Biomedical subjects

S Negoro

Publications and source records attributed to S Negoro.

At least 73 records · Page 4Linked to original sources

PubMed1996

[Late phase II study of LY188011 (gemcitabine hydrochloride) in patient with non-small-cell lung cancer. Gemcitabine Late Phase II Cooperative Study Group A)].

A late phase II study of LY188011 (gemcitabine hydrochloride), a new synthetic anticancer agent, was conducted at 20 Japanese institutions to evaluate the efficacy and safety of the agent administered alone in patients previously untreated with chemotherapy for primary non-small-cell lung cancer (NSCLC). All of the total 73 patients enrolled were eligible and 69 completed at least one course of LY188011 therapy. All patients were evaluated for safety. The response rate was 26.0% (19/73) of eligible patients. The most common adverse reactions included decreased hemoglobin, leukopenia, neutropenia, anorexia, nausea/vomiting, and malaise. Most adverse reactions were of grade 1 or 2 and only a few grade 3 or 4 reactions were reported. However, since a death occurred due to interstitial pneumonia, careful observation for this event is needed. Based on these results, it may be concluded that LY188011, a new anticancer agent, has adequate efficacy for the treatment of NSCLC and causes few clinically relevant adverse reactions.

Adenocarcinoma↗

PubMed1995

A plasmid encoding enzymes for nylon oligomer degradation: nucleotide sequence and analysis of pOAD2.

The entire nucleotide sequence of nylon oligomer degradative plasmid pOAD2 from Flavobacterium sp. KI723T1 was determined. pOAD2 comprises 45519 bp, with a 66.6 mol% G+C content. The precise loci of the four nylon oligomer degradation genes, namely nylA (6-aminohexanoate-cyclic-dimer hydrolase gene), nylB (6-aminohexanoate-dimer hydrolase), nylB' (a gene having 88% homology to nylB) and nylC (endo-type 6-aminohexanoate oligomer hydrolase), and five IS6100 elements were identified on this plasmid. Comparison of the sequence of pOAD2 with those in the GenBank and EMBL databases revealed that the deduced amino acid sequences from eight regions of pOAD2 had significant similarity with the sequences of gene products such as oppA-F (oligopeptide permeases), ftsX (filamentation temperature sensitive), penDE (isopenicillin N-acyltransferase) and rep (plasmid incompatibility). A functional map of pOAD2 is presented.

Amidohydrolases↗

PubMed1995

Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin.

Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 60 mg/m2. The other 13 patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 80 mg/m2 with the granulocyte colony-stimulating factor support (2 micrograms/kg x 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m2 in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT-11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3-4 diarrhea than those with a lower SN-38 level (P = 0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea (P = 0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin.

Adult↗

PubMed1995

Emergence of nylon oligomer degradation enzymes in Pseudomonas aeruginosa PAO through experimental evolution.

Through selective cultivation with 6-aminohexanoate linear dimer, a by-product of nylon-6 manufacture, as the sole source of carbon and nitrogen, Pseudomonas aeruginosa PAO, which initially has no enzyme activity to degrade this xenobiotic compound, was successfully expanded in its metabolic ability. Two new enzyme activities, 6-aminohexanoate cyclic dimer hydrolase and 6-aminohexanoate dimer hydrolase, were detected in the adapted strains.

Amidohydrolases↗

PubMed1995

Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer. Southern Osaka Lung Cancer Study Group.

PURPOSE: To evaluate the response rate, toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3N0-1M0 disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mg/m2 on days 1, 8, 29, and 36), cisplatin (100 mg/m2 on days 1 and 29), and mitomycin (8 mg/m2 on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), followed by 10-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. RESULTS: Of 61 eligible patients, 53 (86.9%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) are alive and disease-free after 2 years. The major toxicity was leukopenia (> or = grade 3, 95%). Other toxicities of > or = grade 3 included thrombocytopenia (45%), anemia (28%), nausea/vomiting (16%), fever (11%), and esophagitis (6%). Treatment-related death occurred in two patients. One patient died of pulmonary toxicity (interstitial pneumonitis) and the other of esophagobronchial fistula with pulmonary infection. CONCLUSION: Concurrent radiotherapy plus chemotherapy with mitomycin, vindesine, and cisplatin (MVP) can be safely administered to patients with stage III NSCLC, with excellent response rates and 2-year survival rates.

