The Experts below are selected from a list of 50043 Experts worldwide ranked by ideXlab platform
Daniel Hohl - One of the best experts on this subject based on the ideXlab platform.
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novel mutations in the gene encoding secreted Lymphocyte Antigen 6 urokinase type plasminogen activator receptor related protein 1 slurp 1 and description of five ancestral haplotypes in patients with mal de meleda
Journal of Investigative Dermatology, 2003Co-Authors: Slaheddine Marrakchi, Stephanie Audebert, Bakar Bouadjar, Christina Has, Caroline Lefevre, Colin S Munro, Susan Cure, Florence Jobard, Susanne Morlot, Daniel HohlAbstract:Mal de Meleda is a recessive, transgressive palmoplantar keratoderma for which we previously identified mutations in the gene encoding secreted Lymphocyte Antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1). In this report we describe two new mutations: (i) a founder mutation, which changes a conserved cysteine residue to tyrosine (C99Y) in a large inbred Tunisian pedigree, and (ii) a signal sequence mutation (W15R), which was homozygous in a German family and heterozygous in a Scottish patient. Four ancestral haplotypes were observed in 69 patients from countries around the Mediterranean basin, and an additional haplotype was found in the German and Scottish patients.
Jyoti Asundi - One of the best experts on this subject based on the ideXlab platform.
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abstract 947 an antibody drug conjugate adc directed to Lymphocyte Antigen 6 complex locus e ly6e delivers targeted chemotherapy to a wide range of solid tumor malignancies
Cancer Research, 2015Co-Authors: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Paul Polakis, Ron FiresteinAbstract:Chemotherapies are limited by a narrow therapeutic index resulting in suboptimal exposure of the tumor to the drug and acquired tumor resistance. One approach to overcome this is through Antibody Drug Conjugates (ADCs); that facilitate greater potency via target specific chemotherapy delivery. In this study, we used a bioinformatics approach to identify Lymphocyte Antigen 6, locus E, (LY6E), an interferon-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein, as a promising ADC target. Immunohistochemical analysis revealed LY6E was overexpressed in a number of tumor types, such as, breast, including triple negative breast cancer, lung, gastric, ovarian, pancreatic and head/neck carcinomas. Characterization of the endocytic pathways for LY6E revealed rapid uptake of the LY6E specific antibody into cells leading to lysosomal accumulation. Consistent with this, a LY6E specific ADC inhibited in vitro cell proliferation and produced durable tumor regression in vivo in high LY6E expressing cancers. Our results identify LY6E as a highly promising molecular ADC target for a variety of solid tumor types with current unmet medical need. Citation Format: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Paul Polakis, Ron Firestein. An antibody drug conjugate (ADC) directed to Lymphocyte Antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 947. doi:10.1158/1538-7445.AM2015-947
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an antibody drug conjugate directed against Lymphocyte Antigen 6 complex locus e ly6e provides robust tumor killing in a wide range of solid tumor malignancies
Clinical Cancer Research, 2015Co-Authors: Jyoti Asundi, Lisa Crocker, Jarrod Tremayne, Peter Chang, Chie Sakanaka, Josh Tanguay, Susan D Spencer, Sreedevi Chalasani, Elizabeth Luis, Karen E GascoigneAbstract:Purpose: Chemotherapies are limited by a narrow therapeutic index resulting in suboptimal exposure of the tumor to the drug and acquired tumor resistance. One approach to overcome this is through antibody–drug conjugates (ADC) that facilitate greater potency via target-specific delivery of highly potent cytotoxic agents. Experimental Design: In this study, we used a bioinformatics approach to identify the Lymphocyte Antigen 6 complex locus E (LY6E), an IFN-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein as a promising ADC target. We developed a monoclonal anti-LY6E antibody and characterized in situ LY6E expression in over 750 cancer specimens and normal tissues. Target-dependent anti-LY6E ADC killing was investigated both in vitro and in vivo using patient-derived xenograft models. Results: Using in silico approaches, we found that LY6E was significantly overexpressed and amplified in a wide array of different human solid tumors. IHC analysis revealed high LY6E protein expression in a number of tumor types, such as breast, lung, gastric, ovarian, pancreatic, kidney and head/neck carcinomas. Characterization of the endocytic pathways for LY6E revealed that the LY6E-specific antibody is internalized into cells leading to lysosomal accumulation. Consistent with this, a LY6E-specific ADC inhibited in vitro cell proliferation and produced durable tumor regression in vivo in clinically relevant LY6E-expressing xenograft models. Conclusions: Our results identify LY6E as a highly promising molecular ADC target for a variety of solid tumor types with current unmet medical need. Clin Cancer Res; 21(14); 3252–62. ©2015 AACR .
Takashi Nakano - One of the best experts on this subject based on the ideXlab platform.
