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Liting Jiang, Yinyin Xie, Li Wei, Qi Zhou, Xing Shen, Xinquan Jiang, Yiming Gao
Angiogenesis mediated by vascular endothelial growth factor (VEGF) is known to play an important role in regulating cartilage remodelling and endochondral ossification. However, the details of how VEGF signalling mechanisms affect condyle remodelling in response to alterations in functional loading remains unclear. To explore this, eighty 16-day-old male SD rats were divided into two equal groups which were fed either a soft/powdery diet or a hard diet for 4 weeks; the stiffness of the diet results in alteration of mastication force and hence temporomandibular joint (TMJ) development...
January 2017: FEBS Open Bio
Jian Yang, Paulina A Samsel, Kalin Narov, Ashley Jones, Daniel Gallacher, John Gallacher, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumor syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR and development of tumors in multiple organs including the kidneys. The mTOR inhibitors rapamycin and everolimus (rapalogs) have demonstrated clinical efficacy in treating TSC-associated tumors including renal angiomyolipomas. However, tumor responses are usually only partial, and regrowth occurs after drug withdrawal. TSC-associated tumors are highly vascular, and TSC patients with renal angiomyolipomas have elevated levels of circulating vascular endothelial growth factor (VEGF) A and VEGFD...
February 2017: Neoplasia: An International Journal for Oncology Research
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, giving rise to veins and lymphatics. Vegfd has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
February 1, 2017: Development
Andrea Rossi, Sebastien Gauvrit, Michele Marass, Luyuan Pan, Cecilia B Moens, Didier Y R Stainier
The mechanisms that allow cells to bypass anti-VEGFA therapy remain poorly understood. Here we use zebrafish to investigate this question and first show that vegfaa mutants display a severe vascular phenotype that can surprisingly be rescued to viability by vegfaa mRNA injections at the one-cell stage. Using vegfaa mutants as an in vivo test tube, we found that zebrafish Vegfbb, Vegfd and Pgfb can also rescue these animals to viability. Taking advantage of a new vegfr1 tyrosine kinase deficient mutant, we determined that Pgfb rescues vegfaa mutants via Vegfr1...
August 24, 2016: Blood
Zara Zelenko, Emily Jane Gallagher, Irini Markella Antoniou, Deepali Sachdev, Anupma Nayak, Douglas Yee, Derek LeRoith
Type 2 diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing the Rag1(-/-) mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate the Rag1(-/-) (Rag/WT) and Rag1(-/-)/MKR(+/+) (Rag/MKR) mice. The female Rag/MKR mice are insulin resistant and have significantly higher nonfasting plasma insulin levels compared with the Rag/WT controls. Therefore, we used these Rag/MKR mice to investigate the role of endogenous hyperinsulinemia on human cancer progression...
September 2016: Endocrine-related Cancer
B B Hassan, S M Elshafae, W Supsavhad, J K Simmons, W P Dirksen, S M Sokkar, T J Rosol
Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines...
January 2017: Veterinary Pathology
Xiaorong Qi, Licheng Du, Xiancheng Chen, Lijuan Chen, Tao Yi, Xiang Chen, Yanjun Wen, Yuquan Wei, Xia Zhao
Lymphatic metastasis is a poor prognostic factor in ovarian cancer, which correlates to the majority of cancer deaths. Matrix protein (MP) of vesicular stomatitis virus (VSV) exhibits potent antitumor and antiangiogenic activities through inducing apoptosis and inhibiting angiogenesis. In this study, the antitumor and antimetastatic effects of MP were further investigated. Wild-type SKOV3 (WT-SK) cells were successfully transfected with empty vector pcDNA3.1 plasmid, or pcDNA3.1-VEGF-D recombinant plasmid to construct cell lines named EV-SK, and VEGFD-SK, respectively...
July 2016: International Journal of Oncology
Hung M Bui, David Enis, Marius R Robciuc, Harri J Nurmi, Jennifer Cohen, Mei Chen, Yiqing Yang, Veerpal Dhillon, Kathy Johnson, Hong Zhang, Robert Kirkpatrick, Elizabeth Traxler, Andrey Anisimov, Kari Alitalo, Mark L Kahn
Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. VEGFC is required for lymphatic development, while VEGFD is not. VEGFC and VEGFD are proteolytically cleaved after cell secretion in vitro, and recent studies have implicated the protease a disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3) and the secreted factor collagen and calcium binding EGF domains 1 (CCBE1) in this process. It is not well understood how ligand proteolysis is controlled at the molecular level or how this process regulates lymphangiogenesis, because these complex molecular interactions have been difficult to follow ex vivo and test in vivo...
June 1, 2016: Journal of Clinical Investigation
Stefan Riwaldt, Johann Bauer, Markus Wehland, Lasse Slumstrup, Sascha Kopp, Elisabeth Warnke, Anita Dittrich, Nils E Magnusson, Jessica Pietsch, Thomas J Corydon, Manfred Infanger, Daniela Grimm
Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line) after a 24 h-exposure on the Random Positioning Machine (RPM) and focused on 3D growth signaling processes...
