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VEGF Inhibitor

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https://www.readbyqxmd.com/read/28738235/treatment-decisions-in-metastatic-colorectal-cancer-beyond-first-and-second-line-combination-therapies
#1
REVIEW
A Vogel, R D Hofheinz, S Kubicka, D Arnold
Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important...
May 4, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28736761/phase-ii-study-of-dovitinib-in-patients-progressing-on-anti-vascular-endothelial-growth-factor-therapy
#2
Thomas J Semrad, Edward J Kim, Michael S Tanaka, Jacob Sands, Chris Roberts, Rebekah A Burich, Yu Li, David R Gandara, Primo Lara, Philip C Mack
BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. METHODS: Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible...
2017: Cancer Treat Res Commun
https://www.readbyqxmd.com/read/28736633/biologics-in-gastrointestinal-and-pancreatic-neuroendocrine-tumors
#3
REVIEW
Iris H Liu, Pamela L Kunz
The development of biologic agents has ushered in a new era of precision medicine, opening the door to new therapeutic options designed to intelligently target cancer cells and their promoting factors, while leaving normal cells relatively unharmed. Biologics for the treatment of neuroendocrine tumors (NETs) have followed in the footsteps of regimens targeting pathways upregulated in other cancers, including the vascular endothelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR). Through a number of clinical trials, the mTOR inhibitor everolimus and the receptor tyrosine kinase (RTK) inhibitor sunitinib were recently approved for NETs...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736629/biologic-therapy-in-esophageal-and-gastric-malignancies-current-therapies-and-future-directions
#4
REVIEW
Pamela Samson, A Craig Lockhart
Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736316/early-actions-of-anti-vascular-endothelial-growth-factor-vascular-endothelial-growth-factor-receptor-drugs-on-angiogenic-blood-vessels
#5
Basel Sitohy, Sunghee Chang, Tracey E Sciuto, Elizabeth Masse, Mei Shen, Peter M Kang, Shou-Ching Jaminet, Laura E Benjamin, Rupal S Bhatt, Ann M Dvorak, Janice A Nagy, Harold F Dvorak
Tumors induce their heterogeneous vasculature by secreting vascular endothelial growth factor (VEGF)-A. Anti-VEGF/VEGF receptor (VEGFR) drugs may treat cancer but the underlying mechanisms remain unclear. An adenovirus expressing VEGF-A (Ad-VEGF-A(164)) replicates the tumor vasculature in mice without tumor cells. Mother vessels (MV) are the first angiogenic vessel type to form in tumors and following Ad-VEGF-A(164). Multiday treatments with a VEGF trap reverted MV back to normal microvessels. We now show that, within hours, a single dose of several anti-VEGF drugs collapsed MV to form glomeruloid microvascular proliferations (GMP), accompanied by only modest endothelial cell death...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28730079/effect-of-angiotensin-ii-type-1-receptor-blocker-and-angiotensin-converting-enzyme-inhibitor-on-the-intraocular-growth-factors-and-their-receptors-in-streptozotocin-induced-diabetic-rats
#6
Ik Soo Byon, Dong Hyun Lee, Eun Sook Jun, Min Kyu Shin, Sung Who Park, Ji Eun Lee
AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan-treated DM, and enalapril-treated DM (each group, n=10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d)] and enalapril [ACEI, 10 mg/(kg·d)] were administered to rats orally for 4wk...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#7
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28728751/a-phase-ii-evaluation-of-brivanib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-gynecologic-oncology-group-study
#8
John K Chan, Wei Deng, Robert V Higgins, Krishnansu S Tewari, Albert J Bonebrake, Michael Hicks, Stephanie Gaillard, Pedro T Ramirez, Weldon Chafe, Bradley J Monk, Carol Aghajanian
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity...
