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Shih-Chi Su, Ming-Ju Hsieh, Yu-Fan Liu, Ying-Erh Chou, Chiao-Wen Lin, Shun-Fa Yang
BACKGROUND: Oral cancer is a common malignancy that is shown to be causally associated with hereditary and acquired factors. ADAMTS14 is a member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin motifs) metalloproteinase family that plays an important role in extracellular matrix (ECM) assembly and degradation. Elevation or deficiency of certain ADAMTS proteinases has been known to be implicated in a wide range of pathological processes including atherosclerosis, arthritis, and cancer...
2016: PloS One
Sumeyya Akyol, Ismail Cömertoğlu, Ridvan Firat, Özlem Çakmak, Yunus Yukselten, Gönül Erden, Veli Ugurcu, Kadir Demircan
Chondrosarcoma is one of the most common bone tumors, and at present, there is no non-invasive treatment option for this cancer. The chondrosarcoma OUMS-27 cell line produces proteoglycan and type II, IX, and XI collagens, which constitutes cartilage tissue. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteases are a group of secreted proteases, which include the procollagen N-proteinases ADAMTS-2, -3 and -14. These procollagen N-proteinases perform a role in the processing of procollagens to collagen and the maturation of type I collagen...
August 2015: Oncology Letters
Hanga Galfalvy, Fatemeh Haghighi, Colin Hodgkinson, David Goldman, Maria A Oquendo, Ainsley Burke, Yung-Yu Huang, Ina Giegling, Dan Rujescu, Alexandre Bureau, Gustavo Turecki, J John Mann
Genome wide array studies have reported limited success in identifying genetic markers conferring risk for suicidal behavior (SB). This may be attributable to study designs with primary outcome other than SB. We performed a GWAS on suicides and cases with a history of nonfatal suicide attempts compared with psychiatric controls and healthy volunteers. A consortium of USA, Canadian and German teams assembled two groups of cases (suicide attempters and suicides, N = 577) and non-attempter psychiatric and healthy controls (N = 1,233)...
October 2015: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Sergio Alonso, Yuichi Dai, Kentaro Yamashita, Shina Horiuchi, Tomoko Dai, Akihiro Matsunaga, Rosa Sánchez-Muñoz, Cristina Bilbao-Sieyro, Juan Carlos Díaz-Chico, Andrei V Chernov, Alex Y Strongin, Manuel Perucho
Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0...
February 20, 2015: Oncotarget
T Poonpet, S Honsawek, N Tammachote, S Kanitnate, R Tammachote
Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. This disease is characterized by breakdown and loss of articular cartilage due to genetic, mechanical and environmental factors. Although the pathophysiology of OA is not completely known, several candidate genes have been reported to be associated with OA susceptibility. We assessed the association between genetic variation in the ADAMTS14 region and knee osteoarthritis susceptibility in the Thai population. The rs4747096 SNP was genotyped by PCR-RFLP on genomic DNA extracted from peripheral blood of 108 OA patients and 119 controls...
2013: Genetics and Molecular Research: GMR
Nynke A Hosper, Ruud A Bank, Paul P van den Berg
In spina bifida, the neural tube fails to close during the embryonic period. Exposure of the neural tube to the amniotic fluid during pregnancy causes additional neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a neural tube defect (NTD) share the same characteristics as AFMCs from a healthy fetus...
March 1, 2014: Stem Cells and Development
Louis El Khoury, Michael Posthumus, Malcolm Collins, Christopher J Handley, Jill Cook, Stuart M Raleigh
OBJECTIVES: Achilles tendon pathology (ATP) is a multifactorial condition for which genetic risk factors have been identified. The ADAMTS, ADAM12 and TIMP2 genes encode enzymes that are important regulators of tendon homeostasis. ADAMTS2 and ADAMTS14 proteins are procollagen N-propeptidases for pro-collagen type I, type II, and type III. ADAMTS2, like COL5A1, has been linked to Ehlers-Danlos syndrome. Variants within ADAMTS5 and ADAM12 have been associated with osteoarthritis. TIMP2, a metalloprotease inhibitor, maintains homeostasis in the ECM by inhibiting ADAM, ADAMTS and MMP functions...
November 2013: Journal of Science and Medicine in Sport
Nader Al Nakouzi, Olivia Bawa, Alain Le Pape, Stéphanie Lerondel, Catherine Gaudin, Paule Opolon, Patrick Gonin, Karim Fizazi, Anne Chauchereau
Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging...
May 2012: Neoplasia: An International Journal for Oncology Research
Iu A Bukurova, S L Nikitina, S L Khankin, G S Krasnov, N A Lisitsin, V L Karpov, S F Beresten'
A new algorithm has been developed for bioinformatics search of putative serum markers of cancer, which includes: 1) identification of microRNAs that are most often and most significantly overexpressed in tumors; 2) selection of mRNA targets regulated by microRNAs; 3) identification of mRNA targets encoding secreted proteins; 4) comparative analysis of mRNA transcription levels in normal and tumor tissues. Application of the algorithm led to discovery of seven putative serum markers of colon cancer: ADAMTS14, ANGPT2, CCL7, DEFA5, MMP11, MMP14, and PLAU...
