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1.
Cancer Sci ; 111(4): 1324-1332, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32012411

RESUMO

Interim results from the two-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum-free interval or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand-1 (PD-L1) tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty-one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. A total of 13 (61.9%) patients had treatment-related adverse events (TRAE), and 5 (23.8%) had grade 3-4 TRAE. There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno B7-H1/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
2.
Invest New Drugs ; 36(3): 424-434, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28965185

RESUMO

Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors. Methods Three to 6 patients were enrolled into sequentially escalating dose cohorts (erdafitinib 2, 4, or 6 mg) with a daily dosing schedule of 21-day cycles or a 7 days-on/7 days-off intermittent schedule (erdafitinib 10 mg or 12 mg) of 28-day cycles. Results Nineteen patients received escalating doses of erdafitinib with a daily or intermittent schedule. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (73.7%), nausea (36.8%), stomatitis (26.3%), dysgeusia (26.3%) and dry mouth (21.1%). The maximum tolerated dose was not reached in this study. No Grade 3 or higher TEAEs, or serious TEAEs were noted and no clinically significant changes in vital signs, laboratory parameters, and electrocardiogram readings were observed. However, one case of dose-limiting toxicity in the 12 mg intermittent dosing group was observed: Grade 2 detachment of retinal pigment epithelium (bilateral) with treatment discontinuation. The maximum plasma concentrations of erdafitinib exhibited a dose-dependent increase. The median tmax ranged from 2 to 3 h after the initial dose to 2-6 h following multiple daily dosing. Based on the safety and PK data, the 10 mg 7 days-on/7 days-off regimen was determined as the recommended phase 2 dose in this study. Conclusions Erdafitinib was well tolerated in Japanese patients with advanced or refractory solid tumors. TRIAL REGISTRATION: NCT01962532.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/farmacocinética , Pirazóis/uso terapêutico , Quinoxalinas/farmacocinética , Quinoxalinas/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Idoso , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Quinoxalinas/efeitos adversos , Quinoxalinas/farmacologia , Resultado do Tratamento
3.
Int J Hematol ; 107(4): 460-467, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29260507

RESUMO

Daratumumab in combination with bortezomib and dexamethasone (DVd) has demonstrated longer progression-free survival than combination of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). In this multicenter, open-label, phase-1 study, the safety, efficacy, and pharmacokinetics (PK) of DVd were evaluated in Japanese patients with RRMM. Eight patients with RRMM aged between 54 and 82 years were enrolled and treated with DVd regimen. Primary endpoints were tolerability and safety. Secondary endpoints were overall response rate (ORR), very good partial response (VGPR) or better, complete response (CR) or better, time to response (TTR), PK, and immunogenicity. All patients (n = 8) experienced Grade ≥ 3 treatment-emergent adverse events (TEAE), with thrombocytopenia (n = 6, 75%) being the most frequent. Mild Grade ≤ 2 infusion-related reactions were reported in five patients. Serious TEAEs were herpes zoster, nasopharyngitis, and prostate cancer (n = 1 each). Three dose-limiting toxicities were observed in two patients. No death or disease progression was reported as of the study cut-off date. ORR was 100% (2 CRs or better, 2 VGPRs, 4 PRs). The median TTR was 0.9 months. PK profiles were comparable to previous studies. The DVd regimen showed acceptable safety with favorable efficacy in Japanese patients with RRMM. CLINICAL TRIAL REGISTRATION NUMBER: NCT02497378.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Povo Asiático , Bortezomib/efeitos adversos , Bortezomib/farmacocinética , Dexametasona/efeitos adversos , Dexametasona/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
4.
Int J Hematol ; 106(4): 541-551, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28643017

RESUMO

Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity. Daratumumab was well-tolerated. Eight patients experienced Grade ≥3 adverse event (AE). Four serious AEs were observed in three patients; no AEs leading to death. Infusion-related reactions occurred in four (44%) patients and were Grade 1 or 2. Mean (SD) cumulative dose of daratumumab was 132.3 (108.5) mg/kg. Median duration of follow-up was 10.5 months (range 2.3, 16.4) for 8 mg/kg cohort and 9.9 months (range 1.7, 13.2) for 16 mg/kg cohort. The ORR (44%) comprised 1 and 3 partial responses in 8 and 16 mg/kg cohorts, respectively. The median PFS was 6 months for 8 mg/kg cohort, 9.5 months for 16 mg/kg cohort. Daratumumab serum exposure was increased with increasing dose. Antibodies against daratumumab were not observed. Daratumumab was safe and well-tolerated in Japanese patients with relapsed /refractory MM.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/mortalidade , Adulto , Assistência ao Convalescente , Idoso , Anticorpos Monoclonais/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Taxa de Sobrevida
5.
J Affect Disord ; 179: 161-6, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25863913

