Long-term effects of hormone replacement therapy on bone mineral density in girls oophorectomized in adolescence.

The object of this study was to examine the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and physical development in oophorectomized adolescent girls. Two adolescent girls had bilateral ovaries removed as the treatment of advanced ovarian neoplasms at 12 years of age, and have been receiving HRT for more than 10 years. The changes in BMD and physical development were recorded. Both patients entered puberty and developed mature female physiques, despite the 3 years' absence of estrogen exposure immediately after oophorectomy. BMD recovered soon after the start of HRT and was kept within the normal range. Normal physical development, including bone mineral density, can be achieved with HRT in adolescent girls castrated before puberty.

Uterine cervical adenofibroma associated with Turner's syndrome in a young woman.

A 32-year-old woman with Turner's syndrome complained of abnormal genital bleeding, which was diagnosed as a delivered myoma. Vaginal myomectomy was performed, and the tumor was histopathologically diagnosed as an adenofibroma of the uterine corpus. As these are extremely rare, we report this case with a review of some of the literature.

Acute disseminated intravascular coagulation developed during menstruation in an adenomyosis patient.

We report a case of acute disseminated intravascular coagulation (DIC) developed during menstruation in an adenomyosis patient. No known predisposing factor for DIC such as infection or pregnancy was involved in this case. As anticoagulation therapy and supplementation of coagulation factors quickly improve the state, surgical removal of the uterus was not required. We speculate that hemorrhage in the adenomyosis legion and subsequent local thrombosis played crucial role in pathophysiology of this case of acute DIC.

Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma.

Malignant transformation of a mature cystic teratoma of the ovary is rare, that of an adenocarcinoma is extremely rare. A 32-year-old woman was suspected as having a malignant transformation of her mature cystic teratoma of the ovary because the preoperative level of carcinoembryonic antigen (CEA) was extremely high. Resections of her ovarian cysts were performed, and this particular tumor was histopathologically diagnosed as an adenocarcinoma arising from a mature cystic teratoma of the left ovary. Because adenocarcinomas arising from mature cystic teratomas of the ovary are extremely rare, we report this case with a review of some of the literature.

A perforated sigmoid diverticulum abscess difficult to differentiate from an ovarian tumor.

We report a case of a perforated sigmoid diverticulum abscess that was difficult to differentiate from an ovarian tumor. A 53-year-old woman was diagnosed with an ovarian tumor, but laparotomy revealed a perforated sigmoid diverticulum abscess and appendicitis, with normal ovaries.

Usefulness of positron emission tomography for diagnosis of malignancy in a calcified lesion: a case report.

When calcified lesions in the liver or spleen are found during follow-up of patients who have undergone debulking surgery and chemotherapy for advanced ovarian carcinoma, it is very difficult to differentiate recurrent cancer from secondary change after chemotherapy. We present here a patient in whom calcified lesions in the liver and spleen were diagnosed as malignancy on the basis of a preoperative PET study. Malignancy was confirmed by histologic examination after surgery.

Expression and distribution of cyclooxygenase-2 in human periovulatory ovary.

Cyclooxygenase, which converts arachidonic acid into prostaglandins, has two types of isoforms, cyclooxygenase-1 and cyclooxygenase-2 (COX-2). The latter is thought to be essential for the ovulatory mechanism. However, expression or distribution of COX-2 in periovulatory human ovary has not been reported. The aim of our study was to examine COX-2 expression and distribution in pre- and postovulatory human ovary. COX-2 was detected by Western blot analysis of pre-ovulatory human ovarian follicular fluid. The levels of COX-2 in preovulatory fluid obtained from 20 subjects underwent in vitro fertilization and embryo transfer, and were assayed using enzyme immunoassay for human COX-2. The results showed 7.3+/-4.1 ng/ml (mean +/- SD) with a COX-2 level range of 2.7 to 19.5 ng/ml of follicular fluid. Detection of COX-2 is considered to reflect its production in the preovulatory follicle. Immunofluorescence microscopic examination of an ovary obtained from a woman at the postovulatory period showed distribution of COX-2 in interstitial but not in granulosa cells in a ruptured follicle. These findings collectively suggest the possibility that COX-2 is mainly produced in follicles in a preovulatory phase, while after ovulation, COX-2 is produced in interstitial cells in human ovary.

