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Genetics vascular tumors

Yunlei Zhang, Wei Ji, Lian He, Yiyan Chen, Xuezhi Ding, Yunjun Sun, Shengbiao Hu, Huijun Yang, Weitao Huang, Youming Zhang, Fei Liu, Liqiu Xia
Purpose: Systemic administration of free chemotherapeutic drugs leads to severe toxic effects, and physiological characteristics of solid tumors restrain the drugs from reaching the hypoxic regions. E. coli Nissle 1917 (EcN) has been known to penetrate the barrier and proliferate in the interface between the viable and necrotic regions of tumors. This study aimed to fabricate a nanoscale minicell via genetic engineering of EcN for targeted delivery of chemotherapeutic drugs to the hypoxic regions of tumors for cancer therapy...
2018: Theranostics
Kavi Devraj, Sylvaine Guérit, Jakranka Macas, Yvonne Reiss
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function...
February 26, 2018: Journal of Visualized Experiments: JoVE
Jaidip Jagtap, Gayatri Sharma, Abdul K Parchur, Venkateswara Gogineni, Carmen Bergom, Sarah White, Michael J Flister, Amit Joshi
Vascular supply is a critical component of the tumor microenvironment (TME) and is essential for tumor growth and metastasis, yet the endogenous genetic modifiers that impact vascular function in the TME are largely unknown. To identify the host TME modifiers of tumor vascular function, we combined a novel genetic mapping strategy [Consomic Xenograft Model] with near-infrared (NIR) fluorescence imaging and multiparametric analysis of pharmacokinetic modeling. To detect vascular flow, an intensified cooled camera based dynamic NIR imaging system with 785 nm laser diode based excitation was used to image the whole-body fluorescence emission of intravenously injected indocyanine green dye...
February 1, 2018: Biomedical Optics Express
Patrícia T Goldenstein, Precil D Neves, Bruno E Balbo, Rosilene M Elias, Alexandre C Pereira, Luiz F Onuchic, Harald Jüppner, Vanda Jorgetti, Hugo Abensur, Rosa Maria Moysés
Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%...
March 14, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Yuh-Charn Lin, Chun-Yu Liu, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Ioanna Keklikoglou, Ece Kadioglu, Stefan Bissinger, Benoît Langlois, Axel Bellotti, Gertraud Orend, Carola H Ries, Michele De Palma
Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA+ stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy...
March 6, 2018: Cell Reports
Huy Gia Vuong, Toru Odate, Uyen N P Duong, Kunio Mochizuki, Tadao Nakazawa, Ryohei Katoh, Tetsuo Kondo
BACKGROUND: Solid variant papillary thyroid carcinoma (SVPTC) is a rare variant of papillary thyroid cancer (PTC) and its prognostic value is still unclear. The purpose of this systematic clinical review and meta-analysis is to investigate the prognostic value of SVPTC in comparison with classical PTC (cPTC). METHODS: Four electronic databases, including PubMed, Scopus, Web of Science, and Virtual Health Library, were searched in June 2017. Extracted data were pooled into odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence interval (CI) using the random-effect model...
March 6, 2018: Head & Neck
Ahmed El Kaffas, Azza Al-Mahrouki, Amr Hashim, Niki Law, Anoja Giles, Gregory J Czarnota
Background: High-dose radiotherapy (>8-10 Gy) causes rapid endothelial cell death via acid sphingomyelinase (ASMase)-induced ceramide production, resulting in biologically significant enhancement of tumor responses. To further augment or solicit similar effects at low radiation doses, we used genetic and chemical approaches to evaluate mechano-acoustic activation of the ASMase-ceramide pathway by ultrasound-stimulated microbubbles (USMB). Methods: Experiments were carried out in wild-type and acid sphingomyelinase (asmase) knockout mice implanted with fibrosarcoma xenografts...
February 28, 2018: Journal of the National Cancer Institute
Amy L Dimachkieh, Allison Dobbie, Damon R Olson, Mark A Lovell, Jeremy D Prager
OBJECTIVE: To review tracheal paragangliomas and describe the clinical presentation, radiologic findings, operative management, and histologic findings of a pediatric patient who presented with stridor refractory to traditional asthma therapy. METHODS: Chart review of an 8-year-old male who presented to a tertiary care pediatric hospital and literature review of tracheal paragangliomas. RESULTS: We present the case of an 8-year-old male who presented with new-onset of wheezing and dyspnea on exertion...
April 2018: International Journal of Pediatric Otorhinolaryngology
Alexandra Nagy, Aparna Bhaduri, Nahid Shahmarvand, Jahanbanoo Shahryari, James L Zehnder, Roger A Warnke, Tariq Mughal, Siraj Ali, Robert S Ohgami
Castleman disease (CD) is a rare lymphoproliferative disorder subclassified as unicentric CD (UCD) or multicentric CD (MCD) based on clinical features and the distribution of enlarged lymph nodes with characteristic histopathology. MCD can be further subtyped based on human herpes virus 8 (HHV8) infection into HHV8-associated MCD, HHV8- /idiopathic MCD (iMCD), and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS)-associated MCD. In a subset of cases of UCD, an associated follicular dendritic cell sarcoma (FDCS) may be seen...
