Browsing by Subject "KIT"

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  • Pulkka, Olli-Pekka; Mpindi, John-Patrick; Tynninen, Olli; Nilsson, Bengt; Kallioniemi, Olli; Sihto, Harri; Joensuu, Heikki (2018)
    The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
  • Jääskeläinen, Anne J.; Sironen, Tarja; Diagne, Cheikh Tidiane; Diagne, Moussa Moise; Faye, Martin; Faye, Oumar; Faye, Ousmane; Hewson, Roger; Mölsä, Markos; Weidmanng, Manfred W.; Watson, Robert; Sall, Amadou Alpha; Vapalahti, Olli (2019)
    Background: During the five decades since their discovery, filoviruses of four species have caused human hemorrhagic fever outbreaks: Marburg (MARV) marburgvirus, and Zaire (EBOV), Sudan (SUDV) and Bundybugyo (BDBV) ebolaviruses. The largest, devastating EBOV epidemic in West Africa in 2014-16, has been followed by outbreaks of MARV in Uganda, 2017, and EBOV in Democratic Republic of Congo, 2018, emphasizing the need to develop preparedness to diagnose all filoviruses. Objectives: The aim of this study was to optimize a new filovirus RT-qPCR to detect all filoviruses, define its limits of detection (LOD) and perform a field evaluation with outbreak samples. Study design: A pan-filovirus RT-qPCR targeting the L gene was developed and evaluated within the EbolaMoDRAD (Ebola virus: modern approaches for developing bedside rapid diagnostics) project. Specificity and sensitivity were determined and the effect of inactivation and PCR reagents (liquid and lyophilized format) were tested. Results: The LODs for the lyophilized pan-filovirus L-RT-qPCR assay were 9.4 copies per PCR reaction for EBOV, 9.9 for MARV, 1151 for SUDV, 65 for BDBV and 289 for Tai Forest virus. The test was set at the Pasteur Institute, Dakar, Senegal, and 83 Ebola patient samples, with viral load ranging from 5 to 5 million copies of EBOV per reaction, were screened. The results for the patient samples were in 100% concordance with the reference EBOVspecific assay. Discussion: Overall, the assay showed good sensitivity and specificity, covered all filoviruses known to be human pathogens, performed well both in lyophilized and liquid-phase formats and with EBOV outbreak clinical samples.
  • Tanoli, ZiaurRehman; Alam, Zaid; Vähä-Koskela, Markus; Ravikumar, Balaguru; Malyutina, Alina; Jaiswal, Alok; Tang, Jing; Wennerberg, Krister; Aittokallio, Tero (2018)
    Drug Target Commons (DTC) is a web platform (database with user interface) for community-driven bioactivity data integration and standardization for comprehensive mapping, reuse and analysis of compound-target interaction profiles. End users can search, upload, edit, annotate and export expert-curated bioactivity data for further analysis, using an application programmable interface, database dump or tab-delimited text download options. To guide chemical biology and drug-repurposing applications, DTC version 2.0 includes updated clinical development information for the compounds and target gene-disease associations, as well as cancer-type indications for mutant protein targets, which are critical for precision oncology developments.
  • Cuadros, Juan; Perez-Tanoira, Ramon; Prieto-Perez, Laura; Martin-Martin, Ines; Berzosa, Pedro; Gonzalez, Vicenta; Tisiano, Gebre; Balcha, Seble; Manuel Ramos, Jose; Gorgolas, Miguel (2015)
    Background In up to one third of the hospitals in some rural areas of Africa, laboratory services in malaria diagnosis are limited to microscopy by thin film, as no capability to perform thick film exists (gold standard in terms of sensitivity for malaria diagnosis). A new rapid molecular malaria diagnostic test called Loop-mediated isothermal DNA amplification (LAMP) has been recently validated in clinical trials showing exceptional sensitivity and specificity features. It could be a reliable diagnostic tool to be implemented without special equipment or training. Objective The objective of this proof of concept study was to confirm the feasibility of using LAMP technique for diagnosis of malaria in a rural Ethiopian hospital with limited resources. Methodology/Principal Findings This study was carried out in Gambo General Hospital, West Arsi Province (Ethiopia), from November 1st to December 31st 2013. A total of 162 patients with a non-focal febrile syndrome were investigated. The diagnostic capability (sensitivity, specificity, positive predictive and negative predictive values) of rapid malaria tests and microscopy by thin film was evaluated in comparison with LAMP. Eleven (6.79%) out of the 162 patients with fever and suspected malaria, tested positive for LAMP, 3 (1.85%) for rapid malaria tests and none of the eleven cases was detected by thin film microscopy. Conclusions/Significance LAMP can be performed in basic rural laboratories without the need for specialized infrastructure and it may set a reliable tool for malaria control to detect a low level parasitemia.
