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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
#1
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/29297707/first-line-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-priming-the-tumor-microenvironment-for-immunotherapy
#2
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/29290798/ultrasound-molecular-imaging-of-vegfr-2-in-clear-cell-renal-cell-carcinoma-tracks-disease-response-to-antiangiogenic-and-notch-inhibition-therapy
#3
Juan D Rojas, Fanglue Lin, Yun-Chen Chiang, Anna Chytil, Diana C Chong, Victoria L Bautch, W Kimryn Rathmell, Paul A Dayton
Metastatic clear-cell renal cell carcinoma (ccRCC) affects thousands of patients worldwide each year. Antiangiogenic therapy has been shown to have beneficial effects initially, but resistance is eventually developed. Therefore, it is important to accurately track the response of cancer to different therapeutics in order to appropriately adjust the therapy to maximize efficacy. Change in tumor volume is the current gold standard for determining efficacy of treatment. However, functional variations can occur much earlier than measurable volume changes...
2018: Theranostics
https://www.readbyqxmd.com/read/29289530/a-vascular-endothelial-growth-factor-dependent-sprouting-angiogenesis-assay-based-on-an-in-vitro-human-blood-vessel-model-for-the-study-of-anti-angiogenic-drugs
#4
Joris Pauty, Ryo Usuba, Irene Gayi Cheng, Louise Hespel, Haruko Takahashi, Keisuke Kato, Masayoshi Kobayashi, Hiroyuki Nakajima, Eujin Lee, Florian Yger, Fabrice Soncin, Yukiko T Matsunaga
Angiogenesis is the formation of new capillaries from pre-existing blood vessels and participates in proper vasculature development. In pathological conditions such as cancer, abnormal angiogenesis takes place. Angiogenesis is primarily carried out by endothelial cells, the innermost layer of blood vessels. The vascular endothelial growth factor-A (VEGF-A) and its receptor-2 (VEGFR-2) trigger most of the mechanisms activating and regulating angiogenesis, and have been the targets for the development of drugs...
December 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29284120/colorimetric-immunoassays-for-the-screening-and-specificity-evaluation-of-molecules-disturbing-vegfs-vegfrs-interactions
#5
Laura Trapiella-Alfonso, Sylvain Broussy, Wang-Qing Liu, Michel Vidal, Edouard Lecarpentier, Vassilis Tsatsaris, Nathalie Gagey-Eilstein
Angiogenesis and its involved proteins, particularly Vascular Endothelial Growth Factor (VEGF) family and VEGF receptors (VEGFRs), have been considered as a target of therapeutic interest for numerous inflammatory and vascular diseases. Acting on this biological process through interaction with VEGFs or VEGFRs has received considerable attention. Indeed, VEGFs and VEGFRs are currently targeted by drugs such as monoclonal antibodies. The feasibility of a therapeutic strategy based on blocking the VEGF/VEGFR interaction by using ligands "other-than-biologics" is also explored...
December 25, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29260199/systemic-inflammation-associated-proteins-and-retinopathy-of-prematurity-in-infants-born-before-the-28th-week-of-gestation
#6
Mari Holm, Tora S Morken, Raina N Fichorova, Deborah K VanderVeen, Elizabeth N Allred, Olaf Dammann, Alan Leviton
Purpose: To assess the association between systemic levels of inflammation-associated proteins and severe retinopathy of prematurity (ROP) in extremely preterm infants. Methods: We collected whole blood on filter paper on postnatal days 1, 7, 14, 21, and 28 from 1205 infants born before the 28th week of gestation, and measured the concentrations of 27 inflammation-associated, angiogenic, and neurotrophic proteins. We calculated odds ratios with 95% confidence intervals for the association between top quartile concentrations of each protein and prethreshold ROP...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29259905/negative-effects-of-transthyretin-in-high-myopic-vitreous-on-diabetic-retinopathy
#7
Jun Shao, Yong Yao
AIM: To analyze the relationship between vitreous transthyretin (TTR) levels, high myopia and diabetic retinopathy (DR). METHODS: We selected 6722 individuals from the southern Jiangsu Province for diabetes and ophthalmic examinations. The TTR concentration in the vitreous of 50 patients with high myopia and diabetes, 50 patients with only DR, and 20 healthy controls were determined by ELISA. Key factors in Tie2 pathway in DR development including vascular endothecial growth factor (VEGF), Tie2, Angpt1, Angpt2, vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were also detected by ELISA...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29258180/major-challenges-and-potential-microenvironment-targeted-therapies-in-glioblastoma
#8
REVIEW
Ali S Arbab, Mohammad H Rashid, Kartik Angara, Thaiz F Borin, Ping-Chang Lin, Meenu Jain, Bhagelu R Achyut
Glioblastoma (GBM) is considered one of the most malignant, genetically heterogeneous, and therapy-resistant solid tumor. Therapeutic options are limited in GBM and involve surgical resection followed by chemotherapy and/or radiotherapy. Adjuvant therapies, including antiangiogenic treatments (AATs) targeting the VEGF-VEGFR pathway, have witnessed enhanced infiltration of bone marrow-derived myeloid cells, causing therapy resistance and tumor relapse in clinics and in preclinical models of GBM. This review article is focused on gathering previous clinical and preclinical reports featuring major challenges and lessons in GBM...
