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Genetics vascular tumors

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https://www.readbyqxmd.com/read/28102487/assessment-of-vascularity-in-glioblastoma-and-its-implications-on-patient-outcomes
#1
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
#2
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
#3
Elisa Rumi, Mario Cazzola
Philadelphia-negative classical myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic 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. Polycythemia vera is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28013320/angiogenesis-and-pro-angiogenic-factors-in-uterine-fibroids-facts-and-myths
#4
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
#5
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
https://www.readbyqxmd.com/read/28009608/fosb-is-a-useful-diagnostic-marker-for-pseudomyogenic-hemangioendothelioma
#6
Yin P Hung, Christopher D M Fletcher, Jason L Hornick
Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a distinctive vascular neoplasm of intermediate biological potential with a predilection for young adults and frequent multifocal presentation. Pseudomyogenic hemangioendothelioma is characterized by loose fascicles of plump spindled and epithelioid cells with abundant eosinophilic cytoplasm and coexpression of keratins and endothelial markers. Recently, a SERPINE1-FOSB fusion has been identified as a consistent genetic alteration in pseudomyogenic hemangioendothelioma...
December 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28002537/cerebral-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-in-acromegalic-patient-with-severe-headache
#7
LuminiŢa Nicoleta Cima, Simona Vasilica Fica, Alice Ioana Albu, Ioana Maria Lambrescu, Ioana SmărăndiŢa Lăcău, Bogdan Ovidiu Popescu, Mihaela Gherghiceanu, Corin Virgil Badiu, Carmen Gabriela Barbu
A 68-year-old female patient was admitted in our clinic with severe frontal bilateral headache, dizziness, depression and cognitive decline in the context of a previously diagnosed acromegaly. She also had high blood pressure, dyslipidemia, secondary diabetes mellitus. Acromegaly was caused by a growth hormone (GH) secreting-pituitary macroadenoma, so a transsphenoidal surgery was performed. The postoperative magnetic resonance imaging (MRI) scan revealed a 20÷22÷25 mm pituitary mass remnant and medical therapy with somatostatin analogues (SSAs) was started...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27992456/prostaglandin-d2-attenuates-bleomycin-induced-lung-inflammation-and-pulmonary-fibrosis
#8
Taiki Kida, Shinya Ayabe, Keisuke Omori, Tatsuro Nakamura, Toko Maehara, Kosuke Aritake, Yoshihiro Urade, Takahisa Murata
Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection...
2016: PloS One
https://www.readbyqxmd.com/read/27981753/association-between-genetic-polymorphisms-involved-in-the-hypoxia-inducible-factor-pathway-and-lung-cancer-risk-a-case-control-study-in-japan
#9
Yuzo Yamamoto, Chikako Kiyohara, Saiko Ogata-Suetsugu, Naoki Hamada, Yoichi Nakanishi
AIM: Hypoxia-inducible factor (HIF) contributes to the adaptation of tumor cells to hypoxic conditions, so genetic polymorphisms involved in this pathway may affect cellular response to hypoxia and be associated with cancer risk. Thus, we examined the association between the lung cancer risk and genetic polymorphisms involved in the HIF pathway. METHODS: This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of HIF1A rs11549467, HIF1A rs11549465, HIF1A rs2057482, HIF2A rs13419896 and vascular endothelial growth factor A (VEGFA) rs833061 on the risk of lung cancer using TaqMan real-time PCR assay...
December 16, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27943279/biology-and-therapeutic-implications-of-vegf-a-splice-isoforms-and-single-nucleotide-polymorphisms-in-colorectal-cancer
#10
REVIEW
Miriam Canavese, Doan T M Ngo, Guy J Maddern, Jennifer E Hardingham, Timothy J Price, Ehud Hauben
Tumor growth, dissemination and metastasis are dependent on angiogenesis. The predominant Vascular Endothelial Growth Factor (VEGF) isoform that plays a major role in angiogenesis is VEGF-A. Indeed, VEGF-A is implicated in promoting angiogenesis of numerous solid malignancies, including colorectal cancer (CRC). A large body of preclinical and clinical evidence indicates that the expression of specific VEGF-A isoforms represents a predominant pro-angiogenic factor, which is associated with formation of metastases and poor prognosis in CRC patients...
December 10, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27940520/exploring-the-benefit-risk-associated-with-antiangiogenic-agents-for-the-treatment-of-non-small-cell-lung-cancer-patients
#11
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting vascular endothelial growth factor-A (VEGF-A), for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-½/3, platelet-derived growth factor receptor (PDGFR)-α/β, fibroblast growth factor receptor (FGFR)-½/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union...
December 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27927704/nogo-a-regulates-vascular-network-architecture-in-the-postnatal-brain
#12
Thomas Wälchli, Alexandra Ulmann-Schuler, Christoph Hintermüller, Eric Meyer, Marco Stampanoni, Peter Carmeliet, Maximilian Y Emmert, Oliver Bozinov, Luca Regli, Martin E Schwab, Johannes Vogel, Simon P Hoerstrup
Recently, we discovered a new role for the well-known axonal growth inhibitory molecule Nogo-A as a negative regulator of angiogenesis in the developing central nervous system. However, how Nogo-A affected the three-dimensional (3D) central nervous system (CNS) vascular network architecture remained unknown. Here, using vascular corrosion casting, hierarchical, synchrotron radiation μCT-based network imaging and computer-aided network analysis, we found that genetic ablation of Nogo-A significantly increased the three-dimensional vascular volume fraction in the postnatal day 10 (P10) mouse brain...
