[Utility of predeposit autologous blood donation by switch back method combined with recombinant human erythropoietin in gynecological surgery].

To apply recombinant human (rh)erythropoietin (EPO) to predeposit autologous blood donation (P.A.B.D.) in cancer patients clinically, (1) we tested the effects of rh-EPO on 2 ovarian cancer cell lines in vitro at first, then, (2) studied the effect of the rh-EPO for switch back (SB) method that is a variant of P.A.B.D. clinically. Rh-EPO (0.068-68U/ml) caused no significant and reproducible stimulation of clonal growth to SHIN-3 (derived from serous cyst adenocarcinoma) and MN-1 (derived from mucinous cyst adenocarcinoma). Twenty-five cases were studied. The change in the hemoglobin concentration (delta Hb) was -0.43 +/- 1.38g/dl (mean +/- SD) and the change in the total amount of hemoglobin (total delta Hb) which is calculated on the basis of whole blood volume was 111.5 +/- 53.2g/body in 16 cases with rh-EPO. The delta Hb and total delta Hb were -3.25 +/- 0.78g/dl and 30.1 +/- 41.7g/body in 9 cases without rh-EPO. The rh-EPO combined cases were significantly increased in both delta Hb and total delta Hb (p < 0.05, unpaired student t test). We therefore conclude that it would be very beneficial to use rh-EPO combined with the SB method in P.A.B.D. for high maximum surgical blood order schedule (MSBOS) cases such as gynecological malignancies.

[Etoposide/cis-platinum (CDDP) combined chemotherapy for ovarian cancer: evaluation of optimum schedule for CDDP administration in chronic continuous exposure of ovarian cancer cells to low-dose etoposide in vitro].

Combined chemotherapy with etoposide and cis-platinum (CDDP) is considered a second line regimen for refractory cases of ovarian cancer. In addition to the time-dependent cytocidal kinetic of etoposide, much attention has been paid to low-dose continuous administration of etoposide. In this study, ovarian cancer cells (SHIN-3) were continuously exposed to low-dose etoposide in vitro to determine the optimum schedule for CDDP administration. Etoposide concentrations of 1-3 micrograms/ml were used; per os administration of etoposide at 25 mg x 2/day has been shown to produce a continuous plasma concentration of etoposide of around 1 microgram/ml. The results were as follows: 1) The IC50 of CDDP after 72 hours of exposure was 8.0 micrograms/ml and that of etoposide after 114 hours was 3.0 micrograms/ml. 2) After 100 hours of exposure to 1 microgram/ml of etoposide, cell cyclic phase analysis showed cells predominantly in G2/M phase arrest. 3) After 24-hour administration of CDDP, it was more than 24 hours before a cytocidal effect was observed. 4) During continuous exposure of SHIN-3 to etoposide (1 microgram/ml) for 6 days, CDDP was added on the 1st, 3rd, and 5th days. The largest ratio of growth inhibition with combined treatment to that with CDDP alone was attained on the 5th day. We conclude that, in combination regimens using low-dose continuous etoposide, CDDP should be added after etoposide administration is begun.

[Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis].

A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)

[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.

[Antiproliferative actions of medroxyprogesterone acetate (MPA) to human ovarian cancer cell lines in vitro].

The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA-added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fundamental and clinical studies of T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

T-1982 (cefbuperazone), a new cephamycin antibiotic, was fundamentally and clinically studied. The following results were obtained. Serum and internal genital tissue levels of T-1982 were measured following intravenous injection or intravenous drip infusion of 1 g. High serum levels of more than 10 micrograms/ml and tissue levels of more than 5 micrograms/g were maintained for 3 hours after intravenous administration. Favourable transfer of T-1982 into the pelvic dead space exudate was observed. The exudate level attained its peak at 2 hours and was 14.6 micrograms/ml on average even at 8 hours after intravenous infusion. With its MIC values, T-1982 was considered to be bactericidal against many Gram-negative bacteria except Pseudomonas sp. A total of 4 cases comprising 2 with pyometra, 1 with pelveoperitonitis and 1 with endometritis complicated with pelveoperitonitis was treated with T-1982 at a dose of 1-2 g twice daily by intravenous drip infusion. The clinical response was excellent in 1 case and good in 2 cases. A case with pyometra due to S. faecalis did not respond to the therapy. Side effects and abnormal laboratory findings due to the drug were not noted.