December 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29250168/anti-angiogenic-effect-of-livistona-chinensis-seed-extract-in-vitro-and-in-vivo
#9
Zhiyun Cao, Liangpu Zheng, Jinyan Zhao, Qunchuan Zhuang, Zhenfeng Hong, Wei Lin
The present study aimed to detect the impact of the ethanol extract of the Livistona chinensis seed (EELC) on angiogenesis in human umbilical vein endothelial cells (HUVECs). A chorioallantoic membrane (CAM) assay was used to detect the anti-angiogenic activity of EELC in vivo. In vitro, the effect of EELC on the proliferation, migration and angiogenesis of HUVECs was determined by an MTT assay, a wound healing assay and a tube formation assay, respectively. The vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)-2 protein and mRNA level were measured with ELISA and reverse transcription-semi-quantitative polymerase chain reaction...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29228696/mp0250-a-vegf-and-hgf-neutralizing-darpin%C3%A2-molecule-shows-high-anti-tumor-efficacy-in-mouse-xenograft-and-patient-derived-tumor-models
#10
Ulrike Fiedler, Savira Ekawardhani, Andreas Cornelius, Pat Gilboy, Talitha R Bakker, Ignacio Dolado, Michael T Stumpp, Keith M Dawson
Background: The VEGF/VEGFR and the HGF/cMET pathways are key mediators of the interplay of tumor cells and their microenvironment. However, inhibition of VEGF has been shown to produce only limited clinical benefit and inhibition of the activation of cMET by HGF has not translated into clinical benefit in pivotal trials. MP0250, a DARPin® molecule that specifically inhibits both VEGF and HGF has been developed to explore the clinical potential of dual inhibition of these pathways. Results: MP0250 binding to VEGF and HGF inhibited downstream signalling through VEGFR2 and cMET resulting in inhibition of proliferation of VEGF- and HGF-dependent cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#11
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228087/analysis-of-angiogenesis-biomarkers-for-ramucirumab-efficacy-in-patients-with-metastatic-colorectal-cancer-from-raise-a-global-randomized-double-blind-phase-iii-study
#12
J Tabernero, R R Hozak, T Yoshino, A L Cohn, R Obermannova, G Bodoky, R Garcia-Carbonero, T-E Ciuleanu, D C Portnoy, J Prausová, K Muro, R W Siegel, R J Konrad, H Ouyang, S A Melemed, D Ferry, F Nasroulah, E Van Cutsem
Background: The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo+FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes...
December 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29226113/in-vitro-evaluation-of-vegf-pseudomonas-exotoxin-a-conjugated-on-tumor-cells
#13
Jahangir Langari, Morteza Karimipoor, Majid Golkar, Hossein Khanahmad, Sirous Zeinali, Skandar Omidinia, Reza Ahangari Cohan, Mahdi Behdani, Jalal Babaie, Roghaye Arezumand, Reza Moazami
Background: Angiogenesis which occurs mandatory in solid tumors, is a critical step in malignancy progression. Vascular endothelial growth factor (VEGF) is mainly responsible for angiogenesis process and facilitates the formation of new vessels. Distribution of monoclonal antibodies against VEGF or VEGF receptor (VEGFR) into the solid tumors is limited because of their huge dimensions. Moreover, many investigations have demonstrated the usefulness of immunotoxins to halt angiogenesis in solid tumors...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29221641/p53-expression-in-patients-with-renal-cell-carcinoma-correlates-with-a-higher-probability-of-disease-progression-and-increased-cancer-specific-mortality-after-surgery-but-does-not-enhance-the-predictive-accuracy-of-robust-outcome-models
#14
Laura Morshaeuser, Matthias May, Maximilian Burger, Wolfgang Otto, Georg C Hutterer, Martin Pichler, Tobias Klatte, Peter Wild, Lorenz Buser, Sabine Brookman-May
OBJECTIVE: Due to lacking external validation, molecular biomarkers are currently not applied for risk-stratification of patients with localized renal cell carcinoma. The objective of this study was to externally validate a molecular multi-marker panel included in a previously proposed prognostic nomogram for the prediction of postoperative disease-free survival. METHODS AND MATERIALS: Besides pathologic tumor stage (pT) and ECOG-Performance Status, the nomogram includes 5 molecular markers (Ki-67, p53, VEGFR-1 endothelial or epithelial, and VEGF-D epithelial)...
