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https://www.readbyqxmd.com/read/28626727/mast-cell-infiltration-in-human-brain-metastases-modulates-the-microenvironment-and-contributes-to-the-metastatic-potential
#1
Ananya Roy, Sylwia Libard, Holger Weishaupt, Ida Gustavsson, Lene Uhrbom, Göran Hesselager, Fredrik J Swartling, Fredrik Pontén, Irina Alafuzoff, Elena Tchougounova
Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28588705/galnt14-genotype-is-associated-with-perineural-invasion-lymph-node-metastasis-and-overall-survival-in-resected-cholangiocarcinoma
#2
Kung-Hao Liang, Ta-Sen Yeh, Ren-Chin Wu, Chun-Nan Yeh, Chau-Ting Yeh
Cholangiocarcinoma is a rare, sporadic and aggressive type of cancer. The genetic basis of cholangiocarcinoma remains poorly understood. The present study investigated the prognostic role of the N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype, an effective therapeutic response predictor for hepatocellular carcinoma in patients with cholangiocarcinoma receiving surgical resection. A cohort of patients with intrahepatic or perihilar cholangiocarcinoma (n=112) were retrospectively recruited. Of these patients, 31...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28567545/host-genetic-modifiers-of-nonproductive-angiogenesis-inhibit-breast-cancer
#3
Michael J Flister, Shirng-Wern Tsaih, Alexander Stoddard, Cody Plasterer, Jaidip Jagtap, Abdul K Parchur, Gayatri Sharma, Anthony R Prisco, Angela Lemke, Dana Murphy, Mona Al-Gizawiy, Michael Straza, Sophia Ran, Aron M Geurts, Melinda R Dwinell, Andrew S Greene, Carmen Bergom, Peter S LaViolette, Amit Joshi
PURPOSE: Multiple aspects of the tumor microenvironment (TME) impact breast cancer, yet the genetic modifiers of the TME are largely unknown, including those that modify tumor vascular formation and function. METHODS: To discover host TME modifiers, we developed a system called the Consomic/Congenic Xenograft Model (CXM). In CXM, human breast cancer cells are orthotopically implanted into genetically engineered consomic xenograft host strains that are derived from two parental strains with different susceptibilities to breast cancer...
May 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28562096/emerging-growth-factor-receptor-antagonists-for-the-treatment-of-advanced-melanoma
#4
Sarah E Fenton, Jeffrey A Sosman, Sunandana Chandra
Therapy for metastatic melanoma has undergone a rapid transformation over the past 5-10 years. Advances in immunotherapy with checkpoint inhibitors, including both anti-CTLA-4 and anti-PD-1/PD-L1, have led to durable responses in up to 50% of patients. As our understanding of the processes driving the transformation of melanocytes has improved, progress in targeted therapies has also continued. Areas covered: Angiogenesis and the tumor's dependence on an expanded vascular supply has been a target for novel therapies since the 1970's, as this tissue is derived from endothelial cells that are genetically stable in adults...
June 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28553953/atf4-promotes-angiogenesis-and-neuronal-cell-death-and-confers-ferroptosis-in-a-xct-dependent-manner
#5
D Chen, Z Fan, M Rauh, M Buchfelder, I Y Eyupoglu, N Savaskan
Activating transcription factor 4 (ATF4) is a critical mediator of metabolic and oxidative homeostasis and cell survival. ATF4 is elevated in response to diverse microenvironmental stresses, including starvation, ER stress damages and exposure to toxic factors. Here we show that ATF4 expression fosters the malignancy of primary brain tumors (WHO grade III and IV gliomas) and increases proliferation and tumor angiogenesis. Hence, ATF4 expression promotes cell migration and anchorage-independent cell growth, whereas siRNA-mediated knockdown of ATF4 attenuates these features of malignancy in human gliomas...
May 29, 2017: Oncogene
https://www.readbyqxmd.com/read/28546328/microrna-15a-16-1-antagomir-ameliorates-ischemic-brain-injury-in-experimental-stroke
#6
Xinxin Yang, Xuelian Tang, Ping Sun, Yejie Shi, Kai Liu, Sulaiman H Hassan, R Anne Stetler, Jun Chen, Ke-Jie Yin
BACKGROUND AND PURPOSE: Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. METHODS: Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1-specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion...
May 25, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28534973/role-of-x%C3%A2-linked-inhibitor-of-apoptosis%C3%A2-associated-factor%C3%A2-1-in-vasculogenic-mimicry-in-ovarian-cancer
#7
Yunxia Wang, Peishu Liu, Xietong Wang, Hongluan Mao
X-linked inhibitor of apoptosis‑associated factor 1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that may reverse the anti‑apoptotic effect of XIAP. Previous studies have revealed that XAF1 serves an important role in cancer angiogenesis. Vasculogenic mimicry (VM) describes the formation of fluid‑conducting channels by highly invasive and genetically dysregulated tumor cells. VM is critical for tumor blood supply and is associated with aggressive actions and metastasis...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28520518/arrested-development-infantile-hemangioma-and-the-stem-cell-teratogenic-hypothesis
#8
Shaghayegh Harbi, Hannah Park, Michael Gregory, Peter Lopez, Luis Chiriboga, Paolo Mignatti
BACKGROUND: Early-life programming is defined by the adaptive changes made by the fetus in response to an adverse in utero environment. Infantile hemangioma (IH), a vascular anomaly, is the most common tumor of infancy. Here we take IH as the tumor model to propose the stem cell teratogenic hypothesis of tumorigenesis and the potential involvement of the immune system. OBJECTIVES: Teratogenic agents include chemicals, heavy metals, pathogens, and ionizing radiation...
