Biomedical subjects

H Katabuchi

Publications and source records attributed to H Katabuchi.

At least 19 recordsLinked to original sources

PubMed2005

Characterization of 17beta-hydroxysteroid dehydrogenase type 4 in human ovarian surface epithelial cells.

The human ovarian surface epithelium (hOSE) is a single layer of mesothelial-type primitive epithelial cells that are potential estrogen targets. It has been reported that hOSE cells can produce estrogen. However, the mechanisms that regulate estrogen level(s) in hOSE cells are not yet known. To elucidate the enzymes involved in these reactions, we examined gene expression of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in primary hOSE (POSE) and OSE2a cells using RT-PCR. We found that POSE cells and cells of the immortalized hOSE line, OSE2a, bidirectionally converted estrone (E1) and 17beta-estradiol (E2). Both cell types expressed mRNA for 17beta-HSD type 1 (17beta-HSD1), suggesting that the enzyme is involved in the E1 to E2 conversion. Interestingly, both cells expressed 17beta-HSD4 mRNA but not 17beta-HSD2 mRNA. We prepared an antibody against the carboxyl terminal of 17beta-HSD4 (anti-17beta-HSD4 antibody), which recognized the 80 and 48 kDa proteins in POSE and OSE2a cells based on immunoblot analysis. Furthermore, immunohistochemical study revealed the presence of 17beta-HSD4 in hOSE cells in the human ovary. These results suggest that 17beta-HSD4 is involved in estrogen inactivation and may protect against an excessive accumulation of E2 in hOSE cells.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability.

Epithelial ovarian carcinoma is thought to derive from ovarian surface epithelium (OSE). The black box of the early molecular changes in ovarian carcinogenesis is being interpreted by the development of experimental systems employing immortalised human OSE cells. However, the existing cell lines of the OSE cells have limited utility due to chromosomal instability. Our goal was to establish new immortalised human OSE cells that retain the original characteristics of the primary cells without chromosomal alterations. Using primary human OSE cells obtained from a postmenopausal patient with endometrial cancer, five cell lines ('HOSE1' lines) were newly established by infection with retroviral expression vectors containing type 16 human papillomavirus (HPV-16) E6, E7, a variant E6 (E6delta151), and Bmi1 polycomb gene, in combination with telomerase reverse transcriptase (hTERT). Consequently, five HOSE1s cell lines, HOSE1s-E6/hTERT, -E7/hTERT, -E6/E7/hTERT, -E6delta151/E7/hTERT, and -E6delta151/Bmi1/hTERT, grew beyond the population doubling number of 200. These cell lines, except for HOSE1-E6/hTERT, essentially showed the original features of the primary human OSE cells. Of them, HOSE1-E7/hTERT preserved diploidy in a kariotype analysis, and did not show transformed phenotypes in anchorage-independent growth and tumour formation. Thus, HOSE1-E7/hTERT may provide a novel model system with which to investigate the mechanisms of early molecular changes.

Animals↗

PubMed2005

Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages.

