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Olelsandr O Minchenko - One of the best experts on this subject based on the ideXlab platform.
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effect of ern1 knockdown on the expression of map3k5 map4k3 cib1 ripk1 and ripk2 genes in u87 glioma cells and its hypoxic regulation
American Journal of Physiology Biochemistry and Pharmacology, 2014Co-Authors: D O Minchenko, Taia V Bakalets, Daria O Tzymbal, O O Ratushna, Yulia M Bashta, Olelsandr O MinchenkoAbstract:ERN1 (endoplasmic reticulum to nucleus signaling 1)-mediated signaling pathway plays an important role in glioma growth. We studied the possible role of protein kinases MAP4K3, MAP3K5, RIPK1, and RIPK2 as well as protein kinase interacting protein CIB1 in suppression of U87 glioma cell proliferation upon ERN1 knockdown. It was shown that blockade of ERN1 signaling enzyme function significantly decreases the expression level of genes encoding MAP4K3, RIPK2, and CIB1 in U87 glioma cells, but increases expression of RIPK1 gene. At the same time, the blockade of ERN1 signaling enzyme does not affect the expression of MAP3K5 gene in glioma cells. Hypoxia down-regulates the expression level of MAP3K5, MAP4K3, RIPK1, and RIPK2 mRNAs in control glioma cells. However, inhibition of ERN1 affected hypoxia-mediated changes in expression of these kinase genes and their magnitude. Results of this investigation clearly demonstrated that the expression of MAP4K3, RIPK1, RIPK2, and CIB1genes in U87 glioma cells in human U87 glioma cells relies on blockade of ERN1-mediated endoplasmic reticulum stress signaling and is mostly down-regulated by hypoxia in dependence of ERN1 enzyme function.
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eff ect of the endoplasmic reticulum to nucleus signaling 1 knockdown on the expression of map3k5 map4k3 cib1 ripk1 and ripk2 genes in u87 glioma cells and its hypoxic regulation
2014Co-Authors: D O Minchenko, Taia V Bakalets, Daria O Tzymbal, O O Ratushna, Yulia M Bashta, Olelsandr O MinchenkoAbstract:Background: ERN1 (endoplasmic reticulum to nucleus signaling 1)-mediated signaling pathway plays an important role in glioma growth through changing the numerous regulatory gene expressions. We studied the possible role of protein kinases MAP4K3, MAP3K5, RIPK1, and RIPK2 as well as protein kinase interacting protein CIB1 in suppression of U87 glioma cell proliferation upon ERN1 knockdown. Materials and Methods: The expression of MAP4K3, RIPK1, RIPK2, and CIB1genes was measured in human U87 glioma cells and its regulation by hypoxia in dependence of ERN1 enzyme function using quantitative PCR. Results: Blockade of ERN1 signaling enzyme function significantly decreases the expression level of genes encoding MAP4K3, RIPK2, and CIB1 in U87 glioma cells, but increases expression of RIPK1 gene. At the same time, the blockade of ERN1 signaling enzyme does not affect the expression of MAP3K5 gene in glioma cells. Hypoxia downregulates the expression level of MAP3K5, MAP4K3, RIPK1, and RIPK2 mRNAs in control glioma cells. However, inhibition of ERN1 affected hypoxia-mediated changes in expression of these kinase genes and their magnitude. Conclusion: Results of this investigation clearly demonstrated that the expression of MAP4K3, RIPK1, RIPK2, and CIB1genes in human U87 glioma cells relies on blockade of ERN1-mediated endoplasmic reticulum stress signaling and is mostly down-regulated by hypoxia in dependence of ERN1 enzyme function.
Christopher J Bowman - One of the best experts on this subject based on the ideXlab platform.
