Immunohistochemical analysis of glutathione S-transferase mu expression in ovarian tumors.

OBJECTIVE: To explore the association between Glutathione S-transferase (GST) -mu expression and clinicopathologic features in ovarian tumors. STUDY DESIGN: Immunohistochemical study was made to investigate GST-mu expression in diverse ovarian tumors. RESULTS: All 75 ovarian tumors expressed GST-mu. There was no significant association between GST-mu immunopositivity and clinicopathological features. In serous cystadenocarcinoma, however, patients with weak GST-mu expression survived longer than those with moderate or strong GST-mu expression. Three of the 8 tumors that had expressed weak GST-mu initially increased GST-mu expression after chemotherapy. CONCLUSION: GST-mu expression is common in ovarian tumors and malignant tumors expressed more GST-mu than benign tumors. GST-mu might play a major role in the development of drug resistance in certain ovarian tumors and could be a useful marker of natural resistance and their future outcome.

Immunohistochemical analysis of P-glycoprotein expression in diverse histological types of epithelial ovarian tumors.

P-glycoprotein is a transmembrane protein which acts as an energy-dependent drug efflux pump for a variety of anti-cancer drugs. The mdr-1 gene which encodes P-glycoprotein was successfully cloned in 1986. To investigate P-glycoprotein expression in diverse ovarian tumors, including benign, low malignant potential and malignant, immunohistochemical study was done using a monoclonal antibody (C 219). Overall, 8 out of the 59 epithelial ovarian tumors (13.6%) expressed P-glycoprotein. It was noted that 5 of the 12 mucinous tumors were found to express P-glycoprotein, while none of the 31 serous tumors were immunohistochemically positive. In 10 malignant ovarian tumors, P-glycoprotein immunostaining was examined both prior to and after chemotherapy. Nine of them did not express any P-glycoprotein before or after chemotherapy. However, one tumor expressed P-glycoprotein after six courses of multidrug resistance-related drug administration. These findings indicate that P-glycoprotein expression is not so common in ovarian tumors, regardless of their malignant potential. Nevertheless, the results suggest a strong association between P-glycoprotein expression and certain histological cell types in epithelial ovarian tumors. It is also possible that P-glycoprotein appears as a result of chemotherapy, but such a phenomenon can not occur unless chemotherapy is administered at high doses for a long period of time.

Proliferative activity in normal endometrium and endometrial carcinoma measured by immunohistochemistry using Ki-67 and anti-DNA polymerase alpha antibody, and by flow cytometry.

The proliferative activity of various parts of normal and malignant endometrium was evaluated using an immunohistochemical approach and flow cytometry (FCM). The two monoclonal antibodies, Ki-67 and anti-DNA polymerase alpha antibody (anti-poly alpha antibody) were used to detect the proliferative activity of cells, and the percentage of the Ki-67 and anti-poly alpha positive cells were measured. Proliferative indices (PI; percentage of S and G2M phase) and DNA ploidy were measured by FCM. Normal endometrial specimens from 29 patients with benign diseases were used and three different parts (fundus, middle, and low part of the uterus) were examined. In the proliferative phase of normal endometrium, there was no significant difference in the proliferative activity in the three parts. In 20 patients with endometrial carcinomas with myometrial invasion, tissues were taken from the myometrial invasive site and the central part of the tumor tissue. In the cases of endometrial carcinoma, the myometrial invasive site had a higher proliferative activity than central part of the tissue. The proliferative activity measured by the immunohistochemistry was correlated with the histological grade of malignancy, but it was not consistent with PI by FCM. This suggests that the proliferative activity measured by the immunohistochemistry is independent of flow cytometric PI.

[A study on the proliferation of the uterine endometrium].

UNLABELLED: A proliferative activity study of the endometrium was evaluated in three different parts by means of an immunohistochemical approach and flow cytometry (FCM). The materials were 29 cases of hysterectomies due to uterine myoma. Twenty-one cases were in the proliferative phase, and 8 cases were in the secretory phase. The three parts of the endometrium obtained from the upper, middle and lower part of the uterine body were investigated by an immunohistochemical technique with Ki-67 and anti-DNA polymerase alpha antibody. Single staining with Propidium Iodide (PI) was used for cell cycle analysis in FCM. RESULTS: (1) The rate of positive Ki-67 cells was 25.9 +/- 6.3% in the upper part, 26.0 +/- 3.3% in the middle part, and 25.5 +/- 5.8% in the lower part. And the rate of positive DNA polymerase alpha cell was 27.2 +/- 5.8% in the upper part, 24.0 +/- 2.9% in the middle part, and 24.8 +/- 4.0% in the lower part. The growth potential of each part was not significant. (2) FCM did not detect a significant difference among the three parts of the endometrium in cell cycle analysis. (3) Hematoxylin-eosin staining showed that the upper part was thicker than the lower part and the number of glands in the upper part was more abundant than in the lower part. This difference was significant (p less than 0.01). (4) Ki-67 was recognized even in the early secretory phase. (5) And each segment of the endometrium proliferated evenly, not focussed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Post-transfusion hepatitis in operated uterine cancer patients].

