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N Saijo

Publications and source records attributed to N Saijo.

At least 361 records · Page 20Linked to original sources

[Comparison of the effects of interferon of various types on the cytotoxic activity of NK cells].

Various types/sources of interferons were tested for their ability to modulate the (cytotoxic) activity of natural killer (NK) cells in different effector cells (human peripheral blood lymphocytes) and target cells (K 562 or PC 9) ratios and the concentration of IFN. NK activity was examined by two methods: IFN and lymphocytes were added in the assay system directly or were precultured before assay. NK activity increased with the dosage of IFN in both experiments and reached a peak level at six to 12 hours preculture with every IFN. The augmenting effect of each interferon on NK activity was different even if the same unit of interferon was used for experiment. For the determination of optimal BRM dose of interferon, the measurement of NK activity provides the essential tool.

Cells, Cultured↗

Detection of NK activity and antibody-dependent cellular cytotoxicity of lymphocytes by human tumor clonogenic assay--its correlation with the 51Cr-release assay.

NK activity of human peripheral blood lymphocytes (PBL) for cells of the human myeloid line K562, and antibody-dependent cellular cytotoxicity (ADCC) of PBL for cells of human lung adenocarcinoma line PC-9 were determined by the human tumor clonogenic assay (HTCA). Incubation of K562 cells or anti-PC-9 serum treated PC-9 cells with PBL before plating inhibited the formation of colonies of these tumor cells. The percent inhibition of tumor cell colony formation was dependent on the effector/target ratio, the incubation time before plating and, in the case of PC-9 cells, on the dilution of anti-PC-9 serum. PBL activated with human T-cell growth factor (TCGF), lymphokine-activated killer (LAK) cells, significantly augmented the inhibition of colony formation of K562 cells, compared to the control lymphocytes. The increase in colony inhibition was dependent on the concentration of TCGF and the time of incubation of PBL with TCGF. The HTCA determining the colony inhibition of K562 cells incubated with LAK or PBL correlated with the 51Cr-release assay (p less than 0.001). The HTCA determining the colony inhibition of anti-PC-9 serum-treated PC-9 cells incubated with PBL also correlated with the 51Cr-release assay (p less than 0.001). We found that the NK activity and ADCC of lymphocytes on K562 and PC9 tumor lines could be detected with HTCA.

Adenocarcinoma↗

Evaluation of a new drug 7-N-(p-hydroxyphenyl)-mitomycin C [KW 2083] against carcinoma of the lung by the human tumor clonogenic assay.

KW 2083, which is a new mitomycin C derivative currently under clinical investigation, was tested for its antitumor effect on the growth of human carcinoma of the lung by using an in vitro clonogenic assay system. The in vitro results in this study were as follows: We succeeded in producing clonal growth at a high rate in all histologic types of carcinoma of the lung in the assay system. That is, 61 of 81 specimens (75%) of either primary or metastatic tumors gave adequate growth for chemosensitivity testing. The in vitro responses to vindesine, adriamycin, mitomycin C and melphalan (substituted for cyclophosphamide in vitro), as standard anticancer drugs for chemotherapy of carcinoma of the lung were 18, 23, 18 and 19%, respectively, which are in good general agreement with the clinical responses to these drugs reported previously. Therefore, the clonogenic assay system might prove to be a very effective tool for an in vitro phase II study of new drugs. The rate of response to KW 2083 tested simultaneously in 51 cancer specimens was 22%, which was superior to that of mitomycin C. These results indicate that KW 2083 might be more useful than mitomycin C in clinical practice.

Adenocarcinoma↗

Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay.

To analyze the discrepancy between the in vitro response in the clonogenic assay and the clinical response, the time-schedule dependencies of various anticancer drugs were determined by comparing the inhibiting effect against colony formation by PC-7 cells treated with the drugs for 1 h with that of those treated for 24 h. According to their schedule dependency the drugs can be divided into a schedule-dependent drug group (5-fluorouracil, methotrexate, bleomycin, pepleomycin, etoposide, cisplatin, teniposide, vindesine, and vinblastine) and a non-schedule-dependent drug group (adriamycin, actinomycin D, ranomustine, mitomycin C, aclacinomycin, daunomycin, nimustine, melphalan, and KW 2083). In the clonogenic assay, the 1-h exposure schedule is appropriate for predicting clinical response for the non-schedule-dependent drugs. However, the effect of the schedule-dependent drugs was underestimated in the same conditions. Therefore, it is necessary to test these drugs in the assay by 24-h exposure for a more accurate assessment of their antitumor activity.