RESUMO

BACKGROUND: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. METHODS: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts. RESULTS: The seropositivity for T. gondii was significantly higher in BD patients as compared to controls (p=0.005). The cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater (p=0.01). LIMITATIONS: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. CONCLUSIONS: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Transtornos Cognitivos/complicações , Transtornos Cognitivos/psicologia , Interleucina-6/sangue , Toxoplasmose/complicações , Toxoplasmose/psicologia , Adulto , Transtorno Bipolar/sangue , Estudos de Casos e Controles , Transtornos Cognitivos/sangue , Estudos Transversais , Feminino , Humanos , Interleucina-6/biossíntese , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Toxoplasmose/sangue
6.
Inflamm Bowel Dis ; 19(3): 526-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23388546

RESUMO

BACKGROUND: A large-scale meta-analysis of a series of European genome-wide association studies revealed 71 susceptibility loci for Crohn's disease (CD). However, it is not clear whether these susceptibility loci are also shared with Japanese populations. METHODS: We genotyped 71 single-nucleotide polymorphisms (SNPs) comprising 1311 CD cases and 6585 controls of Japanese descent, and their associations with CD were evaluated using the Cochran-Armitage trend test. In addition, genotype-phenotype analyses were conducted on the SNPs showing associations with Japanese CD based on the Montreal classification. RESULTS: Twenty-seven SNPs showed at least nominal association (P < 0.05) and 11 of them remained significant even after Bonferroni correction (P < 0.0007). Despite high statistical power, we could not find any association in 17 loci. Moreover, SNPs in 9 loci were rare or absent in the Japanese population. Genetic variations involved in the innate immune system (NOD2, ATG16L1, and IRGM) showed no association with CD susceptibility in the Japanese population. Genotype-phenotype analyses showed that rs3810936, a marker of TNFSF15, correlated with severe CD phenotypes. CONCLUSIONS: Our study suggests that there is a differential genetic background of CD susceptibility between Japanese and European populations.


Assuntos
Doença de Crohn/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , Europa (Continente) , Feminino , Marcadores Genéticos , Humanos , Imunidade Inata/genética , Japão , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
7.
J Affect Disord ; 148(2-3): 444-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23273549

RESUMO

BACKGROUND: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations. METHODS: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation. RESULTS: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR=2.17 CI 95%=1.09-4.36, p=0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population. LIMITATIONS: Our results are to be interpreted with caution because of our small sample size. RESULTS: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments.


Assuntos
Transtorno Bipolar/epidemiologia , Toxoplasmose/epidemiologia , Adulto , Anticorpos Antiprotozoários/isolamento & purificação , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasma/imunologia
8.
PLoS One ; 7(9): e44507, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23049750

RESUMO

Smoking is a major public health problem, but the genetic factors associated with smoking behaviors are not fully elucidated. Here, we have conducted an integrated genome-wide association study to identify common copy number polymorphisms (CNPs) and single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) in Japanese smokers (N = 17,158). Our analysis identified a common CNP with a strong effect on CPD (rs8102683; P=3.8 x 10(-42)) in the 19q13 region, encompassing the CYP2A6 locus. After adjustment for the associated CNP, we found an additional associated SNP (rs11878604; P=9.7 x 10(-30)) located 30 kb downstream of the CYP2A6 gene. Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA F-test P=9.5 x 10(-52)). These haplotypes were also associated with smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease and arteriosclerosis obliterans.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Variações do Número de Cópias de DNA , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Fumar/genética , Alelos , Análise de Variância , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP2A6 , Feminino , Frequência do Gene , Variação Genética , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Japão/epidemiologia , Masculino , Nicotina/metabolismo , Fumar/epidemiologia , Fumar/metabolismo
9.
Nat Genet ; 44(7): 760-4, 2012 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-22634756

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ∼50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.