April 8, 2016: International Journal of Molecular Sciences
Sang-Hee Lee, Eun-Ji Song, Yong Hwangbo, Seunghyung Lee, Choon-Keun Park
The aim of this study was to examine protein expression patterns of uterine histroph (UH) during the follicular phase (FP) and luteal phase (LP) in pigs. Forty-nine common proteins were identified from FP and LP samples; five were significantly down-regulated (>1.5-fold), while 15 were significantly up-regulated (>1.5-fold) in LPUH compared with FPUH (P<0.05). The 20 differentially-expressed proteins are involved in cell proliferation, cell responses, translation, transport, and metabolism and their molecular functions include nucleic acid binding, oxygen activity, enzymatic activity, growth activity, iron binding, and redox binding...
May 2016: Animal Reproduction Science
Teruhiko Sato, Sophie Paquet-Fifield, Nicole C Harris, Sally Roufail, Debra J Turner, Yinan Yuan, You-Fang Zhang, Stephen B Fox, Margaret L Hibbs, Jennifer L Wilkinson-Berka, Richard A Williams, Steven A Stacker, Peter D Sly, Marc G Achen
Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia...
June 2016: Journal of Pathology
Jun Li, Lin Ye, Ping-Hui Sun, Lucy Satherley, Rachel Hargest, Zhongtao Zhang, Wen G Jiang
BACKGROUND: Metastasis-associated protein 1 (MTA1) plays an important role in tumourigenesis and progression of certain cancer types. In the current study, we analyzed the relationship between MTA1 expression and disease progression of colorectal cancer (CRC). MATERIALS AND METHODS: CRC tissues (n=93) and adjacent normal colorectal tissues (n=70) were analyzed by quantitative real-time polymerase chain reaction. MTA1 knockdown was established in RKO and HT115 cells using MTA1 siRNA...
November 2015: Cancer Genomics & Proteomics
O A Peters, J Galicia, A Arias, M Tolar, E Ng, S J Shin
AIM: To evaluate the effects of two types of calcium silicate cements on viability, angiogenic growth factor release, and angiogenic and inflammation-related gene expression in human stem cells from the apical papilla (SCAP). METHODOLOGY: SCAPs were grown for 7 days with either ProRoot mineral trioxide aggregate (MTA) or Biodentine (BD). Cell viability and media concentrations of vascular endothelial growth factor (VEGF/VEGFA) and angiopoietin 1 (ANGPT1) were measured...
December 2016: International Endodontic Journal
César A Briceño, Victor M Elner, Hakan Demirci
PURPOSE: The aim of this study was to evaluate expression patterns of known lymphangiogenic growth factors and chemokines in conjunctival melanoma, and to describe patterns of lymphatic vessel growth in these tumors. METHODS: This was a retrospective chart review comprising 5 participants (6 tumor specimens) and the main outcome measures were expression of growth factors, chemokines, and their receptors known to be important in tumor lymphangiogenesis as well as patterns of lymphatic vessel growth on immunohistochemical sections...
November 2016: Ophthalmic Plastic and Reconstructive Surgery
Harri Nurmi, Pipsa Saharinen, Georgia Zarkada, Wei Zheng, Marius R Robciuc, Kari Alitalo
Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted...
November 2015: EMBO Molecular Medicine
Kazuhide S Okuda, June Pauline Misa, Stefan H Oehlers, Christopher J Hall, Felix Ellett, Sultan Alasmari, Graham J Lieschke, Kathryn E Crosier, Philip S Crosier, Jonathan W Astin
Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS)...
September 14, 2015: Biology Open
R Joseph Bender, Feilim Mac Gabhann
BACKGROUND: The vascular endothelial growth factor (VEGF) family is central to cancer angiogenesis. However, targeting VEGF as an anti-cancer therapeutic approach has shown success for some tumor types but not others. Here we examine the expression of the expanded VEGF family in prostate cancer, including the Semaphorin (Sema) family members that compete with VEGFs for Neuropilin binding and can themselves have pro- or anti-angiogenic activity. RESULTS: First, we used multivariate statistical methods, including partial least squares and clustering, to examine VEGF/Sema gene expression variability in previously published prostate cancer microarray datasets...
2015: BMC Systems Biology
Daniela Mauceri, Anna M Hagenston, Kathrin Schramm, Ursula Weiss, Hilmar Bading
Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression...
September 18, 2015: Journal of Biological Chemistry
Youzhi Xu, Wenjie Lu, Peng Yang, Wen Peng, Chunting Wang, Manli Li, Yan Li, Guobo Li, Nana Meng, Hongjun Lin, Lixin Kan, Siying Wang, Shengyong Yang, Luoting Yu, YingLan Zhao
BACKGROUND: The lymph node metastasis is a key early step of the tumor metastatic process. VEGFD-mediated tumor lymphangiogenesis plays a key role, since down-regulation of p-VEGFR-3 could block the lymph node metastasis. YL529 has been reported to possess potent anti-angiogenesis and antitumor activities; however, its roles in tumor-associated lymphangiogenesis and lymphatic metastasis remain unclear. METHOD: We investigated the effect of YL529 on tumor-associated lymphangiogenesis and lymph node metastasis using in vitro lymph node metastasis models and in vivo subcutaneous tumor models in C57 BL/6 mice...
2015: BMC Cancer
Syeda Kiran Riaz, Yasmeen Iqbal, Muhammad Faraz Arshad Malik
Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
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