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https://www.readbyqxmd.com/read/28212583/role-of-topk-in-lipopolysaccharide-induced-breast-cancer-cell-migration-and-invasion
#1
Min-Ah Seol, Jung-Hwan Park, Ji Heun Jeong, Jungmook Lyu, Seung Yun Han, Sang-Muk Oh
Inflammation has been known to be linked to invasion or metastasis of breast cancer, which has poor prognosis, although the regulatory mechanism remains to be undiscovered. Here we show that T-LAK cell-originated protein kinase (TOPK) mediates pro-inflammatory endotoxin lipopolysaccharide (LPS)-induced breast cancer cell migration and invasion. The mRNA or protein level of TOPK, toll- like receptor4 (TLR4), interleukin (IL)-6, vascular endothelial growth factor (VEGF) or matrix metalloproteinase9 (MMP9) genes related to TLR4 signaling or tumor progression was induced by LPS treatment in MCF7 breast cancer cells, but the induction was abolished by stable knocking down of TOPK in MCF7 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#2
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212363/vegf-inhibitors-in-renal-cell-carcinoma
#3
Pankit Vachhani, Saby George
The arrival of targeted therapies-vascular endothelial growth factor (VEGF) pathway inhibitors and mammalian target of rapamycin (mTOR) inhibitors-and programmed death 1 (PD-1) inhibitors has transformed the management of renal cell carcinoma (RCC). Once considered fatal, with a median survival of approximately 1 year, these agents have nearly tripled overall survival and have raised hopes of a possible cure for advanced RCC. This review begins with a brief discussion of the seminal von Hippel-Lindau/hypoxia-inducible factor axis in RCC...
December 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28212293/targeting-angiogenesis-in-biliary-tract-cancers-an-open-option
#4
REVIEW
Valeria Simone, Oronzo Brunetti, Luigi Lupo, Mario Testini, Eugenio Maiorano, Michele Simone, Vito Longo, Christian Rolfo, Marc Peeters, Aldo Scarpa, Amalia Azzariti, Antonio Russo, Domenico Ribatti, Nicola Silvestris
Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28209257/synthesis-and-evaluation-of-n-benzofuran-5-yl-aromaticsulfonamide-derivatives-as-novel-hif-1-inhibitors-that-possess-anti-angiogenic-potential
#5
Jinlian Wei, Yingrui Yang, Yali Li, Xiaofei Mo, Xiaoke Guo, Xiaojin Zhang, Xiaoli Xu, Zhengyu Jiang, Qidong You
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18...
June 11, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28205552/a-class-of-extracellular-vesicles-from-breast-cancer-cells-activates-vegf-receptors-and-tumour-angiogenesis
#6
Qiyu Feng, Chengliang Zhang, David Lum, Joseph E Druso, Bryant Blank, Kristin F Wilson, Alana Welm, Marc A Antonyak, Richard A Cerione
Non-classical secretory vesicles, collectively referred to as extracellular vesicles (EVs), have been implicated in different aspects of cancer cell survival and metastasis. Here, we describe how a specific class of EVs, called microvesicles (MVs), activates VEGF receptors and tumour angiogenesis through a unique 90 kDa form of VEGF (VEGF90K). We show that VEGF90K is generated by the crosslinking of VEGF165, catalysed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28203296/incorporating-vegf-targeted-therapy-in-advanced-urothelial-cancer
#7
REVIEW
Sujata Narayanan, Sandy Srinivas
Patients with relapsed or refractory urothelial carcinoma (UC) have poor prognosis coupled with few options for systemic treatment. The role of angiogenesis in the evolution of cancers has been established, and studies have shown that it plays a key role in the pathogenesis of UC. Many targeted agents have been used in phase I-II trials for the treatment of UC, with encouraging but modest results. Recently, studies combining angiogenesis inhibitors with other chemotherapeutic agents were able to achieve objective responses higher than most commonly used second-line therapies in UC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28202529/aberrant-syk-kinase-signaling-is-essential-for-tumorigenesis-induced-by-tsc2-inactivation
#8
Ye Cui, Wendy K Steagall, Anthony Lamattina, Gustavo Pacheco-Rodriguez, Mario Stylianou, Pranav Kidambi, Benjamin Stump, Fernanda Golzarri, Ivan O Rosas, Carmen Priolo, Elizabeth P Henske, Joel Moss, Souheil El-Chemaly
Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis (LAM), a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogeneic growth factor VEGF-D are elevated significantly in LAM. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in LAM. Here we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from LAM patients contributes to tumor growth...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197761/the-pigment-epithelium-derived-factor-pedf-an-important-potential-therapeutic-agent-for-infantile-hemangioma
#9
Ming Li, Yanru Chen, Zhihui Guo, Yide Xie, Yakuan Zhou, Chenghong Jiang, Xiaosong Chen
In previous studies, the expression and the role of proangiogenic factors in infantile hemangiomas have been well studied. However, the role of angiogenic inhibitors has been revealed rarely. The expression of PEDF, as the strongest and safe endogenous inhibitor, is still unrecognized until the current study. In order to investigate the expression and significance of the pigment epithelium-derived factor (PEDF) in the proliferating and regressing phases of infantile hemangiomas, the expression of PEDF, VEGF, Ki-67, and CD34 protein in hemangioma tissues was examined with immunohistochemical polymer HRP method in 42 cases during the proliferative phase, 40 cases during the regressing phase, and 11 cases of non-involuting congenital hemangiomas (NICHs)...
