Biomedical subjects

T Ohnoshi

Publications and source records attributed to T Ohnoshi.

At least 55 records · Page 3Linked to original sources

PubMed1992

Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line.

An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

[Treatment of small cell lung cancer in the elderly: the progress and limitation of chemotherapy].

In order to assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients who had entered into protocol studies between 1982 and 1990. Among those, there were 101 elderly patients (age of greater than or equal to 66 years) and 117 non-elderly patients (age of less than or equal to 65 years). Response to chemotherapy with or without chest irradiation was almost comparable for the elderly and the non-elderly; complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were quite similar: The median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. An improvement of patient survival was observed along with the chronology of the protocols, i.e., with a escalation of dose intensity. Of interest, the improvement was rather evident in the elderly than in the non-elderly. Hematologic toxicity was considerable more frequent and severe in the elderly than in the non-elderly with non-significant statistics. The incidense of fever episodes while neutropenic was significantly more frequent in the elderly. Non-hematologic toxicity was almost comparable for the two groups, with a exception that the elderly showed a trend being predisposed to renal toxicity. In conclusion, such elderly patients as eligible for entry into a protocol study can benefit from intensive treatment as equally as non-elderly patients can.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[Serum neuron specific enolase (NSE) levels in patients with non small cell lung cancer].

Serum NSE levels were measured in 126 patients with previously untreated NSCLC. The NSE level was greater than 10 ng/ml in 29 patients (23.0%) and this was considered to be positive. Elevation of serum NSE levels correlated closely with clinical stage except stage I and II. The effect of chemotherapy was evaluated in 74 cases included 22 NSE-positive cases. The response rate was 50% in positive cases and 34.6% in negative cases. However, the median duration of response in positive cases (2.2 months) was significantly shorter than that in negative cases (6.6 months). The median survival time of 6.0 months in positive cases was brief compared with 9.6 months in negative cases. These results indicate that elevation of serum NSE level in patients with NSCLC may be a marker of poor prognosis.

Adenocarcinoma↗

PubMed1992

[New anthracycline analogues in the treatment of lung cancer].

Doxorubicin is one of the most potent drugs for the treatment of small cell lung cancer (SCLC), but less potent for non-small eell lung cancer (NSCLC). The prevalent use of doxorubicin is limited by the development of cardiomyopathy. Therefore, TUT-7 SM-5887, and ME2303 have been under the clinical studies to find new anthracyclines with less cardiotoxicity and higher therapeutic indices not only for SCLC but also for NSCLC. The dose-limiting factor of these drugs determined in phase I studies was leukocytopenia. Phase II studies which are currently under way have indicated that SM-5887 is possibly most potent for the treatment of NSCLC, and that these drugs have less cardiotoxicity compared to the mother compound, doxorubicin.

Anthracyclines↗

PubMed1992

An adriamycin-resistant subline is more sensitive than the parent human small cell lung cancer cell line to lonidamine.

Lonidamine, a unique new type of anticancer agent, has been shown to exert marginal activity in patients with resistant small cell lung cancer. We have assessed cytotoxic activity using seven human small cell lung cancer cell lines and the drug resistant small cell lung cancer sublines, Adriamycin-resistant SBC-3/ADM100, etoposide-resistant SBC-3/ETP and cisplatin-resistant SBC-3/CDDP. Although lonidamine had only a minimal activity in seven human small cell lung cancer cell lines, SBC-3/ADM100 cells were more sensitive to lonidamine than the parent SBC-3 cells to a 1.6-fold extent in terms of IC50. SBC-3/CDDP and SBC-3/ETP had no cross-resistance to lonidamine at all. These observations may be of potential clinical significance in treating small cell lung cancer.

Antineoplastic Agents↗

PubMed1992

[Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in small cell lung cancer at diagnosis and relapse, with special reference to the tissue expression of CEA and response to chemotherapy].

Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug therapy; however, the majority of patients eventually relapse within a few years. Emergence of drug resistance is thought to play a major role in the dismal course of this disease. However, the mechanism of drug resistance in SCLC still remains obscure. Based on the clinical observation that a significant proportion of patients with relapsing tumor show an elevated serum carcinoembryonic antigen (CEA) concentration while serum neuron-specific enolase (NSE) concentration remains normal, we attempted to determine whether the tissue of CEA is indicative of a clonal change in SCLC, in contrast with the tissue expression of NSE and P-glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at diagnosis, and a further three patients showed CEA expression at relapse. It is of note that there were two patients whose tumors expressed NSE alone at diagnosis but expressed CEA alone at relapse. Serum CEA concentration was concordant with the tissue expression of CEA; however, serum NSE concentration was not concordant with the tissue expression of NSE. Tumors with CEA expression at relapse were generally resistant to salvage chemotherapy, while there was no close relationship between the tissue expression of P-gp and refractoriness to drugs at relapse. These findings indicate that the tissue expression of CEA in SCLC is a marker of a clonal change during chemotherapy, and such a clonal change would play a role in the emergence of drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

[A case of locally advanced esophageal cancer effectively treated with concurrent chemotherapy and radiotherapy].