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effect of secreted Lymphocyte Antigen 6 urokinase type plasminogen activator receptor related peptide 1 slurp 1 on airway epithelial cells
Biochemical and Biophysical Research Communications, 2013Co-Authors: Osamu Narumoto, Yuichi Niikura, Satoshi Ishii, Hirofumi Morihara, Saki Okashiro, Takashi Nakahari, Takashi NakanoAbstract:Acetylcholine (ACh) exerts various anti-inflammatory effects through α7 nicotinic ACh receptors (nAChRs). We have previously shown that secreted Lymphocyte Antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), a positive allosteric modulator of α7 nAChR signaling, is down-regulated both in an animal model of asthma and in human epithelial cells treated with an inflammatory cytokine related to asthma. Our aim of this study was to explore the effect of SLURP-1, signal through α7 nAChR, in the pathophysiology of airway inflammation. Cytokine production was examined using human epithelial cells. Ciliary beat frequency of murine trachea was measured using a high speed camera. The IL-6 and TNF-α production by human epithelial cells was augmented by siRNA of SLURP-1 and α7 nicotinic ACh receptor. The cytokine production was also dose-dependently suppressed by human recombinant SLURP-1 (rSLURP-1). The ciliary beat frequency and amplitude of murine epithelial cells were augmented by PNU282987, a selective α7 nAChR agonist. Those findings suggested that SLURP-1 and stimulus through α7 nicotinic ACh receptors actively controlled asthmatic condition by stimulating ciliary beating and also by suppressing airway inflammation.
Satoshi Ishii - One of the best experts on this subject based on the ideXlab platform.
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effect of secreted Lymphocyte Antigen 6 urokinase type plasminogen activator receptor related peptide 1 slurp 1 on airway epithelial cells
Biochemical and Biophysical Research Communications, 2013Co-Authors: Osamu Narumoto, Yuichi Niikura, Satoshi Ishii, Hirofumi Morihara, Saki Okashiro, Takashi Nakahari, Takashi NakanoAbstract:Acetylcholine (ACh) exerts various anti-inflammatory effects through α7 nicotinic ACh receptors (nAChRs). We have previously shown that secreted Lymphocyte Antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), a positive allosteric modulator of α7 nAChR signaling, is down-regulated both in an animal model of asthma and in human epithelial cells treated with an inflammatory cytokine related to asthma. Our aim of this study was to explore the effect of SLURP-1, signal through α7 nAChR, in the pathophysiology of airway inflammation. Cytokine production was examined using human epithelial cells. Ciliary beat frequency of murine trachea was measured using a high speed camera. The IL-6 and TNF-α production by human epithelial cells was augmented by siRNA of SLURP-1 and α7 nicotinic ACh receptor. The cytokine production was also dose-dependently suppressed by human recombinant SLURP-1 (rSLURP-1). The ciliary beat frequency and amplitude of murine epithelial cells were augmented by PNU282987, a selective α7 nAChR agonist. Those findings suggested that SLURP-1 and stimulus through α7 nicotinic ACh receptors actively controlled asthmatic condition by stimulating ciliary beating and also by suppressing airway inflammation.
Hirofumi Morihara - One of the best experts on this subject based on the ideXlab platform.
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effect of secreted Lymphocyte Antigen 6 urokinase type plasminogen activator receptor related peptide 1 slurp 1 on airway epithelial cells
Biochemical and Biophysical Research Communications, 2013Co-Authors: Osamu Narumoto, Yuichi Niikura, Satoshi Ishii, Hirofumi Morihara, Saki Okashiro, Takashi Nakahari, Takashi NakanoAbstract:Acetylcholine (ACh) exerts various anti-inflammatory effects through α7 nicotinic ACh receptors (nAChRs). We have previously shown that secreted Lymphocyte Antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), a positive allosteric modulator of α7 nAChR signaling, is down-regulated both in an animal model of asthma and in human epithelial cells treated with an inflammatory cytokine related to asthma. Our aim of this study was to explore the effect of SLURP-1, signal through α7 nAChR, in the pathophysiology of airway inflammation. Cytokine production was examined using human epithelial cells. Ciliary beat frequency of murine trachea was measured using a high speed camera. The IL-6 and TNF-α production by human epithelial cells was augmented by siRNA of SLURP-1 and α7 nicotinic ACh receptor. The cytokine production was also dose-dependently suppressed by human recombinant SLURP-1 (rSLURP-1). The ciliary beat frequency and amplitude of murine epithelial cells were augmented by PNU282987, a selective α7 nAChR agonist. Those findings suggested that SLURP-1 and stimulus through α7 nicotinic ACh receptors actively controlled asthmatic condition by stimulating ciliary beating and also by suppressing airway inflammation.