July 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28726562/gene-therapy-for-age-related-macular-degeneration
#9
Nicholas A Moore, Peter Bracha, Rehan M Hussain, Nuria Morral, Thomas A Ciulla
In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with 'real world' undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28725539/the-evolving-treatment-landscape-of-advanced-renal-cell-carcinoma-in-patients-progressing-after-vegf-inhibition
#10
REVIEW
Pedro C Barata, Moshe C Ornstein, Jorge A Garcia
Despite significant changes in the therapeutic landscape of renal cell carcinoma, the majority of patients with metastatic disease eventually progress after first-line treatment with vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Understanding existing data on subsequent therapies is crucial to define an optimal treatment sequence following first-line failure. This review examines the data supporting currently approved agents in this setting and provides a framework for decision-making regarding treatment sequencing beyond first-line therapy with VEGFR TKIs...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28725215/prolyl-hydroxylase-domain-2-inhibition-improves-skeletal-muscle-regeneration-in-a-male-murine-model-of-obesity
#11
Indranil Sinha, Dharaniya Sakthivel, Benjamin A Olenchock, Carla R Kruse, Jeremy Williams, David E Varon, Jessica D Smith, Arin L Madenci, Kristo Nuutila, Amy J Wagers
Obesity leads to a loss of muscle mass and impaired muscle regeneration. In obese individuals, pathologically elevated levels of prolyl hydroxylase domain enzyme 2 (PHD2) limit skeletal muscle hypoxia-inducible factor-1 alpha and vascular endothelial growth factor (VEGF) expression. Loss of local VEGF may further impair skeletal muscle regeneration. We hypothesized that PHD2 inhibition would restore vigorous muscle regeneration in a murine model of obesity. Adult (22-week-old) male mice were fed either a high-fat diet (HFD), with 60% of calories derived from fat, or a regular diet (RD), with 10% of calories derived from fat, for 16 weeks...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28724665/the-c-1085a-g-genetic-variant-of-csf1r-gene-regulates-tumor-immunity-by-altering-the-proliferation-polarization-and-function-of-macrophages
#12
Yu-Min Yeh, Shan-Ju Hsu, Peng-Chan Lin, Keng-Fu Hsu, Pei-Ying Wu, Wu-Chou Su, Jang-Yang Chang, Meng-Ru Shen
Purpose: <p>Targeting tumor-associated macrophages with CSF-1R inhibition reveals a strategy for cancer therapy. Here, we studied the impact of CSF1R germline genetic variant on CSF-1R signaling and the susceptibility to CSF-1R inhibitors.</p> <p>Experimental designs: </p> <p>CSF1R germline genetic variants were studied in 140 cancer patients. CSF-1R phosphorylation, endocytosis and macrophage polarization were measured as the response to CSF-1 stimulation. Tumor-associated macrophages in surgical specimens and sensitivity to CSF-1R inhibitors were used to determine macrophage function...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28721753/nintedanib-in-ovarian-cancer
#13
Saira Khalique, Susana Banerjee
Advanced ovarian cancer remains an unmet clinical need. Angiogenesis is considered a therapeutic target in ovarian cancer, with bevacizumab, a monoclonal antibody against VEGF, being the first drug to show a progression-free survival benefit. Nintedanib is an oral tyrosine kinase inhibitor targeting VEGF receptor 1-3, FGFR 1-3 and PDGFR α and β, which has entered phase III trial development in ovarian cancer. Areas covered: This article reviews the preclinical and clinical efficacy of nintedanib in ovarian cancer, its pharmacokinetic and pharmacodynamics profile, safety issues, together with an overview of clinical trials carried out so far...
July 19, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28721456/antiangiogenic-tyrosine-kinase-inhibitors-in-colorectal-cancer-is-there-a-path-to-making-them-more-effective
#14
REVIEW
Thomas B Karasic, Mark A Rosen, Peter J O'Dwyer
Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib has had more limited success. Pharmacodynamic modeling using modalities such as DCE-MRI indicates potent antiangiogenic effects of these TKIs, yet numerous combination therapies, primarily with chemotherapy, have failed to demonstrate an additive benefit...
