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https://www.readbyqxmd.com/read/30515806/challenges-facing-antiangiogenesis-therapy-the-significant-role-of-hypoxia-inducible-factor-and-met-in-development-of-resistance-to-anti-vascular-endothelial-growth-factor-targeted-therapies
#1
REVIEW
Ali Mahdi, Behrad Darvishi, Keivan Majidzadeh-A, Malihe Salehi, Leila Farahmand
It is now fully recognized that along with multiple physiological functions, angiogenesis is also involved in the fundamental process and pathobiology of several disorders including cancer. Recent studies have fully established the role of angiogenesis in cancer progression as well as invasion and metastasis. Consequently, many therapeutic agents such as monoclonal antibodies targeting angiogenesis pathway have been introduced in clinic with the hope for improving the outcomes of cancer therapy. Bevacizumab (Avastin®) was the first anti-vascular endothelial growth factor (VEGF) targeting monoclonal antibody developed with this purpose and soon received its accelerated US Food and Drug Administration (FDA) approval for treatment of patients with metastatic breast cancer in 2008...
December 4, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30513821/human-recombinant-fab-fragment-neutralizes-shiga-toxin-type-2-cytotoxic-effects-in-vitro-and-in-vivo
#2
Daniela Luz, Maria Marta Amaral, Flavia Sacerdoti, Alan Mauro Bernal, Wagner Quintilio, Ana Maria Moro, Marina Sandra Palermo, Cristina Ibarra, Roxane Maria Fontes Piazza
Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causing hemolytic uremic syndrome (HUS), a life-threatening thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure after bacterially induced hemorrhagic diarrhea. Until now, there has been neither an effective treatment nor method of prevention for the deleterious effects caused by Stx intoxication. Antibodies are well recognized as affinity components of therapeutic drugs; thus, a previously obtained recombinant human FabC11:Stx2 fragment was used to neutralize Stx2 in vitro in a Vero cell viability assay...
December 2, 2018: Toxins
https://www.readbyqxmd.com/read/30513637/%C3%AE-melanocyte-stimulating-hormone-attenuates-neovascularization-by-inducing-nitric-oxide-deficiency-via-mc-rs-pka-nf-%C3%AE%C2%BAb-signaling
#3
Wen-Tsan Weng, Chieh-Shan Wu, Feng-Sheng Wang, Chang-Yi Wu, Yi-Ling Ma, Hoi-Hung Chan, Den-Chiung Wu, Jian-Ching Wu, Tian-Huei Chu, Shih-Chung Huang, Ming-Hong Tai
α-melanocyte-stimulating hormone (α-MSH) has been characterized as a novel angiogenesis inhibitor. The homeostasis of nitric oxide (NO) plays an important role in neovascularization. However, it remains unclear whether α-MSH mitigates angiogenesis through modulation of NO and its signaling pathway. The present study elucidated the function and mechanism of NO signaling in α-MSH-induced angiogenesis inhibition using cultured human umbilical vein endothelial cells (HUVECs), rat aorta rings, and transgenic zebrafish...
November 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30511851/pretargeting-and-bioorthogonal-click-chemistry-mediated-endogenous-stem-cell-homing-for-heart-repair
#4
Zhenhua Li, Deliang Shen, Shiqi Hu, Teng Su, Ke Huang, Feiran Liu, Lei Hou, Ke Cheng
Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h)...
December 4, 2018: ACS Nano
https://www.readbyqxmd.com/read/30510764/diffuse-pulmonary-lymphangiomatosis-treated-with-bevacizumab
#5
Ernest Onyeforo, Adrian Barnett, Debbie Zagami, David Deller, Iain Feather
Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease caused by uncontrolled lymphatic vessel proliferation resulting in respiratory dysfunction. Lymphatic vessel growth is influenced by vascular endothelial growth factor (VEGF). It has been shown that bevacizumab, a monoclonal antibody to VEGF type A, may be helpful in treating diseases characterized by excessive vessel proliferation. We report the case of a 51-year-old man with DPL treated with 1 mg/kg bevacizumab every three weeks for 6 months. A significant improvement in lung infiltrates was seen on post-treatment computed tomography (CT) chest with a 17...
January 2019: Respirology Case Reports
https://www.readbyqxmd.com/read/30508942/long-term-use-of-bevacizumab-in-the-treatment-of-triple-negative-breast-cancer-with-giant-tumor-in-chest-wall-a-case-report
#6
Xinyu Gui, Huiping Li, Guohong Song, Bin Shao, Hanfang Jiang
RATIONALE: Triple-negative breast cancer (TNBC) is associated with unfavorable prognosis due to lack of targeted agents. Bevacizumab, an anti-angiogenic monoclonal antibody against vascular endothelial growth factor A, has shown clinical effects in patients with TNBC. PATIENT CONCERNS: We reported a 49-year-old woman presenting with a giant breast tumor. DIAGNOSES: Stage IV TNBC with chest wall metastasis. INTERVENTIONS: The patient underwent long-term use of bevacizumab combined with chemotherapy...
