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S Irino

Publications and source records attributed to S Irino.

At least 55 records · Page 3Linked to original sources
PubMed1992

[Pilot phase II trial of high-dose etoposide combined with cisplatin in the treatment of refractory lung cancer].

The efficacy of combined high-dose etoposide with standard dose cisplatin was evaluated in patients who had refractory lung cancer after standard chemotherapy. Each patient was given etoposide at 500 mg/m2/day on day 1 to 3 continuously (total dose 1,500 mg/m2) and cisplatin at 80 mg/m2 on day 1. Fifteen patients (7 adenocarcinoma, 5 small cell lung cancer, 2 squamous cell lung cancer and 1 sarcoma, which latter was difficult to distinguish from giant cell carcinoma) were entered in this study. The overall response was 41.7% (5 of 12); five partial response, 6 no change, and 1 progressive disease. Three treatment-related deaths were observed; one resulted from sepsis and two from respiratory failure because of tumor progression. All of the patients developed severe myelosuppression; the mean nadir white blood cell count was 400, and the mean nadir platelet count was 24,000 in 28 evaluable courses. The range of maximum concentration of etoposide determined by HPLC was from 17.4 to 39.1 micrograms/ml. These results suggest that high-dose etoposide combined with a standard dose of cisplatin is effective against refractory lung cancer.

Adenocarcinoma↗
PubMed1992

E. coli gpt gene expression effects on K562 human leukemia cell proliferation and erythroid differentiation altered by mycophenolic acid.

Inosine monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) inhibitors including mycophenolic acid (MPA) were reported to induce K562 human leukemia cells to differentiate into erythroid cells. A shuttle vector plasmid pMSG containing E. coli xanthine-guanine phosphoribosyl transferase (Eco gpt) gene was transfected into K562 cells (K562-pMSG cells) to investigate the role of IMPDH in both K562 cell proliferation and erythroid differentiation. Eco gpt provides K562 cells with an additional salvage pathway for GMP production from xanthine. In the presence of xanthine, K562-pMSG cells continued to proliferate and did not differentiate to erythroid cells regardless of the presence of MPA, but they discontinued proliferating and differentiated into the erythroid lineage in the absence of xanthine. Proliferation and differentiation of control K562 cells into erythroid cells were suppressed by MPA regardless of the presence or absence of xanthine. Addition of guanosine maintained the proliferation and blocked the erythroid differentiation of K562 and K562-pMSG cells induced by MPA even in the absence of xanthine. These data indicate that a decrease in the activity of IMPDH and a subsequent decline in the concentration of guanine nucleotides caused by MPA resulted in the induction of the erythroid differentiation and discontinuation of the proliferation of K562 cells.

Blotting, Southern↗
PubMed1991

Induction of erythroid differentiation of K562 cells by 4-carbamoylimidazolium 5-olate (SM-108).

The effects of 4-carbamoylimidazolium 5-olate (SM-108), an antipurine compound, on a human leukemia cell line, K562, were studied. Treatment with SM-108 induced erythroid differentiation of K562 cells. During a 6-day culture with 100 microM SM-108, the cell number decreased to 37% of the control number, 77% of the cells became benzidine-positive, and the hemoglobin content increased from 2.1 +/- 0.2 to 10.6 +/- 1.3 pg/cell. Cell differentiation was associated with reduction of IMP dehydrogenase activity and intracellular GTP content to 25 and 36%, respectively, of the control values within 1.5 hr. The differentiation and decrease in the GTP pool induced by SM-108 were blocked by the presence of 25 microM guanine or guanosine. SM-108 also induced erythroid differentiation of K562 subline cells transfected with pMSG (K562/pMSG), which have an additional salvage pathway for GMP production from xanthine. The addition of 100 microM xanthine prevented erythroid differentiation of this subline and restored the GTP pool. These findings suggest that the induction of erythroid differentiation of K562 cells by SM-108 may be due to an early decrease in IMP dehydrogenase activity and a subsequent decrease in GTP content in the cells. Thus, purine metabolism may have an important role in SM-108-induced differentiation.

Cell Differentiation↗
PubMed1991

Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias.

The discovery of isozymes (types I and II) of IMP dehydrogenase (IMPDH; EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, has attracted attention as a possible novel approach to cancer diagnosis and selective tumor cell chemotherapy. To elucidate differences in expression and regulation of the two IMPDH isozymes, we examined the steady-state levels of these mRNAs in various types of leukemic cells from patients. Northern blot analysis revealed that type II IMPDH was more active transcriptionally (1.5- to 5.1-fold) in all the leukemic cells examined than in normal lymphocytes, whereas type I expression was similar. The increased expression of type II mRNA in leukemic cells was closely linked with the increase in total IMPDH activity (r = 0.92). When leukemic cells from a patient with chronic granulocytic leukemia in blast crisis were separated into blast-rich and mature leukocyte-rich fractions, the expression of type II mRNA correlated positively with the population of immature leukemic cells, whereas type I expression was unchanged. Treatment of leukemic blasts with 12-O-tetradecanoyl-phorbol-13-acetate for 5 days resulted in a 90% decrease in the expression of type II mRNA with macrophage-like differentiation, while the expression of type I mRNA was relatively stable. These observations suggest that expression of type II IMPDH is stringently linked with immature characteristics of leukemic cells; thus, it should be a selective target for antileukemic chemotherapy.