Adenocarcinoma↗

Suppression of natural killer activity in patients treated with cisplatin and methylprednisolone.

The achievable concentrations of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl-3-nitrosourea (ACNU), adriamycin, mitomycin C, vindesine, and epipodophyllotoxin suppressed the natural killer (NK) activity of human peripheral blood lymphocytes in vitro, whereas NK activity was not decreased 24 h after incubation with the maximum achievable concentration of cisplatin (cDDP). NK activity of patients treated with 80 mg per square meter of cDDP alone was not decreased for 3 weeks after cDDP administration. In contrast, NK activity of patients treated with the same dose of cDDP and methylprednisolone was significantly decreased 1 week after cDDP administration. It was concluded that methylprednisolone, used as an antiemetic agent, had an immunosuppressive effect.

Adult↗

The use of human tumor clonogenic assay in predicting combination effect of cisplatin plus vindesine in carcinoma of the lung.

By using a human tumor clonogenic assay, cisplatin plus vindesine regimen was evaluated in 17 carcinoma of the lung. The cisplatin (0.2 microgram/ml) plus vindesine (0.005 microgram/ml) combination was synergistic and additive cell killing in 10 and 4, respectively, of 17 specimens. On the other hand, only three specimens showed antagonistic cell killing from this drug combination. Our results indicated that this in vitro assay provides a new method which can predict the effects of the combination of drugs on individual patients.

Antineoplastic Combined Chemotherapy Protocols↗

[Current perspectives in the management of non-small cell lung cancer].

Unfortunately, unlike small cell lung cancer, clinical trials of chemotherapy for the treatment of non-small cell lung cancer (NSCLC) have not consistently demonstrated a clinical benefit. However, recent studies have indicated some progress in the development of drug combinations using several active antineoplastic agents with no overlapping toxicity, and, in recent years, clinical trials of combination chemotherapy with such agents as VDS and CDDP have consistently produced response rates of 40 approximately 50%. In this review, we are focusing on the details of updated treatment schedules of combination chemotherapy against NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

[Current perspectives in the management of small cell lung cancer].

Considerable progress has been made within the last decade in the management of small cell lung cancer (SCLC) resulting in prolongation of median survival by 4 to 5 times (about 14 and 9 months in limited and extensive disease, respectively), improved quality of life, and an increase of cure rates in 15 approximately 20% of the patients with limited disease. In this review, we are focusing on the details in update treatment schedules of combination chemotherapy against SCLC, prognostic features and staging of SCLC, the role of non-cross resistant alternating chemotherapy, radiotherapy to the primary site including hilar and mediastinal lymph nodes, prophylactic cranial irradiation and surgery in the treatment of SCLC, as well as the complications of treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[cis-Dichlorodiammine platinum (II) in the treatment of advanced colo-rectal cancer].

The effect of CDDP was evaluated in 10 cases of advanced colo-rectal cancer. Prior chemotherapy was done in seven cases and three were fresh cases. The dosage of CDDP was in the range of 70-100 mg/m2 per individual. Seven cases out of 10 receiving the CDDP chemotherapy achieved no change and there were three cases of PD. Response rate was 0%. Values of serum creatinine and BUN were transiently evaluated and bone marrow toxicity was moderate. Emesis of patients treated with CDDP was suppressed by the administration of high doses of metoclopramide (2 mg/kg X 4 times).

Adenocarcinoma↗

Comparison of vindesine plus cisplatin or vindesine plus mitomycin in the treatment of advanced non-small cell lung cancer.

Fifty-eight patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either cisplatin (80 mg/m2 every 3 weeks) or mitomycin (8 mg/m2 weekly X 3, then every 3 weeks). No patients achieved complete response. Among the 28 patients treated with vindesine plus cisplatin, there were 12 partial responders (42.9%); among the 30 patients treated with vindesine plus mitomycin, there were only three partial responders (10%) (P less than 0.005). The median duration of response was 11.5 weeks (range, 4-25) in the patients treated with vindesine plus cisplatin. The median survival times for patients treated with vindesine plus cisplatin and vindesine plus mitomycin were 10.1 and 10.2 months, respectively; there was no statistical difference in survival time between the two groups. Initial performance status was the strong predictor of patient survival. Toxic effects, including moderate myelosuppression, nephrotoxicity, peripheral neuropathy, and gastrointestinal symptoms, were generally manageable. The combination of vindesine and cisplatin appears to be effective against advanced non-small cell lung cancer.

