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Yang X.,University of Houston | Shen F.,University of Houston | Hu W.,University of Houston | Coleman R.L.,University of Houston | And 2 more authors.
Current Opinion in Obstetrics and Gynecology | Year: 2015

PURPOSE OF REVIEW: The aim of this article was to review the recent literature on potential therapeutic strategies for overcoming resistance to antivascular endothelial growth factor drugs in ovarian cancer. RECENT FINDINGS: Although clinical benefits of antivascular endothelial growth factor therapy were observed in ovarian cancer treatment trials, this use yielded only modest improvement in progression-free survival and, with the exception of cediranib, no effect on overall survival. Adaptive resistance and escape from antiangiogenesis therapy is likely a multifactorial process, including induction of hypoxia, vascular modulators, and immune response. New drugs targeting the tumor vasculature or other components of the surrounding microenvironment have shown promising results. SUMMARY: When to start and end antiangiogenesis therapy and the choice of optimal treatment combinations remain controversial. Further evaluation of personalized novel angiogenesis-based therapy is warranted. Defining the critical interaction of these agents and pathways and the appropriate predictive markers will become an increasingly important objective for effective treatment. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Eiring A.M.,Ohio State University | Harb J.G.,Ohio State University | Neviani P.,Ohio State University | Garton C.,Ohio State University | And 21 more authors.
Cell | Year: 2010

MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival of leukemic blasts by simultaneously interacting with the translational regulator poly(rC)-binding protein hnRNP E2 and with the mRNA encoding the survival factor PIM1, respectively. The interaction with hnRNP E2 is independent of the microRNA's seed sequence and it leads to release of CEBPA mRNA from hnRNP E2-mediated translational inhibition. Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins. PaperFlick: {An electronic component is presented}. © 2010 Elsevier Inc. All rights reserved.

Ferrajoli A.,University of Houston | Shanafelt T.D.,Rochester College | Ivan C.,Center for Interference and Non Coding s | Shimizu M.,University of Houston | And 19 more authors.
Blood | Year: 2013

Noncoding RNAs play a pivotal role in the pathogenesis of chronic lymphocytic leukemia (CLL). We hypothesized that microRNAs (miRs) are involved in the transition from monoclonal B-cell lymphocytosis (MBL) to CLL and tested miR-15a/ 16-1 cluster, miR-21, and miR-155 expression in purified B cells of normal individuals, individuals with MBL, and patients with CLL.When we analyzed 224 samples from 2 independent training and validation cohorts, we found that miR-155 was overexpressed in B cells from individuals with MBL, and even more so in B cells from patients with CLL, when compared with B cells from normal individuals. Furthermore, we were able to identify miR-155 in circulating microvesicles from both individuals with MBL and patients with CLL. Next, to examine the prognostic role of miR-155, we measured its expression level in plasma samples collected before treatment initiation in 228 patients with CLL. We found significantly higher miR-155 expression levels in patients who failed to achieve a complete response compared with those who experienced complete response. Our findings support the use of cellular and plasma levels of miR-155 as biomarkers for the risk of progression in individuals with MBL, as well as to identify patients with CLL who may not respond well to therapy. © 2013 by The American Society of Hematology.

Leung C.S.,University of Houston | Leung C.S.,Harvard University | Yeung T.-L.,University of Houston | Yeung T.-L.,Harvard University | And 14 more authors.
Nature Communications | Year: 2014

Ovarian cancer is the most lethal gynecologic malignancy in the United States, and advanced serous ovarian adenocarcinoma is responsible for most ovarian cancer deaths. However, the stroma-derived molecular determinants that modulate patient survival have yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumor samples and find that stromal microfibrillar-associated protein 5 (MFAP5) is a prognostic marker for poor survival. Further functional studies reveal that FAK/CREB/TNNC1 signaling pathways mediate the effect of MFAP5 on ovarian cancer cell motility and invasion potential. Targeting stromal MFAP5 using MFAP5 specific siRNA encapsulated in chitosan nanoparticles significantly decreases ovarian tumor growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.

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