March 2011: Molekuliarnaia Biologiia
J Rodriguez-Lopez, M Pombo-Suarez, J Loughlin, A Tsezou, F J Blanco, I Meulenbelt, P E Slagboom, A M Valdes, T D Spector, J J Gomez-Reino, A Gonzalez
OBJECTIVE: To investigate the effect in OA (Osteoarthritis) susceptibility of putative damaging changes in ADAM (A Disintegrin And Metalloprotease) and ADAMTS (ADAM with ThromboSpondin motif) proteases. METHODS: Non-synonymous single nucleotide polymorphisms (nsSNP) in 18 ADAMTS and 31 ADAM genes were analyzed with two software applications for prediction of functional damage. Four putative damaging nsSNP were found in ADAMTS2, ADAMTS14, ADAMTS16 and ADAM12, respectively...
March 2009: Osteoarthritis and Cartilage
Phillip Johnston, Debbie Larson, Ian M Clark, Adrian J Chojnowski
PURPOSE: We have previously demonstrated that gene expression levels of matrix metalloproteinases (MMPs), related metalloproteinases "a disintegrin and metalloproteinase with thrombospontin motifs" (ADAMTSs), and tissue inhibitors of metalloproteinases (TIMPs) differed when comparing palmar fascia from 19 patients with Dupuytren's disease (DD) with 19 disease-free controls. We undertook to investigate whether the extent of this altered gene expression was related to clinical outcome. METHODS: All the patients with DD were followed up for an average of 14 months from their primary fasciectomy...
September 2008: Journal of Hand Surgery
Phillip Johnston, Adrian J Chojnowski, Rose K Davidson, Graham P Riley, Simon T Donell, Ian M Clark
PURPOSE: Dupuytren's disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD...
March 2007: Journal of Hand Surgery
Carine Le Goff, Robert P T Somerville, Frederic Kesteloot, Kimerly Powell, David E Birk, Alain C Colige, Suneel S Apte
Mutations in ADAMTS2, a procollagen amino-propeptidase, cause severe skin fragility, designated as dermatosparaxis in animals, and a subtype of the Ehlers-Danlos syndrome (dermatosparactic type or VIIC) in humans. Not all collagen-rich tissues are affected to the same degree, which suggests compensation by the ADAMTS2 homologs ADAMTS3 and ADAMTS14. In situ hybridization of Adamts2, Adamts3 and Adamts14, and of the genes encoding the major fibrillar collagens, Col1a1, Col2a1 and Col3a1, during mouse embryogenesis, demonstrated distinct tissue-specific, overlapping expression patterns of the protease and substrate genes...
April 2006: Development
Matthew E Pipkin, Mathias G Lichtenheld
The study of eukaryotic gene transcription depends on methods to discover distal cis-acting control sequences. Comparative bioinformatics is one powerful strategy to reveal these domains, but still requires conventional wet-bench techniques to elucidate their specificity and function. The DNase I hypersensitivity assay (DHA) is also a method to identify regulatory domains, but can also suggest their function. Technically however, the classical DHA is constrained to mapping gene loci in small increments of approximately 20 kb...
2006: Nucleic Acids Research
Robert Goertsches, Manuel Comabella, Arcadi Navarro, Hector Perkal, Xavier Montalban
ADAMTS14 is a novel member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) metalloproteinase family which processes extracellular matrix proteins. In the present study we performed a comprehensive investigation of the ADAMTS14 as a candidate gene for susceptibility to multiple sclerosis (MS). Eight single nucleotide polymorphisms (SNPs) were analyzed in a case-control study of 287 patients with MS [192 with relapsing-remitting MS (RRMS) and 95 with primary-progressive MS (PPMS)], and 285 age- and sex-matched controls...
July 2005: Journal of Neuroimmunology
Lara Kevorkian, David A Young, Clare Darrah, Simon T Donell, Lee Shepstone, Sarah Porter, Sarah M V Brockbank, Dylan R Edwards, Andrew E Parker, Ian M Clark
OBJECTIVE: To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA). METHODS: Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction...
January 2004: Arthritis and Rheumatism
Santiago Cal, Alvaro J Obaya, María Llamazares, Cecilia Garabaya, Víctor Quesada, Carlos López-Otín
ADAMTS (A Disintegrin And Metalloproteinase domain, with ThromboSpondin type-1 modules) is a recently described family of zinc-dependent proteases which play important roles in a variety of normal and pathological conditions, including arthritis and cancer. In this work, we report the identification and cloning of cDNAs encoding seven new human ADAMTSs. These novel enzymes have been called ADAMTS-13, -14, -15, -16, -17, -18, and -19. All of them show a domain organization similar to that of previously characterized family members, consisting of a signal sequence, a propeptide, a metalloproteinase domain, a disintegrin-like domain, a cysteine-rich region, and a variable number of TS-1 repeats...
January 23, 2002: Gene
H Bolz, A Ramírez, B von Brederlow, C Kubisch
ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) proteins constitute a family of zinc metalloproteinases which target and process extracellular matrix proteins. We cloned and characterized a novel human ADAMTS gene, ADAMTS14, which is located on human chromosome 10q2. ADAMTS14 exhibits the characteristic multidomain structure of ADAMTS proteins including four thrombospondin modules and shows highest similarity to ADAMTS3 and ADAMTS2. By RT-PCR analysis we demonstrated that ADAMTS14 is expressed in human retina and also at low levels in adult brain, lung and placenta...
December 30, 2001: Biochimica et Biophysica Acta
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