Adult↗

PubMed1995

[A late phase-II trial comparing KW-2307 with vindesine in non-small cell lung cancer (1). Lung cancer section in KW-2307 Study Group].

A multicenter cooperative study was performed to compare KW-2307 (KW), a novel vinca alkaloid (VA) derivative, and vindesine (VDS), with respect to tumor response and toxicity in patients (pts) with non-small cell lung cancer. In the former part of the trial, pts received monotherapy with KW 25 mg/m2 or VDS 3 mg/m2. Pts refractory to treatment with KW or VDS were crossed over to treatment with VDS (3 mg/m2/W x 3) or KW (20 mg/m2/W x 3), respectively, in combination with cisplatin (CDDP) 80 mg/m2. Both drugs were administered in 4 courses or more once weekly by intravenous bolus injection in monotherapy. In the subsequent combination therapy, non-responders were treated with CDDP on day 1 and KW or VDS on day 1, 8 and 15 with a course of 28 days, and treatment was given in 2 courses or more in principle. According to the method of O'Brien/Fleming, comparison of tumor response between the 2 treatment groups in the 2nd stage was performed in 154 cases. The response rate of KW group (29.4%, 22/75) was significantly better than that of VDS group (9.3%, 7/75). The main adverse effect in both groups was leukopenia (neutropenia), and no significant difference was observed between the incidence in each group. Among other adverse effects, increased GOT, fever and phlebitis were slightly more often found in KW group, and alopecia and paresthesia a little more in the VDS group. In the later part of combination therapy with CD DP, the KW group achieved PR in 10 of 34 pts (29.4%), and no response was observed in the VDS group (28 pts).

Adenocarcinoma↗

PubMed1995

[Recent progress in chemotherapy for advanced lung cancer].

Recent progress in chemotherapy for advanced nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC) maybe summarized as follows. 1) In seven randomized trials of combination chemotherapy compared with best supportive care in stage IV NSCLC, meta-analysis of indicated that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 2) Cisplatin-based combination chemotherapy followed by chest irradiation improves outcomes of patients with stage III unresectable NSCLC as compared with radiation therapy alone. 3) Meta-analysis has shown that survival is prolonged when radiotherapy is used in combination with chemotherapy in the treatment of limited-stage SCLC. 4) Randomized trials evaluating alternating chemotherapy could not demonstrate the survival benefit in the treatment of extensive-stage (ES) SCLC. 5) The approach to increasing dose intensity has been attempted in the treatment of ES-SCLC. The most common approach is weekly chemotherapy. Results of pilot studies have suggest that this approach prolong survival of patients with ES-SCLC. 6) Recently, several new drugs active against NSCLC and SCLC, including CPT-11, taxol, axotere, vinorelbine and gemcitabine, have been developed. In conclusion, despite these advances of treatment, the cure rate remains quite low in lung cancer. Further investigations are needed to improve the treatment results for patients with this disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Photodynamic therapy and/or external beam radiation therapy for roentgenologically occult lung cancer.

BACKGROUND AND METHODS: Thirty-nine roentgenologically occult lung cancers in 29 patients were treated using photodynamic therapy (PDT) and/or thoracic radiotherapy (TRT) from January 1986 to March 1992. With the exception of one mixed-tumor case, all were squamous cell carcinomas. RESULTS: Initial PDT achieved complete responses in 25 of 39 (64%) of the cancers. Of the remaining 14 cancers that showed less than complete response (CR), 10 of the 14 (71.4%) showed a CR when subsequently treated with TRT, yielding an overall CR rate of 89.7% for cancers treated. Although nine patients experienced recurrences, six of these had CR when treated with PDT and/or TRT. To date, 22 patients are alive. Causes of death in the patients enrolled in this study are as follows: pyothorax (2); heart failure due to pulmonary hypertension (1); chronic respiratory insufficiency (1); subsequent primary brain cancer (1); and subsequent primary lung cancer (1). Only one died of primary lung cancer. CONCLUSIONS: These findings suggest that PDT and/or TRT may be used as an alternative to surgery in the treatment of selected patients with roentgenologically occult lung cancer.

Adult↗

PubMed1994

The nylon oligomer biodegradation system of Flavobacterium and Pseudomonas.

