Exercise may improve lung immunity after surgical stress: Evidence from a nephrectomy model via a bioinformatic analysis.

Exercise offers numerous benefits to cancer patients and plays an essential role in postsurgical cancer rehabilitation. However, there is a lack of research examining the effects of exercise after the surgical stress of nephrectomy. To address this gap, we created an animal model that simulated patients who had undergone nephrectomy with or without an exercise intervention. Next, we performed a bioinformatic analysis based on the data generated by the RNA sequencing of the lung tissue sample. An overrepresentation analysis was conducted using two genome databases (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes [KEGG]). A KEGG analysis of the exercise-treated nephrectomy mice revealed enrichment in immune-related pathways, particularly in the NF-κB and B cell-related pathways. The expression of CD79A and IGHD, which are responsible for B cell differentiation and proliferation, was upregulated in the nephrectomy mice. Differential gene expression was categorized as significantly upregulated or downregulated according to nephrectomy and exercise groups. Notably, we identified several gene expression reversals in the nephrectomy groups with exercise that were not found in the nephrectomy without exercise or control groups. Our preliminary results potentially reveal a genetic landscape for the underlying mechanisms of the effects of exercise on our nephrectomy model.

Topical Prevention of Radiation Dermatitis in Breast Cancer Patients: A Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND/AIM: Radiation dermatitis is a common complication of radiation therapy in breast cancer patients. Severe dermatitis may alter treatment schedules and clinical outcomes. The topical prevention strategy is the widely used option to prevent radiation dermatitis. However, the comparison between the current topical prevention strategies is insufficient. Therefore, this study aimed to investigate the topical prevention efficacy of radiation dermatitis in patients with breast cancer through a network meta-analysis. PATIENTS AND METHODS: This study followed The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses guidelines. A random effects model was used to compare different treatments. The treatment modality ranking was evaluated using the P-score. I2 and Cochran's Q test were used to evaluate the heterogeneity among studies. RESULTS: Forty-five studies were analyzed in this systematic review. A total of 19 studies were finally included in this meta-analysis for grade 3 or higher radiation dermatitis, which included 18 treatment arms and 2,288 patients. The forest plot showed that none of the identified regimens were superior to standard care. CONCLUSION: A more effective regimen than standard care for the prevention of grade 3 or higher radiation dermatitis in breast cancer patients was not identified. Our network meta-analysis showed that current topical prevention strategies are similarly efficacious. However, since preventing severe radiation dermatitis is an important clinical challenge, further trials should be conducted to address this issue.

Patients with obstructive sleep apnea are at great risk of flavor disorders: a 15-year population-based cohort study.

OBJECTIVE: Obstructive sleep apnea (OSA) results from upper airway remodeling, which has been suggested to alter sensory and motor neuron function due to hypoxia or snore vibration. This study investigated whether OSA was associated with the risk of flavor disorder (FD). MATERIALS AND METHODS: Seven thousand and eight hundred sixty-five patients with OSA and 7865 propensity score-matched controls without OSA were enrolled between 1999 and 2013 through a nationwide cohort study. The propensity score matching was based on age, sex, comorbidities including hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), asthma, ankylosing spondylitis, and Charlson comorbidity index, and co-medications during the study period, including statins and angiotensin-converting enzyme (ACE) inhibitors. The adjusted hazard ratio (aHR) of incident FD following OSA was derived using a Cox proportional hazard model. A log-rank test was used to evaluate the time-dependent effect of OSA on FD. Age, sex, comorbidities, and co-medications were stratified to identify subgroups susceptible to OSA-associated FD. RESULTS: Patients with OSA were at a significantly great risk of FD (aHR = 1.91, 95% CI = 1.08-3.38), which was time-dependent (log-rank test p = 0.013). Likewise, patients with hyperlipidemia were at a significant great risk of FD (aHR = 2.99, 95% CI = 1.33-6.69). Subgroup analysis revealed that female patients with OSA were at higher risks of FD (aHR = 2.39, 95%CI = 1.05-5.47). CONCLUSIONS: Patients with OSA were at significantly great risk of incident FD during the 15-year follow-up period, especially in female patients with OSA. CLINICAL RELEVANCE: Timely interventions for OSA may prevent OSA-associated FD.

