RESUMO
INTRODUCTION: The molecular bases and clinical features of hereditary angioedema (HAE) have not been systematically documented in Japan or in other Asian countries. Thus, the authors researched the genetic and clinical characteristics of Japanese patients with HAE. METHODS: The authors analyzed the CIINH gene for mutations in 13 unrelated Japanese patients with HAE by means of the polymerase chain reaction and nucleotide sequencing. In addition, the authors searched the literature from January 1969 to October 2010 on Japanese patients with HAE. RESULTS: Seven of the mutations found were novel, including 4 missense mutations (8728T>G, 8831C>A, 16661T>G and 16885C>A), 2 frameshift mutations (2281_2350del70, 14158delT) and 1 large deletion (at least 1 kb-length deletion including exon 4), whereas 6 mutations had previously been reported in European populations. CONCLUSIONS: The genetic and clinical characteristics in Japanese patients with HAE may be similar to those in Western patients although our sample size is small and the authors identified 7 novel mutations.
Assuntos
Angioedemas Hereditários/genética , Povo Asiático/genética , Proteínas Inativadoras do Complemento 1/genética , Mutação , Adolescente , Adulto , Criança , Proteína Inibidora do Complemento C1 , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
The patient was a 75-year-old man whose complaint was back pain and appetite loss. He was diagnosed with unresectable advanced gastric cancer due to multiple liver metastases and direct invasion of pancreas and spleen. He underwent gastrostomy because of esophageal stenosis, and we administered S-1 80 mg/body(4 weeks administration and 2 weeks rest)to the patient through a gastrostogavage tube. On blood examination, the serum level of CYFRA21- 1 was significantly high, while those of CEA and CA19-9 were within normal ranges. After the first course of this chemotherapy, the serum CYFRA21-1 level significantly decreased with reduction of the cancer. After the second course, it sensitively increased before image views detected the progression of the cancer. This case shows that CYFRA21- 1 could be a useful tumor marker of advanced gastric cancer.
Assuntos
Antígenos de Neoplasias/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Queratinas/sangue , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Combinação de Medicamentos , Gastroscopia , Humanos , Queratina-19 , Masculino , Estadiamento de Neoplasias , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X , Falha de TratamentoRESUMO
There are two different pathways for the development of colorectal carcinoma (CRC), adenoma-carcinoma sequence (ACS) and de novo (DN) carcinogenesis. To clarify the molecular and clinicopathological characteristics in colorectal carcinogenesis, we examined endoscopically resected specimens of 30 adenomas, 30 carcinoma in adenomas (CIAs), and 18 early pure colorectal carcinomas without any adenoma component (EPCs, so called DN carcinoma) and compared the expression of Fhit, Mlh1, Msh2, P53 and cellular phenotype (HGM, MUC2 and CD10). Markedly reduced or absent Fhit expression was noted in 8 (44%) of 18 EPCs, but none of the adenomas or CIAs (p<0.0001). Six (33%) of 18 EPCs showed loss of Mlh1 expression, but rarely in adenomas and CIAs (p=0.008). This altered Fhit expression was significantly higher in submucosal invasive cancers (p=0.001), lymphatic or venous invasive cancers (p=0.0018), and tumors with altered expression of Mlh1 (p=0.01). The incidence of P53 overexpression was significantly higher in EPCs (39%) and CIAs (27%) than in adenomas (3.3%) (p<0.05). There were significant differences in phenotypic expression between the adenomatous and carcinomatous areas. Moreover, in CIAs and EPCs, the rate of P53 overexpression was significantly higher in the CD10-positive cases (53%) than CD10-negative cases (19%) (p=0.04). The present findings suggested that aberrant Fhit and Mlh1 expression could be related to DN carcinogenesis and that P53 overexpression and changes in phenotypic expression could contribute to the malignant transformation of colorectal precursor lesions.
Assuntos
Hidrolases Anidrido Ácido/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Adenocarcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas Nucleares/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adenocarcinoma/patologia , Adenoma/metabolismo , Adenoma/patologia , Idoso , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mucina-2 , Mucinas/biossíntese , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/biossíntese , Neprilisina/biossíntese , FenótipoRESUMO
An increasing number of tumor suppressor genes (TSGs) that are inactivated by hypermethylation of CpG islands in the promoter have been reported in gastric carcinomas. The aim of this study is to evaluate the clinical significance of TSG protein expression, which correlates with the promoter status, methylated or not, during the early stages of gastric carcinogenesis and to examine its relationship with mucin phenotype. The protein expression of 4 TSGs including Fhit, Mlh1, p16INK4A and E-cadherin was examined using immunohistochemical methods in 103 early gastric neoplasias, comprising 41 adenomas and 62 intramucosal carcinomas, obtained by endoscopic mucosal resection. In addition, phenotypic expression patterns (gastric-, intestinal- and mixed-phenotypes) were also examined. The expression of Fhit, Mlh1, p16 and E-cadherin was lost or reduced in 7.3, 12.2, 12.2 and 9.8% of the adenomas and in 35.5, 29.0, 29.0 and 32.3% of the intramucosal carcinomas, respectively. The absent expression of p16 was significantly associated with the degree of dysplasia in the adenomas (p=0.038). The average number of proteins among the 4 TSGs, whose expression was lost or reduced per sample, was significantly higher in the intramucosal carcinomas (1.35) than in the adenomas (0.41) (p=0.00013). Similarly, the average number was significantly higher in the gastric-type tumors (2.05) than in the intestinal-type tumors (0.49) (p=0.0000019). We demonstrated an increase in the number of TSG proteins whose expression is reduced or lost in the early stages of gastric tumorigenesis, and that this increase is associated with histological grade and gastric phenotype.