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https://www.readbyqxmd.com/read/29454091/anlotinib-inhibits-angiogenesis-via-suppressing-the-activation-of-vegfr2-pdgfr%C3%AE-and-fgfr1
#1
Binyan Lin, Xiuming Song, Dawei Yang, Dongsheng Bai, Yuyuan Yao, Na Lu
Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29440590/pdgfr-%C3%AE-pdgfr-%C3%AE-vegfr-2-and-cd117-expression-in-canine-mammary-tumours-and-evaluation-of-the-in-vitro-effects-of-toceranib-phosphate-in-neoplastic-mammary-cell-lines
#2
Francesca Gattino, Lorella Maniscalco, Selina Iussich, Ilaria Biasato, Marina Martano, Emanuela Morello, Cecilia Gola, Yolanda Millán Ruiz, Nobuo Saeki, Paolo Buracco, Juana Martín de Las Mulas, Raffaella De Maria
Canine mammary tumours (CMTs) are one of the most common malignancies in bitches. Platelet-derived growth factor receptor (PDGFR) α and β, vascular endothelial growth factor receptor-2 (VEGFR-2) and CD117 are tyrosine kinase receptors involved in several tumours and represent suitable targets for specific therapy with toceranib phosphate. The purpose of this study was to evaluate the expression of these receptors in the pathogenesis and progression of CMTs. PDGFRα, PDGFRβ, VEGFR-2 and CD117 were expressed in 46/83 (55...
February 9, 2018: Veterinary Record
https://www.readbyqxmd.com/read/29427211/treatment-with-5-azacitidine-delay-growth-of-glioblastoma-xenografts-a-potential-new-treatment-approach-for-glioblastomas
#3
Tobias Kratzsch, Susanne Antje Kuhn, Andreas Joedicke, Uwe Karsten Hanisch, Peter Vajkoczy, Jens Hoffmann, Iduna Fichtner
PURPOSE: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas. METHODS: In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft...
February 9, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29423271/dual-roles-of-endothelial-fgf-2-fgfr1-pdgf-bb-and-perivascular-fgf-2-fgfr2-pdgfr%C3%AE-signaling-pathways-in-tumor-vascular-remodeling
#4
Kayoko Hosaka, Yunlong Yang, Masaki Nakamura, Patrik Andersson, Xiaojuan Yang, Yin Zhang, Takahiro Seki, Martin Scherzer, Olivier Dubey, Xinsheng Wang, Yihai Cao
Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRβ signaling for vascular recruitment. FGF-2 sensitizes the PDGFRβ signaling through increasing PDGFRβ levels in pericytes. To ensure activation of PDGFRβ, the FGF-2-FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFRβ, in angiogenic endothelial cells...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29415055/tissue-analyses-reveal-a-potential-immune-adjuvant-function-of-fap-1-positive-fibroblasts-in-non-small-cell-lung-cancer
#5
Thomas Karsten Kilvaer, Mehrdad Rakaee, Turid Hellevik, Arne Østman, Carina Strell, Roy M Bremnes, Lill-Tove Busund, Tom Dønnem, Inigo Martinez-Zubiaurre
OBJECTIVES: Selective targeting of cancer-associated fibroblasts (CAFs) has been proposed to synergize with immune-checkpoint inhibitors. While the roles of CAFs in cancer development are well described, their immune-regulatory properties remain incompletely understood. This study investigates correlations between CAF and immune-markers in tumor stroma from non-small cell lung cancer (NSCLC) patients, and examines whether a combination of CAF and immune cell scores impact patient prognosis...
2018: PloS One
https://www.readbyqxmd.com/read/29408302/the-role-of-small-molecule-platelet-derived-growth-factor-receptor-pdgfr-inhibitors-in-the-treatment-of-neoplastic-disorders
#6
REVIEW
Robert Roskoski
Platelet-derived growth factor (PDGF) was discovered as a serum-derived component necessary for the growth of smooth muscle cells, fibroblasts, and glial cells. The PDGF family is a product of four gene products and consists of five dimeric isoforms: PDGF-AA, PDGF-BB, PDGF-CC, PDGF-DD, and the PDGF-AB heterodimer. This growth factor family plays an essential role in embryonic development and in wound healing in the adult. These growth factors mediate their effects by binding to and activating their receptor protein-tyrosine kinases, which are encoded by two genes: PDGFRA and PDGFRB...