An antibody against anemia-inducing substance inhibits cation influx in red blood cells from cancer patients.

Resealed ghost of red blood cells (RBCs) from advanced cancer patients includes proteins with antigenicities common to an anemia-inducing substance that we separated from plasma of patients with advanced malignant neoplasms. Although cation influx in vitro in RBCs from a cancer patient is larger than that from a normal healthy volunteer, an antibody against anemia-inducing substance inhibited the in vitro cation influx in RBCs from the cancer patient. Activation of the cation influx with N-ethylmaleimide after reaction with the antibody reversed the effect to create a greater cation influx in RBCs from the patient, as compared with that from the healthy volunteer.

Expression of skeletal muscle cells apoptosis regulatory proteins in plasma-perfused VX2 carcinoma-bearing rabbits.

BACKGROUND: In tumor-bearing animals we found that the skeletal muscle apoptosis might be involved in muscle wasting. In this study, we investigated changes in the skeletal muscle cell apoptosis regulatory proteins after cyclic plasma-perfusion (CPP). MATERIALS AND METHODS: We studied changes in body weight, lean body mass (LBM), apoptotic index (AI) and expression of Bax and Bcl-2 in skeletal muscle in VX2 carcinoma-bearing rabbits. RESULTS: 20 days after tumor implantation, LBM had decreased by 5.06+/-1.10%, while the AI had increased to 40.5+/-3.20%. By 40 days, LBM had decreased by 11.0+/-0.81% and the AI was only 0.93+/-0.96%. Bax expression was detected in proportion to the AI, but no Bcl-2 expression was detected in either the experimental or control groups. CPP improved LBM, but did not prevent Bax expression. CONCLUSION: Skeletal muscle cell apoptosis related to Bax was concluded to be the cause of muscle wasting in VX2 carcinoma-bearing rabbits. CPP appears to reduce muscle wasting and increase LBM, but it did not suppress Bax expression or skeletal muscle cell apoptosis.

Angiogenesis in adipose tissues and skeletal muscles with rebound weight-gain after diet-restriction in rabbits.

The mechanisms of excessive body weight gain after diet-restriction are still unclear. In this study, we investigated expression of angiogenic factors in adipose tissue and skeletal muscle of rabbits which had rebound weight gains; trying to make inquiries into the mechanisms of this rebound weight gain. Ten rabbits were divided into two groups. One group had free food intake (group C), and the other group had restricted food intake until day 40 of the experiments and then had free food intake (group DR). Specimens of adipose tissue and skeletal muscle were collected from each rabbit on days 20, 40, and 60 after the initial examination, and expressions of CD34, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) were investigated. Expression of VEGF was significantly strong in the adipose tissue of group DR at the recovery period of body weight. In conclusion, rebound weight gain after a restricted-diet may be associated with angiogenesis in adipose tissue, and the angiogenesis may be induced by VEGF.

Expression of cyclooxygenase-2 in ovarian mature cystic teratomas with malignant transformation.

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor progression and angiogenesis and we previously reported that an increase in COX-2 expression might be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms. In this study, COX-2 expression of ovarian mature cystic teratomas with malignant transformation, a rare entity accounting for just 1.8% of all mature cystic teratomas, was investigated using immunohistochemical techniques. There were 89 cases of mature cystic teratomas treated with surgery as their initial therapy at Osaka City University Medical School Hospital between 1995 and 2001. Ten cases of these were selected for study; five cases of mature cystic teratoma with malignant transformation, and five cases of mature benign teratoma. Expressions of CD34, vascular endothelial growth factor (VEGF), and COX-2 were investigated. Expressions of VEGF and COX-2 were strong in tissues of mature cystic teratomas with squamous cell carcinoma; however, expressions of them were hardly apparent in mature benign teratomas and in mature cystic teratomas with adenocarcinomas. These results tend to suggest that COX-2 is associated with tumor growth and progression in mature cystic teratomas with squamous cell carcinoma, as opposed to mature benign teratomas and mature cystic teratomas with adenocarcinomas.

