Walkerhouston1334

Tumor mutation burden (TMB) and tumor infiltrating lymphocytes have been well-recognized as molecular determinants of immunotherapeutic responsiveness in many types of cancer. However, the relationship between TMB with immune infiltrates and their prognostic role are reported occasionally in skin cutaneous melanoma (SKCM). We obtained the somatic mutation data and transcriptome profiles of 454 SKCM patients from The Cancer Genome Atlas (TCGA) database, and analyzed the mutation profiles using "maftools" package. Correlation analysis revealed that lower TMB levels conferred poor survival outcomes, associated with lower age and advanced pathological stage. Differential analysis was conducted to the genome expression between two TMB groups using "limma" package, and we identified four hub TMB-related immune genes including CNTFR, CRABP2, GAL, and PAEP. We further analyzed the underlying relationships of the copy number variations (CNVs) of four hub genes with immune infiltrates in SKCM microenvironment through TIMER database. The results indicated that diverse forms of CNVs carried by hub genes could commonly inhibit immune infiltrates. Based on the CIBERSORT method, we compared the proportions of 22 immune cells in two TMB groups and assessed their prognostic value. The data revealed that infiltrations levels of regulatory T (Treg) cell and dendritic activated cells in high-TMB group were lower than that in low-TMB group, while M1 and M2 macrophages showed the opposite trend, especially the levels of neutrophil and macrophage correlated positively with prognosis of SKCM. Finally, we constructed a TMB Prognostic Index (TMBPI) to evaluate the predictive accuracy of the four hub TMB-related immune genes. The ROC curve was drawn to assess the predictive accuracy with AUC = 0.664 and higher TMBPI conferred poor survival outcomes, which warranted further investigation and larger samples to validate.The immune system is able to recognize and eliminate tumor cells. Some tumors, including colorectal cancer (CRC), induce immune tolerance via different mechanisms of "immunoediting" and "immune evasion" and can thus escape immune surveillance. The impact of immunotherapy on cancer has been investigated for many years, but so far, the application was limited to few cancer types. Immuno-oncological therapeutic strategies against metastatic colorectal cancer (mCRC), the adaptive immune system activating approaches, offer a high potential for adaptation to the great heterogeneity of CRC. Moreover, novel treatment approaches are currently being tested that might specifically target the disease initiating and maintaining population of colorectal cancer stem cells (CSCs). In this review, we aim to summarize the current state of immune-oncology and tumor immunotherapy of patients with mCRC and discuss different therapeutic modalities that focus on the activation of tumor-specific T-cells and their perspectives such as tumor vaccination, checkpoint inhibition, and adoptive T-cell transfer or on the eradication of colorectal CSCs.

Adjuvant radiotherapy is the main treatment modality for high grade meningioma after surgical resection; however, recurrence and survival outcomes vary. The aim of this study was to create a new "prognostic score" that allows personalized recommendations for post-operative adjuvant radiotherapy in patients with high grade meningioma.

Clinical data were collected from 115 patients with high grade meningioma treated with surgical resection and adjuvant radiotherapy. A prognostic model was built based on the hazards ratios of independent prognostic factors yielded by multivariate cox proportional analysis. Calibration and discrimination of the prognostic score was evaluated using good of fit test and Harrel's C index, respectively.

A total of 115 high grade meningioma patients (72 atypical and 43 anaplastic meningiomas) were enrolled. Three factors were independently associated with progression-free survival (PFS) extent of resection (GTR vs. STR), recurrent status (

vs. recurrent), and Ki-67 labeling index (<5% vs. ≥ 5%). The respective β-coefficients were used to generate the "prognostic score". The cohort was divided into low-risk and high-risk groups based on the median prognostic score. Good of fit test showed strong calibration (P = 0.7133) and Harrel's C index 0.766 indicated a strong discrimination capability of the prognostic score. The Harrel's C index for OS was 0.60.

Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.

Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.

S100A8 plays a key role in many cellular processes and is highly expressed in various solid cancers. However, the prognostic role of S100A8 has not been well defined. Therefore, we conducted a quantitative meta-analysis to investigate whether or not S100A8 could be used as a prognostic biomarker in solid tumors.

PubMed, Web of Science, Embase, and Cochrane library were searched to acquire relevant studies that evaluated the association between expression of S100A8 and prognosis of cancer patients. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were extracted to evaluate the association between S100A8 overexpression and Overall Survival (OS), Disease-Free Survival (DFS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS). The expression of S100A8 was also validated by Flow cytometry, immunohistochemistry (IHC), and western blot.

