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Biomedical subjects

Koji Takeda

Publications and source records attributed to Koji Takeda.

At least 19 recordsLinked to original sources
PubMed2006

Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, which was administered to patients with advanced solid tumors on days 1 and 8 in 3-week courses.

PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of TZT-1027 (soblidotin), a dolastatin 10 analogue, in Japanese patients with advanced solid tumors when administered on days 1 and 8 in 3-week courses. METHODS: Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, and also met the following criteria: prior chemotherapy < or = 2 regimens, Eastern Cooperative Oncology Group (ECOG) performance status < or = 1, and acceptable organ function. The MTD was defined as the highest dose at which no more than one of six patients experienced a DLT during course 1. Pharmacokinetic samples were collected in courses 1 and 2. RESULTS: Eighteen patients were enrolled in the present study. Three doses (1.5, 1.65, and 1.8 mg/m(2)) were evaluated. Neutropenia was the principal DLT at doses of 1.65 and 1.8 mg/m(2). In addition, one patient also experienced grade 3 pneumonia with neutropenia, and another patient experienced grade 3 constipation, neuropathy, grade 4 neutropenia, and hyponatremia as DLTs at 1.65 mg/m(2). Phlebitis, the most frequent nonhematological toxicity, was improved by administration of additional saline after TZT-1027 administration. The MTD was 1.5 mg/m(2), at which DLT was not observed in a total of nine patients. The pharmacokinetic profile did not differ from that for the European population. One patient with metastatic esophageal cancer achieved partial response, and each of two patients with non-small cell lung cancer had a minor response. CONCLUSIONS: When TZT-1027 was administered on days 1 and 8 in 3-week courses to Japanese patients, the MTD was 1.5 mg/m(2) and was lower than the value of 2.4 mg/m(2) in European patients. However, antitumor activity was observed at low doses. TZT-1027 was tolerated well at the MTD, without grade 3 nonhematological toxicities or neutropenia up to grade 2. TZT-1027 is a promising new tubulin polymerization inhibitor that requires further investigation in phase II studies.

Aged↗
PubMed2006

Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904).

PURPOSE: Docetaxel has shown activity in elderly patients with advanced non-small-cell lung cancer (NSCLC). This randomized phase III trial evaluated the efficacy and safety of docetaxel versus vinorelbine (the current standard treatment) in elderly patients. PATIENTS AND METHODS: Chemotherapy-naïve patients age 70 years or older with stage IIIB/IV NSCLC and performance status 2 or lower were eligible. Patients randomly received docetaxel 60 mg/m2 (day 1) or vinorelbine 25 mg/m2 (days 1 and 8) every 21 days for four cycles. The primary end point was overall survival. Overall disease-related symptom improvement was assessed using an eight-item questionnaire. RESULTS: In total, 182 patients were enrolled. Median age was 76 years (range, 70 years to 86 years). There was no statistical difference in median overall survival with docetaxel versus vinorelbine (14.3 months v 9.9 months; hazard ratio, 0.780; 95% CI, 0.561 to 1.085; P = .138). There was a significant difference in median progression-free survival (5.5 months v 3.1 months; P < .001). Response rates were also significantly improved with docetaxel versus vinorelbine (22.7% v 9.9%; P = .019). The most common grade 3 to 4 toxicities were neutropenia (82.9% for docetaxel; 69.2% for vinorelbine; P = .031) and leukopenia (58.0% for docetaxel; 51.7% for vinorelbine). Other toxicities were mild and generally well tolerated. Docetaxel improved overall disease-related symptoms over vinorelbine (odds ratio, 1.86; 95% CI, 1.09 to 3.20). CONCLUSION: Docetaxel improved progression-free survival, response rate, and disease-related symptoms versus vinorelbine. Overall survival was not statistically significantly improved at this time. Docetaxel monotherapy may be considered as an option in the standard treatment of elderly patients with advanced NSCLC.

Aged↗
PubMed2006

Isolation and identification of 2alpha,25-dihydroxyvitamin D3, a new metabolite from Pseudonocardia autotrophica 100U-19 cells incubated with Vitamin D3.

Pseudonocardia autotrophica converted Vitamin D(3) to 25-hydroxyvitamin D(3) and 1alpha,25-dihydroxyvitamin D(3). The hydroxylation of Vitamin D(3) with P. autotrophica was enhanced by the addition of cyclodextrin. In this microbial hydroxylation, a new Vitamin D(3) metabolite was observed in the reaction mixture of P. autotrophica and Vitamin D(3), and was isolated in a pure form by several steps of chromatography. The structure of the new metabolite was determined to be 2alpha,25-dihydroxyvitamin D(3) by UV, NMR and mass spectroscopic analyses. Biological evaluation of the new metabolite was conducted by means of several experiments.

Animals↗
PubMed2006

Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib.

