Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide.

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.

Inhibitory effect of luteinising hormone-releasing hormone analogues on human endometrial cancer in vitro.

We studied the effects of luteinising hormone-releasing hormone (LHRH) agonist leuproreline (1 microM for 96 h) and LHRH antagonist cetrorelix on the cell growth of primary cultures from nine human endometrial cancers using the sulphorhodamine colorimetric test. Histological examinations and reverse transcription and polymerase chain reaction amplification (RT-PCR) for LHRH receptors were also performed. The endometrial cancers examined had a medium to high degree of proliferative activity and a low degree of apoptotic power; furthermore, they expressed the LHRH receptor RNA variably, detectable in 71% of cases. The addition of leuproreline or cetrorelix to cell cultures inhibited growth in a statistically significant way compared to untreated control cells; nevertheless, the percentage of cell growth inhibition obtained was very variable. These data suggest that LHRH analogues can exert differential inhibitory effects on the growth of endometrial cancer, which seems to be independent of the expression of specific LHRH receptors.

Differential inhibitory effects on human endometrial carcinoma cell growth of luteinizing hormone-releasing hormone analogues.

In addition to its function as a key hormone in the regulation of the pituitary-gonadal axis, luteinizing hormone-releasing hormone (LHRH) probably also affects various extrapituitary tissues. LHRH binding sites and in vitro antiproliferative effects of LHRH analogues have been reported in human endometrial cancer. The effects of the LHRH agonist leuproreline and LHRH antagonist antide were studied on the cell growth, DNA synthesis, and cell cycle distribution of the human endometrial cancer cell lines HEC-1A and HEC-1B by the sulforhodamine B (SRB) method, [3H]thymidine assay incorporation, and propidium iodide DNA staining, respectively. In the presence of 1.0-100 microM leuproreline the proliferation of HEC-1A cells was significantly reduced as early as 3 days after drug exposure, with a minimum growth value of 69.9 +/- 3.6% (mean +/- SE) at the highest concentration tested (100 microM). Similar antiproliferative effects were obtained following a 6-day treatment with the LHRH antagonist antide. Also, inhibitory effects on [3H]thymidine incorporation into the DNA of the HEC-1A cell line were noted after a 6-day exposure to both LHRH analogues, in the above-mentioned concentration range. Cell cycle analysis of HEC-1A cells cultured in the presence of 10 microM leuproreline and antide showed a slight accumulation of cells in the G0/G1 phase, while the proportions of cells in the S and G2/M phases concomitantly decreased. No significant effects on proliferation, DNA synthesis, and cell cycle distribution were observed in HEC-1B cells with either leuproreline or antide (up to 100 and 10 microM, respectively) after a 6-day exposure. Both Northern blot analysis and reverse transcription polymerase chain reaction failed to detect expression of mRNA for the LHRH receptor in both HEC-1A and HEC-1B cell lines. In addition, the LHRH analogues did not affect the intracellular free calcium concentration, indicating that the classic signal transduction for LHRH is absent or impaired in HEC-1A cells. The observed direct inhibitory actions on HEC-1A cells support the concept that the two LHRH analogues may exert biological effects via cellular effectors distinct from the "classic" LHRH receptor. Although the mechanism by which these direct actions are produced is still obscure, these results might help to establish the basis for new approaches to the therapy of endometrial cancer.

[Zinc blood levels in 73 puerperal women. Correlation with obstetric and neonatal complications]. / Livelli ematici di zinco in 73 puerpere. Correlazione con complicanze ostetriche e neonatali.

