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https://www.readbyqxmd.com/read/28742793/intracrine-vegf-signalling-mediates-colorectal-cancer-cell-migration-and-invasion
#1
Rajat Bhattacharya, Fan Fan, Rui Wang, Xiangcang Ye, Ling Xia, Delphine Boulbes, Lee M Ellis
BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are key regulators of angiogenesis, affecting endothelial cell survival and function. However, the effect of VEGF-VEGFR signalling on tumour cell function is not well understood. Our previous studies in colorectal cancer (CRC) cells have demonstrated an intracrine VEGF/VEGFR1 signalling mechanism that mediates CRC cell survival and chemo-sensitivity. Since extracellular VEGF signalling regulates migration of endothelial cells and various tumour cells, we attempted to determine whether intracrine VEGF signalling affects CRC cell motility...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28736629/biologic-therapy-in-esophageal-and-gastric-malignancies-current-therapies-and-future-directions
#2
REVIEW
Pamela Samson, A Craig Lockhart
Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736316/early-actions-of-anti-vascular-endothelial-growth-factor-vascular-endothelial-growth-factor-receptor-drugs-on-angiogenic-blood-vessels
#3
Basel Sitohy, Sunghee Chang, Tracey E Sciuto, Elizabeth Masse, Mei Shen, Peter M Kang, Shou-Ching Jaminet, Laura E Benjamin, Rupal S Bhatt, Ann M Dvorak, Janice A Nagy, Harold F Dvorak
Tumors induce their heterogeneous vasculature by secreting vascular endothelial growth factor (VEGF)-A. Anti-VEGF/VEGF receptor (VEGFR) drugs may treat cancer but the underlying mechanisms remain unclear. An adenovirus expressing VEGF-A (Ad-VEGF-A(164)) replicates the tumor vasculature in mice without tumor cells. Mother vessels (MV) are the first angiogenic vessel type to form in tumors and following Ad-VEGF-A(164). Multiday treatments with a VEGF trap reverted MV back to normal microvessels. We now show that, within hours, a single dose of several anti-VEGF drugs collapsed MV to form glomeruloid microvascular proliferations (GMP), accompanied by only modest endothelial cell death...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28730107/induction-of-vascular-endothelial-growth-factor-receptor-expression-in-human-umbilical-vein-endothelial-cells-after-repeated-bevacizumab-treatment-in-vitro
#4
Ji Eun Lee, Jin Young Kim, Jae Ho Jung, Dong Hoon Shin, Sung Who Park
AIM: To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor (VEGF) treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor (VEGFR) expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations (1...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28730071/effect-of-sorafenib-in-a-murine-high-risk-penetrating-keratoplasty-model
#5
Yang Kyung Cho, Eun Young Shin, Hironori Uehara, Balamurali K Ambati
AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#6
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28725539/the-evolving-treatment-landscape-of-advanced-renal-cell-carcinoma-in-patients-progressing-after-vegf-inhibition
#7
REVIEW
Pedro C Barata, Moshe C Ornstein, Jorge A Garcia
Despite significant changes in the therapeutic landscape of renal cell carcinoma, the majority of patients with metastatic disease eventually progress after first-line treatment with vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Understanding existing data on subsequent therapies is crucial to define an optimal treatment sequence following first-line failure. This review examines the data supporting currently approved agents in this setting and provides a framework for decision-making regarding treatment sequencing beyond first-line therapy with VEGFR TKIs...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28720001/differential-effects-of-heat-stress-on-fibre-capillarisation-in-tenotomised-soleus-and-plantaris-muscles
#8
Muthita Hirunsai, Ratchakrit Srikuea
PURPOSE: Capillary regression is commonly observed in response to disuse muscle atrophy. Heat stress is known to alleviate muscle atrophy, while effect of heat exposure on capillary adaptation following disuse atrophy is not defined. Here, we examined the effect of heat treatment on capillarisation and the associated signalling in slow-oxidative soleus and fast-glycolytic plantaris muscles following Achilles tendon ablation (tenotomy). MATERIALS AND METHODS: Male Wistar rats were assigned into control (CON), control with heat stress (CON + HEAT), tenotomy (TEN) and tenotomy with heat stress (TEN + HEAT) groups...