PURPOSE: Interstitial lung disease (ILD) is a serious adverse effect of gefitinib, but its prevalence and risk factors remain largely unknown. We examined the prevalence of and risk factors for gefitinib-induced ILD associated with practical use of the drug in Japanese with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinical information was retrospectively assembled for NSCLC patients who started gefitinib treatment at affiliated institutions of the West Japan Thoracic Oncology Group between August 31 and December 31, 2002. Medical records of patients who developed pulmonary infiltrates were reviewed by a central committee of extramural experts for identification of patients with gefitinib-induced ILD. Multivariate logistic or Cox regression analysis was performed to identify independent predictive factors for ILD, antitumor response, and survival. RESULTS: Seventy cases of and 31 deaths from gefitinib-induced ILD were identified among 1,976 consecutively treated patients at 84 institutions, corresponding to a prevalence of 3.5% and mortality of 1.6%. Gefitinib-induced ILD was significantly associated with male sex, a history of smoking, and coincidence of interstitial pneumonia (odds ratios = 3.10, 4.79, and 2.89, respectively). Predictive factors for response were female sex, no history of smoking, adenocarcinoma histology, metastatic disease, and good performance status (PS), whereas predictive factors for survival were female sex, no history of smoking, adenocarcinoma histology, nonmetastatic disease, good PS, and previous chest surgery. CONCLUSION: ILD is a serious adverse effect of gefitinib in the clinical setting that cannot be ignored. However, patient selection based on sex and smoking history can minimize ILD risk and maximize the clinical benefit of gefitinib.

Adult↗
PubMed2006

Valve repair with maze procedure in acromegaly.

Acromegaly is characterized by a hypersecretion of growth hormone and is frequently associated with valvular abnormality and arrhythmia. The increased morbidity and mortality is primarily caused by stroke and cardiovascular disease. Therefore, valve reconstruction and sinus rhythm recovery will be particularly beneficial. We report herein the successful surgical treatment of two patients with combined valvular insufficiency and chronic atrial fibrillation in the setting of acromegaly.

Acromegaly↗
PubMed2006

Production of alpha, omega-alkanediols using Escherichia coli expressing a cytochrome P450 from Acinetobacter sp. OC4.

Our biotransformation using Escherichia coli expressing a cytochrome P450 (CYP) belonging to the CYP153A family from Acinetobacter sp. OC4 produced a great amount of 1-octanol (2,250 mg per liter) from n-octane after 24 h of incubation. This level of production is equivalent to the maximum level previously achieved in biotransformation experiments of alkanes. In addition, the initial production rate of 1-octanol was maintained throughout the entire incubation period. These results indicate that we have achieved the functional and stable expression of a CYP in E. coli for the first time. Further, our biotransformation system showed alpha,omega-diterminal oxidation activity of n-alkanes, and a large amount of 1,8-octanediol (722 mg per liter) was produced from 1-octanol after 24 h of incubation. This is the first report on the bioproduction of alpha,omega-alkanediols from n-alkanes or 1-alkanols.

Acinetobacter↗
PubMed2006

[A case of intravascular lymphomatosis with no abnormal findings on chest computed tomography and with diffuse pulmonary uptake of 67Ga on scintigraphy].

A 45-year-old man was admitted to our hospital with high-grade fever uncontrolled by antipyretic drugs, and elevation of the serum LDH and sIL-2R levels, and decrease of diffusing capacity for carbon monoxide. Chest computed tomography (CT) showed no abnormal findings but 67Ga scintigraphy revealed diffuse pulmonary uptake. He was given a diagnosis of intravascular lymphomatosis (IVL) based on transbronchial lung biopsy (TBLB) and immunohistochemical analysis. The prognosis of IVL is generally bad, because antemortem diagnosis is difficult. In this case early TBLB enabled satisfactory curative effect of IVL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Isolation and characterization of solvent-tolerant Pseudomonas putida strain T-57, and its application to biotransformation of toluene to cresol in a two-phase (organic-aqueous) system.

Pseudomonas putida T-57 was isolated from an activated sludge sample after enrichment on mineral salts basal medium with toluene as a sole source of carbon. P. putida T-57 utilizes n-butanol, toluene, styrene, m-xylene, ethylbenzene, n-hexane, and propylbenzene as growth substrates. The strain was able to grow on toluene when liquid toluene was added to mineral salts basal medium at 10-90% (v/v), and was tolerant to organic solvents whose log P(ow) (1-octanol/water partition coefficient) was higher than 2.5. Enzymatic and genetic analysis revealed that P. putida T-57 used the toluene dioxygenase pathway to catabolize toluene. A cis-toluene dihydrodiol dehydrogenase gene (todD) mutant of T-57 was constructed using a gene replacement technique. The todD mutant accumulated o-cresol (maximum 1.7 g/L in the aqueous phase) when cultivated in minimal salts basal medium supplemented with 3% (v/v) toluene and 7% (v/v) 1-octanol. Thus, T-57 is thought to be a good candidate host strain for bioconversion of hydrophobic substrates in two-phase (organic-aqueous) systems.

Biotechnology↗
PubMed2005

Determination of micelle mass by electrospray ionization mass spectrometry.

