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https://www.readbyqxmd.com/read/28434110/the-risk-of-radiation-necrosis-following-stereotactic-radiosurgery-with-concurrent-systemic-therapies
#1
Joseph M Kim, Jacob A Miller, Rupesh Kotecha, Roy Xiao, Aditya Juloori, Matthew C Ward, Manmeet S Ahluwalia, Alireza M Mohammadi, David M Peereboom, Erin S Murphy, John H Suh, Gene H Barnett, Michael A Vogelbaum, Lilyana Angelov, Glen H Stevens, Samuel T Chao
To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN)...
April 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28431322/xanthohumol-and-8-prenylnaringenin-ameliorate-diabetic-related-metabolic-dysfunctions-in-mice
#2
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Sílvia Rocha-Rodrigues, Carolina Silva, José Magalhães, Manuel Ferreira-de-Almeida, Rita Negrão, Raquel Soares
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28430711/evaluation-of-kdr-rs34231037-as-a-predictor-of-sunitinib-efficacy-in-patients-with-metastatic-renal-cell-carcinoma
#3
María Apellániz-Ruiz, Meta H Diekstra, Juan M Roldán, Epie Boven, Daniel Castellano, Hans Gelderblom, Ron H J Mathijssen, Jesse J Swen, Stefan Böhringer, Jesús García-Donás, Brian I Rini, Henk-Jan Guchelaar, Cristina Rodríguez-Antona
The identification of biomarkers able to predict clinical benefit from vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors is urgently needed. Recently, Maitland and colleagues described an association between KDR-rs34231037 and soluble VEGFR2 levels as well as pazopanib pharmacodynamics. We investigated in a well-characterized series of metastatic clear cell renal cell carcinoma patients whether rs34231037 could influence sunitinib response. Clinical data and DNA were available from an international series of 276 patients...
April 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#4
Haochen Xu, Yongliang Cao, Xing Yang, Ping Cai, Lijing Kang, Ximin Zhu, Haiyu Luo, Lu Lu, Lixiang Wei, Xiaofei Bai, Yuanbo Zhu, Bing-Qiao Zhao, Wenying Fan
Angiogenic response is essential for ischemic brain repair. However, the mechanisms leading to postischemic neovascularization have not been established, and no therapies have been identified. The VWF-cleaving protease ADAMTS13 is required for endothelial tube formation in vitro However, there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited significantly reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28423739/sialyllactose-suppresses-angiogenesis-by-inhibiting-vegfr-2-activation-and-tumor-progression
#5
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...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421362/selective-imaging-of-vascular-endothelial-growth-factor-receptor-1-and-receptor-2-in-atherosclerotic-lesions-in-diabetic-and-non-diabetic-apoe-mice
#6
Yared Tekabe, Lynne L Johnson, Krissy Rodriquez, Qing Li, Marina Backer, Joseph M Backer
PURPOSE: Plaque vulnerability is associated with inflammation and angiogenesis, processes that rely on vascular endothelial growth factor (VEGF) signaling via two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies accelerated atherosclerosis in diabetic relative to non-diabetic ApoE(-/-) mice. Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we reasoned that selective imaging of each receptor can provide more detailed information on plaque biology...
April 18, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28412217/dalbergia-odorifera-extract-promotes-angiogenesis-through-upregulation-of-vegfrs-and-pi3k-mapk-signaling-pathways
#7
Zhu-Ming Fan, Da-Ying Wang, Jian-Mei Yang, Zhi-Xiu Lin, Ai-Lin Yang, Hua Fan, Min Cao, Su-Yun Yuan, Zong-Jun Liu, Xin Zhou, You-Hua Wang
ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. AIM OF THE STUDY: In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay...
April 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28411406/discovery-of-novel-2-substituted-4-2-fluorophenoxy-pyridine-derivatives-possessing-pyrazolone-and-triazole-moieties-as-dual-c-met-vegfr-2-receptor-tyrosine-kinase-inhibitors
#8
Weijie Gu, Yuxuan Dai, Hao Qiang, Wei Shi, Chen Liao, Fangnuo Zhao, Wenlong Huang, Hai Qian
In our efforts to develop novel dual c-Met/VEGFR-2 inhibitors as potential anticancer agents, a series of 2-substituted-4-(2-fluorophenoxy) pyridine derivatives bearing pyrazolone scaffold were designed and synthesized. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency on both c-Met and VEGFR-2, especially compound 9h, 12b and 12d. Based on the further enzyme assay in vitro, compound 12d was considered as the most promising one, the IC50 values of which were 0...
