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https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#1
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811219/trinucleotide-repeat-containing-6c-tnrc6c-is-essential-for-microvascular-maturation-during-distal-airspace-sacculation-in-the-developing-lung
#2
Hua Guo, Yana Kazadaeva, Fabian E Ortega, Manjunath N Swamy, Tushar J Desai
GW182 (also known asTNRC6) family members are critically involved in the final effector phase of miRNA-mediated mRNA repression. The three mammalian paralogs, TNRC6a, b and c, are thought to be redundant based on Argonaute (Ago) binding, tethering assays, and RNAi silencing of individual members in cell lines. To test this idea, we generated TNRC6a, b and c knockout mice. TNRC6a mutants die at mid-gestation, while b- and c- deleted mice are born at a Mendelian ratio. However, the majority of TNRC6b and all TNRC6c mutants die within 24 hours after birth, the latter with respiratory failure...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#3
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28803935/tnf-%C3%AE-upregulates-hif-1%C3%AE-expression-in-pterygium-fibroblasts-and-enhances-their-susceptibility-to-vegf-independent-of-hypoxia
#4
Kyoung Woo Kim, Soo Jin Lee, Jae Chan Kim
The clinical manifestations of pterygium are characterized by rapid growth and postoperative recurrences. We had previously proposed that hypoxia-inducible factor (HIF)-1α recruits progenitor cells during the development and progression of pterygia. Recently, it was reported that various stimuli, including inflammation, could activate HIF-1α even under normoxic conditions. The ocular surface directly faces external environments, and is thus frequently exposed to inflammatory insults. First, we examined the gene expression of HIF-1α, its downstream molecule, vascular endothelial growth factor (VEGF)-A, and VEGF receptor (VEGFR)-2 in corneal and conjunctival cells compared with cultured human umbilical vein endothelial cells...
August 10, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28797294/the-anti-vascular-endothelial-growth-factor-receptor-1-monoclonal-antibody-d16f7-inhibits-invasiveness-of-human-glioblastoma-and-glioblastoma-stem-cells
#5
Maria Grazia Atzori, Lucio Tentori, Federica Ruffini, Claudia Ceci, Lucia Lisi, Elena Bonanno, Manuel Scimeca, Eskil Eskilsson, Thomas Daubon, Hrvoje Miletic, Lucia Ricci Vitiani, Roberto Pallini, Pierluigi Navarra, Rolf Bjerkvig, Stefania D'Atri, Pedro Miguel Lacal, Grazia Graziani
BACKGROUND: Glioblastoma (GBM) is a highly migratory, invasive, and angiogenic brain tumor. Like vascular endothelial growth factor-A (VEGF-A), placental growth factor (PlGF) promotes GBM angiogenesis. VEGF-A is a ligand for both VEGF receptor-1 (VEGFR-1) and VEGFR-2, while PlGF interacts exclusively with VEGFR-1. We recently generated the novel anti-VEGFR-1 monoclonal antibody (mAb) D16F7 that diminishes VEGFR-1 homodimerization/activation without affecting VEGF-A and PlGF binding. METHODS: In the present study, we evaluated the expression of VEGFR-1 in human GBM tissue samples (n = 42) by immunohistochemistry, in cell lines (n = 6) and GBM stem cells (GSCs) (n = 18) by qRT-PCR and/or western blot analysis...
August 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28797111/angiogenic-t-cell-expansion-correlates-with-severity-of-peripheral-vascular-damage-in-systemic-sclerosis
#6
Mirko Manetti, Sara Pratesi, Eloisa Romano, Silvia Bellando-Randone, Irene Rosa, Serena Guiducci, Bianca Saveria Fioretto, Lidia Ibba-Manneschi, Enrico Maggi, Marco Matucci-Cerinic
The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay...
2017: PloS One
https://www.readbyqxmd.com/read/28792659/molecular-alterations-in-pediatric-brainstem-gliomas
#7
Mikaela Porkholm, Anna Raunio, Reetta Vainionpää, Tarja Salonen, Juha Hernesniemi, Leena Valanne, Jarno Satopää, Atte Karppinen, Minna Oinas, Olli Tynninen, Virve Pentikäinen, Sanna-Maria Kivivuori
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group...
