Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The steroid receptor-positive human ovarian cancer (BG-1) was evaluated to determine its usefulness as a tumor model. This tumor grows in intact male and female nude mice without hormone supplements. Moreover, its growth was significantly accelerated in ovariectomized mice, and the increased growth rate could be reversed by estradiol administration. Evaluation of tumor growth following endocrine therapy revealed that, while antiandrogens did not affect the tumor growth, both an aromatase inhibitor and a luteinizing hormone-releasing hormone agonist significantly impaired growth of this human ovarian tumor. Estradiol was also shown to up-regulate both estrogen and progesterone receptors in tumors grown in ovariectomized mice. Therefore, the BG-1 human ovarian carcinoma grows without hormonal supplements and yet responds to specific forms of endocrine therapy. Moreover, the steroid receptors present in this tumor respond to exogenous steroids. In conclusion, this tumor may serve as an ideal model for the study of hormonal regulation of ovarian tumor growth.
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PMID:Endocrine characterization of a human ovarian carcinoma (BG-1) established in nude mice. 260 60

The presence of steroid receptors (82 tumors) and aromatase activity (39 tumors) in ovarian carcinomas was correlated with patient survival. No statistically significant correlation was found between the presence or absence of estrogen receptors (ER, 56.1%), progesterone receptors (PR, 57.3%), androgen receptors (AR, 91.5%), or aromatase activity (33.3%) and survival. However, high levels of PR were associated with better survival (P less than 0.05). Furthermore, there was a tendency for patients with advanced disease and PR-positive tumors to have better survival than those with advanced disease and PR-negative tumors (P = 0.13). Patients with tumors that did not contain any of the receptors and those in which ER and AR were absent, or in which PR and AR were absent, had poor survival. It is concluded that receptor status, especially of PR, may be of prognostic importance and that status of receptors and aromatase activity may become useful in selecting ovarian cancer patients for endocrine therapy.
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PMID:Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival. 270 71

Eighty-four tumor samples from 70 women with primary ovarian cancer were assayed for cytosol estrogen (ERc) and progestin (PRc) receptor concentrations and aromatase activity. In addition, 22 of the tumors were studied for their response to the aromatase inhibitor, 4-OH-androstenedione, in a soft agar clonogenic cell assay system. Although aromatase activity was detected in almost all of the primary tumors, this enzyme was barely detectable in the majority of metastatic tumor samples. There was no significant correlation between aromatase activity and either the ERc or PRc content of the tumors, or tumor grade. Of 12 tumors grown successfully in the soft agar culture system, only 1 showed a substantial (greater than 50%) reduction in colony-forming efficiency after exposure to the aromatase inhibitor. These results suggest that local estrogen biosynthesis probably does not play an important role in the majority of epithelial ovarian tumors. However, there may be a small subset of estrogen receptor-positive tumors in which aromatase could provide a local growth stimulus.
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PMID:Aromatase activity in human ovarian cancer. 350 13

The possible role of a novel steroid receptor in ovarian malignancy was investigated. The evolutionarily conserved orphan steroid receptor COUP-TF (chicken ovalbumin upstream promoter transcription factor) was originally identified as a protein interacting with an upstream promoter element of the chicken ovalbumin gene. The human receptor protein was purified from a cervical cancer cell line. An immunocytochemical technique for the visualization of COUP-TF was developed using a specific polyclonal rabbit antibody. Four established ovarian cancer cell lines were evaluated. The patterns of COUP-TF expression were compared to the staining intensities of immunocytochemical assays for estrogen receptor (ER), androgen receptor (AR), aromatase, and HER2/neu. A comparison of the ovarian cancer cell lines showed differential expression of COUP-TF in the nucleus. The pattern of COUP-TF expression did not follow the profile of any of the other four variables. In agreement with transfection experiments showing reduction of activity of other steroid receptors by elevated COUP-TF levels, high COUP-TF expression correlated with low ER activity also in native ovarian cancer cells. These data represent the first reported evidence that COUP-TF-like proteins may play a role in the metabolism and possibly in the process of dedifferentiation of human ovarian cancer.
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PMID:Chicken ovalbumin upstream promoter transcription factor (COUP-TF): an orphan steroid receptor with a specific pattern of differential expression in human ovarian cancer cell lines. 790 49

Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P-450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers.
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PMID:Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women. 847 78

We have studied the biochemical effects of paclitaxel (trade name Taxol) in three ovarian cancer (OV Ca) cell lines and JEG-3 choriocarcinoma cells. Paclitaxel (1 microgram/ml) was cytotoxic to approximately 80% of OV Ca cells, and the ED50 ranged from 6 to 9 ng/ml. Paclitaxel was also cytotoxic to JEG-3 cells (ED50 40 ng/ml), but even at 1 microgram/ml, 40-50% of the cells survived paclitaxel treatment. Paclitaxel increased 17 beta-estradiol secretion 3-4 fold in all three OV Ca cell lines with an ED50 range of 3-13 ng/ml. Similarly, paclitaxel increased estradiol secretion from JEG cells with an ED50 of 50 ng/ml. Colchicine also increased estradiol secretion significantly from OV Ca cells at 2 microM while reducing cell number approximately 40% (beta-lumicolchicine, an inactive isomer, was ineffective at this concentration). Paclitaxel (1 microgram/ml) treatment of BR OV Ca cells produced alterations in morphology leading to "rounding" of cells within 6 h of treatment. Simultaneously, paclitaxel increased immunohistochemical staining for aromatase, and this increase was coincident with morphological alterations. The present results demonstrate that low concentrations of paclitaxel can have significant steroidogenic, as well as cytotoxic, effects on OV Ca cells, suggesting that paclitaxel may activate signal transduction pathways in addition to disrupting microtubule function. These findings further suggest that paclitaxel could be efficacious at submicromolar concentrations.
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PMID:The steroidogenic and morphological effects of paclitaxel on cultured ovarian cancer cells. 855 48

Aromatase cytochrome P-450 was immunohistochemically localised exclusively in the cytoplasm of neoplastic cells of benign and malignant nonfunctional ovarian tumours, whilst (progesterone receptors (PR) and estrogen receptors) (ER) were localised exclusively inn the nuclei of neoplastic cells. Aromatase activity and PR were detected in 68% (17/25) and 32% of the malignant tumours and 82% (22/27) and 67% of the benign tumours, respectively. In postmenopausal tumours, the positivity for PR in malignant tumours was less frequent (p < 0.01) than that in benign tumours. The tumours in which both aromatase and PR were positive, were less frequent (p < 0.05) in malignant than in benign tumours. Aromatase activity was detected in 100% (8/8) of the PR-positive tumours but in only 68% (9/17) of the PR-negative tumours. With postmenopausal malignant tumours, there was a positive correlation between aromatase activity and PR level (r = 0.77, p < 0.001). However, there was no significant difference in the positivity of ER. The serum steroid levels did not correlate with the tumour levels of aromatase activity, PR or ER. These findings suggest that aromatase activity is correlated with PR in ovarian tumours of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful factor in ovarian cancer.
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PMID:Immunohistochemical localisation of aromatase and its correlation with progesterone receptors in ovarian epithelial tumours. 861 76

