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https://www.readbyqxmd.com/read/28938544/sialyllactose-suppresses-angiogenesis-by-inhibiting-vegfr-2-activation-and-tumor-progression
#1
Tae-Wook Chung, Eun-Young Kim, Seok-Jo Kim, Hee-Jung Choi, Se Bok Jang, Keuk-Jun Kim, Sun-Hyung Ha, Fukushi Abekura, Choong-Hwan Kwak, Cheorl-Ho Kim, Ki-Tae Ha
The oligosaccharides in human milk have various biological functions. However, the molecular mechanism(s) underlying the anti-angiogenic action of sialylated human milk oligosaccharides (HMOs) are still unclear. Here, we show that siallylactose (SL) found in human milk can inhibit the activation of vascular endothelial growth factor (VEGF)-mediated VEGF receptor-2 (VEGFR-2) by binding to its VEGF binding site (second and third IgG-like domains), thus blocking downstream signal activation. SL also inhibits growth of VEGF-stimulated endothelial cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938160/nilotinib-enhances-tumor-angiogenesis-and-counteracts-vegfr2-blockade-in-an-orthotopic-breast-cancer-xenograft-model-with-desmoplastic-response
#2
Sara Zafarnia, Jessica Bzyl-Ibach, Igor Spivak, Yongping Li, Susanne Koletnik, Dennis Doleschel, Anne Rix, Sibylle Pochon, Isabelle Tardy, Seena Koyadan, Marc van Zandvoort, Moritz Palmowski, Fabian Kiessling, Wiltrud Lederle
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR) blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#3
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28928080/vascular-endothelial-growth-factor-driving-aberrant-keratin-expression-pattern-contributes-to-the-pathogenesis-of-psoriasis
#4
Man Jiang, Bing Li, Jieyu Zhang, Lei Hu, Erle Dang, Gang Wang
Psoriasis is a chronic inflammatory skin disease severely affecting patients' physical and psychological well-being. Aberrant keratin expression in psoriasis plays a crucial role in keratinocyte dysfunction and disease development. Little is yet known about the mechanism of this keratin dysregulation. VEGF (Vascular endothelial growth factor) is significantly elevated in psoriatic patients and VEGFRs are detected on keratinocytes, leading to our hypothesis that this keratin dysregulation may be regulated by VEGF...
September 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28927801/design-synthesis-and-antitumor-activity-of-novel-sorafenib-derivatives-bearing-pyrazole-scaffold
#5
Min Wang, Shan Xu, Huajun Lei, Caolin Wang, Zhen Xiao, Shuang Jia, Jia Zhi, Pengwu Zheng, Wufu Zhu
Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC50 value of compounds 8b on VEGFR-2 kinase was 0...
September 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28927086/quercetin-inhibits-angiogenesis-mediated-human-retinoblastoma-growth-by-targeting-vascular-endothelial-growth-factor-receptor
#6
Wei Song, Xiaofei Zhao, Jiarui Xu, Han Zhang
Retinoblastoma (RB) is the most common malignant intraocular cancer in teenagers, occurrence of which depends on the mutation of multiple genes. Among all the signaling pathways involved in the oncogenesis of RB, the process of angiogenesis has been demonstrated to be associated with the local invasive growth and metastasis of this cancer type. Quercetin (Que) is a typical flavonoid and has been reported to inhibit angiogenesis in various types of tumors. In the present study, the effect of Que on RB cells and angiogenesis of RB was evaluated...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924349/autophagy-promotes-degradation-of-polyethyleneimine-alginate-nanoparticles-in-endothelial-progenitor-cells
#7
Guo-Dong Wang, Yu-Zhen Tan, Hai-Jie Wang, Pei Zhou
Polyethyleneimine (PEI)-alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI-Alg NPs remains unknown. CD34(+)VEGFR-3(+) endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28923539/efficient-vegf-targeting-delivery-of-dox-using-bevacizumab-conjugated-sio2-ldh-for-anti-neuroblastoma-therapy
#8
Rongrong Zhu, Zhaoqi Wang, Peng Liang, Xiaolie He, Xizhen Zhuang, Ruiqi Huang, Mei Wang, Qigang Wang, Yechang Qian, Shilong Wang
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and is highly expressed in carcinoma, which make it an important target for tumor targeting therapy. Neuroblastoma is the main cause for cancer-related death in children. Like most solid tumors, it is also accompanied with the overexpression of VEGF. Doxorubicin Hydrochloride (DOX), a typical chemotherapeutic agent, exhibits efficient anticancer activities for various cancers. However, DOX, without targeting ability, usually causes severe damage to normal tissues...
