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Martin G Klatt, Daniel J Kowalewski, Heiko Schuster, Moreno Di Marco, Jörg Hennenlotter, Arnulf Stenzl, Hans-Georg Rammensee, Stefan Stevanović
Despite recent advances in immunotherapy of renal cell carcinoma (RCC), peptide vaccination strategies still lack an approach for personalized peptide vaccination that takes intra- and inter-tumoral heterogeneity and biological characteristics into account. In this study, we use an immunoprecipitation and mass spectrometry-based approach supplemented by network analysis of HLA ligands to target this goal. By analyzing HLA-presented peptides for HLA class I and II of 11 malignant and 6 non-malignant kidney tissue samples, more than 2,700 peptides and 1,600 corresponding source proteins were identified...
August 2016: Oncoimmunology
Charlotte Gistelinck, Paul Eckhard Witten, Ann Huysseune, Sofie Symoens, Fransiska Malfait, Daria Larionova, Pascal Simoens, Manuel Dierick, Luc Van Hoorebeke, Anne De Paepe, Ronald Y Kwon, MaryAnn Weis, David R Eyre, Andy Willaert, Paul J Coucke
Bruck syndrome (BS) is a disorder characterized by joint flexion contractures and skeletal dysplasia that shows strong clinical overlap with the brittle bone disease Osteogenesis Imperfecta (OI). BS is caused by bi-allelic mutations in either the FKBP10 or the PLOD2 gene. PLOD2 encodes the lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of lysine residues in fibrillar collagen telopeptides. This hydroxylation directs cross-linking of collagen fibrils in the extracellular matrix, which is necessary to provide stability and tensile integrity to the collagen fibrils...
August 19, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Nienke Grotenhuis, Samantha F H De Witte, Gerjo J V M van Osch, Yves Bayon, Johan F Lange, Yvonne M Bastiaansen-Jenniskens
BACKGROUND: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. MATERIALS AND METHODS: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture...
September 2016: Tissue Engineering. Part A
Carina Cohen, Mariana Ferreira Leal, Paulo Santoro Belangero, Eduardo Antônio Figueiredo, Marília Cardoso Smith, Carlos Vicente Andreoli, Alberto de Castro Pochini, Moises Cohen, Benno Ejnisman, Flávio Faloppa
OBJECTIVES: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated. METHODS: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy...
July 2016: Clinics
K Miyamoto, N Seki, R Matsushita, M Yonemori, H Yoshino, M Nakagawa, H Enokida
BACKGROUND: Previous studies have revealed that miR-26a-5p and miR-26b-5p act as tumour suppressors in various types of cancer tissues. Here, we aimed to investigate the functional roles of these miRNAs and to identify their regulatory targets in bladder cancer (BC). METHODS: We performed functional assays in BC cells using transfection of mature microRNAs (miRNAs). In silico and luciferase reporter analyses were applied to identify target genes of these miRNAs...
July 26, 2016: British Journal of Cancer
Carla M Kaneto, Patrícia S P Lima, Dalila Lucíola Zanette, Thiago Yukio Kikuchi Oliveira, Francisco de Assis Pereira, Julio Cesar Cetrulo Lorenzi, Jane Lima Dos Santos, Karen L Prata, João M Pina Neto, Francisco J A de Paula, Wilson A Silva
BACKGROUND: Osteogenesis Imperfecta (OI) (OMIM %259450) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. The majority of OI cases are caused by mutations in COL1A1 or COL1A2. Bruck Syndrome (BS) is a further recessively-inherited OI-like phenotype in which bone fragility is associated with the unusual finding of pterygia and contractures of the large joints. Notably, several studies have failed to show any abnormalities in the biosynthesis of collagen 1 in BS patientes...
2016: BMC Medical Genetics
Akira Kurozumi, Mayuko Kato, Yusuke Goto, Ryosuke Matsushita, Rika Nishikawa, Atsushi Okato, Ichiro Fukumoto, Tomohiko Ichikawa, Naohiko Seki
Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis...
