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https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#1
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28192407/ttf-1-nkx2-1-binds-to-ddb1-and-confers-replication-stress-resistance-to-lung-adenocarcinomas
#2
Z Liu, K Yanagisawa, S Griesing, M Iwai, K Kano, N Hotta, T Kajino, M Suzuki, T Takahashi
TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28160756/receptor-tyrosine-kinase-like-orphan-receptor-1-ror-1-an-emerging-target-for-diagnosis-and-therapy-of-chronic-lymphocytic-leukemia
#3
REVIEW
Leili Aghebati-Maleki, Mahdi Shabani, Behzad Baradaran, Morteza Motallebnezhad, Jafar Majidi, Mehdi Yousefi
Chronic lymphocytic leukemia (CLL) is characterized by reposition of malignant B cells in the blood, bone marrow, spleen and lymph nodes. It remains the most common leukemia in the Western world. Within the recent years, major breakthroughs have been made to prolong the survival and improve the health of patients. Despite these advances, CLL is still recognized as a disease without definitive cure. New treatment approaches, based on unique targets and novel drugs, are highly desired for CLL therapy. The Identification and subsequent targeting of molecules that are overexpressed uniquely in malignant cells not normal ones play critical roles in the success of anticancer therapeutic strategies...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28139652/lnc-ing-ror1-her3-and-hippo-signalling-in-metastasis
#4
Wei Zhuo, Yibin Kang
Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1-HER3 and Hippo-YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28128766/isolation-and-characterization-of-anti-ror1-single-chain-fragment-variable-antibodies-using-phage-display-technique
#5
Leili Aghebati-Maleki, Vahid Younesi, Farhad Jadidi-Niaragh, Behzad Baradaran, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR1) belongs to one of the families of receptor tyrosine kinases (RTKs). RTKs are involved in the various physiologic cellular functions including proliferation, migration, survival, signaling and differentiation. Several RTKs are deregulated in various cancers implying the targeting potential of these molecules in cancer therapy. ROR1 has recently been shown to be expressed in various types of cancer cells but not in normal adult cells. Hence a molecular inhibitor of extracellular domain of ROR1 that inhibits ROR1-cell surface interaction is of great therapeutic importance...
2017: Human Antibodies
https://www.readbyqxmd.com/read/28125717/epigenetic-alterations-affecting-transcription-factors-and-signaling-pathways-in-stromal-cells-of-endometriosis
#6
Iveta Yotova, Emily Hsu, Catherine Do, Aulona Gaba, Matthias Sczabolcs, Sabine Dekan, Lukas Kenner, Rene Wenzl, Benjamin Tycko
Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains...
2017: PloS One
https://www.readbyqxmd.com/read/28114269/a-ror1-her3-lncrna-signalling-axis-modulates-the-hippo-yap-pathway-to-regulate-bone-metastasis
#7
Chunlai Li, Shouyu Wang, Zhen Xing, Aifu Lin, Ke Liang, Jian Song, Qingsong Hu, Jun Yao, Zhongyuan Chen, Peter K Park, David H Hawke, Jianwei Zhou, Yan Zhou, Shuxing Zhang, Han Liang, Mien-Chie Hung, Gary E Gallick, Leng Han, Chunru Lin, Liuqing Yang
Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members. p-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#8
J Yu, L Chen, B Cui, Christina Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf Ii, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27900053/receptor-tyrosine-kinases-in-carcinogenesis
#9
Xiao-Ying Zhang, Pei-Ying Zhang
Receptor tyrosine kinases (RTKs) are cell surface glycoproteins with enzymatic activity involved in the regulation of various important functions. In all-important physiological functions including differentiation, cell-cell interactions, survival, proliferation, metabolism, migration and signaling these receptors are the key players of regulation. Additionally, mutations of RTKs or their overexpression have been described in many human cancers and are being explored as a novel avenue for a new therapeutic approach...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27852699/analysis-of-ror1-protein-expression-in-human-cancer-and-normal-tissues
#10
Ashwini Balakrishnan, Tracy Goodpaster, Julie Randolph-Habecker, Benjamin G Hoffstrom, Florencia G Jalikis, Lisa K Koch, Carolina Berger, Paula L Kosasih, Anusha Rajan, Daniel Sommermeyer, Peggy Porter, Stanley R Riddell
PURPOSE: This study examines cell-surface ROR1 expression in human tumors and normal tissues. ROR1 is considered a promising target for cancer therapy due to putative tumor-specific expression and multiple groups are developing antibodies and/or chimeric antigen receptor-modified T cells to target ROR1. On-target, off-tumor toxicity is a challenge for most non-mutated tumor antigens, however prior studies suggest that ROR1 is absent on most normal tissues. EXPERIMENTAL DESIGN: Our studies show that published antibodies lack sensitivity to detect endogenous levels of cell-surface ROR1 by immunohistochemistry (IHC) in FFPE tissues...
