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https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#1
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28327358/a-cell-autonomous-positive-signaling-circuit-associated-with-the-pdgf-no-id4-regulatory-axis-in-glioblastoma-cells
#2
Kiyoung Eun, Hye-Min Jeon, Sung-Ok Kim, Sang-Hun Choi, Seon Yong Lee, Xiong Jin, Sung-Chan Kim, Hyunggee Kim
Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28323122/exome-analysis-of-the-evolutionary-path-of-hepatocellular-adenoma-carcinoma-transition-vascular-invasion-and-brain-dissemination
#3
Sílvia Vilarinho, Zeynep Erson-Omay, Kisha Mitchell-Richards, Charles Cha, Carol Nelson-Williams, Akdes Serin Harmancı, Katsuhito Yasuno, Murat Günel, Tamar H Taddei
Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with acute abdominal pain and was found to have a 17 cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14 cm moderately differentiated hepatocellular carcinoma (HCC) arising in a shell of a HCA...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28320710/myeloid-p53-regulates-macrophage-polarization-and-venous-thrombus-resolution-by-inflammatory-vascular-remodeling-in-mice
#4
Subhradip Mukhopadhyay, Toni M Antalis, Khanh P Nguyen, Mark H Hoofnagle, Rajabrata Sarkar
Deep venous thrombosis (DVT) remains a common and serious cardiovascular problem with both fatal and long-term consequences. The consequences of DVT include the development of post-thrombotic syndrome (PTS) in 25-60% of DVT patients. Despite the clinical importance of venous thrombus resolution, the cellular and molecular mediators involved are poorly understood, and currently there is no molecular therapy to accelerate this process. Several lines of evidence suggest that a complex and interrelated array of molecular signaling processes are involved in the inflammatory vascular remodeling associated with the resolution of DVT...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28283837/vascular-hyperpermeability-as-a-hallmark-of-phacomatoses-is-the-etiology-angiogenesis-related-to-or-comparable-with-mechanisms-seen-in-inflammatory-pathways-part-ii-angiogenesis-and-inflammation-related-molecular-pathways-tumor-associated-macrophages-and-possible
#5
REVIEW
Yosef Laviv, Burkhard Kasper, Ekkehard M Kasper
Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles...
March 11, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28281318/intracranial-myxoid-mesenchymal-tumors-with-ewsr1-creb-family-gene-fusions-myxoid-variant-of-angiomatoid-fibrous-histiocytoma-or-novel-entity
#6
Tejus A Bale, Angelica Oviedo, Harry Kozakewich, Caterina Giannini, Phani K Davineni, Keith Ligon, Sanda Alexandrescu
BACKGROUND: Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present 3 pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. METHODS: Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) were performed...
March 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28265819/vascular-hyperpermeability-as-a-hallmark-of-phacomatoses-is-the-etiology-angiogenesis-comparable-with-mechanisms-seen-in-inflammatory-pathways-part-i-historical-observations-and-clinical-perspectives-on-the-etiology-of-increased-csf-protein-levels-csf-clotting
#7
REVIEW
Yosef Laviv, Burkhard S Kasper, Ekkehard M Kasper
Phacomatoses are a special group of familial hamartomatous syndromes with unique neuro-cutaneous manifestations as well as disease characteristic tumors. Neurofibromatosis 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. Vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with NF2 and TSC, respectively. These tumors can present with obstructive hydrocephalus due to their location adjacent to or in the ventricles...
March 7, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28248815/recurrent-srf-rela-fusions-define-a-novel-subset-of-cellular-myofibroma-myopericytoma-a-potential-diagnostic-pitfall-with-sarcomas-with-myogenic-differentiation
#8
Cristina R Antonescu, Yun-Shao Sung, Lei Zhang, Narasimhan P Agaram, Christopher D Fletcher
Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery...
February 28, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28238683/endothelial-notch1-activity-facilitates-metastasis
#9
Elfriede Wieland, Juan Rodriguez-Vita, Sven S Liebler, Carolin Mogler, Iris Moll, Stefanie E Herberich, Elisa Espinet, Esther Herpel, Amitai Menuchin, Jenny Chang-Claude, Michael Hoffmeister, Christoffer Gebhardt, Hermann Brenner, Andreas Trumpp, Christian W Siebel, Markus Hecker, Jochen Utikal, David Sprinzak, Andreas Fischer
Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis...
