ABSTRACT
HLA-A2 is present at high frequency in most populations, as identified by serological and biochemical means. The values of these methods are limited by their failures to discriminate the products of the known allelic HLA-A02 variants. The great majority of genetic polymorphism which defines the allelic variants is found in exons 2 and 3 of the HLA-A02 gene. These exons encode the a-1 and a-2 domains of the HLA class I molecules, and the variation within the genes may influence the peptide binding specificity of the gene products of each allele. To determine the 17 known alleles of HLA-A02 an ARMS-PCR was developed. We applied this ARMS-PCR to 10 standard cell lines and we confirmed the specificity and sensitivity of this method. We defined the HLA-A 02 subtypes in 146 healthy Koreans who were serologically identified as HLA-A2. Five subtypes out of the 17 known A02 alleles were detected (A'0201, 0203, 0206, 0207, '0210) and A'0201 was most frequent (53.4%) and A'0206, '0207, '0203, 0210 (37.0%, 18.5%, 2.7%, 2.1%), were followed respectively. By linkage disequilibrium analysis with HLA-B alleles, A*02 subtypes were defined to be associated with many B alleles (B27, 35, 38, 39, 46, 52, 60, and 61). It is suggested that these findings may be helpful for the selection of patients for the specific immunotherapy with HLA-A02 restricted peptide vaccines and for the unrelated bone marrow transplantation in Korean.
Subject(s)
Humans , Alleles , Bone Marrow Transplantation , Cell Line , Exons , HLA-A Antigens , HLA-A2 Antigen , HLA-B Antigens , Immunotherapy , Linkage Disequilibrium , Polymorphism, Genetic , Sensitivity and Specificity , Vaccines, SubunitABSTRACT
The thirteen DRB1, 6 DQA1, and 5 DQB1 alleles were defined in 362 healthy Korean controls using reverse dot blot hybridization method. The twenty-four immobilized SSOs for DRB1, 8 for DQA1, and 6 for DQB1 were used for this study. The frequencies of genotypes were DRB104 (17.1'Yo), '09 (13.1%), and '13 (11.6%); DQA1'01 (46.7%), 03 (30.8%), and '05 (11.7%); DQB1*03 (39.5%), '06 '(29.8%), and 05 (16.0%). ...continue...
Subject(s)
Alleles , Genotype , Haplotypes , HLA-DRB1 ChainsABSTRACT
BACKGROUND: A p53 gene is one of the member of tumor suppressor genes involved in the control of cell cycle. The alteration of the p53 gene induces uncontrolled cellular proliferation leading to the development of tumor. Mutations of the p53 gene were found in various human cancers including hematologic malignancies. The incidence of the p53 mutation in acute myelogenous leukemia was reported to be relatively low, however, there has been no report as to the incidence and the characteristics of the p53 mutation in acute myelogenous leukemia in Korea. METHODS: Polymerase chain reaction and single strand conformational polymorphism(PCR-SSCP) was done to screen abnormal band shifts in exons 5, 6, 7, 8 of p53 gene in myeloid blasts obtained from bone marrow aspirates at the time of diagnosis from patients with de novo acute myelogenous leukemia. Mutation of the p53 gene was confirmed by direct sequencing with Sanger method in the DNAs with abnormal band shifts. Cytogenetic analysis of the bone marrow was performed by G-banding method. RESULTS: Only 1(2%) out of 48 patients with acute myelogenous leukemia showed abnormal band shift in exon 5 with PCR-SSCP. Base sequence of exon 5 of this patient with normal karyotype was found to have silent mutation at codon 143 from GTG(valine) to GTA(valine). He had acute myelogenous leukemia of M6 subtype and the leukemia was refractory to two cycles of standard induction chemotherapy, succumbed to death at last. CONCLUSION: Mutation of the p53 gene was found to be very rare in acute myelogenous leukemia in Korea and it was thought to be involved in leukemogensis only in some patients.
Subject(s)
Humans , Base Sequence , Bone Marrow , Cell Cycle , Cell Proliferation , Codon , Cytogenetic Analysis , Diagnosis , DNA , Exons , Genes, p53 , Genes, Tumor Suppressor , Hematologic Neoplasms , Incidence , Induction Chemotherapy , Karyotype , Korea , Leukemia , Leukemia, Myeloid, Acute , Polymerase Chain ReactionABSTRACT
PURPOSE: Radical gastrectomy is main treatment of gastric cancer. But the result is not satisfactory with surgery alone. Most of pattern of failure remain locoregional recurrence. To improve 5 year survival postoperative chemotherapy with or without radiotherapy has been used. We analyzed patients with stage III and IV stomach cancer who had radical operation and received postoperative radiation therapy combined with or without chemotherapy retrospectively. MATERIAL AND METHOD: From March 1985 to June 1993, 68 patients treated with curative resection and received postoperative adjuvant radiotherapy with 36Gy or more were evaluated. Median age was 60 years(range 28-66 yrs). Patients were followed from 3 to 133 months with median follow up of 48 months. Thirty seven patients had non signet ring adenocarcinoma, 29 signet ring cell, 2 other cell. Patients with stage IIIA, IIIB, IV disease were 19, 25 and 24 respectively. Chemotherapy was given to all patients except two. RESULTS: Five-year overall survival and disease-free survival rate were 36.6% and 33.6%, respectively. Prognostic factor affecting survival were assessed. High ratio of involved/dissected lymph node, signet ring histology showed poor prognosis with statistical significance. Presence of residual tumor after surgery, stageIV, split course of radiation therapy, age, number of involved lymph node, number of lymph node dissection and grade of tumor affected survival without statistical significance. Type of chemotherapy did not affect survival.Recurrence was documented in 34 patients. High recurrence was seen in omentum and peritoneum with 23.5%, and remnant stomach, anastomosis site, A-loop and E-loop had also high recurrence with 13.2%. In field locoregional recurrence was 20.7% and total distant metastases were 39.7%. Total intraabdominal failure was 47.1% and extraabdominal failure was 13.2%. Treatment toxicity was considered to be acceptable. 22.1% of patients had grade 3 and only 1 patient had grade 4 leukopenia. Six patients(8.8%) had weigh loss more than 10%. CONCLUSION: Treatment toxicity was acceptable with combined treatment with chemotherapy and radiotherapy. Locoregional recurrence was relatively low compared to distant failure with addition of irradiation. Peritoneal and omental seeding was high. Five-year surival was increased with combined modality. Radiation may eradicate minimal residual disease and improve survival. To evaluate role of radiation prospective randomized study employing chemotherapy alone and chemotherapy plus radiation is necessary. Futhermore to reduce intraabdominal failure, role of intraabdominal chemotherapy in addition to combined chemotherapy plus radiation has to be explored.