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Biomedical subjects

S Ryu

Publications and source records attributed to S Ryu.

At least 19 recordsLinked to original sources

Stimulation of the onset of sporulation of Clostridium perfringens type A by netropsin and distamycin.

The basic peptide antibiotics, netropsin and distamycin, previously shown to inhibit sporulation of Bacillus subtilis, stimulated low levels of sporulation of Clostridium perfringens strain NCTC 8798 at concentrations of 1.0 and 0.1 microgram/ml respectively. Most sporulating cells produced in the presence of the antibiotics were defective. These were blocked at Stage III of sporulation, and many possessed forespores exterior to the sporangium. The same antibiotics could also inhibit the caffeine-induced stimulation of sporulation of this strain.

Clostridium perfringens

Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study.

Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large-cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted.

Adult

The necessity of differential immunosuppression for prevention of immune rejection by FK506 in rat islet allografts transplanted into the liver or beneath the kidney capsule.

The purpose of the present study was to achieve prevention of immune rejection in rat islet allografts by FK506. WKA/Qdj (RT1u) islets were transplanted either into the liver via the portal vein (p.v.) or beneath the kidney capsule (k.c.) of streptozotocin (60 mg/kg) induced diabetic Lewis (RT1(1)) rats. Fresh or cultured (24 degrees C, 1 week) islets were used as donors. A miniosmotic pump (0.2 ml, Alzet 2001) containing 5 mg FK was implanted s.c. at the time of transplantation for continuous delivery of FK506 for 7 days after transplantation. The mean survival time (MST) of the fresh p.v. grafts with a pump was offater than 61.4 +/- 37.2 days (mean +/- SD, n = 17) (control 5.5 +/- 0.6, n = 4). Ten out of 17 were normoglycemic for more than 90 days after transplantation. When low-temperature cultured islets were used and FK506 was delivered for 7 days, all the rats were normoglycemic for more than 90 days after transplantation. The MST of the fresh or cultured k.c. grafts with a pump was 22.0 +/- 14.2 or 24.7 +/- 5.0 days, respectively. Long-term administration of FK506 by repeated implantations (5 times; days 0, 7, 14, 21, and 28) of pumps containing 5 mg FK506 produced marked prolongation of the fresh or cultured k.c. graft survival with an MST of greater than 58.7 +/- 22.1 or greater than 56.9 +/- 18.0 days, respectively. These findings clearly demonstrate that the prevention of immune rejection in the islet allografts transplanted into the liver was achieved by short-term post-transplant administration of FK506 and low-temperature culture of donor islets, and also show that long-term continuous administration of FK506 was needed for the prolongation of the graft survival when the renal subcapsular space was the site for implantation of islets. Thus, the present study indicates that in different transplant sites different immunosuppressive regimes are needed for the control of rejection by FK506 in rat islet allografts.

Animals

Sensitivity and specificity of lung cancer screening in Osaka, Japan.

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981-1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.

Adult

[A case of pulmonary aspergillosis with a tumor shadow, diagnosed by transbronchial aspiration cytology].

A 41-year-old female was admitted because of cough and hemosputum. She had no underlying disease and the presence of respiratory disease had not been pointed out. Chest X-ray and CT scan showed a solid, homogeneous tumor with a distinct margin near the right hilum. The tumor measured approximately 5 x 4 cm. Because other laboratory data concerning the serum levels of tumor marker and anti-aspergillus antibody were normal, benign lung tumor or malignant lymphoma was suspected at first. Transbronchial cytology and biopsy were performed, but there were no significant findings. However transbronchial aspiration cytology of the specimen obtained from the bifurcation between the right upper lobe bronchus and the truncus intermedius demonstrated Aspergillus. After the administration of antifungal drugs, the tumor decreased in size, and an air crescent sign appeared. This was thought to be a very rare case of locally invasive form of pulmonary aspergillosis, as described by Sider et al demonstrating a necrotic fungal ball during its clinical course.

Adult

[High-dose Tegafur (FT) for primary lung cancer: a phase I trial].

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.

Drug Administration Schedule

Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer.

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.

Aged

Combination chemotherapy with or without radiation therapy in small cell lung cancer. An analysis of a 5-year follow-up.

From January 1978 to March 1984, a series of 159 patients with newly diagnosed small cell lung cancer (SCLC) was treated with combination chemotherapy with or without chest radiation at the Osaka Prefectural Habikino Hospital. By March 31, 1989, ten patients (6.3%) had survived for 5 years or more after the initial chemotherapy, including nine of 95 patients (9.5%) with limited disease and one of 64 patients (1.6%) with extensive disease. All these 5-year disease-free survivors, except for one patient whose response could not be assessed by chest radiograph because of radiation fibrosis, had a complete response. Nine of the 71 patients (12.7%) treated with combination regimens containing doxorubicin survived 5 years or more, and only one of the 88 (1.1%) treated with regimens without doxorubicin had long-term survival (P less than 0.01). The sex, performance status (PS), and chest radiation after systemic chemotherapy did not correlate statistically with long-term survival (P greater than 0.05). Three of the ten patients died free of SCLC. Two of the ten patients (20%) developed second malignancies and died. The remaining patient died of pneumonia. The Cox regression analysis identified the PS and doxorubicin-containing regimens as important factors indicating improved survival. Combination regimens containing doxorubicin have, therefore, been found to be very effective in improving survival and achieving long-term survival.