February 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#10
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28166200/upregulation-of-marcks-in-kidney-cancer-and-its-potential-as-a-therapeutic-target
#11
C-H Chen, L W R Fong, E Yu, R Wu, J F Trott, R H Weiss
Targeted therapeutics, such as those abrogating hypoxia inducible factor (HIF)/vascular endothelial growth factor signaling, are initially effective against kidney cancer (or renal cell carcinoma, RCC); however, drug resistance frequently occurs via subsequent activation of alternative pathways. Through genome-scale integrated analysis of the HIF-α network, we identified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) as a potential target molecule for kidney cancer...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28160948/the-radiologist-s-role-in-the-management-of-papillary-renal-cell-carcinoma
#12
M Á Corral de la Calle, J Encinas de la Iglesia, M R Martín López, G C Fernández Pérez, D S Águeda Del Bas
Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization...
February 1, 2017: Radiología
https://www.readbyqxmd.com/read/28144881/association-of-caa-and-tatc-insertion-deletion-genetic-polymorphisms-in-rtn4-3-utr-with-hepatocellular-carcinoma-risk
#13
NaNa Wang, KeYu Chen, Jia Xu, Fang Yuan, HongYu Li, FengMei Deng, LuShun Zhang
Evidence from recent researchers suggested that RTN4 is a multifunctional gene, including tumor suppression, apoptosis, vascular remodeling, and inhibition of axonal regeneration. The CAA and TATC insertion/deletion polymorphisms (CAA/TATC polymorphisms) of RTN4 3″-untranslated regions (UTRs) have been linked to cervical squamous cell carcinoma (CSCC), uterine leiomyomas (UL) and non-small cell lung cancer (NSCLC). However, the association between these two polymorphisms sites with Hepatocellular Carcinoma (HCC) risk was not carry out before...
January 31, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28143503/genetic-polymorphisms-in-key-hypoxia-regulated-downstream-molecules-and-phenotypic-correlation-in-prostate-cancer
#14
MULTICENTER STUDY
Avelino Fraga, Ricardo Ribeiro, André Coelho, José Ramon Vizcaíno, Helena Coutinho, José Manuel Lopes, Paulo Príncipe, Carlos Lobato, Carlos Lopes, Rui Medeiros
BACKGROUND: In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. METHODS: Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray...
January 31, 2017: BMC Urology
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#15
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28102487/assessment-of-vascularity-in-glioblastoma-and-its-implications-on-patient-outcomes
#16
Ben G McGahan, Beth K Neilsen, David L Kelly, Rodney D McComb, S A Jaffar Kazmi, Matt L White, Yan Zhang, Michele R Aizenberg
There is little data on why glioblastomas (GBM) hemorrhage and how it may affect patient outcomes. The aim of this study was to investigate the mechanisms of hemorrhage in glioblastoma by examining molecular and genetic features by immunohistochemistry (IHC) and mRNA expression profiles in association with imaging and clinical outcomes. An observational retrospective cohort analysis was performed on 43 FFPE GBM tissue samples. MR images were assessed for the presence of hemorrhage and extent of resection. Specimens were examined for CD34 and CD105 expression using IHC...
January 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28045923/germline-genetic-variants-in-tek-angpt1-angpt2-mmp9-fgf2-and-vegfa-are-associated-with-pathologic-complete-response-to-bevacizumab-in-breast-cancer-patients
#17
Issam Makhoul, Valentina K Todorova, Eric R Siegel, Stephen W Erickson, Ishwori Dhakal, Vinay R Raj, Jeannette Y Lee, Mohammed S Orloff, Robert J Griffin, Ronda S Henry-Tillman, Suzanne Klimberg, Laura F Hutchins, Susan A Kadlubar
BACKGROUND: We previously reported improved pathologic complete response (pCR) in a prospective phase II study using neoadjuvant bevacizumab in combination with chemotherapy compared to chemotherapy alone in breast cancer patients (41% vs. 25%, p = 0.0291). In this study, we queried germline single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes for their impact on pCR and overall survival (OS). METHODS: DNA for genotyping was available from 34 subjects who received bevacizumab in addition to chemotherapy and 29 subjects who did not...
2017: PloS One
https://www.readbyqxmd.com/read/28028026/diagnosis-risk-stratification-and-response-evaluation-in-classical-myeloproliferative-neoplasms
#18
REVIEW
Elisa Rumi, Mario Cazzola
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation...
February 9, 2017: Blood
https://www.readbyqxmd.com/read/28013320/angiogenesis-and-pro-angiogenic-factors-in-uterine-fibroids-facts-and-myths
#19
Monika Konarska, Anna Natalia Wrona, Veronika Aleksandrovych, Tomasz Bereza, Marek Sajewicz, Barbara Gach-Kuniewicz, Maciej Lis, Kinga Komnata, Mateusz Paziewski, Aleksandra Maleszka, Paweł Depukat, Bernard Solewski, Łukasz Warchoł
Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion...
2016: Folia Medica Cracoviensia
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#20
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
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