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https://www.readbyqxmd.com/read/29313214/backbone-and-side-chain-chemical-shift-assignments-of-the-kringle-domain-of-human-receptor-tyrosine-kinase-like-orphan-receptor-1-ror1
#1
Xiaofang Ma, Yingying Zhang, Bin Liu, Jiahui Yang, Kaifeng Hu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) expresses at high level in many cancers and has been suggested as a potential therapeutic target. It was reported that the Kringle (KNG) domain of ROR1 extracellular region is involved in ROR1/ROR2 heterooligomerization. Monoantibodies that target KNG domain of ROR1 could induce apoptosis of chronic lymphocytic leukemia cells. Here we present the backbone and side chain assignments of KNG domain of ROR1, which lays a foundation for its further structural and function research...
January 8, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29296874/crosstalk-between-ror1-and-bcr-pathways-defines-novel-treatment-strategies-in-mantle-cell-lymphoma
#2
Hanna Karvonen, David Chiron, Wilhelmiina Niininen, Sara Ek, Mats Jerkeman, Elaheh Moradi, Matti Nykter, Caroline A Heckman, Olli Kallioniemi, Astrid Murumägi, Daniela Ungureanu
Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin B-cell lymphoma with poor prognosis due to drug resistance. Introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has markedly improved MCL therapy outcome, but drug resistance remains a challenge. The selective cell-surface expression of oncogenic receptor tyrosine kinase-like orphan receptor 1 (ROR1) pseudokinase in hematological malignancies has made this receptor a promising candidate for targeted therapy. We sought to identify the molecular mechanism underlying divergent ROR1-mediated apoptotic responses in MCL cell lines and primary samples...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29212222/antitumor-activity-of-a-newly-developed-monoclonal-antibody-against-ror1-in-ovarian-cancer-cells
#3
Zhengna Yin, Mengyun Gao, Sasa Chu, Yiping Su, Chunping Ye, Yiquan Wang, Zhuanqin Pan, Zhuming Wang, Huilin Zhang, Hua Tong, Jin Zhu
Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) is a tyrosine-protein kinase transmembrane receptor and ROR1 overexpression is associated with a poor prognosis in various cancers, including ovarian cancer. Targeting of ROR1 has been evaluated as a novel cancer therapy strategy. This study developed a novel chimeric anti-ROR1 Fab antibody (named ROR1-cFab) and then assessed the antitumor activity of this antibody in ovarian cancer cells, an in vitro model of preclinical cancer therapy. A ROR1-cFab prokaryotic expression vector was constructed from positive fusion cells (splenocytes from mice with high ROR1 immune titers were fused with myeloma cells) after three rounds of sub-clone affinity screening...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29175316/inhibition-of-tumor-growth-by-mouse-ror1-specific-antibody-in-a-syngeneic-mouse-tumor-model
#4
Hadi Hassannia, Mohammad Mehdi Amiri, Farhad Jadidi-Niaragh, Reza Hosseini-Ghatar, Jalal Khoshnoodi, Ramezan-Ali Sharifian, Forough Golsaz-Shirazi, Mahmood Jeddi-Tehrani, Fazel Shokri
INTRODUCTION: Immunotherapy with tumor-associated antigens (TAAs) is a potentially powerful approach to eradicate tumor cells. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) plays a crucial role for survival of tumor cells and is overexpressed in various malignancies. In the present study, we developed a syngeneic mouse tumor model to assess anti-tumor effect of mouse ROR1 specific polyclonal antibody (pAb) in vivo. MATERIALS AND METHODS: Mouse ROR1 specific antibody was produced in rabbit using recombinant ROR1 protein...
November 22, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29122990/expression-of-cobll1-encoding-novel-ror1-binding-partner-is-robust-predictor-of-survival-in-chronic-lymphocytic-leukemia
#5
Hana Plešingerová, Pavlína Janovská, Archana Mishra, Lucie Smyčková, Lucie Poppová, Antonín Libra, Karla Plevová, Petra Ovesná, Lenka Radová, Michael Doubek, Šárka Pavlová, Šárka Pospíšilová, Vítězslav Bryja
Chronic lymphocytic leukemia is a disease with upregulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29113297/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#6
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29070775/expression-of-ror2-associated-with-fibrosis-of-the-submandibular-gland
#7
Daiki Takahashi, Hiroaki Suzuki, Yasumasa Kakei, Kimi Yamakoshi, Yasuhiro Minami, Takahide Komori, Michiru Nishita
The submandibular gland (SMG) is one of the major salivary glands that play important roles for variety of physiological functions, such as digestion of foods, prevention of infection, and lubrication of the mouth. Dysfunction of the SMG, often associated with a salivary inflammation, adversely influences a person's quality of life. However, the mechanism underlying inflammation-driven dysfunction of the SMG is largely unknown. Here, we used a mouse model in which the main excretory duct of the SMG is ligated unilaterally to induce inflammation of the gland and examined the expression of Wnt5a, Ror1 and Ror2 genes, encoding Wnt5a ligand and its cognate receptors, which have been implicated in tissue damage or inflammatory responses in variety of tissues...