We examined the incidence of non-A, non-B hepatitis (NANB) in post-transfusion hepatitis in uterine cancer patients treated by surgery at our hospital. The diagnosis of NANB was based on the diagnostic standards for post-transfusion hepatitis of the Japanese Society of Gastroenterology 1985. In 587 patients with blood transfusions from 1978 to 1988, 80 patients (13.6%) were diagnosed as NANB. The proportions of blood components were, preserved whole blood 44.1%, concentrated red blood cells (CRBC)+ fresh frozen plasma 31.2%, and CRBC 12.8%. The proportions of blood components changed over the years, but since 1987 those of blood components in blood transfusion have been greatly decreased. No difference in the incidence of NANB was seen in patients with up to 10 units of blood transfused, but a high incidence was observed to patients who had received over 10 units. The number of patients treated by radical hysterectomy was five hundred and sixty-two (95.7%) out of a total of five hundred and eighty seven. The average blood loss in the operation was 1,392 ml.

[Therapy of recurrent cervical cancer].

1,122 uterine cancer patients above FIGO stage I a were treated at our hospital in the decade from 1980 to 1989. Total 69 patients diagnosed as recurrent cervical cancer had 82 lesions in 11 sites. The most frequent recurrent sites were uterus, vaginal stump and vaginal wall; the second sites were parametrium and pelvic wall. Radiotherapy and hyperthermia were done to patients with these lesions. Chemotherapy and radiotherapy were used to patients with distant metastatic lesions to left supraclavicular lymph nodes and lung. But there has been no good results.

[A case of ovarian germ cell tumor].

PVP (CDDP, VBL, PEP) regimens were administered to a case of ovarian embryonal carcinoma (Higuchi-Kato) Group C, which had metastatic lesions of liver, lumbar bones, and paraaortic lymph nodes soon after operation, with good results.

[Pharmacokinetics of carboplatin (CBDCA) and tissue concentration of platinum in gynecologic organs].

A pharmacokinetics and platinum concentration in the gynecologic organs were measured following the intravenous drip infusion of 375 mg/m2 of CBDCA. Total platinum (TP) in plasma decreased biphasically and free platinum (FP) was almost monophasically eliminated. The t 1/2 of FP was about 51 min. and the percentage of FP out of TP at four hours after administration was more than 92%, which was much higher proportion compared with that of cisplatin (CDDP). A cumulative excretion of platinum in the urine within 24 hours was 69%. The platinum concentration in the benign part of portio and endocervix were higher than that of malignant portion, although there were no significant differences in other pelvic organs such as ovary and tubes. However, pelvic lymph-nodes showed less platinum concentration both in metastatic and non-metastatic tissues. Platinum concentration in the tissue did not change significantly with lapse of time. Bone marrow suppression was observed especially in the patients who had received chemotherapy or radiotherapy. No renal toxicity was observed even without any hydration and gastro-intestinal toxicity was much milder than that of CDDP.

[Fundamental and clinical studies of cefpimizole in obstetrics and gynecology].

The findings from recent fundamental and clinical studies of the efficacy of cefpimizole (AC-1370) in obstetrics and gynecology are reported in this paper. The AC-1370 concentrations in genital tissues sampled 30 to 56 minutes (a mean of 41.4 minutes) after intravenous injection of 1 g of the drug were 14 to 76 micrograms/g (a mean of 32.4 micrograms/g). The mean transfer ratios of the drug into the genital tissues to the concentration in the uterine arterial blood were such that the transfer ratio into the portio vaginalis was the highest, followed by the uterine cervix and the myometrium, and that into the oviduct was the lowest with about 1/2 that into the portio vaginalis. The concentration in the antecubital venous blood and that in the uterine arterial blood remained similar for all patients. The transfer of AC-1370 into the pelvic dead space exudate reached a peak (49.5 micrograms/ml) 1 hour, and also a peak (49.8 micrograms/ml) 2 hours after the intravenous injection. It then decreased gradually, but remained high, being higher than that in the antecubital venous blood about 50 minutes after the intravenous injection. Ten patients with infections in gynecology were treated with 1.0 to 4.0 g daily of AC-1370, to a total dose of 6 to 52 g, over a period of 3 to 13 days. One of them showed excellent response, 8 showed moderate response, and another showed poor response to the treatment: in other words, a response rate of 90% was achieved. Bacteriologically, pathogens were eradicated from 3 and decreased in 3, and microbial substitution occurred in another patient. No side effects of the drug were observed except for eruption in 1 patient. None of the 10 patients showed any abnormalities in laboratory findings. From the present fundamental and clinical studies of AC-1370, we have drawn the conclusion that the drug is one of extremely useful antibiotics in the treatment of infections in obstetrics and gynecology.

