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Christoph Hölscher, Lisa Heitmann, Ellis Owusu-Dabo, Rolf D Horstmann, Christian G Meyer, Stefan Ehlers, Thorsten Thye
The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB...
2016: Mediators of Inflammation
Sandra N Freiberger, Phil F Cheng, Guergana Iotzova-Weiss, Johannes Neu, Qinxiu Liu, Piotr Dziunycz, John R Zibert, Reinhard Dummer, Kresten Skak, Mitchell P Levesque, Günther F L Hofbauer
Squamous cell carcinoma (SCC) is the second most common human skin cancer and the second leading cause of skin cancer-related death. Recently, a new compound, ingenol mebutate, was approved for treatment of actinic keratosis, a precursor of SCC. As the mechanism of action is poorly understood, we have further investigated the mechanism of ingenol mebutate-induced cell death. We elucidate direct effects of ingenol mebutate on primary keratinocytes, patient-derived SCC cells, and a SCC cell line. Transcriptional profiling followed by pathway analysis was performed on ingenol mebutate-treated primary keratinocytes and patient-derived SCC cells to find key mediators and identify the mechanism of action...
September 2015: Molecular Cancer Therapeutics
Noboru Shibasaki, Toshinari Yamasaki, Toru Kanno, Ryuichiro Arakaki, Hiromasa Sakamoto, Noriaki Utsunomiya, Takahiro Inoue, Tatsuaki Tsuruyama, Eijiro Nakamura, Osamu Ogawa, Tomomi Kamba
Vascular endothelial growth factor (VEGF) and mammalian target of rapamycin are well-known therapeutic targets for renal cell carcinoma (RCC). Sunitinib is an agent that targets VEGF receptors and is considered to be a standard treatment for metastatic or unresectable clear cell RCC (ccRCC). However, ccRCC eventually develops resistance to sunitinib in most cases, and the mechanisms underlying this resistance are not fully elucidated. In the present study, we established unique primary xenograft models, KURC1 (Kyoto University Renal Cancer 1) and KURC2, from freshly isolated ccRCC specimens...
2015: PloS One
L Evenepoel, F H Van Nederveen, L Oudijk, T G Papathomas, D F Restuccia, E J T Belt, G J H Franssen, R A Feelders, S Van Eeden, H Timmers, W W De Herder, S Aydin, M Vikkula, R R De Krijger, W N M Dinjens, A Persu, E Korpershoek
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGL) are relatively rare and mostly benign tumours. Approximately 10% of PPGL are malignant, as defined by the presence of metastases, i.e chromaffin tissue at a location that usually does not contain chromaffin cells. However, up to 35% of tumours in patients carrying an SDHB mutation appears to be malignant. Nowadays, no reliable marker allows to predict whether a PPGL is, or will become malignant. In addition, there are no curative treatments if metastases occur...
June 2015: Journal of Hypertension
D O Minchenko, V V Davydov, O A Budreiko, O S Moliavko, D K Kulieshova, O V Tiazhka, O H Minchenko
The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. We studied the expression of the subset of genes, which responsible for control of cell growth and glucose metabolism, in blood cells of obese boys with normal and impaired insulin sensitivity as well as in normal (control) individuals. It was shown that obesity with normal insulin sensitivity enhances the expression of IRS1, RIPK2, IL13RA2, RSPO1, IQSEC, and CCN2 genes but decreases the expression level IRS2 and DNAJC15 genes in the blood cells as compared to control group...
2015: Fiziolohichnyĭ Zhurnal
Michelle Cotterchio, Elizabeth Lowcock, Zoe Bider-Canfield, Mathieu Lemire, Celia Greenwood, Steven Gallinger, Thomas Hudson
BACKGROUND: Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. METHODS: A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls...
2015: PloS One
Viktor Soukup, Marta Kalousová, Otakar Capoun, Roman Sobotka, Zuzana Breyl, Michael Pešl, Tomas Zima, Tomáš Hanuš
OBJECTIVES: To determine the combination of urinary protein markers for noninvasive detection of primary and recurrent urothelial bladder carcinomas. METHODS: Urinary concentrations of 27 biomarkers (NSE, ATT, AFABP, Resistin, Midkine, Clusterin, Uromodulin, ZAG2, HSP27, HSP 60, NCAM1/CD56, Angiogenin, Calreticulin, Chromogranin A, CEACAM1, CXCL1, IL13Ra2, Progranulin, VEGFA, CarbAnhydIX, Annexin-V, TIM4, Galectin1, Cystatin B, Synuclein G, ApoA1 and ApoA2) were assessed by enzyme-linked immunosorbent assay or by electrochemiluminiscence immunoassay...
