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https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#1
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mattew, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jun Song, Rose Ackermann, Yui Koike, Anna Schwendeman, Liangxue Lai, Subramaniam Pennathur, Minerva Garcia-Barrio, Jianglin Fan, Y Eugene Chen
OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28426730/functional-genetic-variant-of-ww-domain-containing-oxidoreductase-wwox-gene-is-associated-with-hepatocellular-carcinoma-risk
#2
Hsiang-Lin Lee, Hsin-Lin Cheng, Yu-Fan Liu, Ming-Chih Chou, Shun-Fa Yang, Ying-Erh Chou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk. METHODOLOGY/PRINCIPAL FINDINGS: Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC...
2017: PloS One
https://www.readbyqxmd.com/read/28420319/bcor-ccnb3-undifferentiated-sarcoma-does-immunohistochemistry-help-in-the-identification
#3
Kathrin Ludwig, Rita Alaggio, Angelica Zin, Marica Peron, Vincenza Guzzardo, Stefania Benini, Alberto Righi, Marco Gambarotti
Recent methodology has enabled the identification of some new genetic subgroups within the melting pot of lesions presently classified by the 2013 WHO classification as "undifferentiated/unclassified sarcomas". One of these subgroups is characterized by a paracentric inversion of the X chromosome with consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features of these tumors overlap with the Ewing sarcoma family as well as other soft tissue sarcomas, thus making them difficult to diagnose...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28420166/hypaphorine-attenuates-lipopolysaccharide-induced-endothelial-inflammation-via-regulation-of-tlr4-and-ppar-%C3%AE-dependent-on-pi3k-akt-mtor-signal-pathway
#4
Haijian Sun, Xuexue Zhu, Weiwei Cai, Liying Qiu
Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418921/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#5
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#6
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28393435/pathogenetic-significance-and-possibility-as-a-therapeutic-target-of-platelet-derived-growth-factor
#7
REVIEW
Yoko Ishii, Takeru Hamashima, Seiji Yamamoto, Masakiyo Sasahara
Platelet-derived growth factor (PDGF) is one of the major mitogens and chemoattractants for mesenchymal and glial cells. Nowadays, the expression of PDGFs are recognized widely in our body, and emerging data indicate the relevance of PDGFs in the homeostatic control of systemic connective tissue as well as parenchymal cells such as neurons. Aberrant PDGF signal is primarily tumorigenic, and also regulates tumor microenvironments. The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti-PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment...
April 10, 2017: Pathology International
https://www.readbyqxmd.com/read/28379521/arterial-aging-mediates-the-effect-of-tnf-a-and-ace-polymorphisms-on-mental-health-in-elderly-individuals-insights-from-ikaria-study
#8
George Georgiopoulos, Christina Chrysohoou, Alessandra Errigo, Gianni Pes, Vasiliki Metaxa, Marina Zaromytidou, John Skoumas, Maria Kariori, George Lazaros, Georgia Vogiatzi, Michel Poulain, Dimitris Tousoulis, Christos Pitsavos, Christodoulos Stefanadis
Background: Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices ïf arterial aging in nonagenarian individuals. Design: 178 consecutive subjects above 75 years that permanently inhabit in the island of Ikaria, Greece were recruited...
April 3, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28363643/genetic-features-of-aflatoxin-associated-hepatocellular-carcinomas
#9
Weilong Zhang, Huan He, Mengya Zang, Qifeng Wu, Hong Zhao, Ling-Ling Lu, Peiqing Ma, Hongwei Zheng, Nengjin Wang, Ying Zhang, Siyuan He, Xiaoyan Chen, Zhiyuan Wu, Xiaoyue Wang, Jianqiang Cai, Zhihua Liu, Zongtang Sun, Yi-Xin Zeng, Chunfeng Qu, Yuchen Jiao
BACKGROUND & AIMS: Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. METHODS: We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38...
