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H Meden

Publications and source records attributed to H Meden.

At least 19 recordsLinked to original sources
PubMed2001

Detection of serum autoantibodies to tumor suppressor gene p53 with a new enzyme-linked immunosorbent assay in patients with ovarian cancer.

Sera from 99 ovarian cancer patients were assayed for serum autoantibodies to p53 using a newly developed enzyme-linked immunosorbent assay (ELISA). Results were compared to the investigation using the former ELISA. The incidence of autoantibodies (25%) was lower using the newly developed ELISA as compared to the previous results (41%). The results were consistent in 79% of patients (P < .001). The incidence of autoantibodies was lower in patients with complete remission (19%) as compared to that of patients with recurrence (30%) and before primary surgery (26%). No statistically significant correlation was found among p53 serum autoantibody status and tumor stage, degree of malignancy, histologic subtype, and residual tumor after primary surgery. Use of the newly developed ELISA resulted in a higher consensus between immunohistochemically negative and autoantibody negative cases. Owing to further purifying of the prepared human recombinant p53. the newly developed ELISA seems to be of higher specificity as compared to the former ELISA.

Adenocarcinoma, Clear Cell↗
PubMed2000

nm23-H1 expression defines a high-risk subpopulation of patients with early-stage epithelial ovarian carcinoma.

The role of the nm23 gene in human ovarian cancer is still controversial. We studied the expression of the nm23-H1 gene in 247 human epithelial ovarian carcinomas. The patients were followed-up until their death, or for a minimum of 5 years if they survived. The expression of the gene was studied by means of immunohistochemistry and a semiquantitative scoring system considering the staining intensity and the number of reactive tumour cells. Patients carrying tumours with higher expression scores (4-6 on a scale from 0 to 6) had a significantly lower survival (P = 0.01) than the rest. Further stratified statistical analysis revealed that this effect was mainly attributable to the subgroup of patients with early-stage (I and II), well- and moderately differentiated tumours. In fact, a multivariate analysis carried out for this subset of patients showed nm23-overexpression to be the only significant independent predictor of an ominous prognosis. The association of nm23-overexpression with a worse prognosis was most probably not due to mutation of the nm23 gene, since mutational analysis in 60 tumours by means of single-strand conformational polymorphism and direct sequencing disclosed only one mutation, which was located outside the open reading frame. Our results seem to indicate that nm23 expression is associated with a significantly worse prognosis in early-stage, well-differentiated epithelial ovarian carcinoma, a finding with important clinical implications, considering that many patients with ovarian cancers showing these features do not undergo any further treatment beyond surgical staging. If confirmed, they could help in tailoring the treatment of these patients in the future.

Aged↗
PubMed1999

Long term results of definitive radiotherapy for cervical carcinoma using four applications of high dose rate afterloading.

BACKGROUND: In definitive radiotherapy for cervical carcinoma, combined modality treatment using external beam radiotherapy and brachytherapy is standard. Although the optimal number of afterloading applications is controversial, the majority of authors recommend three applications. METHODS: In this study, the authors investigated the use of 4 applications with iridium-192 afterloading with a dose of 7.5 grays (Gy). Standardized radiotherapy doses were adapted to the individual tumor anatomy using a prospective schedule. RESULTS: In the 73 study patients, actuarial and tumor-related 5-year survival rates by T classification were: T1b: 30% (100% cause specific survival); T2a: 55% (76% cause specific survival); T2b: 50% (60% cause specific survival); T3a: 50% (67% cause specific survival); T3b: 39% (50% cause specific survival); and T4a: 40% (40% cause specific survival). Morbidity, graded according to the National Cancer Institute's Common Toxicity Criteria (CTC) were low: CTC Grade 1: 7 patients (7.6%); CTC Grade 2: 7 patients (7.6%); CTC Grade 3: 1 patient (1.4%); and CTC Grade 4: 1 patient (1.4%). In a multivariate analysis, the T classification was the only significant independent prognostic factor for actuarial survival, tumor related (cause specific) survival, local tumor control and freedom of metastatic disease. The number of afterloading applications was an independent prognostic factor for local tumor control. CONCLUSIONS: Based on the long term results of the current study, external beam radiotherapy combined with 4 afterloading high dose rate applications (total of 30 Gy) appears to be clinically feasible and results in satisfactory survival rates and few side effects.

Adenocarcinoma↗
PubMed1999

Effects of paclitaxel in combination with radiation on human head and neck cancer cells (ZMK-1), cervical squamous cell carcinoma (CaSki), and breast adenocarcinoma cells (MCF-7).