April 8, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28408241/maternal-retinoids-increase-pdgfr%C3%AE-progenitor-population-and-beige-adipogenesis-in-progeny-by-stimulating-vascular-development
#9
Bo Wang, Xing Fu, Xingwei Liang, Zhixiu Wang, Qiyuan Yang, Tiande Zou, Wei Nie, Junxing Zhao, Pengfei Gao, Mei-Jun Zhu, Jeanene M de Avila, Joseph Maricelli, Buel D Rodgers, Min Du
Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα(+) adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA...
April 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28405689/differential-effects-of-sulforaphane-in-regulation-of-angiogenesis-in-a-co-culture-model-of-endothelial-cells-and-pericytes
#10
Yichong Wang, Zhigang Zhou, Wei Wang, Ming Liu, Yongping Bao
Aberrant neovascularization supports nutrients and the oxygen microenvironment in tumour growth, invasion and metastasis. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to possess chemopreventive properties. In the present study, the effects of SFN on cell proliferation and tubular formation have been investigated using endothelial cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on the growth of ECs and pericytes with IC50 values 46...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28403784/synthesis-characterization-of-4-anilino-6-7-dimethoxy-quinazoline-derivatives-as-potential-anti-angiogenic-agents
#11
Saligrama Devegowda Preethi, Balaji Kyathegowdanadoddi Srinivas, Prasanna Doddakunche Shivaramu, Swaroop Toreshettahally Ramesh, Shankar Jayarama, Rangappa KanchKanchugarakoppal Subbegowda, Lokesh Siddalingaiah Gowda
A series of novel 4-anilino-6,7-dimethoxy quinazoline derivatives were synthesized and characterized using 1H, 13C NMR and FT-IR and mass spectroscopic techniques. Cytotoxicity assays were performed for all compounds against different cell lines such as human colon carcinoma (HCT116), human chronic myeloid leukemia (K562) and human breast cancer (SKBR3) cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), Tryphan blue and Lactose dehydrogenase release assay. Among all compounds, RB4, RB7 showed moderate activity whereas RB1 showed most potent activity comparable with that of the standard drug cisplatin against all three cells lines...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28403086/a-case-report-of-apatinib-in-treating-osteosarcoma-with-pulmonary-metastases
#12
Yong Zhou, Wengeng Zhang, Fan Tang, Yi Luo, Li Min, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu
RATIONALE: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Pulmonary metastases lead to a significantly increased risk of death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast cancer. However, its efficacy in metastatic osteosarcoma has not been reported yet...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28400373/association-between-vegf-a-and-vegfr-2-polymorphisms-and-response-to-treatment-of-neovascular-amd-with-anti-vegf-agents-a-meta-analysis
#13
Mingxing Wu, Haibo Xiong, Yan Xu, Xiaojing Xiong, Hongmi Zou, Minming Zheng, Xiuqing Wang, Xiyuan Zhou
AIMS: The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD). METHODS: We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD. RESULTS: For the single nucleotide polymorphisms (SNPs) within VEGF-A and VEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT:OR=2...
October 21, 2016: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28400300/locoregional-therapy-and-recurrent-hepatocellular-carcinoma-after-liver-transplantation
#14
Min Xu, Majella Doyle, Babak Banan, Neeta Vachharajani, Xuanchuan Wang, Nael Saad, Katherine Fowler, Elizabeth M Brunt, Yiing Lin, William C Chapman
BACKGROUND: Neoadjuvant locoregional therapies (LRT) have been widely used to reduce tumor burden or downstage hepatocellular carcinoma (HCC) prior to orthotopic liver transplantation (OLT). We examined the impact of LRT response on HCC recurrence after OLT. STUDY DESIGN: We performed a retrospective study of 384 HCC patients treated by OLT. Tumor necrosis was determined by pathologic evaluation. The vascular and lymphatic vessels were localized by immunofluorescence (IF) staining in formalin-fixed, paraffin-embedded tissue; expressions of VEGFR-2 and VEGFR-3 were analyzed by Western Blot...