Human gonads and non-gonadal organs/tissues express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors. This study aimed to identify the LH/CG receptors and to clarify their function in human placental chorionic villous macrophages. Macrophages as well as syncytiotrophoblasts of human chorionic villous tissues were immunohistochemically positive for LH/CG receptor throughout gestation. By reverse transcription-nested polymerase chain reaction methods, villous macrophages were shown to express a variant type of LH/CG receptor, the sequencing of which revealed a deletion of exon 9. For experiments in vitro, a monocyte-macrophage cell line, THP-1, was transfected with vector alone, wild-type LH/CG receptor, and exon 9-deleted LH/CG receptor after phorbol 12-myristate 13-acetate (PMA) treatment. Non-PMA-treated THP-1 cells transfected with vector alone were also examined. THP-1 cells expressed exon 9-deleted LH/CG receptor after treatment with PMA. After the cells of the four groups were cultured in medium containing intact human CG (hCG), the concentrations of hCG and its beta-core fragment (beta-CF) were measured in the supernatant of the culture medium and in the cell cytosol. Time-dependent hCG uptake was observed in both non-PMA-treated and PMA-treated THP-1 cells, suggesting that the variant receptor is not directly involved in the ingestion of hCG. The degradation of hCG and excretion of beta-CF were progressed in PMA-treated cells but not in the un-treated cells. In the cell cytosol, the ratio of beta-CF and hCG concentrations (beta-CF/hCG) was significantly higher in the PMA-treated cells than in non-PMA-treated cells; however, it did not differ between the PMA-treated cells transfected with exon 9-deleted receptor and those transfected with vector alone. Macrophages may express the variant receptor in order to recognize the intracytoplasmic hCG and transport it to the lysosome. Among the two PMA-treated cells, the ratio was lower in those transfected with wild-type receptor. The expression of the variant receptor may modulate the degradation of hCG but be reduced by expression of the wild-type receptor in its lacking macrophages. Our data suggest a potentially important role for exon 9-deleted LH/CG receptors expressed in human placental villous macrophages in the local metabolism of hCG.

Base Sequence↗

PubMed2001

Characterization and tumorigenicity of human ovarian surface epithelial cells immortalized by SV40 large T antigen.

OBJECTIVES: Epithelial ovarian cancers are considered to arise from neoplastic transformation of the ovarian surface epithelium (OSE). However, the earliest events in ovarian carcinogenesis have not been clearly defined because patients are often diagnosed in the advanced stages and useful in vivo and in vitro experimental systems using human OSE cells are lacking. We aimed to improve the availability of experimental models for the study of human ovarian carcinogenesis. METHODS: Subcultured human OSE cells were transfected with SV40 large T antigen. Resulting OSE cell lines were characterized using immunocytochemistry and tested tumorigenicity. RESULTS: Six immortalized OSE cell lines were obtained. All cell lines essentially retained the original morphological features of normal OSE cells and showed higher proliferation rates and saturation density. Although they were all nontumorigenic in athymic mice, OSE2b-2 sv cells, which were selected in soft agar from colonies of an SV40 large T antigen-expressing transfectant, OSE2b sv, produced tumors on the peritoneal surface, mesothelium, and diaphragm and induced ascites after being injected intraperitoneally. Solid tumors also grew when mice were inoculated subcutaneously. The tumor cells were formed in a solid sheet arrangement and no evidence of glandular or squamous differentiation was present. They were weakly immunostained with an antibody against cytokeratin, and intercellular junctions resembling attachment devices were ultrastructurally present between cells. The tumors were histologically diagnosed as undifferentiated carcinomas. CONCLUSIONS: The established cell lines may provide a model system to investigate the mechanisms of cytogenic and molecular changes from normal OSE cells through the various steps of transformation.

Aged↗

PubMed2001

Expression of monocyte chemoattractant protein-1 in peritoneal endometriotic cells.

It is well known that the number of peritoneal macrophages is increased in patients with pelvic endometriosis. We measured the concentration of monocyte chemoattractant protein-1 (MCP-1) using an enzyme-linked immunosorbent assay (ELISA) in the peritoneal fluid of women with and without endometriosis. The expression of MCP-1 in pelvic endometriotic lesions obtained from the peritoneum was also examined using immunohistochemistry and nonradioactive in situ hybridization. The mean concentration of MCP-1 in the peritoneal fluid was significantly higher in the patients with endometriosis (P<0.05). The most significant elevation, compared with non-endometriosis patients, was found in stage I of the disease (P<0.05). However, no statistically significant difference was found among endometriosis stages I, II, III, and IV. Immunohistochemical staining revealed that MCP-1-positive cells were localized in the glandular epithelium of the endometriotic lesions and in the stromal macrophages distributed in those lesions, but normal peritoneal cells were negative. The in situ hybridization method demonstrated expression of MCP-1 mRNA on the endometriotic glandular epithelium and stromal macrophages. These findings suggest that MCP-1 may be involved in the histogenesis and early development of peritoneal endometriosis.

