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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 793 records · Page 44Linked to original sources
PubMed1986

Long-term survival in patients with small cell lung cancer.

Of the 66 patients with small cell lung cancer (SCLC) who were treated by combination chemotherapy with or without radiation therapy from July 1978 to December 1983 at the National Cancer Center Hospital, Tokyo, 12 (18%) survived over two years and nine (14%) have remained disease-free over three years. The two-year survival rates were compared according to the patient characteristics of sex, performance status (PS), extent of disease, histologic subtype, regimen of the initial chemotherapy and response to treatment. Sex, extent of disease and response to the initial chemotherapy were the most important prognostic factors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patients who were treated by surgical resection after chemotherapy, achieved complete response (CR) with chemotherapy with or without radiation therapy. Eleven of the 12 two-year survivors achieved CR. Because of the small number of patients in our study, it will be necessary to evaluate further the influence of prognostic factors in patients with SCLC in future studies.

Adult↗
PubMed1986

Cytogenetic effects of multiagent chemotherapy on the peripheral lymphocytes of patients with small cell lung cancer.

Peripheral lymphocytes of 8 patients with small cell lung cancer (SCLC), who received combination chemotherapy consisting of cisplatin and VP-16 (PVP), were examined for frequency of sister chromatid exchange (SCE) and chromosomal aberrations. Three of the 8 patients were treated with the PVP regimen only; however, the others had previously been treated with multiagent chemotherapy consisting of a cyclophosphamide, adriamycin, and vincristine (CAV) regimen or a cyclophosphamide, ACNU and vincristine (CAV') regimen with or without radiotherapy. Significantly increased SCE frequency was observed in previously untreated patients 3 or 4 days after PVP treatment, compared with the pretreatment values. The earlier analysis in the previously treated patients also showed increased SCE frequency, which seemed to return to the normal value as time elapsed after PVP. In addition, abnormal chromosome count distribution and/or increased incidence of structural changes were observed in cultures from all the patients. In general, striking changes in chromosomes were observed in previously treated patients. The aberrations observed in pretreated patients consisted of chromatid gaps and breaks, exchanges, fragments and dicentric chromosomes. In addition to these abnormalities, double minutes like microchromosomes were seen irrespective of radiotherapy. Further studies are needed to elucidate whether any of the chromosomal aberrations observed in this study could participate in the induction of secondary neoplasms.

Aged↗
PubMed1986

Antitumor effect of two-drug simultaneous or sequential use of cisplatin, vindesine or etoposide on human pulmonary adenocarcinoma cell lines in tumor clonogenic assay.

The antitumor effects of two-drug simultaneous or sequential use of cisplatin, vindesine or etoposide were examined in human pulmonary adenocarcinoma cell lines by human tumor clonogenic assay. Different tumor cell lines (PC-9, PC-13 and PC-14) that originated from the same histological cell type responded quite variably to simultaneous and/or sequential therapy. The antitumor effects of various sequential combinations of cisplatin, vindesine and etoposide depended strongly on the nature of the individual tumor cell line tested.

Adenocarcinoma↗
PubMed1986

Interstitial deletion of the short arm of chromosome 6 as a new cytogenetic marker of T-cell lymphoma.

Three patients with malignant lymphoma, two of T-cell type and the other probably also of T-cell type, had an interstitial deletion of the short arm of chromosome 6, del (6)(p21p23), in common in their lymphoma cells. These findings suggest that this new type of chromosome deletion may be a specific marker for T-cell lymphoma and may play an important role in the lymphomagenesis and the expression of the T-cell phenotype.

Adolescent↗
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

Reduction of pulmonary metastases of B16 melanoma by human recombinant interleukin 2 and lymphokine-activated killer cells in immunosuppressed C57BL/6 mice receiving anticancer agent.

The immunosuppressive effect of a water-soluble nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), was evaluated in terms of the cytotoxicity of spleen lymphocytes, and the restoring effect of lymphokine-activated killer (LAK) cells and/or human recombinant interleukin-2 (rIL-2) on the cytotoxicities of spleen lymphocytes was examined in ACNU-treated C57BL/6 mice. In addition, we tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases. The administration of LAK cells and/or human rIL-2 restored the cytotoxicity of spleen lymphocytes against YAC-1 and syngeneic B-16 melanoma cells in ACNU-treated mice, and these treatments partially suppressed the increased numbers of artificial pulmonary metastases of B-16 melanoma cells in ACNU-treated mice. These results are extremely important in providing a rationale for the introduction of adoptive immunotherapy using LAK cells and rIL-2 in patients with advanced cancer who are being treated with anticancer agent(s).

Animals↗
PubMed1986

A bioassay of cisplatin by human tumor clonogenic assay.

