Emerging Roles of SRSF3 as a Therapeutic Target for Cancer.

Ser/Arg-rich (SR) proteins are RNA-binding proteins known as constitutive and alternative splicing (AS) regulators that regulate multiple aspects of the gene expression program. Ser/Arg-rich splicing factor 3 (SRSF3) is the smallest member of the SR protein family, and its level is controlled by multiple factors and involves complex mechanisms in eukaryote cells, whereas the aberrant expression of SRSF3 is associated with many human diseases, including cancer. Here, we review state-of-the-art research on SRSF3 in terms of its function, expression, and misregulation in human cancers. We emphasize the negative consequences of the overexpression of the SRSF3 oncogene in cancers, the pathways underlying SRSF3-mediated transformation, and implications of potential anticancer drugs by downregulation of SRSF3 expression for cancer therapy. Cumulative research on SRSF3 provides critical insight into its essential part in maintaining cellular processes, offering potential new targets for anti-cancer therapy.

The biological function and clinical significance of SF3B1 mutations in cancer.

Spliceosome mutations have become the most interesting mutations detected in human cancer in recent years. The spliceosome, a large, dynamic multimegadalton small nuclear ribonucleoprotein composed of small nuclear RNAs associated with proteins, is responsible for removing introns from precursor mRNA (premRNA) and generating mature, spliced mRNAs. SF3B1 is the largest subunit of the spliceosome factor 3b (SF3B) complex, which is a core component of spliceosomes. Recurrent somatic mutations in SF3B1 have been detected in human cancers, including hematological malignancies and solid tumors, and indicated to be related to patient prognosis. This review summarizes the research progress of SF3B1 mutations in cancer, including SF3B1 mutations in the HEAT domain, the multiple roles and aberrant splicing events of SF3B1 mutations in the pathogenesis of tumors, and changes in mutated cancer cells regarding sensitivity to SF3B small-molecule inhibitors. In addition, the potential of SF3B1 or its mutations to serve as biomarkers or therapeutic targets in cancer is discussed. The accumulated knowledge about SF3B1 mutations in cancer provides critical insight into the integral role the SF3B1 protein plays in mRNA splicing and suggests new targets for anticancer therapy.

Activity-Tuning of Supported Co-Ni Nanocatalysts via Composition and Morphology for Hydrogen Storage in MgH2.

Developing cheap metal nanocatalysts with controllable catalytic activity is one of the critical challenges for improving hydrogen storage in magnesium (Mg). Here, it is shown that the activity of graphene-anchored Co-Ni nanocatalysts can be regulated effectively by tuning their composition and morphology, which results in significantly improved hydrogen storage in Mg. The catalytic activity of supported Co-Ni nanocatalysts is demonstrated to be highly dependent on their morphology and composition. When Ni was partly substituted by Co, the shape of these nanocatalysts was changed from spherical to plate-like, thus corresponding to a decrease in activity. These alterations intrinsically result in enhanced hydrogen storage properties of MgH2, i.e., not only does it exhibit a decreased peak desorption temperature but also a positive change in the initial activation for sorption. The results obtained provide a deep understanding of the tuning of catalytic activity via composition and morphology and further provide insights into improving hydrogen storage in Mg-based materials.

Acoustic radiation force impulse (ARFI) imaging of preliminary mucosa associated lymphoid tissue (MALT) lymphoma in the breast: a case report.

Primary lymphoma is a rare neoplasm in the breast accounting for between 0.04% and 0.5% of all malignant mammary tumors. The majority of cases lack typical features of breast malignancy or lymphoma, and likely to be misdiagnosed during daily clinical practice. In this report we describe a case of primary breast lymphoma assessed with acoustic radiation force impulse (ARFI) technology.

The role of vascular epithelial growth factor receptor-tyrosine kinase inhibitors in the treatment of advanced breast cancer: a meta-analysis of 12 randomized controlled trials.

AIM: To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer. METHODS: A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy. CONCLUSIONS: The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).