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VEGF Inhibitor

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https://www.readbyqxmd.com/read/29332242/selective-ikk2-inhibitor-imd0354-disrupts-nf-%C3%AE%C2%BAb-signaling-to-suppress-corneal-inflammation-and-angiogenesis
#1
Anton Lennikov, Pierfrancesco Mirabelli, Anthony Mukwaya, Mira Schaupper, Muthukumar Thangavelu, Mieszko Lachota, Zaheer Ali, Lasse Jensen, Neil Lagali
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea...
January 13, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29330051/anti-tumor-effects-of-triptolide-on-angiogenesis-and-cell-apoptosis-in-osteosarcoma-cells-by-inducing-autophagy-via-repressing-wnt-%C3%AE-catenin-signaling
#2
Xugui Li, Qilin Lu, Wei Xie, Yang Wang, Guanqing Wang
Osteosarcoma is a common malignant bone tumor occurring in adolescents and children. The poor prognosis and low 5-year survival rate of osteosarcoma partly due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from Tripterygium wilfordii, is widely used in cancer treatment. In our present study, we aimed to study the effect of TPL in osteosarcoma treatment and explore the associated regulation mechanism. Our study revealed that TPL inhibited angiogenesis by suppressing the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in dose dependent manner...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329598/treatment-outcome-of-anti-angiogenesis-through-vegf-pathway-in-the-management-of-gastric-cancer-a-systematic-review-of-phase-ii-and-iii-clinical-trials
#3
Brian Mawalla, Xianglin Yuan, Xiaoxiao Luo, Phillip L Chalya
OBJECTIVES: Advanced gastric cancer poses a therapeutic challenge worldwide. In randomised clinical trials, anti-VEGF has been reported as an essential agent for the treatment of advanced gastric cancer. This review aims at assessing the treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the management of patients with advanced gastric cancer. RESULTS: During this review, 38 clinical trials were identified. Of these, 30 clinical trials were excluded, leaving eight trials of phase II and III...
January 12, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#4
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29329032/targeting-expression-of-adenosine-receptors-during-hypoxia-induced-angiogenesis-a-study-using-zebrafish-model
#5
Navina Panneerselvan, Malathi Ragunathan
Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known...
January 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29328465/effects-of-diphyllin-as-a-novel-v-atpase-inhibitor-on-te-1-and-eca-109-cells
#6
Haijiao Chen, Pengfei Liu, Ting Zhang, Yi Gao, Yingdi Zhang, Xiuyun Shen, Xiao Li, Weidong Shen
Diphyllin is a natural component of traditional Chinese medicine, which effectively inhibits V-ATPase activity and affects the progression of cancer. However, few studies have been conducted on esophageal cancer, and the mechanisms remain to be elucidated. The present study revealedthat diphyllin inhibited proliferation and induced S arrest in esophageal cancer cell lines TE-1 and ECA-109. Further experiments revealed that diphyllin inhibited V-ATPase activity and decreased the mRNA expression of mammalian target of rapamycin complex 1 (mTORC1), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF)...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29325434/collection-of-real-world-data-on-nivolumab-s-effectiveness-in-renal-cell-carcinoma-rationale-for-an-observational-study
#7
Jens Bedke, Marc-Oliver Grimm, Viktor Grünwald
Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth (women) most frequent cancer in western countries. After one or more lines of VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in patients with metastatic RCC. Nivolumab is the first, and so far, only approved programmed death 1 (PD-1) immune checkpoint inhibitor to demonstrate a gain in overall survival in RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a prospective, noninterventional cohort study investigating the effectiveness of nivolumab...
January 12, 2018: Future Oncology
https://www.readbyqxmd.com/read/29325224/hereditary-kidney-cancer-syndromes-genetic-disorders-driven-by-alterations-in-metabolism-and-epigenome-regulation
#8
Hisashi Hasumi, Masahiro Yao
Although hereditary kidney cancer syndrome accounts for around five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, U.S.A. and the first kidney cancer associated gene, VHL was identified through kindred analysis of von Hippel-Lindau syndrome in 1993...
January 11, 2018: Cancer Science
https://www.readbyqxmd.com/read/29324807/vegf-may-contribute-to-macrophage-recruitment-and-m2-polarization-in-the-decidua
#9
Karen C Wheeler, Manoj K Jena, Bhola S Pradhan, Neha Nayak, Subhendu Das, Chaur-Dong Hsu, David S Wheeler, Kang Chen, Nihar R Nayak
It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1...
2018: PloS One
https://www.readbyqxmd.com/read/29323560/the-prospects-for-combination-therapy-with-capecitabine-in-the-rapidly-evolving-treatment-landscape-of-renal-cell-carcinoma
#10
Mehmet Asim Bilen, Jennifer Wilkinson-Carlisle, Guru Sonpavde
Although significant advances have been made in the treatment of advanced renal cell carcinoma (RCC), patients still develop resistance to standard therapies and require the administration of subsequent lines of treatment. New therapeutic approaches are thus imperative to improve the prognosis for patients with RCC. Areas covered: Based on the current literature, we summarize the treatment of metastatic RCC, including the use of cytotoxic chemotherapy, in this review article. We also review the existing scientific literature regarding the role of capecitabine in the treatment of RCC...
January 11, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29318404/does-alk-rearrangement-predict-favorable-response-to-the-therapy-of-bevacizumab-plus-pemetrexed-in-advanced-non-small-cell-lung-cancer-case-report-and-literature-review
#11
Zhichao Liu, Youting Bao, Butuo Li, Xindong Sun, Linlin Wang
BACKGROUND: Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive...
