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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 595 records · Page 33Linked to original sources

Two novel cell surface antigens on small cell lung carcinoma defined by mouse monoclonal antibodies NE-25 and PE-35.

Two mouse monoclonal antibodies, NE-25 and PE-35, defining novel cell surface antigens of small cell lung carcinoma (SCLC) were produced. The molecular weight of NE-25 and PE-35 antigens estimated by radioimmunoprecipitation was 25,000 and 35,000, respectively. NE-25 antigen was expressed on the majority of cell lines and tumor specimens of SCLC among lung carcinoma. These NE-25-positive cell lines showed typical growth morphology as SCLC classic lines and expressed high levels of neuroendocrine biomarkers, such as aromatic L-amino acid decarboxylase, while NE-25 antigen-negative lines lacked apparent neuroendocrine properties. This antigen was expressed also on a subset of neoplastic cells with (neuro)endocrine properties, including pulmonary carcinoid, and on various tumors of nervous tissues, such as neuroblastoma. Among the normal cells, Kulchitski cells of lung, thyroid gland, adrenal gland, Langerhans islet, and nervous tissues were positive. Thus, the expression of NE-25 antigen is closely associated with the neural and/or (neuro)endocrine differentiation state. On the contrary, PE-35 antigen was present on four major types of lung carcinomas as well as on squamous cell carcinoma and adenocarcinomas of various tissues, but it was absent from nervous tissue tumors. Thus, PE-35 antibody showed a "pan-epithelial" reactivity. Analysis by NE-25 and PE-35 antibodies provided evidence for the heterogeneities of SCLC by demonstrating four surface phenotypes, with the NE-25+/PE-35+ phenotype being most common. In addition, the results supported the current understanding that various histological types of lung carcinoma, including SCLC, are derived from a stem cell of the bronchial epithelium.

Antibodies, Monoclonal↗

[A case of hepatoma with a remarkable response to gamma-interferon administration].

A 59-year-old male was admitted to our hospital with complaints of general fatigue, abdominal distension and edema in the legs in February, 1985. Laboratory findings were as follows: GOT 152 IU/l, GPT 129 IU/l, LDH 555 IU/l, ALP 1147 IU/l, gamma-GTP 413 IU/l, T.-Bil 2.1 mg/dl and AFP 422.6 ng/ml. Multiple SOLs were recognized in both lobes of the liver by abdominal CT scan and echography. Interferon-gamma (gamma-IFN: KW-2202; Kyowa Hakko Co.) therapy was started in March from an initial dose of 1 X 10(6) units and was increased up to 4 X 10(6) units, 2 X 10(6) units being administered as a maintenance therapy for 12 weeks. The tumors became remarkably smaller in size, AFP was decreased to 38.8 ng/ml, and PR was obtained. The only side effect was temporary fever. The patient was subsequently followed without gamma-IFN at an outpatient clinic for about 100 days, but finally died due to rupture of esophageal varices and hepatic failure.

Carcinoma, Hepatocellular↗

[Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta].

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.

Animals↗

[Intraarterial bolus infusion followed by rapid removal of anticancer agents with hemocarboperfusion under local hyperthermia in advanced hepatic cancer].

Reported herein is a new multidisciplinary treatment modality for unresectable hepatic cancer in which local hyperthermia and intraarterial infusion of bolus anticancer agent are simultaneously undertaken while anticancer agent leaking from the hepatic bed into the general circulation is rapidly removed by charcoal hemoperfusion. Local hyperthermia induced by exposure to 13.56-MHz radiofrequency waves was conducted between one and one and a half hours once or twice a week. During the hyperthermia treatment, a bolus of either 1 mg/kg Mitomycin C or 2 mg/kg Adriamycin was injected into the hepatic artery via a Vascular Access Port, the catheter portion of which had been surgically inserted into the hepatic artery and the reservoir of which had been implanted subcutaneously. In general, a regular dose of 6 mg of Mitomycin C was injected into the Vascular Access Port during the following hyperthermia procedures. In seven of nine patients (78%) treated with this method, a marked reduction in tumor size of more than 50% was observed on computed tomograms. A light to moderate degree of side effects such as leukocytopenia, thrombocytopenia, liver dysfunction or hair loss were noticed after the bolus infusion, but were not so serious as to threaten the patients' lives.