Involvement of angiogenesis in weight-loss in tumor-bearing and diet-restricted animals.

The body's weight loss mechanism while in a tumor-bearing state is still unclear. In this study, we investigated expressions of angiogenic factors in the adipose tissue of tumor-bearing and diet-restricted rabbits evaluating the differences between the two groups. We postulated that low nutrition induced vasculogenesis to transport nutrition in the adipose tissues of diet-restricted rabbits, unlike in tumor-bearing rabbits, and that vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were related to angiogenesis of the adipose tissues. Although we investigated the expressions of VEGF and PD-ECGF immunohistochemically in tumor-bearing and diet-restricted rabbits, there was no significant difference between the two groups. Whether angiogenesis of the adipose tissue in the diet-restricted animals may be observed during the nutritional recovery period should be investigated.

Comparison of expression of apoptosis regulatory proteins in the adipose tissue of tumor-bearing and diet-restricted rabbits.

We investigated the expression of apoptosis regulatory proteins in the adipose tissue of tumor-bearing and diet-restricted rabbits, and analyzed the differences between the two groups. The apoptotic index in the tumor-bearing group was 25.1+/-12.4 on day 10 and increased to 27.2+/-14.4 by day 20. Thereafter, however, it gradually decreased, falling to 11.2+/-7.8 on day 30 and 0.67+/-0.88 on day 40. By contrast, no apoptotic cells were detected in the diet-restricted group at any of the times examined. Bcl-2 immunoreactivity was either not detected at all, or was only weakly observed in both groups. Bax expression, on the other hand, gradually increased after implantation in the tumor-bearing group. In 2 of the 5 tumor-bearing rabbits, Bax expression in adipocytes was moderate 10 days after tumor implantation, and strong by day 20, but steadily decreased thereafter. By contrast, hardly any Bax-immunopositive cells were detected in the diet-restricted group. These results suggested that loss of body weight in the tumor-bearing group was different from that in the diet-restricted group, and that it was related to adipocyte apoptosis.

Cyclooxygenase-2 expression in malignant mesenchymal tumors and related uterine lesions.

The aim of this study was to determine whether the expression of cyclooxygenase-2 (COX-2) in uterine sarcoma cells and carcinosarcoma cells is associated with cell type. Nineteen sections of tissues from uterine sarcomas, carcinosarcomas, and an adenosarcoma, and endometrial stromal sarcomas, were immunohistochemically analyzed for the cellular expression of COX-2. Positive immunostaining for COX-2 was observed in 88.9% (8/9) uterine carcinosarcomas, uterine adenosarcomas but was not observed in uterine sarcomas and the endometrial stromal sarcoma (0/10). But positive immunostaining for COX-2 was observed in some sarcomatoid cells in carcinosarcoma tissue. These findings suggest that some of the sarcoma cells in uterine carcinosarcomas resemble epithelial malignant cells in regard to the increase in COX-2 expression, and support the hypothesis that some uterine carcinosarcomas are combination tumors. This may serve as a basis for new chemoprevention and treatment strategies for uterine carcinosarcomas through the inhibition of COX-2 activity.

Pharmacokinetics and pharmacodynamics of serum platinum of gynecologic cancer patients treated with nedaplatin.