Cell Differentiation↗
PubMed1991

Characterization of the stimulatory effect of galanin on growth hormone release from the rat anterior pituitary.

The present study was undertaken to investigate the direct actions of rat galanin (R-GAL) on growth hormone (GH) release from the rat anterior pituitary in vitro. R-GAL modestly but significantly stimulated GH release without an increase in intra- and extracellular cyclic AMP levels in monolayer cultures of rat anterior pituitary cells. This stimulatory effect of R-GAL was dose-dependent but not additive with that of GH-releasing factor (GRF). R-GAL-stimulated GH release was less sensitive to the inhibitory effect of somatostatin than was GRF-stimulated GH release. In perfusions of rat anterior pituitary fragments, R-GAL induced a gradual and sustained increase of GH release. Incremental GH release derived in part from preformed stored GH. These data confirm that R-GAL acts at the pituitary level to stimulate GH release by a mechanism distinct from that of GRF.

Animals↗
PubMed1991

Usefulness of a small scale indirect 125I-labelled protein A binding assay for detection of monoclonal antibodies against hematopoietic cell surface antigens.

We describe a small-scale solid-phase indirect 125iodine protein A binding assay (IPA) and discuss its usefulness for detection of hematopoietic cell surface antigens and for screening hybridoma clones producing monoclonal antibodies (McAbs) against K562 cell surface antigens correlated with differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). This assay was performed in polystyrene Terasaki microtest plates instead of 96-well microtiter plates, using hematopoietic cells attached to the wells by air drying. This method facilitates washing procedures and reduces the radioactive waste. The specificity of this IPA method is as high as those of RIAs and ELISAs generally used. Titration curves of a McAb, My7, specific for CD13 on HL60 and TPA-treated HL60 (HL60-TPA) cells, were linear between the 10(-1) and 10(-4) dilutions. A difference in the CD13 expression between HL60 and HL60-TPA cells could be detected by both IPA and flow cytometry using My7 at 10(-1)-10(-3) dilutions. At the 10(-3) dilution, however, CD13 expressed on HL60 cells was detected by the IPA method but not by flow cytometry. These results show that the sensitivity of IPA is superior to that of flow cytometry. By screening hybridoma clones with this IPA method, we succeeded in producing three interesting and useful McAbs (21H73, 37G7 and 49C12) against K562 cell surface antigens whose expression was altered after the differentiation induced by TPA. We also demonstrated that the IPA method is suitable for cell surface marker analysis of leukemia cells freshly isolated from patients.

Animals↗
PubMed1991

Monoclonal antibodies raised against K562 cells reacted with human haematopoietic pluripotent stem cells.

We describe the properties of three monoclonal antibodies (McAbs) (21H73, 37G7 and 49C12) against K562 cell surface antigens correlated with differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Each of the McAbs immunoprecipitated K562 cell surface antigen with molecular weight (MW) of approximately 51 kD, 82 kD or 92 kD, respectively. The antigens detected by McAbs 21H73 and 37G7 were not immunoprecipitated from K562 cells differentiated into monocyte-macrophages by TPA (K562-TPA). On the other hand, 49C12 immunoprecipitated an antigen with MW of 92 kD from K562-TPA cells, but not from undifferentiated K562 cells. To examine the distribution of these antigens among human haematopoietic stem cells, bone marrow cells were separated by the panning method using these McAbs and subjected to colony-forming assays. The McAb 21H73 reacted with CFU-mix and BFU-E but with neither CFU-E nor CFU-GM. CFU-mix and BFU-E were enriched approximately 6.2-14.7-fold and 2-fold by the panning procedure using 21H73, respectively. On the other hand, 37G7 reacted only with BFU-E, and 49C12 reacted with CFU-GM but not with any other haematopoietic progenitor cells. We also examined the reactivity of these McAbs with leukaemia cells freshly isolated from 26 patients. The antigen defined by 21H73 was not expressed on any leukaemia cells from patients except for cells from an acute lymphocytic leukaemia (ALL, L3) and a CML in blastic crisis. The McAb 37G7 reacted with several types of leukaemia cells. The antigen defined by 49C12 was expressed on almost all leukaemia cells isolated from patients. These results suggest that 21H73 allows purification and enrichment of normal haematopoietic pluripotent stem cells from both normal and leukaemia patients' bone marrow specimens, especially following the step to remove leukaemia cells and haematopoietic progenitor cells other than CFU-mix by using 37G7 and/or 49C12.

Antibodies, Monoclonal↗
PubMed1991

Establishment and biochemical properties of cis-diamminedichloroplatinum(II)-resistant A549 lung cancer cells.