April 8, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28397047/efficacy-and-safety-of-chemotherapy-with-or-without-targeted-therapy-in-biliary-tract-cancer-a-meta-analysis-of-7-randomized-controlled-trials
#15
Xin Zhuang, Ya-Ping Xiao, Ling-Hua Tan, Lu-Ting Wang, Qian Cao, Gui-Fang Qu, Shuang Xiao, Hua-Xin Duan
The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28391576/phase-i-trial-and-pharmacokinetic-study-of-tanibirumab-a-fully-human-monoclonal-antibody-to-vascular-endothelial-growth-factor-receptor-2-in-patients-with-refractory-solid-tumors
#16
Su Jin Lee, Seon Young Lee, Weon Sup Lee, Jin San Yoo, Jong-Mu Sun, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Myung-Ju Ahn, Ho Yeong Lim, Won Ki Kang, Young Suk Park
Background Tanibirumab is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of tanibirumab in patients with solid tumors refractory to standard chemotherapy. Primary endpoints were evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Methods We designed our study to escalate tanibirumab at 9 different dose levels with a 3 + 3 method and tanibirumab (1-28 mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses...
April 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28386328/kallistatin-protects-against-bleomycin-induced-idiopathic-pulmonary-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#17
Xiaoping Huang, Xiao Wang, Xiaolan Xie, Shulan Zeng, Zhaofa Li, Xianxiang Xu, Huiyong Yang, Fei Qiu, Junsheng Lin, Yong Diao
Aberrant angiogenesis and vascular remodeling are the main features of idiopathic pulmonary fibrosis. Kallistatin is an anti-angiogenic peptide with known effects on endothelial cells. This study aimed to demonstrate that kallistatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in a rat model by inhibiting angiogenesis. Twenty-five rats were randomly divided into five experimental groups: (A) Saline only (SA)-as the negative control, (B) BLM only (BLM)-as the model group, (C) BLM and 0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28383032/anti-tumour-activity-of-tivozanib-a-pan-inhibitor-of-vegf-receptors-in-therapy-resistant-ovarian-carcinoma-cells
#18
Majid Momeny, Zahra Sabourinejad, Ghazaleh Zarrinrad, Farima Moghaddaskho, Haniyeh Eyvani, Hassan Yousefi, Shahab Mirshahvaladi, Ensieh M Poursani, Farinaz Barghi, Arash Poursheikhani, Leila Dardaei, Davood Bashash, Mahmoud Ghazi-Khansari, Seyyed M Tavangar, Ahmad R Dehpour, Marjan Yaghmaie, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378918/a-pharmacometric-framework-for-axitinib-exposure-efficacy-and-safety-in-metastatic-renal-cell-carcinoma-patients
#19
Emilie Schindler, Michael A Amantea, Mats O Karlsson, Lena E Friberg
The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, 2, 3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP) and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker time-courses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, 2 and 3 production, and VEGF degradation...
April 5, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28377484/phase-ib-ii-study-of-safety-efficacy-of-combination-therapy-with-multikinase-vegf-inhibitor-pazopanib-and-mek-inhibitor-trametinib-in-advanced-soft-tissue-sarcoma
#20
Vivek Subbiah, Christian Meyer, Ralph Zinner, Funda Meric-Bernstam, Marianna L Zahurak, Ashley O'Connor, Jason Roszik, Kenna Shaw, Joseph A Ludwig, Razelle Kurzrock, Nilofer A Azad
Purpose: Pazopanib, a multi-receptor tyrosine kinase inhibitor targeting primarily vascular endothelial growth factor receptors 1-3 (VEGFRs1-3), is approved for advanced soft tissue sarcoma and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using a trametinib would synergize with pazopanib in advanced soft tissue sarcoma (STS). <p>Experimental Design: In an open-label, multicenter, investigator-initiated NCCN-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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