February 14, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28195067/the-effect-of-short-term-treatment-with-probiotic-vsl-3-on-various-clinical-and-biochemical-parameters-in-patients-with-liver-cirrhosis
#10
W Marlicz, E Wunsch, M Mydlowska, M Milkiewicz, K Serwin, M Mularczyk, P Milkiewicz, J Raszeja-Wyszomirska
The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28195036/gsk-3%C3%AE-inhibition-induced-neuroprotection-regeneration-and-functional-recovery-after-intracerebral-hemorrhagic-stroke
#11
Yingying Zhao, Zheng Zachory Wei, James Ya Zhang, Yongbo Zhang, Soonmi Won, Jinmei Sun, Shan Ping Yu, Jimei Li, Ling Wei
Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3'-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8 to 10-week old C57BL/6 mice. BIO (8 µg/kg, i.p.) was administered following either an acute delivery (0 - 2 hr delay) or a prolonged regimen (every 48 hrs starting at 3 days postICH)...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28194552/a-novel-synthetic-small-molecule-yf-452-inhibits-tumor-growth-through-antiangiogenesis-by-suppressing-vegf-receptor-2-signaling
#12
Yongrui Liu, Yuan He, Feifei Yang, Xiaonan Cong, Jinhua Wang, Shihong Peng, Dan Gao, Weifang Wang, Liping Lan, Xuexiang Ying, Mingyao Liu, Yihua Chen, Zhengfang Yi
Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway...
February 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28193521/pharmacological-inhibition-of-magl-lipase-attenuates-experimental-colon-carcinogenesis
#13
Ester Pagano, Francesca Borrelli, Pierangelo Orlando, Barbara Romano, Martina Monti, Lucia Morbidelli, Gabriella Aviello, Roberta Imperatore, Raffaele Capasso, Fabiana Piscitelli, Lorena Buono, Vincenzo Di Marzo, Angelo A Izzo
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR...
February 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28190892/slit2-robo4-signaling-potential-role-of-a-vegf-antagonist-pathway-to-regulate-luteal-permeability
#14
I Bekes, V Haunerdinger, R Sauter, I Holzheu, W Janni, A Wöckel, C Wulff
Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway - Slit2/Robo4 - and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured...
January 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28190652/novel-6-methoxycarbonyl-indolinones-bearing-a-pyrrole-mannich-base-moiety-as-angiokinase-inhibitors
#15
Mingze Qin, Shuang Yan, Lei Wang, Haotian Zhang, Ye Tian, Yanfang Zhao, Ping Gong
Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis...
January 25, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28188409/tipe2-inhibits-the-expression-of-asthma-related-inflammatory-factors-in-hyperstretched-bronchial-epithelial-cells-through-the-wnt-%C3%AE-catenin-pathway
#16
Xinrong Sun, Lu Chen, Wen Yan
Childhood asthma, an airway inflammatory disease, is a serious threat to the child's quality of life. Recently, TIPE2 expression was reported to be decreased in children with asthma. Therefore, additional studies focusing on TIPE2 might provide an approach for treating childhood asthma. In this study, we found that TIPE2 was poorly expressed in hyperstretched human bronchial epithelial cells (BEAS-2B). TIPE2 overexpression also significantly suppressed the stretch-induced secretion of asthma-related inflammatory factors (TNF-α, TSLP, MMP-9, and VEGF)...
February 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#17
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28184938/new-insights-and-future-perspectives-in-the-therapeutic-strategy-of-adrenocortical-carcinoma-review
#18
Antonio Stigliano, Lidia Cerquetti, Pina Lardo, Elisa Petrangeli, Vincenzo Toscano
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an incidence ranging from 0.7 to 2.0 cases/million people per year. Hypercortisolism represents the most common clinical presentation in many patients although, less frequently, some ACC secreting androgens and estrogens are even more pathognomonic compared to cortisol secretion. Currently, radical surgery, when feasible, is still the only curative therapy. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in combination with chemotherapy drugs in metastatic disease...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28184324/comparison-of-anticancer-effects-of-carbamazepine-and-valproic-acid
#19
Ladan Akbarzadeh, Taraneh Moini Zanjani, Masoumeh Sabetkasaei
BACKGROUND: Valproic acid (VPA) and carbamazepine (CBZ), two widely used antiepileptic drugs, have recently been found to inhibit histone deacetylases (HDAC). HDAC inhibitors (HDACIs) have various effects on cancer cells. OBJECTIVES: The aim of this study was to compare the anticancer activity of these drugs on SW480 colon cancer cell lines. METHODS: In the present experimental study, implemented during 2014 - 2015 in Iran, after incubation of cells into 96-well plates with 5,500 cells/well, the tested drugs were added, and cytotoxic effects were assessed by MTT...
October 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28183800/tnfsf15-inhibits-vegf-stimulated-vascular-hyperpermeability-by-inducing-vegfr2-dephosphorylation
#20
Gui-Li Yang, Zilong Zhao, Ting-Ting Qin, Dong Wang, Lijuan Chen, Rong Xiang, Zhen Xi, Rongcai Jiang, Zhi-Song Zhang, Jianning Zhang, Lu-Yuan Li
Vascular hyperpermeability is critical in ischemic diseases, including stroke and myocardial infarction, as well as in inflammation and cancer. It is well known that the VEGF-VEGFR2 signaling pathways are pivotal in promoting vascular permeability; however, counterbalancing mechanisms that restrict vascular permeability to maintain the integrity of blood vessels, are not yet fully understood. We report that TNF superfamily member 15 (TNFSF15), a cytokine largely produced by vascular endothelial cells and a specific inhibitor of the proliferation of these same cells, can inhibit VEGF-induced vascular permeability in vitro and in vivo, and that death receptor 3 (DR3), a cell surface receptor of TNFSF15, mediates TNFSF15-induced dephosphorylation of VEGFR2...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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