Biomedical subjects

N Saijo

Publications and source records attributed to N Saijo.

At least 325 records · Page 18Linked to original sources

PubMed1987

In vitro growth inhibition of cisplatin-resistant human lung cancer cell lines by recombinant human tumor necrosis factor and/or recombinant human interferon-gamma by virtue of collateral sensitivity.

The colony-inhibitory effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-gamma (rH-IFN-gamma) were evaluated in four human lung cancer cell lines and their cisplatin-resistant sublines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), H69 and N231 (small cell lung cancer) and four cisplatin-resistant sublines, PC-7/1.0, PC-9/0.5, H69/0.2 and N231/0.2, which were 20.0, 7.1, 4.8 and 8.4 fold resistant to cisplatin, respectively, compared to the respective parental cell line in terms of IC50 in a soft agar colony assay. All parental cell lines were resistant to rH-TNF and rH-IFN-gamma, alone or in combination. However, two resistant sublines showed sensitivity to rH-TNF and rH-IFN-gamma. Colony formation by PC-9/0.5 was significantly inhibited, in the absence or presence of cisplatin, by 10(2) U/ml of rH-TNF (less than 50% of control) and the inhibition was synergistic with that produced by 10(3) or 10(4) U/ml of rH-IFN-gamma. RH-IFN-gamma inhibited the colony formation of H69/0.2 only at the highest concentration tested (10(4) U/ml) (less than 50% of control) and the combined effect with rH-TNF was additive. These results suggest that rH-TNF and rH-IFN-gamma may have some potential in overcoming cisplatin resistance by virtue of collateral sensitivity.

Cisplatin↗

PubMed1987

A case report of adenocarcinoma of the lung in which a partial response was achieved by carboplatin.

A 56-year-old housewife was incidentally discovered to have an abnormal shadow in the right B6 area upon a chest X-ray film being taken. A transcutaneous lung biopsy of the mass revealed adenocarcinoma of the lung (WHO classification). A brain computed tomography (CT) scan demonstrated multiple brain metastasis. Following whole brain irradiation, carboplatin (CBDCA) (450 mg/m2) was administered by intravenous drip infusion on March 7, 1986. After three weeks of initial treatment with CBDCA, the size of the tumor in the primary site was found to have decreased on the chest X-ray film by more than 50%, following which, similar doses of CBDCA were administered twice, and reduced (330 mg/m2) doses three times every three to four weeks. She showed a partial response and, for seven months after the beginning of the CBDCA treatment, no progression was seen on the chest X-ray film. It is suggested that there is a need for further phase II studies of CBDCA against non-small cell lung cancer.

Adenocarcinoma↗

PubMed1987

[A randomized controlled trial of acute and delayed cisplatin-induced emesis with metoclopramide, dexamethasone and prochlorperazine].

Forty patients with advanced lung cancer who had received chemotherapy containing cisplatin (80 mg/m2) were accrued for a randomized controlled trial to evaluate the additional effect of prochlorperazine on the combination of high-dose metoclopramide and dexamethasone for the treatment of acute cisplatin-induced emesis. The effect of intravenous metoclopramide and dexamethasone in emesis occurring more than 24 hours after cisplatin administration was also evaluated. Excellent emetic control (no emesis during 24 hours after cisplatin administration) was achieved in 70% (14/20) and 76% (16/21) of the patients who received the combination of prochlorperazine, metoclopramide and dexamethasone and the combination of metoclopramide and dexamethasone, respectively. The overall toxicities associated with both regimens were not serious and were similar. Patients treated with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared with those treated with a placebo (delayed emesis, 25% versus 50%, respectively, p = 0.105; more than 4 days of nausea, 10% versus 35%, respectively, p = 0.059; less than 3 days of anorexia, 80% versus 50%, respectively, p = 0.048). It was concluded that metoclopramide and dexamethasone showed an excellent antiemetic effect on acute drug-induced emesis, as well as on delayed emesis, induced by cisplatin.

Adult↗

PubMed1987

A case report of pulmonary adenocarcinoma responding to (glycolato-0,0') diammineplatinum (II), a new platinum complex.