Adult↗

T cell receptor beta chain gene rearrangements in leukemias with immature T cell phenotype.

The arrangements of the T cell receptor (TCR) beta genes were studied in leukemias with immature T cell phenotype. Three cases of acute lymphocytic leukemia (ALL) and one case of chronic myelocytic leukemia in blastic crisis (CML-BC), which expressed only Tp40 antigen of cluster of differentiation (CD) 7 without erythrocyte rosette receptor (E), did not show rearrangements of TCR beta chain genes. Two of 5 ALL cases which expressed an additional T cell antigen, T1 of CD5, showed rearrangements of TCR beta genes. Two cases of CML-BC expressing T1 and Tp40, however, had unrearranged TCR beta genes. The results altogether showed that a part of E- T1+ Tp40+ ALL cases is of T cell origin.

Blast Crisis↗

[Cardiotoxicity of mitoxantrone].

Cardiotoxicity induced by mitoxantrone was studied in 50 closely followed patients receiving chemotherapy with mitoxantrone. Serial electrocardiograms were recorded. The electrocardiographic parameters (heart rate, P-Q interval, QRS interval, QRS voltage, and QTc interval) were analyzed. The patients who received mitoxantrone showed no significant changes in these parameters. Furthermore, in order to investigate the details of acute cardiotoxicity of mitoxantrone and adriamycin, Holter ECGs were recorded and some of the electrocardiographic parameters were analyzed. The basic rhythm was sinus rhythm in all cases except for only one case which developed intermittent atrial fibrillation after adriamycin therapy. No effect on the specialized conduction system was observed on either group. Supraventricular premature beat showed no significant changes, but ventricular premature beat showed a tendency to increase and the mode of appearance of the ventricular extrasystole was very dangerous in the adriamycin-administered group. Developed ST-T changes were also seen in the adriamycin group. In conclusion, mitoxantrone seemed to have less cardiotoxicity in comparison with that of adriamycin.

Adolescent↗

[Pathological features and treatment of T lymphoma].

T lymphomas are classified into two types from surface phenotype, thymic T (T1) and Peripheral T (T2) lymphoma, and T2 lymphomas, are furthermore subdivided to inducer/helper (Ti/h or T4) and cytotoxic/suppressor (Tc/s or T8) type. But even in ATLL (adult T cell leukemia/lymphoma) believed to be a model of Ti/h type, the heterogeneities of surface phenotype are reported frequently. All of the pleomorphic and lymphoblastic and a part of small cell, medium-sized cell, mixed and large cell types have a T-cell phenotype. In addition to these histologies, AILD/IBL/IBL-like T lymphoma, T-zone lymphoma and So-called Lennert's lymphoma also hold T-cell nature. The heterogenecity and the existence of the borderline area between neoplasm and reactive lymphadenitis or hyperplasia often confused the clinicians and hematopathologists. From our experience, forty nine percent 5 year survival of T lymphoma other than lymphoblastic and pleomorphic type suggests the propriety of classifying T lymphoma into high grade and intermediate grade malignancies. Treatment of T lymphomas are basically distinguishable to two categories, for T1 and T2 lymphomas. The treatment of T1 lymphoma should be an aggressive one including CNS prophylaxis. At present, the recommendable treatment of T2 lymphoma is to apply the best regimens obtained from B cell lymphoma study. As aggressive treatment for ATL does not always yield favorable results, the concept of therapy will become clear near future. An intensive supportive therapy including T-S prophylaxis should be combined actively in the treatment program.

Antineoplastic Combined Chemotherapy Protocols↗

[Flow cytometric analysis of the effect of THP-adriamycin on the cell cycle traverse of RPMI-8402 cells--comparison with adriamycin].