July 18, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28717175/snake-venom-vegf-vammin-induces-a-highly-efficient-angiogenic-response-in-skeletal-muscle-via-vegfr-2-nrp-specific-signaling
#9
Pyry I Toivanen, Tiina Nieminen, Johanna P Laakkonen, Tommi Heikura, Minna U Kaikkonen, Seppo Ylä-Herttuala
Vascular Endothelial Growth Factors (VEGFs) are promising molecules for the treatment of ischemic diseases by pro-angiogenic therapy. Snake venom VEGFs are a novel subgroup with unique receptor binding profiles and as such are potential new therapeutic agents. We determined the ligand-receptor interactions, gene regulation and angiogenic properties of Vipera ammodytes venom VEGF, Vammin, and compared it to the canonical angiogenic factor VEGF-A to evaluate the use of Vammin for therapeutic angiogenesis. Vammin efficiently induced VEGFR-2 mediated proliferation and expression of genes associated with proliferation, migration and angiogenesis...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713958/lipo%C3%A2-prostaglandin-e1-modifies-cognitive-impairment-in-rats-with-vascular-cognitive-impairment-by-promoting-angiogenesis-via-the-vegf-vegfr-pathway
#10
Bohui Liu, Suping Zhang, Xifeng Xiong, Li Ling, Rui He, Muzhen Wang, Wanqing Deng, Zhihe Liu, Yi Li
The pathological mechanism of vascular cognitive impairment (VCI) involves ischemic lesions in the hippocampus. Prostaglandin E1 (PGE1) serves roles in the promotion of vascular endothelial growth factor (VEGF) expression, angiogenesis and enhances blood flow to ischemic regions. However, the effect of PGE1 on cognitive function in VCI rats and the underlying mechanism are unknown. In the current study, learning and memory function in VCI rats treated by lipo‑PGE1 injection was assessed through Morris Water Maze test...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28707601/potential-role-of-natural-compounds-as-anti-angiogenic-agents-in-cancer
#11
Muthu K Shanmugam, Sudha Warrier, Alan Prem Kumar, Gautam Sethi, Frank Arfuso
BACKGROUND: Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis...
July 12, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28700345/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#12
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687807/efficient-activation-of-the-lymphangiogenic-growth-factor-vegf-c-requires-the-c-terminal-domain-of-vegf-c-and-the-n-terminal-domain-of-ccbe1
#13
Sawan Kumar Jha, Khushbu Rauniyar, Terhi Karpanen, Veli-Matti Leppänen, Pascal Brouillard, Miikka Vikkula, Kari Alitalo, Michael Jeltsch
The collagen- and calcium-binding EGF domains 1 (CCBE1) protein is necessary for lymphangiogenesis. Its C-terminal collagen-like domain was shown to be required for the activation of the major lymphangiogenic growth factor VEGF-C (Vascular Endothelial Growth Factor-C) along with the ADAMTS3 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-3) protease. However, it remained unclear how the N-terminal domain of CCBE1 contributed to lymphangiogenic signaling. Here, we show that efficient activation of VEGF-C requires its C-terminal domain both in vitro and in a transgenic mouse model...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28686443/identification-of-peptidic-antagonists-of-vascular-endothelial-growth-factor-receptor-1-by-scanning-the-binding-epitopes-of-its-ligands
#14
Lei Wang, Lingyu Zhou, Marie Reille-Seroussi, Nathalie Gagey-Eilstein, Sylvain Broussy, Tianyu Zhang, Lili Ji, Michel Vidal, Wang-Qing Liu
Cancer angiogenesis is mainly initiated by the vascular endothelial growth factors (VEGFs). Based on the reported crystal structures of three natural ligands (VEGF-A, -B and PlGF) with the major receptors VEGFR-1 and VEGFR-2, we scanned receptor-binding epitopes of these ligands by designing linear and cyclic peptides in aim to disrupt the VEGF-A/VEGFR-1 interaction, which is implicated in cancer development. The ability of peptides to inhibit this interaction was evaluated by an ELISA-based assay. Several peptides, especially those mimicking loop one (L1) of these ligands that binds primarily to domain D3 of VEGFRs, have demonstrated higher inhibition for VEGF-A/VEGFR-1 binding...
