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Vascular tumors + genetics

Mahtab Babadi, Ahmad Khorshidi, Esmat Aghadavood, Mansooreh Samimi, Elham Kavossian, Fereshteh Bahmani, Alireza Mafi, Rana Shafabakhsh, Mahbobeh Satari, Zatollah Asemi
This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 109  CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks...
December 8, 2018: Probiotics and Antimicrobial Proteins
Tatsuya Nagano, Motoko Tachihara, Yoshihiro Nishimura
Lung cancer is the leading cause of cancer death worldwide. Molecular targeted therapy has greatly advanced the field of treatment for non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancers. Indeed, gefitinib, which was the first molecular targeted therapeutic agent, has actually doubled the survival time of NSCLC patients. Vigorous efforts of clinicians and researchers have revealed that lung cancer develops through the activating mutations of many driver genes including the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), v-Raf murine sarcoma viral oncogene homolog B (BRAF), and rearranged during transfection (RET) genes...
December 9, 2018: Current Cancer Drug Targets
Varsha I Shah, Gareth L Rowlands, Ian W Thompson, Vaiyapuri P Sumathi, W Glenn McCluggage
Angiosarcomas of the female genital tract are rare and primary angiosarcoma of the cervix is extremely rare with only one prior case report. We report a case of a primary cervical angiosarcoma in a 43-yr-old woman who presented with heavy vaginal bleeding. Cervical biopsy and subsequent radical hysterectomy showed a malignant vascular tumor which was composed of spindled and epithelioid cells and formed abortive vascular channels. Immunohistochemically, the tumor cells were diffusely positive for CD31, CD34, ERG, and cyclin D1 and focally positive for D2-40...
December 3, 2018: International Journal of Gynecological Pathology
Michael Bartoschek, Nikolay Oskolkov, Matteo Bocci, John Lövrot, Christer Larsson, Mikael Sommarin, Chris D Madsen, David Lindgren, Gyula Pekar, Göran Karlsson, Markus Ringnér, Jonas Bergh, Åsa Björklund, Kristian Pietras
Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium...
December 4, 2018: Nature Communications
Heather N Hayenga, Andrew J Bishop, Zabi Wardak, Chandra Sen, Bruce Mickey
BACKGROUND: Hemangiopericytomas (HPCs) are rare vascular tumors that resemble meningiomas on imaging and have a high rate of local recurrence and metastases. There remains a paucity of data to guide management decisions of intraspinal dissemination of HPC in the literature, and none specifically related to anaplastic HPCs. CASE DESCRIPTION: Case report of a 34-year-old female with locally and distantly recurrent anaplastic hemangiopericytoma (HPC) (WHO grade III)...
November 29, 2018: World Neurosurgery
Jianbo Huang, Xiangyu Wang, Ying Zhu, Zheng Wang, Jianhua Li, Da Xu, Shenghao Wang, Tian-En Li, Lu Lu
BACKGROUND: The hepatitis B virus (HBV)-related intrahepatic cholangiocarcinoma (iCCA) was recognized as a unique subtype of iCCA, within particular features in demography, clinicopathology, and genealogy. However, how they predict prognosis, in particular, for HBV- and non-HBV-related iCCA is still unclear. METHODS: Demographic, clinicopathologic, and genetic features were retrospectively collected and reviewed to determine the specific prognostic factors, precisely predicting the overall survival (OS) in HBV-related (n = 119) and non-HBV-related ( n = 149) iCCA patients, respectively...
November 27, 2018: Journal of Surgical Oncology
Brendan T Heiden, Nathan Patel, Derek J Nancarrow, Matthew Hermann, Richard K J Brown, Mark B Orringer, Jules Lin, Andrew C Chang, Philip W Carrott, William R Lynch, Lili Zhao, David G Beer, Rishindra M Reddy
BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography is an imaging modality critical to the diagnosis and staging of esophageal cancer. Despite this, the genetic abnormalities associated with increased 18F-fluorodeoxyglucose (FDG)-maximum standardized uptake value (SUVmax) have not been previously explored in esophageal adenocarcinoma. MATERIALS AND METHODS: Treatment-naïve patients, for whom frozen tissue and 18F-fluorodeoxyglucose positron emission tomography data were available, undergoing esophagectomy from 2003 to 2012, were identified...