August 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28791841/vascular-endothelial-growth-factor-vegf-c-vegf-d-vegfr-3-and-d2-40-expressions-in-primary-breast-cancer-association-with-lymph-node-metastasis
#8
Aydan Eroğlu, Cevriye Ersöz, Durdu Karasoy, Serpil Sak
BACKGROUND: Two members of the vascular endothelial growth factor (VEGF) family, VEGF-C and -D, are known as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis via activation of the VEGF receptor (VEGFR)-3, which is expressed in lymphatic endothelial cells. D2-40 is a specific antibody for lymphatic vessel density (LVD). OBJECTIVES: In the present study, we have aimed to evaluate whether intraand peri-tumoral D2-40-positive lymphatic vessels affect lymph node metastasis and to investigate the relationship between LVD and lymph node metastasis in breast cancer...
March 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28782793/alginate-gelatin-encapsulation-of-human-endothelial-cells-promoted-angiogenesis-in-in-vivo-and-in-vitro-milieu
#9
Sorour Nemati, Aysa Rezabakhsh, Ali Baradar Khoshfetrat, Alireza Nourazarian, Çığır Biray Avci, Bakiye Goker Bagca, Hamed Alizadeh Sardroud, Majid Khaksar, Mahdi Ahmadi, Aref Delkhosh, Emel Sokullu, Reza Rahbarghazi
Up to present, many advantages have been achieved in the field of cell-based therapies by applying sophisticated methodologies and delivery approaches. Microcapsules are capable to provide safe microenvironment for cells during transplantation in a simulated physiological 3D milieu. Here, we aimed to investigate the effect of alginate-gelatin encapsulation on angiogenic behavior of human endothelial cells over a period of 5 days. Human umbilical vein endothelial cells were encapsulated by alginate-gelatin substrate and incubated for 5 days...
August 7, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28780387/evaluation-of-the-response-of-intracranial-xenografts-to-vegf-signaling-inhibition-using-multiparametric-mri
#10
Jessica K R Boult, Gary Box, Maria Vinci, Lara Perryman, Suzanne A Eccles, Chris Jones, Simon P Robinson
Vascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic strategies to target brain malignancies, both primary brain tumors, particularly in pediatric patients, and metastases, are lacking, but targeting angiogenesis may be a promising approach. Multiparametric MRI was used to investigate the response of orthotopic SF188(luc) pediatric glioblastoma xenografts to small molecule pan-VEGFR inhibitor cediranib and the effects of both cediranib and cross-reactive human/mouse anti-VEGF-A antibody B20-4...
August 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28777742/dramatic-response-of-ctnnb1-and-vegfr-2-mutant-temporal-bone-squamous-cell-carcinoma-to-bevacizumab-in-combination-with-pemetrexed
#11
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...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28776079/evaluation-of-a-xenogeneic-vascular-endothelial-growth-factor-2-vaccine-in-two-preclinical-metastatic-tumor-models-in-mice
#12
Sofie Denies, Bregje Leyman, Hanne Huysmans, Francis Combes, Séan Mc Cafferty, Laetitia Cicchelero, Marjan Steppe, Joyca De Temmerman, Niek N Sanders
In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor...