BACKGROUND AND PURPOSE: The anticancer drug paclitaxel, a natural product from Taxus brevifolia, is a microtubule-stabilising agent, which has been shown to block different cells in the G2/M phase of the cell cycle and so modulate their radioresponsiveness. We investigated the radiosensitizing potential of paclitaxel in human head and neck cancer cells (ZMK-1), in cervical squamous cell carcinoma cells (CaSki) and in breast adenocarcinoma cells (MCF-7). METHODS: ZMK-1 cells were incubated with paclitaxel for 3, 9, or 24 h before irradiation. ZMK-1-, CaSki- and MCF-7 cells were incubated with paclitaxel for 24 h after irradiation. The paclitaxel concentration (70 nM, 7 nM, 0.7 nM) was chosen to obtain equivalent toxicity at the different incubation times (3 h, 9 h, 24 h respectively). Radiation doses were from 0 to 8 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of paclitaxel to cause accumulation of cells in the G2/M phase of the cell cycle. RESULTS: Paclitaxel alone was cytotoxic in a time- and concentration-dependent manner. Up to 36% of the ZMK-1 cells accumulated in G2/M after treatment for 24-36 h. If the cells were incubated with paclitaxel before irradiation the isoeffect enhancement ratios for ZMK-1 cells, determined at the 37% survival level, were 0.81, 1.48 and 1.15 for 3-h, 9-h, and 24-h pre-incubations respectively. For a paclitaxel incubation of 24 h after irradiation, the isoeffect enhancement ratios, determined at the 37% survival level, were 0.72, 0.76 and 1.2 for the ZMK-1. CaSki, and MCF-7 cells respectively. CONCLUSION: In the three cell lines no radiosensitizing effect of paclitaxel could be demonstrated unambiguously. The use of asynchronized cells or the support of cellular repair mechanisms while the cells are blocked in G2/M could partly explain the results.

Adenocarcinoma↗
PubMed1999

[Efficiency, safety and tolerability of recombinant human interleukin-3 (rhIL-3) as supportive therapy accompanying dose-intensive carboplatin containing chemotherapy in ovarian cancer with special regard to thrombocytopenia].

OBJECTIVE: In a prospective, randomized, placebo-controlled double-blind trial we evaluated to what extent a dose-intensification of adjuvant chemotherapy is possible with the help of Interleukin-3 (rhIL-3). MATERIAL AND METHODS: Following initial surgery, 12 patients with primary ovarian cancer have been treated with Carboplatin and Cyclophosphamide (dosage: AUC 4 according to Calvert). After randomisation, a group of 6 patients prophylacticly received rhIL-3 against myelosuppression on days 3-12 of the cycle, in contrast to a group of 6 patients who received placebo-injections. RESULTS: The patients treated with rhIL-3 showed less hematologic side-effects. Adherence to 4-weekly chemotherapy courses was more frequent in the rhIL-3-group (73% vs. 44%, p = 0.005). An intensification of the chemotherapy with 3-weekly courses did not succeed significantly. Observed side-effects of rhIL-3-therapy were headaches, fever, flu-like symptoms, rashes and blisters at the site of injection which excluded 2 of 6 patients from the study. CONCLUSIONS: Supportive rhIL-3 to adjuvant Carboplatin-based chemotherapy enables a better keeping of 4-weekly courses in contrast to the placebo-group due to faster recovery of hematologic parameters. Due to the side-effects, of IL-3, this cytokine cannot be recommended for routine clinical use.

Adult↗
PubMed1998

Activated protein C resistance and factor V Leiden in patients with hemolysis, elevated liver enzymes, low platelets syndrome.

OBJECTIVE: Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is characterized by a distinct activation of the coagulation system. A mutation of the gene coding for coagulation Factor V (Factor V Leiden) has been identified as the most frequent risk factor for thrombosis. To identify risk factors for HELLP syndrome, we determined coagulation parameters and the Factor V Leiden mutation in women who previously had developed HELLP syndrome. METHODS: Coagulation parameters (activated protein C resistance, antithrombin, protein C, protein S) were determined in 21 women 6 months to 9 years after they had developed HELLP syndrome in the third trimester. In addition, these women were analyzed for the presence of the Factor V Leiden mutation. RESULTS: Of these analyzed women, 33% (seven of 21) had an activated protein C resistance (activated protein C ratio less than 2.0). Another 38% of the women had subnormal activated protein C ratios (2.0-2.3). Only 57% of the women with an activated protein C resistance were identified as heterozygous carriers of the Factor V Leiden mutation (four of seven). CONCLUSION: Women with HELLP syndrome have a higher incidence of Factor V Leiden mutations. This increased incidence does not, however, account fully for the increased frequency of activated protein C resistance in these patients.

