The tumor suppressor role and ceRNA network of miR-1294 in cancer.

miRNAs are endogenous small RNAs that are important regulators of gene expression. miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators. miR-1294 affects the proliferation, migration, invasion, and apoptosis of cancer cells. The target genes of miR-1294 are involved in the PI3K/AKT/mTOR, RAS, and JAK/STAT signaling pathways. Six target genes of miR-1294 are the targets of a variety of drugs. Low expression of miR-1294 is associated with resistance to cisplatin and TMZ and a poorer prognosis in patients with ESCC, GC, EOC, PDAC, or NSCLC. Therefore, this work outlines the molecular mechanisms and provides a basis for the clinical significance of the tumor suppressor miR-1294 in cancer.

Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine.

Background: This study aimed to investigate the impact of early adverse events (AE) following the initiation of lapatinib plus capecitabine on the progression-free survival (PFS) and overall survival (OS) outcomes of human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer (ABC) patients. Methods: A secondary analysis of participants treated with lapatinib plus capecitabine, or ado-trastuzumab emtansine in the clinical trial EMILIA was conducted. Cox proportional hazard analysis was used to assess the impact of AE occurring within the first 42 days of lapatinib plus capecitabine therapy on the PFS and OS outcomes of ABC patients. Results: The study included 488 HER2-positive (ABC) patients initiated on lapatinib plus capecitabine. Rash (Hazard Ratio (HR) [95% Confidence Interval (CI)]: Grade 1 = 0.67 [0.46-0.98], Grade 2+ = 0.71 [0.42-1.19]; p = 0.046) and hand-foot syndrome (HR [95% CI]: Grade 1 = 0.58 [0.43-0.80], Grade 2+ = 0.61 [0.43-0.86]; p = <0.001) occurring within the first 42 days of lapatinib plus capecitabine therapy were significantly associated with improved OS. Conversely, nausea and vomiting occurring within the first 42 days of lapatinib plus capecitabine therapy was significantly associated with worsened OS (HR [95% CI]: Grade 1 = 1.08 [0.82-1.42], Grade 2+ = 1.52 [1.13-2.03]; p = 0.027). Conclusions: Rash and hand-foot syndrome occurring early after the initiation of on lapatinib plus capecitabine were significantly associated with improved OS, while early nausea and vomiting was associated with worse OS. In HER2-positive ABC patients initiating lapatinib plus capecitabine, consideration should be given to more closely monitoring patients at risk of nausea and vomiting, while rash and hand foot syndrome are AE associated with improved survival.

Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells.

Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo.

Polarization and apoptosis of T cell subsets in idiopathic thrombocytopenic purpura.

It is well known that idiopathic thrombocytopenic purpura (ITP) is an acquired organ-specific autoimmune hemorrhagic disease and dysfunctional cellular immunity is considered important in the pathophysiology of ITP, however, polarization and apoptosis profiles of T lymphocytes remain unclear completely. In this paper, we investigated the polarization of T cell subsets, the expressions of apoptotic proteins Fas/FasL on T cell subsets and the level of antiapoptotic gene bcl-2 and bax mRNA in the bcl-2 family, then discussed the role of them in ITP pathogenesis. We demonstrated that the ratios of Th1/Th2 and Tc1/Tc2 in ITP children increased obviously, the average percentages of Th1 and Th2 also increased clearly, but the average percentages of Tc1 and Tc2 did not changed. In ITP children, the expressions of Fas, FasL on Th, Th1, Th2, Tc, Tc1 and Tc2 increased significantly. The expressions of FasL on Th1 and Tc1 increased sharply vs. Fas, whereas the expressions of Fas on Th2 and Tc2 increased obviously vs. FasL. The expressions of bcl-2 mRNA in ITP children increased significantly, but the expressions of bax mRNA decreased, the ratios of bcl-2/bax mRNA were improved obviously and there were positive correlation between the ratios of Th1/Th2 (IFN-gamma(+)T/IL-4(+)T) and the ratios of bcl-2/bax mRNA. Taken together, our findings indicate that ITP is Th1 type cell predominant disease although the precise mechanisms await further functional assay. This abnormal polarization of T cell subsets might be related to the high ratios of bcl-2/bax mRNA and the abnormal expressions of Fas, FasL on T cell subsets, as can involve in ITP immunopathogenesis.