October 25, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#8
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29024461/reproducible-diagnosis-of-chronic-lymphocytic-leukemia-by-flow-cytometry-an-european-research-initiative-on-cll-eric-european-society-for-clinical-cell-analysis-escca-harmonisation-project
#9
Andy C Rawstron, Karl-Anton Kreuzer, Asha Soosapilla, Martin Spacek, Olga Stehlikova, Peter Gambell, Neil McIver-Brown, Neus Villamor, Katherina Psarra, Maria Arroz, Raffaella Milani, Javier de la Serna, M Teresa Cedena, Ozren Jaksic, Josep Nomdedeu, Carol Moreno, Gian Matteo Rigolin, Antonio Cuneo, Preben Johansen, Hans E Johnsen, Richard Rosenquist, Carsten Utoft Niemann, Wolfgang Kern, David Westerman, Marek Trneny, Stephen Mulligan, Michael Doubek, Sarka Pospisilova, Peter Hillmen, David Oscier, Michael Hallek, Paolo Ghia, Emili Montserrat
The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as "required" or "recommended" for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate "required" markers using normal peripheral blood was developed...
October 10, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#10
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#11
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo J Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#12
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28790171/the-ror1-receptor-tyrosine-kinase-plays-a-critical-role-in-regulating-satellite-cell-proliferation-during-regeneration-of-injured-muscle
#13
Koki Kamizaki, Ryosuke Doi, Makoto Hayashi, Takeshi Saji, Motoi Kanagawa, Tatsushi Toda, So-Ichiro Fukada, Hsin-Yi Henry Ho, Michael Eldon Greenberg, Mitsuharu Endo, Yasuhiro Minami
The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#14
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28730475/characterization-of-ligand-binding-to-pseudokinases-using-a-thermal-shift-assay
#15
Isabelle S Lucet, James M Murphy
The protocol herein describes a robust and proven method for the measurement of pseudokinase-ligand interaction using a fluorescence-based thermal shift assay (TSA). Pseudokinases are kinase-like proteins that have recently emerged as crucial regulatory modules of signal transduction pathways and may well represent a novel class of drug targets. However, unlike kinases, the regulatory activity of pseudokinases is mainly conferred through protein-protein interactions. Understanding the mechanisms that underlie pseudokinase conformational changes through ligand binding and how such conformational changes can tune signaling pathways is a necessary step to unravel their biological functions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28703283/wnt-signaling-pathways-in-chronic-lymphocytic-leukemia-and-b-cell-lymphomas
#16
REVIEW
Pavlína Janovská, Vítězslav Bryja
In this review, we discuss the intricate roles of the WNT signaling network in the development and progression of mature B cell-derived hematological malignancies, with a focus on chronic lymphocytic leukemia (CLL) and related B cell lymphomas. We review the current literature and highlight the differences between the β-catenin-dependent and independent branches of WNT signaling. Special attention is paid to the role of the non-canonical WNT/Planar cell polarity (PCP) pathway, mediated by the WNT5-ROR1-Dishevelled (DVL) signaling axis in CLL...
July 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28687750/5t4-specific-chimeric-antigen-receptor-modification-promotes-the-immune-efficacy-of-cytokine-induced-killer-cells-against-nasopharyngeal-carcinoma-stem-cell-like-cells
#17
Xueyang Guo, Hang Zheng, Weiren Luo, Qianbing Zhang, Jingxian Liu, Kaitai Yao
Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropriate tumour-associated antigens predominantly expressed on NPC stem cells (NPCSCs) and determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell therapy against NPC. By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues but absent in non-cancerous nasopharyngeal tissues...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28557790/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#18
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28557546/inflammation-associated-dna-methylation-patterns-in-epithelium-of-ulcerative-colitis
#19
Alan Barnicle, Cathal Seoighe, John M Greally, Aaron Golden, Laurence J Egan
Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate <0.2) mapping to 210 genes. From gene expression data from the same epithelial cells, we identified 62 differentially expressed genes with increased expression in the presence of inflammation at prostate cancer susceptibility genes PRAC1 and PRAC2...
August 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28470690/diverse-roles-for-the-ror-family-receptor-tyrosine-kinases-in-neurons-and-glial-cells-during-development-and-repair-of-the-nervous-system
#20
REVIEW
Mitsuharu Endo, Yasuhiro Minami
The Ror-family of receptor tyrosine kinases (RTKs) are involved critically in tissue-genesis and organo-genesis during development. In mammals, Ror1 and Ror2, members of the Ror-family RTKs, have been shown to mediate cell polarity, migration, proliferation, and differentiation through the activation of non-canonical Wnt signaling by acting as receptors or co-receptors for Wnt5a. Nematodes bearing mutations within the cam-1 gene, encoding a Ror2 ortholog, exhibit defects in various developmental processes of the nervous system, including neuronal cell migration, polarization, axonal extension, and synaptic transmission...
May 3, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
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