A new bioassay method for cis-diamminedichloroplatinum (CDDP) using a human tumor clonogenic assay (HTCA) was developed and used to examine the pharmacokinetics of the active form of CDDP in different schedules of administration. The inhibition of colony growth of tumor cells decreased with increase in the % of fetal calf serum in RPMI1640 containing CDDP. By means of this assay, four administration schedules (A, B, C and D) of CDDP were examined. In patients given 40 mg/m2 of CDDP by iv infusion on day 1 twice with a 1 hr interval (schedule A), total platinum was still detectable in plasma at 6 hr by atomic absorption assay. However, the active form of CDDP was no longer detectable at 30 min. In patients treated with 20 mg/m2 of CDDP iv for 20 min daily (schedule B) from day 1 to day 4, the level of total platinum showed a cumulative increase. However, the active form of CDDP was no longer detectable at 30 min, and no cumulative effect was observed. In patients given a high dose (120 mg/m2) of CDDP iv for 30 min on day 1 (schedule C), the peak concentration of active form of CDDP was determined to be 5.0 to 7.0 micrograms/ml, and a level of more than 1.0 micrograms/ml was maintained even after 2 hr in one case. In 2 patients of this group the concentrations of active form of CDDP determined by HTCA were the same as those of ultrafiltrable platinum detected by atomic absorption assay. In 2 of 3 patients given 100 mg of CDDP into the pleural cavity, the active form of CDDP was detected in sera. High-dose CDDP administration was concluded to be preferable to low-dose therapy because of the higher peak concentration and longer residence time of the active form of CDDP in the plasma. Furthermore, it is suggested that a systemic effect of CDDP can be expected even when CDDP is given by intrapleural administration.

Adult↗
PubMed1986

Inhibitory effect of murine recombinant interferon (beta) on the pulmonary metastasis of B-16 melanoma.

The antitumor effect of murine recombinant interferon (beta) [Mu-rIFN(beta)] was examined on artificial metastasis of B-16 melanoma in C57BL/6 mice. The numbers of pulmonary nodules were significantly decreased to 16.7 +/- 4.7 (P less than 0.01), 9.5 +/- 4.2 (P less than 0.01), 7.1 +/- 5.6 (P less than 0.01) in mice given 20,000 units of Mu-rIFN(beta) intraperitoneally (ip) 24, 6, and 3 hr before intravenous tumor inoculation, respectively, compared with the control group of mice (57.1 +/- 1.4), if B-16 melanoma cells (5 X 10(5] were intravenously injected 28 days before the experiment. In mice given 20,000 units of Mu-rIFN(beta) ip 24, 6, and 3 hr before the experiment, the natural killer (NK) activities of spleen cells against YAC-1 cells were elevated to 45.5 +/- 6.1%, 53.7 +/- 3.4%, 43.2 +/- 6.5%, respectively, compared with NK activities in control mice (20.3 +/- 3.1%). Similarly, NK activities against B-16 melanoma cells were also elevated in mice given Mu-rIFN(beta). Pretreatment with anti-asialo GM1 antibody and carrageenan reduced the inhibitory effect of Mu-rIFN(beta) on the pulmonary metastasis. In vitro colony inhibition of more than 50% was not observed even if B-16 melanoma cells were incubated with 100,000 units/ml of Mu-rIFN(beta). From these results, it can be concluded that the inhibition of pulmonary metastasis by Mu-rIFN(beta) is mediated via host defense mechanisms and that NK cells and macrophages are both important for the inhibition.

Animals↗
PubMed1986

Detection of amplified DNA sequences in gastric cancers by a DNA renaturation method in gel.

A DNA renaturation method in gel was used to detect amplified DNA fragments in eight gastric cancer cell lines, KATO-III, OKAJIMA, SCH, MKN1, MKN7, MKN28, MKN45 and MKN74 cells, and tissues of three metastases of gastric cancers to lymph nodes. There were amplified DNA sequences in three gastric cancer cell lines. Judging from the intensities of the bands, HindIII-digested DNA fragments were amplified several hundred times in the KATO-III and MKN7 cell lines. DNA from OKAJIMA cell line contained multiple bands with less intensity. KATO-III cells were found to contain a homogeneously staining region in chromosome 11.

Base Sequence↗
PubMed1986

[Concentration of imipenem/cilastatin sodium in bone marrow blood following intravenous drip infusion].

