Estradiol production during controlled ovarian hyperstimulation correlates with treatment outcome in women undergoing in vitro fertilization-embryo transfer.

Objective: To study the value of E(2) production during controlled ovarian hyperstimulation (COH) in predicting IVF-ET outcome.

Design: Historical cohort.

Setting: Academic infertility center.

Area under the curve for estradiol levels do not consistently reflect estradiol levels on the day of hCG administration in patients undergoing controlled ovarian hyperstimulation for IVF-ET.

Purpose: Most studies reported estradiol (E2) levels attained on day of hCG administration when investigating effect of E2 on IVF outcome. We studied whether a relationship exists between the area under the curve for E2 levels (AUC-E2) and E2 levels on hCG day during IVF-ET.

Methods: Retrospectively, we analyzed data for 313 patients who completed one IVF-ET cycle each.

Live birth following intracytoplasmic sperm injection after a 15-hour weather-related delay in cryopreservation of testicular sperm.

Objective: To report a live birth after transfer of cryopreserved blastocysts derived from testicular sperm that were cryopreserved 15 hours after biopsy due to inclement weather.

Design: Case report.

Setting: University-affiliated private clinic.

Environmental PCB exposure and risk of endometriosis.

Background: Hormonally active environmental agents have recently been associated with the development of endometriosis.

Methods: We undertook a study to assess the relationship between endometriosis, an estrogen-dependent gynaecological disease, and 62 individual polychlorinated biphenyl (PCBs) congeners. We enrolled 84 eligible women aged 18-40 years undergoing laparoscopy for study, which included an interview and blood specimen (n=79; 94%).

N-Acylethanolamines in human reproductive fluids.

N-Acylethanolamines (NAEs) are an important family of lipid-signaling molecules. Arachidonylethanolamide (anandamide) (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) are co-produced from similar phospholipid precursors when neurons are stimulated. AEA is an endogenous agonist (endocannabinoid) for cannabinoid receptors.

Evidence that anandamide-signaling regulates human sperm functions required for fertilization.

Ejaculated mammalian sperm require several hours exposure to secretions in female reproductive tracts, or incubation in appropriate culture medium in vitro, before acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also known as anandamide, is a novel lipid-signal molecule that is an endogenous agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by high-performance liquid chromatography/mass spectrometry.

Angiogenic balance in human melanoma: expression of VEGF, bFGF, IL-8, PDGF and angiostatin in relation to vascular density of xenografts in vivo.

Tumor angiogenesis, a major requirement for tumor outgrowth and metastasis formation, is regulated by pro- and anti-angiogenic factors. We have studied the expression of a panel of angiogenic factors, and of the angiogenesis inhibitor angiostatin, in a panel of human melanoma cell lines giving rise to xenografts with different vascular densities. Angiogenic-factor expression was analyzed in vitro (cell lines) and in vivo (xenografts), both at mRNA (RT-PCR and Northern blot) and at protein level (ELISA and Western blot).

Adrenal dynamic responses to physiologic and pharmacologic adrenocorticotropic hormone stimulation before and after ovarian steroid modulation in women with polycystic ovary syndrome.

Objective: To test the hypothesis that in women with polycystic ovary syndrome (PCOS), adrenal cytochrome P450c 17alpha activity is different after physiologic vs. pharmacologic ACTH stimulation and that ovarian activity promotes adrenal hyperactivity that is different after physiologic vs. pharmacologic ACTH stimulation.

Inhibition of FGF-1 receptor tyrosine kinase activity by PD 161570, a new protein-tyrosine kinase inhibitor.

Through direct synthetic efforts we discovered a small molecule which is a 40 nanomolar inhibitor of the human FGF-1 receptor tyrosine kinase. 1-Tert-butyl-3-[6-(2,6-dichloro-phenyl)-2-(4-diethylamino-butylamino)-py rido[2,3-d]pyrimidin-7-yl]-urea (PD 161570) had about 5- and 100-fold greater selectivity toward the FGF-1 receptor (IC50 = 40 nM) compared with the PDGFbeta receptor (IC50 = 262 nM) or EGF receptor (IC50 = 3.7 microM) tyrosine kinases, respectively.