Ascitic Fluid↗

PubMed2001

Glial implants in gliomatosis peritonei arise from normal tissue, not from the associated teratoma.

Metaplasia of subcoelomic mesenchyme has been implicated, but not proven, in the pathogenesis of common gynecological diseases such as endometriosis and rarer entities such as leiomyomatosis peritonealis disseminata and gliomatosis peritonei (GP). GP is associated with ovarian teratomas and is characterized by numerous peritoneal and omental implants composed of glial tissue. Two theories to explain the origin of GP have been proposed. In one, glial implants arise from the teratoma, whereas in the other, pluripotent Müllerian stem cells in the peritoneum or subjacent mesenchyme undergo glial metaplasia. To address the origin of GP, we exploited a unique characteristic of many ovarian teratomas: they often contain a duplicated set of maternal chromosomes and are thus homozygous at polymorphic microsatellite (MS) loci. In contrast, DNA from matched normal or metaplastic tissue (containing genetic material of both maternal and paternal origin) is expected to show heterozygosity at many of these same MS loci. DNA samples extracted from paraffin-embedded normal tissue, ovarian teratoma and three individual laser-dissected glial implants were studied in two cases of GP. In one case, all three implants and normal tissue showed heterozygosity at each of three MS loci on different chromosomes, whereas the teratoma showed homozygosity at the same MS loci. Similar results were observed in the second case. Our findings indicate that glial implants in GP often arise from cells within the peritoneum, presumably pluripotent Müllerian stem cells, and not from the associated ovarian teratoma. This finding has important implications for more common gynecological entities with debatable pathogenesis, such as endometriosis, by definitively demonstrating the metaplastic potential of stem cells within the peritoneal cavity.

Chromosome Mapping↗

PubMed2001

Clinical value of thymidine kinase in patients with cervical carcinoma.

OBJECTIVE: Our purpose was to determine the clinical value of thymidine kinase (TK), which is an important pyrimidine pathway enzyme involved in salvage DNA synthesis, in patients with cervical carcinoma. METHODS: We examined TK mRNA expression by reverse transcription polymerase chain reaction in 19 tissue specimens of invasive cervical carcinoma and 9 normal cervices and related it to thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA expressions. Serum TK level was determined by radioenzymatic assay in 79 patients with invasive cervical carcinoma, 7 patients with microinvasive carcinoma, 21 patients with carcinoma in situ and 32 normal women. RESULTS: TK mRNA expression was upregulated in invasive cervical carcinoma compared with the normal cervix (p < 0.05) and significantly correlated with TS mRNA expression (p < 0.0001) but not with TP mRNA expression. The serum TK level was significantly higher in patients with invasive carcinoma than in normal women and patients with carcinoma in situ (p < 0.01 and p < 0.05). In patients with invasive cervical carcinoma, the serum TK level significantly correlated with TK mRNA expression (p < 0.05), but not with any conventional clinicopathologic factors. High serum TK levels significantly correlated with a poorer survival (p < 0.05), and multivariate analysis showed serum TK level to be an independent prognostic factor (p < 0.05). CONCLUSION: TK may play an important role in influencing the malignant behavior of cervical carcinoma, and measurement of the serum TK level may be useful in predicting survival in patients with cervical carcinoma.

Adult↗

PubMed2001

Detailed morphology of human ovarian surface epithelium focusing on its metaplastic and neoplastic capability.