November 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27830754/ror1-is-a-novel-prognostic-biomarker-in-patients-with-lung-adenocarcinoma
#11
Yu-Zhu Zheng, Rui Ma, Jian-Kang Zhou, Cheng-Lin Guo, Yong-Sheng Wang, Zheng-Guang Li, Lun-Xu Liu, Yong Peng
Currently, there is no reliable biomarker to clinically predict the prognosis of lung adenocarcinoma (ADC). The receptor-tyrosine-kinase like orphan receptor 1 (ROR1) is reported to be overexpressed and associated with poor prognosis in several tumors. This study aimed to examine the expression of ROR1 and evaluate its prognostic significance in human lung ADC patients. In this present study, Western blot analysis and immunohistochemistry were performed to characterize expression of ROR1 protein in lung ADC patients...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815263/high-level-ror1-associates-with-accelerated-disease-progression-in-chronic-lymphocytic-leukemia
#12
Bing Cui, Emanuela M Ghia, Liguang Chen, Laura Z Rassenti, Christopher DeBoever, George F Widhopf, Jian Yu, Donna S Neuberg, William G Wierda, Kanti R Rai, Neil E Kay, Jennifer R Brown, Jeffrey A Jones, John G Gribben, Kelly A Frazer, Thomas J Kipps
ROR1 is an oncoembryonic orphan receptor found on chronic lymphocytic leukemia (CLL) B cells, but not on normal postpartum tissues. ROR1 is a receptor for Wnt5a that may complex with TCL1, a coactivator of AKT that is able to promote development of CLL. We found the CLL cells of a few patients expressed negligible ROR1 (ROR1(Neg)), but expressed TCL1A at levels comparable to those of samples that expressed ROR1 (ROR1(Pos)). Transcriptome analyses revealed that ROR1(Neg) cases generally could be distinguished from those that were ROR1(Pos) in unsupervised gene-expression clustering analysis...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27709494/identification-of-noncanonical-wnt-receptors-required-for-wnt-3a-induced-early-differentiation-of-human-neural-stem-cells
#13
Nora Bengoa-Vergniory, Irantzu Gorroño-Etxebarria, Inmaculada López-Sánchez, Michele Marra, Pierluigi Di Chiaro, Robert Kypta
Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27363264/-combination-of-tlr7-agonist-t7-ethacrynic-acid-conjugate-with-ror1-has-a-stronger-anti-breast-cancer-effect
#14
Na Zhang, Guangyi Jin, Zhenchao Jin, Bing Liu, Boya Peng, Ningning Gao, Yunlong Hu, Li Tang
Objective To investigate the synergistic anti-breast cancer effect of Toll-like receptor 7 agonist T7-ethacrynic acid conjugate (T7-EA) in combination with receptor-tyrosine-kinase-like orphan receptor 1 (ROR1). Methods ROR1 cytotoxic T lymphocyte (CTL) epitope was predicted using Syfpeithi online software. Mouse spleen lymphocytes and bone marrow dendritic cells (DCs) were separately stimulated with 4 μmol/L T7-EA and 4 μmol/L ROR1 alone or in combination. ELISA assay was used to measure the levels of interferon-γ (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α)...
July 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27239958/migration-and-invasion-is-inhibited-by-silencing-ror1-and-ror2-in-chemoresistant-ovarian-cancer
#15
C E Henry, E Llamosas, A Djordjevic, N F Hacker, C E Ford
Ovarian cancer survival remains poor despite recent advances in our understanding of genetic profiles. Unfortunately, the majority of ovarian cancer patients have recurrent disease after chemotherapy and lack other treatment options. Wnt signalling has been extensively implicated in cancer progression and chemoresistance. Therefore, we investigated the previously described Wnt receptors ROR1 and ROR2 as regulators of epithelial-to-mesenchymal transition (EMT) in a clinically relevant cell line model. The parental A2780- and cisplatin-resistant A2780-cis cell lines were used as a model of ovarian cancer chemoresistance...