A solution of 0.5 g of imipenem (MK-0787) and 0.5 g of cilastatin sodium (MK-0791) in 100 ml of saline was administered to adult patients before the surgery by intravenous drip infusion during 30 minutes. Fifty samples of bone marrow blood were obtained from 26 clinical cases. After centrifugation, the supernatant was mixed with the same amount of a solution of stabilizer then stored at -80 degrees C. The peripheral blood was obtained at the same time as bone marrow blood was sampled and serum was served as control. The concentration of MK-0787 in bone marrow blood at 35 minutes after the start of the infusion was 50 micrograms/ml in 1 case, and decreased to 3.8 micrograms/ml at 260 minutes. The half-life was 1.62 hours. When the concentration of MK-0787 in bone marrow blood was compared to that in serum, the former was higher than the latter in 26 of the 50 samples (52%). In remained 24 samples, the concentration of MK-0787 in bone marrow blood showed to be lower than that in serum (48% of 50 samples). The half-life of MK-0791 in bone marrow blood was 1.10 hours and the level of the drug in bone marrow blood was similarly higher than that in serum in 18 of 40 samples (45%). In other 22 samples, the concentration of MK-0791 in bone marrow blood was lower than that in serum (55%). It was also found that the concentration of MK-0787 in bone marrow blood decreases with time along a similar curve of decrease observed in serum. This agent appears useful for the treatment of bone and joint infections and also for prophylaxis for major surgeries of skeletal tissues.

Adult↗
PubMed1986

[Effect of imipenem/cilastatin sodium in thirty cases of bone and joint infection].

Thirty cases of bone and joint infections were treated by a chemotherapy with imipenem/cilastatin sodium (MK-0787/MK-0791). An overall curative rate was 87%. It was 96% in cases of acute inflammatory state and 50% in cases of chronic state. Thirteen cases received surgical intervention with chemotherapy and showed complete healing, but curative rate of 16 cases without surgery was 76%. Twenty strains of microorganisms were isolated and identified from these patients. The MIC of MK-0787 against S. aureus was as small as less than or equal to 0.012 to 0.024 micrograms/ml to a 10(6)/ml suspension. Thus antibacterial action of MK-0787 was very strong. The MIC against E. coli was 0.20 micrograms/ml. Incidence of adverse reactions was small as only in two cases occurred slight nausea. Laboratory examinations of blood, liver and kidney function found no influence of the drug.

Adult↗
PubMed1986

[Clinical evaluation of a new tumor marker, CA 15-3, in breast cancer; a comparative study with CEA].

Recently, a new RIA method has been developed by Centocor Co., utilizing the monoclonal antibody CA 15-3. We performed a clinical trial to evaluate its utility as a tumor marker for breast cancer in comparison with CEA. We set 15 U/ml as the cut-off value of serum CA 15-3 level from results acquired from controls; 10 volunteers and 17 patients with non-malignant diseases. The CA 15-3 positive rate among the cases of primary breast cancer was 13.3%, which was of poor diagnostic value. In the recurrent cases the positive rate of CA 15-3 was 72.0%, which was valuable compared with that of serum CEA, 52.0%. In the cases of primary cancers other than breast cancer, the positive rate of CA 15-3 was 6.9%.

Adult↗
PubMed1986

[Strategy of cancer treatment using human recombinant interleukin 2 and lymphokine activated killer cells].

There are two strategies for evaluating the antitumor effect of IL-2. In the first approach IL-2 has been used to support the proliferation of T-effector cells or LAK cells in vitro in the hope that large quantities of these effector cells can be used therapeutically. This approach has shown some efficacy in animal models if LAK cells are administered in combination with IL-2. However, it is extremely difficult to standardize the numbers of lymphocytes and the biological activity of effector cells for clinical use. Recently the cloning of IL-2 has made available large quantities of purified recombinant IL-2 (rIL-2) for preclinical and clinical trials. Accordingly there have been recent attempts at injecting rIL-2 directly to stimulate effector cells in vivo. In this study, in vivo and in vitro augmentation of the cytotoxicity of spleen lymphocytes against syngeneic B-16 melanoma cells (induction of LAK cells) and the suppression of artificial pulmonary and liver metastases of B-16 melanoma in C57BL/6 mice was tried by subcutaneous multiple injections of high-dose human rIL-2. In addition, the immunosuppressive effect of a water-soluble nitrosourea derivative (ACNU) was determined in terms of the cytotoxicity of spleen lymphocytes, and the restoring effect of lymphokine-activated killer (LAK) cells and/or human recombinant interleukin-2 (rIL-2) on the cytotoxicities of spleen lymphocytes were examined in ACNU-treated C57 BL/6 mice. It was also tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The cytotoxicity of spleen lymphocytes against YAC-1 cells as well as 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 high-dose rIL-2 into C57BL/6 mice for more than 3 consecutive days. In animals injected with multiple high doses of rIL-2 subcutaneously, the numbers of tumor nodules in the lung were significantly decreased 21 days after intravenous tumor inoculation. In addition, in these groups of animals no liver metastases were observed although liver metastases were detected in 6/11 of control mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