THP-adriamycin (THP) is a new derivative of adriamycin (ADM) which is reported to have a lower cardiotoxicity than ADM. In this report, the effects of THP on cell growth, cell cycle traverse and colony-forming ability of RPMI-8402 cells were investigated in comparison with ADM. The growth-inhibitory effect of THP was equal or superior to that of ADM in this system. Analysis of the DNA histogram obtained by flow cytometry showed that THP exerted its growth-inhibitory effect by blocking cells at the G2 phase. At higher concentrations, THP inhibited the traverse of cells through the S phase and further through the whole cell cycle completely. These effects were quite similar to those of ADM, which suggested a similar mechanism of action for the two drugs from the aspect of the cell cycle. A follow-up study of cells accumulated at the G2 phase and a study on colony-forming ability revealed that the G2 phase accumulation was an irreversible and fatal effect of THP, so that G2-phase accumulation could be considered as a cytocidal effect of THP, indicating the clinical usefulness of this system for evaluation of the drug effect. From these results and the low cardiotoxicity, it was suggested that THP could be a good candidate for use as an antitumor agent in clinics.

Cell Cycle↗

[Phase II study of mitoxantrone in advanced breast cancer].

A phase II study of mitoxantrone in cases of advanced breast cancer was conducted by a cooperative study group involving 7 institutions. Mitoxantrone was administered at doses of 10-12 mg/m2 at 3-4-week intervals. A total of 36 patients were entered and 31 were evaluable. There were 4 CRs (13%) and 3 PRs (10%) with an overall response rate of 23% and the durations of responses were between 6 and 25 weeks. Leukopenia was a dose-limiting effect of toxicity and occurred in all patients, while gastrointestinal toxicity and alopecia were mild.

Adult↗

[Antitumor effect of 1,3,3,5,5-pentaziridino-1-thia-2,4,6-triaza-3,5- diphoshorine-1-oxide].

The antitumor activity of 1.3.3.5.5-pentaziridino-1-thia-2.4.6-triaza-3.5-diphospho rine-1-oxide (SOAz) was investigated in vitro and in vivo. The results obtained were as follows: SOAz showed marginal cytotoxicity against growth of L1210 cells cultured in vitro. In the cell-cycle traverse of RPMI 8402 cells, SOAz prolonged the duration of the S phase, leading to the eventual accumulation of cells at the G2 phase. At the highest concentration, SOAz stopped the cell cycle progression completely. SOAz was found to have similar activity to carbazilquinone, cyclophosphamide or mitomycin C on P388 leukemia. SOAz showed marked antitumor effect against early-stage L1210 leukemia, and was also effective against advanced-stage L1210 leukemia. The therapeutic efficacy of SOAz depends on the treatment schedule. Single injection and intermittent treatment were superior to daily treatment. Oral administration of SOAz was effective as well as i.p., i.v. and i.m. administration.

Animals↗

[Results of follow-up studies on prognosis after immunotherapy with bestatin in acute nonlymphocytic leukemia].

We have recently performed a prognostic investigation of a randomized controlled trial with bestatin for acute non-lymphocytic leukemia in adults. Out of 115 patients registered in this study, 101 patients (48 in a bestatin group and 53 in a control group) were evaluated as eligible. The 50% remission duration was 20.4 months for the bestatin group compared with 11.3 months for the control group. Long-term remission rate at 4 years was 36.5% for the bestatin group compared with 24.1% for the control group, and their respective 50% survival time were 33.0 and 18.1 months, while the long-term survival rate at 4 years was 46.0% for the bestatin group compared with 25.5% for the control group. The bestatin group had a longer remission duration and survival time than the control group. The remission duration and survival time in patients under 49 years of age were not different between the groups. However, in patients over 50 years of age, the bestatin group had a significantly longer remission duration and survival time than the control group. Side effects of bestatin were mild and transient. These data suggest the usefulness of bestatin for the treatment of adult acute nonlymphocytic leukemia.

Aclarubicin↗

Response of interstitial cells of the testes in the house musk shrew, Suncus murinus L., to various gonadotropins.

Testicular interstitial cells of the house musk shrew culture in vitro released testosterone in response to ovine LH with a quite similar dose response relationship to that found in the cells of rats. The dose response curves suggested that a single testicular cell of the shrew has the same potency to secrete testosterone as that of the rat. In the shrew as well as in the rat, neither ovine PRL added alone nor together with oLH could stimulate the testosterone release from testicular cells, although a very limited enhancement of testosterone secretion was observed in the cell cultured with a large dose of oFSH in both species.

Journal Article↗