February 2, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29402204/glomeruloid-microvascular-proliferation-desmoplasia-and-high-proliferative-index-as-potential-indicators-of-high-grade-canine-choroid-plexus-tumors
#7
Luisa Vera Muscatello, Giancarlo Avallone, Fabienne Serra, Torsten Seuberlich, Maria Teresa Mandara, Silvia Sisó, Barbara Brunetti, Anna Oevermann
Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29397577/aging-affects-the-in%C3%A2-vivo-regenerative-potential-of-human-mesoangioblasts
#8
Alessio Rotini, Ester Martínez-Sarrà, Robin Duelen, Domiziana Costamagna, Ester Sara Di Filippo, Giorgia Giacomazzi, Hanne Grosemans, Stefania Fulle, Maurilio Sampaolesi
Sarcopenia is the age-related loss of muscle mass, strength, and function. Although the role of human satellite cells (SCs) as adult skeletal muscle stem cells has been deeply investigated, little is known about the impact of aging on muscle interstitial stem cells. Here, we isolated the non-SC CD56- fraction from human muscle biopsies of young and elderly subjects. The elderly interstitial cell population contained a higher number of CD15+ and PDGFRα+ cells when compared to young samples. In addition, we found that the CD56- /ALP+ cells were well represented as a multipotent stem cell population inside the CD56- fraction...
February 4, 2018: Aging Cell
https://www.readbyqxmd.com/read/29380207/the-pdgf-pathway-in-breast-cancer-is-linked-to-tumour-aggressiveness-triple-negative-subtype-and-early-recurrence
#9
Sara Jansson, Kristina Aaltonen, Pär-Ola Bendahl, Anna-Karin Falck, Maria Karlsson, Kristian Pietras, Lisa Rydén
PURPOSE: The platelet-derived growth factor (PDGF) signalling pathway is often dysregulated in cancer and PDGF-receptor expression has been linked to unfavourable prognostic factors in breast cancer (e.g. ER negativity, high Ki67 and high grade). This study aimed to evaluate the expression of PDGFRα, PDGFRβ and ligand PDGF-CC in breast cancer in relation to molecular subtypes and prognosis. METHODS: Protein expression of tumour and/or stromal cell PDGFRα, PDGFRβ and PDGF-CC was evaluated in primary tumours (N = 489), synchronous lymph node metastases (N = 135) and asynchronous recurrences (N = 39) using immunohistochemistry in a prospectively maintained cohort of primary breast cancer patients included during 1999-2003...
January 29, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29341790/postnatal-tendon-growth-and-remodeling-requires-platelet-derived-growth-factor-receptor-signaling
#10
Kristoffer B Sugg, James F Markworth, Nathaniel P Disser, Andrew M Rizzi, Jeffrey R Talarek, Dylan C Sarver, Susan V Brooks, Christopher L Mendias
Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response...
December 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29328399/mir%C3%A2-378a-enhances-the-sensitivity-of-liver-cancer-to-sorafenib-by-targeting-vegfr-pdgfr%C3%AE-and-c%C3%A2-raf
#11
Hongxia Fu, Jicai Zhang, Tongshan Pan, Shuying Ai, Li Tang, Fengqin Wang
Liver cancer is a globally prevalent cancer with poor prognosis. The present study investigated the link between microRNA-378a (miR‑378a) expression and the sensitivity of hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cancers to sorafenib therapy. miR‑378a expression was determined in liver tissue samples from healthy candidates and patients with liver cancer using the reverse transcription‑quantitative polymerase chain reaction. The antitumor effects of miR‑378a alone and in combination with sorafenib were investigated in the HB cell line HepG2 and the HCC cell line SMMC‑7721 with methyl thiazoyl tetrazolium, colony formation, flow cytometry and Transwell migration assays...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29313814/biomarker-integrated-neoadjuvant-dasatinib-trial-in-resectable-malignant-pleural-mesothelioma
#12
Anne S Tsao, Heather Lin, Brett W Carter, J Jack Lee, David Rice, Ara Vaporcyan, Steven Swisher, Reza Mehran, John Heymach, Monique Nilsson, Youhong Fan, Maria Nunez, Lixia Diao, Jing Wang, Junya Fujimoto, Ignacio I Wistuba, Waun Ki Hong
Window-of-opportunity trials in malignant pleural mesothelioma (MPM) are challenging but can yield important translational information about a novel agent. We treated MPM patients (n=24) with 4 weeks of oral dasatinib followed by surgery with or without radiotherapy and then an optional 2 years of maintenance dasatinib. The primary endpoint was biomarker modulation of p-SrcTyr419. For all patients, the median PFS was 7.5 months and OS 19.1 months. No significant responses were seen after 4 weeks of dasatinib therapy, however, modulation of p-SrcTyr419 immunohistochemistry (IHC) scores (median (interquartile range) = 70 (37...
December 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29303444/reductions-in-brain-pericytes-are-associated-with-arteriovenous-malformation-vascular-instability
#13
Ethan A Winkler, Harjus Birk, Jan-Karl Burkhardt, Xiaolin Chen, John K Yue, Diana Guo, W Caleb Rutledge, George F Lasker, Carlene Partow, Tarik Tihan, Edward F Chang, Hua Su, Helen Kim, Brian P Walcott, Michael T Lawton
OBJECTIVE Brain arteriovenous malformations (bAVMs) are rupture-prone tangles of blood vessels with direct shunting of blood flow between arterial and venous circulations. The molecular and/or cellular mechanisms contributing to bAVM pathogenesis and/or destabilization in sporadic lesions have remained elusive. Initial insights into AVM formation have been gained through models of genetic AVM syndromes. And while many studies have focused on endothelial cells, the contributions of other vascular cell types have yet to be systematically studied...
