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Vascular tumors genetics

Naoshi Nishida, Takafumi Nishimura, Toshimi Kaido, Kosuke Minaga, Kentaro Yamao, Ken Kamata, Mamoru Takenaka, Hiroshi Ida, Satoru Hagiwara, Yasunori Minami, Toshiharu Sakurai, Tomohiro Watanabe, Masatoshi Kudo
Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related deaths; an HCC subset shows rapid progression that affects survival. We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for TP53 , CTNNB1 , and TERT promoter mutation, methylation of 8 tumor suppressor genes, and 3 repetitive DNA sequences to estimate promoter hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was calculated to represent chromosomal instability through microsatellite analysis...
September 29, 2018: Cancers
Jaidip Jagtap, Gayatri Sharma, Abdul K Parchur, Venkateswara Gogineni, Carmen Bergom, Sarah White, Michael J Flister, Amit Joshi
[This corrects the article on p. 543 in vol. 9, PMID: 29552392.].
June 1, 2018: Biomedical Optics Express
Narasimhan P Agaram, Lei Zhang, Paolo Cotzia, Cristina R Antonescu
Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, rarely metastasizing vascular neoplasm with predilection to affect young adults. The tumors often present as multiple nodules involving various tissue planes, including superficial and deep soft tissues as well as bone. Recurrent SERPINE1-FOSB gene fusions have been reported as the hallmark genetic abnormality in PHE, however, in our experience, a number of cases with typical histology lack this genetic abnormality. In this study, we identify a novel ACTB-FOSB gene fusion, which is as prevalent as the initial translocation reported...
September 25, 2018: American Journal of Surgical Pathology
Diana Klein
Genetic and pathophysiologic criteria prearrange the uncontrolled growth of neoplastic cells that in turn initiates new vessel formation, which is prerequisite for further tumor growth and progression. This first endothelial lining is patchy, disordered in structure and thus, angiogenic tumor vessels were proven to be functionally inferior. As a result, tumors were characterized by areas with an apparent oversupply in addition to areas with an undersupply of vessels, which complicates an efficient administration of intravenous drugs in cancer therapy and might even lower the response e...
2018: Frontiers in Oncology
Yanqi Jiang, Yalan Yang, Ting Yang, Yueling Li, Liling Chen, Jin Yan, Yanfang Yang
OBJECTIVE: To explore the association between UCP2 rs659366 polymorphisms and the outcomes of patients after surgery for colorectal cancer. METHODS: The study was conducted among a cohort of 501 patients with primary colorectal cancer who had surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes of the patients were followed up. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect UPC2 rs659366 genotypes...
May 25, 2018: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Cheng-Mao Lin, Paul M Titchenell, Jason M Keil, Adolfo Garcia-Ocaña, Mark T Bolinger, Steven F Abcouwer, David A Antonetti
Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Vascular endothelial growth factor (VEGF) induces retinal permeability and macular thickening in these diseases. However, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in patients unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-α induce permeability through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC)...
October 2018: American Journal of Pathology
Pratiek N Matkar, Eric D Jong, Ramya Ariyagunarajah, Gerald J Prud'homme, Krishna K Singh, Howard Leong-Poi
Neuropilins (NRPs) have been described as receptors for class 3 semaphorins and coreceptors for a plethora of ligands, such as members of the vascular endothelial growth factor (VEGF) family of angiogenic cytokines and transforming growth factor (TGF). Initial studies using genetic models have indicated that neuropilin-1 (NRP-1) is essential for axonal guidance during neuronal and cardiovascular development, regulated via semaphorins and VEGF, respectively, whereas the other homolog of neuropilin, NRP-2, has been shown to play a more specific role in neuronal patterning and lymphangiogenesis...
September 14, 2018: Cancer Medicine
Raghav Oberoi, Ann-Kathrin Vlacil, Jutta Schuett, Florian Schösser, Harald Schuett, Uwe J F Tietge, Bernhard Schieffer, Karsten Grote
BACKGROUND AND AIMS: Atherosclerosis is critically fueled by vascular inflammation through oxidized lipids and inflammatory cytokines such as tumor necrosis factor (TNF)-α. Genetic disruption of Tnf-α reduces atherosclerosis in experimental mouse models. However, less is known about the therapeutic potential of Tnf-α blockage by pharmacological inhibitors such as monoclonal antibodies, which are already approved for several inflammatory disorders in patients. Therefore, we investigated the effect of pharmacological TNF-α inhibition on plaque development in experimental atherosclerosis...
August 27, 2018: Atherosclerosis
S I Shiran, L Ben-Sira, R Elhasid, J Roth, U Tabori, M Yalon, S Constantini, R Dvir
BACKGROUND AND PURPOSE: Biallelic constitutional mutations in DNA mismatch repair genes cause a distinct syndrome, constitutional mismatch repair deficiency syndrome (CMMRD), characterized by cancers from multiple organs, most commonly brain tumors, during childhood. Surveillance protocols include total and brain MR imaging among other modalities to enable early detection of tumors. Brain surveillance scans revealed prominent brain developmental venous anomalies (DVAs) in some patients...