Polyamine levels in gynecologic malignancies.

Polyamines are closely related to many aspects of cell growth. Since increased amounts of polyamines in the urine of human cancer patients were reported in 1971, polyamines have been studied from the standpoint of tumor markers. In this study, polyamines in erythrocytes, plasma and urine were determined in 42 controls and 105 patients with gynecologic malignant tumors. The changes in polyamine levels were investigated before and after treatment. With advances in the stage of uterine cervical cancer, the frequency of abnormal levels of polyamines (concentrations greater than two standard deviations above the mean control level) became greater, and reached nearly 80% in recurrent and ovarian cancer. In the early stage of cancer, the diagnostic value was low. Comparison with carcinoembryonic antigen (CEA) was also performed. The polyamines lack specificity for malignant diseases, but they can be used to some extent as a tumor marker in the gynecologic field.

[Changes of red blood cells' polyamines during fetal and neonatal periods (author's transl)].

Polyamines are ubiquitously distributing amines in living organs, and have close relation to nucleic acids and cell proliferation. But there are few reports about polyamines in the obstetric field. So we measured blood polyamines, i.e. putrescine, spermidine and spermine in pregnancy, delivery, puerperium and neonatal period, using high-performance liquid chromatography (HPLC). We discuss about red blood cell polyamines because RBCs contain about 80% blood polyamines. Spermidine and spermine concentration begin to increase with pregnancy, and rapidly increase from the 5th lunar month and keep high levels during the 7-9th lunar month, the decrease at term. In puerperium, spermine, as opposed to spermidine, takes higher value than that of the term. Putrescine, however, keeps almost the same level as non-pregnangs during pregnancy and puerperium. At delivery, the umbilical blood contains significantly higher polyamines than the maternal blood, but there are no differences between umbilical artery and vein. In neonatal period, each polyamine shows slight increase at the first day after birth. Thereafter, putrescine keeps the same level till the 7th day, but spermidine and spermine gradually decrease day by day. These data suggest that polyamines are reflecting the function of bone marrow erythropoiesis and reproduction.

[The clinical significance of determination of red blood cell and urinary polyamines in gynecologic malignancy (author's transl)].

The polyamines spermidine (spd) and spermine (spm), and their diamine precursor, putrescine (put) were separately determined in red blood cells (RBC) and 24-hour urine samples of gynecologic malignant and non-malignant cases using high-pressure liquid chromatography (HPLC) technique. The results are as follows: 1) Patients with malignancy (49 cases) had the polyamine levels of RBC-spd; 5.85 +/- 3.32 (mean +/- SD), RBC-spm; 7.00 +/- 5.53 (nmol/ml packed RBC), urinary put; 3.92 +/- 4.13, urinary spd; 2.17 +/- 1.74 (mg/day) in pre-therapeutic state. These levels were greatly higher than those of control cases. 2) The diagnostic rate was 100% in the fourth stage of uterine cervical cancer, and 80% in the recurrent cases. 3) Patients with long-term abnormal polyamine levels had the tendency of poor prognosis. 4) In many cases, RBC polyamines and urinary polyamines showed somewhat different fluctuations in the course of treatment. In conclusion, it is suggested that the measurement of polyamines is very useful in the diagnosis of progressive cases and recurrent cases, and can be helpful in the evaluation of therapeutic effects and prognosis.

Alterations of red blood cells' polyamines during pregnancy and neonatal period.

Red blood cell polyamines were measured using high-performance liquid chromatography. Spermidine and spermine continued to increase with pregnancy and retained a high level during 24-35 weeks of gestation, then decreased at term; putrescine, however, kept the low nonpregnant level during pregnancy and puerperium. At delivery, umbilical blood showed a significantly higher polyamine level than maternal blood (p less than 0.005 or p less than 0.001). In the neonatal period, each polyamine showed a slight increase on the 1st day after birth, then spermidine and spermine decreased day by day, but putrescine kept the same level. Alterations of polyamines seemed to have some relation to the erythropoiesis in bone marrow and rapid cell proliferations.