The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling.

Background and Objectives: PNU-74654, a Wnt/ß-catenin inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. Materials and Methods: HepG2 and Huh7 liver cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver cancer cells in response to PNU-74654 was assessed by cell viability assays, and the apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. Results: Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. Conclusions: PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.

Topical Prevention of Radiation Dermatitis in Head and Neck Cancer Patients: A Network Meta-analysis.

BACKGROUND/AIM: Head and neck cancer is a major malignancy worldwide. The treatment strategy for head and neck cancer usually involves radiotherapy. The main side effect of radiotherapy is radiation dermatitis. Thus, determining the most effective topical regimen for the prevention of radiation dermatitis in head and neck cancer patients is a critical issue. PATIENTS AND METHODS: PRISMA-NMA guidelines were used in this network meta-analysis. We included only randomized control trials. A random effects model was used. Heterogeneity was evaluated by I2 and Cochran's Q tests. RESULTS: We included a total of 1,304 patients in the network meta-analysis. Among them, olive oil was the only effective regimen when compared with usual care (OR=0.18, 95%CI=0.03-0.95). The I2 value was 56%. The test of heterogeneity yielded a p-value of 0.10. CONCLUSION: Olive oil was the most effective regimen for the prevention of radiation dermatitis.

Intravesical Instillation of Azacitidine Suppresses Tumor Formation through TNF-R1 and TRAIL-R2 Signaling in Genotoxic Carcinogen-Induced Bladder Cancer.

Azacitidine, an inhibitor of DNA methylation, shows therapeutic effects against several malignancies by inducing apoptosis and inhibiting tumor cell proliferation. However, the anti-tumor effects of azacitidine on urinary bladder urothelial carcinoma (UBUC), especially following intravesical instillation (IVI), are not established. Here, UBUC cell lines were used to analyze the in vitro therapeutic effects of azacitidine. Potential signaling pathways were investigated by antibody arrays and Western blotting. The N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat UBUC model was used for in vivo quantitative analysis of tumor burden. Azacitidine significantly inhibited DNMT expression in UBUC cell lines and reduced cell viability and clonogenic activity, as determined by MTT and colony formation assays, while also inducing significant cytotoxic effects in the form of increased sub-G1 and Annexin V-PI populations (all p < 0.05). Antibody arrays confirmed the in vitro suppression of TNF-R1 and the induction of TRAIL-R2 and their downstream signaling molecules. TNF-R1 suppression reduced claspin and survivin expression, while TRAIL-R2 activation induced cytochrome C and caspase 3 expression. Rats with BBN-induced bladder cancer had a significantly reduced tumor burden and Ki67 index following IVI of azacitidine (p < 0.01). Our study provides evidence for a reduction in BBN-induced bladder cancer by IVI of azacitidine through alterations in the TRAIL-R2 and TNF-R1 signaling pathways. These findings might provide new insights for further clinical trials.

In silico identification of potential targets and drugs for non-small cell lung cancer.

Lung cancer is one of the leading causes of death in both the USA and Taiwan, and it is thought that the cause of cancer could be because of the gain of function of an oncoprotein or the loss of function of a tumour suppressor protein. Consequently, these proteins are potential targets for drugs. In this study, differentially expressed genes are identified, via an expression dataset generated from lung adenocarcinoma tumour and adjacent non-tumour tissues. This study has integrated many complementary resources, that is, microarray, protein-protein interaction and protein complex. After constructing the lung cancer protein-protein interaction network (PPIN), the authors performed graph theory analysis of PPIN. Highly dense modules are identified, which are potential cancer-associated protein complexes. Up- and down-regulated communities were used as queries to perform functional enrichment analysis. Enriched biological processes and pathways are determined. These sets of up- and down-regulated genes were submitted to the Connectivity Map web resource to identify potential drugs. The authors' findings suggested that eight drugs from DrugBank and three drugs from NCBI can potentially reverse certain up- and down-regulated genes' expression. In conclusion, this study provides a systematic strategy to discover potential drugs and target genes for lung cancer.