTS: HDACi efficiently induced cell apoptosis and TRPM2 upregulation in a time- and dose-dependent manner in T24 bladder cancer cells. Functional analysis revealed that TRPM2 overexpression promotes apoptosis of T24 cells. Conversely, TRPM2 depletion remarkably antagonized HDACi-induced apoptosis. Furthermore, HDAC inhibition-elicited TRPM2 upregulation is caused by the increase of acetylated H3K9 (H3K9Ac) enrichment in TRPM2 promoter. CONCLUSIONS: These data suggest that the HDACi-elicited upregulation of TRPM2 expression is required for HDACi-induced apoptosis in bladder cancer cells and that HDACi activated the enrichment of H3K9Ac-represented permissive chromatin in TRPM2 promoter.

Bicalutamide 150 mg as secondary hormonal therapy for castration-resistant prostate cancer.

PURPOSE: This study was aimed to evaluate the effect and tolerability of bicalutamide 150 mg therapy in patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 48 patients with histologically confirmed prostate cancer were included. They had been treated with continuous maximal androgen blockade therapy, but their serum prostate-specific antigen (PSA) increased after initial hormonal therapy. Patients were given bicalutamide (150 mg per day). Serum PSA testing was performed every 3 months. The response was defined according to PSA decline from baseline: PSA decline ≥85% as complete response, ≥50 % but <85% as partial response, and <50 % as failure. Response duration was defined as the time from PSA response until PSA increased ≥25 % or ≥2 ng/mL from the nadir. The potential predictive factors (Gleason score, clinical stage and serum PSA) were investigated. RESULTS: The time of follow-up was 3-30 months. A PSA decline ≥50% was observed in 37 of 48 patients including 18 ≥ 50% but <85% and 19 ≥ 85% responders. The median response duration was 12 months for partial responders and 20 months for complete responders. Patients with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen achieved more benefits. Moreover, bicalutamide 150 mg therapy was well tolerated. CONCLUSIONS: Bicalutamide 150 mg therapy was an appropriate therapeutic method for patients of CRPC, especially for those with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen.

Enhanced bioelectricity generation by improving pyocyanin production and membrane permeability through sophorolipid addition in Pseudomonas aeruginosa-inoculated microbial fuel cells.

Improvement on electron shuttle-mediated extracellular electron transfer (EET) is of great potential to enhance the power output of MFCs. In this study, sophorolipid was added to enhance the performance of Pseudomonas aeruginosa-inoculated MFC by improving the electron shuttle-mediated EET. Upon sophorolipid addition, the current density and power density increased ∼ 1.7 times and ∼ 2.6 times, respectively. In accordance, significant enhancement on pyocyanin production (the electron shuttle) and membrane permeability were observed. Furthermore, the conditions for sophorolipid addition were optimized to achieve maximum pyocyanin production (14.47 ± 0.23 µg/mL), and 4 times higher power output was obtained compared to the control. The results substantiated that enhanced membrane permeability and pyocyanin production by sophorolipid, which promoted the electron shuttle-mediated EET, underlies the improvement of the energy output in the P. aeruginosa-inoculated MFC. It suggested that addition of biosurfactant could be a promising way to enhance the energy generation in MFCs.

CXCR4-mediated Stat3 activation is essential for CXCL12-induced cell invasion in bladder cancer.

CXCL12/CXCR4 signaling plays important roles in tumor cell metastasis in many types of cancers, and CXCR4 is the key regulator of cell motility in bladder cancer. Emerging evidence suggests that transcription-3 (Stat3) activation is associated with bladder cancer cell growth and survival, while the relationship between CXCL12/CXCR4 signal and Stat3 activation remains unclear. In this study, expression analysis of bladder cancer and adjacent normal tissues showed that higher CXCR4 expression was associated with Stat3 phosphorylation. CXCR4 knockdown in bladder cancer T24 cells impaired CXCL12-induced cell invasion and Stat3 activation. Furthermore, blocking Stat3 activity with the chemical inhibitor Stattic inhibited CXCL12-triggered Stat3 phosphorylation and cell invasion in T24 cells, suggesting that Stat3 activation is required for CXCL12 function in the mobility of bladder cancer. Taken together, CXCR4 is necessary for CXCL12 signal transduction in bladder cancer, and CXCL12/CXCR4 promotes invasion of bladder cancer cells through activation of Stat3 transcriptional activity.

[Clinical significance of prostatic-specific antigen levels in patients with benign prostatic hyperplasia complicated by low urinary tract syndrome].

OBJECTIVE: To evaluate the clinical significance of prostatic-specific antigen (PSA) levels in patients with benign prostatic hyperplasia (BPH) complicated by low urinary tract syndrome( LUTS). METHODS: The levels of tPSA, fPSA and fPSA/tPSA ratio were detected and compared in 520 cases of BPH with LUTS and 196 cases without LUTS. RESULTS: The mean levels of tPSA in the cases of BPH with LUTS and without LUTS were (5.13 +/- 2.49) microg/L and (1.73 +/- 1.26) microg/L respectively (P<0.01). The mean levels fPSA were (1.57 +/- 0.80) microg/L and (0.54 +/- 0.38) microg/L respectively (P < 0.01). The mean ratios of fPSA/tPSA were (0.31 +/- 0.09) and (0.30 +/- 0.11) respectively ( P > 0.05). CONCLUSION: The levels of tPSA, fPSA are significantly higher in the cases of BPH with LUTS than those in the cases without LUTS, but the ratio of fPSA/tPSA is stable in BPH.

[Modified cystectomy with preservation of erectile and ejaculatory functions in men with nonmalignant bladder disease].

OBJECTIVES: To evaluate modified cystectomy with preservation of erectile and ejaculatory functions in men with nonmalignant bladder disease. METHODS: Seven cases with average age of 27 years presented with bladder disease necessitating cystectomy, including 2 cases of tuberculous contractile bladder, 1 case of extensive polypoid cystitis glandularis, 4 cases of late stage of neurogenic bladder. All patients wished to maintain erectile and ejaculatory functions after the operation. We performed a modified simple cystectomy with preservation of the vasa deferens, seminal vesicles, prostate and neurovascular bundles, as well as construction of an Indiana pouch or ileal neobladder. RESULTS: Average operative time was 5 h 45 min without perioperative complications in this group. Follow-up ranged from 9 to 60 months. Erectile and ejaculatory functions were normal in all cases. All patients remained completely continent and no dysuria in neobladder, and there was no difficulty in inserting catheter to empty pouch. Upper urinary tract was in good condition 3 and 24 months after operation. CONCLUSIONS: Modified cystectomy with preservation of the vasa deferens, seminal vesicles, prostate and neurovascular bundles is an effective and reliable option for the patients who wish to maintain their fertility and erectile function after surgery.