Adult↗
PubMed1998

Expression of the c-erbB-2-encoded oncoprotein p185 (HER-2/neu) in pregnancy as a model for oncogene-induced carcinogenesis.

Although oncogenes are involved in tumor development and progression, their activation during human ontogenesis is inseparably associated with normal fetal development. The c-erbB-2-encoded oncoprotein p185 (HER-2/neu) is overexpressed on fetal epithelial cells, in the placenta, and in several human carcinomas. In patients with p185-overexpressing tumors and in pregnant women at term, increased serum levels of a 105 kDa proteolytic breakdown product corresponding to the extracellular domain of oncoprotein p185 are detectable. Estrogens have been described to be potent inhibitors of p185 expression in human breast cancer cells and to influence also p105 serum levels in females. Regarding the significantly poorer prognosis of patients with c-erbB-2-positive tumors, we discuss common features and differences between c-erbB-2 oncoprotein overexpression in pregnancy and in carcinogenesis.

Cell Transformation, Neoplastic↗
PubMed1998

Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer.

Drug resistance is one of the most important clinical problems in the treatment of ovarian cancer. This study was designed to determine whether expression of p53 could be used as a marker for predicting the response to chemotherapy of ovarian cancer. Tissue blocks were obtained from 187 patients with diagnosed untreated ovarian cancer. Paraffin sections from the primaries were immunohistochemically analysed for p53 expression. All patients underwent platinum-based chemotherapy after surgery. We analysed whether the number of chemotherapy cycles was related to survival in women with p53 positive and p53 negative ovarian cancer. 27/187 cases were p53 positive. Expression of p53 was associated with other factors of unfavourable prognosis. Patients with p53 positive tumours had a significantly worse prognosis compared with patients with p53 negative tumours (P = 0.037). There was a statistically significant dose-response effect of platinum-based chemotherapy in patients with p53 negative tumours, which could not be seen in patients with p53 positive tumours (P = 0.01 versus P = 0.553). This could also be observed in patients with residual tumour after surgery (P = 0.0001 versus P = 0.8866). Expression of p53 may be an additional useful marker in predicting response to chemotherapy. Thus, it is possible to identify a subgroup of patients who may benefit from alternative therapy regimens.

Adult↗
PubMed1998

Overexpression of the oncogene c-erbB-2 (HER2/neu) and response to chemotherapy in patients with ovarian cancer.

This study was designed to determine whether c-erbB-2 overexpression could be used as a marker to identify a subgroup of patients with ovarian cancer more likely than others to benefit from chemotherapy. Paraffin sections from tissue blocks from 208 patients with newly diagnosed untreated ovarian cancer were analyzed for c-erbB-2 overexpression. All patients underwent postoperative platin-based chemotherapy. Patients with c-erbB-2 positive tumors had a significantly worse prognosis as compared to patients with c-erbB-2 negative tumors (p = 0.0003). c-erbB-2 findings were not related to tumor stage or histologic findings. There was clear evidence of a dose-response effect with regard to survival in patients with c-erbB-2 negative tumors, which could not be seen in patients with c-erbB-2 positive tumors (p = 0.0341 vs p = 0.3775). We conclude that there is a significant total dose-response effect of platin-based chemotherapy in ovarian cancer patients without overexpression of c-erbB-2 but not in patients with c-erbB-2 overexpression. Overexpression of c-erbB-2 may be a useful marker to identify patients who are most likely to benefit from high-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical study of 54 cases.

OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras expression and ploidy in borderline tumors of the ovary by assessing their frequency, and relationship to histologic type, tumor recurrence and survival. METHODS: Fifty-four patients with borderline tumors were followed 3-140 months (median: 38 months). Paraffin-embedded sections were stained using monoclonal antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras. The immunohistochemical findings were correlated to histologic subtype, tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24% (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive, Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl-2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases, respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER-2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with ovarian borderline tumors. Further studies to evaluate their prognostic value are warranted.

Adult↗
PubMed1998

Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma.

PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS AND METHODS: In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.

Adult↗
PubMed1997

The effect of paclitaxel on the radiosensitivity of gynecological tumor cells.