BACKGROUND: Low plasma zinc concentrations in pregnant women have been associated with certain obstetric and foetal complications. However, there is no agreement in previous studies and mediterranean populations have not been extensively studied. METHODS: The plasmatic zinc was tested in 73 mothers, within 24 hours post-partum, in order to evaluate an association between plasmatic zinc and various obstetric and fetal complications. The women were all from the Florence province and were admitted for delivery at the II Maternity Ward of the University of Florence (Third level Center); mothers of twins and foreign mothers were excluded. Subjects were consecutively included in the study. The values pointed out in a control group (n = 28) were compared with the hematic zinc of a) women who delivered by cesarean section (CS) for acute fetal distress or by operative delivery with vacuum extractor (n = 9), b,c) mothers whose children weighted over the 90th (LGA: n = 11) or under the 10th percentile (SGA: n = 13), and d) mothers who delivered prematurely (n = 12). The subjects included in two or more groups, were not considered. RESULTS: The plasmatic zinc of the control group has been significantly higher than that of mothers who delivered by vacuum extractor or by urgent CS (p < 0.0001) and than that of mothers whose newborns were LGA (p < 0.0024). The hematic zinc of the control group is not higher than that of mothers with SGA or premature children. CONCLUSIONS: The conclusions is drawn that even a relative zinc deficiency may negatively potentiate certain obstetric abnormalities in fetal development or in delivering.

Morphological and functional aspects of the endometrium of asymptomatic post-menopausal women: does the endometrium really age?

The morphological and functional aspects of the endometrium were investigated in 28 asymptomatic post-menopausal women to evaluate the ageing phenomenon of this tissue. Haematoxylin-eosin staining showed an atrophic endometrium in 12 cases and a hyperplastic endometrium in the other 16 cases. Masson's trichrome identified moderate fibrosis in all post-menopausal endometrial stroma. Immunohistochemical analyses were performed on the endometrial specimens to evaluate the distribution of the capillary system, the cellular proliferation index and the presence of oestrogen and progesterone receptors. Our data showed a discrepancy between the morphological pictures and the functional aspects of the post-menopausal endometrium. In fact, the morphological pictures suggested an involution of this tissue according to the increase in collagen fibres, the decrease in vascular distribution and the frequent atrophic patterns. On the other hand, data from steroid receptors and the cell proliferation index suggest that post-menopausal endometrium is an active structure. So, endometria from normal post-menopausal women appear to be in a more quiescent state than in a really atrophic condition. This leads to the question: does the endometrium really age?

CA125 in culture medium of preimplantation embryo.

The first stage of the implantation is the adhesion of the embryonic pole of the blastocyst to the decidua. Such a phenomenon has been demonstrated to be dependent on the presence of glycoproteic compounds, produced partly by the decidua and partly by the embryo. CA125 is an antigenic determinant associated to a glycoprotein expressed by various embryonic tissues. The objective of our research has been to measure the production of CA125 by the embryo in the initial phase of its development. Patients were recruited from our in vitro fertilization program. The culture medium used for the oocytes and for the embryos was collected and CA125 levels were measured. The results indicate that there is not a statistically significative difference between the values of CA125 measured in the mediums where a pronucleus or an embryo was present and the negative controls. From our data, therefore, it can be concluded that CA125 expression begins later in the human embryonic development than 8-cells-stage embryo.

I. Aging of the human endometrium: a basic morphological and immunohistochemical study.

OBJECTIVE: To evaluate if human endometrium presents morphological variations suggestive of an age-related decline in endometrial receptivity. STUDY DESIGN: Peri-implantation endometrium of younger (<30 years of age: n = 13) and older (>40 years of age: n = 17) normally menstruating women was studied. Endometrial specimens were routinely fixed in buffered formalin and embedded in paraffin. Sections (5 mu m) were stained with hematoxylin-eosin, periodic acid-Schiff (PAS) and Trichrome conforming to Masson according to conventional histologic examination. Several consecutive sections were used for the following immunohistochemical study: vascular localization (CD34), cellular proliferation index (PCNA), progesterone and estrogen receptors. RESULTS: Using both the traditional morphological evaluation and monoclonal antibodies, no significant differences were found between the endometria of women <30 years of age and those of women >40. CONCLUSIONS: Our results suggest that human endometrium does not age, at least while cyclic hormonal stimulation and menstruation are present.