This review article is a compendium of the available information on the degradation of a man-made compound, 6-aminohexanoate-oligomer, in Flavobacterium and Pseudomonas strains, and discusses the molecular basis for adaptation of microorganisms toward these xenobiotic compounds. Three plasmid-encoded enzymes, 6-aminohexanoate-cyclic-dimer hydrolase (EI), 6-aminohexanoate-dimer hydrolase (EII), and endo-type 6-aminohexanoate-oligomer hydrolase (EIII) are responsible for the degradation of the oligomers. Two repeated sequences, designated RS-I and RS-II, are found on plasmid pOAD2, which is involved in 6-aminohexanoate degradation in Flavobacterium. RS-I appears 5 times on the pOAD2, and all copies have the same sequences as insertion sequence IS6100. RS-II appears twice on the plasmid. RS-IIA contains the gene encoding EII, while RS-IIB contains the gene for the analogous EII' protein. Both EII and EII' are polypeptides of 392 amino acids, which differ by 46 amino acid residues. The specific activity of the EII enzyme is 200-fold higher than that of EII'. Construction of various hybrid genes demonstrated that only the combination of two amino acid residues in the EII' enzyme can enhance the activity of the EII' to the same level as that of EII enzyme.

Amino Acid Sequence↗

PubMed1994

Clinicopathological characterization of cardiac free wall rupture in patients with acute myocardial infarction: difference between early and late phase rupture.

Differences in morphological characteristics have been described in early phase and late phase post-infarction cardiac rupture. In this study, the clinicopathological characteristics of early and late phase rupture have been clarified by reviewing the clinical records of 1450 consecutive patients with acute myocardial infarction (AMI). Rupture of the left ventricular free wall (blow-out type) developed in 27 of the 1450 patients, and these patients were divided into two groups on the basis of the rupture time: early phase (< 72 h) and late phase (> 4 days). Only one patient had a history of prior infarction. Early phase rupture was characterized by an abrupt slit-like tear in the infarcted myocardium, a preference for anterior infarction sites, no prior myocardial infarction, and no difference in incidence in conventional and reperfusion therapy, while late phase rupture was characterized by the presence of infarct expansion, no preferential infarct site and a very low incidence in patients with successful reperfusion. Hence, early and late phase cardiac rupture differ in their pathogenesis, and thus the approach to the prevention and prediction of early and late phase cardiac rupture should be different.

Aged↗

PubMed1994

Insertion sequence IS6100 on plasmid pOAD2, which degrades nylon oligomers.

The nucleotide sequence of repeated sequence I, which appears in five regions on nylon oligomer-degrading plasmid pOAD2, harbored in Flavobacterium sp. strain K172, was determined. The five regions of repeated sequence I had 880 bp of identical sequence, and the sequence was identical to that of IS6100, an insertion sequence classified in the IS6 family, initially found in Mycobacterium fortuitum. Sequences homologous to that of IS6100 were found for another nylon oligomer-degrading plasmid, pNAD2, harbored in Pseudomonas sp. strain NK87, by Southern hybridization experiments.

Amino Acid Sequence↗

PubMed1994

Postinflammatory bronchiectatic cavity observed by fibreoptic bronchoscopy.

A 55 year old female, complaining of bloody sputum and fever, was referred to our institution. The chest roentgenogram on admission revealed a large thin-walled cavitary shadow in the right upper lobe. We could clearly observe the inner surface of the postinflammatory bronchiectatic cavity in the right B3 bronchus by fibreoptic bronchoscopy. This is the first case in which interesting bronchoscopic findings of a bronchiectatic cavity could be directly observed.

Bronchi↗

PubMed1994

Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer.

