Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF­κB signaling pathway.

Frizzled family protein 2 (FZD2) is widely associated with tumor development and metastasis. The present study aimed to gain an insight into the role and regulatory mechanism of FZD2 in glioma. The expression level of FZD2 in normal astrocyte and glioma cells was determined by reverse transcription-quantitative PCR and western blotting, and cell transfection was conducted for FZD2 expression knockdown. Malignant behaviors including cell proliferation, migration and invasion, vasculogenic mimicry (VM) and cell stemness were determined using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU) staining, colony formation, wound healing, Transwell, 3D culturing and sphere formation assays. The expression levels of proteins related to stemness, epithelial-mesenchymal transition (EMT) and Notch/NF-κB signaling were measured by western blotting. Then, the Notch agonist, Jagged-1 (JAG), was adopted for rescue experiments. The results demonstrated that FZD2 was highly expressed in glioma cells. Interference of FZD2 expression suppressed the proliferation of glioma cells, as evidenced by the reduced cell viability and the number of EdU+ cells and colonies. Meanwhile, the reduced sphere formation ability and decreased protein expression of Nanog, Sox2 and Oct4 following FZD2 knockdown confirmed that FZD2 repressed cell stemness in glioma. Additionally, FZD2 knockdown suppressed the migration, invasion, EMT and VM formation capabilities of glioma cells, and also blocked the Notch/NF-κB signaling pathway. Furthermore, activation of Notch by JAG treatment partially reversed the aforementioned FZD2 knockdown-mediated changes in glioma cell malignant behaviors. In conclusion, FZD2 may contribute to glioma progression through activating the Notch/NF-κB signaling pathway, providing a plausible therapeutic target for the treatment of glioma.

Role of Radiation-related Lung Function Genes in Prognosis and Immune Infiltration of Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common malignant tumor with no obvious clinical symptoms in its early stages. Patients can be divided into radiotherapysensitive groups (RS) and radiotherapy-resistant groups (RR) due to their varying conditions. The therapeutic effect of radiotherapy is quite different between the two groups. Therefore, this paper explores the role of radiation-related lung function genes in LUAD and its immune landscape. METHODS: Firstly, we divided LUAD samples from the TCGA cohort into RS and RR groups and analyzed differential expression to obtain differentially expressed genes (DEGs). Then, DEGs and patients' grouping information were input into the weighted co-expression network, and the genes in the radiotherapy-related modules were identified. Furthermore, after the intersection of DEGs and lung function-related genes, the prognosis-related genes were obtained through univariate Cox and Lasso-Cox analyses, respectively, and the risk model was constructed. Finally, the differences in prognosis and immunity of the samples in the risk model were explored. Additionally, we also performed a qPCR experiment on lung function-related genes. RESULTS: In this paper, radiation-related genes of LUAD were identified through a series of bioinformatics analyses. By conducting enrichment analysis on these genes, several pathways related to LUAD radiation were identified, and DEGs associated with significant prognosis were determined. Furthermore, a radiation-related risk model of LUAD was developed. All samples were divided into high-risk and low-risk groups based on the risk score, and the differences in immune cell infiltration abundance and immune function between these groups were evaluated. The qPCR experimental results demonstrated a significant difference in the expression of genes related to lung function. CONCLUSION: The prognosis-related genes identified in this paper and the risk model created can serve as a reference for diagnosing and treating LUAD.

Current and future research on the association between gut microbiota and breast cancer.

Breast cancer (BC) is a prevalent malignancy. There exists a strong association between gut microbiota (GM) and the development of BC. The GM composition in individuals with BC significantly differs from that in their healthy counterparts. Furthermore, the distribution of GM varies significantly among individuals with different types of BC. The GM can impact BC through metabolite secretion, the gut-mammary axis, and other pathways. Modulating the GM can serve as a very promising potential therapeutic strategy in the treatment of BC. This article will summarize existing research, focusing on the relationship between intestinal microbiota and BC. At the same time, the project will also analyze the application value of intestinal microorganisms in BC intervention work, so as to provide a reference for the further development of BC prevention and treatment work.

Prognostic value of lymphocyte-C-reactive protein ratio in patients with liver cancer: a meta-analysis.