Adenocarcinoma↗

Phase II study of vindesine in patients with non-small cell lung cancer.

A phase II study of vindesine (VDS) was carried out in 21 patients with non-small cell lung cancer (NSCLC). There were 13 and 8 patients with and without prior chemotherapy, respectively. VDS was administered at a weekly iv dose of 3 mg/m2. Partial response was observed in two of 15 adenocarcinomas and one of 2 adenosquamous cell carcinomas, and the overall response rate was 14.3% (3/21). Myelosuppression, especially leukopenia, was the most common dose-limiting side effect. Neurotoxicity was also a common side effect but the degree was mild. It was concluded that VDS at a dose of 3 mg/m2 every week seems to be active against NSCLC.

Adenocarcinoma↗

[Clinical phase II study of 5'-DFUR for cancer of the digestive organs by a cooperative study group].

Phase II study of a new 5-fluorouracil derivative, 5'-deoxy-5-fluorouridine (5'-DFUR), was performed with oral administration. Forty-nine patients with advanced cancer of the digestive organs, lung and breast were entered, and 8 institutions in Hokkaido were involved. 5'-DFUR was administered three or four times a day at a daily dosage of 600 to 1200 mg. Partial response was observed in three gastric cancer cases and two breast cancer cases out of 39 evaluable cases, and minor response was observed in one colorectal cancer case. Overall response rate was 12.8%, 15.8% in gastric cancer and 66.7% in breast cancer. Side effects were observed in 15 cases out of 45 (33.3%), which mainly consisted of gastro-intestinal disturbances such as diarrhea.

Adenocarcinoma↗

[The control of chemotherapy-induced nausea and vomiting].

A growing interest has been shown in antiemetics with important advances in understanding the physiology of vomiting and the development of new anticancer agents having high emetic potential such as cisplatin. At present, high-dose metoclopramide, dexamethasone and butyrophenones have shown effective antiemetic action. In addition, antiemetic drug combinations that affect more than one neurotransmitter receptor have achieved improved emesis control. While improvements have been made in acute chemotherapy-induced emesis, anticipatory and delayed emesis is still a difficult problem. Further studies under well-designed trials are necessary to establish which of the available agents, doses, routes of administration, and schedules are best for reducing emesis depending on the chemotherapeutic drugs used.

Antiemetics↗

[The role of chemotherapy in metastatic pulmonary tumors in a disease-oriented phase II study of anticancer agent].

It is essential to conduct a precise and scientific phase II study of anticancer agent to ascertain active drugs for the establishment of standard chemotherapeutic regimens. In this review, we discuss the rationales of phase II study of agents against metastatic pulmonary tumors as well as of postsurgical adjuvant chemotherapy. The results of the phase II study of cisplatin against metastatic pulmonary tumors in the National Cancer Center Hospital are discussed from the standpoint of a drug- and disease-oriented phase II study.

Anthraquinones↗

Phase II study of cis-diamminedichloroplatinum in patients with non-small cell lung cancer.

A phase II study of cis-diamminedichloroplatinum (CDDP, 80 mg/m2, every 3 weeks) was performed in patients with non-small cell lung cancer (NSCLC). The overall response rate to CDDP was 14% (6/42). In patients without prior chemotherapy, the response rate was 20% (2/10), and in patients with prior chemotherapy, the response rate was 13% (4/31). The major side effect was gastrointestinal toxicity. It was concluded that CDDP at a dose of 80 mg/m2 every 3 weeks is effective against NSCLC.

Adenocarcinoma↗

Phase II study of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083) in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors.

Twenty-six patients with non-small cell carcinoma of the lung and 25 with metastatic pulmonary tumors were treated by intravenous injection of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083), a derivative of mitomycin C, either at a single 70-mg/m2 dose or at a dose of 20-30 mg/m2 once a week for 3 weeks. Two patients with adenocarcinoma among 21 evaluable patients with non-small cell carcinoma of the lung, and one with embryonal cell carcinoma among 21 patients with metastatic pulmonary tumors achieved partial response lasting 5 to 7 weeks. In these three patients, KW2083 was administered by a single 70-mg/m2 dose, and no patients who received a dose of 20-30 mg/m2 weekly achieved objective response. Myelosuppression, primarily thrombocytopenia, was pronounced with either treatment regimen and it was the major dose-limiting toxicity.

Adult↗