The first patient to respond to [(glycolato-0,0') diammineplatinum (II)] (254-S) in a clinical phase I study is reported. The patient was a 52-year-old man complaining of nausea and weight loss. A chest X-ray demonstrated a diffuse infiltrating shadow in the right lung. A transbronchoscopic brushing of the right upper lobe and a biopsy specimen from the right supraclavicular lymph node revealed adenocarcinoma of the lung. He was diagnosed as having primary lung cancer with distant lymph node metastasis. 254-S was administered by intravenous drip infusion to a dose of 100 mg/m2. Two weeks after the second 254-S treatment, a chest X-ray demonstrated a more than 50% reduction in the pulmonary shadow and met the WHO criteria for a partial response. Thrombocytopenia, leukocytopenia and moderate nausea were observed as adverse effects of 254-S but renal toxicity was not found. Pharmacokinetics of free platinum in this patient demonstrated biphasic decay with a peak plasma concentration of 8.09 micrograms/ml. A disease-oriented phase II study of 254-S against non-small cell lung cancer should be performed to establish the efficacy of this new platinum complex.

Adenocarcinoma↗

PubMed1987

[Phase I-II study of recombinant interleukin-2].

A phase I-II study of recombinant interleukin 2 (rIL-2) (Shionogi Pharmaceutical Co.) was conducted against carcinoma of the lung (20 cases) and stomach (1 case) as well as metastatic pulmonary tumor (17 cases). The cytotoxicity of lymphocytes against K562, PC-9, PC-14 and Daudi cells was examined before and 1, 2, 3, 5, 7, 14, 21 and 28 days after rIL-2 administration. The subsets of lymphocytes and pharmacokinetics of rIL-2 were also analyzed. Four administration methods were used. 2-h drip infusion of 6.7 X 10(5) U/m2/day (A1: 6 cases) or 2.2 X 10(6) U/m2/day (A2: 8 cases) for 5 consecutive days, subcutaneous injection of 6.7 X 10(5) U/m2/day (B: 3 cases) for 28 consecutive days, 4-h continuous drip infusion of 3.3 X 10(5) U/m2/day (C1: B cases), 6.7 X 10(5) U/m2/day (C2: 7 cases) or 1.1 X 10(6) U/m2/day (C3: 5 cases) for 28 consecutive days, and (D) 24-h continuous drip infusion of 6.7 X 10(5) U/m2/day (D: 6 cases) for 5 consecutive days every week, repeating four cycles of the course. We discussed whether or not the problems of the phase I study with BRMs could be solved.

Drug Administration Schedule↗

PubMed1987

Synergistic effect of recombinant interleukin-2 on the inhibition of growth of adenocarcinoma 755 by mitomycin.

The increase in life-span (ILS) of tumor-bearing mice caused by recombinant interleukin-2 (RIL-2) was studied in the solid tumor adenocarcinoma 755 system. With long-term treatment (Days 5-12), RIL-2 (10(5) U/mouse) showed a weak effect (24% ILS), but short-term RIL-2 treatment (Days 5-8 or 9-12) had hardly any effect. Mitomycin, at 2 mg/kg (maximum nontoxic dose), caused 35% ILS with Days 5-8 treatment and only 12% ILS with Days 9-12 treatment. Sequential treatment with mitomycin (Days 5-8) and RIL-2 (Days 9-12) markedly enhanced antitumor activity (88% ILS). This value is significantly greater than that of mitomycin alone or RIL-2 alone (P less than 0.01). Furthermore, mitomycin followed by RIL-2 markedly augmented killing activity of spleen cells that are cytotoxic in vitro. These results indicate that RIL-2 markedly affects the inhibition of growth of a tumor treated with an antitumor agent.

Adenocarcinoma↗

PubMed1987

[In vitro drug sensitivity test].

Human tumor clonogenic assay(HTCA) not only offers potential advantages for prediction of the sensitivity of individual patients, to anticancer drugs, but also for the development and preclinical testing of prospective new antineoplastic agents. However, HTCA has several theoretical and technical problems, such as a low success rate, the requirement of large numbers of tumor cells and the long time period necessary for evaluation. In order to solve these problems, the MINI-hybrid assay has been developed. We reviewed our experiences to date with chemosensitivity testing by MINI-hybrid assay. Twenty-two of 23 tumors gave evaluable chemosensitivity results (95.6%), and the range of thymidine incorporation for evaluable assays was 7 X 10(2)-1.2 X 10(5)cpm. In addition, the results of drug sensitivity testing of cultured cell lines by MINI-hybrid assay were well correlated with those obtained by HTCA. With its high evaluability rates, the need for fewer cells, the short duration (5 days) required and ease of quantitation, the MINI-hybrid assay is widely applicable to the chemosensitivity testing of human tumors.

Antineoplastic Agents↗

PubMed1987

A case of adenocarcinoma of the lung which was successfully treated by chemotherapy with patient survival without recurrence for more than three years.

A 63-year-old man was admitted to the National Cancer Center Hospital on December 20, 1983 for a close examination of the abnormal shadows found in chest roentgenograms. Chest radiographs showed a massive right pleural effusion, a large tumor in the right hilar region and swelling of the left hilar nodes. Transcutaneous needle biopsy revealed the tumor's cytological type to be adenocarcinoma. The clinical stage was considered to be T3N2M1 (American joint committee (AJC) stage III M1), and his performance status was 4, so he was given etoposide (VP-16) alone as the initial chemotherapy treatment. He showed a partial response upon two courses of VP-16 therapy. Subsequently, one course of cisplatin (80 mg/m2) + vindesine (3.3 mg/m2), two courses of VP-16 (80 mg/m2 D1-4), five courses of cyclophosphamide (80 mg/m2) + adriamycin (50 mg/m2) + vincristine (1.4 mg/m2) and two courses of VP-16 (100 mg/m2 D1, 3, 5) were administered sequentially until May 31, 1985. No radiation therapy was given and, up to March 31, 1987, no sign of recurrence had been observed.

Adenocarcinoma↗

PubMed1986

The value of two-dimensional echocardiography in detecting malignant tumors in the heart.

Six unusual cases of tumor involvement of the heart and pericardium, diagnosed antemortem by two-dimensional echocardiography (2DE), are described. The tumors consisted one each of sacral chordoma, mediastinal seminoma, leiomyosarcoma of the uterus, osteosarcoma, invasive thymoma, and lung cancer. The current study again recognizes the concept that any type of malignant tumor has a possibility of involving the heart. If cardiac involvement is suspected, 2DE examination should be performed in patients with any kind of malignant tumor. The information obtained not only provides guidance for therapeutic maneuvers, but also is beneficial for follow-up observation of the patients and assessment of the therapy.

Adenocarcinoma↗

PubMed1986

Serial plasma carcinoembryonic antigen measurement for monitoring patients with advanced lung cancer during chemotherapy.

The plasma carcinoembryonic antigen (CEA) levels in 243 patients with untreated advanced lung cancer were studied to assess their value for prognosis and for indicating the effectiveness of chemotherapy. Of patients with adenocarcinoma, small cell carcinoma, squamous cell carcinoma, and large cell carcinoma, 43%, 24%, 7%, and 13%, respectively, had elevated CEA levels of 20 ng/ml or greater before treatment. Pretreatment CEA levels were elevated to above 20 ng/ml for 38% of 163 patients with extensive disease and for 22% of 80 patients with limited disease (P less than 0.02). In patients with adenocarcinoma of the lung, the pretreatment CEA levels were not correlated with response to chemotherapy and patients' survival. Serial measurement of plasma CEA was a useful noninvasive technique for monitoring the response to chemotherapy in patients whose pretreatment levels were 20 ng/ml or higher. All of 18 patients with complete or partial responses and 5 of 6 patients with minor responses showed greater than 36% decrease in the CEA level compared with the pretreatment level. In all of nine patients with progressive disease, the CEA levels increased after chemotherapy. Therefore, an increase of greater than 36% beyond the baseline level was a useful guideline criterion for a significant change for determination of tumor response to chemotherapy, although 41% of 22 patients with stable disease exceeded the pretreatment level by 36% or more in either direction (mean percent change +/- standard deviation, -4.1% +/- 52.2%), and 4 of 9 patients with progressive disease did not have levels greater than 36% above the baseline levels.