June 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28494747/new-diagnostic-and-therapeutic-aspects-of-pancreatic-ductal-adenocarcinoma
#9
Harald Mangge, Tobias Niedrist, Wilfried Renner, Stefan Lyer, Christoph Alexiou, Johannes Haybaeck
Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis, leaving sufficient time for curative therapy that effectively lowers the very high mortality rate of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. < 6% five-year survival rates). New data, including particular genetic signatures and features of the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively long-lasting painless expansion, and why chemotherapy so frequently fails...
May 10, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28488085/novel-loss-of-function-mutation-in-krit1-ccm1-is-associated-with-distinctly-progressive-cerebral-and-spinal-cavernous-malformations-after-radiochemotherapy-for-intracranial-malignant-germ-cell-tumor
#10
Alexandra Russo, Marie Astrid Neu, Johanna Theruvath, Bettina Kron, Arthur Wingerter, Silla Hey-Koch, Yasemin Tanyildizi, Joerg Faber
PURPOSE: Cerebrospinal cavernous malformations (CCMs) are vascular lesions characterized by dilated and leaky capillary caverns. CCMs can cause seizures, focal neurological deficits or acute intracranial hemorrhage; however, most patients are asymptomatic. CCMs occur either sporadically or as a familial autosomal-dominant disorder. We present a clinical and molecular study of a patient with distinctive cerebral and spinal cavernous malformations following radiochemotherapy for a malignant brain tumor...
May 9, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28479387/the-effects-of-tlr3-trif-and-traf3-snps-and-interactions-with-environmental-factors-on-type-2-diabetes-mellitus-and-vascular-complications-in-a-han-chinese-population
#11
Zixing Zhou, Chengli Zeng, Lihong Nie, Shiqi Huang, Congcong Guo, Di Xiao, Yajing Han, Xiaohong Ye, Meiling Ou, Chuican Huang, Xingguang Ye, Zihao Wen, Guang Yang, Chunxia Jing
Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated...
May 4, 2017: Gene
https://www.readbyqxmd.com/read/28473444/role-of-adipose-tissue-endothelial-adam17-in-age-related-coronary-microvascular-dysfunction
#12
Huijuan Dou, Attila Feher, Alec C Davila, Maritza J Romero, Vijay S Patel, Vinayak M Kamath, Monika Beck Gooz, R Daniel Rudic, Rudolf Lucas, David J Fulton, Neal L Weintraub, Zsolt Bagi
OBJECTIVE: A disintegrin and metalloproteinase ADAM17 (tumor necrosis factor-α [TNF]-converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction in obesity. APPROACH AND RESULTS: Coronary arterioles (CAs, ≈90 µm) from right atrial appendages and mediastinal AT were examined in patients (aged: 69±11 years, BMI: 30...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28469956/targeting-nras-q61k-mutant-delays-tumor-growth-and-angiogenesis-in-non-small-cell-lung-cancer
#13
Zhaowei Song, Fenghai Liu, Jie Zhang
Tumor cells require vascular supply for their growth, and they express proangiogenic growth factors that promote the formation of vascular networks. Many oncogenic mutations that may potentially lead to tumor angiogenesis have been identified. Somatic mutations in the small GTPase NRAS are the most common activating lesions found in human cancer and are generally associated with poor response to standard therapies. However, the mechanisms by which NRAS mutations affect tumor angiogenesis are largely unknown...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28466788/vanadium-iii-l-cysteine-enhances-the-sensitivity-of-murine-breast-adenocarcinoma-cells-to-cyclophosphamide-by-promoting-apoptosis-and-blocking-angiogenesis
#14
Abhishek Basu, Arin Bhattacharjee, Rathindranath Baral, Jaydip Biswas, Amalesh Samanta, Sudin Bhattacharya
Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium-based compounds. In addition to its preventive efficacy, studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively toward malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium complex, vanadium(III)-l-cysteine...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28459461/mir-181b-modulates-egfr-dependent-vcam-1-expression-and-monocyte-adhesion-in-glioblastoma
#15
Y-S Liu, H-Y Lin, S-W Lai, C-Y Huang, B-R Huang, P-Y Chen, K-C Wei, D-Y Lu
Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28447667/tweak-blockade-decreases-atherosclerotic-lesion-size-and-progression-through-suppression-of-stat1-signaling-in-diabetic-mice
#16
Valvanera Fernández-Laso, Cristina Sastre, Nerea Méndez-Barbero, Jesús Egido, Jose L Martín-Ventura, Carmen Gómez-Guerrero, Luis M Blanco-Colio
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK/Tnfsf12) is a cytokine implicated in different steps associated with vascular remodeling. However, the role of TWEAK under hyperglycemic conditions is currently unknown. Using two different approaches, genetic deletion of Tnfsf12 and treatment with a TWEAK blocking mAb, we have analyzed the effect of TWEAK inhibition on atherosclerotic plaque progression and stability in streptozotocin-induced diabetic ApoE deficient mice. Genetic inactivation of Tnfsf12 reduced atherosclerosis extension and severity in diabetic ApoE deficient mice...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#17
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mathew, 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...
June 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
#18
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
#19
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
#20
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
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