November 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30508547/impact-of-secukinumab-on-endothelial-dysfunction-and-other-cardiovascular-disease-parameters-in-psoriasis-patients-over-52-weeks
#7
Esther von Stebut, Kristian Reich, Diamant Thaçi, Wolfgang Koenig, Andreas Pinter, Andreas Körber, Tienush Rassaf, Ari Waisman, Venkatesh Mani, Denise Yates, Jennifer Frueh, Christian Sieder, Nima Melzer, Nehal N Mehta, Tommaso Gori
Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomized to 300 mg or 150 mg secukinumab until week 52, or placebo until week 12 then 300 mg or 150 mg secukinumab until week 52...
November 30, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30505782/expression-of-vascular-endothelial-growth-factor-and-microvessel-density-in-psoriatic-skin-lesions
#8
Priya T Rajan, T N Suresh, T S Rajashekar
Background: Psoriasis is a common chronic and immune-mediated skin disorder having a significant impact on the patient's quality of life. An analysis of the role of angiogenic vascular endothelial growth factor (VEGF) expression and microvessel density in psoriatic skin lesions may help in better understanding of the disease pathogenesis. The aim of this study was to examine the expression of vascular endothelial growth factor (VEGF) and microvessel density using CD34 antibodies in psoriatic skin lesions by immunohistochemical examination using normal skin of healthy individuals as controls...
November 2018: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/30504621/angptl3-inhibitors-their-role-in-cardiovascular-disease-through-regulation-of-lipid-metabolism
#9
Eleni Geladari, Panagiota Tsamadia, Natalia G Vallianou
Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis...
November 30, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/30504334/complement-driven-anemia-more-than-just-paroxysmal-nocturnal-hemoglobinuria
#10
REVIEW
Samuel A Merrill, Robert A Brodsky
Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/30504039/functionalized-cd133-antibody-coated-stent-surface-simultaneously-promotes-epcs-adhesion-and-inhibits-smooth-muscle-cell-proliferation-a-novel-approach-to-prevent-in-stent-restenosis
#11
Magdalena Wawrzyńska, Maciej Duda, Edyta Wysokińska, Leon Strządała, Dariusz Biały, Agnieszka Ulatowska-Jarża, Wojciech Kałas, Sebastian Kraszewski, Robert Pasławski, Paweł Biernat, Urszula Pasławska, Aleksandra Zielonka, Halina Podbielska, Marta Kopaczyńska
We report a multistep strategy of biochemical surface modifications that resulted in the synthesis of new, effective and biocompatible intravascular implants coating with immobilized anti-CD133 antibodies, that proved to be the most effective in endothelial progenitor cells capture and reduced smooth muscle cells growth. Biomolecules were immobilized on differently functionalized surfaces. The distribution, nanostructural characteristics and intramolecular interactions of anti-CD133 molecules as well as their ability to bind EPCs was evaluated...
November 26, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/30499512/-polishing-of-bowman-s-membrane-with-diamond-burr-in-the-treatment-of-recurrent-corneal-erosion-syndrome
#12
V R Mamikonyan, S V Trufanov, L Yu Tekeeva, S A Malozhen, A M Subbot, A A Fyodorov
PURPOSE: To study the effectiveness of polishing Bowman's membrane with a diamond burr (DBPBM) in the treatment of recurrent corneal erosion syndrome (RCES). MATERIAL AND METHODS: The study included 22 patients (22 eyes) with RCES aged 20-56 years who underwent our original modification of DBPBM. All patients had keratotopography examined, endothelial cell density measured, and optical coherence tomography (OCT) of the cornea taken before and after the procedure...
2018: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/30498080/loss-of-human-icosl-results-in-combined-immunodeficiency
#13
Lucie Roussel, Marija Landekic, Makan Golizeh, Christina Gavino, Ming-Chao Zhong, Jun Chen, Denis Faubert, Alexis Blanchet-Cohen, Luc Dansereau, Marc-Antoine Parent, Sonia Marin, Julia Luo, Catherine Le, Brinley R Ford, Mélanie Langelier, Irah L King, Maziar Divangahi, William D Foulkes, André Veillette, Donald C Vinh
Primary immunodeficiencies represent naturally occurring experimental models to decipher human immunobiology. We report a patient with combined immunodeficiency, marked by recurrent respiratory tract and DNA-based viral infections, hypogammaglobulinemia, and panlymphopenia. He also developed moderate neutropenia but without prototypical pyogenic infections. Using whole-exome sequencing, we identified a homozygous mutation in the inducible T cell costimulator ligand gene ( ICOSLG ; c.657C>G; p.N219K). Whereas WT ICOSL is expressed at the cell surface, the ICOSLN219K mutation abrogates surface localization: mutant protein is retained in the endoplasmic reticulum/Golgi apparatus, which is predicted to result from deleterious conformational and biochemical changes...
November 29, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/30497977/ectopic-high-endothelial-venules-in-pancreatic-ductal-adenocarcinoma-a-unique-site-for-targeted-delivery
#14
Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K Eskandari, Nasim Annabi, Jonathan S Bromberg, Leonard D Shultz, Dale L Greiner, Reza Abdi
BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79. METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC)...
