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Vascular tumors genetics

Pichai Raman, Ravikanth Maddipati, Kian Huat Lim, Aydin Tozeren
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US. Despite multiple large-scale genetic sequencing studies, identification of predictors of patient survival remains challenging. We performed a comprehensive assessment and integrative analysis of large-scale gene expression datasets, across multiple platforms, to enable discovery of a prognostic gene signature for patient survival in pancreatic cancer. PDAC RNA-Sequencing data from The Cancer Genome Atlas was stratified into Survival+ (>2-year survival) and Survival-(<1-year survival) cohorts (n = 47)...
2018: PloS One
Jian-Ching Wu, Han-En Tsai, Guei-Sheung Liu, Chieh-Shan Wu, Ming-Hong Tai
Hypoxia in tumors is known to trigger the pro-survival pathways such as autophagy. Systemic proopiomelanocortin (POMC) gene therapy suppresses melanoma through apoptosis induction and neovascularization blockage. In this study, we investigated the crosstalk between autophagic and apoptotic signaling in POMC-mediated melanoma suppression. By histological and immunoblot analysis, it was shown that POMC-treated melanoma tissues exhibited the prominent LC3 immunostaining, which was correlated with reduced CD31-positive tumor vascularization...
2018: Cell Death Discovery
Weikun Qian, Jie Li, Ke Chen, Zhengdong Jiang, Liang Cheng, Cancan Zhou, Bin Yan, Junyu Cao, Qingyong Ma, Wanxing Duan
AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases and has few effective and reliable therapeutic strategies. The anti-tumor effect of metformin is widely known, however, there is only limited evidence regarding the anti-angiogenesis effect and chemosensitization of metformin and its underlying mechanisms in PDAC. MAIN METHODS: In the present study, we adopted a spontaneous PDAC mouse model named LSL‑KrasG12D/+ ; Trp53fl/+ ; Pdx1‑Cre (KPC) mice to explore the mechanism of the modulation of tumor angiogenesis and chemosensitization of metformin by treating KPC mice with metformin, gemcitabine or a combination of the two...
July 24, 2018: Life Sciences
Eric D Schadler, Bernhard Ortel, Stephanie L Mehlis
Psoriasis is a chronic, systemic, inflammatory disease that affects approximately 7.5 million people in the United States. The disease results in significant suffering, morbidity, and economic impact. Psoriasis is considered a multifaceted disease with a strong genetic component. Genetic data has revealed the presence of particular risk alleles found in patients with psoriasis. Triggers of the disease have been elucidated and include factors such as trauma, obesity, infection, stress, and medications. At its core, psoriasis is a result of a dysfunctional immune response with T-cells at the center of immunogenesis...
July 20, 2018: Disease-a-month: DM
Lindsay N Sausville, Mahesha Gangadhariah, Manuel Chiusa, Shaojun Mei, Shouzuo Wei, Roy Zent, James M Luther, Megan M Shuey, Jorge H Capdevila, John R Falck, F Peter Guengerich, Scott M Williams, Ambra Pozzi
Increased expression of cytochrome P450 CYP2C9, together with elevated levels of its products epoxyeicosatrienoic acids (EETs), is associated with aggressiveness in cancer. Cytochrome P450 variants CYP2C9*2 and CYP2C9*3 encode proteins with reduced enzymatic activity, and individuals carrying these variants metabolize drugs more slowly than individuals with wild-type CYP2C9*1, potentially impacting their response to drugs and altering their risk of disease. Although genetic differences in CYP2C9-dependent oxidation of arachidonic acid (AA) have been reported, the roles of CYP2C9*2 and CYP2C9*3 in EET biosynthesis and their relevance to disease are unknown...
