RESUMO
HLA-DQB1*04:01:05 differs from DQB1*04:01:01 by a single nucleotide substitution at codon 30 (TAC>TAT).
Assuntos
Alelos , Povo Asiático/genética , Cadeias beta de HLA-DQ/genética , Sequência de Bases , Éxons/genética , Teste de Histocompatibilidade , Humanos , Alinhamento de SequênciaRESUMO
The new allele HLA-C*03:03:35 showed one nucleotide difference with C*03:03:01:01 at position 408 (G>T).
Assuntos
Alelos , Antígenos HLA-C/genética , Sequência de Bases , Éxons/genética , Loci Gênicos , Teste de Histocompatibilidade , Humanos , Alinhamento de SequênciaRESUMO
The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOPMT. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response, defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.
Assuntos
Adenocarcinoma/patologia , Proteínas Nucleares/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Ubiquitinação , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Estudos de Coortes , Humanos , Masculino , Camundongos , Camundongos Knockout , Mutação , Proteínas Nucleares/genética , Próstata/metabolismo , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Inibidores de Proteassoma/farmacologia , Receptores Androgênicos/metabolismo , Proteínas Repressoras/genética , Complexos Ubiquitina-Proteína LigaseRESUMO
HLA-B*40:332 differs from B*40:01:02 by 1 nucleotide difference at nucleotide position 439.
Assuntos
Alelos , Éxons , Antígeno HLA-B40/genética , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Substituição de Aminoácidos , Povo Asiático , Sequência de Bases , Códon/química , Expressão Gênica , Genótipo , Antígeno HLA-B40/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
The HLA-A*26:01:01:03N allele shows a single nucleotide difference compared with HLA-A*26:01:01:01 in intron 4(1846 G>A).
Assuntos
Alelos , Genoma Humano , Antígenos HLA-A/genética , Íntrons , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Povo Asiático , Sequência de Bases , Éxons , Genótipo , Antígenos HLA-A/imunologia , Transplante de Células-Tronco Hematopoéticas , Heterozigoto , Teste de Histocompatibilidade , Humanos , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
The new allele, HLA-C*03:280 differs from C*03:04:01 by one nucleotide substitution at codon 35 (CGGâCAG).
Assuntos
Genes MHC da Classe II , Antígenos HLA-C/isolamento & purificação , Adulto , Alelos , Substituição de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Éxons/genética , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Humanos , Masculino , Dados de Sequência Molecular , República da Coreia , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
HLA-A*29:01:09 differs from A*29:01:01:01 by one nucleotide difference at nucleotide position 414.
Assuntos
Alelos , Antígenos HLA-A/genética , Povo Asiático , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNARESUMO
The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I-related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs.
Assuntos
Variação Genética , Genoma/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Suínos/genética , Regiões 5' não Traduzidas , Alelos , Animais , Sequência de Bases , Cruzamento , Linhagem Celular , Impressões Digitais de DNA , Éxons , Loci Gênicos , Técnicas de Genotipagem , Antígenos de Histocompatibilidade Classe I/classificação , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/classificação , Antígenos de Histocompatibilidade Classe II/imunologia , Íntrons , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Suínos/imunologiaRESUMO
The new allele, HLA-B*40:301 differs from B*40:01:02 by one nucleotide substitution at codon 239 (AGA â AAA).
Assuntos
Alelos , Antígenos HLA-B/genética , Teste de Histocompatibilidade , Análise de Sequência de DNA , Sequência de Bases , Éxons/genética , Humanos , Masculino , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
The HLA-C*15:02:01:03 allele differs from the HLA-C*15:02:01:01 allele by a single-nucleotide substitution in the 5' untranslated region (-42 C>A).
Assuntos
Alelos , Antígenos HLA-C/genética , Leucemia/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Éxons , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Leucemia/diagnóstico , Leucemia/terapia , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , República da Coreia , Análise de Sequência de DNA , Doadores de Tecidos , TransplantadosRESUMO
HLA-B*15:263 differs from HLA-B*15:18:01 by a single nucleotide exchange at position 824, C>G (codon 251 TCT>TGT).
Assuntos
Alelos , Substituição de Aminoácidos , Antígeno HLA-B15/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Códon , Éxons , Expressão Gênica , Antígeno HLA-B15/imunologia , Teste de Histocompatibilidade , Humanos , Leucemia/imunologia , Leucemia/patologia , Leucemia/terapia , Masculino , Dados de Sequência Molecular , República da Coreia , Alinhamento de Sequência , TransplantadosRESUMO
The new allele, DRB1*04:10:03, showed one nucleotide difference with DRB1*04:10:01 (705C>T).
Assuntos
Alelos , Cadeias HLA-DRB1/genética , Sequência de Bases , Éxons/genética , Humanos , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.
Assuntos
Adenocarcinoma/cirurgia , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Radiocirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
HLA-A*02:428 differs from A*02:06:01 by a non-synonymous mutation at codon 260 (CAT to GAT) in exon 4.
Assuntos
Alelos , Antígeno HLA-A2/genética , Mutação , Análise Mutacional de DNA , Feminino , Humanos , MasculinoRESUMO
Single-cell injection with lipophilic dyes following immunocytochemistry is extremely valuable for revealing the morphology of a cell expressing a protein of interest, and is a more reliable technique for cell type classification than standard morphological techniques. This study focuses on calretinin (CR), which is used as a selective marker for distinct subpopulations of neurons in the rabbit retina. The present study used single-cell injection after immunocytochemistry to describe the density and types of CR-containing retinal ganglion cells (RGCs) in rabbit. The density of CR-immunoreactive cells in the rabbit RGC cell layer was 426cells/mm(2). CR-containing RGCs were identified by immunocytochemistry and were then iontophoretically injected with a lipophilic dye, DiI. Subsequently, confocal microscope was used to characterize the morphology of CR-immunoreactive RGCs based on their dendritic field size, branching pattern, and stratification of the inner plexiform layer. Our results show that 10 morphologically different types of rabbit RGCs expressed CR. CR-containing RGCs were heterogeneous in their morphology. This approach to integrate the selective expression of a particular protein with spatial patterns of dendritic arborization will lead to a better understanding of RGCs.
Assuntos
Calbindina 2/análise , Imuno-Histoquímica/métodos , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Animais , Carbocianinas/análise , Contagem de Células , Feminino , Masculino , CoelhosRESUMO
The new allele B*40:02:18 showed one nucleotide difference with B*40:02:01 at codon 111 (CGC/CGT).
Assuntos
Genes MHC Classe I , Antígenos HLA-B/genética , Alelos , Sequência de Bases , Genótipo , Humanos , Dados de Sequência Molecular , República da Coreia , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
PURPOSE: A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010. METHODS: A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed. RESULTS: Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m(2) (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O(+) recipients. CONCLUSIONS: The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs.