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Biomedical subjects

H Futami

Publications and source records attributed to H Futami.

At least 55 records · Page 3Linked to original sources
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of U-937 cells.

Exposure of U-937 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine metabolism. Within 24 h after treatment with 1.62 x 10(-9) M TPA, the reciprocal alteration in the activities of opposing enzymes of thymidine metabolism observed during normal cell culture growth was reversed. In TPA-treated cells, the activities of anabolic enzymes thymidine kinase (EC 2.7.1.75)and thymidylate synthase (EC 2.1.1.45) declined with time linearly to 20 and 16% of those of untreated cells by 72 h. Incorporation of [3H]thymidine and [3H]deoxyuridine into acid-insoluble fractions also decreased in parallel with the decline in enzyme activities. In contrast, the activities of catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrothymine dehydrogenase (EC 1.3.1.2) increased. The rise in thymidine phosphorylase activity peaked at 48 h with 406% elevation over the control. The activity of dihydrothymine dehydrogenase was not altered for the first 24 h, but it increased up to 338% by 96 h. Immunotitration of dihydrothymine dehydrogenase with monoclonal antibody against this enzyme showed that the rise in activity in the differentiated cells was due to the increase in the amount of enzyme protein. No significant difference was observed in the Km values for the substrate of each enzyme between untreated and TPA-treated cells. These metabolic alterations during induced differentiation were in line with the changes in cell morphology and accompanied by an accumulation of the cells in G1 at the expense of S phase. These observations indicate that induced differentiation of U-937 cells results in a reversal of the enzymic phenotype of thymidine metabolism and suggest that emergence of thymidine metabolic imbalance may serve as an early marker of differentiation of these cells.

Cell Cycle↗
PubMed1989

Effects of the combination of acivicin and cis-diamminedichloroplatinum(II) on thymidylate synthesis of A549 lung cancer cells.

Compared to either compound alone, the combination of acivicin and cis-diamminedichloroplatinum(II) markedly enhanced the inhibition of the activities of thymidylate synthase and thymidine kinase, the enzymes involved in the final steps of the de novo and salvage pathways in pyrimidine metabolism in A549 lung cancer cells. The enhancement of enzymic inhibition paralleled that of cell growth inhibition. These results indicate that the combination of these drugs can inhibit the capacities of the pyrimidine pathways, resulting in an efficient reduction of DNA synthesis.

Antimetabolites↗
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of HL-60 cells.

Exposure of HL-60 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine (TdR) metabolism. Within 12 h after treatment with 1.62 nM TPA, the reciprocal alteration in the activities of opposing pathways of TdR metabolism observed during normal culture cell growth was reversed. In TPA-treated cells, the activities of anabolic enzymes, TdR kinase (TK; EC 2.7.1.21) and thymidylate synthase (TS; EC 2.1.1.45), declined to 15% and 18% of those of untreated cells by 96 h. Incorporation of 3H-TdR and 3H-deoxyuridine also decreased in parallel with decline in enzyme activities. In contrast, the activities of catabolic enzymes, TdR phosphorylase (TP; EC 2.4.2.4) and dihydrothymine dehydrogenase (DHT DH; EC 1.3.1.2), increased to 399% and 318% by 96 h. Immunotitration of DHT DH with monoclonal antibody showed that the rise in activity in the differentiated cells was due to the increase in protein amount. Kinetic properties of the enzymes were not altered during differentiation. These metabolic alterations were accompanied by an accumulation of the cells in G1 at the expense of S-phase. Present data indicate that induced differentiation of HL-60 cells results in a reversal of enzymic phenotype of TdR metabolism due to a consequence of decreased proliferation and suggest that emergence of TdR metabolic imbalance may serve as early markers of differentiation of these cells.

Cell Cycle↗
PubMed1989

[Adriamycin, cisplatin, and etoposide combination chemotherapy for small cell lung cancer].

Twenty-three patients with small cell lung cancer (11 with limited disease and 12 with extensive disease) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated at 3- or 4-week intervals for 3 to 5 treatment cycles. Among 22 evaluable patients, 5 showed complete response and 17 had a partial response (response rate 100%). The median response duration of 12 extensive disease patients was 21 months. There were 5 survivors for more than 2 years. Toxicity included moderate to severe hematologic toxicity, alopecia, nausea and vomiting. This combination chemotherapy appears to be optimal for the treatment of small cell lung cancer.

Aged↗
PubMed1989

[Peripheral neuropathy caused by cisplatin in patients with lung cancer].

