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VEGF Inhibitor

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https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#1
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28915658/oxidative-stress-mediates-an-increased-formation-of-vascular-endothelial-growth-factor-in-human-hepatocarcinoma-cells-exposed-to-erlotinib
#2
Nataliya Rohr-Udilova, Florian Klinglmüller, Martha Seif, Hubert Hayden, Martin Bilban, Matthias Pinter, Klaus Stolze, Wolfgang Sieghart, Markus Peck-Radosavljevic, Michael Trauner
The tyrosine kinase inhibitor erlotinib targets the receptor of epidermal growth factor (EGFR) involved in development of hepatocellular carcinoma (HCC). Although inefficient in established HCC, erlotinib has been recently proposed for HCC chemoprevention. Since Cyp3A4 and Cyp1A2 enzymes metabolize erlotinib in the liver, the insights into the mechanisms of erlotinib effects on liver cells with maintained drug metabolizing activity are needed. We applied erlotinib to both commercially available (SNU398, Huh7) and established in Austria HCC cell lines (HCC-1...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912141/macropinocytosis-of-bevacizumab-by%C3%A2-glioblastoma-cells-in-the-perivascular-niche-affects-their-survival
#3
Gaëlle M Müller-Greven, Cathleen Carlin, Monica E Burgett, Manmeet Singh Ahluwalia, Adam Lauko, Amy S Nowacki, Cameron J Herting, Maha A Qadan, Markus Bredel, Steven A Toms, Justin D Lathia, Dolores Hambardzumyan, Jann N Sarkaria, Petra Hamerlik, Candece L Gladson
PURPOSE: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors. EXPERIMENTAL DESIGN: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133+ cells derived from GBM tumors in vitro...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28910744/advanced-glycation-end-products-induced-il-6-and-vegf-a-production-and-apoptosis-in-osteocyte-like-mlo-y4-cells-by-activating-rage-and-erk1-2-p38-and-stat3-signalling-pathways
#4
Helin Chen, Wenjia Liu, Xiangnan Wu, Min Gou, Jiefei Shen, Hang Wang
Advanced glycation end products (AGEs) are involved in osteopenia in people with diabetes and the elderly. Interleukin-6 (IL-6) and vascular endothelial growth factor-A (VEGF-A) are potent regulators of bone metabolism, and in bone tissue, osteocytes are an important source of these regulators. However, whether AGEs can directly regulate IL-6 and VEGF-A secretion by osteocytes is unknown. In this study, we evaluated the effect of AGEs on IL-6 and VEGF- A production as well as apoptosis in osteocyte-like MLO-Y4 cells...
September 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28905243/3d-endothelial-cell-spheroid-human-vitreous-humor-assay-for-the-characterization-of-anti-angiogenic-inhibitors-for-the-treatment-of-proliferative-diabetic-retinopathy
#5
Sara Rezzola, Imtiaz M Nawaz, Anna Cancarini, Cosetta Ravelli, Stefano Calza, Francesco Semeraro, Marco Presta
Proliferative diabetic retinopathy (PDR) represents a main cause of acquired blindness. Despite the recognition of the key role exerted by vascular endothelial growth factor (VEGF) in the pathogenesis of PDR, limitations to anti-VEGF therapies do exist. Thus, rapid and cost-effective angiogenesis assays are crucial for the screening of anti-angiogenic drug candidates for PDR therapy. In this context, evaluation of the angiogenic potential of PDR vitreous fluid may represent a valuable tool for preclinical assessment of angiostatic molecules...
September 13, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28904226/tumor-lymphangiogenesis-promotes-t-cell-infiltration-and-potentiates-immunotherapy-in-melanoma
#6
Manuel Fankhauser, Maria A S Broggi, Lambert Potin, Natacha Bordry, Laura Jeanbart, Amanda W Lund, Elodie Da Costa, Sylvie Hauert, Marcela Rincon-Restrepo, Christopher Tremblay, Elena Cabello, Krisztian Homicsko, Olivier Michielin, Douglas Hanahan, Daniel E Speiser, Melody A Swartz
In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C...
September 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28903416/overriding-tki-resistance-of-renal-cell-carcinoma-by-combination-therapy-with-il-6-receptor-blockade
#7
Kei Ishibashi, Tobias Haber, Ines Breuksch, Susanne Gebhard, Takashi Sugino, Hitoshi Kubo, Junya Hata, Tomoyuki Koguchi, Michihiro Yabe, Masao Kataoka, Soichiro Ogawa, Hiroyuki Hiraki, Tomohiko Yanagida, Nobuhiro Haga, Joachim W Thüroff, Dirk Prawitt, Walburgis Brenner, Yoshiyuki Kojima
Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902350/trophic-and-neurotrophic-factors-in-human-pituitary-adenomas-review
#8
Marialuisa Spoletini, Samanta Taurone, Mario Tombolini, Antonio Minni, Giancarlo Altissimi, Venceslao Wierzbicki, Felice Giangaspero, Pier Paolo Parnigotto, Marco Artico, Lia Bardella, Enzo Agostinelli, Francesco Saverio Pastore
The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#9
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28888101/what-s-new-in-sclc-a-review
#10
REVIEW
Bryan Oronsky, Tony R Reid, Arnold Oronsky, Corey A Carter
A few years ago the answer to the question in the title of this review would have been, "unfortunately not much" or even "nothing", likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals...
September 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28886304/the-roles-of-vasohibin-and-its-family-members-beyond-angiogenesis-modulators
#11
Hua Du, Jing Zhao, Ling Hai, Jing Wu, Hua Yi, Yonghong Shi
Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues...
