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Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao, Xingang Li
Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion...
April 4, 2017: Oncotarget
Hongzhi Du, Mao Pang, Xiaoying Hou, Shengtao Yuan, Li Sun
Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis...
April 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ye Song, Shihao Zheng, Jizhou Wang, Hao Long, Luxiong Fang, Gang Wang, Zhiyong Li, Tianshi Que, Yi Liu, Yilei Li, Xi'an Zhang, Weiyi Fang, Songtao Qi
Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo...
March 30, 2017: Oncotarget
Yulong Chen, Masahiko Terajima, Priyam Banerjee, Houfu Guo, Xin Liu, Jiang Yu, Mitsuo Yamauchi, Jonathan M Kurie
Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and -wild-type murine embryonic fibroblasts...
April 5, 2017: Scientific Reports
Emily B Lurier, Donald Dalton, Will Dampier, Pichai Raman, Sina Nassiri, Nicole M Ferraro, Ramakrishan Rajagopalan, Mahdi Sarmady, Kara L Spiller
Alternatively activated "M2" macrophages are believed to function during late stages of wound healing, behaving in an anti-inflammatory manner to mediate the resolution of the pro-inflammatory response caused by "M1" macrophages. However, the differences between two main subtypes of M2 macrophages, namely interleukin-4 (IL-4)-stimulated "M2a" macrophages and IL-10-stimulated "M2c" macrophages, are not well understood. M2a macrophages are characterized by their ability to inhibit inflammation and contribute to the stabilization of angiogenesis...
February 20, 2017: Immunobiology
Belal Neyazi, Levent Tanrikulu, Ludwig Wilkens, Christian Hartmann, Klaus-Peter Stein, Claudia A Dumitru, I Erol Sandalcioglu
BACKGROUND: and Purpose: Brain arteriovenous malformations (bAVM) are severe conditions which can cause severe neurological deficits and mortality. The underlying cellular and molecular mechanisms associated with bAVM growth and rupture still remain unclear. The objective of this study was to explore the potential role of PLOD2 (Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) in the pathophysiology of bAVM. METHODS: Expression and localization of PLOD2 were analyzed on tissue microarrays from bAVM patients (n=60) by immunohistochemistry...
March 6, 2017: World Neurosurgery
Jose A Caparros-Martin, Mona S Aglan, Samia Temtamy, Ghada A Otaify, Maria Valencia, Julián Nevado, Elena Vallespin, Angela Del Pozo, Carmen Prior de Castro, Lucia Calatrava-Ferreras, Pilar Gutierrez, Ana M Bueno, Belen Sagastizabal, Encarna Guillen-Navarro, Maria Ballesta-Martinez, Vanesa Gonzalez, Sarenur Y Basaran, Ruksan Buyukoglan, Bilge Sarikepe, Cecilia Espinoza-Valdez, Francisco Cammarata-Scalisi, Victor Martinez-Glez, Karen E Heath, Pablo Lapunzina, Victor L Ruiz-Perez
BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases...
January 2017: Molecular Genetics & Genomic Medicine
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 biallelic 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 crosslinking of collagen fibrils in the extracellular matrix, which is necessary to provide stability and tensile integrity to the collagen fibrils...
November 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
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