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Minoru Takada

Publications and source records attributed to Minoru Takada.

28 records · Page 2Linked to original sources

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death in the world. Lymph node metastasis is not only an important factor in estimating the extent and the metastatic potential of an NSCLC but also in prognosticating the patient outcome. Preoperative prediction of lymph node metastasis might greatly facilitate the choice of appropriate surgical and medical options in patients with NSCLC. METHODS AND RESULTS: Using a cDNA array, we analyzed the expression profiles of 1,289 genes in 92 cancer tissues of NSCLC (37 squamous cell carcinomas and 55 adenocarcinomas). We divided the patients into two groups (classes) for each of various pathological factors, such as lymph node metastasis and pT-stage. For each pair of classes, we searched for an optimal combination of genes to classify the cases using a sequential forward selection algorithm starting from a gene set that showed significant difference in expression between the classes. We used the leave-one-out error cross-validation on a k-nearest neighbor classifier to sequentially choose the gene. Using the optimized set of genes, it was possible to stratify the patients for lymph node metastasis (pN-stage) and pT-stage at, respectively, 100% (23 genes) and 100% (55 genes) for cases with squamous cell carcinomas and 94% (43 genes) and 92% (35 genes) for those with adenocarcinomas. CONCLUSION: We conclude that expression profiling using feature selection provides a powerful means of stratification (personalization) of NSCLC patients and choice in treatment options, particularly for factors such as lymph node metastasis whose radiological diagnosis is presently incomplete.

Adenocarcinoma↗

Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data.

OBJECTIVE: To better understand the nature of the malignancy of biliary tract carcinoma and evaluate the feasibility of its prediction by gene expression profiles. METHODS AND RESULTS: We explored the gene expression profiles characteristic of progression and invasiveness in the cDNA array data obtained from 37 biliary tract carcinomas (15 bile duct, 11 gallbladder, 11 of ampulla of Vater). We pre-selected 51 and 100 genes for the presence versus absence of lymph node metastasis and perineural invasion on the basis of statistical difference. To search optimized sets of genes for prediction, we applied a sequential forward feature selection, minimizing leave-one-out error rates on a k-nearest neighbor classifier. We could predict lymph node metastasis and perineural invasion with an accuracy of 94 and 100%, respectively. When the 6-stage IA cancers without perineural invasion were precluded, a marked difference in gene expression (147 gene), discriminable with 100% accuracy, was noted between positive versus negative perineural invasion, suggesting that the acquisition of invasive character is rather a later molecular pathological event in biliary tract cancer. CONCLUSION: The present method provides a powerful means of classifying biliary tract carcinomas. We also suggest that perineural invasion is an important target of array databased pattern classification, which may predict patient outcomes and facilitate the determination of the extent of surgery to minimize the risk of recurrence.

Biliary Tract↗

[Subset analysis of data in the Japanese patients with NSCLC from IDEAL 1 study on gefitinib].

The multinational, multi-institutional clinical Phase II trial of gefitinib monotherapy, IDEAL (IRESSA Dose Evaluation in Advanced Lung Cancer) 1, included Japanese and non-Japanese patients with advanced non-small-cell lung cancer (NSCLC) pretreated with one or more chemotherapy regimens, at least one including platinum. To investigate whether survival is affected by gender or histological type of cancer, a retrospective, exploratory subset analysis was conducted including only Japanese patients from IDEAL 1 (n = 102 in total, 51 each in 250 and 500 mg/day groups). The median survival time of the 102 patients was 12.0 months and the one year survival rate was 50%. The median survival time was 13.8 months for the 250 mg/day group and 11.2 months for the 500 mg/day group and the one-year survival rate was 57% and 45% respectively. Survival was longer in patients with adenocarcinoma than those with other histological types of cancer, and was longer in those with symptom improvement than without. The median survival time in females was longer than that in males. The results suggest that gefitinib could be superior to classical anticancer agents with regard to not only the response rate but also survival time in patients with NSCLC, particularly adenocarcinoma, previously treated with chemotherapy. Further studies are needed to identify factors affecting survival.

Adult↗

Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.

PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT. PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm. CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.

Adult↗

Frequent and histological type-specific inactivation of 14-3-3sigma in human lung cancers.

One isoform of the 14-3-3 family, 14-3-3sigma, plays a crucial role in the G2 checkpoint by sequestering Cdc2-cyclinB1 in the cytoplasm, and the expression of 14-3-3sigma is frequently lost in breast cancers. This loss of expression is thought to cause a G2 checkpoint defect, resulting in chromosomal aberrations. Since lung cancers frequently carry numerous chromosomal aberrations, we examined the DNA methylation status and expression level of the 14-3-3sigma gene in 37 lung cancer cell lines and 30 primary lung tumor specimens. We found that small cell lung cancer (SCLC) cell lines frequently showed DNA hypermethylation (9 of 13 lines, 69%), and subsequent silencing of the 14-3-3sigma gene. Among non-small cell lung cancers (NSCLC), large cell lung cancer cell lines showed frequent hypermethylation and silencing of 14-3-3sigma (4 or 7 lines, 57%). In contrast, in other NSCLC cell lines, hypermethylation occurred very rarely (1 of 17 lines, 6%). All eight primary SCLC specimens examined also showed a loss or significant reduction in 14-3-3sigma expression in vivo, while a loss or reduction of 14-3-3sigma expression was very rare in primary NSCLC specimens (1 of 22 tissues, 5%). This is the first description that indicates lung cancers frequently show significant inactivation of the 14-3-3sigma gene mainly due to DNA hypermethylation in SCLC, but rarely in NSCLC, suggesting involvement of the 14-3-3sigma gene in lung tumorigenesis in a histological type-specific manner.

14-3-3 Proteins↗

[Amrubicin].

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Animals↗

Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer.

The purpose of this study was to evaluate the efficacy and toxicity of single-agent paclitaxel given weekly to patients with relapsed and refractory small cell lung cancer (SCLC). Patients were treated with 80 mg/m2 paclitaxel administered weekly for 1 h for 6 weeks in an 8-week cycle. Twenty-two patients were enrolled, 21 of whom were eligible. The patient characteristics included: 20 males, 1 female; median age 66 years (range 48-75); performance status 0/1 in 19 and 2 in 5 patients. Grade 3/4 leukopenia and neutropenia occurred in 47.5% and 64%, respectively. Other grade 3/4 toxicities included infection, skin rash, neuropathy and pulmonary toxicity. There were 5 partial responses in 3 out of the 11 sensitive cases and 2 out of the 10 refractory cases, respectively. Paclitaxel, administered as a weekly infusion at a dose of 80 mg/m2, was effective in treating relapsed and refractory SCLC.

Aged↗