BACKGROUND: Paclitaxel, a natural product from Taxus brevifolia, is a microtubule stabilizing agent, which has been shown to block different cells in the G2/M phase of the cell cycle and consequently, to modulate their radioresponsiveness. Our aim was to test the cytotoxic and radiosensitizing potential of paclitaxel, with respect to different gynecological tumors with varying radiosensitivities. MATERIAL AND METHOD: We performed clonogenic assays and flow cytometry on 2 cell lines, MCF-7 (breast) and CaSki (cervix) cells, and on 2 primary ovarian tumor samples (OC-I and OC-II). The cells were irradiated with 200 kV X-rays, radiation doses of up to 8 Gy were applied either as single doses or in 2 Gy fractions. Paclitaxel concentrations varied from 0.07 to 700 nM, incubation times varied from 3 to 120 h. RESULTS: Paclitaxel alone changed the cell cycle distribution of the cells tested and was cytotoxic in a time and concentration dependent manner. When combined with radiation, most schedules resulted in additive effects of the combined treatments. However, for MCF-7 cells, when 7 nM paclitaxel, applied 24 h before irradiation, were combined with fractionated irradiation a supra-additive effect with a SER of 1.2 was found. For CaSki cells, under comparable conditions the SER was 1.13 but the effects were not statistically significant. CONCLUSION: Under specific conditions, paclitaxel exerted a weak radiosensitizing effect on breast and cervical carcinoma cells. A therapeutic gain may be possible on the basis of an optimal paclitaxel/radiation scheduling.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new prognostic factor.

Ovarian cancer is the leading cause of death in gynecological cancers. To date, there are no prognostic factors in ovarian cancer that adequately account for tumor biology and the course of the disease. In recent years, some reports have described the prognostic significance of the amplification and overexpression of the oncogene c-erbB-2 (HER2/neu) in various human cancers, including ovarian cancer. The c-erbB-2 proto-oncogene is located on the long arm of chromosome 17. It encodes a 185 kD transmembrane glycoprotein receptor (p185HER2) that has sequence similarities with the epidermal growth factor receptor (EGF-R). In ovarian cancer, the percentage of c-erbB-2 positive cases varies from 9 to 32%. Correlation with tumor stage and the degree of histological differentiation was not observed. The overexpression of c-erbB-2 is a new and statistically independent prognostic factor. The overexpression of oncogene c-erbB-2 in ovarian cancer can-be detected by immunohistochemistry staining for the protein p185 and characterizes a group with unfavorable tumor biology and a significantly worse prognosis. Elevated serum levels of the c-erbB-2 oncoprotein have been identified in patients with various cancers known to overexpress the c-erbB-2 oncogene. The detection of a p185 oncoprotein fragment in the sera of ovarian cancer patients was recently published by our group. Antiproliferative effects of monoclonal antibodies directed against p185 have been demonstrated in breast cancer patients. This may lead to a new approach in ovarian carcinoma therapy, too, over and above the diagnostic aspects.

Female↗
PubMed1997

Extended phase II study of paclitaxel as a 3-h infusion in patients with ovarian cancer previously treated with plantinum.

An extended phase II study was performed to evaluate single-agent paclitaxel as salvage chemotherapy for ovarian cancer. The aim of this study was to evaluate the 3-h infusion schedule of paclitaxel in terms of toxicity and antitumour efficacy. Furthermore, we analysed the impact on response and survival of the extent of prior chemotherapy and status of resistance against platinum. This study was an open, non-randomised, multicentre trial. The dose of paclitaxel used was 175 mg/m2 in patients who had received one or two prior therapies, and 135 mg/m2 in patients who had received three prior therapies. Paclitaxel was given as a 3-h infusion. Courses were repeated every 3 weeks. 114 patients with platinum-pretreated epithelial ovarian cancer were recruited of whom 112 were found eligible and evaluable for toxicity. 104 patients with bidimensionally measurable disease who received more than one course of chemotherapy were evaluable for response, progression-free (PFS) and survival. Toxicity was generally manageable. Main toxicities were non-cumulative neutropenia with 22.3% of courses with WHO grade 3/4 and peripheral neuropathy which occurred in more than half of the courses and was of WHO grade 2 and 3 in 20.1 and 1.3% of the courses, respectively. Neuropathy was associated with the higher dose per course and with cumulative paclitaxel dose. Objective responses were reported in 20% (21/104) of the patients (95% CI 13-29%) with a median response duration of 36.7 weeks. Survival and PFS for the whole group were 45.9 and 15.1 weeks, respectively. Performance status, number of tumour lesions and extent of prior chemotherapy were found to be prognostic factors for survival. Extent of prior chemotherapy was the only prognostic factor for PFS. Platinum resistance did not predict response to treatment. Paclitaxel 175 mg/m2 given as a 3-h infusion is an appropriate treatment for patients with platinum-resistant ovarian cancer who have not previously received more than two chemotherapy regimens. Paclitaxel did not show results superior to historical data for platinum retreatment in patients with platinum-sensitive, recurrent ovarian cancer.