By electrospray ionization (ESI) mass spectrometry, micelle solutions of sodium cholate were investigated in detail in the presence and absence of ethanol. The average aggregation number could be evaluated from the spectra acquired under conditions where soft collisions adequate to measure the micelle solution were induced, and the value agreed well with that obtained previously by other methods. From the dependence on ethanol content, it was also found that the average aggregation number in aqueous solution without organic solvent could be reliably estimated. The ESI method proved to be a useful tool for determining the micelle mass in the original aqueous phase.

Journal Article↗
PubMed2005

[Persistent apnea in an obese patient with myotonic dystrophy].

We report a case of a 35-year-old woman with myotonic dystrophy and severe obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian resection. The patient received an iv induction with minimum dose of propofol and vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and 50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was administered twice. Surgery was performed uneventfully within 130 minutes and iv propofol was discontinued. The patient awoke promptly after termination of nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60 mmHg. Because she could obey the order to breathe, the endotracheal tube was removed 40 minutes after discontinuation of propofol. Spontaneous breathing at the rate of 17 x min(-1) started soon after extubation. We assume that this apnea was caused by breath holding. Whether this breath holding is specific to myotonic dystrophy or not, anesthesia for patients with this disease requires careful attention for perioperative respiratory management.

Adult↗
PubMed2004

Biotransformation of various alkanes using the Escherichia coli expressing an alkane hydroxylase system from Gordonia sp. TF6.

Biotransformation using alkane-oxidizing bacteria or their alkane hydroxylase (AH) systems have been little studied at the molecular level. We have cloned and sequenced genes from Gordonia sp. TF6 encoding an AH system, alkB2 (alkane 1-monooxygenase), rubA3 (rubredoxin), rubA4 (rubredoxin), and rubB (rubredoxin reductase). When expressed in Escherichia coli, these genes allowed the construction of biotransformation systems for various alkanes. Normal alkanes with 5 to 13 carbons were good substrates for this biotransformation, and oxidized to their corresponding 1-alkanols. Surprisingly, cycloalkanes with 5 to 8 carbons were oxidized to their corresponding cycloalkanols as well. This is the first study to achieve biotransformation of alkanes using the E. coli expressing the minimum component genes of the AH system. Our biotransformation system has facilitated assays and analysis leading to improvement of AH systems, and has indicated a cycloalkane oxidation pathway in microorganisms for the first time.

Alkanes↗
PubMed2004

[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↗
PubMed2003

Highly active catalyst for the heterogeneous Suzuki-Miyaura reaction: assembled complex of palladium and non-cross-linked amphiphilic polymer.

An assembled insoluble catalyst, PdAS, prepared from palladium ((NH4)2PdCl4 (1)) and non-cross-linked amphiphilic copolymer poly(N-isopropylacrylamide-co-4-diphenylstyrylphosphine) (2) was developed. It was found that PdAS is an excellent catalyst for the Suzuki-Miyaura reaction on three points: (1) The use of 8 x 10(-7) to 5 x 10(-4) mol equiv of PdAS afforded the coupling products efficiently after easy workup, with the turnover number reaching up to 1,250,000. (2) The catalyst was reusable many times without loss of catalytic activity. (3) PdAS showed good stability in any reaction medium (i.e., water or aqueous or anhydrous organic solvents). Analytical study of PdAS indicates that the phosphines in 2 coordinate to palladium to form PdCl2(PPh2Ar)2 species.

Journal Article↗
PubMed2003

A phase II study of topotecan in patients with relapsed small-cell lung cancer.

An early phase II study of topotecan produced favorable results in a small number of untreated and previously treated patients with small-cell lung cancer (SCLC). This multicenter study was conducted in patients with relapsed SCLC at 19 medical institutions in Japan. Topotecan 1.0 mg/m2/day was administered for 5 consecutive days every 3 weeks. Fifty-three patients were enrolled in the study. One patient was withdrawn before the commencement of study treatment, and 2 patients were unable to continue study treatment due to an interruption in the supply of study medication. The response rate was 26.0% in 13 of the 50 evaluable patients who were eligible and completed protocol-specified treatment and procedures. The median time to progression and overall survival were 133 days and 262 days, respectively. The most frequently reported toxicity was reversible myelosuppression, such as leukopenia, neutropenia, anemia (decreased hemoglobin), and thrombocytopenia. Nonhematological toxicity was also reported but the incidence of grade 3/4 symptoms was low. The results of this study indicate that topotecan is effective against relapsed SCLC with good tolerability.

Journal Article↗
PubMed2002

An assembled complex of palladium and non-cross-linked amphiphilic polymer: a highly active and recyclable catalyst for the Suzuki-Miyaura reaction.

An insoluble and assembled catalyst of palladium and a non-cross-linked amphiphilic polymer were developed. In the presence of 50-500 ppm mol equiv of catalyst, the Suzuki-Miyaura reaction proceeded efficiently under organic solvent-free conditions. The catalyst was reused 10 times without any decrease in activity and was recycled without any special treatment.[structure: see text]

Journal Article↗
PubMed2002

Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer.

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.

Adult↗