Nedaplatin (cis-diammine glycolate platinum) is one of the effective platinum agents for gynecologic carcinoma. In order to assess the pharmacokinetics and pharmacodynamics of serum platinum of gynecologic cancer patients treated with nedaplatin, we calculated 10 course AUCs (area under the curve) of the free and total platinum from blood samples of 4 patients. Peak serum platinum concentrations were dependent on infusion times. In the case of a patient with renal dysfunction or ascites, the concentration of serum platinum tended to stay at a high level for a long time. Serum-free platinum ratios were maintained longer than cisplatin. Low dose nedaplatin administration and divided administration were effective, but total AUC was not so great. The relation between AUC ratio (free platinum AUC/total platinum AUC) and dose/m(2) was not clarified.

Association between overexpression of cyclooxygenase-2 and suppression of apoptosis in advanced cancer of the uterine cervix after cyclic balloon-occluded arterial infusion.

Recent advances in cancer chemotherapy have drawn the attention of investigators to the usefulness of chemotherapy for cancer of the uterine cervix in general, and we ourselves have previously reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI), which enabled treatment by hysterectomy in patients with advanced cervical cancer. Nevertheless, there have been some patients in whom CDDP therapy by BOAI was ineffective, and hysterectomy was impracticable. In the present study we investigated the expression of cyclooxygenase-2 (COX-2) in these cases in an attempt to identify the cause of the lack of efficacy. The subjects of the study were 38 women with advanced cervical cancer classified as FIGO (International Federation of Gynecology and Obstetrics) stage III or higher who were admitted to the Department of Gynecology of Osaka City University Medical School Hospital between July 1993 and April 2000. All of these patients were treated by BOAI, and expression of COX-2, angiogenic factors, and cancer cell apoptosis, before and after BOAI were examined, and survival rates were compared. The 18 patients in whom BOAI was ineffective showed significantly higher expression of COX-2 after BOAI, and cancer cell apoptosis was inhibited. The 5-year survival rate of these patients was 16.8%, as opposed to 54.1% in the 20 patients in whom BOAI was effective. These results suggest that overexpression of COX-2 inhibits cancer cell apoptosis and adversely influences the prognosis.

Transient shrinkage of a uterine leiomyosarcoma treated with GnRH agonist for a presumed uterine leiomyoma: comparison of magnetic resonance imaging finding before and during GnRH agonist treatment.

We present a case of a premenopausal woman treated with GnRH agonist for a presumed uterine leiomyoma. This tumor reduced at first, but subsequent surgical specimens revealed a leiomyosarcoma. Magnetic resonance imaging (MRI), one of the most useful modalities for distinguishing between uterine leiomyoma and leiomyosarcoma, was undertaken twice, before GnRH agonist administration and then after 6 months of GnRH agonist administration. Apparent differences were observed between these MRI findings. Tumor-size reduction with GnRH agonist treatment does not always mean that the possibility of a leiomyosarcoma should be ruled out.

Probucol decreases total body fat loss in VX2-carcinoma-induced cachectic rabbits.

We previously reported the continuous decrease of total body fat in VX2-carcinoma-bearing rabbits after tumor implantation, as well as changes in the serum lipid profile. Probucol, an antioxidant drug, has a cholesterol lowering effect against hyperlipidemic subjects. VX2-carcinoma-bearing rabbits fed with a diet containing 1% probucol did not show any difference in serum lipid compositions as compared with rabbits fed with a control diet. Similarly serum lipolytic activity showed no differences, whether probucol was administered or not, while the decrease in total body fat was significantly less when probucol was administered.

Expression of angiogenic factors in extrapelvic endometriosis.

The expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were immunohistochemically examined in both pelvic and extrapelvic endometriotic lesions. Different expressions of VEGF and COX-2 were observed in both lesions. VEGF immunoreactivity was distributed mainly in the cytoplasm of the adenocytes in inguinal tumors, but was not seen in ovarian tumors. COX-2 showed the same findings. These results suggest that angiogenesis may be involved in the pathogenesis of extrapelvic endometriosis.