PURPOSE: For patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC), radiotherapy (RT) has been used conventionally for many years. Few prospective trials have determined the role of RT. Recently, chemotherapy (CT) has been shown to produce excellent responses in regionally advanced disease. We therefore conducted a randomized trial using cisplatin (P)-based CT regimens with or without thoracic irradiation. PATIENTS AND METHODS: We randomly assigned 92 patients with locally advanced NSCLC to receive one of three arms of P-based combination chemotherapy: vindesine (V) plus P, mitomycin (M) plus V plus P, or etoposide (E) plus P alternating with V plus M. After two cycles of CT, patients were reevaluated and those with stage III were again randomized to receive RT or not. RT consisted of 50 to 60 Gy in 5 to 6 weeks; 2 Gy was delivered once daily in conventional fractions. RESULTS: Sixty-three patients were included in the second randomization. The patients in the CT/RT group (n = 32) and CT-alone group (n = 31) were comparable in terms of age, sex, performance status, histologic features, stage of disease, and induction CT regimen. The median durations of survival were similar for the two groups (461 days in CT/RT group and 447 days in CT-alone group). The survival rate in the CT/RT group was 58% at 1 year, 36% at 2 years, and 29% at 3 years, as compared with 66%, 9%, and 3% at 1, 2, and 3 years, respectively, in the CT-alone group. One patient in the CT/RT group died of pneumonitis, but there were no CT-related deaths. CONCLUSION: In locally advanced NSCLC, P-based combination CT followed by chest irradiation significantly increases the number of long-term survivors as compared with CT alone. RT to bulky disease in the thorax is thus an important part of combined modality therapy, and a necessary part of further studies in locally advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer].

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.

Adult↗

PubMed1993

Characterization of the 6-aminohexanoate-dimer hydrolase from Pseudomonas sp. NK87.

The DNA base sequence of the Pseudomonas sp. NK87 gene (P-nylB) for 6-aminohexanoate-dimer hydrolase (P-EII), a xenobiotic-compound-degrading enzyme, was determined. It has an open reading frame of 1188 bp, initiated by ATG and terminated by TAG, and coding for 396 amino acids. The base sequence of the open reading frame has 53% sequence similarity to that of the gene for the same enzyme of Flavobacterium sp. KI72 (F-nylB) and 35% sequence similarity with respect to the deduced amino acid sequence. The P-EII enzyme was purified from an Escherichia coli clone in which the P-EII gene was highly expressed. The P-EII enzyme was inhibited by a serine protease inhibitor, diisopropyl fluorophosphate, as was the F-EII enzyme. Double reciprocal plots obtained from various concentrations of 6-aminohexanoate-dimer indicated that the kcat value of the P-EII enzyme (9.2 s-1) was approximately half that of the F-EII enzyme (19 s-1), and the P-EII enzyme had higher affinity toward this substrate (Km for P-EII, 0.6 mM; Km for F-EII, 15 mM). The P-EII enzyme had a temperature optimum of 48 degrees C, and a pH optimum of 7.5. It is speculated that since the P-nylB and F-nylB genes are more diverged from each other than the corresponding nylA genes, the latter may have evolved more recently.

Amidohydrolases↗

PubMed1993

Enhanced antitumor efficacy of a combination of CPT-11, a new derivative of camptothecin, and cisplatin against human lung tumor xenografts.

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c (nu/nu) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.

Animals↗

PubMed1993

Nylon oligomer degradation gene, nylC, on plasmid pOAD2 from a Flavobacterium strain encodes endo-type 6-aminohexanoate oligomer hydrolase: purification and characterization of the nylC gene product.

A new type of nylon oligomer degradation enzyme (EIII) was purified from an Escherichia coli clone harboring the EIII gene (nylC). This enzyme hydrolyzed the linear trimer, tetramer, and pentamer of 6-aminohexanoate by an endo-type reaction, and this specificity is different from that of the EI (nylA gene product) and EII (nylB gene product). Amino acid sequencing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified EIII demonstrated that the enzyme is made of two polypeptide chains arising from an internal cleavage between amino acid residues 266 and 267.

Amidohydrolases↗

PubMed1992

The effect of taurine on the age-related decline of the immune response in mice: the restorative effect on the T cell proliferative response to costimulation with ionomycin and phorbol myristate acetate.

1. Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. 2. The degree of the age-related decline was more significant in T cells than in B cells. 3. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. 4. The augmentation of the proliferative response by taurine was more marked in old T cells than in young T cells. 5. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in old T cells when stimulated with PMA and ionomycin than observed in young T cells. 6. In the presence of taurine, the concentration of [Ca2+]i in the old T cells significantly increased under stimulation by PMA and ionomycin. 7. The results indicate that taurine improved the proliferative response in old T cells by restoration of the increment of the concentration of [Ca2+]i under the stimulation by PMA and ionomycin.

Aging↗