November 26, 2018: EBioMedicine
https://www.readbyqxmd.com/read/30497530/time-series-analysis-of-neoadjuvant-chemotherapy-and-bevacizumab-treated-breast-carcinomas-reveals-a-systemic-shift-in-genomic-aberrations
#15
Elen Kristine Höglander, Silje Nord, David C Wedge, Ole Christian Lingjærde, Laxmi Silwal-Pandit, Hedda vdL Gythfeldt, Hans Kristian Moen Vollan, Thomas Fleischer, Marit Krohn, Ellen Schlitchting, Elin Borgen, Øystein Garred, Marit M Holmen, Erik Wist, Bjørn Naume, Peter Van Loo, Anne-Lise Børresen-Dale, Olav Engebraaten, Vessela Kristensen
BACKGROUND: Chemotherapeutic agents such as anthracyclines and taxanes are commonly used in the neoadjuvant setting. Bevacizumab is an antibody which binds to vascular endothelial growth factor A (VEGFA) and inhibits its receptor interaction, thus obstructing the formation of new blood vessels. METHODS: A phase II randomized clinical trial of 123 patients with Her2-negative breast cancer was conducted, with patients treated with neoadjuvant chemotherapy (fluorouracil (5FU)/epirubicin/cyclophosphamide (FEC) and taxane), with or without bevacizumab...
November 29, 2018: Genome Medicine
https://www.readbyqxmd.com/read/30485637/effects-of-intravitreal-bevacizumab-in-gram-positive-and-gram-negative-models-of-ocular-inflammation
#16
J Daniel Lafreniere, J T Toguri, Rishi R Gupta, Arif Samad, Dan M O'Brien, John Dickinson, Alan Cruess, Melanie Em Kelly, M E Seamone
BACKGROUND: Exogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti-inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against Vascular Endothelial Growth Factor (VEGF), has anti-inflammatory properties in experimental models of Gram-positive and Gram-negative inflammation...
November 28, 2018: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/30485480/endothelin-1-triggers-human-peritoneal-mesothelial-cells-proliferation-via-erk1-2-ets-1-signaling-pathway-and-contributes-to-endothelial-cell-angiogenesis
#17
Nan Zhu, Lijie Gu, Jieshuang Jia, Xuan Wang, Ling Wang, Man Yang, Weijie Yuan
BACKGROUND: Dysfunction of the peritoneum as a dialysis organ may result from progressive membrane injury on peritoneal dialysis (PD). It has been increasingly recognized that the human peritoneal mesothelial cells (HPMCs) play a key role in peritoneal membrane early injury. Recently, it has been reported that bioincompatible PD fluid with high concentrations of glucose and glucose degradation products, low pH, high osmolality, and peritonitis stimulates HPMCs to release endothelin-1 (ET-1)...
November 28, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30485433/laminin-%C3%AE-2-enriched-extracellular-vesicles-of-oral-squamous-cell-carcinoma-cells-enhance-in-vitro-lymphangiogenesis-via-intergrin-%C3%AE-3-dependent-uptake-by-lymphatic-endothelial-cells
#18
Ssu-Han Wang, Gunn-Guang Liou, Szu-Heng Liu, Jeffrey S Chang, Jenn-Ren Hsiao, Yi-Chen Yen, Yu-Lin Chen, Wan-Ling Wu, Jang-Yang Chang, Ya-Wen Chen
Oral squamous cell carcinoma (OSCC) LN1-l cells previously showed greater capacities for lymphangiogenesis and lymph node metastasis compared to their parental OEC-M1 cells, in addition to an ability to enhance the migration and tube formation of lymphatic endothelial cells (LECs). Purified by a series of differential centrifugations and characterized using electron microscopy, dynamic light scattering, and western blot, LN1-1 cell-derived extracellular vesicles (LN1-1 EVs) were shown to promote LEC migration, tube formation, and uptake by LECs more effectively than did OEC-M1 cell-derived EVs (OEC-M1 EVs)...
November 28, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30484894/myd88-overexpression-deteriorates-ang-ii-induced-ed-via-upregulating-mpo-and-cox2-and-downregulating-enos-in-the-corpus-cavernosum-of-rats
#19
Haishan Zhang, Shujuan Zhang, Linpei Jia, Hai Li
INTRODUCTION: Erectile dysfunction (ED) is a common sexual problem for men and the exploration of its treatment is still in mire demand. We aim to investigate the role of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the pathogenesis of angiotensin II (Ang-II) induced ED. METHODS: Male Sprague-Dawlay rats were treated with Ang-II and intracavernous pressure (ICP) was measured to confirm the occurrence of ED...
November 28, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30483898/effects-of-vegfr1-hematopoietic-progenitor-cells-on-pre-metastatic-niche-formation-and-in-vivo-metastasis-of-breast-cancer-cells
#20
Du Meng, Min Meng, Anqi Luo, Xin Jing, Guanying Wang, Shangke Huang, Minna Luo, Shan Shao, Xinhan Zhao, Rui Liu
The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1)+ CD133+ hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung...
November 27, 2018: Journal of Cancer Research and Clinical Oncology
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