2015: Urologia Internationalis
Juan F Sánchez Muñoz-Torrero, Maria D Rivas, Jose Zamorano, Rodrigo Alonso, Pedro Joya-Vazquez, Teresa Padró, Pedro Mata
BACKGROUND: Interleukin-4 (IL-4) has been linked with atherogenic effects and some single nucleotide polymorphisms (SNPs) of the IL4/13 receptors (ILR4/13) have been associated with enhanced response to IL-4. OBJECTIVES: We investigated the frequency of SNP ILR4/13 in patients with familial hypercholesterolemia (FH) compared with control relatives without FH and their possible association with cardiovascular disease (CVD). METHODS: ILR4/13 polymorphisms were studied in 626 subjects included in the Spanish FH cohort, 408 patients with FH and 218 healthy relative control subjects...
July 2014: Journal of Clinical Lipidology
D Tews, V Schwar, M Scheithauer, T Weber, T Fromme, M Klingenspor, T F Barth, P Möller, K Holzmann, K M Debatin, P Fischer-Posovszky, M Wabitsch
Brown and white adipocytes have been shown to derive from different progenitors. In this study we sought to clarify the molecular differences between human brown and white adipocyte progenitors cells. To this end, we performed comparative gene array analysis on progenitor cells isolated from paired biopsies of deep and subcutaneous neck adipose tissue from individuals (n = 6) undergoing neck surgery. Compared with subcutaneous neck progenitors, cells from the deep neck adipose tissue displayed marked differences in gene expression pattern, including 355 differentially regulated (>1...
September 2014: Molecular and Cellular Endocrinology
Ayumu Taguchi, Allen D Taylor, Jaime Rodriguez, Müge Celiktaş, Hui Liu, Xiaotu Ma, Qing Zhang, Chee-Hong Wong, Alice Chin, Luc Girard, Carmen Behrens, Wan L Lam, Stephen Lam, John D Minna, Ignacio I Wistuba, Adi F Gazdar, Samir M Hanash
Cancer/testis (CT) antigens are potential immunotherapeutic targets in cancer. However, the expression of particular antigens is limited to a subset of tumors of a given type. Thus, there is a need to identify antigens with complementary expression patterns for effective therapeutic intervention. In this study, we searched for genes that were distinctly expressed at a higher level in lung tumor tissue and the testes compared with other nontumor tissues and identified members of the VCX/Y gene family as novel CT antigens...
September 1, 2014: Cancer Research
Dan Wu, Weipin Tan, Qiuli Zhang, Xuchao Zhang, Hong Song
OBJECTIVE: To explore the possible link between ozone and asthma through analyzing Th1/Th2 differentiation of T cells following incubation with conditioned medium from the BEAS-2B cells exposed to ozone in vitro. METHOD: Bronchial epithelial cell line, BEAS-2B, was cultured using an air-liquid interface culture system in a CO2 incubator and exposed to 0 or 0.16 or 0.25 mg/m3 of ozone for 8 h. The amounts of IL-1β, IL-6 and RANTES in the cell supernatant were detected...
March 2014: Asian Pacific Journal of Allergy and Immunology
Rachel E Beard, Daniel Abate-Daga, Shannon F Rosati, Zhili Zheng, John R Wunderlich, Steven A Rosenberg, Richard A Morgan
PURPOSE: The success of immunotherapy for the treatment of metastatic cancer is contingent on the identification of appropriate target antigens. Potential targets must be expressed on tumors but show restricted expression on normal tissues. To maximize patient eligibility, ideal target antigens should be expressed on a high percentage of tumors within a histology and, potentially, in multiple different malignancies. DESIGN: A Nanostring probeset was designed containing 97 genes, 72 of which are considered potential candidate genes for immunotherapy...
September 15, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Anton Gossner, Hazel Wilkie, Anagha Joshi, John Hopkins
This study exploited Blackface lambs that varied in their resistance to the abomasal nematode parasite, Teladorsagia circumcincta. Infection of these lambs over 3 months identified susceptible (high adult worm count, high faecal egg count and low IgA antibody) and resistant animals that had excluded all parasites. Previous work had shown that susceptibility and resistance is dependent on the differential immune response to the parasite, which occurs within the abomasal (gastric) lymph node (ALN) that drains the site of infection...