March 13, 2018: Blood Advances
Shu-Fang Hsu, Yu-Bin Lee, Ying-Chu Lee, Ai-Ling Chung, Maria Karmella Apaya, Lie-Fen Shyur, Ching-Feng Cheng, Feng-Ming Ho, Tzu-Ching Meng
Tumor necrosis factor (TNF)-α activates a diverse array of signaling pathways in vascular endothelial cells (ECs), leading to the inflammatory phenotype that contributes to the vascular dysfunction and neutrophil emigration in patients with sepsis. To date, it is not well understood what key regulator might coordinate signaling pathways to achieve inflammatory response in TNF-α-stimulated ECs. This study investigated the role of dual specificity phosphatase-6 (DUSP6) in the regulation of endothelial inflammation...
March 1, 2018: FEBS Journal
Emily A Aherne, Linda M Pak, Debra A Goldman, Mithat Gonen, William R Jarnagin, Amber L Simpson, Richard K Do
PURPOSE: On computed tomography (CT), intrahepatic cholangiocarcinomas (ICC) are a visibly heterogeneous group of tumors. The purpose of this study was to investigate the associations between CT imaging phenotypes, patient survival, and known genetic markers. METHODS: A retrospective study was performed with 66 patients with surgically resected ICC. Pre-surgical CT images of ICC were assessed by radiologists blinded to tumor genetics and patient clinical data. Associations between qualitative imaging features and overall survival (OS) and disease-free survival (DFS) were performed with Cox proportional hazards regression and visualized with Kaplan-Meier plots...
February 28, 2018: Abdominal Radiology
Emily Kim, Stefan Zschiedrich
von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity...
2018: Frontiers in Pediatrics
Ghulam Jilany Khan, Li Sun, Sara Khan, Shengtao Yuan, He Nongyue
BACKGROUND AND OBJECTIVE: Tumor growth, development, progression, metastasis, invasion and resistivity against drugs, solely depends on the recruitment of surrounding cells, extra cellular matrix and tumor microenvironment (TME). TME is directly as well as indirectly associated with cancer associated fibroblasts (CAF). The interactions of CAF with tumor surrounding cells, their origination, activation, transformation and ability to recruit other non-tumor cells for the clemency of tumor, are very complex and under active research since long...
February 19, 2018: Current Drug Targets
Varun Monga, Umang Swami, Munir Tanas, Aaron Bossler, Sarah L Mott, Brian J Smith, Mohammed Milhem
Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis...
February 17, 2018: Cancers
Qirui Wang, Zhenqiang He, Menggui Huang, Tianrun Liu, Yanling Wang, Haineng Xu, Hao Duan, Peihong Ma, Lin Zhang, Scott S Zamvil, Juan Hidalgo, Zhenfeng Zhang, Donald M O'Rourke, Nadia Dahmane, Steven Brem, Yonggao Mou, Yanqing Gong, Yi Fan
Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α...
February 8, 2018: Nature Communications
Fabrizio Tabbò, Alessia Nottegar, Francesco Guerrera, Enrica Migliore, Claudio Luchini, Francesca Maletta, Nicola Veronese, Licia Montagna, Marcello Gaudiano, Filomena Di Giacomo, Pier Luigi Filosso, Luisa Delsedime, Giovannino Ciccone, Aldo Scarpa, Anna Sapino, Alberto Oliaro, Enrico Ruffini, Giorgio Inghirami, Marco Chilosi
Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic "cell of origin", allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003-2013) from Torino Institutional Repository identifying: i) marker positivity by immunohistochemistry ii) main morphological appearance by light microscopy, iii) presence of "hot spot" mutations of candidate genes by Sequenom technology...
January 30, 2018: Human Pathology
Rahul A Sheth, Andrew Niekamp, Keith B Quencer, Fadi Shamoun, Martha-Gracia Knuttinen, Sailendra Naidu, Rahmi Oklu
Venous thromboembolism (VTE) is the second most common cause of mortality in cancer patients. The mechanisms of cancer-associated thrombosis (CAT), much like cancer itself, are multi-factorial and incompletely understood. Cancer type, stage, tumor-derived factors and genetics all affect CAT risk. Furthermore, cancer therapies as well as the indwelling vascular devices through which these therapies are delivered can increase the risk for CAT. In this review, we summarize mechanisms of hypercoagulability in cancer patients, patterns of thrombosis associated with cancer, current guidelines for the diagnosis and management of CAT, and important considerations regarding the placement of implantable vascular devices in the care of cancer patients with VTE...
December 2017: Cardiovascular Diagnosis and Therapy
Marianne Jäger, Astrid Hubert, Rajinikanth Gogiraju, Magdalena L Bochenek, Thomas Münzel, Katrin Schäfer
AIMS: Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of receptor tyrosine kinase signaling. In this study, we determined the importance of PTP1B expressed in endothelial cells for the vascular response to arterial injury in obesity. RESULTS: Morphometric analysis of vascular lesions generated by 10% ferric chloride (FeCl3) revealed that tamoxifen-inducible endothelial PTP1B deletion (Tie2.ERT2-Cre × PTP1Bfl/fl; End.PTP1B knockout, KO) significantly increased neointima formation, and reduced numbers of (endothelial lectin-positive) luminal cells in End...
February 1, 2018: Antioxidants & Redox Signaling
Lynette L Studer, Dale M Selby
Epithelioid hemangioendothelioma is a rare vascular tumor, composed of epithelioid and histiocytoid vascular endothelial cells in myxoid or fibrotic stroma, which can arise in multiple locations throughout the body. In the liver, this neoplasm usually presents on imaging as an incidental finding of multifocal, heterogeneously enhancing nodules in both lobes or presents clinically with nonspecific abdominal symptoms. Histologically, the tumor has been mistaken for metastatic carcinoma, angiosarcoma, hepatocellular carcinoma, and cholangiocarcinoma...
February 2018: Archives of Pathology & Laboratory Medicine
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