Adenocarcinoma↗

PubMed1986

In vivo augmentation of the cytotoxicity of spleen lymphocytes against syngeneic B-16 melanoma cells and the suppression of the artificial metastases in C57BL/6 mice by subcutaneous multiple injections of high dose human recombinant interleukin-2 (rIL-2).

The cytotoxicity of spleen lymphocytes against YAC-1 cells, against syngeneic B-16 and F-10 melanoma cells was augmented not only by incubation of spleen lymphocytes with human recombinant interleukin-2 (rIL-2) in vitro, but also by injecting C57BL/6 mice with high dose rIL-2 for more than 3 consecutive days. In animals injected s.c. with multiple high dose rIL-2, the numbers of tumor nodules in the lung were significantly decreased 21 days after i.v. tumor inoculation. In addition, in these groups of animals no liver metastases were observed although liver metastases were detected in 6/11 control mice.

Animals↗

PubMed1986

Detection of cytotoxicity of freshly obtained lymphocytes and of lymphocytes activated with recombinant interleukin II (rIL-2) against lung cancer cell lines by human tumor clonogenic assay (HTCA).

The cytotoxicity of freshly obtained human peripheral blood lymphocytes and lymphocytes activated with human recombinant interleukin II (rIL-2) was evaluated against lung cancer cell lines by the human tumor clonogenic assay. Colony formation of all human lung cancer cell lines, PC-1, 3, 6, 7, 9, 13 and 14 were suppressed by lymphocytes activated with 100 units/ml of human rIL-2 for 72 hr. However, the degree of the suppression of colony formation by lymphocytes activated with rIL-2 was different for each cell line. The per cent inhibition of colony formation obtained by HTCA correlated well with the per cent cytolysis obtained by 51Cr-release assay for all cell lines. HTCA provides a very useful tool for the detection of cytotoxicity of lymphocytes against clonogenic tumor cells.

Cell Division↗

PubMed1986

Biological, pathological and clinical features of small cell lung cancer.

Small cell lung cancer, which is not uncommon, and is one of the most malignant and relatively well investigated solid tumors of adults, has been reviewed concerning its biology, pathology and clinical aspects. Although it is histologically very simple, its poorly differentiated epithelial cell characteristics are complicated by features of neuroendocrine cells, such as amine and peptide hormone production and specific enzyme activities, some of which have been found to be good monitoring markers during and after treatment. Because of the relative ease of establishing cell lines in vitro, cell characteristics have been studied in detail. This has led to subtyping of cell lines and may further lead to subtyping of histology. However, accumulation of further evidence has disclosed exceptions and unclassifiable cell lines. The same can be said about chromosomal abnormality. The reactivity of monoclonal antibodies and also oncogenes supports the prevalent concept discriminating small cell cancer from non-small cell cancer. However, concepts concerning histogenesis are still changing. Although it is one of the solid tumors most sensitive to radiation and chemotherapy, the response rate of the tumor to non-surgical treatment appears to have reached a plateau. In order to make a breakthrough in the treatment, strategies based on biological findings must be applied.

Antibodies, Monoclonal↗

PubMed1986

A case of small cell lung cancer successfully treated with VM26.

A 79-year-old man was admitted to our hospital for a close examination of an abnormal shadow on a routine chest roentgenogram. A large tumorous shadow in the right S1 segment, and hilar and mediastinal node swelling were observed. Transbronchial biopsy revealed that the histologic type of the tumor was oat cell carcinoma. The clinical stage was considered to be limited disease. Because of his age, 79 years, he was treated with VM26 as a single agent. VM26 was administered by intravenous drip infusion of 60 mg/m2 daily for five consecutive days every three to four weeks. After the third course of treatment with VM26, he achieved partial response, and then radiation therapy to the primary site and the hilar and mediastinal nodes was given at a total dose of 6,000 rad. There have been few phase II studies of VM26 in patients with small cell lung cancer (SCLC). Further phase II studies should be conducted for confirmation of the reproducibility of the phase II study of VM26 in SCLC, and the efficacy of combination chemotherapy including VM26 against SCLC should also be tested.