December 2018: Journal of Surgical Research
Meeli Sirotkina, Konstantinos Douroudis, Magnus Westgren, Nikos Papadogiannakis
INTRODUCTION: Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done. MATERIALS AND METHODS: Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method...
November 14, 2018: Pediatric and Developmental Pathology
Mario Buono, Marie-Laëtitia Thézénas, Alessandro Ceroni, Roman Fischer, Claus Nerlov
The ligand for the c-Kit receptor, KitL, exists as a membrane-associated (mKitL) and a soluble form (sKitL). KitL functions outside c-Kit activation have not been identified. We show that co-culture of c-Kit- and mKitL-expressing NIH3T3 cells results in signaling through mKitL: c-Kit-bound mKitL recruits calcium-modulating cyclophilin ligand (CAML) to selectively activate Akt, leading to CREB phosphorylation, mTOR pathway activation, and increased cell proliferation. Activation of mKitL in thymic vascular endothelial cells (VECs) induces mKitL- and Akt-dependent proliferation, and genetic ablation of mKitL in thymic VECs blocks their c-Kit responsiveness and proliferation during neonatal thymic expansion...
November 8, 2018: Nature Communications
Federico Innocenti, Chen Jiang, Alexander B Sibley, Amy S Etheridge, Ace J Hatch, Stefanie Denning, Donna Niedzwiecki, Ivo D Shterev, Jiaxing Lin, Yoichi Furukawa, Michiaki Kubo, Hedy L Kindler, J Todd Auman, Alan P Venook, Herbert I Hurwitz, Howard L McLeod, Mark J Ratain, Raluca Gordan, Andrew B Nixon, Kouros Owzar
Angiogenesis is essential in tumor biology and is regulated by vascular endothelial growth factor (VEGF) ligands and receptors. Here we aimed to discover genetic variants associated with levels of circulating angiogenic proteins in cancer patients. Plasma was collected at baseline in 216 pancreatic and 114 colorectal cancer patients. Thirty-one angiogenic proteins were measured by ELISA. 484,523 Single Nucleotide Polymorphisms (SNP) were tested for association with plasma levels for each protein in pancreatic cancer patients...
November 5, 2018: Scientific Reports
Hung V-T Nguyen, Alexandre Detappe, Nolan M Gallagher, Hui Zhang, Peter Harvey, Changcun Yan, Clelia Mathieu, Matthew R Golder, Yivan Jiang, Maria Francesca Ottaviani, Alan Jasanoff, Andrzej Rajca, Irene Ghobrial, P Peter Ghoroghchian, Jeremiah A Johnson
Nitroxides occupy a privileged position among plausible metal-free magnetic resonance imaging (MRI) contrast agents (CAs) due to their inherently low-toxicity profiles; nevertheless, their translational development has been hindered by a lack of appropriate contrast sensitivity. Nanostructured materials with high nitroxide densities, where each individual nitroxide within a macromolecular construct contributes to the image contrast, could address this limitation, but the synthesis of such materials remains challenging...
November 27, 2018: ACS Nano
Tine Van Bergen, Isabelle Etienne, Fiona Cunningham, Lieve Moons, Reinier O Schlingemann, Jean H M Feyen, Alan W Stitt
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. Upon binding to VEGF- and neuropilin-receptor sub-types, PlGF modulates a range of neural, glial and vascular cell responses that are distinct from VEGF-A. As PlGF expression is selectively associated with pathological angiogenesis and inflammation, its blockade does not affect the healthy vasculature. PlGF actions have been extensively described in tumor biology but more recently there has been accumulating preclinical evidence that indicates that this growth factor could have an important role in retinal diseases...
October 30, 2018: Progress in Retinal and Eye Research
William J Anderson, Jason L Hornick
Sarcomas encompass a broad group of malignant mesenchymal neoplasms, whose accurate diagnosis and classification relies on the integration of clinical, histopathological and molecular features. Our understanding of the latter has increased dramatically in recent years with the widespread application of high-throughput sequencing. Concomitantly, the role of immunohistochemistry has continued to expand, as many genomic alterations have been exploited by the development of novel diagnostic markers that act as surrogates for their detection...