September 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28884378/efficacy-of-topical-tofacitinib-in-promoting-hair-growth-in-non-scarring-alopecia-possible-mechanism-via-vegf-induction
#12
Jitlada Meephansan, J Thummakriengkrai, S Ponnikorn, W Yingmema, R Deenonpoe, P Suchonwanit
Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation...
September 7, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#13
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881773/apatinib-inhibits-vegfr-2-and-angiogenesis-in-an-in-vivo-murine-model-of-nasopharyngeal-carcinoma
#14
Qiu-Xia Peng, Yun-Wei Han, Yan-Ling Zhang, Jie Hu, Juan Fan, Shao-Zhi Fu, Shan Xu, Qiang Wan
Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880966/the-prolyl-4-hydroxylase-inhibitor-gsk360a-decreases-post-stroke-brain-injury-and-sensory-motor-and-cognitive-behavioral-deficits
#15
Jin Zhou, Jie Li, Daniel M Rosenbaum, Jian Zhuang, Carrie Poon, Pu Qin, Katrina Rivera, John Lepore, Robert N Willette, Erding Hu, Frank C Barone
There is interest in pharmacologic preconditioning for end-organ protection by targeting the HIF system. This can be accomplished by inhibition of prolyl 4-hydroxylase (PHD). GSK360A is an orally active PHD inhibitor that has been previously shown to protect the failing heart. We hypothesized that PHD inhibition can also protect the brain from injuries and resulting behavioral deficits that can occur as a result of surgery. Thus, our goal was to investigate the effect of pre-stroke surgery brain protection using a verified GSK360A PHD inhibition paradigm on post-stroke surgery outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28880274/the-functional-relationship-between-transglutaminase-2-and-transforming-growth-factor-%C3%AE-1-in-the-regulation-of-angiogenesis-and-endothelial-mesenchymal-transition
#16
Zhuo Wang, Mileidys Perez, Eun-Seo Lee, Soichi Kojima, Martin Griffin
The importance of transglutaminase 2 (TG2) in angiogenesis has been highlighted in recent studies, but other roles of this multi-functional enzyme in endothelial cell (EC) function still remains to be fully elucidated. We previously showed that the extracellular TG2 is involved in maintaining tubule formation in ECs by a mechanism involving matrix-bound vascular endothelial growth factor (VEGF) signalling. Here, by using the ECs and fibroblast co-culture and ECs 3D culture models, we demonstrate a further role for TG2 in both endothelial tubule formation and in tubule loss, which involves its role in the regulation of transforming growth factor β1 (TGFβ1) and Smad signalling...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28879504/-tki%C3%A2-2-0-changes-in-the-medical-treatment-of-renal-cell-carcinoma
#17
REVIEW
V Stühler, S Kruck, M Hegemann, M Notohamiprodjo, T Todenhöfer, N Kröger, A Stenzl, J Bedke
Only for renal cell carcinoma (RCC) in a local stage curative treatment option by surgical resection exists. For metastatic disease the 5‑year survival rate decreases radically. A factor that contributes to this is the low sensibility to radiation and chemotherapeutics. Since the approval of the tyrosine kinase inhibitors in 2006 effective drugs for the treatment of mRCC is available. The specific inhibition of the vascular-endothelial-growth (VEGF)-receptor and the "mammalian Target of Rapamycin" (mTOR) leads to a prolongation of the progression-free survival as well as the overall survival rate...
September 6, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28877644/a-time-course-of-bevacizumab-anti-vegf-effect-on-rat-peritoneum-relations-between-antiadhesive-action-and-fibrin-regulation-enzymes
#18
Aikaterini-Eftychia Micha, Kyriakos Psarras, Odysseas Ouroumidis, Evangelia Siska, Efthymia Vlachaki, Aristotelis Lymperopoulos, Nikolaos Symeonidis, Christina Nikolaidou, Ioannis Venizelos, George Koliakos, Theodoros E Pavlidis
BACKGROUND: To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab. METHODS: Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum...
September 1, 2017: Surgical Innovation
https://www.readbyqxmd.com/read/28875970/-evaluation-of-selected-vascular-active-factors-in-patients-after-myocardial-infarction-subjected-to-cardiac-rehabilitation
#19
Joanna Kapusta, Anna Mejer-Barczewska, Edward Kowalczyk, Robert Irzmański, Jan Kowalski
Atherosclerosis is an inflammatory process that develops in the coronary arteries. Clinically active agents such as proinflammatory interleukins, TNF-α, tissue inhibitors of metalloproteinases (including TIMP-1), and vascular endothelial growth factor (VEGF), are important factors in the development of acute coronary syndromes. AIM: The aim of the study was to evaluate the effect of cardiac rehabilitation (stage II) on the concentration of selected vascular active factors (IL- 1, IL-6, TIMP-1, VEGF)...
August 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28873177/hypoxia-inducible-factor-dependent-expression-of-angiopoietin-like-4-by-conjunctival-epithelial-cells-promotes-the-angiogenic-phenotype-of-pterygia
#20
Qianli Meng, Yaowu Qin, Monika Deshpande, Fabiana Kashiwabuchi, Murilo Rodrigues, Qiaozhi Lu, Hui Ren, Jennifer H Elisseeff, Gregg L Semenza, Silvia V Montaner, Akrit Sodhi
Purpose: Disappointing results from clinical studies assessing the efficacy of therapies targeting vascular endothelial growth factor (VEGF) for the treatment of pterygia suggest that other angiogenic mediators may also play a role in its development. We therefore explore the relative contribution of VEGF, hypoxia-inducible factor (HIF)-1α (the transcription factor that regulates VEGF expression in ocular neovascular disease), and a second HIF-regulated mediator, angiopoietin-like 4 (ANGPTL4), to the angiogenic phenotype of pterygia...
September 1, 2017: Investigative Ophthalmology & Visual Science
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