August 3, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28775329/transient-ingrowth-of-lymphatic-vessels-into-the-physiologically-avascular-cornea-regulates-corneal-edema-and-transparency
#13
Deniz Hos, Anne Bukowiecki, Jens Horstmann, Felix Bock, Franziska Bucher, Ludwig M Heindl, Sebastian Siebelmann, Philipp Steven, Reza Dana, Sabine A Eming, Claus Cursiefen
Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774835/current-and-emerging-biomarkers-in-tumors-of-the-central-nervous-system-possible-diagnostic-prognostic-and-therapeutic-applications
#14
REVIEW
Ishaq N Khan, Najeeb Ullah, Deema Hussein, Kulvinder S Saini
Recent investments in research associated with the discovery of specific tumor biomarkers important for efficient diagnosis and prognosis of the patients are beginning to bear fruit. Key biomarkers could potentially outweigh traditional radiological or pathological methods by enabling specificity of early detection, when coupled with tumor molecular profiling and clinical associations. Only few biomarkers are approved by regulatory authorities for Central Nervous System Tumors (CNSTs), despite the evaluation of a large number of CNST related markers during clinical trials...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28765707/design-synthesis-and-evaluation-of-vegfr-targeted-macromolecular-mri-contrast-agent-based-on-biotin-avidin-specific-binding
#15
Yongjun Liu, Xiaoyun Wu, Xiaohe Sun, Dan Wang, Ying Zhong, Dandan Jiang, Tianqi Wang, Dexin Yu, Na Zhang
Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28762754/flow-responsive-vegfr-pkc%C3%A9-signaling-mediates-glycolytic-metabolites-for-vascular-repair
#16
Kyung In Baek, Rongsong Li, Nelson Jen, Howard Choi, Amir Kaboodrangi, Peipei Ping, David Liem, Tyler Beebe, Tzung K Hsiai
Aims - Hemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive VEGF receptor-PKCɛ-PFKFB3 signaling modulates glycolytic metabolites for vascular repair. Results - Bidirectional oscillatory flow (OSS: 0.1 ± 3 dyne·cm<sup>-2</sup> at 1 Hz) up-regulated VEGFR-dependent PKCɛ expression to a greater degree than did unidirectional pulsatile flow (PSS: 23 ± 8 dyne·cm<sup>-2</sup> at 1 Hz) in human aortic endothelial cells (HAEC) (<i>p < 0...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28756136/addressing-the-best-treatment-for-non-clear-cell-renal-cell-carcinoma-a-meta-analysis-of-randomised-clinical-trials-comparing-vegfr-tkis-versus-mtori-targeted-therapies
#17
Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Francesco Massari, Davide Bimbatti, Emanuela Fantinel, Vincenzo De Marco, Antonio Benito Porcaro, Guido Martignoni, Walter Artibani, Giampaolo Tortora
AIM: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients...
July 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28755050/glutamate-neonatal-excitotoxicity-modifies-vegf-a-vegf-b-vegfr-1-and-vegfr-2-protein-expression-profiles-during-postnatal-development-of-the-cerebral-cortex-and-hippocampus-of-male-rats
#18
Jose Luis Castañeda-Cabral, Carlos Beas-Zarate, Graciela Gudiño-Cabrera, Monica E Ureña-Guerrero
Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp...
July 29, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28754869/total-flavones-of-abelmoschus-manihot-enhances-angiogenic-ability-both-in-vitro-and-in-vivo
#19
Lingyi Tang, Wu Pan, Guisong Zhu, Zhihui Liu, Dongling Lv, Meng Jiang
Angiogenesis is a process of new blood vessel formation from pre-existing vessels. It is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. Total flavones of Abelmoschus manihot (TFA) are the major constituents of the traditional Chinese herb Abelmoschus manihot L. Medic. The aim of this study is to investigate the effect of TFA on angiogenic ability using human umbilical vein endothelial cells (HUVECs) in vitro and chick chorioallantoic membrane (CAM) in vivo...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753861/e2f1-signalling-is-predictive-of-chemoresistance-and-lymphogenic-metastasis-in-penile-cancer-a-pilot-functional-study-reveals-new-prognostic-biomarkers
#20
Ferdinand Fenner, Deborah Goody, Chris Protzel, Andreas Erbersdobler, Christin Richter, Juliane M Hartz, Carsten M Naumann, Holger Kalthoff, Ottmar Herchenröder, Oliver W Hakenberg, Brigitte M Pützer
BACKGROUND: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. OBJECTIVE: To identify functional biomarkers that can predict malignant progression and treatment responsiveness. DESIGN, SETTING, AND PARTICIPANTS: We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments...
March 1, 2017: European Urology Focus
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