Objective  To evaluate the outcome of conservative treatment of young women with endometrial cancer. Design  Observational study. Setting  Gifu University Hospital, Japan from 1988 to 2002. Population  Twelve women with endometrial cancer, FIGO IA estimated by MRI under 35 years. Methods  Patients were treated with medroxyprogestreone acetate (400–600 mg/day) for 6–10 months, with endometrial curettage performed every four weeks. Main outcome measures  Response to therapy, pregnancies and reoccurrence of disease during follow up over a 30‐month period. Results  All cases had pathological complete remissions within 6–10 months. Seven of 10 wishing to have babies conceived, and five of them were delivered of full‐term babies. Eight of nine cases receiving long term follow up (over 30 months) developed recurrent disease, with four opting for hysterectomy. No patient developed distant metastases or had disease‐related death. Conclusion  Conservative therapy is feasible in carefully selected young women with endometrial cancer. Recurrence rates were high during long term observation even after pathological complete remissions. Therefore, close follow up is recommended.

ndometrial cancer is one of the most common gynecologic cancers.

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17ß (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-• (P<0.005), estrogen receptors (ER)-• (P<0.001) and ER-ß (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-•, ER-• and-ß.

Abstract. We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E 2 )-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1· and TNF-· mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1· and TNF-·. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer. IntroductionGlycyrrhizin (GL), a major constituent of Glycyrrhizae radix (Gl radix) which is ~10% of the dry weight of Gl radix extract, is the calcium and potassium salt of glycyrrhizinic acid. GL glycoside loses its sweet taste and upon hydrolysis is then converted to aglycone glycyrrhetinic acid plus two molecules of glucuronic acid. GL has an anti-estrogenic as well as an estrogenic effect (1). There is some evidence that GL has a protective effect on the skin (2,3) or liver carcinogenesis (4,5).It is known that Gl radix is widely used as a Kampo medicine in Asian countries and ~75% of traditional Japanese and Chinese medicines contain this agent. We have previously reported that Gl radix has a preventive effect on endometrial carcinogenesis in mice, and this effect is related to the inhibition of the expression of estrogen-stimulated genes c-fos/jun mRNA and proteins (6). We also proved that the herbal complex containing Gl radix suppresses cell proliferation in a chemo-endocrine resistant cancer cell line (7). In general, the anti-estrogenic effects are considered to have a protective effect against the occurrence of estrogendependent cancers. Such effects are confirmed in animal models of uterine endometrial cancer (8).Cyclooxygenase (COX), an enzyme that activates the production of prostaglandins from arachidonic acid, has two isoforms. COX-2 has attracted considerable attention in connextion with carcinogenesis in organs such as the large bowel, mammary glands and breast carcinogenesis (9-11). There is evidence that the COX activity is related to the promotion and progression in the tumorigenesis of the prostatic gland, stomach and lung (12)(13)(14). It remains unclear whether COX-2 is involved in E 2 related mouse endometrial carcinogenesis, although a high expression level of COX-2 has been confirmed in human endometrial carcinomas (15). In this study, we examined the possible association of the preventive effects of GL on E 2 -induced mouse endometrial carcinogenesis with COX-2 activity.We have reported that the expression of internal cytokines, interleukin (IL)-1· and tumor necrosis factor (TNF)-·, increase after E 2 treatment (16). Such an increase of the internal cytokines is suggested to contribute to both tumor promotion and progression (17)(18)(19). Such circumstances ...

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