Basic fibroblast growth factor and receptor expression in human ovarian cancer.

Basic fibroblast growth factor (bFGF) and other members of the FGF family share several biological properties that have the potential to mediate neoplastic cell growth. To test the hypothesis that bFGF may play a role in human ovarian cancer cell growth, three ovarian cancer cell lines, A90, A121(P), and A121(A), were investigated for their ability to respond to bFGF as a mitogen, to express endogenous bFGF protein or message for FGF proteins, and to exhibit FGF receptor or its message. Addition of bFGF to cultures of all three cell lines maintained in chemically defined media resulted in a statistically significant increase in cell number.

Comparison of cisplatin and carboplatin cytotoxicity in human ovarian cancer cell lines using the MTT assay.

In this study, we compared the cytotoxicity of cisplatin and carboplatin against a panel of human ovarian cancer cell lines using the MTT assay, a rapid colorimetric test that can be used to evaluate the number of residual viable tumor cells following chemotherapy. The established human ovarian cancer cell line OVCAR-3 and the recently isolated and characterized A721, A90, A286, A1, and A121A cell lines were evaluated for chemosensitivity. Each cell line was treated separately with cisplatin and carboplatin at concentrations ranging from 500 to 0.

Three related near-haploid clones in a primary endometrioid carcinoma of the ovary.

We report the cytogenetic findings in a primary endometrioid carcinoma of the ovary from a 29-year-old woman. Three clones with counts of 30, 29, and 27 chromosomes were observed. The predominant clone had 29 chromosomes and the following karyotype: 29, X, -X, -3, -3, +der(3)ins(3;?) (q21;?), -4, -5, -6, -8, -9, -11, -13, -14, -15, -16, -17, -18, -19, -21, -22, +mar.

Correlation between clinical, endocrinologic and nuclear magnetic resonance findings in women with suspected pituitary adenomas.

Twenty-nine women with suspected pituitary adenomas were evaluated with nuclear magnetic resonance (NMR). Twenty-six had prolactin levels less than 100 ng/mL, and three had levels greater than 100. We tried to correlate the clinical findings with the prolactin levels and NMR findings.

Characterization of human ovarian and endometrial carcinoma cell lines established on extracellular matrix.

Six cell lines were established from four patients with advanced carcinoma of the ovary and from one patient with carcinoma of the endometrium. These lines were established from fresh tumor material maintained initially on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Two of the six lines continue to require ECM as a substrate for optimal growth while the remaining four lines will proliferate on ECM or plastic substrate.

Borderline epithelial tumors of the ovary: ovarian intraepithelial neoplasia.

Although the concept of low malignant potential and/or borderline malignancy of some epithelial ovarian tumors was endorsed by the World Health Organization in 1973, uncertainty exists regarding the biologic behavior aspects of these lesions and this may account for the discrepancy in the 5-year survival figures reported for patients afflicted with these malignancies (76-95 per cent). We have reviewed the clinicopathologic aspects of 26 cases of borderline epithelial ovarian tumors and searched the literature. Based on our analysis, we have concluded that: 1) rupture of the cyst at surgery did not affect the patient's outcome but positive peritoneal fluid cytology did.

Primary fallopian tube carcinoma: treatment and spread pattern.

The clinicopathologic aspects of seven cases of Fallopian tube adenocarcinoma are analyzed. Potential early spread of this malignancy to the retroperitoneal lymph nodes and right subdiaphragmatic area is documented. Multimodality treatment of tubal cancer to include surgery, radiation, and drug therapy (alkylating agents, progestins, with or without 5-fluorouracil and adriamycin) appears feasible and promising.

t(10;17) as the sole chromosome change in a uterine leiomyosarcoma.

A cytogenetic analysis in a primary uterine leiomyosarcoma revealed a t(10;17) as the only chromosome change. This finding is discussed in relation to cytogenetic analyses on uterine leiomyomas and leiomyosarcomas reported previously.

