Activity

0074) and DCB (

= 0.0008) while low CNA was associated with prolonged PFS (

= 0.0060) and DCB (

= 0.0018). However, TMB alone did not distinguish benefits among

-mutant patients. Notably, when combining TMB and CNA, low TMB and high CNA revealed worse outcomes of ICI therapy (mPFS 2.20m,

= 0.0023; proportion of DCB 24%,

= 0.0001).

The combination of TMB and CNA provides more sensible and accurate prediction of ICI response than individual factors in

-mutant LUAD. Moreover, low TMB and high CNA can be utilized as a potential biomarker to predict adverse outcome in

-mutant LUAD.

The combination of TMB and CNA provides more sensible and accurate prediction of ICI response than individual factors in KRAS-mutant LUAD. Moreover, low TMB and high CNA can be utilized as a potential biomarker to predict adverse outcome in KRAS-mutant LUAD.Background Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age ( less then 65 years vs. ≥65 years). Methods A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progression-free survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. selleck inhibitor Results A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients ( less then 65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young ( less then 65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [ less then 65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.Current treatment of T-cell acute lymphoblastic leukemia (T-ALL) is primarily based on high-intensity combination chemotherapy, which has serious side effects. Therefore, developments of novel targeted therapeutics are urgently needed for treatment of T-ALL. In this study, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a novel promising therapeutic target for treatment of T-ALL. MALT1 inhibitor MI-2 significantly suppressed the cell growth, proliferation, and colony formation of T-ALL cells. Furthermore, MI-2 induced cell apoptosis of T-ALL via a mitochondrial-dependent pathway. In a T-ALL mouse model, MI-2 significantly reduced leukemic burden and prolonged the survival of leukemia-bearing mice. Mechanistically, MALT1 inhibition effectively blocked both baseline and Notch1-induced activation of nuclear factor κB pathway, which mediates T-ALL cell survival. In conclusion, our results highlight the potential role of MALT1 as an attractive target for treatment of T-ALL and support the potential of MI-2 or other MALT1 inhibitors to clinical trials in T-ALL.Factor V (FV) is a critical component in the blood coagulation cascade. In patients, FV inhibitors have been reported to be associated with malignancy. FV is present in plasma and platelets, which exhibit physical and functional differences. However, the functions of FV in cancer progression remain poorly understood. We evaluated the impact of different levels of FV in plasma and platelets on the haematogenous mouse pulmonary metastasis model to determine whether FV determines the metastatic potential of circulating tumor cells. The role of platelet-derived FV was evaluated using a murine B16F10 pulmonary metastasis model, an assay of tumor cell adhesion to endothelial cells, and western blotting. By combining genetic models and FV inhibitory antibody, the transgenic mice with lower platelet FV expression showed significant increases in metastases compared with mice with higher platelet FV expression. In vitro, labeled B16F10 melanoma cells appeared to exhibit increased adhesion to endothelial cells that were treated with lower levels of platelet FV, but not platelet-poor plasma. Furthermore, platelets from mice with lower platelet FV levels expressed TFPIα at lower levels than with mice with higher platelet FV expression. Based on these findings, platelet-derived FV contributes to haematogenous pulmonary metastasis and is associated with the regulation of tumor cell adhesion to the vessel wall.Glioblastoma multiforme is an aggressive malignancy, resistant to standard treatment modalities and associated with poor prognosis. We analyzed the role of the IGF system in intracerebral glioma growth using human and rat glioma cells. The glioma cells C6 and U87MG were transduced with a genetically engineered retrovirus expressing type 1 insulin-like growth factor (IGF-IR) antisense RNA, either before or after intra-cerebral implantation of the cells into Sprague Dawley rats or nude mice, respectively and tumor growth and animal survival were monitored. Rat glioma cells transduced prior to orthotopic, intra-cerebral implantation had a significantly increased apoptotic rate in vivo and a significantly reduced tumor volume as seen 24 days post implantation (p less then 0.0015). This resulted in increased survival, as greater than 70% of the rats were still alive 182 days after tumor implantation (p less then 0.01), as compared to 80% mortality by day 24 in the control group. Histomorphology and histochemicition of a dormant state in the brain.