Adult

FK506 as the sole immunosuppressive agent for prolongation of islet allograft survival in the rat.

The purpose of the present study was to determine immunosuppressive effects of a new immunosuppressive agent, FK506, on rat islet allografts and also whether FK is toxic to the islet grafts since the diabetogenic effects of FK is controversial. Hand-picked clean fresh islets (WKA/Qdj:RT1u) were transplanted either beneath the renal capsule or into the liver via the portal vein of the diabetic (STZ, 60 mg/kg) rats (Lewis:RT1(1)). FK506 was administered s.c. for 7 days after transplantation. The mean survival times (MST)* of the renal subcapsular grafts receiving 0 (control), 0.32 or 1.0 mg/kg FK were 7.2 +/- 1.1 (mean +/- SD, n = 5), 13.8 +/- 4.8 (n = 4), and 20.2 +/- 8.0 days (n = 5), respectively. The MST of the intrahepatic grafts receiving 0, 0.1, 0.32, or 1.0 mg/kg FK were 4.4 +/- 1.1 (n = 5), 7.2 +/- 0.8 (n = 5), greater than 45.3 +/- 23.1 (n = 6) or greater than 54.4 +/- 8.8 days (n = 5), respectively. Histologically, islets were found easily in the liver of normoglycemic recipients for more than 60 days after transplantation and appeared intact, with well-granulated beta cells. Foci of mononuclear cells were occasionally seen adjacent to the islet cells. The plasma glucose of the recipients with 1.0 mg/kg FK fluctuated between 150 and 350 mg/dl without rejection. In the recipients treated with 3.2 mg/kg FK the plasma glucose of all the recipients (n = 3) returned to pretransplant levels by 21 days after transplantation. However, islet cells were present in the liver of all these recipients without mononuclear cell infiltration. Immunohistochemically islet grafts stained weakly for insulin, but to the same extent as the controls for glucagon and somatostatin. These findings clearly demonstrate the immunosuppressive effect of FK506 on islet allografts and the importance of the transplant site for prolongation of graft survival by FK, and also suggest that FK has toxic effects on the islet grafts (B cells) when used in high dosages.

Animals

Combination therapy with bestatin in inoperable lung cancer. A randomized trial.

A randomized trial of combination therapy with bestatin (30 mg daily, every day) was performed in 238 patients with inoperable primary lung cancer from August, 1981 through April, 1984. Of the 238 patients, 227 were evaluable: 113 treated by bestatin combination therapy and 114 controls. There was no statistically significant difference in response rate or survival between the 2 groups. In squamous cell cancer response was observed in 34.5% of the bestatin group and 17.9% of the control group. The analysis, including Cox's proportional hazard model, revealed that the survival tended to be longer in the bestatin group (median survival 40 weeks) than in the control group (median survival 24 weeks; p = 0.051). This suggests that addition of bestatin might be beneficial in squamous cell cancer of the lung but further, more rigidly controlled, clinical trials are necessary before more definitive conclusions can be drawn.

Aged

[Prognostic factors affecting survival and response in patients with advanced non-small cell lung cancer treated with combination chemotherapy].

One-hundred and ninety-nine patients who had an inoperable stage III or IV non-small cell lung cancer (NSCLC) and collected were analyzed on the basis of factors affecting survival duration and response to chemotherapy. These patients were registered into a prospective randomized trial conducted from May of 1986 to April of 1988, and received either cisplatin and vindesine, cisplatin, vindesine and mitomycin C, or cisplatin and etoposide alternating with vindesine and mitomycin C. In the univariate analysis, sex, ECOG's performance status (PS), weight loss within previous 6 months, clinical stage, serum albumin value, serum lactate dehydrogenase level and hemoglobin (Hb) level were considered to be significant factors for survival (p less than 0.05). In the multivariable analysis using Cox's proportional model, clinical stage, PS, sex, weight loss and Hb level were proven to be significant variables for survival in the order of importance. When the response to chemotherapy was included in a conditional multivariable analysis, it was strongly associated with survival duration. A multivariable analysis of response using the logistic regression method demonstrated that female sex, cisplatin, vindesine and mitomycin combination regimen, squamous cell type, and no weight loss were significantly predictive of response outcome. These results are useful when comparing the response data and survival of completed studies and designing future trials in advanced NSCLC.

Adult

Three-year disease-free survivors of small cell lung cancer treated with combination chemotherapy with or without chest irradiation.

One hundred and seventy-four patients with small cell lung cancer (SCLC) treated with combination chemotherapy, with or without chest radiation, were analyzed. Fourteen patients (8%) survived for 3 years or more. Three-year disease-free survival continued for 12 of the 101 patients (12%) with limited disease, and one of 75 (1%) with extensive disease (P less than 0.05). Patients' sex and performance status were not important in achieving long-term survival. All disease-free survivors, except two who could not be evaluated, achieved a complete response. Although the treatment programs had some influence on the long-term survival rates (P less than 0.05), thoracic radiation did not have significant impact on long-term survival. Three of the 13 patients (23%) developed second malignancies and died, and one of these patients also suffered from a progressive neurologic deterioration with dementia. Two other patients died free of SCLC. Consequently, eight have remained alive and free of disease. The last relapse was observed at 1.5 years from beginning of treatment. The disease-free survival may offer the hope of cure of SCLC. However, the survivors are at an increased risk of developing late complications including second malignancies and neurologic abnormalities. Therefore, careful follow-up will be necessary.

Adult