Aged↗

PubMed1986

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

A phase II study of UFT (a mixture of uracil and tegafur; molar ratio of uracil to tegafur = 4) was undertaken in 21 patients with advanced non-small cell lung cancer (NSCLC). UFT was administered orally at a dose of 400 mg/m2 every day, for more than four weeks. Of 16 adequately treated patients, one (6.3%) showed a partial response. Toxic effects included minimal myelosuppression, anorexia, nausea, vomiting and epigastralgia. Gastrointestinal toxicity was well tolerated. Considering the poor response and mild toxicity, a further phase II study of higher-dose UFT is necessary for patients without prior therapy.

Adult↗

PubMed1986

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

A phase II study of mitoxantrone was performed in 24 patients with non-small cell lung cancer (NSCLC). Mitoxantrone was administered by intravenous drip infusion of 12 mg/m2 every three weeks. There were no responders among the 21 evaluable patients including five patients without prior therapy. The major hematological toxic effect was leukocytopenia. Thrombocytopenia and decrease in hemoglobin were slight. A change in the electrocardiogram was observed in one patient and one patient experienced cardiogenic shock. Mitoxantrone is not acceptable for the treatment of NSCLC because of its low antitumor activity, and careful observation is needed for administration of this agent to patients with pre-existing risk factors, such as prior anthracycline exposure, mediastinal radiation or underlying cardiovascular disease.

Aged↗

PubMed1986

The protective effect of 2-mercapto-ethane sulfonate (MESNA) on hemorrhagic cystitis induced by high-dose ifosfamide treatment tested by a randomized crossover trial.

High-dose ifosfamide (one or two courses of 6 g/m2) with or without mesna was administered to 13 patients with advanced non-small cell lung cancer. The protective effect of 2-mercapto-ethane sulfonate (mesna) against the urotoxic side effects induced by ifosfamide was examined by a randomized crossover trial. A significant reduction in the incidence of hematuria was observed in the patients receiving mesna. Macroscopic hematuria was observed in only one patient who received treatment with mesna versus seven patients treated with ifosfamide alone. Other symptoms, such as frequency and dysuria, tended to be diminished in the patients receiving mesna, although the difference was not statistically significant. Our results suggest that mesna is effective in preventing or diminishing ifosfamide-induced hemorrhagic cystitis. Concomitant use of mesna should allow the administration of a high dose of ifosfamide although more extensive studies are needed to define the optimal dose and schedule of administration of mesna to prevent or attenuate the hemorrhagic cystitis.

Adult↗

PubMed1986

A case report of a three-year survivor with advanced non-small cell lung cancer producing alpha-fetoprotein.

An 80-year-old patient with poorly differentiated adenocarcinoma of the left lung with metastasis to both lungs and supraclavicular lymph nodes, stage III M1 (T2N2M1), was treated with cisplatin (cis-diamminedichloroplatinum, CDDP) at a dose of 80 mg/m2 intravenously. He achieved a partial response, however, he could not continue therapy with CDDP because of its renal toxicity. He was then given etoposide and vindesine as a single chemotherapeutic agent, but no response was observed. Therefore, CDDP was administered again in a fractionated regimen, the first course of treatment achieved a minor response, but the second course resulted in stable disease. He therefore received combination chemotherapy consisting of mitomycin, vindesine and CDDP, and tumor regression of more than 30% was observed after one course of this combination chemotherapy. After three years from the initiation of chemotherapy, he had no symptoms except for hoarseness, and has been followed up on an ambulatory basis. In addition, the tumor was producing alpha-fetoprotein (AFP), which was shown by immunohistochemical staining with polyclonal antibody against AFP. The changes in serum AFP level correlated well with the disease status.

Adenocarcinoma↗