Effective multimodality treatment of epithelial ovarian tumors.

Forty patients with epithelial ovarian tumors underwent cyto-reductive surgery followed by a five drug (Adriamycin, D.D.P.

Role of glycosidases in human ovarian carcinoma cell mediated degradation of subendothelial extracellular matrix.

Penetration of the extracellular matrix (ECM) by tumor cells, an event which occurs at various stages of the metastatic process, involves tumor cell glycosidase mediated hydrolysis of proteoglycans (PG). Recently, we observed that human ovarian carcinoma cell lines (HOCC) derived from primary tumors, peritoneal effusions, and distant metastases possess a varying ability to degrade radiolabeled PG of the ECM, while normal cells (human mesothelial cells or ovarian fibroblasts) fail to do so. To determine whether a quantitative relationship exists between glycosidase activity and degradation of ECM, both intracellular and extracellular glycosidase activities were measured for HOCC and normal cell lines.

In vitro degradation of extracellular matrix by human ovarian carcinoma cells.

Better in vitro models are needed to elucidate the mechanisms underlying tissue destruction by human tumor cells. To address this matter recently isolated and characterized human ovarian carcinoma cell lines derived from either primary tumors, ascitic effusions or metastatic growths were plated in direct contact with extracellular matrix (ECM) previously deposited on culture dishes by bovine corneal endothelial cells. Light and electron microscopy of four of the five ovarian tumor cell lines demonstrated morphologic digestion with penetration of ECM by tumor cell microvilli, along with associated rarefaction.

Borderline malignant serous tumors of the ovary maintained on extracellular matrix: evidence for clonal evolution and invasive potential.

Four cases of advanced stage (II or III) and one case of early stage (IC) borderline malignant serous cystadenocarcinomas of the ovary were maintained on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Cells harvested for chromosomal analysis after 2-3 days showed diploid or near-diploid modalities in all cases. Banded chromosome studies in two cases revealed nonrandom clonal abnormalities with trisomy 2, 7, and 12 in seven of 13 metaphases.

Adhesion, growth and morphology of human mesothelial cells on extracellular matrix.

Human mesothelial cells (HMC) cover a variety of serosal surfaces and have been shown to rest upon an underlying subcellular basement membrane in vivo. Bovine corneal endothelial cells produce an extracellular matrix (ECM) in vitro that mimics HMC subcellular basement membrane and was found to modulate HMC adhesion, morphology and proliferation in vitro. Our results indicated that within minutes after plating, a high percentage (greater than 80%) of HMC firmly attached to ECM.

Methodologic advances in the cytogenetic analysis of human solid tumors.

The major obstacle to successful cytogenetic analysis of human solid tumors is the acquisition of sufficient numbers of good quality metaphases for detailed cytogenetic analysis. At present, no single methodologic approach has been proven to provide successful chromosomal analysis of all human solid tumors. The technical aspects of cell culture, chromosome harvesting, and chromosome banding were the focus of considerable discussion during the First Workshop on Chromosomes in Solid Tumors.

Extracellular matrix-coated culture dishes: an in vitro model for primary human gynecologic tumors.

Culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells were utilized to investigate human gynecologic carcinomas of epithelial origin. A high culture success rate was achieved for both solid tumor (83%) and ascitic fluid (75%) derived from specimens from 59 patients. Because of the high percentage of tumor cells attaching to the ECM and actively proliferating, a variety of in vitro studies (karyotypic analysis, morphologic appearance on ECM, and ability to digest the ECM) could be done.

Interactions of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix. An in vitro model system for studying tumor cell adhesion and invasion.

Human ovarian tumors metastasize by direct extension into the peritoneal cavity leading to tumor cell implantation onto peritoneal surfaces. Successful formation of peritoneal implants is dependent on the ability of ascitic tumor cells to infiltrate the mesothelium, and become firmly adherent to the underlying extracellular matrix (ECM). In order to investigate this process in more detail, an in vitro model system was developed employing human mesothelial cells grown on ECM-coated culture dishes.