[Use of a GnRH analogue in the treatment of certain forms of endometrial hyperplasia associated with menometrorrhagia]. / Impiego di un analogo del GnRH nel trattamento di alcune forme di patologia iperplastica endometriale associate a menometrorragia.

Hyperestrogenism is a powerful factor inducing the development of endometrial hyperplasia that in its turn may represent the first step in the natural history of endometrial carcinoma. During menopause it is possible to have a condition to relative hyperestrogenism induced by a residual hormonal activity and by aromatisation of androgens in the adipose tissue. Therapeutical approach in this pathology aims to control hyperplastic development of the endometrial mucosa and to exclude menometrorrhagia. This study has been performed according to an open uncontrolled design in 14 women (4 menopausal women) with abnormal uterine bleeding and hysteroscopic endometrial cystic or adenomatous hyperplasia. At the beginning and at the end of treatment all patients underwent routine biohumoral blood-tests, hysteroscopy and diagnostic curretage. The GnRH analogue (tryptorelin) 3.75 mg 1 ampoule i.m. every 28 days was administered during a 6-month treatment cycle. At the end of therapy bleeding had disappeared in all menopausal women; in the premenopausal group 8 patients have shown a normal menstrual cycle while 2 are still amenorrhoic. The final hysteroscopic evaluation displayed atrophic endometrium in 9 patients and simple proliferative endometrium in 5 cases. Safety was excellent: 3 cases of slight increase of systolic blood pressure and 1 case of slight increase of weight took place. Our results demonstrate therapeutic efficacy of GnRH analogues in the treatment of endometrial hyperplasia with menometrorrhagia either in premenopausal or menopausal women.

Detection of circulating immune complexes in gynecological malignancies.

Extensive studies have demonstrated that immune complexes represent an important affidable tumor marker with a significant value as diagnostic and prognostic indicator of malignant diseases. In this view, we have studied a group of 11 healthy donors and a group of 11 patients with gynecological malignancies, pre- and post-operatively. Blood samples stored at -30 degrees C were tested by a new competitive immunoenzymatic assay (C3bi test). The data obtained, showed significant differences between healthy donors and tumor patients (p less than 0.001). Furthermore it is notable that the results obtained pre- and post-operatively could be proved with further longitudinal studies.

[Interrelationship between oral contraceptives and some parameters of the coagulative-fibrinolytic function (author's transl)].

PIP: The effect of 2 oral contraceptives (OCs) (0.05 mg ethinyl estradiol + 0.250 mg norgestrel; 0.03 mg ethinyl estradiol + 0.125 mg norgestrel) on some parameters of the coagulative-fibrinolytic function was studied in a group of young women 19-26 years of age. To this end, blood samples were taken before OC use and during the 2nd month of suspension after 3, 6, 12, 18, 24, 30, 36, 42, and 48 months of treatment. The parameters examined were: fibrinogen, plasminogen, antithrombin 3, chi 2 macroglobulin, and FDP. The most significant data (presented in tabular form) were: the gradual reduction of antithrombin 3 until the 36th month of treatment, the diminution of chi 2 macroglobulin, the progressive increase of FDP, and the stability of fibrinogen and plasminogen during the period of observation. (author's)^ieng

[Oestroprogestogen interference on some haematochemical parameters: glycaemia, lipid metabolism and hepatic functionality (author's transl)].

PIP: The collateral effects of 2 oral contraceptives (OCs) (0.05 mg ethinyl estradiol + 0.250 mg norgestrel; 0.03 mg ethinyl estradiol + 0.125 mg norgestrel) were studied in a group of young women ages 19-26. These effects were investigated by evaluating some hemato-chemical parameters such as glycemia; lipid metabolism (triglycerides, cholesterol, and total lipids); and hepatic functionality (SGOT, SGPT, serum bilirubin, alkaline phosphatase). Blood samples were taken before OC use and then during the 2nd month of suspension after 3, 6, 12, 18, 24, 30, 36, 42, and 48 months of treatment. This research, carried out over a period of 4 years found no significant variations which would necessitate cessation of treatment. (author's)^ieng