instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Exosomes are 30-100 nm membrane vesicles of endocytic origin, mediating diverse biological functions including tumor cell invasion, cell-cell communication and antigen presentation through transfer of proteins, mRNAs and microRNAs. Recent evidence suggests that microRNAs can be released through ceramide-dependent secretory machinery regulated by neutral sphingomyelinase 2 (nSMase2) enzyme encoded by the smpd3 gene that triggers exosome secretion. However, whether exosome-mediated microRNA transfer plays any role in cell invasion remains poorly understood. Thus, the aim of this study was to identify the exosomal microRNAs involved in breast cancer invasion.', 'The expression level of endogenous and exosomal miRNAs were examined by real time PCR and the expression level of target proteins were detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study its uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-10b was estimated by invasion assay.', 'In this study, we demonstrate that microRNA carrying exosomes can be transferred among different cell lines through direct uptake. miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cancer cells or non-malignant breast cells; it is actively secreted into medium via exosomes. In particular, nSMase2 or ceramide promotes the exosome-mediated miR-10b secretion whereas ceramide inhibitor suppresses this secretion. Moreover, upon uptake, miR-10b can suppress the protein level of its target genes such as HOXD10 and KLF4, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could induce the invasion ability of non-malignant HMLE cells.\Question: Does exosome-mediated transfer of miR-10b promote cell invasion in breast cancer?
answer:
Together, our results suggest that a set of specific microRNAs may play an important role in modulating tumor microenvironment through exosomes. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.


question:
Context: Data on combined coronary artery bypass grafting (CABG) and restrictive annuloplasty in patients with ischemic cardiomyopathy are scarce, and the effect on reverse left ventricular (LV) remodeling is unknown.', '51 patients with ischemic LV dysfunction (LV ejection fraction 31+/-8%) and severe mitral regurgitation (grade 3 to 4+) underwent CABG and restrictive annuloplasty with stringent downsizing of the mitral annulus (by 2 sizes, Physio-ring, mean size 28+/-2). Serial transthoracic echocardiographic studies were performed (before surgery and within 3 months and 1.5 years after surgery) to assess mitral regurgitation, transmitral gradient, leaflet coaptation, and left atrial and LV reverse remodeling. Clinical follow-up (New York Heart Association [NYHA] class, survival, events) was assessed at 2-year follow-up. Early operative mortality was 5.6%; at 2-year follow-up, all patients were free of endocarditis and thromboembolism, and 1 needed re-operation for recurrent mitral regurgitation; 2-year survival was 84%. NYHA class improved from 3.4+/-0.8 to 1.3+/-0.4 (P<0.01), with all patients in class I/II. Intraoperative transesophageal echo showed minimal (grade 1+) mitral regurgitation in 8 patients and none in 43, without stenosis. Leaflet coaptation was 0.8+/-0.2 cm. These values remained unchanged; all patients had no or minimal (grade 1+) mitral regurgitation at 2-year follow-up. LV end-systolic and end-diastolic dimensions decreased from 51+/-10 to 43+/-12 mm (P<0.001) and from 64+/-8 to 58+/-11 mm (P<0.001). Left atrial dimension decreased from 53+/-8 to 47+/-7 mm (P<0.001).\Question: Does restrictive annuloplasty and coronary revascularization in ischemic mitral regurgitation result in reverse left ventricular remodeling?
answer:
Excellent results of combined restrictive annuloplasty and CABG were obtained. Residual mitral regurgitation was absent/minimal at 2-year follow-up, associated with a significant reduction in left atrial dimension and LV reverse remodeling.


question:
Context: Arsenic trioxide (ATO) strongly induces apoptosis and differentiation in acute promyelocytic leukemia, and induces cell cycle arrest in most solid tumors. Although many signaling pathways are involved in its antitumor mechanism, a detailed investigation of the transforming growth factor beta-bone morphogenetic protein signaling pathway has not been performed.', 'A microarray containing 113 genes associated with the pathway was used to screen important molecules that participate in the antitumor effects of ATO. The expression levels of the inhibitors of DNA binding-2 (ID2) in 4 different types of cancer cells were determined by quantitative reverse transcription PCR and Western blotting. Human esophageal squamous cell carcinoma cell line Eca109 and pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting ID2 and scrambled control siRNA. Cell proliferation was evaluated by methyl thiazolyl tetrazolium assay.', 'Eighteen upregulated and 12 downregulated genes were identified. After verification at the transcriptional and translational levels in 4 different cancer cells, ID2 was identified as an ATO antitumor-associated protein. In addition, specific silencing of ID2 could enhance ATO-induced cell proliferation inhibition in cancer cells.\Question: Does upregulation of ID2 antagonize arsenic trioxide-induced antitumor effects in cancer cells?
answer:

A combination of ATO and ID2-targeted agents may have considerable therapeutic benefits in cancers.