Differential expression of galectin-1 and galectin-3 during first trimester human embryogenesis.

Development of complex organisms requires specific temporospatial differentiation and expression of the correct phenotype through activation of a variety of genes. Galectins are mammalian lectins able to interact with various extracellular matrix glycoconjugates and have been implicated in several biological events including cell attachment, differentiation, apoptosis, embryogenesis, and cancer invasion and metastasis. In this study, we have examined the expression of galectin-1 and galectin-3 during human first trimester embryogenesis using immunohistochemistry and Western blotting. Variable amounts of galectin-1 and galectin-3 were detected in all tissue protein extracts. Galectin-1 expression was demonstrated in the connective tissue and derived tissues such as smooth and striated muscle cells, and in some epithelia, such as in the basal layers of the skin after 14 weeks and in the epithelial cells of the gonads. Galectin-3 was detected mainly in epithelia, such as the skin, epithelial lining of the digestive and respiratory tract, and urothelium and excretory tubes of the kidney, but also in the myocardial cells, in the peripheral and preossifying hypertrophic chondrocytes, and in the notochord and in the liver. Our study constitutes the first demonstration of galectin-1 and galectin-3 during human embryogenesis. The differential expression of these two lectins suggests that they could participate in the complex processes of tissue differentiation.

Comparison of two estradiol transdermal systems (Oesclim 50 and Estraderm TTS 50). II. Local skin tolerability.

OBJECTIVES: The objectives were to compare the local skin tolerability of a matrix-type estradiol transdermal system, Oesclim 50, with that of the reservoir-type system, Estraderm TTS 50. METHODS: Two randomised studies were performed. In the first study, the modified Draize-Shelanski-Jordan method of sensitization was used in an open, parallel-group trial to compare the cutaneous tolerability of repeated applications of Oesclim 50 with that of Estraderm TTS 50 in 24 healthy postmenopausal women. The second study was an open, randomised, parallel-group, multi-centre clinical trial involving 283 healthy menopausal women. A total of 143 women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS 50. The treatment duration was four months. RESULTS: The first study showed that the treatments, Oesclim 50 and Estraderm TTS 50, had no sensitizing potential and did not induce allergic reactions. In the second study, 4.2% of applications in the Oesclim group provoked reactions compared with 9.5% in the Estraderm group (P < 0.001). Thirty-seven patients (25.9%) treated with Oesclim and 55 patients (39.9%) receiving Estraderm experienced one or more reactions (P < 0.05). Redness and itching were the most frequent types of application site reaction in both treatment groups. The durations of the reactions were significantly shorter in the Oesclim group (P < 0.01), with a higher percentage of durations of less than 1 h and a lower percentage of durations of over 48 h than in the Estraderm TTS 50 group. None of the reactions in the Oesclim group led to premature removal of the patch, compared with 11 (3.4%) in the Estraderm group (P < 0.05). The number of patients who discontinued treatment due to application site reactions was one (0.7%) in the Oesclim group and seven (5.1%) in the Estraderm group (P < 0.05). Efficacy and general safety were comparable in the two treatment groups. CONCLUSIONS: In the first study, neither Oesclim nor Estraderm induced allergic reactions. In the second study, the local skin tolerability of Oesclim was significantly better than that of Estraderm, in terms of the number, duration and severity of the application site reactions.

Comparison of two estradiol transdermal systems (Oesclim 50 and Estraderm TTS 50). I. Tolerability, adhesion and efficacy.

OBJECTIVES: The objectives were to compare the tolerability, adhesion and efficacy of a new matrix-type estradiol transdermal system, Oesclim 50, with those of Estraderm TTS 50, a reservoir-type system. METHODS: This was an open, randomised, parallel-group, multi-centre clinical trial, performed in six European countries. A total of 143 healthy menopausal women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS 50. The transdermal systems were applied twice weekly for 24 days out of each 28-day cycle, over a period of four cycles. Oral progestogen treatment was taken by non-hysterectomised patients for the last 12 days of estrogen therapy in each cycle. RESULTS: The local skin tolerability of the Oesclim 50 transdermal system was significantly better than that of Estraderm TTS 50. In the Oesclim 50 group, 4.2% of applications caused a reaction, compared with 9.5% in the Estraderm TTS 50 group (P < 0.001). Safety assessments showed both treatments to be well tolerated. Seven patients in the Oesclim 50 group, and 12 in the Estraderm TTS 50 group, discontinued due to adverse events. Of these discontinuations, one (0.7% of patients) in the Oesclim 50 group and seven (5.1% of patients) in the Estraderm TTS 50 group were due to application site reactions (P < 0.05). There was no statistically significant difference between the two groups in the percentage of patients with signs of hyperestrogenism (29 patients (20.3%) in the Oesclim group and 28 patients (20.0%) in the Estraderm TTS 50 group). Adhesion was significantly better for the Oesclim 50 transdermal system, with 6.0% of Oesclim 50 applications becoming detached compared with 11.3% of Estraderm TTS 50 applications (P < 0.001). The greater adhesion of Oesclim 50 was particularly apparent when the systems were exposed to water, with three times fewer Oesclim 50 systems becoming detached during a shower or bath (P < 0.001 in each case). Both treatments produced significant and comparable improvements in vasomotor symptoms, other menopausal symptoms and gynaecological assessments. A near-maximal effect on vasomotor symptoms was observed after approximately 1 month of treatment, and was maintained for the entire treatment period. CONCLUSION: Overall, Oesclim 50 provided statistically significantly better local skin tolerability and adhesion than Estraderm TTS 50, together with comparable efficacy and safety.

[Epithelial cancers of the ovary. Recent trends]. / Cancers épithéliaux de l'ovaire. Acquisitions récentes.

