Toshiko Murase

Overexpressions of c-fos/jun mRNA and their oncoproteins (Fos/Jun) in the mouse uterus treated with three natural estrogens

To further understand hormonal carcinogenesis of natural estrogens (estrone, 17 beta-estradiol (E2) and estriol), we determined the expressions of c-fos/jun mRNA, and their oncoproteins (Fos/Jun) with intracellular localization in the uterus of ovarectomized mice treated with these estrogens. Mid-term chronic, as well as short-term assays were examined. Of three estrogens examined, mid-term chronic E2-treatment significantly increased the expression of c-fos/jun mRNA, and their oncoproteins (Fos/Jun). These were most prominently expressed in glandular cells of E2-treated mouse endometrium. Therefore, mid-term chronic E2-treatment might partially induce glandular cell transformation of uterine endometrium via overexpression of Fos/Jun.

Enhancing effects of estrogens on endometrial carcinogenesis initiated by N-methyl-N-nitrosourea in ICR mice

The present study was undertaken to examine the effects of estrogens, such as estrone (E1), 17β‐estradiol (E2) and estriol (E3), on endometrial Carcinogenesis initiated by N‐methyl‐N‐nitrosourea (MNU) in mice. A total of 120 female ICR mice received MNU solution (1 mg/100 g body wt.) and normal saline at 10 weeks of age into their left and right uterine corpora, respectively. One week later, they were divided into four groups and treated as follows: Group 1 (30 mice) was given 25 ppm E1‐containing diet; Group 2 (30 mice) was fed 5 ppm E2‐containing diet; Group 3 (30 mice) was given 25 ppm E3‐containing diet; and Group 4 (30 mice) was fed the basal diet alone. At the termination of the experiment (Week 30), all surviving animals were autopsied and histopathological examinations revealed that endometrial adenocarcinomas had developed in all groups. The incidence of adenocarcinomas in the MNU‐treated uterine corpus in Group 1 (25 ppm E1‐feeding, 9/23, 39%) was significantly higher than that in Group 4 (basal diet, 3/26, 12%, P<0.05). Also, the incidences of adenocarcinomas in the MNU‐treated uterine corpus in Groups 2 (5 ppm E2‐feeding, 8/24, 33%) and 3 (25 ppm E3‐feeding, 7/26, 28%) were higher than in Group 4, but the difference was not statistically significant. Feeding of diet containing E1, E2 and E3 increased the incidences of the preneoplastic endometrial lesions (atypical, adenomatous or cystic glandular hyperplasia). In the uterine cervix, small numbers of squmous cell carcinomas, dysplasias or hyperplasias were occasionally found in all groups. These results indicate enhancing effects of the above three types of estrogens on the endometrial carcinogenesis induced by MNU in ICR mice.

Successful pregnancy in a patient with endometrial carcinoma treated with medroxyprogesterone acetate

A 32-year infertile Japanese woman suffered from endometrial cancer, which was treated with repeated endometrial curettage and medroxyprogesterone acetate for 6 months. The patient then became pregnant and was delivered of a live-born male infant at 37 weeks gestation by cesarean section for placenta previa. At cesarean section there were no abnormal findings in the uterine cavity or other pelvic organs.

Inhibitory effects of medroxyprogesterone acetate on mouse endometrial carcinogenesis

The present study was undertaken to examine the effects of cyclic administration of low‐dose progestogen on endometrial carcinogenesis in mice. A total of 115 female ICR mice, 10 weeks of age, were divided into four experimental and control groups. Mice in groups 1–3 received laparotomy and were injected with N‐methyl‐N‐nitrosourea (MNU) solution at a dose of 1 mg/100 g body weight to the left uterine tube and with normal saline to the right uterine tube. From one week after the MNU exposure, groups 1 and 2 were given 5 ppm 17β‐estradiol (E2)‐containing diet throughout the experiment. Mice in group 1 received 5 s.c. injections of medroxyprogesterone acetate (MPA) (2 mg/ mouse) at intervals of 4 weeks from week 7. Group 3 was treated with MNU/normal saline alone. Group 4 consisted of mice treated with MPA alone. At the termination of the experiment (week 30), all animals were killed and autopsied for pathological examinations. It was found that adenocarcinomas and preneoplastic lesions developed in the bilateral uterine corpora in mice of groups 1–3. MPA treatment significantly decreased the weight of the uterine corpus (P< 0.05) and the incidences of endometrial adenocarcinoma and atypical or adenomatous (P< 0.001) but not cystic glandular hyperplasias in the MNU/E2‐treated groups. Additionally, MPA treatment tended to decrease the proliferating cell nuclear antigen‐labeling index in endometrial glandular cells. These data indicate that MPA, even at low dose, has an inhibitory effect on mouse endometrial carcinogenesis induced by MNU and E2.

