Etoposide soft capsule combined with anlotinib in the third-line treatment of advanced non-small cell lung cancer: a retrospective cohort study.

Background: The physical tolerance in the advanced non-small cell lung cancer (NSCLC) patient often deteriorates, with a limited effective rate of the third-line treatment. This study retrospectively analyzed the efficacy and safety of etoposide soft capsules combined with anlotinib in the third-line treatment of advanced NSCLC. Methods: A retrospective study was conducted on 46 patients with advanced NSCLC who had failed second-line treatment. Progression-free survival (PFS) of advanced NSCLC patients served as an endpoint. Kaplan-Meier survival curves were applied to evaluate the short-term efficacy of anlotinib treatment in advanced NSCLC patients. Results: Among 46 third-line NSCLC patients, none had complete remission (CR), 9 had partial remission (PR), 29 had stable disease (SD), and 8 had progressive disease (PD). The objective response rate (ORR) was 19.57%, the disease control rate (DCR) was 82.61%, the median progression-free survival (mPFS) was 6.3 months, and the median overall survival (mOS) was 10.1 months. Common adverse reactions included fatigue, hypertension, nausea, stomatitis, leukopenia, hand-foot syndrome, abnormal liver function, proteinuria, hemoptysis, and hypothyroidism, among others. The incidence of grade 3 adverse reactions was 8.9%, and there were no grade 4 adverse reactions. Conclusions: Etoposide soft capsule combined with anlotinib demonstrated a marked effect on the third-line treatment of advanced NSCLC patients, and is well tolerated.

Identification of Key Carcinogenic Genes in Colon Adenocarcinoma.

Background: We aimed to probe carcinogenic genes associated with colon adenocarcinoma (COAD) development. Methods: The gene expression profile of COAD were downloaded from TCGA. Differentially expressed genes (DEGs) were identified; GO and KEGG pathway enrichment were analyzed. Applying the up-mRNA-and-down-miRNA pairs and the down-mRNA-and-up-miRNA pairs, the miRNA target network was generated. The important genes were further analyzed towards the influence on overall survival and immune infiltration. In addition, essential miRNAs were selected for expression validation using real-time qPCR. Results: Together, from 2020-2021, in Central Laboratory of the Second Affiliated Hospital of Fujian Medical University, we found 3060 up-regulated transcripts and 2254 down-regulated transcripts in mRNA expression, with 235 up-regulated and 263 down-regulated miRNAs. We discovered 98 enriched GO terms using the up-regulated DEGs and 315 enriched GO terms using downregulated DEGs. There were 14 enriched KEGG pathways based on the down-regulated DEGs and only one pathway based on the up-regulated DEGs. There were 61 up-mRNA-and-down-miRNA pairs, including 7 miRNAs and 41 carcinogenic targets, among which HOXC13, FOXL2NB, ALOXE3, and ZIC2 were found related to a poorer OS. ZIC2 located at the subnet with the most targets (the miR-129-5p subnet). ZIC2 expression was correlated with immune-cell infiltration. Conclusion: These risk genes, interaction networks, and enrichments may provide a better understanding of the complex molecular mechanisms in COAD development and potential therapeutic targets for clinical treatment of COAD.

Expression and clinical significance of PD-1 and NLRP3 in follicular thyroid carcinoma tissues / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨甲状腺滤泡癌（FTC）组织中程序性死亡蛋白1（PD-1）和NOD样受体蛋白3（NLRP3）的表达及其与患者临床病理特征和预后的关系。方法：收集2015年1月至2020年6月福建医科大学附属第二医院手术切除的60例FTC患者的癌和配对癌旁组织标本，采用免疫组织化学染色法检测癌及癌旁组织中PD-1和NLRP3的阳性表达率，χ²检验或者Fisher精确检验法分析PD-1和NLRP3表达与FTC患者临床病理特征的关系，Pearson相关性分析PD-1与NLRP3表达的关系，Kaplan-Meier生存和Logistic回归分析PD-1和NLRP3表达与患者预后的关系。结果：在60例FTC组织中，PD-1和NLRP3均有较高的阳性表达率（46.67%与63.33%）。PD-1表达与FTC患者肿瘤分期、肿瘤大小、血管侵犯、复发与否具有显著相关性（均P<0.05），NLRP3表达与患者肿瘤大小、血管侵犯、甲状腺外浸润以及复发具有显著相关性（均P<0.05）。PD-1与NLRP3的表达成负相关，前者与患者更好的预后相关，后者是FTC复发的独立风险因素。结论：PD-1和NLRP3在FTC组织中有较高的阳性表达率，前者与患者更好的预后相关，后者是FTC复发的独立风险因素，且两者的表达呈负相关。

USP11 facilitates colorectal cancer proliferation and metastasis by regulating IGF2BP3 stability.

The abnormal expression of ubiquitin-specific protease 11 (USP11) is thought to be related to tumor development and progression; however, few studies have reported the biological function and clinical importance of USP11 in colorectal cancer (CRC). Therefore, it is necessary to further explore the role of USP11 in CRC. Immunohistochemical staining was used to explore the association between prognosis and USP11 expression in CRC. Cholecystokinin octapeptide (CCK-8), colony formation, transwell, and animal assays were used to study the abilities of proliferation, migration, and invasion in CRC cells. Co-immunoprecipitation assays, Western blotting, ubiquitination assays, and rescue experiments were performed to elucidate the interaction between USP11 and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3). We verified that USP11 was overexpressed in CRC tissues and was associated with the depth of tumor invasion and metastasis. USP11 knockdown or overexpression could weaken or reinforce the abilities of proliferation, migration, and invasion in CRC cells in vivo or in vitro. IGF2BP3 was protected by USP11 from degradation via deubiquitination. The rescue experiments revealed that IGF2BP3 overexpression could effectively reverse the decrease in cell proliferation, migration, and invasion caused by USP11 knockdown. Therefore, USP11 might be involved in CRC tumorigenesis and development through a USP11-IGF2BP3 axis pathway, and USP11 overexpression might be a novel indicator for poor prognosis and a potential therapeutic target in CRC patients.

YAP regulates ALDH1A1 expression and stem cell property of bladder cancer cells.

BACKGROUND: Yes-associated protein (YAP), a key player of the Hippo pathway, has been identified to have more and more important roles in tumorigenesis and may be an important biomarker for cancer therapy. YAP is important for bladder cancer cell migration, metastasis, and drug resistance; however, its function in bladder cancer stem cells remains unknown. PURPOSE: The aim of this work was to examine the expression and role of YAP in bladder cancer stem cells. MATERIALS AND METHODS: We identified that the expression level of YAP was significantly enriched in bladder cancer stem cells compared to noncancer stem cell population. Moreover, the effect of YAP on stem cell self-renewal was examined in bladder cancer cells by siRNA silencing approach. In addition, we showed that YAP is required for aldehyde dehydrogenase activity in bladder cancer cells. RESULTS: RNAseq analysis and quantitative real-time PCR results showed that silencing of YAP inhibited the expression of ALDH1A1 gene. CONCLUSION: Collectively, our findings for the first time elucidated that YAP serves as a cancer stem cell regulator in bladder cancer, which provided a promising therapy strategy for patients with bladder cancer.