November 1, 2018: Genes, Chromosomes & Cancer
Xueru Zhu, Yiwei Wang, Wenji Xue, Ruifen Wang, Lifeng Wang, Mei-Ling Zhu, Leizhen Zheng
OBJECTIVE: Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic variations with the prognosis of gastric cancer (GC). METHOD: We collected the clinical information of patients with GC and extracted genomic DNA from paraffin-embedded tissues...
October 31, 2018: Cancer Biology & Therapy
James J Hsieh, Valerie H Le, Toshinao Oyama, Christopher J Ricketts, Thai Huu Ho, Emily H Cheng
Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype, and metastatic ccRCC is associated with 5-year survival rates of 10% to 20%. Genetically, ccRCC originates from sequential losses of multiple tumor suppressor genes. Remarkably, chromosome 3p loss occurs in more than 90% of sporadic ccRCCs. This results in concurrent one-copy loss of four tumor suppressor genes that are also mutated individually at high frequency in ccRCC (ie, VHL, 80%; PBRM1, 29% to 46%; BAP1, 6% to 19%; and SETD2, 8% to 30%)...
October 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Er-Shun Liang, Wen-Wu Bai, Hao Wang, Jian-Ning Zhang, Fan Zhang, Yang Ma, Fan Jiang, Mei Yin, Ming-Xiang Zhang, Xiao-Mei Chen, Wei-Dong Qin
Abdominal aortic aneurysm (AAA) is a common vascular degenerative disease. PARP-1 (poly[ADP-ribose] polymerase 1) is a nuclear enzyme, which plays a critical role in vascular diseases. We hypothesized that PARP-1 inhibition might have protective effects on AAA. In vivo, Ang II (angiotensin II) was continuously infused by a micropump for 28 days to induce AAA in mice. In vitro, aortic endothelial cells and smooth muscle cells were stimulated by Ang II for 24 hours. Ang II infusion increased PARP-1 expression and activity and successfully induced AAA formation partly with a hemorrhage in ApoE-/- mice...
November 2018: Hypertension
Sylwia M Figarska, Stefan Gustafsson, Johan Sundström, Johan Ärnlöv, Anders Mälarstig, Sölve Elmståhl, Tove Fall, Lars Lind, Erik Ingelsson
Objective- Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results- We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years)...
October 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Jiao Xu, Tuochen Zheng, Wenli Hong, Haifeng Ye, Chuan Hu, Yuehui Zheng
The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians...
2018: Cellular Physiology and Biochemistry
Miki Nagashima, Madoka Koyanagi, Yutaka Arimura
Allergic diseases have increased in the last three decades. Mast cells play a critical role in allergic diseases along with allergen-specific immunoglobulin E (IgE). Following mast cell degranulation elicited by ligation of the IgE-FcεRI receptor complex with allergen, allergic reactions are followed by various symptoms such as vascular hyperpermeability, mucous secretion, itching, sneezing, wheezing, rashes, fever, and anaphylactic shock. Susceptibility or inclination to allergy varies depending on individual genetic traits and living environment, and it has long been believed that such an inclination is determined by an immunologic balance of T helper cell types...
October 18, 2018: Immunological Investigations
Meng Cai, Sitao Li, Yunfei Shuai, Jie Li, Jieqiong Tan, Qiyi Zeng
Tumor necrosis factor α (TNF-α), a pivotal cytokine in sepsis, protects the host against pathogens by promoting an inflammatory response while simultaneously inducing apoptosis of the vascular endothelium. Unfortunately, inhibitors targeting certain components of the TNF-α signaling pathway to reduce cellular apoptosis have failed to translate into clinical applications, partly due to the adverse effects of excessive immunosuppression. In an attempt to discover potential targets in the TNF-α signaling pathway to modulate moderate inflammation and apoptosis during the development of sepsis, we performed a pooled genome-wide CRISPR/Cas9 knockout screen in human umbilical vein endothelial cells (HUVECs)...
October 14, 2018: Journal of Cellular Physiology
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