A total of 2,817 patients from 13 independent studies, ranging from 43 to 1,117 patients in size, were statistically analyzedpotential a prognostic biomarker in breast cancer and bladder cancer. More well-designed studies with adequate prognostic data are needed to confirm the prognostic role of S100A8 revealed in this study.The cell cycle protein cyclin G2 is considered a tumor suppressor. However, its regulatory effects and potential mechanisms in oral cancers are not well understood. This study aimed to investigate the effect of cyclin G2 on oral squamous cell carcinoma (OSCC). The data from 80 patients with OSCC were utilized to predict the abnormal expression of cyclin G2. The proliferation and metastasis were determined by a cell counting Kit-8 assay, flow cytometry, a wound-healing assay, and a cell invasion assay. The expression of key proteins and genes associated with the cyclin G2 signaling pathways was determined by western blotting and real-time PCR, respectively. The orthotopic nude mice model was established by a mouth injection of SCC9 cells overexpressing cyclin G2. We showed that the low level of cyclin G2 in OSCC, which is negatively correlated with clinical staging, was a negative prognostic factor for the disease. We also found that cyclin G2 inhibited the proliferation, metastasis, and blocked the cell cycle at G1/S of OSCC cells, suggesting that cyclin G2 has an inhibitory effect in OSCC. Mechanistically, cyclin G2 inhibited the growth and metastasis of OSCC by binding to insulin-like growth factor binding protein 3 (IGFBP3) and regulating the focal adhesion kinase (FAK) -SRC-STAT signal transduction pathway. Cyclin G2 competed with integrin to bind to IGFBP3; the binding between integrin and IGFBP3 was reduced after cyclin G2 overexpression, thereby inhibiting the phosphorylation of FAK and SRC. These results showed that cyclin G2 inhibited the progression of OSCC by interacting with IGFBP3 and that it may be a new target for OSCC treatment.Purpose To investigate the risk-stratifying utility of tumor size and a threshold for further stratification on cancer-specific mortality of thyroid cancer (TC) patients in stage IVB. Methods One thousand three hundred and forty-five patients (620 males and 725 females) with initial distant metastasis over 55 years between 2004 and 2016 from Surveillance, Epidemiology, and End Results databases were investigated, with a median follow-up time of 23 months [interquartile range (IQR), 5-56 months] and a median age of 70 years (IQR, 63-77 years). TC-specific mortality rates were calculated under different classifications. Cox regressions were used to calculate hazard ratios (HRs) and Kaplan-Meier Analyses were conducted to investigate TC-specific survivals. Results In the whole cohort, patients with tumors >4 cm had the highest TC-specific mortality (67.9%, 330/486), followed by tumor size >1 cm but ≤ 4 cm (43.08%, 190/441), and tumor size ≤ 1 cm (32.69%, 34/104). Kaplan-Meier curves showed the increased tumor size was associated with a statistically significant decrease in TC-specific survival (P 4 cm had significantly higher hazard ratios (HRs) of 2.84 (1.72-4.70) and 3.11 (1.84-5.26) after adjusting age, gender, race, and radiation treatment, compared with patients with tumors ≤ 1 cm (P less then 0.001). The TC-specific mortalities and survivals were further investigated among more detailed subgroups divided by different tumor size, and a threshold of 3 cm could be observed (P less then 0.005) for risk stratification. Conclusions Mortality risk increased with tumor size in PTC patients in stage IVB. Our findings demonstrated the possibility of further stratification in IVB stage in current TNM staging system. Patients with tumor size over 3 cm had an excessively high risk of PTC-specific mortality, which may justify the necessity of more aggressive treatment for them.T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive subtype of leukemia for which important progress in treatment efficiency have been made in the past decades to reach a cure rate of 75%-80% nowadays. It is nevertheless mandatory to find new targets and active molecules for innovative therapeutic strategies as relapse is associated with a very dismal outcome. We designed an experimental workflow to highlight the conserved core pathways associated with leukemogenesis by confronting the gene expression profiles (GEPs) of human T-ALL cases to the GEP of a murine T-ALL representative model, generated by the conditional deletion of the PTEN tumor suppressor gene in T cell precursors (tPTEN-/-). We identified 844 differentially expressed genes, common GEPs (cGEP) that were conserved between human T-ALL and murine signatures, and also similarly differentially expressed, compared to normal T cells. Using bioinformatic tools we highlighted in cGEPan upregulation of E2F, MYC and mTORC1. Next, using Connectivity Map (CMAP) and CMAPViz a visualization procedure for CMAP data that we developed, we selected in silico three FDA-approved, bioactive molecule candidates α-estradiol (α-E), nordihydroguaiaretic acid (NDGA) and prochlorperazine dimaleate (PCZ). Fasiglifam clinical trial At a biological level, we showed that the three drugs triggered an apoptotic cell death in a panel of T-ALL cell lines, activated a DNA damage response and interfered with constitutive mTORC1 activation and c-MYC expression. This analysis shows that the investigation of conserved leukemogenesis pathways could be a strategy to reveal new avenues for pharmacological intervention.