To identify novel hematologic tumor-specific differentially methylated regions, we performed DNA methylation analysis of 7 new candidate genes (ZAR1, GATA4, CDH22, SOX3, SLC16A5, EHD3 and TBPL1), which has been identified to be aberrantly methylated in human cancers or animal models of human cancer. Bone marrow or peripheral blood samples from 20 patients with leukemia (including 10 AML and 6 ALL) before treatment and normal lymphocyte cells from 4 healthy individuals as well as eight human leukemia/lymphoma cell lines were used in this study and analyzed with quantitative DNA methylation analysis using the Sequenom MassARRAY system. All four normal control samples showed no or very low level of cytosine methylation in all of the genomic regions examined. However, leukemia/lymphoma cell lines showed frequent hypermethylation of the ZAR1, SLC16A5, EDH3, GATA4, CDH22 and SOX3 genes. DNA hypermethylation of SOX3 was also frequently observed in most of hematologic malignancy cases. Aberrant hypermethylation of ZAR1, GATA4 and CDH22 was also frequently observed in both Philadelphia chromosome positive and negative ALL samples but not in all 10 AML cases. We identified novel genomic regions of ZAR1, GATA4, CDH22 and SOX3 with aberrant cytosine methylation in hematological malignancies. Among those, aberrant DNA methylation of ZAR1, GATA4 and CDH22 may be involved in carcinogenesis of lymphoid populations.
Purpose: Although the short-term effects of tiotropium for patients with Stage II-IV COPD have been established, the effects on patients in earlier stages are not known. We studied the short-term effects of tiotropium on pulmonary function, quality of life (QOL), and clinical symptoms in patients at risk for and with mild COPD. Subjects and methods: The subjects enrolled the study consist of 85 patients who visited the clinics due to respiratory symptoms, were more than 40 years old, and had a smoking history of more than 10 pack-years were enrolled. They were divided into an At risk-Stage I COPD group and a Stages II-IV COPD group. After the administration of tiotropium for 12 weeks, the changes in the pulmonary function test, QOL, and subjective symptoms were compared before and after the therapy. Results: Tiotropium increased the FEV1, FVC, and IC and improved the SGRQ scores in the patients in the Stage II-IV COPD group, while it did not cause a significant difference in the At risk-Stage I groups. Some patients in the At risk-Stage I group who experienced an improvement in their subjective symptoms. Conclusions: We could not show that the patients in the At risk-Stage I group benefited from tiotropium. However, some patients in the At risk-Stage I groups showed improvements in their symptoms. Tiotropium may be effective to relieve symptoms in some patients even when they are in the At risk-Stage I groups.
Background: The question in the title remains unanswered and also is both old and new among gastric surgeons. Although there have been many reports about the early-stage quality of life and postoperative morbidity, they have failed to conclude about the advantages of these two reconstructions after distal gastrectomy. In this study, we summarized more than 30 years of experience and evaluated whether the Billroth I or Billroth II reconstruction procedure is better for patient survival after distal gastrectomy. Methods: From January 1977 to August 2005, a total of 1410 gastric cancer patients underwent distal gastrectomy with Billroth I (n=1184) or Billroth II (n=226) reconstruction in the Department of Gastroenterological Surgery, Tokai University. The 10- and 20-year follow-up cases numbered 980 (82.8%) and 692 (58.4%) for Billroth I, and 213 (94.2%) and 195 (86.3%) for Billroth II as of September 2009, respectively. Among them, 1015 patients (72.0%) received curative resection and were followed to evaluate the types of recurrence. Results: In the patients with Billroth I and Billroth II, the 5-, 10-, 15-, and 20-year survival rates were 77.4%, 66.6%, 56.0%, and 45.7%, and 39.7%, 32.8%, 25.9%, and 19.6%, respectively (P<0.0001; relative risk, 2.683; 95% confidence interval, 2.261?3.183). The patients in stages 1A and 4 showed significantly better survival with Billroth I than with Billroth II. The patients with Billroth II (10/86, 11.6%) showed significantly higher hematogenous recurrence than those with Billroth I (41/929, 4.4%). Conclusions: If gastric cancer patients must receive distal gastrectomy, we recommend they receive Billroth I reconstruction.
In the present study, the efficacy of TJ-14 for the prevention and/or treatment of chemotherapy induced oral mucositis is investigated in a randomized double-blind, placebo-controlled experimental clinical trial in colorectal cancer patients. The primary endpoint of this study is the incidence of persisting≧grade 2 oral mucositis, which is compared between the TJ-14 and placebo groups. The secondary endpoints include the duration of grade≧2 oral mucositis, and the worst oral mucositis grade throughout the protocol therapy, and time to disappearance of oral mucositis. Ninety patients are reqired in the study.
Some previous studies reported the relationship between the mutation status of epidermal growth factor receptor (EGFR) gene and serum carcinoembryonic antigen (CEA) level in advanced or recurrent lung adenocarcinomas. In the present study, this relationship was examined in resected lung adenocarcinomas. One hundred thirty five resected lung adenocarcinoma patients were reviewed retrospectively. Mutations of the EGFR gene were detected in 64 of the 135 patients, the most common being deletions in exon 19 and the L858R mutations in exon 21. The patients with normal serum CEA level had favorable prognosis, whereas those with high had poor prognosis. The 5-year survival of the patients with EGFR mutation-negative was significantly worse than that of the patients with EGFR mutation-positive. Both univariate and multivariate analyses indicated an independent prognostic impact of the combined use of serum CEA level and the status of EGFR mutation. There was no difference in the rate of EGFR gene mutations according to the serum CEA level. Furthermore we also failed to find the differences in the serum CEA level based on the EGFR mutation status. The rate of deletions in exon 19 and/or the L858R mutation in exon 21 was not also related to the serum CEA level. In conclusions we failed to find the relationship between the serum CEA level and the EGFR mutation status in resected lung adenocarcinomas.