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Langerhans cell histiocytosis associated with lymphoma: an incidental finding that is not associated with BRAF or MAP2K1 mutations
Modern Pathology, 2017Co-Authors: Sergio Pina-oviedo, L Jeffrey Medeiros, Shaoying Li, Joseph D Khoury, Keyur P Patel, Khaled Alayed, R Craig Cason, Christopher J BowmanAbstract:Langerhans cell histiocytosis is characterized by a localized or systemic proliferation of Langerhans cells. BRAF mutations have been reported in 40–70% of cases and MAP2K1 mutations have been found in BRAF -negative cases, supporting that Langerhans cell histiocytosis is a true neoplasm, at least in mutated cases. In a small subset of patients, Langerhans cell histiocytosis is detected incidentally in a biopsy involved by lymphoma. These lesions are usually minute and rarely have been assessed for mutations. We assessed for BRAF and MAP2K1 mutations in seven cases of Langerhans cell histiocytosis detected incidentally in biopsies involved by lymphoma. We performed immunohistochemical analysis for phosphorylated (p)-ERK. There were four men and three women (median age, 54 years; range, 28–84). The biopsies included lymph nodes ( n =6) and chest wall ( n =1). The lymphomas included five classical Hodgkin lymphoma, one mantle cell lymphoma, and one angioimmunoblastic T-cell lymphoma. All cases were negative for BRAF V600E and MAP2K1 mutations. Nevertheless, three of seven cases showed ERK activation as shown by expression of p-ERK. We performed mutation analysis using a panel of 134 commonly mutated genes (including BRAF and MAP2K1) by next-generation sequencing on three cases, including two cases positive for p-ERK by immunohistochemistry. No mutations were detected in any of the three cases assessed. Six patients received therapy appropriate for their lymphoma. With a median follow-up of 21 months (range, 6–89), no patients developed disseminated or recurrent Langerhans cell histiocytosis. We conclude that lymphoma-associated Langerhans cell histiocytosis is a clinically benign process that is not associated with BRAF V600E or MAP2K1 mutations and, as suggested by others, the designation Langerhans cell hyperplasia may be more appropriate. Nevertheless, the expression of p-ERK in three cases suggests that the RAS–RAF–MAP2K–ERK pathway is activated, perhaps by non-mutational mechanisms induced by the presence of lymphoma or lymphoma–microenvironment interactions.
Sancy A Leachman - One of the best experts on this subject based on the ideXlab platform.
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a case of multiple pagetoid spitz nevi
2017Co-Authors: Kalynne Harris, Jason Papenfuss, Mona S Jahromi, Scott R Florell, Pamela B Cassidy, Jessica D. Schiffman, John Quackenbush, Wendy Kohlmann, Sancy A LeachmanAbstract:Observations: We present a unique case of multiple pagetoid Spitz nevi initially diagnosed as multiple in situ melanomas. Germline karyotyping, CDK4 and CDKN2A sequencing, and comparative genomic hybridization of HRAS, BRAF, KRAS, RAF1, CDKN2A, Rb1, MAP2K1, MAP2K2, PTEN, and PTPN11 genes did not identify mutations in this case. Germline and somatic sequencing of BRAF exon 15 revealed no mutations at V600D/E/K. In addition, singlenucleotide polymorphism microarray analysis (330K) on lesional and normal skin revealed no genome-wide copy number changes or loss of heterozygosity.
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melanoma mimic a case of multiple pagetoid spitz nevi
Archives of Dermatology, 2012Co-Authors: Kalynne Harris, Jason Papenfuss, Mona S Jahromi, Scott R Florell, Pamela B Cassidy, Jessica D. Schiffman, John Quackenbush, Wendy Kohlmann, Sancy A LeachmanAbstract:Background Differentiating Spitz nevi from melanoma can be difficult. Pagetoid spread of melanocytes is among the features making diagnosis difficult. Rare reports of isolated pagetoid Spitz nevi exist. Observations We present a unique case of multiple pagetoid Spitz nevi initially diagnosed as multiple in situ melanomas. Germline karyotyping, CDK4 and CDKN2A sequencing, and comparative genomic hybridization of HRAS, BRAF, KRAS, RAF1, CDKN2A, Rb1, MAP2K1, MAP2K2, PTEN, and PTPN11 genes did not identify mutations in this case. Germline and somatic sequencing of BRAF exon 15 revealed no mutations at V600D/E/K. In addition, single-nucleotide polymorphism microarray analysis (330K) on lesional and normal skin revealed no genome-wide copy number changes or loss of heterozygosity. Conclusions Clinicians should be aware of the occurrence of multiple pagetoid Spitz nevi to avoid morbidity associated with the misdiagnosis of multiple melanomas. The genetic mechanisms of pagetoid spread of melanocytes are not fully understood.