Ovarian epithelial tumors are thought to derive from the surface epithelium of the ovary, which differentiates after invagination of the coelomic mesothelium over the gonadal ridges during early embryonic development. On the putative mullerian potential of this epithelium, endometriosis, including ovarian endometriosis, can be explained by a metaplastic process from the peritoneum. In the present study, we assessed specific changes in the architecture and in the cytological characteristics of human ovarian epithelial cells on the surface and within the inclusion cyst. Grossly normal ovaries were retrieved from 215 patients undergoing incidental oophorectomy and 33 patients with contralateral ovarian tumor. In addition, 75 patients diagnosed with epithelial ovarian cancer and 26 ovarian endometriosis patients undergoing oophorectomy were selected. The incidence of cortical invagination, epithelial papillomatosis and pseudostratification was not different in normal ovaries between pre- and post-menopausal women, whereas inclusion cysts were more frequently observed in post-menopausal women (p<0.05). The occurrence rates of invagination and inclusion cysts were significantly higher in normal ovaries examined after incidental oophorectomy (p<0.05) and in those with contralateral ovarian tumor (p<0.05), respectively. Although serous metaplastic change with cilia was most common and it did not differ before and after menopause, the frequency of mucinous, endometrioid and transitional cell changes was low in the two groups of pre- and post-menopausal women. Mucinous metaplasia was more frequently observed in patients with contralateral ovarian tumor than those without ovarian tumor (12.1% vs. 1.9%; p<0.05). Four (5.3%) of 75 ovarian cancer patients revealed malignant transformed cells from a single layer of normal epithelium covering the ovarian surface or inclusion cyst. Ovarian or extraovarian endometriosis was identified in 16 (21.3%) of 75 epithelial ovarian cancer patients analyzed. An in situ carcinogenesis in the endometriotic cyst was seen in three epithelial ovarian cancers (4.0%). In seven (26.9%) of 26 ovarian endometriosis cases, epithelial cells on the ovarian surface or within the inclusion cyst were histologically changed to endometriotic gland cells. Careful and extensive observations of surgical specimens with ovarian carcinoma and ovarian endometriosis showed that they originated from the ovarian epithelium lining the surface and cortical small cysts.

Endometriosis↗

PubMed2000

An immunohistochemical and ultrastructural study of a follicle-stimulating hormone-secreting gonadotroph adenoma occurring in a 10-year-old girl.

Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-beta monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140-260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.

Adenoma↗

PubMed2000

Somatic mutations in the STK11/LKB1 gene are uncommon in rare gynecological tumor types associated with Peutz-Jegher's syndrome.

Peutz-Jegher's syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation, hamartomatous polyposis, and predisposition to benign and malignant tumors of the gastrointestinal tract, breast, ovary, uterine cervix, and testis. Germline-inactivating mutations in one allele of the STK11/LKB1 gene at chromosome 19p13.3 have been found in most PJS patients. Although ovarian sex cord tumors with annular tubules (SCTATs) and minimal deviation adenocarcinomas (MDAs) of the uterine cervix are very rare in the general population, both tumor types occur with increased frequency in women with PJS. An earlier report indicated that the 19p13.3 region containing the STK11 gene was affected by loss of heterozygosity (LOH) in nearly 50% of MDAs of the uterine cervix. We investigated the role of STK11 mutations and LOH of the 19p13.3 region in two PJS-associated SCTATs and in five SCTATs and eight MDAs of the uterine cervix, which occurred in patients lacking features of PJS (referred to here as "sporadic" cases). Germline mutations in the STK11 gene, accompanied by LOH of markers near the wild-type STK11 allele, were found in the two PJS-associated SCTATs. Somatic mutations in the coding region of STK11 were not found in any of the sporadic SCTATs or MDAs studied, although LOH of the 19p13.3 region was seen in three of eight MDAs. Our findings indicate that STK11, like other tumor suppressor genes, is affected by biallelic inactivation in gynecological tumors of PJS patients. In addition, although LOH of the 19p13.3 region was seen in sporadic MDAs, somatic STK11 mutations are rare. A yet-to-be-defined tumor suppressor gene in the 19p13.3 region may be the specific target of inactivation in these tumors.

AMP-Activated Protein Kinase Kinases↗

PubMed2000

The molar vesicle fluid contains the beta-core fragment of human chorionic gonadotropin.

