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Biomedical subjects

K Minato

Publications and source records attributed to K Minato.

At least 91 records · Page 5Linked to original sources
PubMed1988

The difference in surface phenotypes between cytotoxic lymphocytes induced in vivo by systemic administration of human recombinant interleukin-2 and lymphokine activated killer cells induced in vitro.

The cytotoxicity of spleen lymphocytes of C57BL/6 mice is augmented both by incubation of spleen lymphocytes with human recombinant interleukin-2 (rIL-2) in vitro (LAK cell) and by systemic administration of high doses of rIL-2 into C57BL/6 mice for more than 3 consecutive days. In this study, the precursors and effectors of LAK cells and the cytotoxic cells induced by systemic administration of rIL-2 were characterized by using anti-asialoGM1 and anti-Thy1.2 antibody. The in vitro induced LAK cells were demonstrated to be derived partly from asialoGM1 negative cells and the cytotoxicities of LAK cells induced in vitro with rIL-2 were partially resistant to lysis by anti-asialoGM1 antibody plus complement in comparison with NK cells. Contrary to this, the cytotoxicities of spleen lymphocytes of C57BL/6 mice pretreated with anti-asialoGM1 antibody were not augmented by in vivo injection of rIL-2. In addition, the cytotoxic activities of spleen lymphocytes, augmented by systemic administration of rIL-2, were completely suppressed by anti-asialoGM1 antibody and complement in vitro. These findings indicate that the cytotoxic lymphocytes induced in vivo by systemic administration of rIL-2 are different from in vitro induced LAK cells and have the same surface phenotype as NK cells.

Animals↗
PubMed1988

Phase II study of carboplatin in small cell lung cancer.

Carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylate platinum II), a new platinum analogue, was administered to 18 patients with small cell lung cancer (SCLC) at a dose of 300-450 mg/m2 intravenously every four weeks, in a phase II study. All patients could be evaluated to assess response and 17 for toxicity. The overall response rate was 28% (5/18), including one complete response. Of eight patients previously untreated, four (50%) showed a response, including one complete response. The response rate in patients with no previous cisplatin-treatment was 50% (5/10). Response durations in five responders were 2, 3, greater than 4, greater than 10 and 11 months. Toxicity was primarily hematologic, with thrombocytopenia being dose-limiting. Thrombocytopenia (less than 75,000/mm3) was observed in 12 patients (71%), six requiring platelet transfusion. Leukopenia (less than 3,000/mm3) was observed in 11 patients (65%). There were no episodes of serious infection or bleeding, however. Myelosuppression was more severe in heavily pretreated patients than in patients previously untreated. Dose reductions were required following multiple treatments for cumulative myelotoxicity. Mild to moderate nausea and vomiting occurred in seven patients (44%). Nephrotoxicity and ototoxicity were not observed. Carboplatin was demonstrated to be an active agent against SCLC. Further investigation into dose and schedule of CBDCA in combination chemotherapy is warranted.

Aged↗
PubMed1988

Concurrent adult T-cell leukemia and acute myeloblastic leukemia.

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.

Antibodies, Viral↗
PubMed1988

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Treatment for small cell lung cancer--present status and future prospects.

Strategies for the treatment of small cell lung cancer (SCLC) were reviewed depending on the recent results of treatment. The development of new anti-cancer drugs are essential for the further improvement results of SCLC. However, the candidate of patient for phase II study of new anticancer drug is controversial. Intensified chemotherapy is essential in order to obtain long term survivors, however, the toxic death rate should be less than 5% of whole patients. The theory of non-cross resistant alternative chemotherapy has also been applied to the treatment of SCLC. The protocol study supported by grant-in-aid from the Ministry of Health and Welfare is now on-going by cooperative study. There are many discussions about the efficacy of combined modality in SCLC. However, present randomized trials gave clear answers about the priority of combined modality in SCLC. There are numerous biological studies about SCLC. These studies will contribute to improve the treatment results of SCLC.

Carcinoma, Small Cell↗
PubMed1988

[Detection of multidrug resistant phenotype in leukemia and lymphoma by monoclonal antibodies].

Two monoclonal antibodies, MRK16 and MRK20 that recognize P-glycoprotein and P-85 kd protein on the surface of adriamycin (ADM) resistant cells, respectively, were tested for the reactivity with 40 cultured leukemia/lymphoma cell lines. F(ab')2 form is essential to avoid false reaction through Fc gamma-R. Drug sensitivity of 19 representative cell lines were also examined in vitro. From this study, it was found that these cell lines were classified into 4 groups. Group 1 (4 cell lines) was insensitive to ADM, mitoxantron (MXT), etoposide (VP-16) and vincristine (VCR), and reactive to MRK16 and MRL20. Group II (1 cell line) was insensitive to the 4 drugs, but not reactive to both antibodies. Group III (3 cell lines) was insensitive to ADM, MXT and VP-16, but sensitive to VCR, and reactive to MRK20, but not to MRK16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. From these results, MRK16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK20 does P 85-kd-associated another type MDR (cross resistance to ADM, MXT and VP-16, but not to VCR). MRK20 reacted with monocytes, but MRK16 did not with any WBC type. One hundred and ninety eight clinical samples obtained from blood cancer were tested for the reactivity with MRK16. MRK16 did not react with any of 98 samples obtained before treatment, but did with 9 of 100 obtained at relapse or refractory stage after chemotherapy. The results indicate that MRK16 is useful to detect drug resistance phenotype of leukemia and lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Clinicopathologic, immunophenotypic, and immunogenotypic analyses of immunoblastic lymphadenopathy-like T-cell lymphoma.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.