Ovarian carcinomas constitute the major cause of the mortality and morbidity in gynaecology. Most ovary carcinomas are epithelial tumours. Our understanding of ovarian cancerogenesis has been hampered by the lack of a well defined precursor lesion, the lack of knowledge about tumour progression, and by the relative inaccessibility of the ovaries in the abdominal cavity. Recent studies using experimental models allow us to better define the fundamental mechanisms of carcinogenesis from the serous ovarian cells and of invasion of the abdominopelvic cavity by proximity. This review article tries to update on epidemiology, genetic syndromes, biology, screening, and therapy of these epithelial tumours, and about the new directions taken by basic and clinical research. We will present data concerning oncogenes and tumour suppressor genes involved in epithelial ovarian tumours, regulation of tumour cells by growth factors, genes involved in tumour invasion, and mechanisms used by the cancer cell to resist to therapies. Non-epithelial ovarian tumours will not be examined in this manuscript.

Inverse expression of two laminin binding proteins, 67LR and galectin-3, correlates with the invasive phenotype of trophoblastic tissue.

Tumor invasion of host tissues and trophoblastic penetration of the endometrium share common biological features. Both processes involve the invasion of basement membranes, an event that is initiated by adhesion of cancer or trophoblast cells to basement membrane components and particularly to laminin. Adhesion to this latter glycoprotein is mediated through a variety of cell surface receptors. We have previously shown that the 67 kD Laminin Receptor (67LR) and a 31 kD Human Laminin Binding Protein, recently renamed galectin-3, are inversely modulated as the invasive phenotype of cancer cells progresses, with up regulation of the former, and down regulation of the latter, respectively. In this study, we examined the expression of these two proteins in 27 human trophoblastic specimens at different gestational ages using Northern and Western blot techniques. Expression of the 67LR increased from 7 weeks to a maximum at 12 weeks, when invasion is maximal, and then decreased. Expression of galectin-3 was inversely modulated by the gestational age, with a minimum expression at 12 weeks. Our data demonstrate that invasive trophoblast displays the same pattern of laminin binding proteins expression than invasive cancer cells, and further demonstrates that invasion of the extracellular matrix by trophoblast and cancer cells share common molecular mechanisms.

[Tamoxifen in the treatment of breast cancer]. / Le tamoxifène dans le traitement du cancer du sein.

Tamoxifen is the most often prescribed non steroidal antioestrogenic agent in the world for breast cancer. Worldwide collaboration. has centralized the results, of different trials throughout the world on oral adjuvant therapy in the early stages of breast cancer. A significative regression of the tumour was observed in most cases. Moreover, recent epidemiological studies suggest that tamoxifen could prevent new contralateral primary tumours. The risk of the disease should thus be reduced by the prophylactic use of antioestrogens such as tamoxifen. Investigations using a variety of models have evaluated the effect of tamoxifen on tumour promotion and cell growth. Tamoxifen-induced growth inhibition is associated with major changes in biochemical events in cultured human breast cancer cells including cell proliferation or growth factor production. Growth inhibition of oestrogen-responsive human breast cancer cells is associated with an induced secretion of autoinhibitory polypeptides (TGF beta) and an antagonistic effect on the synthesis of proliferative proteins (TGF alpha,...). The first step in the mechanism of action of the drug is binding of tamoxifen to the oestrogen receptors. Development of resistance to tamoxifen treatment is a great problem in treatment of breast cancer patients and the mechanism of resistance will require further study: under the influence of the drug, tumours could become remodelled as selected subpopulations emerge resistant-tamoxifen. The fact that some breast cancers which are oestrogen receptor-negative respond to antioestrogen suggests that parallel but separate pathways for oestrogen and antioestrogen action may exist. This paper summarizes the results of the most recent studies concerning this promising drug.

Study of the artefacts induced by linear array transvaginal ultrasound scanning in urodynamics.

In patients with incontinence problems, endovaginal urodynamic ultrasonography is a technique which easily complements manometric examination by permitting a precise study of peri-urethral soft tissue. Use of a linear array probe under standardised conditions gives, at present, the best results. To validate the technique, it is, however, important to understand the artefacts it provokes. Thirty-four patients underwent urethral profilometry at rest and during effort with and without the ultrasonographic probe. In the patients studied, none of the classical urodynamic parameters were modified. However, in cases of narrow vaginas (distance between the arcuate ligament and the ultrasonographic probe less than 12 mm), a small increase in the maximum urethral closure pressure (5 cm H2O) could be observed. The angle between an intra-urethral cotton swab and the horizontal plane was measured at rest and during maximum coughing effort, both with and without the ultrasonographic probe. A significant reduction of the angle was observed at rest and during effort. However, since linear regression is particularly effective in modelling these two artefacts (R2 = 0.8 and 0.7), they can be considered as constants and are not bothersome in clinical practice. Abdominal ultrasound was used in 10 patients during the introduction of the endovaginal ultrasonographic probe to study its impact on the base of the bladder. A clear increase in the posterior urethro-vesical angle was observed, which was shown to be a function of the degree of probe insertion in the vagina. As this artefact was variable and could not be controlled, this angle should no longer be measured using this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

[Utero-trophoblastic interface: transitory stage in human placentation]. / L'interface utérotrophoblastique: étape transitoire de la placentation humaine.

In the past, the intervillous space of the human placenta has been studied on samples provided by spontaneous abortions. Using the endocavitary ultrasonography and the chorionoscopy in normal pregnancies, the intervillous space during the first trimester has been observed as filled by a plasmatic fraction cell free of the maternal blood. During the first trimester, the human placenta doesn't have its theoretical functional specificities.