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Anirudh Sattiraju, Kiran Kumar Solingapuram Sai, Ang Xuan, Darpan N Pandya, Frankis G Almaguel, Thaddeus J Wadas, Denise M Herpai, Waldemar Debinski, Akiva Mintz
Glioblastoma (GBM) is the most aggressive primary malignant brain cancer that invariably results in a dismal prognosis. Chemotherapy and radiotherapy have not been completely effective as standard treatment options for patients due to recurrent disease. We and others have therefore developed molecular strategies to specifically target interleukin 13 receptor alpha 2 (IL13RA2), a GBM restricted receptor expressed abundantly on over 75% of GBM patients. In this work, we evaluated the potential of Pep-1L, a novel IL13RA2 targeted peptide, as a platform to deliver targeted lethal therapies to GBM...
June 27, 2017: Oncotarget
Mahavir Singh, Suresh C Tyagi
AIM: To test whether homocysteine (Hcy) can influence the transcriptional profile, we hypothesized that Hcy can lead to the induction of proinflammatory molecules in the retinal cells of aging people. METHODS: An unbiased in vitro inflammatory pathway focused study was designed employing retinal pigment epithelial (RPE) cell line, ARPE-19. Cells were cultured in the presence or absence of Hcy to capture target genes' expression profile. Three different concentrations of Hcy were added in the culture medium of confluent monolayers...
2017: International Journal of Ophthalmology
Kiran Kumar Solingapuram Sai, Anirudh Sattiraju, Frankis G Almaguel, Ang Xuan, Stephanie Rideout, Rahul S Krishnaswamy, JoAnn Zhang, Denise M Herpai, Waldemar Debinski, Akiva Mintz
Peptides that target cancer cell surface receptors are promising platforms to deliver diagnostic and therapeutic payloads specifically to cancer but not normal tissue. IL13RA2 is a tumor-restricted receptor found to be present in several aggressive malignancies, including in the vast majority of high-grade gliomas and malignant melanoma. This receptor has been successfully targeted for diagnostic and therapeutic purposes using modified IL-13 ligand and more recently using a specific peptide, Pep-1L. In the current work, we establish the in vitro and in vivo tumor binding properties of radiolabeled Pep-1L, designed for tumor imaging...
March 24, 2017: Oncotarget
Michael J Rosen, Rebekah Karns, Jefferson E Vallance, Ramona Bezold, Amanda Waddell, Margaret H Collins, Yael Haberman, Phillip Minar, Robert N Baldassano, Jeffrey S Hyams, Susan S Baker, Richard Kellermayer, Joshua D Noe, Anne M Griffiths, Joel R Rosh, Wallace V Crandall, Melvin B Heyman, David R Mack, Michael D Kappelman, James Markowitz, Dedrick E Moulton, Neal S Leleiko, Thomas D Walters, Subra Kugathasan, Keith T Wilson, Simon P Hogan, Lee A Denson
BACKGROUND & AIMS: There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes...
May 2017: Gastroenterology
Phillip Dettleff, Thomas Moen, Nina Santi, Victor Martinez
The infectious salmon anemia virus (ISAv) produces a systemic infection in salmonids, causing large losses in salmon production. However, little is known regarding the mechanisms exerting disease resistance. In this paper, we perform an RNA-seq analysis in Atlantic salmon challenged with ISAv (using individuals coming from families that were highly susceptible or highly resistant to ISAv infection). We evaluated the differential expression of both host and ISAv genes in a target organ for the virus, i.e. the spleen...
February 2017: Fish & Shellfish Immunology
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
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