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Genetics vascular tumors

Y Korkmaz, H C Roggendorf, O G Siefer, J Seehawer, T Imhof, M Plomann, W Bloch, A Friebe, C U Huebbers
The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and β subunit. NO binds to heme of the β1 -subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required...
May 1, 2018: Journal of Dental Research
Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
Ran An, Rafael Schmid, Anne Klausing, Jan W Robering, Maximilian Weber, Tobias Bäuerle, Rainer Detsch, Aldo R Boccaccini, Raymund E Horch, Anja M Boos, Annika Weigand
Endothelial progenitor cells (EPCs) contribute to neovascularization in tumors. However, the relationship of EPCs and tumor-induced angiogenesis still remains to be clarified. The present study aimed at investigating the influence of 4 different tumor types on angiogenic properties of EPCs in an in vitro and in vivo rat model. It could be demonstrated that in vitro proliferation, migration, and angiogenic abilities and genetic modifications of EPCs are controlled in a tumor-type-dependent manner. The proangiogenic effect of mammary carcinoma, osteosarcoma, and rhabdomyosarcoma cells was more pronounced compared to colon carcinoma cells...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Zubair Baloch, Ozgur Mete, Sylvia L Asa
The application of immunohistochemistry to the diagnosis of thyroid lesions has increased as new biomarkers have emerged. In this review, we discuss the biomarkers that are critical for accurate diagnosis, prognosis, and management. Immunohistochemical markers are used to confirm that an unusual tumor in the thyroid is indeed of thyroid origin, either of follicular epithelial or C-cell differentiation; the various mimics include nonthyroidal lesions such as parathyroid tumors, paragangliomas, thymic neoplasms, and metastatic malignancies...
May 9, 2018: Endocrine Pathology
Ai Peng Tan, Patricia Svrckova, Frances Cowan, Wui Khean Chong, Kshitij Mankad
Intracranial hemorrhage (ICH) in neonates often results in devastating neurodevelopmental outcomes as the neonatal period is a critical window for brain development. The neurodevelopmental outcomes in neonates with ICH are determined by the maturity of the brain, the location and extent of the hemorrhage, the specific underlying etiology and the presence of other concomitant disorders. Neonatal ICH may result from various inherited and acquired disorders. We classify the etiologies of neonatal ICH into eight main categories: (1) Hemorrhagic stroke including large focal hematoma, (2) Prematurity-related hemorrhage, (3) Bleeding diathesis, (4) Genetic causes, (5) Infection, (6) Trauma-related hemorrhage, (7) Tumor-related hemorrhage and (8) Vascular malformations...
April 24, 2018: European Journal of Paediatric Neurology: EJPN
Benjamin Theek, Maike Baues, Felix Gremse, Robert Pola, Michal Pechar, Inka Negwer, Kaloian Koynov, Benjamin Weber, Matthias Barz, Willi Jahnen-Dechent, Gert Storm, Fabian Kiessling, Twan Lammers
Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of ~10-20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl) methacrylamide)...
May 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ibrahim Abdullah Al Balawi, Rashid Mir, F M Abu-Duhier
Aim: VEGF gene polymorphisms can induce either increase or inhibition of VEGF secretion, with altered promoter activity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breast carcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene with breast cancer risk in Saudi women. Methodology: Genotyping of the VEGF-gene variation (-2578A>C) was performed using the amplification refractory mutation system PCR. We investigated the association of VEGF gene variants with different clinicopathological features of breast cancer patients...
April 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Miguel Sáinz-Jaspeado, Lena Claesson-Welsh
Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological conditions such as inflammation, tissue repair and tumor growth. Conditions of dysfunctional lymphatics exist after surgical interventions or in certain genetic diseases. A key lymphangiogenic stimulator is vascular endothelial growth factor-C (VEGFC) acting on VEGF receptor-3 (VEGFR3) expressed on lymphendothelial cells...