The correlation between peripheral neuropathy and cisplatin (CDDP) was elucidated in 27 patients with primary and metastatic lung cancer, who were treated with Adriamycin 30 mg/m2 day 1, CDDP 80 mg/m2 day 1, and VP-16 70 mg/m2 day 1-5 every 4 weeks. The incidence of peripheral neuropathy was 33% (9 of 27 patients) and it increased to 60% in the patients who received over 320 mg/m2 of CDDP, demonstrating a positive correlation between the incidence of this toxicity and the total dose of CDDP. However, no significant relation was observed between the grade of neuropathy and CDDP. The neuropathy was manifested in the sensory system of the distal extremities and was developed into proximal portions. The peripheral neuropathy with grade 3 was irreversible, resulting in the dose-limiting factor of this regimen.

Adult↗
PubMed1989

[A case of pulmonary tuberculosis in a long-term survivor with small cell carcinoma of the lung].

A 64-year-old woman complained of chest pain, back pain and dry cough. Chest X-ray film showed marked left hilar enlargement and left pleural effusion. Biopsy of the bronchial mucosa and demonstrated small cell carcinoma of the lung. Treatment with cisplatin, adriamycin and etoposide led to regression of symptoms and chest X-ray findings within 3 months. She received maintenance chemotherapies at the outpatient clinic for 2 years after the first therapy. Thirty-months after the first admission, chest X-ray film showed multiple small nodules in the left upper lobe. Chest tomography and high-resolution computed tomography showed acinar or lobular nodules disseminated in the left upper lobe. Mycobacterium tuberculosis was obtained from bronchoalveolar lavage fluid of the left upper lobe. Pulmonary tuberculosis in a long-term survivor of small cell carcinoma of the lung is very rare.

Carcinoma, Small Cell↗
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

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

Differences of host immune response and of sensitivity to chemotherapeutic agents between two clones of rat fibrosarcoma with different metastatic potential.

Differences of host immune response and of chemosensitivity between two clones derived from a methylcholanthrene-induced rat fibrosarcoma and exhibiting different tumorigenic and metastatic potentials were examined. Clone G, which has no metastatic potential, was more sensitive to natural killer cytotoxicity by syngeneic rat spleen cells than clone A, which is highly metastatic. The colony formation of clone G was strongly inhibited by the supernatant obtained from coculture of lymphocytes with either of these two clones. In contrast, the colony formation of clone A was not inhibited by these supernatants. Inhibition of the colony formation of clone G was dependent on the dilution of the supernatant and the incubation time of the lymphocytes and tumor cells used to generate the supernatant. The supernatant from cocultures of lymphocytes and clone G inhibited the colony formation of clone G more strongly than the supernatant from cocultures of lymphocytes and clone A. There was no difference between these two clones in chemosensitivity to seven of the ten chemotherapeutic drugs tested.

Animals↗
PubMed1986

[Fundamental study and clinical testing of human tumor clonogenic assay (HTCA)].

Through our retrospective analysis of HTCA and clinical effects as well as fundamental studies, the following results were obtained: In this retrospective study, HTCA for lung cancer showed a predictive accuracy of 71%, a true positive rate of 50% and a true negative rate of 77%. To obtain good predictive accuracy, HTCA should be modified to provide conditions comparable to those in vivo with regard to drug concentration and drug exposure time. More precise analysis of the pharmacokinetics of anticancer agents might yield methodological improvement. A decrease in the chemosensitivity spectrum in vitro was observed after chemotherapy. This might be related to evidence that patients with prior chemotherapy exhibited a poor response rate to chemotherapy. There were no active anticancer agents against specimens with aplating efficiency of more than 0.04%. More extensive prospective trials will be necessary to determine the clinical value of HTCA. HTCA could be a superior assay for detecting the anti-tumor activity of new agents and a useful method for in vitro phase II study.

Antineoplastic Agents↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

[Randomized control study of high-dose metoclopramide in the prevention of CDDP-induced emesis].

The effect of high-dose metoclopramide (2 mg/kg, 4 times every 2 hours) on the emesis of patients treated with CDDP (80 mg/m2) was examined by randomized control trial. The above metoclopramide regimen significantly suppressed the frequency of vomiting on the day of CDDP administration. The duration of nausea and anorexia after CDDP treatment was also shortened by high-dose metoclopramide administration.

Adult↗
PubMed1985

[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↗
PubMed1985

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↗