  • Hakala, Kalle (Helsingfors universitet, 2012)
    Tämän lisensiaatintutkielman tavoitteena on selvittää pohjoissuomenkarjan naudoilla esiintyvän gonadien hypoplasian eli sukurauhasten vajaakehittyneisyyden syitä. Sukurauhasten vajaakehittyneisyyden tiedetään johtuvan itusolujen puutteesta sukurauhasissa. Itusolujen puutos on havaittavissa jo varhaisessa sikiönkehityksen vaiheessa ja sen epäillään johtuvan häiriöstä alkuitusolujen soluvaelluksessa. KIT-reseptorin (tunnetaan myös nimellä Ckit tai C-Kit) tiedetään olevan merkittävässä roolissa alkuitusolujen soluvaelluksessa ja nykyisten geenitutkimusmenetelmien avulla pyrittiin selvittämään sen osuutta pohjoissuomenkarjan sukurauhasten vajaakehittyneisyydessä. Yhteensä 303 pohjoissuomenkarjan nautaa tutkittiin kliinisesti sukurauhasten vajaakehittyneisyyden varalta. Sonnien ja sonnivasikoiden tutkimus suoritettiin mittaamalla ja tunnustelemalla niiden kivekset. Lehmillä ja hiehoilla munasarjat tutkittiin rektaalisesti palpoimalla. Lisäksi osalta eläimiä otettiin 9 ml laskimoverta EDTA-putkeen DNA-tutkimusta varten. Lehmillä ja hiehoilla todettiin toinen tai molemmat munasarjat vajaakehittyneiksi, mikäli niiden koko oli hyvin pieni tai ne olivat mahdottomat löytää rektaalitutkimuksessa. Sonneilla kives todettiin vajaakehittyneeksi, jos sen koko oli korkeintaan kolmasosa normaalin kiveksen koosta. Sonnivasikoilla kives todettiin vajaakehittyneeksi, jos sen koko oli korkeintaan puolet normaalin kiveksen koosta. Lisäksi 42 eläimen sukurauhaset tutkittiin teurastuksen tai kliinisen kastraation jälkeen. Vajaakehittyneeksi sukurauhaset todettiin aiemmin kuvatun mukaisesti ja histologisten leikkeiden avulla, jos niistä ei löytynyt sukusoluja tai niiden esiasteita. DNA-näytteet genotyypitettiin 96 naudan osalta Illumina BovineHD sirun ja Illumina's Beadstudio ohjelmiston avulla. Koko genominlaajuista assosiaatiotutkimusta (GWAS) varten naudat jaettiin ryhmiin sairauden ja värityksen mukaan. Tutkituista 345 pohjoissuomenkarjan naudoista 16 eläimellä oli hypoplastiset sukurauhaset. Genotyyppaustulosten mukaan kromosomi 29 oli vahvasti yhteydessä sukurauhasten vajaakehittyneisyyteen ja kopioluvun vaihteluita (CNV) löytyi kaikkiaan 2101 kappaletta ja kromosomista 6 löydetty CNV sisälsi KIT-geenin kokonaisuudessaan. Toinen kromosomista 29 löydetty CNV-segmentti oli GWAS-tutkimuksessa löydetyn alueen välittömässä läheisyydessä. Kromosomista 29 löydetty ektooppinen KIT-geeni liittyy sukurauhasten vajaakehitykseen pohjoissuomenkarjan naudoilla. Löydös on hypoteesin mukainen, mutta tarkkaa sukurauhasten vajaakehityksen syytä ei tutkimuksen tuloksista pystytä määrittelemään.