Rare occurrence of p53 and ras gene mutations in preneoplastic and neoplastic mouse endometrial lesions induced by N-methyl-N-nitrosourea and 17β-estradiol

To examine K-, H-, or N-ras and p53 gene mutations in mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-estradiol, we performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 13 adenocarcinomas and 11 other preneoplastic lesions. A significant shifted band in exon 5 of p53 using PCR-SSCP was detected in one of 13 adenocarcinomas. Direct sequencing showed that the mutation was TCA-to-TGA (Ser-to-End) transition. These results suggest that ras gene mutations were not related to carcinogenesis and inactivation of p53 may occur with low frequency during the mouse endometrial carcinogenesis in this model.

Chronological observation of mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17β-estradiol

Chronological observation of the neoplastic endometrial lesions induced by N-methyl-N-nitrosourea (MNU) and 17 beta-estradiol (E2) were studied. E2 induced cystic glandular hyperplasia, but adenomatous hyperplasia was induced predominantly by MNU. Atypical hyperplasia and adenocarcinoma were induced cooperatively by E2 and MNU, and first found at week 12; the incidence of adenocarcinoma increased in accordance with the week-course. Some atypical hyperplasia might be changed to adenocarcinoma. Mean AgNORs numbers in (pre)neoplastic lesions increased in accordance with neoplastic changes. This model was useful for clarifying histogenesis of human endometrial carcinogenesis.

Semi-quantitative analysis of DNA topoisomerase-I mRNA level using reverse transcription-polymerase chain reaction in cancer cell lines: its relation to cytotoxicity against camptothecin derivative.

Expression of DNA topoisomerase (Topo)‐I mRNA in various cancer cell lines was detected using the reverse transcription‐polymerase chain reaction (RT‐PCR) method. The cytoplasmic polyadenylated RNA isolated from cancer cell lines was reverse‐transcribed and the complementary DNA was amplified by PCR primed with Topo‐I specific primers. Fidelity of the amplified sequence was confirmed by restriction endonuclease digestion and Southern blot hybridization. The level of Topo‐I mRNA was correlated positively with the cytotoxicity of a Topo‐I inhibitor, a camptothecin derivative. This RT‐PCR method may be applicable to the assessment of sensitivity of cells to Topo‐I targeted drugs, especially when only small quantities of cell samples are available.

Silver-stained nucleolar organizer regions in the uterine myomatous tumors

The numbers of silver-stained nucleolar organizer regions (AgNORs) were counted in uterine myomatous tumors, and compared with those in corresponding normal myometria. The mean number of AgNORs in myomatous tumors tended to increase according to the neoplastic changes. The mean number of AgNORs in leiomyosarcoma (6.4 +/- 0.9) was significantly higher than that in cellular leiomyoma (4.5 +/- 0.7, P < 0.01). or leiomyoma (3.0 +/- 0.5, P < 0.001). In the normal myometria, the mean number of AgNORs (3.3 +/- 0.4) in the premenopausal women showed a higher tendency than that in the post-menopausal women (2.4 +/- 0.5). These results therefore suggest that AgNOR counts may be useful for diagnosis of cellular activity in uterine myomatous tumors.

Aberrant adnexal blood supply

The chief blood supply to the ovary is through the ovarian artery. Each artery may originate as a branch of the abdominal aorta, or less frequently may arise from the renal artery. In the pelvis, the arteries transverse the folds of the suspensory ligament of the ovary into the mesovarium and then reach the ovary. An additional blood supply is formed from anastomosis with the.ovarian branch of the uterine artery, which courses along the attached border of the ovary. Some clinical [l] and anatomical [2] reports describe variations only in the level of aortic origin and course; no description is available concerning the defect or supernumerary run of the ovarian artery. We encountered a rare case with an abnormal disappearance or lack of right ovarian artery and a large branch from the right uterine artery during routine surgery. A 37-year-old Japanese woman, nulligravida, was referred to Gifu University Medical Center due to a progressive abdominal distention for the past 2 months. The findings on abdominal ultrasonography and magnetic resonance imaging led to a diagnosis of probable epithelial cystoadenocarcinoma of the ovary. Throughout radical sur-

Ultrasonically guided follicular aspiration during a pregnancy with massive ovarian cysts following ovulation induction by gonadotropins

In this report, the treatment by follicular aspiration was evaluated in a pregnant patient with severe ovarian cysts subsequent to ovulation induction with CC and gonadotropins. The patient had dramatic and immediate improvement of the symptoms and general condition as well as a significant shorter hospital stay. The procedure was, under meticulous US guidance, safe and effective, providing additional improvement or increased therapeutic confidence in the severe complications after ovulation induction, as an assisted option during pregnancy.