April 19, 2018: Current Opinion in Immunology
Tomás Reinert, Angélica Nogueira-Rodrigues, Fabiola Procacci Kestelman, Patricia Ashton-Prolla, Márcia Silveira Graudenz, José Bines
This narrative literature review addresses the problem of an adnexal mass discovered during the course of breast cancer (BC) care, which may represent a benign condition, a metastatic process, or a primary ovarian cancer (OC), clinical scenarios associated with distinct physiopathology and prognosis. Furthermore, the coexistence of BC and OC in the same patient may be owing to a hereditary disorder, deserving specific management strategies and counseling. The initial detection and evaluation of an adnexal mass in a patient with BC requires a high index of suspicion, and the initial workup should include a thorough medical history and physical examination, measurement of tumor markers, complete blood count, and imaging tests...
March 12, 2018: Clinical Breast Cancer
Dae Hee Lee, Myeong Youl Lee, Youngsuk Seo, Hyo Jeong Hong, Hyun Joo An, Jong Soon Kang, Ho Min Kim
Limitation of current anti-Vascular Endothelial Growth Factor (VEGF) cancer therapy is transitory responses, inevitable relapses and its insufficient tumor-targeting. Thus, multifaceted approaches, including the development of bispecific antibodies and combination strategies targeting different pathways have been proposed as an alternative. Here, we developed a novel multi-paratopic VEGF decoy receptor, Cetuximab-VEGF-Grab and Trastuzumab-VEGF-Grab, by genetically fusing VEGF decoy receptor (VEGF-Grab) to a single chain Fv of anti-Epidermal Growth Factor Receptor (EGFR) antibody (Cetuximab and Trastuzumab)...
April 16, 2018: Biomaterials
Mitali Ray, Khatuna Gabunia, Christine N Vrakas, Allison B Herman, Farah Kako, Sheri E Kelemen, Laurel A Grisanti, Michael V Autieri
OBJECTIVE: To test the hypothesis that loss of IL (interleukin)-19 exacerbates atherosclerosis. APPROACH AND RESULTS: Il19 -/- mice were crossed into Ldlr -/- (low-density lipoprotein receptor knock out) mice. Double knockout (dKO) mice had increased plaque burden in aortic arch and root compared with Ldlr -/- controls after 14 weeks of high-fat diet (HFD). dKO mice injected with 10 ng/g per day rmIL-19 had significantly less plaque compared with controls. qRT-PCR and Western blot analysis revealed dKO mice had increased systemic and intraplaque polarization of T cells and macrophages to proinflammatory Th 1 and M1 phenotypes, and also significantly increased TNF (tumor necrosis factor)-α expression in spleen and aortic arch compared with Ldlr -/- controls...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Douglas W Brown, Arya J Bahrami, David A Canton, Anandaroop Mukhopadhyay, Jean S Campbell, Robert H Pierce, Richard J Connolly
Intratumoral electroporation of plasmid DNA encoding the proinflammatory cytokine interleukin 12 promotes innate and adaptive immune responses correlating with anti-tumor effects. Clinical electroporation conditions are fixed parameters optimized in preclinical tumors, which consist of cells implanted into skin. These conditions have little translatability to clinically relevant tumors, as implanted models cannot capture the heterogeneity encountered in genetically engineered mouse models or clinical tumors...
April 9, 2018: Bioelectrochemistry
Peace Mabeta
Genetic lesions in proto-oncogenes result in the perturbation of angiogenesis, the formation of neovessels from a pre-existing microvasculature. Similarly, the subversion of tumor suppressor genes promotes tumor vascularization. Excessive neovessel formation is associated with various neoplasms such as infantile hemangiomas (IH). Hemangiomas are the most common tumors in pediatric patients and at present have no definitive treatment. The pathogenesis of IH is not well understood; however, both vasculogenesis and angiogenesis are associated with hemangioma genesis...