Background: The impact of lymphocyte-C-reactive protein ratio (LCR) on clinical outcomes has been reported in liver cancer such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), but the results remain inconsistent. Methods: We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for relevant studies evaluating the association of LCR with survival outcomes and clinicopathological parameters. Results: Eight studies with 4316 patients were included in this meta-analysis. Low LCR was significantly associated with poor overall survival, disease-free survival/relapse-free survival and disease progression clinicopathological parameters in patients with HCC or ICC. Conclusion: Low pretreatment LCR was an adverse prognostic indicator in patients with HCC or ICC. In addition, it was correlated with clinicopathological parameters indicating a higher stage of malignancy.

Prognostic Significance of Advanced Lung Cancer Inflammation Index, a Nutritional and Inflammation Index, in Patients With Gastrointestinal Cancers: A Meta-analysis.

Previous studies have investigated the prognostic value of the advanced lung cancer inflammation index (ALI) in gastrointestinal (GI) cancers; however, the results are controversial. This meta-analysis aimed to evaluate the prognostic and clinicopathological role of ALI in patients with GI cancers. A systematic search of electronic databases was conducted to evaluate the prognostic and clinicopathological value of ALI in GI cancers. Nine studies comprising 3,750 patients were included in this meta-analysis. The pooled results showed that a low ALI was significantly associated with worse overall survival (OS, hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.53-2.47, P < 0.001, I2 = 63.9%) and disease-free survival/relapse-free survival (DFS/RFS, HR = 1.49, 95% CI = 1.28-1.73, P < 0.001, I2 = 0%) in patients with GI cancers. In addition, decreased ALI correlated with the depth of tumor invasion and presence of distant metastasis and tended to be associated with male sex, high carcinoembryonic antigen levels, lymph node metastasis, and right-sided colon cancer. Low ALI was associated with adverse OS and DFS/RFS in patients with GI cancer. In addition, decreased ALI also correlated with clinicopathological factors, indicating higher stage of the malignancy.

Nomogram for predicting the survival of patients with small cell carcinoma of the esophagus: A population study based on the surveillance, epidemiology, and end results database.

ABSTRACT: This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722-0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients' survival and prognosis on an individual basis.

Brain metastases from esophageal cancer: A case report.

INTRODUCTION: At present, there is no uniform consensus on the treatment of brain metastases from esophageal cancer. The studies on the treatment of brain metastases from esophageal cancer by radiotherapy combined with temozolomide (TMZ) are even rarer. PATIENT CONCERNS: A 69-year-old woman was admitted to our hospital for brain metastases from esophageal cancer after thoracic irradiation. DIAGNOSES: Magnetic resonance imaging of the head showed a round, heterogeneous metastatic tumor in the left parietal lobe. Brain magnetic resonance imaging showed edema around brain metastasesInterventions: After radiotherapy plus TMZ in this patient's head, the brain metastatic tumor was significantly decreased. OUTCOMES: At the end of radiotherapy, and 1 and 2 months after the end of radiotherapy, the metastatic tumor continued to shrink, and no obvious side effects were observed. LESSONS: This study suggests that radiotherapy plus TMZ might be a feasible option for brain metastases from esophageal cancer.

Incidence and risk of proteinuria associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis of randomized controlled trials.

Objective: We performed a meta-analysis to quantify the overall incidence and risk of proteinuria associated with five newly approved VEGFR-TKIs (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) in cancer patients.Methods: Pubmed, Embase, ASCO abstracts, and ESMO abstracts were searched to identify relevant studies. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were estimated using random or fixed effects models according to the heterogeneity of included studies.Results: A total of 9,446 patients from 20 RCTs were included for the meta-analysis. The use of newly approved VEGFR-TKIs was associated with an increased risk of all-grade (RR 2.35, 95% CI 1.69-3.27, P < 0.001) and high-grade (RR 3.70, 95% CI 2.09-6.54, P < 0.001) proteinuria. On subgroup analysis, lenvatinib, axitinib, and vandetanib significantly increased the risk of all-grade proteinuria, and lenvatinib was associated with an increased risk of high-grade proteinuria. In addition, the risk of developing high-grade proteinuria events was significant for patients with hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), but not for patients with colorectal cancer (CRC) and thyroid cancer (TC).Conclusion: Treatment with newly approved VEGFR-TKIs significantly increases the risk of developing proteinuria events in cancer patients, especially for patients treated with lenvatinib.

