Author
Guillermo N. Armaiz-Pena
Other affiliations: University of Texas Health Science Center at Houston
Bio: Guillermo N. Armaiz-Pena is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Ovarian cancer & Cancer. The author has an hindex of 36, co-authored 61 publications receiving 5152 citations. Previous affiliations of Guillermo N. Armaiz-Pena include University of Texas Health Science Center at Houston.
Papers
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TL;DR: Chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model, and β-adrenergic activation of the cAMP–PKA signaling pathway is identified as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth.
Abstract: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
1,046 citations
TL;DR: Findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplasticThrombocytosis, which fuels tumor growth.
Abstract: From the Departments of Gynecologic Oncology and Reproductive Medicine (R.L.S., A.M.N., H.D.H., J.B.-M., W.H., H.G., K.M., M.M.K.S., E.R.K., A.K.S.), Cancer Biology (R.R., G.L.-B., A.K.S.), Experimental Therapeutics (G.N.A.-P., I.T., B.O., G.L.-B.), Hematology and Oncology (C.V.P.), Pathology (M.T.D.), Benign Hematology (H.G.V., V.A.-K.), Biostatistics (D.U.), and Leukemia (F.G.), and the Center for RNA Interference and Non-Coding RNA (H.D.H., G.L.-B.,
643 citations
TL;DR: In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-κB and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression.
Abstract: Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-κB (NF-κB). This study evaluates the effects of curcumin on ovarian cancer growth using an orthotopic murine model of ovarian cancer. Experimental Design: In vitro and in vivo experiments of curcumin with and without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8-MDR in athymic mice. NF-κB modulation was ascertained using electrophoretic mobility shift assay. Evaluation of angiogenic cytokines, cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31), and apoptosis (terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling) was done using immunohistochemical analyses. Results: Curcumin inhibited inducible NF-κB activation and suppressed proliferation in vitro. In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-κB and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression. In the SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% ( P = 0.08) and 55% ( P = 0.01) reductions in mean tumor growth compared with controls, whereas when combined with docetaxel elicited 96% ( P P = 0.05). In SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both proliferation ( P P P Conclusions: Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.
417 citations
University of Texas MD Anderson Cancer Center1, Wayne State University2, National Institutes of Health3, Henry Ford Health System4, Baylor College of Medicine5, Samsung Medical Center6, University of Puerto Rico7, University of California, San Francisco8, Kwandong University9, Hacettepe University10, China Medical University (Taiwan)11, Asia University (Taiwan)12, Harvard University13
TL;DR: It is shown that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome, and the potential for targeting ezh2 as an important therapeutic approach is supported.
370 citations
TL;DR: It is found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high-invasive OVCA cells are markedly glutamine dependent, and the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis.
Abstract: Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine‐addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high‐invasive OVCA cells by blocking glutamine9s entry into the TCA cycle, along with targeting low‐invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.
247 citations
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01 Jan 2000
3,536 citations
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic. In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.
3,210 citations
Journal Article•
2,777 citations
TL;DR: Curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin", a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis.
1,897 citations
TL;DR: Global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic, highlighting the importance of miRNA dysregulation in cancer.
Abstract: MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and overexpression of individual 'oncomiRs' or genetic loss of tumour suppressor miRNAs are associated with human cancer and are sufficient to drive tumorigenesis in mouse models. Furthermore, global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic. This, together with the recent identification of novel miRNA regulatory factors and pathways, highlights the importance of miRNA dysregulation in cancer.
1,659 citations