May 2016: International Journal of Oncology
Masafumi Sada, Kenoki Ohuchida, Kohei Horioka, Takashi Okumura, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura
Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture...
March 28, 2016: Cancer Letters
Daniela Pankova, Yulong Chen, Masahiko Terajima, Mark J Schliekelman, Brandi N Baird, Monica Fahrenholtz, Li Sun, Bartley J Gill, Tegy J Vadakkan, Min P Kim, Young-Ho Ahn, Jonathon D Roybal, Xin Liu, Edwin Roger Parra Cuentas, Jaime Rodriguez, Ignacio I Wistuba, Chad J Creighton, Don L Gibbons, John M Hicks, Mary E Dickinson, Jennifer L West, K Jane Grande-Allen, Samir M Hanash, Mitsuo Yamauchi, Jonathan M Kurie
UNLABELLED: Intratumoral collagen cross-links heighten stromal stiffness and stimulate tumor cell invasion, but it is unclear how collagen cross-linking is regulated in epithelial tumors. To address this question, we used Kras(LA1) mice, which develop lung adenocarcinomas from somatic activation of a Kras(G12D) allele. The lung tumors in Kras(LA1) mice were highly fibrotic and contained cancer-associated fibroblasts (CAF) that produced collagen and generated stiffness in collagen gels...
March 2016: Molecular Cancer Research: MCR
Masum M Mia, Ruud A Bank
Excessive accumulation of a collagen-rich extracellular matrix (ECM) by myofibroblasts is a characteristic feature of fibrosis, a pathological state leading to serious organ dysfunction. Transforming growth factor beta1 (TGFβ1) is a strong inducer of myofibroblast formation and subsequent collagen production. Currently, there are no remedies for the treatment of fibrosis. Activation of the nuclear factor kappa B (NF-κB) pathway by phosphorylating IκB with the enzyme IκB kinase (IKK) plays a major role in the induction of fibrosis...
December 2015: Journal of Cellular and Molecular Medicine
Paulo Santoro Belangero, Mariana Ferreira Leal, Carina Cohen, Eduardo Antônio Figueiredo, Marília Cardoso Smith, Carlos Vicente Andreoli, Alberto de Castro Pochini, Benno Ejnisman, Moises Cohen
The molecular alterations involved in the capsule deformation presented in shoulder instability patients are poorly understood. Increased TGFβ1 acts as a signal for production of matrix macromolecules by fibrogenic cells at joint injury sites. TGFβ1, through its receptor TGFβR1, regulates genes involved in collagen cross-linking, such as LOX, PLOD1, and PLOD2. We evaluated TGFβ1, TGFβR1, LOX, PLOD1, and PLOD2 gene expression in the antero-inferior (macroscopically injured region), antero-superior and posterior regions of the glenohumeral capsule of 29 shoulder instability patients and eight controls...
March 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
A Tsezou
Recent developments in genetics/genomics of osteoarthritis (OA) are discussed to improve our understanding of OA pathophysiology. The discovery of a novel variant near the NCOA3 (nuclear receptor coactivator 3) gene associated with hip OA and the regulation of GDF5 gene by four transcription factors via the OA susceptibility locus rs143383 are among important findings in OA genetics. Several microarray-based gene expression studies were published for different tissues of the joint. In OA synovium elevation of collagens and cross-linking enzymes (COL1A1, COL5A1, PLOD2, LOX and TIMP1) responsive to TGF-β was found as well as differential expression pattern between different areas of the osteoarthritic synovial membrane...