A case of a 69-year-old man with locally advanced esophageal cancer was reported. The patient received five courses of chemotherapy consisting of cisplatin (30 mg i.v. days 1-5), 5-fluorouracil (500 mg i.v. days 1-5) and bleomycin (5 mg i.m. days 1-5) every four weeks with a split course irradiation at a dose of 50 Gy, which was concurrently given at the second, third and fourth course of the chemotherapy. Treatment was effectively carried out without severe toxicities. The patient achieved a histologically-confirmed complete remission after completion of the treatment. The patient is disease-free and fully active 28 months after the beginning of chemotherapy. The treatment modality appears to be useful for advanced esophageal cancer.

Aged↗

PubMed1992

[Malignancies in patients with sarcoidosis].

We evaluated the occurrence and type of malignant tumors in 148 patients with sarcoidosis followed at the Okayama University Hospital. Nine patients had malignancies; in 2 of 9 patients the development of malignancy preceded that of sarcoidosis, and one patient presented with sarcoidosis and malignancy at the same time. Six patients developed six types of malignancy following the development sarcoidosis; one case each of stomach cancer, lung cancer, breast cancer, thyroid cancer, testicular tumor, laryngeal cancer, and chronic lymphocytic leukemia. There was no significant difference between sexes (3 males and 3 females). The mean age of the cancer group at the onset of sarcoidosis was 56 years, which was significantly higher (p less than 0.05) than that of the control group. In these 6 patients, the mean interval from onset of sarcoidosis to detection of cancer was 11.7 years (range 1.5 to 30.2 years). The relative risk of malignancy was calculated based on the data for 148 patients with sarcoidosis with a total of 1371 person-years. The expected incidences of cancer for all sites and specific sites were estimated by applying age- and sex-adjusted person-years. The observed incidence of cancer was significantly (p less than 0.05) greater than the expected incidence for thyroid cancer, laryngeal cancer, and leukemia. No significant difference in incidence was found for all sites or for the other sites of cancer. The increased cancer incidence in sarcoidosis may be secondary to immunological abnormalities associated with this disease.

Adult↗

PubMed1992

[Six cases of primary pulmonary cryptococcosis].

Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2. Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection. However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy. They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X-ray findings. These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis.

Adult↗

PubMed1992

[Release of interleukin-6 by alveolar macrophages in patients with sarcoidosis].

The supernatants from cultures of alveolar macrophages from 12 patients with sarcoidosis and 7 control subjects were assayed for interleukin-6 (IL-6) using an ELISA system. IL-6 was detectable without a stimulant in supernatants from all subjects with sarcoidosis and controls. However, the supernatants from 4 of 12 untreated patients with sarcoidosis contained significantly greater amounts of IL-6. When macrophages were stimulated by Propionibacterium acnes (P. acnes), the mean level of IL-6 in the supernatant of patients with sarcoidosis was 5.18 +/- 1.46 ng/ml, which was significantly higher than in controls (3.34 +/- 0.39) (p less than 0.05). Furthermore, in patients with sarcoidosis, the mean level of IL-6 in the supernatant was significantly correlated with the percentage of lymphocytes in bronchoalveolar lavage fluid (p less than 0.05), the level of interleukin-1 released by alveolar macrophages stimulated by P. acnes (p less than 0.05), and the phagocytic index of alveolar macrophages (p less than 0.05). The large amount of IL-6 in the supernatant after stimulation by LPS was measured in patients with sarcoidosis (24.49 +/- 13.36) and in controls (12.4 +/- 8.53), and there was no significant difference between patients with sarcoidosis and controls. Small amounts of IL-6 were detectable in bronchoalveolar fluid from only 2 of 26 patients with sarcoidosis; however, it was detected in none of 15 controls. It is suggested that the enhancement of IL-6 release by alveolar macrophages has a role in the activation of immune effector cells at sites of sarcoidosis.

Adult↗

PubMed1991

Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamide-induced urinary disorders.

In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Adult↗

PubMed1991

Phase II study of ifosfamide, cisplatin, and vindesine combination in advanced non-small cell lung cancer.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.

Adult↗

PubMed1991

A case of non-Hodgkin's lymphoma associated with hypercalcemia.

A patient with a diffuse, small cleaved cell, non-Hodgkin's lymphoma associated with marked hypecalcemia was described. Antibody to the adult T-cell leukemia-lymphoma virus was absent. Although bone marrow was infiltrated by lymphoma cells, destructive or lytic bone lesions could not be detected. The serum level of immunoreactive parathyroid hormone C-terminal (PTH-C) was normal. The serum level of 1, 25-dihydroxyvitamin D was lower than normal. This case suggests that other humoral substances produced by lymphoma cells may be responsible for hypercalcemia.

Humans↗

PubMed1991

[Double cancer in small cell lung cancer patients treated with intensive chemotherapy with or without radiation therapy].