August 30, 2018: AJNR. American Journal of Neuroradiology
Reem Al Argan, Avi Saskin, Ji Wei Yang, Maria Daniela D'Agostino, Juan Rivera
Glucocorticoid resistance syndrome (GRS) is a rare genetic disorder caused by inactivating mutations of the NR3C1 gene which encodes the glucocorticoid receptor. The phenotypic spectrum is broad but typically include symptoms of adrenal insufficiency, mineralocorticoid excess and hyperandrogenism. We report a new case associated with a novel NR3C1 mutation. A 55-year-old woman with lifelong history of low body weight, hyperandrogenism and anxiety was seen at the endocrine clinic after left adrenalectomy and salpingoophorectomy for lesions suspicious of ovarian cancer and adrenal metastasis...
August 30, 2018: Endocrine Journal
Giuseppina Caiazzo, Gabriella Fabbrocini, Roberta Di Caprio, Annunziata Raimondo, Emanuele Scala, Nicola Balato, Anna Balato
Nowadays, it is well established a link between psoriasis and cardiovascular (CV) diseases. A series of different overlapping mechanisms including inflammation, homeostasis dysregulation, and genetic susceptibility are thought to underlie this association. Advances in understanding the molecular patterns involved in the complex scenario of psoriasis have highlighted a tight correlation with atherosclerosis. Indeed, common profiles are shared in term of inflammatory cytokines and cell types. In the last decade, the management of psoriasis patients has been revolutionized with the introduction of biological therapies, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-12/23, and IL-17 inhibitors...
2018: Frontiers in Immunology
Inga-Marie Schaefer, Jason L Hornick
Although some soft tissue and bone tumors can be identified based on histologic features alone, immunohistochemistry plays a critical diagnostic role for most mesenchymal tumor types. The discovery of recurrent genomic alterations in many benign and malignant mesenchymal neoplasms has added important biologic insights and expanded the spectrum of some diagnostic subgroups. Some tumors are defined by unique genomic alterations, whereas others share abnormalities that are not tumor-specific and can be observed in a sometimes broad range of biologically unrelated neoplasms...
November 2018: Advances in Anatomic Pathology
Matteo Bocci, Jonas Sjölund, Ewa Kurzejamska, David Lindgren, Nour-Al-Dain Marzouka, Michael Bartoschek, Mattias Höglund, Kristian Pietras
Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor-β superfamily...
August 21, 2018: Angiogenesis
Manja Idorn, Per Thor Straten
While cancer immune therapy has revolutionized the treatment of metastatic disease across a wide range of cancer diagnoses, a major limiting factor remains with regard to relying on adequate homing of anti-tumor effector cells to the tumor site both prior to and after therapy. Adoptive cell transfer (ACT) of autologous T cells have improved the outlook of patients with metastatic melanoma. Prior to the approval of checkpoint inhibitors, this strategy was the most promising. However, while response rates of up to 50% have been reported, this strategy is still rather crude...
August 17, 2018: Cells
Naohito Hatta
Most patients with extramammary Paget's disease (EMPD) show a good prognosis; however, some patients develop fatal metastases. Early detection is important for improving prognosis, due to the difficulties associated with the treatment of distant EMPD metastases. Several studies have emphasized the importance of the invasion level of the primary lesion for predicting the presence of metastasis, and deeper invasion or increased thickness is correlated with poorer prognosis. Vascular tumor invasion of the primary lesion can also predict the risk of metastasis...
August 15, 2018: Current Treatment Options in Oncology
Emmanuel N Kontomanolis, Sofia Kalagasidou, Stamatia Pouliliou, Xanthoula Anthoulaki, Nikolaos Georgiou, Valentinos Papamanolis, Zacharias N Fasoulakis
Objective: Notch signaling pathway is a vital parameter of the mammalian vascular system. In this review, the authors summarize the current knowledge about the impact of the Notch signaling pathway in breast cancer progression and the therapeutic role of Notch's inhibition. Methods: The available literature in MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast cancer progression was searched for related articles from about 1973 to 2017 including terms such as "Notch," "Breast Cancer," and "Angiogenesis...
2018: TheScientificWorldJournal
X L Xu, J G Liu, M Sun, L Yu, Q Y Liu, Q M Bai, L J Wu, J Wang
Objective: To investigate the clinicopathologic and genetic features, pathologic diagnosis and differential diagnosis of angiofibroma of soft tissue(AFST). Methods: The clinicopathologic characteristics of 24 cases diagnosed at Fudan University Shanghai Cancer Center from 2011 to 2017 were analyzed; immunohistochemical staining and interphase fluorescence in situ hybridization (FISH) were performed, and the literatures were also reviewed. Results: There were 15 male and 9 female (male∶female=1.7∶1.0) patients with age of onset ranging from 8 to 68 years (mean, 45 years)...
August 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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...
September 1, 2018: Life Sciences
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