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In conclusion, Our preclinical findings position that oxamate not only inhibits tumor growth at a high safe dose but also enhances the efficacy of pembrolizumab in Hu-PBMC-CDX mice. Our study also provides a preclinical model for exploring the efficacy of other immune-based combination therapies for NSCLC.Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.

Few studies have addressed the role of immune-related genes in the survival and prognosis of different esophageal cancer (EC) sub-types. We established two new prognostic model indexes by bioinformatics analysis to select patients with esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) who may benefit from immunotherapy.

Based on TCGA and ImmPort data sets, we screened immune genes differentially expressed between tumor and normal tissues in ESCC and EAC and analyzed the relationship between these genes and patient survival outcomes. We established the risk score models of immune-related genes in ESCC and EAC by multivariate COX regression analysis.

We identified 12 and 11 immune-related differentially expressed genes associated with the clinical prognosis of ESCC and EAC respectively, based on which two prognostic risk score models of the two EC sub-types were constructed. It was found that the survival probability of patients with high scores was significantly lower than that of patients with low scores (p < 0.001). BMP1, EGFR, S100A12, HLA-B, TNFSF18, IL1B, MAPT and OXTR were significantly related to sex, TNM stage or survival outcomes of ESCC or EAC patients (p < 0.05). In addition, the risk score of ESCC was significantly correlated with the level of B cell infiltration in immune cells (p < 0.05).

The prognosis-related immune gene model indexes described herein prove to be useful prognostic biomarkers of the two EC sub-types in that they may provide a reference direction for looking for the beneficiaries of immunotherapy for EC patients.

The prognosis-related immune gene model indexes described herein prove to be useful prognostic biomarkers of the two EC sub-types in that they may provide a reference direction for looking for the beneficiaries of immunotherapy for EC patients.Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Adavosertib supplier Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a range of cancer cell types. The RGG-derived peptide dysregulates SAFA binding and regulation of alternatively spliced targets and decreases levels of key spliceosome proteins in a cell-type specific manner. In contrast, the SAP-derived peptide reduces active histone marks, promotes chromatin compaction, and activates the DNA damage response and cell death in a subset of cancer cell types. Our findings reveal an unprecedented function of SAFA-derived peptides in regulating diverse SAFA molecular functions as a tumor suppressive mechanism and demonstrate the potential therapeutic utility of SAFA-peptides in a wide range of cancer cells.Online MRI-guided radiotherapy (MRgRT) is one of the most recent technological advances in radiotherapy. MRgRT permits the visualization of tumorous and healthy tissue while the patient is on the treatment table and online daily plan adaptations following the observed anatomical changes. In the context of rectal cancer, online MRgRT is a very promising modality due to the pronounced geographical variability of tumor tissues and the surrounding healthy tissues. This current paper will discuss the possible applications of online MRgRT, in particular, in terms of radiotherapy dose escalation and response prediction in organ preservation approaches for rectal cancer.

There is usually a surgical wait time before nephrectomy for patients with clinically localized renal cell carcinoma, and many factors can influence this preoperative wait time. A relatively prolonged wait time may cause tumor progression. Therefore, we assessed the effect of preoperative wait time on the prognosis of patients with clinically localized renal cell carcinoma.

The outcomes of 561 patients with clinically localized renal cell carcinoma who underwent nephrectomy between July 2011 and March 2017 were retrospectively evaluated. According to the wait time before surgery, we divided the patients into three groups short-wait group (≤ 30 days), intermediate-wait group (> 30 and ≤ 90 days), and long-wait group (>90 days). The clinicopathological characteristics were evaluated, and the survival rates of the three groups were compared.

This study included 370 male (66%) and 191(34%) female patients, with a median age of 64 years. There were 520 patients with stage T1 and 41 patients with stage T2 tumors.