Extramedullary plasmacytoma of the trachea: A case report and review of the literature.

RATIONALE: Extramedullary plasmacytomas (EMPs) are rare solitary soft tissue tumors characterized by monoclonal proliferation of plasma cells. Most lesions occur in the head and neck, but primary tracheal lesions are very rare. PATIENT CONCERNS: In this report, we describe a case of tracheal EMP discovered in a 48-year-old man who presented with a history of progressive dyspnea. DIAGNOSES: Computed tomography (CT) revealed a well-defined nodular mass in the posterior wall of trachea without signs of invasion of the tracheal walls. Then, a reddish mass occluding approximately 90% of the trachea was evidenced by bronchoscopic examination. INTERVENTIONS: The patient was treated with surgery followed by adjuvant radiotherapy to achieve better local control. OUTCOMES: After the surgery, there was immediate symptomatic relief. There was no recurrence or metastasis during a 6-month follow-up. LESSONS: This study presents a rare case of tracheal EMP occluding approximately 90% of the lumen that was successfully managed by surgery followed by radiotherapy.

The role of NRAGE subcellular location and epithelial-mesenchymal transition on radiation resistance of esophageal carcinoma cell.

BACKGROUND: Neurotrophin receptor-interacting MAGE homolog (NRAGE) has been considered as a tumor suppressor. In the previous study, we established human esophageal carcinoma resistance cell line TE13R120 and found the difference of NRAGE expression between TE13 and TE13R120 cells by gene microarray. Herein, we further discuss the possible molecular mechanism of NRAGE on participating the radiation sensitivity of esophageal carcinoma cells. MATERIALS AND METHODS: We used colony formation assay to measure the surviving fraction and relevant radiobiological parameters. NRAGE expression was estimated by immunofluorescence and Western blot. Tumor growth factor-ß (TGF-ß) was used for inducing epithelial-mesenchymal transition (EMT) in TE13 cells to detect the relationship between NRAGE and EMT; the capacity of cell migration was also assessed by wound healing assay. RESULTS: TE13R120 cells were showed significantly radioresistance compared with TE13. The D0, Dq, and N value of TE13R120 were all higher than those of TE13 (2.499, 1.991, and 2.219 vs. 2.242, 0.854, and 1.645), as well as SF2 (0.734 vs. 0.538). Results of immunofluorescences showed that NRAGE was mainly expressed in the nucleus of TE13R120 cells, but in TE13 cells, it was mainly in cytoplasm. In addition, EMT phenotype was observed in TE13R120 cells and TGF-ß-induced EMT in TE13 cells, E-cadherin expression was decreased, but vimentin was upregulated. Furthermore, TE13 cells have a rising tendency in NRAGE nucleus expression after treatment with TGF-ß. Results of wound healing assay showed that the cell migration of TE13R120 and TGF-ß-induced EMT in TE13 cells were remarkably enhanced. CONCLUSIONS: Our results indicate that NRAGE subcellular localization is related to radiation resistance of esophageal carcinoma cell and EMT may be involved in NRAGE subcellular location.

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis.

PURPOSE: Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors. METHODS: PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were randomized controlled trials of cancer patients treated with PD-1 inhibitors with adequate data on hepatic AEs. RESULTS: A total of nine randomized controlled trials with a variety of solid tumors were eligible for the meta-analysis. The use of PD-1 inhibitors significantly increased the risk of developing all-grade hepatic AEs but not for high-grade hepatic AEs in comparison with chemotherapy or everolimus control. Additionally, the risk of all-grade and high-grade hepatic AEs with a nivolumab/ipilimumab combination was substantially higher than ipilimumab. No significant differences in the risk of all-grade and high-grade hepatic AEs were found between PD-1 inhibitors monotherapy and ipilimumab. CONCLUSION: While the use of PD-1 inhibitors is associated with an increased risk of developing hepatic AEs in cancer patients, this is primarily for lower grade events.

Risk of severe rash in cancer patients treated with EGFR tyrosine kinase inhibitors: a systematic review and meta-analysis.