September 15, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28921926/inhibition-of-vascular-endothelial-growth-factor-receptor-decreases-regenerative-angiogenesis-in-axolotls
#9
Angela M Ritenour, Renee Dickie
Angiogenesis is crucial for tissue growth and repair in mammals, and is chiefly regulated by Vascular Endothelial Growth Factor (VEGF) signaling. We evaluated the effect of chemical inhibition of VEGF receptor signaling in animals with superior regenerative ability, axolotl salamanders, to determine the impact on vascularization and regenerative outgrowth. Following tail amputation, treated animals (100nM PTK787) and controls were examined microscopically and measured over the month-long period of regeneration...
September 16, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28916481/identification-of-2-4-dihydroxy-5-pyrimidinyl-imidothiocarbomate-as-a-novel-inhibitor-to-y-box-binding-protein-1-yb-1-and-its-therapeutic-actions-against-breast-cancer
#10
Vinoth Prasanna Gunasekaran, Kumari Nishi, Dakshinamurthy Sivakumar, Thirunavukkarasu Sivaraman, Ganeshan Mathan
In spite of advances in breast cancer treatment and early diagnosis, drug toxicity, cancer relapse, multidrug resistance and metastasis are the major impediment to the developments of efficient drugs. However, unique druggable targets of cancer cells distinct from the normal cells provide new rationale in cancer treatment. Previous reports clearly emphasize the differential expression and localization of Y box binding protein-1 (YB-1) between normal breast tissues and different stages of breast cancer. Y box binding protein-1 is DNA as well as RNA binding protein involved in transcription and translation regulation of various proteins involved in cancer progression, apoptosis, cell cycle, epithelial to mesenchymal transition (EMT) and drug resistance...
September 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28916371/ramucirumab-plus-docetaxel-versus-placebo-plus-docetaxel-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-after-platinum-based-therapy-range-a-randomised-double-blind-phase-3-trial
#11
Daniel P Petrylak, Ronald de Wit, Kim N Chi, Alexandra Drakaki, Cora N Sternberg, Hiroyuki Nishiyama, Daniel Castellano, Syed Hussain, Aude Fléchon, Aristotelis Bamias, Evan Y Yu, Michiel S van der Heijden, Nobuaki Matsubara, Boris Alekseev, Andrea Necchi, Lajos Géczi, Yen-Chuan Ou, Hasan Senol Coskun, Wen-Pin Su, Miriam Hegemann, Ivor J Percent, Jae-Lyun Lee, Marcello Tucci, Andrey Semenov, Fredrik Laestadius, Avivit Peer, Giampaolo Tortora, Sufia Safina, Xavier Garcia Del Muro, Alejo Rodriguez-Vida, Irfan Cicin, Hakan Harputluoglu, Ryan C Widau, Astra M Liepa, Richard A Walgren, Oday Hamid, Annamaria H Zimmermann, Katherine M Bell-McGuinn, Thomas Powles
BACKGROUND: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy...