July 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28720439/outcomes-of-patients-with-long-term-treatment-response-to-vascular-endothelial-growth-factor-targeted-therapy-for-metastatic-renal-cell-cancer
#15
Tomas Buchler, Alexandr Poprach, Zbynek Bortlicek, Radek Lakomy, Renata Chloupková, Rostislav Vyzula, Milada Zemanova, Katerina Kopeckova, Marek Svoboda, Ondrej Slaby, Igor Kiss, Hana Studentova, Jana Hornova, Ondrej Fiala, Jindrich Kopecky, Jindrich Finek, Ladislav Dusek, Bohuslav Melichar
BACKGROUND: Although targeted therapies with inhibitors of the vascular endothelial growth factor (VEGF) are the mainstay of treatment for metastatic renal cell carcinoma, there are limited data on the outcome of patients with long-term response to this treatment. PATIENTS AND METHODS: In a retrospective, registry-based study, patients continuously treated with first-line anti-VEGF agents for at least 24 months were included. In total, 219 patients had evaluable data and were included in the outcome analysis...
June 29, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28720098/arcyriaflavin-a-a-cyclin-d1-cyclin-dependent-kinase4-inhibitor-induces-apoptosis-and-inhibits-proliferation-of-human-endometriotic-stromal-cells-a-potential-therapeutic-agent-in-endometriosis
#16
Tomoko Hirakawa, Kaei Nasu, Yoko Aoyagi, Kanetoshi Takebayashi, Hisashi Narahara
BACKGROUND: We previously showed that microRNA-503 (miR-503) transfection into endometriotic cyst stromal cells (ECSCs) induced cell cycle arrest at the G0/G1 phase by suppressing cyclin D1. This finding prompted us to evaluate the potential therapeutic effects of cyclin D1 inhibitors in endometriotic cells. This study aimed to determine whether arcyriaflavin A, a representative inhibitor of cyclin D1-cyclin-dependent kinase 4 (CDK4), is beneficial in the treatment of endometriosis. METHODS: ECSCs were isolated from the ovarian endometriotic tissues of 32 women...
July 18, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28719888/inhibition-of-single-routes-of-intracellular-signaling-is-not-sufficient-to-neutralize-the-biphasic-disturbance-of-a-retinal-endothelial-cell-barrier-induced-by-vegf-a165
#17
Heidrun L Deissler, Gerhard K Lang, Gabriele E Lang
BACKGROUND/AIMS: Hallmark of diabetic macular edema is the enhanced permeability of retinal endothelial cells (REC) induced by vascular endothelial growth factor (VEGF-A165), which acts through activating specific receptors. To improve the predictability of inhibitors' potentials to block harmful effects of VEGF-A165, we investigated if its signaling pathways triggered in REC are redundant. METHODS: Immortalized bovine REC monolayers were treated with inhibitors specific for various protein kinases in combination with VEGF-A165...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28716525/peri-tumor-associated-fibroblasts-promote-intrahepatic-metastasis-of-hepatocellular-carcinoma-by-recruiting-cancer-stem-cells
#18
Jinghua Jiang, Fei Ye, Xue Yang, Chen Zong, Lu Gao, Yang Yang, Qiudong Zhao, Zhipeng Han, Lixin Wei
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human peri-tumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues-derived fibroblasts (CM-TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-β, HGF and VEGF...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715845/apatinib-an-inhibitor-of-vascular-endothelial-growth-factor-receptor-2-suppresses-pathologic-ocular-neovascularization-in-mice
#19
Koung Li Kim, Wonhee Suh
Purpose: Vascular endothelial growth factor (VEGF) signaling via VEGF receptor 2 (VEGFR2) plays a crucial role in pathologic ocular neovascularization. In this study, we investigated the antiangiogenic effect of apatinib, a pharmacologic inhibitor of VEGFR2 tyrosine kinase, against oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) in mice. Methods: Western blotting and in vitro angiogenesis assays were performed using human retinal microvascular endothelial cells (HRMECs)...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28715819/effect-of-microrna-135a-on-cell-proliferation-migration-invasion-apoptosis-and-tumor-angiogenesis-through-the-igf-1-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer
#20
Yufei Zhou, Shaoxia Li, Jiangtao Li, Dongfeng Wang, Quanxing Li
OBJECTIVE: This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC). METHODS: NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein...
July 17, 2017: Cellular Physiology and Biochemistry
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