Development of double cancer was evaluated in 311 small cell lung cancer patients who had received intensive chemotherapy with or without radiotherapy. Of those, 10 patients (3.2%) developed a second malignancy:stomach cancer in four, non-small cell lung cancer in three, acute myelogenous leukemia in two, and liver cancer in one. The cumulative risk for the development of double cancer was 1.0% at 1-year, 17.0% at 3-years, and 100% at 8.1 years. The relative risk for the development of double cancer calculated by person-year method utilizing age and sex adjusted cancer incidence in Japan was 2.96-fold (p less than 0.01). The risk of non-small cell lung cancer (6.65-fold) and acute myelogenous leukemia (54.9-fold) was particularly high. Of 21 patients who survived disease-free for more than 2 years, 8 patients died; four patients (50%) died of second malignancy, two died of infectious disease, and only two patients died from recurrent small cell lung cancer. These results indicate that a cautious follow-up program for the detection of double cancer is indicated in patients surviving small cell lung cancer.

Adult↗

PubMed1991

[A statistical analysis of serum sialyl Lewis X-1 (SLX), CEA, SCC and NSE levels in patients with lung cancer].

Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.

Adenocarcinoma↗

PubMed1991

[Early phase II study of MST-16 (sobuzoxane) on malignant lymphoma].

Early phase II study of MST-16[4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxy-methyl-2, 6-piperazinedione], a derivative of ICRF-154, on malignant lymphoma was conducted by multi-institutional cooperative group. MST-16 was administered orally at doses of 1,600 mg/body/day for 5 days or 1,200 mg/body/day for 10-14 days, mainly. The number of registered and evaluated patients were 29 and 28, respectively (Hodgkin's disease 3 patients and non-Hodgkin lymphoma 25). Twenty-seven of 28 patients had received prior chemotherapy and/or radiation therapy. Of 28 evaluable patients, overall response rate (CR + PR) was 32.1%. In high-dose administration group, the response rate was not significantly high. The response rate seemed to be high in patients who were treated repeatedly (number of courses greater than 3). Major side effects observed were myelosuppression and gastro-intestinal disorders which were reversible in a rest period. Myelosuppression seemed to be severe in high-dose administration group. This study indicated that MST-16 was a useful agent against malignant lymphoma including primary resistant or relapsed patients, and that the recommended regimen for a late phase II study was considered to be 1,600-2,400 mg/body/day for 5-7 days repeatedly with a pause of several days. Furthermore, the study should be considered at the dose of 3,200 mg/body because half cases administered at this dose showed some response.

Adult↗

PubMed1990

[Effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with lung cancer].

In an attempt to evaluate rG-CSF for preventing and reducing the period of chemotherapy-induced neutropenia, phase II studies of the agent, KRN 8601, have been conducted in patients receiving chemotherapy for lung cancer. In the cooperative study, 53 patients with lung cancer were fully evaluated. The chemotherapy regimen for the patients enrolled in the study was not specified, but an identical regimen with an identical dose and schedule was mandatory for the first cycle in which the patients did not receive the rG-CSF, and for the following cycles in which they received it after completion of chemotherapy for 14 days consecutively. Patients were allocated to receive the agents either at a dose of 100, 200 or 400 micrograms/m2 via intravenous drip infusion; or at as ub cutaneous dose of 25, 75, or 125 micrograms. In the author's study, all the 9 patients with non-small cell lung cancer received a 3-drug combination of vindesine, ifosfamide, and cisplatin(VIP) at an identical dose throughout the cycles. The rG-CSF was administered on the second and the following cycles at a dose of 100 micrograms/m2, subcutaneously, in the same manner as the above. Myelogram and neutrophil functions, i.e., superoxide anion production, chemotactic, and phagocytic activity, were serially determined in these patients. With intravenous dose of 100 micrograms/m2, the rG-CSF considerably elevated the nadir count of neutrophils and significantly reduced the duration of neutropenia. Subcutaneously administered rhG-CSF at 75 micrograms doses did as with intravenous infusion. The optimal dose of the agent in conventional chemotherapy was estimated to be 100 micrograms/m2 when infused intravenously, and 75-125 micrograms subcutaneously. Subcutaneously administered rG-CSF at a dose of 100 micrograms/m2 did not contribute to spare the nadir count of neutrophils, but contributed toward reducing the period of neutropenia induced by the 3-drug combination which was much more myelosuppressive than conventional regimens. Thus, the optimal dose of the agent should be determined according to the dose-intensity of chemotherapy. Peripheral neutrophils obtained after recovery from VIP-induced neutropenia showed a normal activity in superoxide anion production and mobility when combined with rG-CSF, although the activity showed a trend to remain subnormal in the recovered neutrophils without rG-CSF. In conclusion, rG-CSF considerably reduces the neutropenia and possibly reduces infections caused by intensive chemotherapy. Hereafter, clinical trials must determine whether rG-CSF improve the therapeutic outcomes of patients receiving chemotherapy in terms of response rate and patient survival.

Adenocarcinoma↗

PubMed1990

[Patterns of relapse in patients with small cell lung cancer--the effect of chest irradiation and prophylactic cranial irradiation combined with intensive chemotherapy on long-term survival].

The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p less than 0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.

Adult↗