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https://www.readbyqxmd.com/read/27909701/immunological-quality-and-performance-of-tumor-vessel-targeting-car-t-cells-prepared-by-mrna-ep-for-clinical-research
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27825811/superficial-acral-fibromyxoma-clinicopathologic-immunohistochemical-and-molecular-study-of-11-cases-highlighting-frequent-rb1-loss-deletions
#9
Abbas Agaimy, Michael Michal, Johannes Giedl, Ladislav Hadravsky, Michal Michal
Superficial acral fibromyxoma (SAF) is an uncommon benign dermal mesenchymal lesion of adults with predilection for acral sites, in particular the nail region. To date, <300 cases have been reported. SAFs consistently express CD34 but other diagnostic markers or specific genetic alterations have not been established yet. We describe 11 SAFs occurring in 7 males and 4 females aged 37 to 86years (median, 48). Mean size was 6mm (range, 4-20mm). Affected sites were fingers (n=5), toes (n=3), heel (n=1), calf (n=1) and unspecified digit (n=1)...
November 4, 2016: Human Pathology
https://www.readbyqxmd.com/read/27823583/norrin-frizzled4-signalling-in-the-preneoplastic-niche-blocks-medulloblastoma-initiation
#10
Erin A Bassett, Nicholas Tokarew, Ema A Allemano, Chantal Mazerolle, Katy Morin, Alan J Mears, Brian McNeill, Randy Ringuette, Charles Campbell, Sheila Smiley, Neno T Pokrajac, Adrian M Dubuc, Vijay Ramaswamy, Paul A Northcott, Marc Remke, Philippe P Monnier, David Potter, Kim Paes, Laura L Kirkpatrick, Kenneth J Coker, Dennis S Rice, Carol Perez-Iratxeta, Michael D Taylor, Valerie A Wallace
The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch(+/-) mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB...
November 8, 2016: ELife
https://www.readbyqxmd.com/read/27818284/cardiac-angiosarcoma-histopathologic-immunohistochemical-and-cytogenetic-analysis-of-10-cases
#11
Charles Leduc, Sarah M Jenkins, William R Sukov, Jeannette G Rustin, Joseph J Maleszewski
Angiosarcoma (AS) is the most common cardiac sarcoma with differentiation, and is poorly characterized from a molecular genetic standpoint. Prognosis remains poor, owing to several factors including aggressive tumor biology, poor response to adjuvant therapy, and lack of targeted therapy. The clinical, pathologic and molecular cytogenetic features were studied in ten cardiac AS surgically resected at Mayo Clinic (1994-2015) using a whole genome single nucleotide polymorphism based platform (OncoScan). Mean patient age was 47...
November 3, 2016: Human Pathology
https://www.readbyqxmd.com/read/27809686/association-of-promoter-polymorphism-857c-t-rs1799724-in-tumor-necrosis-factor-gene-with-intracerebral-hemorrhage-in-korean-males
#12
Hae Jeong Park, Su Kang Kim, Hyun-Kyung Park, Joo-Ho Chung
BACKGROUND AND PURPOSE: Tumor necrosis factor (TNF) has been shown to be involved in the pathogenesis of hemorrhagic stroke, having deleterious effects on cerebral arteries by promoting inflammation and apoptosis in vascular and immune cells. In this study, we investigated genetic association between TNF gene and intracerebral hemorrhage (ICH) in a Korean population. METHODS: Single nucleotide polymorphisms (SNPs) of TNF gene [-857C/T (rs1799724) and -308G/A (rs1800629)] were selected and genotyped using direct sequencing in 144 ICH patients and 455 control subjects...
November 4, 2016: Neurological Research
https://www.readbyqxmd.com/read/27777714/giant-adrenal-cavernous-hemangioma-in-a-patient-with-familial-adenomatous-polyposis
#13
Dhouha Bacha, Abir Chaabane, Fatma Khanche, Saloua Néchi, Hassen Touinsi, Emna Chelbi
Adrenal hemangioma is an uncommon benign vascular tumor that is often discovered incidentally. It has never been reported in association with familial adenomatous polyposis. We report a case of a 60-year old man with a history of familial adenomatous polyposis, in whom a huge retroperitoneal cyst of 18x17 cm was discovered during routine radiologic evaluation. Because of the impossibility of ruling out the presence of malignancy, surgical cystectomy was performed, associated to a scheduled total colectomy. Pathological examination revealed that the cyst corresponded to an adrenal cavernous hemangioma...