December 5, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29221123/vegf-induced-intracellular-ca2-oscillations-are-down-regulated-and-do-not-stimulate-angiogenesis-in-breast-cancer-derived-endothelial-colony-forming-cells
#15
Francesco Lodola, Umberto Laforenza, Fabio Cattaneo, Federico Alessandro Ruffinatti, Valentina Poletto, Margherita Massa, Richard Tancredi, Estella Zuccolo, Dlzar Alì Khdar, Alberto Riccardi, Marco Biggiogera, Vittorio Rosti, Germano Guerra, Francesco Moccia
Endothelial colony forming cells (ECFCs) represent a population of truly endothelial precursors that promote the angiogenic switch in solid tumors, such as breast cancer (BC). The intracellular Ca2+ toolkit, which drives the pro-angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that they are seemingly insensitive to this growth factor. This feature could underlie the relative failure of anti-VEGF therapies in cancer patients. Herein, we investigated whether and how VEGF uses Ca2+ signalling to control angiogenesis in BC-derived ECFCs (BC-ECFCs)...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218108/the-synergistic-effect-of-esophageal-squamous-cell-carcinoma-kyse150-cells-and-m2-macrophages-on-lymphatic-endothelial-cells
#16
Miao-Miao Sun, Lu-Lu He, Hong-Xin Zhang, Na Wei, Wei-Wei Wang, Guo-Zhong Jiang, Zheng-Yang Wang, Dong-Mei Zhao, Kui-Sheng Chen
Objective: This study aimed to investigate whether tumor-associated macrophages (TAMs) and esophageal squamous cell carcinoma (ESCC) cells could synergistically influence the generation of lymphatic vessels via the VEGF-C/VEGFR-3 signaling pathway and to address its mechanism. Methods: M2 macrophages were sorted with immunomagnetic beads and induced in vitro. VEGF-C siRNA plasmids were constructed and transfected into M2 macrophages and the ESCC cell line KYSE150. Different conditioned culture media before and after transfection were collected and classified into different groups for culturing ESCC-associated lymphatic endothelial cells (ESCC-LECs)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29218079/vegf-c-mediated-enhancement-of-lymphatic-drainage-reduces-intestinal-inflammation-by-regulating-il-9-il-17-balance-and-improving-gut-microbiota-in-experimental-chronic-colitis
#17
Xiaolei Wang, Jin Zhao, Li Qin
BACKGROUND: Inflammation-associated lymphangiogenesis (IAL) induced by vascular endothelial growth factor (VEGF)-C/VEGF receptor-3 (VEGFR-3) pathway plays a crucial role in chronic intestinal inflammation. This study aimed to investigate the effects of VEGF-C mediated enhancement of lymphatic drainage on the intestinal inflammation in experimental chronic colitis (CC) and the potential mechanism was explored. METHODS: Mouse CC model was established by three cycles of 2% DSS administration for 5 days following water administration for 5 days...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29208350/efficient-differentiation-of-bone-marrow-mesenchymal-stem-cells-into-endothelial-cells-in%C3%A2-vitro
#18
Chengen Wang, Yuan Li, Min Yang, Yinghua Zou, Huihui Liu, Zeyin Liang, Yue Yin, Guochen Niu, Ziguang Yan, Bihui Zhang
OBJECTIVE: Endothelial cells (ECs) play an important role in neovascularisation, but are too limited in number for adequate therapeutic applications. Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial lineage cells, which makes them attractive candidates for therapeutic angiogenesis. The aim of this study was to investigate efficient differentiation of MSCs into ECs by inducing medium in vitro. METHODS: MSCs were isolated from bone marrow by density gradient centrifugation...
December 2, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/29207605/vegf121-is-predictor-for-survival-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-is-related-to-an-immune-response-gene-signature-conserved-in-cancers
#19
Julien Broséus, Samia Mourah, Gérard Ramstein, Sophie Bernard, Nicolas Mounier, Wendy Cuccuini, Philippe Gaulard, Christian Gisselbrecht, Josette Brière, Rémi Houlgatte, Catherine Thieblemont
Tumor microenvironment including endothelial and immune cells plays a crucial role in tumor progression and has been shown to dramatically influence cancer survival. In this study, we investigated the clinical relevance of the gene expression of key mediators of angiogenesis, VEGF isoforms 121, 165, and 189, and their receptors (VEGFR-1 and R-2) in a cohort of patients (n = 37) with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL)...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29188530/histopathological-vascular-investigation-of-the-peritumoral-brain-zone-of-glioblastomas
#20
Ryota Tamura, Kentaro Ohara, Hikaru Sasaki, Yukina Morimoto, Kazunari Yoshida, Masahiro Toda
To date, no histopathological vascular investigation focusing on peritumoral brain zone (PBZ) has been reported for glioblastoma. We analyzed 10 newly diagnosed cases of glioblastomas. For these PBZs, histopathological investigation was performed by hematoxylin-eosin (H&E) staining and immunohistochemistry was analyzed for CD31, CD34, Factor VIII, VEGF, VEGFR-1/2, Ki67, p53 and nestin. Although it was difficult to identify PBZ by H&E, Ki67 and p53 staining, there were apparent differences in nestin staining among PBZ, tumor core (TC), and normal zone (NZ)...
November 29, 2017: Journal of Neuro-oncology
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