The human chorionic gonadotropin (hCG) beta-core fragment (beta-CF) is a major molecular form of hCG beta subunit (hCGbeta) immunoreactivity in the urine of pregnant women and patients with trophoblastic disease. The majority of evidence supports the fact that the beta-CF is a degradative product of intact hCG and free hCGbeta in the kidneys. We found a beta-CF-like substance in the fluid of molar vesicles from a patient with complete hydatidiform mole. The molar fluid beta-CF (mbeta-CF) was indistinguishable from the beta-CF in the patient's urine (ubeta-CF) by immunoreactivity and by elution profile on gel chromatography. The binding study to lectins, however, showed that mbeta-CF contains a carbohydrate moiety that differs from that of ubeta-CF. Immunohistochemistry with anti-beta-CF antibody demonstrated a strong immunoreactivity in a large number of macrophages in the molar villous stroma. In vitro incubation of intact hCG with peritoneal macrophages showed a slow increase of intact hCG in the cell cytosol with the appearance of beta-CF-like substance in the cell supernatant. In conclusion, the source of beta-CF in molar fluid is likely to be macrophages existing in the villous stroma. Thus macrophages may ingest intact hCG and act as a local regulator of gonadotropic hormones.

Body Fluids↗

PubMed2000

Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation in vitro.

In human chorionic villi, numerous macrophages, so-called Hofbauer cells, are located adjacent to trophoblasts. To determine the role of the macrophages in the proliferation and differentiation of trophoblasts, cytotrophoblast cells were cultured in serum-free culture-conditioned media of villous macrophages (VMCM), peritoneal macrophages (PMCM), and villous fibroblasts (VFCM). In VMCM, proliferation of cytotrophoblast cells was detected at 24 h by immunocytochemistry with Ki-67-antibody. A large number (P < 0.001) of multinucleated syncytia was formed in VMCM. In VMCM, cytotrophoblast cell fusion was completed by 96 h, which coincided with the peak of hCG secretion and initiation of human placental lactogen (hPL) release. Levels of hCG (P < 0.001) and hPL (P < 0. 001) secretion from syncytial cells were significantly higher in VMCM than in PMCM or in VFCM. Concentrations of macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) analyzed by ELISA were greater in VMCM than in PMCM or in VFCM, whereas monocyte chemoattractant protein-1 (MCP-1) concentration was high in PMCM. The expression patterns of M-CSF, VEGF, and MCP-1 in villous macrophages and peritoneal macrophages by reverse transcriptase-polymerase chain reaction were similar to their secretion patterns. Thus, villous macrophages have a greater ability to stimulate hCG and hPL secretion than do peritoneal macrophages. This study suggests that macrophages within the villous stroma may stimulate the growth and differentiation of trophoblasts through their secreted substances.

Cell Differentiation↗

PubMed1999

Increased serum levels of 5-S-cysteinyldopa and intercellular adhesion molecule-1 in a patient with a uterine amelanotic metastasis from a primary vaginal malignant melanoma.

A 75-year-old Japanese woman, who had an enlarged uterus and two nodules on the anterior vaginal wall, underwent wide excision of the anterior vaginal wall, bilateral inguinal lymphadenectomy, modified radical hysterectomy, and pelvic lymph node dissection. Her serum level of 5-S-cysteinyldopa (5-S-CD) was elevated, but her serum intercellular adhesion molecule-1 (ICAM-1) level was within normal limits. Histologic examination of the vaginal wall revealed atypical melanocytes at the dermoepidermal junction and numerous melanin-containing granules in the cytoplasm of the tumor cells. The tumor in the uterus consisted of sheets of anaplastic cells with evidence of diminished melanization. Five months after her initial presentation, she developed a recurrence and expired. The serum level of ICAM-1 was beyond the normal limit at the time of recurrence. Both the serum 5-S-CD and the ICAM-1 levels became elevated after recurrence and appeared to be correlated with disease progression.

Aged↗

PubMed1999

A novel in vitro experimental model for ovarian endometriosis: the three-dimensional culture of human ovarian surface epithelial cells in collagen gels.