January 5, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29298329/molecular-and-functional-analysis-of-anchorage-independent-treatment-evasive-neuroblastoma-tumorspheres-with-enhanced-malignant-properties-a-possible-explanation-for-radio-therapy-resistance
#14
Tamara J Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D Sandler
Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures...
2018: PloS One
https://www.readbyqxmd.com/read/29284681/a-novel-aggf1-pdgfrb-fusion-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#15
LETTER
Matthew S Zabriskie, Orlando Antelope, Anupam R Verma, Lauren R Draper, Christopher A Eide, Anthony D Pomicter, Thai Hoa Tran, Brian J Druker, Jeffrey W Tyner, Rodney R Miles, James M Graham, Jae-Yeon Hwang, Katherine E Varley, Reha M Toydemir, Michael W Deininger, Elizabeth A Raetz, Thomas O'Hare
No abstract text is available yet for this article.
February 2018: Haematologica
https://www.readbyqxmd.com/read/29275861/natural-killer-cells-control-tumor-growth-by-sensing-a-growth-factor
#16
Alexander D Barrow, Melissa A Edeling, Vladimir Trifonov, Jingqin Luo, Piyush Goyal, Benjamin Bohl, Jennifer K Bando, Albert H Kim, John Walker, Mary Andahazy, Mattia Bugatti, Laura Melocchi, William Vermi, Daved H Fremont, Sarah Cox, Marina Cella, Christian Schmedt, Marco Colonna
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest...
December 20, 2017: Cell
https://www.readbyqxmd.com/read/29237806/afatinib-is-a-new-therapeutic-approach-in-chordoma-with-a-unique-ability-to-target-egfr-and-brachyury
#17
Paola Magnaghi, Barbara Salom, Liviana Cozzi, Nadia Amboldi, Dario Ballinari, Elena Tamborini, Fabio Gasparri, Alessia Montagnoli, Laura Raddrizzani, Alessio Somaschini, Roberta Bosotti, Christian Orrenius, Fabio Bozzi, Silvana Pilotti, Arturo Galvani, Josh Sommer, Silvia Stacchiotti, Antonella Isacchi
Chordomas are rare bone tumors with no approved therapy. These tumors express several activated tyrosine kinase receptors, which prompted attempts to treat patients with tyrosine kinase inhibitors. Although clinical benefit was observed in Phase II clinical trials with imatinib and sorafenib, and sporadically also with EGFR inhibitors, therapies evaluated to date have shown modest activity. With the goal of identifying new drugs with immediate therapeutic potential for chordoma patients, we collected clinically approved drugs and other advanced inhibitors of MET, PDGFRβ and EGFR tyrosine kinases, and assessed their anti-proliferative activity against a panel of chordoma cell lines...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29182023/pdgfr%C3%AE-specific-affibody-directed-delivery-of-a-photosensitizer-ir700-is-efficient-for-vascular-targeted-photodynamic-therapy-of-colorectal-cancer
#18
Qiuxiao Shi, Ze Tao, Hao Yang, Qing Fan, Danfeng Wei, Lin Wan, Xiaofeng Lu
Vascular-targeted photodynamic therapy (PDT) is an important strategy for cancer therapy. Conventional vascular-targeted PDT has been achieved by passive photosensitizer (PS) delivery, which involves a high risk of adverse effects. Active PS delivery is urgently required for vascular-targeted PDT. Although endothelial cells and pericytes are major cellular components of tumor blood vessels, little attention has been paid to pericyte-targeted PDT for cancer therapy. PDGFRβ is abundantly expressed in the pericytes of various tumors...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29180757/discovery-of-high-affinity-pdgf-vegfr-interactions-redefining-rtk-dynamics
#19
Spencer B Mamer, Si Chen, Jared C Weddell, Alexandra Palasz, Ashley Wittenkeller, Manu Kumar, P I Imoukhuede
Nearly all studies of angiogenesis have focused on uni-family ligand-receptor binding, e.g., VEGFs bind to VEGF receptors, PDGFs bind to PDGF receptors, etc. The discovery of VEGF-PDGFRs binding challenges this paradigm and calls for investigation of other ligand-receptor binding possibilities. We utilized surface plasmon resonance to identify and measure PDGF-to-VEGFR binding rates, establishing cut-offs for binding and non-binding interactions. We quantified the kinetics of the recent VEGF-A:PDGFRβ interaction for the first time with KD = 340 pM...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29166712/-effects-of-endostatin-pretreatment-on-fibrosis-of-human-skin-fibroblasts-and-the-mechanisms
#20
H T Ren, Y Li, S D Wang, C M Han
Objective: To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms. Methods: Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-β(1) (TGF-β(1)), and endostatin+ TGF-β(1) groups according to the random number table, with 3 wells in each group...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
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