AIM: We performed a meta-analysis to evaluate the incidence and risk factors of severe rash associated with the use of EGFR tyrosine kinase inhibitors (TKIs). METHODS: PubMed, EMBASE and oncology conference proceedings were searched for articles published till March 2016. RESULTS: A total of 18,309 patients from 37 randomized controlled trials were available for the meta-analysis. The overall incidence for severe rash was 6.6% (95% CI: 5.2-8.3%) among patients receiving EGFR-TKIs. The use of EGFR-TKIs significantly increased the risk of developing severe rash (risk ratio: 7.70; 95% CI: 5.79-10.23) in cancer patients. On subgroup analysis, the increased risk of severe rash was driven predominantly by drug type (p = 0.002). CONCLUSION: EGFR-TKIs significantly increase the risk of developing severe rash in cancer patients.

Risk of mTOR inhibitors induced severe pneumonitis in cancer patients: a meta-analysis of randomized controlled trials.

BACKGROUND: A meta-analysis of randomized controlled trials was performed to determine the overall risk of noninfectious severe pneumonitis associated with mTOR inhibitors (mTORi) in cancer patients. MATERIALS & METHODS: PubMed, EMBASE and oncology conference proceedings were searched for relevant studies. RESULTS: A total of 8377 patients from 16 randomized controlled trials were included. The incidence of severe pneumonitis associated with mTORi was 1.7% (95% CI: 1.1-2.5%). The use of mTORi significantly increased the risk of severe pneumonitis compared with controls (odds ratio: 3.36; 95% CI: 2.20-5.12). The analysis was stratified for drug types, tumor types, controlled therapy and mTORi-based regimens, but no significant differences in odds ratios were observed. CONCLUSION: mTORi significantly increase the risk of severe pneumonitis in cancer patients.

Incidence and risk of severe infections associated with aflibercept in cancer patients: a systematic review and meta-analysis.

AIMS: Aflibercept is an engineered humanized vascular endothelial growth factor (VEGF)-targeted agent. Severe infections are serious adverse event associated with aflibercept. However, the contribution of aflibercept to infection is still unknown. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing severe infections in cancer patients treated with aflibercept. METHODS: Electronic databases including PubMed, Embase and abstracts presented at American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meeting were searched. Eligible studies were phase II and III prospective clinical trials of aflibercept in cancer patients with toxicity profile on infections. Summary incidences, relative risk (RR), odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 4310 patients with a variety of solid tumours from 10 prospective clinical trials were included in the meta-analysis. The incidence of high grade infections associated with aflibercept was 7.3% (95% CI 4.3, 12.0%), with a mortality of 2.2% (95% CI 1.5, 3.1%). In addition, patients treated with aflibercept had a significantly increased risk of developing high grade (RR 1.87, 95% CI 1.52, 2.30; P < 0.001) and fatal (OR 2.16, 95% CI 1.14, 4.11; P = 0.018) infections. No evidence of publication bias was observed. Furthermore, the risk of infections with aflibercept was substantially higher than bevacizumab. CONCLUSIONS: Aflibercept is associated with a significant increased risk of developing severe infections in patients with solid tumours. Frequent clinical monitoring and appropriate management for infections should be emphasized during aflibercept treatment.

Prognostic role of elevated platelet count in patients with lung cancer: a systematic review and meta-analysis.

Recently, more and more studies have shown that platelet count (PLT) may be associated with the prognosis of lung cancer (LC). However, the prognostic role of PLT in lung cancer is still controversial. In the present study, we conducted a meta-analysis of all available English studies to evaluate the prognostic value of PLT in lung cancer. In order to investigate the association between PLT and overall survival (OS), the hazard ratio (HR) and its 95% confidence interval (CI) was evaluated. The odds ratio (OR) with its 95% confidence interval (CI) was used to assess the relationship between PLT and clinicopathological parameters. There were 12 studies (n = 5,884) were involved in this meta-analysis. The pooled results showed that elevated PLT was a negative predictor for OS and the pooled HRs was significant at 1.74 (95% confidence interval, 1.39-2.19). Elevated PLT was also significantly associated with advanced TNM stage (OR: 2.65, 95% CI: 1.77-3.97) and smoking history (OR: 2.70, 95% CI: 1.79-4.08). In addition, there was no significant correlation between elevated PLT and squamous cell carcinoma (OR: 1.54, 95% CI: 0.77-3.07). Our results demonstrated that elevated PLT denotes a poor prognosis in patients with LC.