BACKGROUND: Gene expression can be posttranscriptionally regulated by a complex network of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification. However, little is known about both its influence and biogenesis in tumor development. METHODS: This study analyzed TCGA data of patients with five kinds of gastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of the nine known m1A-related enzymes in GI cancers were investigated. Using a variety of bioinformatics approach, the impact of m1A regulators on its downstream signaling pathway was studied. To further confirm this regulation, the effect of m1A writer ALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS: Dysregulation and multiple types of genetic alteration of putative m1A-related enzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR, and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. The expression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown. Furthermore, Gene Ontology analysis revealed that m1A downstream genes were associated with cell proliferation, and the results showed that m1A genes are reliably linked to mTOR. CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer.

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This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.

This review provides insight into the role of engineered T-cell receptors (TCRs) in immunotherapy. Novel approaches have been developed to boost anticancer immune system, including targeting new antigens, manufacturing new engineered or modified TCRs, and creating a safety switch for endo-suicide genes. In order to re-activate T cells against tumors, immune-mobilizing monoclonal TCRs against cancer (ImmTAC) have been developed as a novel class of manufactured molecules which are bispecific and recognize both cancer and T cells. The TCRs target special antigens such as NY-ESO-1, AHNAKS2580F or ERBB2H473Y to boost the efficacy of anticancer immunotherapy. The safety of genetically modified T cells is very important. Therefore, this review discusses pros and cons of different approaches, such as ImmTAC, Herpes simplex virus thymidine kinase (HSV-TK), and inducible caspase-9 in cancer immunotherapy. Clinical trials related to TCR-T cell therapy and monoclonal antibodies designed for overcoming immunosuppression, and recent advances made in understanding how TCRs are additionally examined. New approaches that can better detect antigens and drive an effective T cell response are discussed as well.

Rationale: Methylation at the N6 position of adenosine (m 6 A) is the most prevalent RNA modification within protein-coding mRNAs in mammals, and it is a reversible modification with various important biological functions. The formation and function of m 6 A are regulated by methyltransferases (writers), demethylases (erasers), and special binding proteins (readers) as key factors. However, the underlying modification mechanisms of m 6 A in gastrointestinal (GI) cancer remain unclear. Here, we performed comprehensive molecular profiling of the nine known m 6 A writer, eraser, and reader proteins in GI cancer. Methods: Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used. Gene alteration and pathway analysis were done in cBioportal. The protein network of m 6 A regulators and its related pathway members was analyzed in STRING online platform. Phylogenetic tree was constructed in MEGA7. m 6 A modification sites were predicted by SRAMP. m 6 A related SNPs were analyzed by m 6 ASNP. The modulation of m 6 A on its related pathway members was validated by m 6 A-seq, real-time PCR and phosphor-MAPK array. Results: We found that m 6 A regulators were mostly upregulated in GI cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m 6 A modification in most human cancers, including GI cancer, which was further verified by m 6 A-Seq and phospho-MAPK array. Conclusions: Our findings suggest that m 6 A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The efficacy of immunotherapy usually depends on the interaction of immunomodulation in the tumor microenvironment (TME). This study aimed to explore the potential stromal-immune score-based prognostic genes related to immunotherapy in HCC through bioinformatics analysis.Methods: ESTIMATE algorithm was applied to calculate the immune/stromal/Estimate scores and tumor purity of HCC using the Cancer Genome Atlas (TCGA) transcriptome data. Functional enrichment analysis of differentially expressed genes (DEGs) was analyzed by the Database for Annotation, Visualization, and Integrated Discovery database (DAVID). Univariate and multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed for prognostic gene screening. The expression and prognostic value of these genes were further verified by KM-plotter database and the Human Protein Atlas (HPA) database. The correlation of the selected genes and the immune cell infiltration were analyzed by single sample gene set enrichment analysis (ssGSEA) algorithm and Tumor Immune Estimation Resource (TIMER).Results: Data analysis revealed that higher immune/stromal/Estimate scores were significantly associated with better survival benefits in HCC within 7 years, while the tumor purity showed a reverse trend. DEGs based on both immune and stromal scores primarily affected the cytokine–cytokine receptor interaction signaling pathway. Among the DEGs, three genes (CASKIN1, EMR3, and GBP5) were found most significantly associated with survival. Moreover, the expression levels of CASKIN1, EMR3, and GBP5 genes were significantly correlated with immune/stromal/Estimate scores or tumor purity and multiple immune cell infiltration. Among them, GBP5 genes were highly related to immune infiltration.Conclusion: This study identified three key genes which were related to the TME and had prognostic significance in HCC, which may be promising markers for predicting immunotherapy outcomes.

ObjectivesTo understand knowledge about, and acceptability of, cervical cancer screening and HPV vaccines among medical students; and to explore potential factors that influence their acceptability in China.MethodsWe conducted a survey among medical students at six universities across southwest China using a 58-item questionnaire regarding knowledge and perceptions of HPV, cervical cancer, and HPV vaccines.ResultsWe surveyed 1878 medical students with a mean age of 20.8 years (standard deviation: 1.3 years). Of these, 48.8% and 80.1% believed cervical cancer can be prevented by HPV vaccines and screening respectively, while 60.2% and 71.2% would like to receive or recommend HPV vaccines and screening. 35.4% thought HPV vaccines ought to be given to adolescents aged 13–18 years. 32% stated that women should start to undergo screening from the age of 25. 49.2% felt that women should receive screening every year. Concern about side effects (38.3% and 39.8%), and inadequate information (42.4% and 35.0%) were the most cited barriers to receiving or recommending HPV vaccination and cervical cancer screening. Females were more likely to accept HPV vaccines (OR, 1.86; 95% CI: 1.47–2.35) or cervical cancer screening (OR, 3.69; 95% CI: 2.88–4.74). Students with a higher level of related knowledge were much more willing to receive or recommend vaccines (P<0.001) or screening (P<0.001). Students who showed negative or uncertain attitudes towards premarital sex were less likely to accept either HPV vaccines (OR, 0.67; 95% CI: 0.47–0.96), or screening (OR, 0.68; 0.47–0.10). Non-clinical students showed lower acceptability of cervical screening compared to students in clinical medicine (OR, 0.74; 95% CI: 0.56–0.96).ConclusionsThe acceptability of HPV vaccines and cervical cancer screening is relatively low among medical students in southwest China. Measures should be taken to improve knowledge about cervical cancer and awareness of HPV vaccines and screening among medical students at university.

The introduction of targeted therapy is the biggest success in the treatment of cancer in the past few decades. However, heterogeneous cancer is characterized by diverse molecular alterations as well as multiple clinical profiles. Specific genetic mutations in cancer therapy targets may increase drug sensitivity, or more frequently result in therapeutic resistance. In the past 3 years, several novel targeted therapies have been approved for cancer treatment, including drugs with new targets (i.e., anti-PD1/PDL1 therapies and CDK4/6 inhibitors), mutation targeting drugs (i.e., the EGFR T790M targeting osimertinib), drugs with multiple targets (i.e., the EGFR/HER2 dual inhibitor neratinib) and drug combinations (i.e., encorafenib/binimetinib and dabrafenib/trametinib). In this perspective, we focus on the most up-to-date knowledge of targeted therapy and describe how genetic mutations influence the sensitivity of targeted therapy, highlighting the challenges faced within this era of precision medicine. Moreover, the strategies that deal with mutation-driven resistance are further discussed. Advances in these areas would allow for more targeted and effective therapeutic options for cancer patients.