July 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28680747/arginase-inhibition-suppresses-lung-metastasis-in-the-4t1-breast-cancer-model-independently-of-the-immunomodulatory-and-anti-metastatic-effects-of-vegfr-2-blockade
#15
Chiara Secondini, Oriana Coquoz, Lorenzo Spagnuolo, Thibaud Spinetti, Sanam Peyvandi, Laura Ciarloni, Francesca Botta, Carole Bourquin, Curzio Rüegg
Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to anti-angiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679123/advanced-alveolar-soft-part-sarcoma-responds-to-apatinib
#16
Yong Zhou, Fan Tang, Yiying Wang, Li Min, Yi Luo, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu
Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678054/exercise-training-prevents-dexamethasone-induced-rarefaction
#17
Naiara A Herrera, Isley Jesus, Evandro J Dionísio, Thiago J Dionísio, Carlos F Santos, Sandra L Amaral
Dexamethasone (DEX) causes rarefaction. In contrast, training (T) prevents rarefaction and stimulates angiogenesis. This study investigated the mechanisms responsible for the preventive role of T in DEX-induced rarefaction. Rats underwent T or were kept sedentary (8 weeks) and were treated with DEX or saline during the following 14 days. Tibialis anterior (TA) muscle was used for measurements of capillary density (CD), capillary-to-fiber ratio (C:F ratio), superoxide dismutase CuZn (SOD-1), superoxide dismutase MnSOD (SOD-2), catalase (CAT) mRNA as well as SOD-1, SOD-2, CAT, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGF-R2), cyclooxygenase-2 (COX-2), B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), p-Bax and caspase-3 cleaved protein levels...
May 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28677792/peroxisome-proliferator%C3%A2-activated-receptor-%C3%AE-mediates-porcine-placental-angiogenesis-through-hypoxia-inducible-factor%C3%A2-vascular-endothelial-growth-factor%C3%A2-and-angiopoietin%C3%A2-mediated-signaling
#18
Juzuo Zhang, Xuan Peng, Anwen Yuan, Yang Xie, Qing Yang, Liqun Xue
Peroxisome proliferator-activated receptor (PPAR) γ has been reported to be implicated in placentation in mice. Previous studies have demonstrated that PPARγ is also expressed in porcine placenta, primarily localized in vascular endothelial cells (VECs). The present study aimed to investigate the roles of PPARγ during porcine placental angiogenesis and examine the molecular mechanisms involved in its actions. VECs were incubated with the PPARγ agonist rosiglitazone and the antagonist T0070907, and their angiogenic potential was evaluated using cellular impedance, wound healing and tube formation assays...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28670361/the-effect-of-high-sox3-expression-on-lymphangiogenesis-and-lymph-node-metastasis-in-esophageal-squamous-cell-carcinoma
#19
Yi-Feng Zheng, Kun Li, Qing-Yong Cai, Lie Yang, Qun-You Tan, Wei Guo, Ru-Wen Wang
OBJECTIVE: This study aimed to investigate the effect of Sox3 expression on biological behaviors of esophageal squamous cell carcinoma (ESCC) and explore its possible mechanism. METHODS: ESCC cell lines that highly expressed Sox3 were selected and transfected with lentivirus carrying sox3 siRNA to establish ESCC cell lines which expressed Sox3 of different levels. Using in vitro experiments including cell invasion, cell scratch, cell proliferation and tube formation of lymphatic endothelial cells, as well as an in vivo experiment of axillary lymph node metastasis in a nude mouse model of a xenotransplanted tumor, the effect of Sox3 expression variation on lymphangiogenesis and lymph node metastasis in ESCC cells was investigated...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28669039/blockade-of-mmp-2-and-mmp-9-inhibits-corneal-lymphangiogenesis
#20
Hai-Tao Du, Ling-Ling Du, Xian-Ling Tang, Hong-Yan Ge, Ping Liu
PURPOSE: To investigate the roles of a selective MMP-2 and -9 inhibitor (SB-3CT) in corneal inflammatory lymphangiogenesis. METHODS: The expression of MMP-2 and -9 in the cornea after suture inplacement, treated with SB-3CT or negative control, was detected by real-time polymerase chain reaction (PCR). Inflammatory corneal neovascularization (NV) was induced by corneal suture placement. Mice were treated with SB-3CT eye drops (twice daily for 1 week, 5 μL per drop; 50, 100, or 200 μM)...
July 1, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
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