Adult↗
PubMed1997

A simple and reliable reverse-phase high-performance liquid chromatographic procedure for determination of paclitaxel (taxol) in human serum.

A simple, fast, and reliable isocratic (mobile phase: acetonitrile/methanol/water [48/11/41], reverse-phase (C18 column) high-performance liquid chromatography method for the determination of paclitaxel concentration in human serum is presented. The procedure uses a new and convenient one-step sample-purification procedure that requires only 400 microliters of sample and uses N-heptylbenzamide as an internal standard. Paclitaxel is detected by UV absorbance measurement at 227 nm. The method has a broad linear range (0.01 to 10 mg/l, or 0.012 to 11.7 mumol/l; r > 0.999), and the detection limit is 0.01 mg/l (0.012 mumol/l). The deviation from target value is < or = 1.5%, and coefficients of variation are < or = 13.8% within runs and < or = 15.3% between runs. Recovery paclitaxel is > or = 92.6%. No interferences were observed from endogenous compounds or from more than 30 drugs that may be administered with paclitaxel. Docetaxel, which is not concurrently administered, coeluted with paclitaxel. Compared with previously published high-performance liquid chromatography procedures for the determination of paclitaxel, the particular advantage of the method presented here is its simple and rapid single-step sample-purification procedure, which makes a high recovery of paclitaxel from serum samples possible and results in a pure extract, avoiding interferences from endogenous compounds. The method is suitable for pharmacological studies and routine analysis.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Elevated serum levels of the c-erbB-2 encoded oncoprotein fragment in cases of pure preeclampsia and HELLP syndrome.

OBJECTIVE: During normal human ontogenesis an overexpression of the c-erbB-2 encoded oncoprotein p185 (HER2/neu) occurs in the placenta and on fetal epithelial cells. It is accompanied by the increase of a 105 kD fragment (p105) in both maternal serum and cord blood. We examined whether p105 levels in maternal serum are influenced by destructions of placental tissue, fetal growth disturbances and placental circulation disorders. METHODS: We analysed p105 serum concentrations in patients with abortion (n = 25), ectopic pregnancy (n = 5), intrauterine growth retardation (n = 9), pregnancy induced hypertension (n = 24) and compared them with normal pregnancies of a corresponding gestational age. RESULTS: Patients with abortions showed normal p105 values. Intrauterine growth retardation was associated with lower p105 levels (p < 0.05) whereas patients with pure preeclampsia (p < 0.001) and HELLP syndrome (p < 0.05) had significantly higher levels. CONCLUSION: The elevation of p105 in sera of preeclamptic women could be due to an increased fetomaternal transfer of p105.

Abortion, Missed↗
PubMed1997

In vivo effects of estrogens on c-erbB-2 oncoprotein levels in chorionic villous tissue and maternal serum.

The c-erbB-2-encoded oncoprotein p185 (HER2) is overexpressed in the fetal epithelium, the placenta and several carcinomas. Elevated serum levels of the released ectodomain (p105) were found in cancer patients and pregnant women at term. In cultured breast cancer cells estradiol inhibited p185 expression and induced growth arrest. These results prompted us to investigate the in vivo influence of serum estradiol and estriol on c-erbB-2 protein levels in pregnancy. We examined chorionic villous tissue extracts and maternal sera obtained from six legal abortions in the first trimester and 20 vaginal deliveries at term. For quantification of c-erbB-2 protein we employed an ELISA. In the first trimester maternal p105 serum levels were significantly (p < 0.0001) lower and p185 tissue levels significantly (p < 0.05) higher than in the third trimester. The highest p105 values were found in additionally examined cord blood. Interindividual regression analyses yielded inverse correlation between estradiol concentrations and placental p185 expression in the first (r = -0.58) and third trimester (r = -0.38) as well as p105 serum levels in the first trimester (r = -0.83). Estriol was correlated positively with p105 values in maternal and umbilical serum but not with placental p185 expression. We conclude that estradiol down-regulates p185 expression in pregnancy whereas the level of maternal p105 depends on the total amount of fetoplacental p185.

Chorionic Villi↗