September 12, 2017: Lancet
https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#12
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/28915721/dramatic-response-of-ctnnb1-and-vegfr-2-mutant-temporal-bone-squamous-cell-carcinoma-to-bevacizumab-in-combination-with-pemetrexed
#13
Lai Wei, Lizhi Wang, Ziye Liu, Meiyi Wang, Weili Lu, Dewei Zhao, Bin Yang, Xuejun Kong, Yan Ding, Zhiqiang Wang
High recurrence rates and poor survival rates for late stage/advanced temporal bone squamous cell carcinoma with the standard treatments continues to be a significant challenge to otolaryngologists. Targeted therapy for temporal bone squamous cell carcinoma after relapse has not been reported. Here we present a 58-year-old man who was diagnosed with recurrent temporal bone squamous cell carcinoma and treated with a regimen developed using whole exome sequencing. Somatic mutations in genes encoding catenin beta 1 and vascular endothelial growth factor receptor 2 were identified in the patient's tumor sample compared to the normal tissue...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914404/development-and-characterization-of-hybrid-tubular-structure-of-plcl-porous-scaffold-with-hmscs-ecs-cell-sheet
#14
Azizah Intan Pangesty, Takaaki Arahira, Mitsugu Todo
Tissue engineering offers an alternate approach to providing vascular graft with potential to grow similar with native tissue by seeding autologous cells into biodegradable scaffold. In this study, we developed a combining technique by layering a sheet of cells onto a porous tubular scaffold. The cell sheet prepared from co-culturing human mesenchymal stem cells (hMSCs) and endothelial cells (ECs) were able to infiltrate through porous structure of the tubular poly (lactide-co-caprolactone) (PLCL) scaffold and further proliferated on luminal wall within a week of culture...
September 15, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28911729/chemotherapy-and-tyrosine-kinase-inhibitors-for-medullary-thyroid-cancer
#15
REVIEW
Julien Hadoux, Martin Schlumberger
Medullary thyroid cancer (MTC) represents 3% of all clinical thyroid cancers and arises from thyroid C cells that produce calcitonin. Locally advanced or metastatic MTC requires a careful work-up including measurement of serum calcitonin and carcinoembryonic antigen, determination of their doubling time and comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for treatment. Cytotoxic chemotherapy can control tumor burden in some patients with response rates of around 20% in old series...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28905937/somcl-085-a-novel-multi-targeted-fgfr-inhibitor-displays-potent-anticancer-activity-in-fgfr-addicted-human-cancer-models
#16
Xi-Fei Jiang, Yang Dai, Xia Peng, Yan-Yan Shen, Yi Su, Man-Man Wei, Wei-Ren Liu, Zhen-Bin Ding, Ao Zhang, Ying-Hong Shi, Jing Ai
Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies, especially those lacking effective treatments. SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor. Here, we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo. Among a panel of 20 tyrosine kinases screened, SOMCL-085 potently inhibited FGFR1, FGFR2 and FGFR3 kinase activity, with IC50 values of 1.8, 1.9 and 6.9 nmol/L, respectively. This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR, but without obvious inhibitory effect on other 12 tyrosine kinases...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28904226/tumor-lymphangiogenesis-promotes-t-cell-infiltration-and-potentiates-immunotherapy-in-melanoma
#17
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/28894382/apatinib-in-the-treatment-of-advanced-lung-adenocarcinoma-with-kras-mutation
#18
Da-Xiong Zeng, Chang-Guo Wang, Jian-An Huang, Jun-Hong Jiang
Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28888797/will-molecular-target-agents-enable-the-multidisciplinary-treatment-in-stage-iv-gastric-cancer
#19
REVIEW
Kozo Kataoka, Angélique Deleersnijder, Florian Lordick
A detailed molecular characterization of gastric cancer has been revealed by global initiatives and a number of new molecular agents are under investigation. Currently only trastuzumab, a monoclonal antibody for human epidermal growth factor receptor 2 (HER2), is clinically used for HER2 positive advanced gastric cancer patients and ramucirumab, a monoclonal antibody directed against the extracellular ligand-binding domain of vascular endothelial growth factor receptor (VEGFR)2, can be used in second line. However, despite the progress in gastric cancer treatment, the prognosis of stage IV gastric cancer patients remains dismal...
August 30, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28886175/cabozantinib-versus-everolimus-nivolumab-axitinib-sorafenib-and-best-supportive-care-a-network-meta-analysis-of-progression-free-survival-and-overall-survival-in-second-line-treatment-of-advanced-renal-cell-carcinoma
#20
Billy Amzal, Shuai Fu, Jie Meng, Johanna Lister, Helene Karcher
BACKGROUND: Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. METHODOLOGY & FINDINGS: Systematic literature search identified 5 studies for inclusion in this analysis...
2017: PloS One
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