Assuntos
Carcinoma Hepatocelular/genética , Cromatina/genética , Neoplasias Hepáticas/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Genoma Viral/genética , Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite C/genética , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Telomerase/genética , Integração Viral/genética
10.
Blood ; 115(3): 653-6, 2010 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-19965687

RESUMO

DNA vaccination and all-trans retinoic acid (ATRA) result in a survival advantage in a mouse model of acute promyelocytic leukemia (APL). Depletion of CD4(+) or CD8(+) cells abolished this effect. CD4(+) depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating the need of both CD4(+) and CD8(+) subsets for the generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4(+) cells in the maintenance of durable remissions. Degranulation and cytotoxic carboxyfluorescein diacetate succinimidyl ester-based assays showed major histocompatibility complex-restricted APL-specific T cell-mediated immune responses. Sorted APL-specific CD8(+)CD107a(+) T cells showed an increase of antileukemic activity. Effectors from ATRA + DNA-treated mice were shown to secrete interferon-gamma when stimulated with either APL cells or peptides from the promyelocytic leukemia-RARalpha vaccine-derived sequences as detected by ELISpot assays. Our results demonstrate that DNA vaccination with ATRA confers the effective boosting of interferon-gamma-producing and cytotoxic T cells in the leukemic mice.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular , Leucemia Promielocítica Aguda/terapia , Tretinoína/administração & dosagem , Vacinas de DNA/administração & dosagem , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Terapia Combinada , Modelos Animais de Doenças , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/genética , Leucemia Promielocítica Aguda/imunologia , Leucemia Promielocítica Aguda/patologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Camundongos , Proteínas de Fusão Oncogênica/administração & dosagem , Proteínas de Fusão Oncogênica/genética , Análise de Sobrevida , Resultado do Tratamento , Células Tumorais Cultivadas , Vacinas de DNA/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Biochem Biophys Res Commun ; 335(2): 566-74, 2005 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-16087163

RESUMO

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP70/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Alelos , Estudos de Casos e Controles , Marcadores Genéticos , Predisposição Genética para Doença , Variação Genética , Genótipo , Haplótipos , Humanos , Japão , Chaperonas Moleculares/genética , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único/genética
12.
Hum Mol Genet ; 13(19): 2221-31, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15294872

RESUMO

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigens and has a significant genetic component. Antisense RNA transcripts have been implicated in gene regulation. Here we have identified a novel zinc-finger gene, designated ZFAT (zinc-finger gene in AITD susceptibility region), as one of the susceptibility genes in 8q23-q24 through an initial association analysis using the probands in the previous linkage analysis and a subsequent association analysis of the samples from a total of 515 affected individuals and 526 controls. The T allele of the single-nucleotide polymorphism (SNP), Ex9b-SNP10 located in the intron 9 of ZFAT, is associated with increased risk for AITD (dominant model: odds ratio = 1.7, P = 0.000091). The Ex9b-SNP10 falls into the 3'-UTR of truncated-ZFAT (TR-ZFAT) and the promoter region of the small antisense transcript of ZFAT (SAS-ZFAT). In peripheral blood lymphocytes, SAS-ZFAT is exclusively expressed in CD19+ B cells and expression levels of SAS-ZFAT and TR-ZFAT seemed to correlate with the Ex9b-SNP10-T-associated ZFAT-allele, inversely and positively, respectively. The Ex9b-SNP10 is critically involved in the regulation of SAS-ZFAT expression in vitro and this expression results in a decreased expression of TR-ZFAT. These results suggested that the SNP-associated ZFAT-allele plays a critical role in B cell function by affecting the expression level of TR-ZFAT through regulating SAS-ZFAT expression and that this novel regulatory mechanism of SNPs might be involved in controlling susceptibility or resistance to human disease.


Assuntos
Linfócitos B/metabolismo , DNA Antissenso/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Tireoidite Autoimune/genética , Dedos de Zinco/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Humanos , Tireoidite Autoimune/diagnóstico
13.
No Shinkei Geka ; 30(8): 869-73, 2002 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-12187733

RESUMO

Chronic renal failure is one of the risk factors for carotid atherosclerosis. We report two cases of stenosis of the carotid bifurcation treated by carotid endarterectomy. A 66-year-old man with a 17-year history of hemodialysis experienced repeated episodes of right hemiparesis. Cerebral angiography showed severe stenosis of the cervical carotid bifurcation bilaterally. Left and right carotid endarterectomy operations were performed one month apart. The postoperative course was uneventful, and the patient returned home without neurological symptoms. The second case was in a 49-year-old woman with a 15-year history of hemodialysis had vertigo of one month duration. Cerebral angiography revealed occlusion of the left subclavian artery, and the distal left axillary artery was filled by retrograde flow from the left vertebral artery. Stenosis of the right carotid bifurcation was also noted. Right carotid endarterectomy was performed without any complications. Although a high incidence of intraoperative complications and of recurrent stroke after carotid endarterectomy (CEA) has been reported in chronic renal failure patients, the poor prognosis of the natural history of severe carotid stenosis in chronic renal failure should be taken into consideration. The cases reported indicate that carotid endarterectomy is safe and justified for carotid stenosis in chronic renal failure patients.


Assuntos
Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/cirurgia , Arteriosclerose/etiologia , Arteriosclerose/cirurgia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
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