April 13, 2018: International Journal of Molecular Sciences
Effat Alemzadeh, Ali Dehshahri, Keramatolah Izadpanah, Fatemeh Ahmadi
Nanoparticles have been gained much attention for biomedical applications. A promising type of nanocarriers is viral nanoparticles (VNPs) which are natural bio-nanomaterials derived from different type of viruses. Amongst VNPs, plant VNPs present several pros over general nanoparticles such as liposomes, dendrimers or quantum dots. Some of these advantages include: degradability, safety for human, known structures to atomic level, possibility of attaching ligand with vigorous control on structure, availability for genetic and chemical manipulations and very flexible methods to prepare them...
March 26, 2018: Colloids and Surfaces. B, Biointerfaces
D Gramatzki, P Roth, E J Rushing, J Weller, N Andratschke, S Hofer, D Korol, L Regli, A Pangalu, M Pless, J Oberle, R Bernays, H Moch, S Rohrmann, M Weller
Background: The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the US and Switzerland, but not the European Union, in 2009. Here we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010-2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log rank test and Cox proportional hazards models...
March 30, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Prakamya Gupta, Pinaki Dutta
Apoplectic pituitary adenomas cause significant morbidity and even mortality. The pituitary apoplexy denotes a pituitary adenoma presenting with hemorrhage and/or infarction, implementation in remedial effects of various of drugs in pituitary apoplexy is a promising pharmacogenomic field in the near future adenoma treatment. Indisputably, this is an important horizon for complicated pituitary adenomas. In a pituitary adenoma, the interplay between genetic, cytokine, and growth factors promotes the pathogenic transformation into an apoplectic formation...
2018: Frontiers in Endocrinology
Carlos A Orozco, Neus Martinez-Bosch, Pedro E Guerrero, Judith Vinaixa, Tomás Dalotto-Moreno, Mar Iglesias, Mireia Moreno, Magdolna Djurec, Françoise Poirier, Hans-Joachim Gabius, Martin E Fernandez-Zapico, Rosa F Hwang, Carmen Guerra, Gabriel A Rabinovich, Pilar Navarro
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Chiara Cremolini, Carlotta Antoniotti, Beatrice Borelli, Tetsuo Mashima, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Sara Lonardi, Toshiharu Yamaguchi, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz
BACKGROUND: The C-C motif chemokine ligand 5/C-C motif chemokine receptor 5 (CCL5/CCR5) pathway has been shown to induce endothelial progenitor cell migration, resulting in increased vascular endothelial growth factor A expression. We hypothesized that genetic polymorphisms in the CCL5/CCR5 pathway predict efficacy and toxicity in patients with metastatic colorectal cancer (mCRC) treated with regorafenib. PATIENTS AND METHODS: We analyzed genomic DNA extracted from 229 tumor samples from 2 different cohorts of patients who received regorafenib: an evaluation cohort of 79 Japanese patients and a validation cohort of 150 Italian patients...
February 27, 2018: Clinical Colorectal Cancer
Jeroen Bijnens, Ludwig Missiaen, Geert Bultynck, Jan B Parys
Kawasaki disease is a multi-systemic vasculitis that generally occurs in children and that can lead to coronary artery lesions. Recent studies showed that Kawasaki disease has an important genetic component. In this review, we discuss the single-nucleotide polymorphisms in the genes encoding proteins with a role in intracellular Ca2+ signaling: inositol 1,4,5-trisphosphate 3-kinase C, caspase-3, the store-operated Ca2+ -entry channel ORAI1, the type-3 inositol 1,4,5-trisphosphate receptor, the Na+ /Ca2+ exchanger 1, and phospholipase Cß4 and Cß1...
May 2018: Cell Calcium
Seung Won Choi, Hyemi Shin, Jason K Sa, Hee Jin Cho, Harim Koo, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam
Glioblastomas are among the most fatal brain tumors. Although no effective treatment option is available for recurrent glioblastomas (GBMs), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor. We retrospectively reviewed patients with recurrent GBM who received bevacizumab to identify biomarkers for predicting clinical response to bevacizumab. Following defined criteria, the patients were categorized into two clinical response groups, and their genetic and transcriptomic results were compared...
March 23, 2018: Cancer Medicine
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