Expression of retinoic acid receptors in human endometrial carcinoma.

The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RAR alpha, RAR beta, and RAR gamma using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.

Surgical anatomy of intrapelvic fasciae and vesico-uterine ligament in nerve-sparing radical hysterectomy with fresh cadaver dissections.

Radical hysterectomy has been performed for invasive cervical cancer, and autonomic nerve-sparing procedures have been developed to preserve bladder function. To perform and improve the nerve-sparing radical hysterectomy, it is important to understand anatomy of the intra pelvic fasciae, specially vesico-uterine ligament (VUL), because most of injuries to the nerves occurred during incision of the VUL in radical hysterectomy procedures. The objectives of the present study were to provide histological understanding of major structures found in nerve-sparing radical hysterectomy. Serial macroscopic slices (15-20 mm thick) from five female pelves were trimmed and prepared for paraffin-embedded histology. We noted an anatomical entity as "the visceroparietal fascial bridge", which corresponds with the macroscopically identified arcus tendineus fasciae pelvis. A histologically identifiable neurovascular pedicle to the bladder neck corresponded with the deep portion of VUL. These findings could help better preservation of autonomic nerves during radical hysterectomy and improve patient's quality of life after the operation. Translation of surgical anatomy into anatomic terminology enables us to have fruitful discussions with persuasive power by excluding any bias from individual surgeons.

Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: This phase I clinical trial for cervical carcinoma had three objectives: to evaluate the toxicity of a concurrent chemoradiation regimen featuring weekly nedaplatin; to determine the recommended dose of nedaplatin for a phase II concurrent chemoradiation trial; and to evaluate the formula for predicting area under the curve data for nedaplatin through pharmacokinetic studies. PATIENTS AND METHODS: Twelve patients with locally advanced squamous cell carcinoma of the uterine cervix were enrolled. Nedaplatin was administered once a week for 6 weeks. The starting dose of nedaplatin was 25 mg/m(2)/week, with increments of 5 mg/m(2)/week planned for each dose level. Three cases were enrolled at each of the dose levels. Radiation therapy was delivered with both external beam teletherapy and intracavitary brachytherapy with HDR-RALS. Volunteering patients underwent pharmacokinetics studies during the second course. RESULTS: Nedaplatin at a dose of 25, 30, and 35 mg/m(2) was safely administered for three cases at each dose level. At a dose of 40 mg/m(2), however, all three cases had Grade 3 neutropenia. Observed area under the curve value and predicted value was closely correlated, with differences between the two area under the curve values within 25%. All 12 cases achieved a clinical complete response, as evaluated with RECIST. CONCLUSIONS: Our recommended dose for a phase II trial of concurrent chemoradiation with weekly nedaplatin is 35 mg/m(2). The formula can predict unbound concentration of nedaplatin based on area under the curve within 25% error.

Lactation and risk of endometrial cancer in Japan: a case-control study.

The incidence of endometrial cancer is rapidly increasing in Japan. Although the risk factors in European populations have been well described, there are few epidemiologic studies regarding risk factors for endometrial cancer in Japanese women. This hospital-based case-control study among Japanese women was carried out from 1998 to 2000. The cases were selected from women with endometrial cancer (n =155), and the controls selected from women attending the university gynecological outpatient clinic for cervical cancer screening (n = 96). Subjects were interviewed to ascertain breast feeding practices, contraceptive usage, as well as potential risk factors for endometrial cancer. We observed a lower risk of endometrial cancer associated with oral contraceptive (OC) and a higher risk associated with higher body mass index (BMI), and older ages at first and last delivery. Gravidity reduced odds ratio (OR) for endometrial cancer to 0.34 (95% confidence interval [CI] 0.13-0.92). Compared with parous women who had never breastfed, the multivariate OR for women with a history of breastfeeding was 0.37 (95% CI, 0.17-0.82). Additionally, a greater lapse of time since breastfeeding increased OR for endometrial cancer by over three times. In conclusion, the present study has indicated that breastfeeding reduces the risk of endometrial cancer in Japanese women.