It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed these changes using histoculture of 15 human endometrial cancers and 9 ovarian cancers. Five of the fifteen endometrial cancers and four of the nine ovarian cancers demonstrated decreased [3H]thymidine uptake or Ki67 labeling index after 14alpha-hydroxy-4-androstene-3,6,17-trione (NKS01) treatment. In ovarian cancer cases, the responsive cases tended to be associated with higher aromatase and estrogen receptor alpha (ER) expression compared with the other cases but this was not seen in the endometrial cancer cases. There were no changes in ER and aromatase expression before and after NKS01 treatment in either ovarian or endometrial cancer cases. We then studied the same primary human breast tumors before and after aminoglutethimide (AMG, n=3) and 4-hydroxyandrostenedione (4-OHA, n=3) treatment. Tumor aromatase activity increased in 3 cases and decreased or was unchanged in 3 cases but aromatase immunoreactivity in stroma and adipocytes was unaltered in 5 cases. There were no changes in the ER labeling index before or after treatment. Five of the six cases including the responsive cases tended to be associated with decreased cell proliferation or Ki67 expression and increased apoptosis when examined by the TUNEL method. These results indicate that aromatase inhibitors may exert their effects on human breast and other cancers through decreasing proliferation and increasing apoptosis, possibly without altering ER status.
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PMID:Effects of aromatase inhibitors on the pathobiology of the human breast, endometrial and ovarian carcinoma. 1073 Nov 9

The hereditary breast (BC) and ovarian (OC) cancer syndrome (HBOC) includes genetic alterations of various susceptibility genes such as TP53, ATM, PTEN or MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6, BRCA1 and BRCA2. Germline mutations of the cancer-susceptibility genes BRCA1 and BRCA2 seem to be the major aetiology of the HBOC. Genetic counselling and identification of high-risk families may be essential (1) to provide the best method for genetic testing by explaining the sensitivity and specificity of the methods, (2) to offer the opportunity to participate in specific early cancer detection programmes (breast (self) palpation, ultrasound, mammography and magnetic resonance tomography for breast cancer; vaginal exploration and ultrasound for ovarian cancer), (3) to inform them about prophylactic medication (oral contraceptive pill (OCP), chemoprevention (tamoxifen, raloxifen, aromatase inhibitors)) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfil these broad demands, an inter-disciplinary counselling approach (gynaecological oncology, human genetics, molecular biology, psychotherapy) in the setting of a cancer genetic clinic seems the most appropriate. There, participation in predictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the subjects. In particular, preventive options are emotionally disturbing for the subjects, and in cases of previous cancer. BC chemoprevention for high-risk women does not seem to be as effective as expected. However, OCP reduces the risk for OC. For prophylactic surgery, various points have to be considered, including: (1) individual risk assessment and gain in life expectancy, (2) value of screening and early detection methods or medical prevention, (3) disease characteristics and prognosis, and (4) anxiety and quality of life. Decisions regarding these options have to be individualized and psychological support must be offered during the period of decision and follow-up.
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PMID:Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer. 1095 53

Approximately two thirds of breast cancer patients have estrogen-dependent carcinomas. The biosynthesis of estrogens is catalyzed by the microsomal enzyme aromatase. Mechanisms controlling human aromatase gene expression are complicated by the existence of multiple tissue specific promoters. The most proximally located Pll promoter is mainly active in ovarian granulosa cells. PlI can be switched on in human breast cancer cells. Since there are strong silencer elements located within the 3' portion of the PlI promoter, we propose that the function of these silencer elements could be reversed by breast cancer cell specific signals/factors, resulting in aberrant expression of aromatase. We have identified and characterized a novel silencer element, S2, which is upstream of S1, a silencer element recently identified by another group. S2, a 54-bp fragment 100% conserved between humans and rodents, functions in both orientation- and promoter-independent manners. The core region of S2 contains two consensus binding sites for members of the GATA transcription factors. GATA-4 was found to be expressed in three out of four human breast cancer cell lines examined by RT-PCR, and transfection with GATA-4 partially reversed the repressive function of S2. However, we were unable to demonstrate that DNA-protein complexes formed between nuclear extracts of human breast and ovarian cancer cells and S2 contain GATA-4 using a supershifting approach. We suggest that the expression of GATA-4, and more importantly, other yet to be identified GATA or GATA-related factor(s), are implicated in provoking aberrant expression of aromatase, and therefore, the biosynthesis of estrogens, in human breast cancer cells.
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PMID:Characterization of a novel silencer element in the human aromatase gene PII promoter. 1101 53


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