December 2014: Osteoarthritis and Cartilage
Michaela Tausendschön, Michael Rehli, Nathalie Dehne, Christian Schmidl, Claudia Döring, Martin-Leo Hansmann, Bernhard Brüne
Macrophages (MΦ) often accumulate in hypoxic areas, where they significantly influence disease progression. Anti-inflammatory cytokines, such as IL-10, generate alternatively activated macrophages that support tumor growth. To understand how alternative activation affects the transcriptional profile of hypoxic macrophages, we globally mapped binding sites of hypoxia-inducible factor (HIF)-1α and HIF-2α in primary human monocyte-derived macrophages prestimulated with IL-10. 713 HIF-1 and 795 HIF-2 binding sites were identified under hypoxia...
January 2015: Biochimica et Biophysica Acta
Annalisa Nicastri, Marco Gaspari, Rosario Sacco, Laura Elia, Caterina Gabriele, Roberto Romano, Antonia Rizzuto, Giovanni Cuda
Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery...
November 7, 2014: Journal of Proteome Research
Peiran Zhou, Yi Liu, Fang Lv, Min Nie, Yan Jiang, Ou Wang, Weibo Xia, Xiaoping Xing, Mei Li
Bruck syndrome (BS) is an extremely rare form of osteogenesis imperfecta characterized by congenital joint contracture, multiple fractures and short stature. We described the phenotypes of BS in two Chinese patients for the first time. The novel compound heterozygous mutations c.764_772dupACGTCCTCC (p.255_257dupHisValLeu) in exon 5 and c.1405G>T (p.Gly469X) in exon 9 of FKBP10 were identified in one proband. The novel compound heterozygous mutations c.1624delT (p.Tyr542Thrfs*18) in exon 14 and c.1880T>C (p...
2014: PloS One
Eugênia R Valadares, Túlio B Carneiro, Paula M Santos, Ana Cristina Oliveira, Bernhard Zabel
OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera...
November 2014: Jornal de Pediatria
Sheng Tan, Keshuo Ding, Rui Li, Weijie Zhang, Gaopeng Li, Xiangjun Kong, Pengxu Qian, Peter E Lobie, Tao Zhu
INTRODUCTION: Estrogen signaling is pivotal in the progression of estrogen receptor positive breast cancer primarily by the regulation of cell survival and proliferation. Micro (mi)RNAs have been demonstrated to be regulated by estrogen to mediate estrogenic effects. Herein, we determined the role of estrogen regulated miR-26 and its underlying molecular mechanisms associated with estrogen receptor (ER)+ breast cancer proliferation. METHODS: The expression of miR-26a and miR-26b was evaluated by real-time quantitative (RT)-PCR...
2014: Breast Cancer Research: BCR
Ana Maria Buga, Claudiu Margaritescu, Claus Juergen Scholz, Eugen Radu, Christine Zelenak, Aurel Popa-Wagner
Despite the obvious clinical significance of post-stroke angiogenesis in aged subjects, a detailed transcriptomic analysis of post-stroke angiogenesis has not yet been undertaken in an aged experimental model. In this study, by combining stroke transcriptomics with immunohistochemistry in aged rats and post-stroke patients, we sought to identify an age-specific gene expression pattern that may characterize the angiogenic process after stroke. We found that both young and old infarcted rats initiated vigorous angiogenesis...
2014: Frontiers in Aging Neuroscience
D F G Remst, A B Blom, E L Vitters, R A Bank, W B van den Berg, E N Blaney Davidson, P M van der Kraan
OBJECTIVE: Synovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor β (TGFβ), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGFβ in OA as a therapeutic intervention for fibrosis is not an option since TGFβ is crucial for cartilage maintenance and repair. Therefore, we undertook the present study to seek targets downstream of TGFβ for preventing OA-related fibrosis without interfering with joint homeostasis...
March 2014: Arthritis & Rheumatology
Thilo J Witsch, Pawel Turowski, Elpidoforos Sakkas, Gero Niess, Simone Becker, Susanne Herold, Konstantin Mayer, István Vadász, Jesse D Roberts, Werner Seeger, Rory E Morty
Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed...
February 2014: American Journal of Physiology. Lung Cellular and Molecular Physiology
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