March 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28358393/on-chip-human-microvasculature-assay-for-visualization-and-quantification-of-tumor-cell-extravasation-dynamics
#10
Michelle B Chen, Jordan A Whisler, Julia Fröse, Cathy Yu, Yoojin Shin, Roger D Kamm
Distant metastasis, which results in >90% of cancer-related deaths, is enabled by hematogenous dissemination of tumor cells via the circulation. This requires the completion of a sequence of complex steps including transit, initial arrest, extravasation, survival and proliferation. Increased understanding of the cellular and molecular players enabling each of these steps is key to uncovering new opportunities for therapeutic intervention during early metastatic dissemination. As a protocol extension, this article describes an adaptation to our existing protocol describing a microfluidic platform that offers additional applications...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28356974/gastrointestinal-stromal-tumor-with-a-pdgfra-mutation-masquerading-as-gastric-plexiform-fibromyxoma-a-comparative-clinicopathological-study-of-two-cases
#11
Jun Zhou, Jingjing Xu, Guozhong Jiang, Yihui Ma, Jingwen Qi, Wencai Li, Dandan Zhang
Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28356760/the-associations-between-five-polymorphisms-of-vascular-endothelial-growth-factor-and-renal-cell-carcinoma-risk-an-updated-meta-analysis
#12
Jiao Wang, ChangXin Shen, YouRong Fu, Tian Yu, JingJing Song
BACKGROUND: Vascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28349192/-interstitial-processes-of-the-lungs-in-childhood
#13
H Popper
Interstitial processes in the lungs of children can be due to several underlying diseases. Knowledge of the child's age is important as genetic aberrations play a major role in diseases in the first 2 years, whereas immunological diseases are more common starting in kindergarden age. In general lung diseases are rare in children, which makes the diagnostics difficult and results in a delayed diagnosis. In addition, pediatric pulmonologists are often very reluctant to perform lung biopsies due to a lack of a specialized pathologist...
March 27, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28338502/sellar-atypical-teratoid-rhabdoid-tumor-at-rt-a-clinicopathologically-and-genetically-distinct-variant-of-at-rt
#14
Satoshi Nakata, Sumihito Nobusawa, Takanori Hirose, Shinji Ito, Naoko Inoshita, Shunsuke Ichi, Vishwa J Amatya, Yukio Takeshima, Kazuhiko Sugiyama, Yukihiko Sonoda, Hironori Haga, Junko Hirato, Yoichi Nakazato, Hideaki Yokoo
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive tumors of the central nervous system that predominantly affect infants. Although adult AT/RT are rare, accumulated cases have revealed adult-specific AT/RT in the sellar region. Twelve previously reported cases of sellar AT/RT exclusively occurred in adult females, suggesting biological differences from conventional infant AT/RT. We herein investigated a series of 6 sellar AT/RT for histopathologic features, the molecular status of the INI1/SMARCB1 gene, and clinical courses...
March 23, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#15
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28327358/a-cell-autonomous-positive-signaling-circuit-associated-with-the-pdgf-no-id4-regulatory-axis-in-glioblastoma-cells
#16
Kiyoung Eun, Hye-Min Jeon, Sung-Ok Kim, Sang-Hun Choi, Seon Yong Lee, Xiong Jin, Sung-Chan Kim, Hyunggee Kim
Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit...
March 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28323122/exome-analysis-of-the-evolutionary-path-of-hepatocellular-adenoma-carcinoma-transition-vascular-invasion-and-brain-dissemination
#17
Sílvia Vilarinho, Zeynep Erson-Omay, Kisha Mitchell-Richards, Charles Cha, Carol Nelson-Williams, Akdes Serin Harmancı, Katsuhito Yasuno, Murat Günel, Tamar H Taddei
Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with acute abdominal pain and was found to have a 17 cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14 cm moderately differentiated hepatocellular carcinoma (HCC) arising in a shell of a HCA...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28320710/myeloid-p53-regulates-macrophage-polarization-and-venous-thrombus-resolution-by-inflammatory-vascular-remodeling-in-mice
#18
Subhradip Mukhopadhyay, Toni M Antalis, Khanh P Nguyen, Mark H Hoofnagle, Rajabrata Sarkar
Deep venous thrombosis (DVT) remains a common and serious cardiovascular problem with both fatal and long-term consequences. The consequences of DVT include the development of post-thrombotic syndrome (PTS) in 25-60% of DVT patients. Despite the clinical importance of venous thrombus resolution, the cellular and molecular mediators involved are poorly understood, and currently there is no molecular therapy to accelerate this process. Several lines of evidence suggest that a complex and interrelated array of molecular signaling processes are involved in the inflammatory vascular remodeling associated with the resolution of DVT...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28283837/vascular-hyperpermeability-as-a-hallmark-of-phacomatoses-is-the-etiology-angiogenesis-related-to-or-comparable-with-mechanisms-seen-in-inflammatory-pathways-part-ii-angiogenesis-and-inflammation-related-molecular-pathways-tumor-associated-macrophages-and-possible
#19
REVIEW
Yosef Laviv, Burkhard Kasper, Ekkehard M Kasper
Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles...
March 11, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28281318/intracranial-myxoid-mesenchymal-tumors-with-ewsr1-creb-family-gene-fusions-myxoid-variant-of-angiomatoid-fibrous-histiocytoma-or-novel-entity
#20
Tejus A Bale, Angelica Oviedo, Harry Kozakewich, Caterina Giannini, Phani K Davineni, Keith Ligon, Sanda Alexandrescu
Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present three pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) were performed...
March 9, 2017: Brain Pathology
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