November 10, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27909701/immunological-quality-and-performance-of-tumor-vessel-targeting-car-t-cells-prepared-by-mrna-ep-for-clinical-research
#13
Kanako Inoo, Ryo Inagaki, Kento Fujiwara, Shigemi Sasawatari, Takashi Kamigaki, Shinsaku Nakagawa, Naoki Okada
We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6-12 hours after mRNA-EP...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27897011/a-spatiotemporal-model-to-simulate-chemotherapy-regimens-for-heterogeneous-bladder-cancer-metastases-to-the-lung
#14
Kimberly R Kanigel Winner, James C Costello
Tumors are composed of heterogeneous populations of cells. Somatic genetic aberrations are one form of heterogeneity that allows clonal cells to adapt to chemotherapeutic stress, thus providing a path for resistance to arise. In silico modeling of tumors provides a platform for rapid, quantitative experiments to inexpensively study how compositional heterogeneity contributes to drug resistance. Accordingly, we have built a spatiotemporal model of a lung metastasis originating from a primary bladder tumor, incorporating in vivo drug concentrations of first-line chemotherapy, resistance data from bladder cancer cell lines, vascular density of lung metastases, and gains in resistance in cells that survive chemotherapy...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27881867/endothelial-cell-colony-forming-units-derived-from-malignant-breast-diseases-are-resistant-to-tumor-necrosis-factor-%C3%AE-induced-apoptosis
#15
Chen-Pin Chou, Shih Sheng Jiang, Huay-Ben Pan, Yi-Chen Yen, Hui-Hwa Tseng, Yu-Ting Hung, Ssu-Han Wang, Yu-Lin Chen, Ya-Wen Chen
Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874206/spitz-nevi-and-other-spitzoid-neoplasms-in-children-overview-of-incidence-data-and-diagnostic-criteria
#16
REVIEW
Emi Dika, Giulia Maria Ravaioli, Pier Alessandro Fanti, Iria Neri, Annalisa Patrizi
Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors...
November 22, 2016: Pediatric Dermatology
https://www.readbyqxmd.com/read/27871494/current-surgical-management-of-carotid-body-tumors
#17
Victor J Davila, James M Chang, William M Stone, Richard J Fowl, Thomas C Bower, Michael L Hinni, Samuel R Money
BACKGROUND: Carotid body tumors (CBTs) are rare. Management guidelines may include genetic testing for succinate dehydrogenase (SDH) mutations. We performed an institutional review of the surgical management of CBT. METHODS: A retrospective analysis (1994-2015) of CBT excisions at our institution was performed. Data obtained included demographics, genetic testing (if performed), intraoperative details, postoperative morbidity, and long-term outcomes. Data from the first CBT excision were included in patients with bilateral tumors...
December 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27867584/birt-hogg-dube-syndrome-accompanied-by-pulmonary-arteriovenous-malformation
#18
Noriyuki Matsutani, Hitoshi Dejima, Yusuke Takahashi, Hirofumi Uehara, Hisae Iinuma, Fumihiko Tanaka, Masafumi Kawamura
A 25-year-old male with Birt-Hogg-Dube (BHD) syndrome who developed hemothorax caused by ruptured of pulmonary arteriovenous malformation was reported. The patient was admitted to the hospital due to chest pain. A chest X-ray showed pleural fluid in his left lung, and a chest CT showed the presence of a tumor with enhanced contrast in the lower left lobe of approximately 5 cm in a diameter. Pleural fluid was collected by tap and indicated the presence of blood; therefore, hemothorax was suspected. Thoracoscopic surgery was performed to remove the mass for homostasis...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27863376/cxcr4-increases-in-vivo-glioma-perivascular-invasion-and-reduces-radiation-induced-apoptosis-a-genetic-knockdown-study
#19
Viveka Nand Yadav, Daniel Zamler, Gregory J Baker, Padma Kadiyala, Anat Erdreich-Epstein, Ana C DeCarvalho, Tom Mikkelsen, Maria G Castro, Pedro R Lowenstein
Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion, autovascularization and vascular co-option occur throughout the disease and lead to tumor invasion and progression. The molecular basis for perivascular invasion, i.e., the interaction of glioma tumor cells with endothelial cells is not well characterized. Recent studies indicate that glioma cells have increased expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular invasion of glioma cells using shRNA-mediated knock down of CXCR4...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834402/macrophages-form-functional-vascular-mimicry-channels-in-vivo
#20
Faith H Barnett, Mauricio Rosenfeld, Malcolm Wood, William B Kiosses, Yoshihiko Usui, Valentina Marchetti, Edith Aguilar, Martin Friedlander
Macrophages, key cells of the innate immune system, are known to support angiogenesis but are not believed to directly form vessel walls. Here we show that macrophages structurally form primitive, NON-ENDOTHELIAL "vessels" or vascular mimicry (VM) channels in both tumor and angiogenesis in vivo models. These channels are functionally connected to the systemic vasculature as they are perfused by intravenously injected dye. Since both models share hypoxic micro-environments, we hypothesized that hypoxia may be an important mediator of VM formation...
November 11, 2016: Scientific Reports
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