A 6.2-fold cis-diamminedichloroplatinum(II) (CDDP) resistant human lung cancer cell line (A549/CDDP5), which was capable of proliferating in the presence of 5 microM CDDP, was developed. Compared to the parent cell line, A549/CDDP5 subline had a significantly longer doubling time, increased population of S phase, enhanced sensitivity to 5-FU and elevated activities of dTMP synthase (EC 2.1.1.45) and thymidine kinase (EC 2.7.1.21) by 5.4- and 2.0-fold of the parent cells. These results suggest that the capacity of dTMP synthesis might have an important role in the acquisition of CDDP resistance of A549 cells.

Cell Division↗
PubMed1991

[Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer].

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) 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 as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.

Adult↗
PubMed1991

Mechanism of transient increase in intracellular concentration of free calcium ions in HL-60 cell differentiation induced by vitamin D3 and phorbol ester.

A promyelocytic leukemia cell line, HL-60, was induced to differentiate into monocyte-macrophage lineage cells by treatment with active vitamin D3 and phorbol esters, and into granulocyte lineage ones by retinoic acid and dimethylsulfoxide. The changes in intracellular concentration of free calcium ions ([Ca2+]i) were measured and analyzed by calcium-imaging analysis with Fura 2-AM. A significant and transient increase in [Ca2+]i was observed in active vitamin D3 and phorbol ester systems; however, no change was detected with retinoic acid and dimethylsulfoxide. This increase was due to the influx of calcium ions from outside of the cells, and L-type calcium channels were shown to mainly contribute to this influx. Protein kinase C was also shown to be involved in the increase in [Ca2+]i.

Calcitriol↗
PubMed1991

[Treatment of severe infections in hematologic malignancies with piperacillin sodium].

Combination antibiotic therapies using piperacillin (PIPC) were evaluated in 60 episodes of severe infections in 38 neutropenic patients with hematologic malignancies. 1. The overall efficacy rate was 46.7%. Efficacy rates were 30% in patients with pneumonia, 60% in patients with sepsis and 50% in patients with suspected sepsis in which causative organisms were not identified. 2. Eradication rates were 44.4% for Gram-negative bacilli, 50% for Pseudomonas aeruginosa and 22.2% for Gram-positive cocci. 3. Efficacy rates were 33.3% in patients with initial count of neutrophil less than 100/microliters, 60% in patients with those 100 to 500/microliters and 66.7% in patients with those higher than 500/microliters. Initial neutrophil counts correlated well with efficacies of PIPC on severe infection in patients with hematologic malignancies. 4. Mild increases of transaminase were observed in 2 cases. From these results it is concluded that PIPC is one of the most important antibiotics in the treatment of severe infections in neutropenic patients with hematologic malignancies.

Adolescent↗
PubMed1991

[Enhancement of susceptibility of sulbactam/cefoperazone-treated bacteria to phagocytes].

Effects of sulbactam/cefoperazone (SBT/CPZ) on the host-parasite relationship were studied using an established mouse macrophage cell line. Since SBT inactivates some types of beta-lactamase strongly, a combination of SBT with CPZ shows marked antibacterial activities against the bacteria producing beta-lactamases. In addition, sub-MIC levels of SBT/CPZ made Escherichia coli more susceptible to bactericidal activity of macrophage. This study provides evidence that SBT/CPZ works in partnership with host defense mechanism against bacterial infections in clinical situations.

Cefoperazone↗
PubMed1991

[Heterogeneity of anticardiolipin antibody].

The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss-DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis.

Abortion, Spontaneous↗
PubMed1991

[An improved method for biochemical measurement of the activity of neutrophil alkaline phosphatase and its application to myeloproliferative disorders].

The activity of neutrophil alkaline phosphatase (NAP) has been commonly measured semi-quantitatively by rating the intensity and number of positive granules on cytochemical staining. This method has been widely adopted because of quickness and simplicity. However, the scoring system, in itself, seems to have several demerits that it has poor reproducibility and has limit for expressing enhanced NAP activity. We improved previous methods for measuring biochemical activities of NAP. Our method was as quick and simple as cytochemical measurement and had more excellent reproducibility. Biochemical activities of NAP ("b-NAP"s) in extract from 2 x 10(6) neutrophils of 7 patients with polycythemia vera were about six times as high as those of 7 cases of essential thrombocythemia [144.8 +/- 33.2, 23.1 +/- 9.1 U, respectively], while NAP scores in the former showed only twice the degree of elevation of those in the latter. These observations suggest that our method can represent high NAP activity more exactly than NAP score and may be a potential tool in differentiating polycythemia vera from essential thrombocythemia.

Alkaline Phosphatase↗
PubMed1991

[A case of second-degree atrioventricular block caused by high dose cisplatin treatment].

A 56-year-old man was admitted to our hospital because of stage IV squamous cell carcinoma of the lung. He was treated with two courses of high dose cisplatin (40 mg/m2/day, day 1-5). On day 4 of each course, a second-degree atrioventricular block was observed, which disappeared after cisplatin treatment. This case suggests that, although the cardiotoxicity caused by cisplatin is believed to be rare, one should take special care in high dose usage.

Carcinoma, Squamous Cell↗