July 16, 2018: Cancer Research
O Karray, A Saadi, M Chakroun, H Ayed, M Cherif, A Bouzouita, M R B Slama, A Derouiche, M Chebil
INTRODUCTION: Paragangliomas, defined as extra-adrenal chromaffin-cells tumors, are rarely located in the retro-peritoneum. Clinical presentation is similar to pheochromocytoma, and mainly depends on the producing character of the tumor. Positive diagnosis requires plasmatic and urinary hormonal assays. Radiological and isotopic explorations are essential before surgery. The only curative therapeutic strategy is surgical, associated to peri-operative prevention and monitoring of the frequently reported hemodynamic and cardiovascular disorders...
July 5, 2018: Progrès en Urologie
Marta Sbaraglia, Angelo P Dei Tos
Soft tissue sarcomas represent a heterogeneous group of rare malignancies exhibiting mesenchymal differentiation with an overall incidence of around 5/100,000/year. Rarity and morphologic heterogeneity significantly affect diagnostic accuracy; therefore, expertise can be achieved only through access to large number of cases. Soft tissue sarcomas are currently classified on the basis of the 2013 WHO classification of soft tissue tumors that integrate conventional morphology with immunohistochemistry and molecular genetics...
June 12, 2018: La Radiologia Medica
M Chakhtoura, M S Ramnitz, N Khoury, G Nemer, N Shabb, A Abchee, A Berberi, M Hourani, M Collins, S Ichikawa, G El Hajj Fuleihan
Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c...
June 20, 2018: Osteoporosis International
Yu Zheng, Yu-Ping Wang, Hongbao Cao, Qiusheng Chen, Xi Zhang
Although hundreds of genes have been linked to chronic myelogenous leukemia (CML), many of the results lack reproducibility. In the present study, data across multiple modalities were integrated to evaluate 579 CML candidate genes, including literature‑based CML‑gene relation data, Gene Expression Omnibus RNA expression data and pathway‑based gene‑gene interaction data. The expression data included samples from 76 patients with CML and 73 healthy controls. For each target gene, four metrics were proposed and tested with case/control classification...
August 2018: Molecular Medicine Reports
Marion Bretault, Claire Carette, Charles Barsamian, Sébastien Czernichow
Hypothalamic obesity (HO) is a rare and serious disease of various origins: tumor, traumatism, radiotherapy, vascular, genetic, or even psychotropic drug use. HO usually begins in childhood with eating disorders and progresses with an aggregate of severe comorbidities. Transition from pediatric to adult health care is a critical period to assure weight stability and a good management of comorbidities. In case of loss to follow-up, there is an increased risk of major weight gain and long-term complications with severe obesity...
2018: Endocrine Development
Michelle L Chadwick, Adam Lane, Dana Thomas, Amanda R Smith, Angela R White, Dominique Davidson, Yuxin Feng, Elisa Boscolo, Yi Zheng, Denise M Adams, Anita Gupta, André Veillette, Lionel M L Chow
Angiosarcoma is an aggressive malignancy of vascular origin that occurs de novo or in the context of previous cancer therapy. Despite multi-modal aggressive treatment including surgical resection, chemotherapy, and radiation, five-year overall survival remains poor at 35%. Due to its rarity, little is known about its molecular pathology and clinical trials have been extremely difficult to conduct. Development of animal models for rare diseases like angiosarcoma is critical to improve our understanding of tumorigenesis and to test novel treatment regimens...
May 15, 2018: Oncotarget
Mark A Socinski, Robert M Jotte, Federico Cappuzzo, Francisco Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodríguez-Abreu, Denis Moro-Sibilot, Christian A Thomas, Fabrice Barlesi, Gene Finley, Claudia Kelsch, Anthony Lee, Shelley Coleman, Yu Deng, Yijing Shen, Marcin Kowanetz, Ariel Lopez-Chavez, Alan Sandler, Martin Reck
BACKGROUND: The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy. METHODS: We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both...