May 30, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27193728/effects-of-pamam-dendrimers-with-various-surface-functional-groups-and-multiple-generations-on-cytotoxicity-and-neuronal-differentiation-using-human-neural-progenitor-cells
#16
Yang Zeng, Yoshika Kurokawa, Tin-Tin Win-Shwe, Qin Zeng, Seishiro Hirano, Zhenya Zhang, Hideko Sone
Polyamidoamine (PAMAM) dendrimers have potential for biological applications as delivery systems for genes, drugs, and imaging agents into the brain, but their developmental neurotoxicity remains unknown. We investigated the effects of PAMAM dendrimers with various surface functional groups and multiple generations on neuronal differentiation using human neural progenitor cells at an equal mass concentration. Only PAMAM dendrimers containing amine (NH2) surface groups at concentrations of 10 μg/mL significantly reduced cell viability and neuronal differentiation, compared with non-amine-terminated dendrimers...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27162350/ror1-is-essential-for-proper-innervation-of-auditory-hair-cells-and-hearing-in-humans-and-mice
#17
Oscar Diaz-Horta, Clemer Abad, Levent Sennaroglu, Joseph Foster, Alexandra DeSmidt, Guney Bademci, Suna Tokgoz-Yilmaz, Duygu Duman, F Basak Cengiz, M'hamed Grati, Suat Fitoz, Xue Z Liu, Amjad Farooq, Faiqa Imtiaz, Benjamin B Currall, Cynthia Casson Morton, Michiru Nishita, Yasuhiro Minami, Zhongmin Lu, Katherina Walz, Mustafa Tekin
Hair cells of the inner ear, the mechanosensory receptors, convert sound waves into neural signals that are passed to the brain via the auditory nerve. Little is known about the molecular mechanisms that govern the development of hair cell-neuronal connections. We ascertained a family with autosomal recessive deafness associated with a common cavity inner ear malformation and auditory neuropathy. Via whole-exome sequencing, we identified a variant (c.2207G>C, p.R736T) in ROR1 (receptor tyrosine kinase-like orphan receptor 1), cosegregating with deafness in the family and absent in ethnicity-matched controls...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27153396/analyzing-somatic-genome-rearrangements-in-human-cancers-by-using-whole-exome-sequencing
#18
Lixing Yang, Mi-Sook Lee, Hengyu Lu, Doo-Yi Oh, Yeon Jeong Kim, Donghyun Park, Gahee Park, Xiaojia Ren, Christopher A Bristow, Psalm S Haseley, Soohyun Lee, Angeliki Pantazi, Raju Kucherlapati, Woong-Yang Park, Kenneth L Scott, Yoon-La Choi, Peter J Park
Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using >4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions. We find that the 5' fusion partners of functional fusions are often housekeeping genes, whereas the 3' fusion partners are enriched in tyrosine kinases...
May 5, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27126945/-down-regulation-of-receptor-tyrosine-kinase-like-orphan-receptor-1-suppresses-cell-growth-and-enhances-apoptosis-in-human-colorectal-carcinoma
#19
Wenqi Ma, Xin He, Hongli Zhang, Ting Liu, Xiaolei Feng, Qi Zhou
OBJECTIVE: To investigate the expression of receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) and its role in cell growth in human colorectal carcinoma (CRC). METHODS: Real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of ROR1 in CRC (n=60) and matched tumor-adjacent tissues. The relationship between the expression of ROR1 and clinical features was analyzed by Pearson chi-square test. siRNA was used to down-regulate the expression of ROR1 in SW480 cells in vitro...
May 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27086035/dishevelled-proteins-are-significantly-upregulated-in-chronic-lymphocytic-leukaemia
#20
Abdul Salam Khan, Mohammad Hojjat-Farsangi, Amir Hossein Daneshmanesh, Lotta Hansson, Parviz Kokhaei, Anders Österborg, Håkan Mellstedt, Ali Moshfegh
Dishevelled (DVL) proteins are components of the Wnt signalling pathways, and increased expression is associated with various malignancies. Information on DVLs in chronic lymphatic leukaemia (CLL) is limited. The aim of the present study was to investigate the role of DVLs in CLL cells and association with Wnt pathways downstream of ROR1. DVL1, 2 and 3 were exclusively expressed in CLL cells as compared to normal peripheral blood mononuclear cells (PBMCs). The expression of DVL1 and DVL3 proteins was significantly more pronounced in progressive than in non-progressive disease (p < 0...
September 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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