Adult↗
PubMed1988

Major prognostic factors of adult patients with advanced B-cell lymphoma treated with vincristine, cyclophosphamide, prednisone and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M).

Eighty-two adult patients with advanced B-lymphoma, treated between 1981 and 1983 with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate) in a prospective randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 74% and 45%, respectively. The relapse rate was 51%. Stage of disease only was negatively associated with the CR rate in a multivariate analysis. The primary extranodal tumor site other than upper gastrointestinal (GI) tract and high grade pathology were found to affect disease-free survival adversely in a Cox proportional hazards model. Poor performance status, advanced stage, primary extranodal tumor site other than upper GI tract, advanced age, high grade pathology and prior therapy by either surgery or radiation, were significantly associated with shortened survival in a Cox proportional hazards model. These results indicate advanced B-lymphoma in Japan to be generally similar to advanced non-Hodgkin's lymphoma in the West in terms of prognostic factor characteristics, but the importance of the primary site in predicting survival has not been reported in the West. Also, the lack of a survival plateau in patients with diffuse large cell lymphoma indicates more intensive chemotherapy regimens than VEPA or VEPA-M to be needed. It was also found that the significant prognostic factors in patients with advanced B-lymphoma were very different from those with T-lymphoma. The five factors: pathology, stage, primary site, age, prior therapy by surgery or radiation, for which the risk ratio was more than 2.3, were used to construct a model containing 23 categories of patients running an increasing risk of shortened survival; this divided patients into three groups. The CR and 4-year survival rates of low-, moderate- and high-risk groups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively. The risk-grouping provides indications for determining optimal therapy for individual patients and the need for new therapeutic trials in patients at high risk.

Adult↗
PubMed1987

In vitro antitumor effect of recombinant human tumor necrotizing factor on cultured human cancer cell lines and freshly isolated lung cancer cells by the human tumor clonogenic assay.

In vitro antitumor effects of human recombinant tumor necrotizing factor (rH-TNF) were examined against nine lung cancer cell lines including six non small and three small cell lung cancer, four stomach cancer cell lines and 30 freshly isolated lung cancer cell samples by the human tumor clonogenic assay. rH-TNF did not show any inhibitory effect on the colony formations of lung and stomach cancer cell lines, except for PC10 established from squamous cell carcinoma even at the high concentration. The overall response rate of fresh material was 11.5%. The colony formations of only two materials from 20 patients without prior chemotherapy were significantly suppressed by rH-TNF in vitro. Three specimens of adenocarcinoma exhibited more than 70% decrease in colony number by treating with 100 and 1000 u/ml of rH-TNF resulting in the response rate of 15.8% (3/19). From these results, it can be concluded that rH-TNF has modest direct cytotoxic effect on lung cancer, and additional study against adenocarcinoma of the lung might be warranted.

Antineoplastic Agents↗
PubMed1987

High-frequency transfection of mouse FM3A mammary carcinoma cells in suspension culture with plasmid DNA.

High-frequency transfection of mouse FM3A cells, grown in suspension, with plasmid pSV2neo DNA was achieved by incubation of the cells with DNA plus polybrene for 6 h followed by an osmotic shock with a hypertonic NaCl solution. When incubated for 20 min at 34 degrees C, FM3A cells showed resistance to the osmolarity change from 0.1 to 9.0% NaCl in the medium. Within this concentration range, 5-7% gave the highest efficiency of transfection. Both linear and circular forms of plasmid DNA produced transformants with equal efficiency. This method was simple, reproducible, and carrier DNA was not required. The efficiency was about 100 times higher than that of the method with DNA-calcium phosphate precipitates. Transformed cells were stable and different numbers of plasmid DNA copies were detected.

Animals↗
PubMed1987

Chromosome aberrations and clinical features of adult T cell leukemia-lymphoma not associated with human T cell leukemia virus type I.

Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL.

Acute Disease↗
PubMed1987

Prediction of hematologic toxicity of carboplatin by creatinine clearance rate.

Twenty-six patients with histologically proven lung cancer, treated with carboplatin at the National Cancer Center Hospital between October 1985 and October 1986, were retrospectively analyzed to determine the hematologic toxicity of carboplatin (CBDCA) and to develop guidelines for dose modification. A total of 34 courses of CBDCA were administered, of which 21 were adequate for assessment of the myelosuppression in relation to the renal function. One of three doses of CBDCA was administered by iv drip infusion over one hour (450 mg/m2, 19 courses; 400 12; 300, 3). Myelosuppression was dose-limiting, with thrombocytopenia being more sensitive than leukopenia, neutropenia or anemia. No significant correlation of the absolute count of platelets, white blood cells, polymorphoneutrophils, or hemoglobin with patient's creatinine clearance (Ccr) and dose of CBDCA administered was found. However, the percent reduction in platelets, white blood cells, polymorphoneutrophils, or hemoglobin correlated well with the relative dose of CBDCA [RD = total dose of carboplatin administered (mg/m2)/pretreatment Ccr/m2]. As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5.34) x [(1-desired platelet count nadir/pretreatment platelet count) x 100-12.9]. After consideration of the range of thrombocytopenia, we have further developed a simple equation to use CBDCA easily and safely: Dosage (mg/m2) = (1/10) x Ccr/m2 x desired % reduction in platelet count nadir = 10 x Ccr/m2 x (1-desired platelet count nadir/pretreatment platelet count. The clinical validity of these two equations is now being evaluated in prospective studies.

Adult↗