Hitomi Niijima - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the BRAF and MAP2K1 mutations in patients with Langerhans cell histiocytosis in Japan
International Journal of Hematology, 2020Co-Authors: Tomomi Hayase, Shiori Saito, Yoko Shioda, Toshihiko Imamura, Kenichiro Watanabe, Kentaro Ohki, Takako Yoshioka, Yukiko Oh, Yuta Kawahara, Hitomi NiijimaAbstract:In Langerhans cell histiocytosis (LCH), somatic gene mutations in the mitogen-activated protein kinase pathway have been identified in more than 80% of cases in Western countries, in which mutually exclusive BRAF and MAP2K1 mutations are involved. Among them, BRAF V600E mutation is the major contributor (50–60%). In 59 patients (50 children and nine adults) with LCH (not including pulmonary LCH) in Japan, we first screened for BRAF V600E in all patients followed by target sequencing for other gene mutations in 17 of BRAF V600E-negative patients. As a result, BRAF V600E mutation was detected in 27/59 (46%) patients. We also identified BRAF mutations other than V600E in five and MAP2K1 mutations in nine patients. Thus, gene mutations in BRAF or MAP2K1 were identified in 41/44 (93%) of the fully tested patients. Regarding the correlation of clinical features and genotype in pediatric patients, we found that BRAF V600E mutation status was not correlated with sex, age at diagnosis, disease extent, response to first-line therapy, relapse, or CNS-related sequelae. Interestingly, MAP2K1 exon 2 in-frame deletion was related to the risk organ involvement; however, further studies are required to clarify the impact of these gene mutations on the clinical features of patients with LCH.
D O Minchenko - One of the best experts on this subject based on the ideXlab platform.
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effect of ern1 knockdown on the expression of map3k5 map4k3 cib1 ripk1 and ripk2 genes in u87 glioma cells and its hypoxic regulation
American Journal of Physiology Biochemistry and Pharmacology, 2014Co-Authors: D O Minchenko, Taia V Bakalets, Daria O Tzymbal, O O Ratushna, Yulia M Bashta, Olelsandr O MinchenkoAbstract:ERN1 (endoplasmic reticulum to nucleus signaling 1)-mediated signaling pathway plays an important role in glioma growth. We studied the possible role of protein kinases MAP4K3, MAP3K5, RIPK1, and RIPK2 as well as protein kinase interacting protein CIB1 in suppression of U87 glioma cell proliferation upon ERN1 knockdown. It was shown that blockade of ERN1 signaling enzyme function significantly decreases the expression level of genes encoding MAP4K3, RIPK2, and CIB1 in U87 glioma cells, but increases expression of RIPK1 gene. At the same time, the blockade of ERN1 signaling enzyme does not affect the expression of MAP3K5 gene in glioma cells. Hypoxia down-regulates the expression level of MAP3K5, MAP4K3, RIPK1, and RIPK2 mRNAs in control glioma cells. However, inhibition of ERN1 affected hypoxia-mediated changes in expression of these kinase genes and their magnitude. Results of this investigation clearly demonstrated that the expression of MAP4K3, RIPK1, RIPK2, and CIB1genes in U87 glioma cells in human U87 glioma cells relies on blockade of ERN1-mediated endoplasmic reticulum stress signaling and is mostly down-regulated by hypoxia in dependence of ERN1 enzyme function.
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eff ect of the endoplasmic reticulum to nucleus signaling 1 knockdown on the expression of map3k5 map4k3 cib1 ripk1 and ripk2 genes in u87 glioma cells and its hypoxic regulation
2014Co-Authors: D O Minchenko, Taia V Bakalets, Daria O Tzymbal, O O Ratushna, Yulia M Bashta, Olelsandr O MinchenkoAbstract:Background: ERN1 (endoplasmic reticulum to nucleus signaling 1)-mediated signaling pathway plays an important role in glioma growth through changing the numerous regulatory gene expressions. We studied the possible role of protein kinases MAP4K3, MAP3K5, RIPK1, and RIPK2 as well as protein kinase interacting protein CIB1 in suppression of U87 glioma cell proliferation upon ERN1 knockdown. Materials and Methods: The expression of MAP4K3, RIPK1, RIPK2, and CIB1genes was measured in human U87 glioma cells and its regulation by hypoxia in dependence of ERN1 enzyme function using quantitative PCR. Results: Blockade of ERN1 signaling enzyme function significantly decreases the expression level of genes encoding MAP4K3, RIPK2, and CIB1 in U87 glioma cells, but increases expression of RIPK1 gene. At the same time, the blockade of ERN1 signaling enzyme does not affect the expression of MAP3K5 gene in glioma cells. Hypoxia downregulates the expression level of MAP3K5, MAP4K3, RIPK1, and RIPK2 mRNAs in control glioma cells. However, inhibition of ERN1 affected hypoxia-mediated changes in expression of these kinase genes and their magnitude. Conclusion: Results of this investigation clearly demonstrated that the expression of MAP4K3, RIPK1, RIPK2, and CIB1genes in human U87 glioma cells relies on blockade of ERN1-mediated endoplasmic reticulum stress signaling and is mostly down-regulated by hypoxia in dependence of ERN1 enzyme function.