2013: Veterinary Research
Amina Toumi, O Abida, M Ben Ayed, A Masmoudi, H Turki, H Masmoudi
Polymorphism in the genes of TH2 cytokines and/or theirs receptors can influence serum cytokine levels in and the switch to the pathologic IgG4 auto-antibodies. In order to underline the role of these genes in the aethiopathogenesis of Pemphigus Foliaceus, we conduct a familial and a case control studies including 80 Tunisian patients, 147 related subjects and 160 matched healthy controls. We investigated, by PCR-RFLP technique, seven nucleotide polymorphisms: rs2243250 in promoter region of IL4 gene, rs47877948, rs3024530 and rs30246223 in the IL4R gene, rs1881457and rs205412 SNPs in IL13 gene and rs535036 in IL13RA2 gene...
May 2013: Human Immunology
Lisa G Johnson, Stephen M Schwartz, Mari Malkki, Qin Du, Effie W Petersdorf, Denise A Galloway, Margaret M Madeleine
BACKGROUND: Human papillomavirus is the acknowledged cause of cervical cancer. We hypothesized that allergies, characterized by hyperimmune reaction to common allergens and which have been associated with various cancers, may be related to cervical cancer, and that genetic variation in cytokine genes related to allergies might impact cervical cancer risk. METHODS: We investigated the risk of invasive squamous cell cervical cancer (SCC) associated with self-reported allergies and with variation in allergy-related cytokine genes using data from a case-control study (561 cases, 1,258 controls) conducted in Washington State...
January 2011: Cancer Epidemiology, Biomarkers & Prevention
Sheau-Fang Ng, Ruby C Y Lin, D Ross Laybutt, Romain Barres, Julie A Owens, Margaret J Morris
The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell 'dysfunction' in rat F(1) female offspring...
October 21, 2010: Nature
Matthew J Burton, Saul N Rajak, Julien Bauer, Helen A Weiss, Sonda B Tolbert, Alice Shoo, Esmail Habtamu, Alphaxard Manjurano, Paul M Emerson, David C W Mabey, Martin J Holland, Robin L Bailey
Trachoma is a poorly understood immunofibrogenic disease process, initiated by Chlamydia trachomatis. Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with [TTI] or without [TT] inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and C. trachomatis PCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI, n = 13; TT, n = 15; C, n =14)...
January 2011: Infection and Immunity
Matthias Hecker, Zbigniew Zaslona, Grazyna Kwapiszewska, Gero Niess, Anna Zakrzewicz, Eduard Hergenreider, Jochen Wilhelm, Leigh M Marsh, Daniel Sedding, Walter Klepetko, Jürgen Lohmeyer, Stefanie Dimmeler, Werner Seeger, Norbert Weissmann, Ralph T Schermuly, Nikolaus Kneidinger, Oliver Eickelberg, Rory E Morty
RATIONALE: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary artery smooth muscle cell (paSMC) hyperplasia. Inflammation is proposed to play a role in vessel remodeling associated with IPAH. IL-13 is emerging as a regulator of tissue remodeling; however, the contribution of the IL-13 system to IPAH has not been assessed. OBJECTIVES: The objective of this study was to assess the possible contribution of the IL-13 system to IPAH...
September 15, 2010: American Journal of Respiratory and Critical Care Medicine
Makoto Saka, Takayuki Amano, Koji Kajiwara, Koichi Yoshikawa, Makoto Ideguchi, Sadahiro Nomura, Hirosuke Fujisawa, Shoichi Kato, Masami Fujii, Koji Ueno, Yuji Hinoda, Michiyasu Suzuki
OBJECT: The Il13ra2 gene is often overexpressed in brain tumors, making Il13ra2 one of the vaccine targets for immunotherapy of glioma. In this study, using a mouse glioma model, the authors tested the hypothesis that vaccination using dendritic cells transfected with Il13ra2 mRNA induces strong immunological antitumor effects. METHODS: A plasmid was constructed for transduction of the mRNAs transcribed in vitro into dendritic cells. This was done to transport the intracellular protein efficiently into major histocompatibility complex class II compartments by adding a late endosomal/lysosomal sorting signal to the Il13ra2 gene...
August 2010: Journal of Neurosurgery
B Beghé, I P Hall, S G Parker, M F Moffatt, A Wardlaw, M J Connolly, L M Fabbri, C Ruse, I Sayers
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. METHODS: Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6- were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992)...
April 2010: Allergy
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