1
40
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Text
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<a href="http://doi.org/10.1158/1535-7163.MCT-18-0953" target="_blank" rel="noreferrer noopener">http://doi.org/10.1158/1535-7163.MCT-18-0953</a>
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Title
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Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin beta1 Blocking Antibody OS2966.
Publisher
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Molecular cancer therapeutics
Date
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2019
2019-03
Creator
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Lee Tae Jin; Nair Mitra; Banasavadi-Siddegowda Yeshavanth Kumar; Liu Joseph; Nallanagulagari Tejaswini; Jaime-Ramirez Alena Cristina; Guo Jeffrey Yunhua; Quadri Haroon; Zhang Jianying; Bockhorst Kurt H; Aghi Manish K; Carbonell W Shawn; Kaur Balveen; Yoo Ji Young
Description
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Integrin beta1 receptor, expressed on the surface of tumor cells and macrophages in the tumor microenvironment (TME), has been implicated in both tumor progression as well as resistance to multiple modalities of therapy. OS2966 is the first clinical-ready humanized monoclonal antibody to block integrin beta1 and was recently orphan designated by FDA Office of Orphan Products Development (OOPD). Here, we tested therapeutic potential of OS2966-mediated integrin beta1 blockade to enhance the efficacy of oncolytic herpes simplex virus-1 (oHSV) through evaluation of virus replication, tumor cell killing efficiency, effect on the antiviral signaling pathway, co-culture assays of oHSV-infected cells with macrophages, and in vivo bioluminescence imaging on mammary fat pad triple negative breast cancer xenograft and subcutaneous and intracranial glioma xenografts. OS2966 treatment decreased interferon signaling and pro-inflammatory cytokine induction in oHSV-treated tumor cells and inhibited migration of macrophages, resulting in enhanced oHSV replication and cytotoxicity. OS2966 treatment also significantly enhanced oHSV replication and oHSV-mediated anti-tumor efficacy in orthotopic xenograft models including triple negative breast cancer and glioblastoma. The results demonstrated the synergistic potential of the combinatory treatment approach with OS2966 to improve anti-tumor efficacy of conventional oHSV therapy.
Identifier
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<a href="http://doi.org/10.1158/1535-7163.MCT-18-0953" target="_blank" rel="noreferrer noopener">10.1158/1535-7163.MCT-18-0953</a>
2019
Aghi Manish K
Banasavadi-Siddegowda Yeshavanth Kumar
Bockhorst Kurt H
Carbonell W Shawn
Guo Jeffrey Yunhua
Jaime-Ramirez Alena Cristina
Kaur Balveen
Lee Tae Jin
Liu Joseph
Molecular cancer therapeutics
Nair Mitra
Nallanagulagari Tejaswini
NEOMED College of Medicine
NEOMED College of Medicine Student
NEOMED Student Publications
Quadri Haroon
Yoo Ji Young
Zhang Jianying
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1158/1535-7163.mct-13-0132" target="_blank" rel="noreferrer noopener">http://doi.org/10.1158/1535-7163.mct-13-0132</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
2389-2399
Issue
11
Volume
12
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The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Paclitaxel-Hyaluronic NanoConjugates Prolong Overall Survival in a Preclinical Brain Metastases of Breast Cancer Model
Publisher
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Molecular Cancer Therapeutics
Date
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2013
2013-11
Subject
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stem-cells; in-vivo; Oncology; central-nervous-system; lipid rafts; antitumor-activity; multidrug-resistance; acid-paclitaxel; cd44 expression; p-glycoprotein; targeted drug-delivery
Creator
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Mittapalli R K; Liu X L; Adkins C E; Nounou M I; Bohn K A; Terrell T B; Qhattal H S; Geldenhuys W J; Palmieri D; Steeg P S; Smith Q R; Lockman P R
Description
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Brain (central nervous system; CNS) metastases pose a life-threatening problem for women with advanced metastatic breast cancer. It has recently been shown that the vasculature within preclinical brain metastasis model markedly restricts paclitaxel delivery in approximately 90% of CNS lesions. Therefore to improve efficacy, we have developed an ultra-small hyaluronic acid (HA) paclitaxel nanoconjugate (similar to 5 kDa) that can passively diffuse across the leaky blood-tumor barrier and then be taken up into cancer cells (MDA-MB-231Br) via CD44 receptor-mediated endocytocis. Using CD44 receptor-mediated endocytosis as an uptake mechanism, HA-paclitaxel was able to bypass p-glycoprotein-mediated efflux on the surface of the cancer cells. In vitro cytoxicity of the conjugate and free paclitaxel were similar in that they (i) both caused cell-cycle arrest in the G(2)-M phase, (ii) showed similar degrees of apoptosis induction (cleaved caspase), and (iii) had similar IC50 values when compared with paclitaxel in MTT assay. A preclinical model of brain metastases of breast cancer using intracardiac injections of Luc-2 transfected MDA-MB-231Br cells was used to evaluate in vivo efficacy of the nanoconjugate. The animals administered with HA-paclitaxel nanoconjugate had significantly longer overall survival compared with the control and the paclitaxel-treated group (P < 0.05). This study suggests that the small molecular weight HA-paclitaxel nanoconjugates can improve standard chemotherapeutic drug efficacy in a preclinical model of brain metastases of breast cancer. (C) 2013 AACR.
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<a href="http://doi.org/10.1158/1535-7163.mct-13-0132" target="_blank" rel="noreferrer noopener">10.1158/1535-7163.mct-13-0132</a>
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Journal Article or Conference Abstract Publication
2013
acid-paclitaxel
Adkins C E
antitumor-activity
Bohn K A
cd44 expression
central-nervous-system
Geldenhuys W J
in-vivo
Journal Article or Conference Abstract Publication
lipid rafts
Liu X L
Lockman P R
Mittapalli R K
Molecular cancer therapeutics
multidrug-resistance
Nounou M I
oncology
p-glycoprotein
Palmieri D
Qhattal H S
Smith Q R
Steeg P S
stem-cells
targeted drug-delivery
Terrell T B