August 8, 2016: Clinics and Practice
https://www.readbyqxmd.com/read/27775419/blood-pressure-regulation-in-stress-focus-on-nitric-oxide-dependent-mechanisms
#14
A Puzserova, I Bernatova
Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results concerning a causal relationship between stress and long-term elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hypertension include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial function including decreased nitric oxide (NO) bioavailability...
October 24, 2016: Physiological Research
https://www.readbyqxmd.com/read/27763657/renal-recruitment-of-b-lymphocytes-exacerbates-tubulointerstitial-fibrosis-by-promoting-monocyte-mobilisation-and-infiltration-after-unilateral-ureteral-obstruction
#15
Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B cell-deficient μMT mice or CD20 antibody-mediated B cell depleted mice...
October 20, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27757723/identification-of-two-distinct-mesenchymal-stromal-cell-populations-in-human-malignant-glioma
#16
Andreas Svensson, Tania Ramos-Moreno, Sofia Eberstål, Stefan Scheding, Johan Bengzon
Gene profiling has revealed that malignant gliomas can be divided into four distinct molecular subtypes, where tumors with a mesenchymal gene expression are correlated with short survival. The present investigation was undertaken to clarify whether human malignant gliomas contain endogenous mesenchymal stromal cells (MSC), fulfilling consensus criteria defined by The International Society for Cellular Therapy, recruited from the host. We found that MSC-like cells can be isolated from primary human malignant gliomas...
October 18, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27756792/a-microrna302-367-erk1-2-klf2-s1pr1-pathway-prevents-tumor-growth-via-restricting-angiogenesis-and-improving-vascular-stability
#17
Jingjiang Pi, Ting Tao, Tao Zhuang, Huimin Sun, Xiaoli Chen, Jie Liu, Yu Cheng, Zuoren Yu, Helen H Zhu, Wei-Qiang Gao, Yuanzhen Suo, Xunbin Wei, Paul Chan, Xiangjian Zheng, Ying Tian, Edward Morrisey, Lin Zhang, Yuzhen Zhang
RATIONALE: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367cluster in angiogenesis and tumors has not yet been fully evaluated. OBJECTIVE: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases...
October 18, 2016: Circulation Research
https://www.readbyqxmd.com/read/27748689/takayasu-arteritis-an-update
#18
Emire Seyahi
PURPOSE OF REVIEW: Takayasu arteritis has long been considered as an uncommon disease, rather specific to the Far-East; however recent surveys show that the disease can be seen in all ethnicities around the world with increasing prevalence rates. Nowadays, it would not be fair to consider Takayasu arteritis as a rare disease. RECENT FINDINGS: Although involvement of the thoracic aorta and its branches was more common among females, males had a tendency toward limited involvement of the abdominal aorta and its branches...
January 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27741515/compound-genetically-engineered-mouse-models-of-cancer-reveal-dual-targeting-of-alk1-and-endoglin-as-a-synergistic-opportunity-to-impinge-on-angiogenic-tgf-%C3%AE-signaling
#19
Nikolas M Eleftheriou, Jonas Sjölund, Matteo Bocci, Eliane Cortez, Se-Jin Lee, Sara I Cunha, Kristian Pietras
Angiogenesis occurs early in tumor development, sustains primary tumor growth and provides a route for metastatic escape. The TGF-β family receptors modulate angiogenesis via endothelial-cell specific pathways. Here we investigate the interaction of two such receptors, ALK1 and endoglin, in pancreatic neuroendocrine tumors (PanNET). Independently, ALK1 and endoglin deficiencies exhibited genetically divergent phenotypes, while both highly correlate to an endothelial metagene in human and mouse PanNETs. A concurrent deficiency of both receptors synergistically decreased tumor burden to a greater extent than either individual knockdown...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27739311/-prognostic-and-predictive-factors-for-pancreatic-adenocarcinoma
#20
P Karásek, M Hermanová
BACKGROUND: Pancreatic ductal adenocarcinoma is a highly aggressive disease with 5-year overall survival not exceeding 5%. In the Czech Republic, the incidence of this tumor has been increasing; according to recent statistics, the Czech Republic is already number one worldwide in the occurrence of this malignancy. Delayed diagnosis due to asymptomatic course of the disease in the early stages is characteristic for this disease. AIM: The objective of this article is to give an overview of the most important factors, which according to current knowledge of pancreatic adenocarcinoma have a prognostic and predictive potential...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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