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Biomedical subjects

T Ohnoshi

Publications and source records attributed to T Ohnoshi.

At least 127 records · Page 7Linked to original sources

Tumor stem cell assay for detecting metastases of human lung cancer.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.

Bone Marrow↗

Combination chemotherapy for small cell carcinoma of the lung: evaluation of four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

Adult↗

Cytological and histological correlation of primary lung cancer: a preliminary study of 106 cases with resectable tumors.

In order to increase the accuracy of diagnosis in lung cancer, analysis concerning cytological and histological correlation was attempted. The present study consists of 106 patients, who were seen during the past approximately five years and underwent radical surgery to remove tumors completely; mere biopsy specimens were excluded. These patients were 63 years old on the average, 78 males and 28 females, 29 cases of the hilar type (H) and 77 of the peripheral type (P), and 27 and 76 cases of the clinical stage I in H and P, respectively. Histologically, there were 53 adenocarcinomas (Ad), 38 squamous cell carcinomas (Sq), 4 adenosquamous cell carcinomas (Ad + Sq), 5 large cell carcinomas (LCC), and 6 small cell carcinomas (SCC); among them, 3 Ad and 21 Sq in H, and 50 Ad and 17 Sq in P. The overall positive percentages were 65.5 (H) and 26.0 (P) by combination of spontaneous, airsol-induced and Saccomanno's methods, against 96.6 (H) and 72.8 (P) with inclusion of brushing method. 94.8% of Sq in H and 66.7% of Ad and 70.6% of Sq in P were positive by the brushing. A comparative study of these four methods, performed at least once on the same patient, also confirmed the superiority of brushing. Cyto- and histological agreement was 21/21 (100%) for Sq in H, whereas 30/34 (88.2%) for Ad and 13/15 (86.7%) for Sq in P. In conclusion, cyto- and histological findings in H and P corresponded well, and as far as cytology of peripheral type is concerned, a combined method, especially with brushing, is strongly recommended.

Adult↗

In vivo antitumor activity of neocarzinostatin (NCS)-tumor antibody conjugate against a transplantable human leukemia cell line (BALL-1).

The in vivo antitumor activity of NCS-immune immunoglobulin G (IgG) [Neocarzinostatin (NCS) conjugated with rabbit IgG antibody against a human leukemia cell line (NALL-1)] was evaluated in immunosuppressed newborn Syrian hamsters into which a transplantable human leukemia cell line, BALL-1 was implanted. After intraperitoneal (i.p.) injection of the conjugate, hamsters preinoculated i.p. with BALL-1 cells survived longer than hamsters treated with control solutions (p less than 0.01). The control solutions were NCS, immune IgG, a mixture of NCS and immune IgG, NCS-normal IgG conjugate and physiological saline. There was no change in body weight in the NCS-immune IgG-treated hamsters. The growth of subcutaneously (s.c.) implanted BALL-1 tumors was also inhibited by i.p. administration of NCS-immune IgG; however, the degree of inhibition was not significantly different from that obtained by administration of NCS alone, a mixture of NCS and immune IgG or NCS-normal IgG conjugate. These results indicate that NCS-immune IgG was effective against i.p. BALL-1 tumors, but was less effective against s.c. implanted tumors.

Animals↗

Spontaneous, complete remission in adult T-cell leukemia: a case report.

A 36-year-old man with adult T-cell leukemia gradually improved to the point of complete remission without any anticancer treatment. The patient was referred to our hospital because of the appearance of morphologically abnormal lymphocytes. Thirty percent of the peripheral blood white cells were morphologically abnormal lymphocytes which had lobulated or indented nuclei, and were E rosette-forming and mature T-cell antigen-positive. No hepatosplenomegaly, lymphadenopathy or mediastinal mass was noted. He had a cough with sputum one and a half years before entry. After admission, skin nodules occurred and were diagnosed histologically as non-Hodgkin's lymphoma, diffuse pleomorphic. Serum antibodies against an adult T-cell leukemia-associated antigen were detected at a titer of 1:40. Chest X-ray films, a pulmonary function test, bronchographic examination, bronchoalveolar lavage and transbronchial lung biopsy demonstrated no relationship between the pulmonary symptoms and the adult T-cell leukemia. After treatment with antibiotics and a beclomethasone inhaler, the symptoms decreased, and then the abnormal lymphocytes and skin nodules disappeared. The spontaneous, complete remission has continued for four years.

Adult↗

[Phase II study of mitoxantrone for hematologic malignancies].

A phase II study of mitoxantrone (MIT) was performed in 21 patients with hematologic malignancies refractory to combination chemotherapy including anthracyclines. MIT was administered intravenously at doses of 8 to 13 mg/m2 on day 1 for 12 malignant lymphoma patients, and 1 to 3.3 mg/m2 on day 1 through 5 for 7 acute leukemia patients and 2 malignant lymphoma patients. Four malignant lymphoma patients (2 each of Hodgkin's disease and non-Hodgkin's lymphoma) achieved partial response lasting 19, 14, 8+, and 4 weeks, respectively. Although no definite response was obtained in acute leukemia patients, a marked cytoreduction was observed in 2 patients. Myelosuppression was a major toxicity, however, life-threatening toxicities were not observed in this study.

Acute Disease↗

[Phase I study of an oral administration of VP 16-213].