January 9, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29317493/characterization-of-the-interactions-of-potent-allosteric-inhibitors-with-glutaminase-c-a-key-enzyme-in-cancer-cell-glutamine-metabolism
#12
Qingqiu Huang, Clint Stalnecker, Chengliang Zhang, Lee A McDermott, Prema Iyer, Jason O'Neill, Shawn Reimer, Richard A Cerione, William P Katt
Altered glycolytic flux in cancer cells (the Warburg effect) causes their proliferation to rely upon elevated glutamine metabolism (glutamine addiction). This requirement is met by the overexpression of glutaminase C (GAC), which catalyzes the first step in glutamine metabolism and therefore represents a potential therapeutic target. The small molecule CB-839 was reported to be more potent than other allosteric GAC inhibitors, including the parent compound BPTES, and is in clinical trials. Recently, we described the synthesis of BPTES analogs having distinct saturated heterocyclic cores as a replacement for the flexible chain moiety, with improved microsomal stability relative to CB-839 and BPTES...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29315294/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#13
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Rose Parkinson, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
This corrects the article DOI: 10.1038/bjc.2017.119.
January 9, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29313954/phase-1-2-trial-of-temsirolimus-and-sorafenib-in-the-treatment-of-patients-with-recurrent-glioblastoma-north-central-cancer-treatment-group-study-alliance-n0572
#14
David Schiff, Kurt A Jaeckle, S Keith Anderson, Evanthia Galanis, Caterina Giannini, Jan C Buckner, Phillip Stella, Patrick J Flynn, Bradley J Erickson, John F Schwerkoske, Vesna Kaluza, Erin Twohy, Janet Dancey, John Wright, Jann N Sarkaria
BACKGROUND: Mitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma. METHODS: Patients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible...
January 3, 2018: Cancer
https://www.readbyqxmd.com/read/29311252/pazopanib-induced-hypertension-in-patients-with-renal-cell-carcinoma-is-associated-with-low-urine-excretion-of-no-metabolites
#15
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29305324/real-world-outcomes-in-patients-with-neovascular-age-related-macular-degeneration-treated-with-intravitreal-vascular-endothelial-growth-factor-inhibitors
#16
REVIEW
Hemal Mehta, Adnan Tufail, Vincent Daien, Aaron Lee, Vuong Nguyen, Mehmet Ozturk, Daniel Barthelmes, Mark C Gillies
Clinical trials identified intravitreal vascular endothelial growth factor inhibitors (anti-VEGF agents) have the potential to stabilise or even improve visual acuity outcomes in neovascular age-related macular degeneration (AMD), a sight-threatening disease. Real-world evidence allows us to assess whether results from randomised controlled trials can be applied to the general population. We describe the development of global registries, in particular the Fight Retinal Blindness! registry that originated in Australia, the United Kingdom AMD Electronic Medical Records User Group and the IRIS registry in the USA...
January 2, 2018: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/29299781/slit2-robo1-signaling-is-involved-in-angiogenesis-of-glomerular-endothelial-cells-exposed-to-a-diabetic-like-environment
#17
Junhui Liu, Weiping Hou, Tao Guan, Luyao Tang, Xufei Zhu, Yi Li, Shihui Hou, Jun Zhang, Hua Chen, Yunjian Huang
Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N...
January 3, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29299743/basic-fibroblast-growth-factor-protects-astrocytes-against-ischemia-reperfusion-injury-by-upregulating-the-caveolin-1-vegf-signaling-pathway
#18
Meixia Liu, Yudan Wu, Yidian Liu, Zhenzhen Chen, Shujuan He, Huimei Zhang, Liang Wu, Fengxia Tu, Yun Zhao, Chan Liu, Xiang Chen
A previous in vivo study demonstrated that intracerebroventricular injection of basic fibroblast growth factor (bFGF) in middle cerebral artery occlusion rats increased the expression of caveolin-1 (cav-1) and vascular endothelial growth factor (VEGF) in cerebral ischemia penumbra. Because astrocytes are the largest population in the brain, the aim of this in vitro study was to investigate the influence of bFGF on cav-1 and VEGF expression in rat astrocytes following oxygen glucose deprivation/reoxygenation (OGD/R)...
January 3, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29297707/first-line-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-priming-the-tumor-microenvironment-for-immunotherapy
#19
Nizar Tannir, Hans Hammers, Asim Amin
Despite improved outcomes with systemic vascular endothelial growth factor (VEGF)-targeted agents in patients with advanced renal cell carcinoma (RCC), the majority of patients will eventually develop treatment resistance and disease progression. With the emergence of checkpoint inhibitors as potential treatment approaches, studies suggest that ideally combining or sequencing them with VEGF receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) may provide more effective treatments that reduce or delay disease progression...
January 3, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29296234/the-pyrazolyl-urea-gege3-inhibits-tumor-angiogenesis-and-reveals-dystrophia-myotonica-protein-kinase-dmpk-1-as-a-novel-angiogenesis-target
#20
Elda Meta, Beat A Imhof, Patricia Ropraz, Richard J Fish, Chiara Brullo, Olga Bruno, Adama Sidibé
The limitation of targeting VEGF/VEGFR2 signalling to stop angiogenesis in cancer therapy has been blamed on re-activation of alternative receptor tyrosine kinases by compensatory angiogenic factors. Targeting MAPK and PI3K signaling pathways in endothelial cells may be an alternative or complementary approach. Herein we aimed to evaluate the antitumor and antiangiogenic potential of a novel pyrazolyl-urea kinase inhibitor, GeGe3, and to identify its kinase targets. We found GeGe3 to inhibit the proliferation of HUVEC and endothelial tube formation...
December 8, 2017: Oncotarget
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