June 14, 2018: New England Journal of Medicine
Lisa Mäder, Anna E Blank, David Capper, Janina Jansong, Peter Baumgarten, Naita M Wirsik, Cornelia Zachskorn, Jakob Ehlers, Michael Seifert, Barbara Klink, Stefan Liebner, Simone Niclou, Ulrike Naumann, Patrick N Harter, Michel Mittelbronn
Epithelial-to-mesenchymal transition (EMT) is supposed to be responsible for increased invasion and metastases in epithelial cancer cells. The activation of EMT genes has further been proposed to be important in the process of malignant transformation of primary CNS tumors. Since the cellular source and clinical impact of EMT factors in primary CNS tumors still remain unclear, we aimed at deciphering their distribution in vivo and clinico-pathological relevance in human gliomas. We investigated 350 glioma patients for the expression of the key EMT factors SLUG and TWIST by immunohistochemistry and immunofluorescence related to morpho-genetic alterations such as EGFR -amplification, IDH-1 (R132H) mutation and 1p/19q LOH...
May 8, 2018: Oncotarget
Małgorzata Figlus, Beata Kaczorowska, Dariusz J Jaskólski, Łukasz Kępczyński
Von Hippel-Lindau disease (vHL, familial cerebello-retinal angiomatosis) is a rare genetic autosomal dominant disorder associated with predisposition to vascular tumors. Mutations of VHL tumor suppressor gene, located on chromosome 3p25-26, are responsible for clinical manifestation of the disease. The VHL gene product encodes VHL protein, which is responsible for HIF-1 (hypoxia-inducible factor-1) dependent cell cycle regulation and cellular pathways mediated by VEGF, PDGF, TGF-α, EPO. The mechanism substantiates the hypoxia dependent vascular tumor growth caused by loss of wild-type VHL protein...
May 25, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Yuhua Wang, Ram Naresh Pandey, Stephen Riffle, Hemabindu Chintala, Kathryn A Wikenheiser-Brokamp, Rashmi S Hegde
DNA damage repair capacity is required for cells to survive catastrophic DNA damage and proliferate under conditions of intratumoral stress. The ability of the minor histone protein H2AX to serve as a hub for the assembly of a productive DNA damage repair complex is a necessary step in preventing DNA damage-induced cell death. The Eyes Absent (EYA) proteins dephosphorylate the terminal tyrosine residue of H2AX, thus permitting assembly of a productive DNA repair complex. Here, we use genetic and chemical biology approaches to separately query the roles of host vascular endothelial cell and tumor cell EYA in tumor growth...
August 2018: Molecular Cancer Therapeutics
S David Nathanson, David Krag, Henry M Kuerer, Lisa A Newman, Markus Brown, Dontscho Kerjaschki, Ethel R Pereira, Timothy P Padera
Breast cancer metastasizes through the lymphovascular system to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Renewed interest in the route by which tumor cells gain access to blood and lymphatic capillaries are the subject of research at mechanical, anatomic, pathologic, genetic, epidemiologic and molecular levels. Two papers presented at the 7th International Symposium on Cancer Metastasis in San Francisco showed tumor cells entering the systemic circulation through the sentinel lymph node...
May 23, 2018: Clinical & Experimental Metastasis
Cristina Espinosa-Diez, RaeAnna Wilson, Namita Chatterjee, Clayton Hudson, Rebecca Ruhl, Christina Hipfinger, Erin Helms, Omar F Khan, Daniel G Anderson, Sudarshan Anand
MicroRNAs (miRs) contribute to biological robustness by buffering cellular processes from external perturbations. Here we report an unexpected link between DNA damage response and angiogenic signaling that is buffered by a miR. We demonstrate that genotoxic stress-induced miR-494 inhibits the DNA repair machinery by targeting the MRE11a-RAD50-NBN (MRN) complex. Gain- and loss-of-function experiments show that miR-494 exacerbates DNA damage and drives endothelial senescence. Increase of miR-494 affects telomerase activity, activates p21, decreases pRb pathways, and diminishes angiogenic sprouting...
May 24, 2018: Cell Death & Disease
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
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