A phase I study of VP-16-213 oral capsule was performed in 25 patients with various malignant tumors refractory to standard treatments. Doses were escalated from 50 mg/d to 300 mg/d by a 5-day administration. Leukopenia was dose-related and nadirs at 200 mg/d, 250 mg/d and 300 mg/d were 2,000, 1,600 and 700/cmm respectively, reaching in about 2 weeks and approximately one week was required for recovery. Thrombocytopenia was also dose-related but generally less frequent and milder than leukopenia. Gastrointestinal toxicities such as anorexia, nausea and vomiting occurred in about 20% of patients but well tolerated; alopecia was observed in 40%. The result indicated that an optimal dose of oral VP-16-213 for phase II study was daily 200 mg/d (approximately 130 mg/m2) for 5 consecutive administration in 3-week intervals.

Administration, Oral↗

Pretreatment serum albumin concentration and lactic dehydrogenase activity as prognostic factors in patients with small cell lung cancer.

Pretreatment laboratory parameters were analyzed as prognostic factors in patients with small cell lung cancer. Serum lactic dehydrogenase activity, serum albumin concentration, PPD skin reaction, and peripheral lymphocyte count were of prognostic importance. When these factors were evaluated by multivariate analysis together with performance status and disease extent, lactic dehydrogenase and albumin were the most influential factors related to survival.

Carcinoma, Small Cell↗

Bone marrow examination for detection of metastasis in patients with bronchogenic carcinoma: an evaluation of 107 patients.

As a staging procedure before treatment, examination of bone marrow from the posterior iliac crest was performed on a total of 107 patients with bronchogenic carcinoma. Among them, 11 patients (10.3%) had metastasis in the bone marrow: five of 39 adenocarcinomas, five of 33 small cell carcinomas, one of four large cell carcinomas, and none of 31 epidermoid carcinomas. Leukoerythroblastosis was found exclusively in the patients with metastasis, although the presence of tumor cells in the bone marrow did not correlate well with peripheral blood cell counts. Survival following an intensive chemotherapy in patients with bone marrow metastasis was substantially longer for those with small cell carcinoma than for those with other histologic types of bronchogenic carcinoma.

Biopsy↗

Combination chemotherapy of advanced non-Hodgkin's lymphoma with adriamycin, vincristine, ifosfamide and prednisolone (AVIP): a preliminary report.

Eighteen patients with advanced non-Hodgkin's lymphoma other than the diffuse histiocytic type were treated with a combination of adriamycin, vincristine, ifosfamide and prednisolone (AVIP). The objective response rate was 83% (15/18); 61% (11/18) achieved complete remission. The median duration of complete remission was 11 months ranging from 2 to 39+ months. Eleven of the 18 patients are still alive during the median follow-up time of 13 months. The median survival was 14+ months for complete responders, and 9.5 months for partial and nonresponders. A myelosuppressive toxicity was well tolerated. AVIP offers some hope as treatment of advanced non-Hodgkin's lymphoma.

Adolescent↗

[Inhibitory effect of antineoplastic agents on human cholinesterases].

Human motor endplate acetylcholinesterase was inhibited in vitro by alkylating antineoplastic agents, most strongly by mechlorethamine, followed by DTIC, ACNU, cyclophosphamide and ifosfamide. Eleven other antineoplastic agents did not inhibit the enzyme substantially nor interfered with cholinesterase measurement. Cyclophosphamide and mechlorethamine inhibited human plasma pseudocholinesterase most strongly, followed by thiotepa, ACNU, DTIC, ifosfamide and BCNU. Mechlorethamine, ACNU and ifosfamide inhibited the motor endplate and plasma cholinesterase practically equally, DTIC inhibited motor endplate cholinesterase more strongly, while cyclophosphamide was a more selective inhibitor of plasma cholinesterase. Inhibition of human red blood cell acetylcholinesterase was identical to that of motor endplate acetylcholinesterase; therefore, red cells would be a preferable indicator in monitoring cholinesterase inhibition by antineoplastic agents.

Acetylcholinesterase↗

Establishment of methotrexate-resistant human acute lymphoblastic leukemia cells in culture and effects of folate antagonists.

A human acute lymphoblastic T-cell line, MOLT-3, was fed with Roswell Park Memorial Institute Medium 1640-10% fetal bovine serum-antibiotics, containing increasing concentrations of methotrexate (MTX). After 10 months of feeding, the cells became resistant to 10(-7) M MTX; resistance was not reversed when the cells were placed in the original MTX-free medium. At 10(-7) M MTX, the concentration which produced complete inhibition of the parent MOLT-3 cell growth, the resistant cells were not inhibited at all. On a 50% inhibitory concentration basis, the resistant cells were approximately 30-fold more resistant to MTX. The parent MOLT-3 and the resistant line had the same doubling time of approximately 36 hr. There were no differences in light microscopic morphology. MOLT-3 produced loose colonies on 0.5% agar enriched with fetal bovine serum, whereas the colonies of the resistant line were tightly packed. The development of resistance was accompanied by a 4- to 5-fold decrease in [3H]MTX transport (MOLT-3/MTXt). Kinetic analysis of MTX uptake showed that the resistant subline did not have an altered Km for MTX (6.6 microM) but had a decreased Vmax of about 20% of the parent cell line. These data suggest that either the number of folate transport sites or the turnover rate of these sites has been reduced in the MTX-resistant cell line. Dihydrofolate reductase was only minimally elevated in the resistant cell line. The MTX-resistant cell line was cross-resistant to dichloromethotrexate. The sensitivity of the resistant line to the substituted 2,4-diaminoquinazoline and pyrimidine compounds, 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline (JB-11) and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine, increased more than 3-fold. While leucovorin equally reversed the MTX effects on the parent and resistant cells, leucovorin reversal of 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine effects was limited only to the parent cell line. 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline or 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine plus leucovorin might prove to be unique in treating patients with acute lymphoblastic leukemia when the leukemic cells develop transport resistance to MTX.

Animals↗