OBJECTIVE: To develop an in vitro experimental model of ovarian endometriosis using human cells and to investigate the pathogenesis of endometriosis. DESIGN: Controlled in vitro coculture study. SETTING: A department of obstetrics and gynecology at a university hospital. PATIENT(S): Ovaries and endometrium were obtained from patients who underwent a hysterectomy because of gynecologic disease. INTERVENTION(S): Human ovarian surface epithelial (OSE) cells were cultured alone and OSE cells and endometrial stromal (ES) cells were cultured together in a three-dimensional collagen gel culture system with or without the addition of E2. MAIN OUTCOME MEASURE(S): The aggregated collagen gels containing the cultured cells were examined morphologically. RESULT(S): The OSE cells in single culture with E2 formed circular arrangements. These cells were immunohistochemically positive for cytokeratin but negative for epithelial membrane antigen. In the cocultures of OSE and ES cells with E2, the OSE cells formed a lumen structure surrounded by ES cells. Immunoreactivity for cytokeratin and epithelial membrane antigen was detected in the glandular cells and cilia were identified on the cell surface by electron microscopy. Without the addition of E2, no structures were detected. CONCLUSION(S): A new in vitro experimental model was established with the aid of human OSE cells. Endometriotic lesions can arise through a process of metaplasia from OSE cells in the presence of E2 and ES cells.

Adult↗

PubMed1999

A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement in a 10-year-old girl.

OBJECTIVE: To report a rare case of gonadotroph adenoma accompanied by ovarian enlargement in a child. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 10-year-old Japanese girl with multiple cysts of both ovaries. INTERVENTION(S): Endocrinologic assays, immunohistochemical staining, ultrastructural observations, and in vitro analysis. MAIN OUTCOME MEASURE(S): The endocrinologic assays showed an elevated serum FSH level. The tumor cells excised from the gonadotroph adenoma were immunohistochemically positive for antihuman FSH monoclonal antibody. When cultured in vitro, the tumor cells secreted FSH in the primary culture. RESULT(S): The gonadotroph adenoma produced FSH. After transsphenoidal surgery, both ovaries decreased in size. CONCLUSION(S): The ovarian enlargement was induced by endogenous FSH from the gonadotroph adenoma. To our knowledge, this is the first reported case of gonadotroph adenoma accompanied by ovarian enlargement in childhood or adolescence.

Adenoma↗

PubMed1999

Expression of the thymidine phosphorylase gene in epithelial ovarian cancer.

Thymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumours. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear cell and two undifferentiated) were analysed by polymerase chain reaction of RNA after reverse transcription. These included eight of low malignant potential. Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the beta2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III-IV was significantly higher than that of TP gene expression in stage I-II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases after complete resection of the primary tumours by surgical operation was performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to, or greater than, median) was to be significantly worse than patients with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumour phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated.

Adult↗

PubMed1999

Coelomic metaplasia theory of endometriosis: evidence from in vivo studies and an in vitro experimental model.

Ultrastructure studies of pelvic peritoneal tissue from women undergoing laparotomy suggest that before endometriosis has become established in the peritoneum, there might be a metaplastic change by peritoneal mesothelial cells into endometrial glandular cells. A new in vitro experimental model of endometriosis using human ovarian surface epithelium cells has shown evidence that endometriotic lesions can arise by a process of metaplasia from the ovarian surface epithelium. In this model, when both ovarian surface epithelium and ovarian stromal cells were cocultured with 17beta estradiol in a three-dimensional collagen gel lattice, the ovarian surface epithelium cells formed a lumen structure, surrounded by endometrial stromal cells with an epithelial mesenchymal structure. Immunoreactivity for epithelial membrane antigen and cytokeratin was shown in the glandular cells and cilia, as well as in the microvilli. Electron microscopy showed evidence of tight junctions on cell surfaces. These findings suggest that endometriosis may manifest as a serial change from the adjacent mesothelial cells.

Cells, Cultured↗

PubMed1999

Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging.

PURPOSE: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. MATERIAL AND METHODS: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. RESULTS: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29+/-0.11). The size ratio for the hypointense tumors was 0.82+/-0.14, and 0.82+/-0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). CONCLUSION: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas.

Administration, Inhalation↗