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Biomedical subjects

Jean-Christophe Noel

Publications and source records attributed to Jean-Christophe Noel.

9 recordsLinked to original sources
PubMed2006

Proliferating activity in columnar cell lesions of the breast.

With the introduction of mammographic screening, columnar cell lesions (CCLs) are observed more and more frequently because they are often associated with microcalcifications. Until now, the proliferative activity of these lesions has not been previously evaluated. Ki67 index was performed by immunohistochemistry in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade intraductal carcinoma (DIN 2-3 n = 20). Adjacent terminal duct-lobular unit (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA, in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean 8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS). Lastly, the Ki67 index is higher in DIN 2-3 (mean 25.4%) than in CCLs without atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells with columnar configuration but different proliferative characteristics. These data represent findings of biological interest which could help us to better understand these controversial lesions.

Breast↗
PubMed2006

Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation.

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.

Aged↗
PubMed2005

Mapping labels in the human developing visual system and the evolution of binocular vision.

Topographic representation of visual fields from the retina to the brain is a central feature of vision. The development of retinotopic maps has been studied extensively in model organisms and is thought to be controlled in part by molecular labels, including ephrin/Eph axon guidance molecules, displayed in complementary gradients across the retina and its targeting areas. The visual system in these organisms is primarily monocular, with each retina mapping topographically to its contralateral target. In contrast, mechanisms of retinal mapping in binocular species such as primates, characterized by the congruent, aligned mapping of both retinas onto the same brain target, remain completely unknown. Here, we show that the distribution of ephrin/Eph genes in the human developing visual system is fundamentally different from what is known in model organisms. In the human embryonic retina, EphA receptors are displayed along two gradients, sloping down from the center of the retina to its periphery. The EphB1 receptor, which controls the ipsilateral routing of retinal axons in the mouse, is expressed throughout the human temporal retina in coordination with the changes in EphA gene expression. In the dorsal lateral geniculate nucleus, ephrin-A/EphAs are displayed along complementary retinotopic gradients. Our data point to an evolutionary model in which the coordinated divergence of the distribution of the receptors controlling retinal guidance and retinal mapping enabled the emergence of a fully binocular system. They also indicate that ephrin/Eph signaling plays a potentially major role in the development of neuronal connectivity in humans.

Biological Evolution↗
PubMed2002

Desferrioxamine enhances AIDS-associated Kaposi's sarcoma tumor development in a xenograft model.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, we have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS). We have also shown that the iron chelator desferrioxamine (DFO) has a potent anti-KS activity in vitro, suggesting that it may represent a potential therapeutic approach for the treatment of KS. The present study was designed to investigate the effect of DFO on the growth of human KS xenografts in immunodeficient mice. Unexpectedly, we found that mice treated with DFO (400 mg/kg, 3 times weekly) (n = 30) exhibited a marked enhancement of tumor growth compared with control mice (n = 33) (230 +/- 134 mm(2) versus 143 +/- 70 mm p < 0.01). No enhancement of tumor growth was seen in mice treated with iron-saturated DFO. At least 2 findings suggest that this paradoxic pro-KS activity occurred independently of mice iron stores. First, treatment with DFO had only a marginal effect on ferritin and hematocrit levels. Second, induction of effective iron depletion by an iron-poor diet (6.7 mg iron/kg diet) (n = 23) did not have a deleterious effect on the growth of the KS xenografts. The lesions obtained from the DFO-treated animals exhibited a significantly decreased apoptotic index (p < 0.05), indicating that some antiapoptotic mechanism induced by DFO may be operating in vivo to favour tumor growth. In conclusion, our data show that DFO has a stimulatory effect on KS growth in immunodeficient mice, suggesting that this drug is not indicated in patients with KS.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Antiproliferative and apoptotic effects of iron chelators on human cervical carcinoma cells.

OBJECTIVE: Cervical carcinoma is a human papillomavirus (HPV)-associated cancer for which treatment options still mainly rely on surgical procedures, with or without adjuvant radiotherapy and chemotherapy. As iron may participate in the pathogenesis of viral infections and cancer in several ways, the present study was designed to investigate the effect of iron chelation on HPV-16- and HPV-18-positive cervical carcinoma cell lines. METHODS: Desferrioxamine and deferiprone, two chemically unrelated iron chelators, were used to investigate the effect of iron chelation on SiHa and HeLa cells. Proliferation was investigated by cells counts, by [(3)H]thymidine uptake assay, and by immunostaining with Ki-67 and proliferating cell nuclear antigen (PCNA). Apoptosis was determined by morphological analysis, by a TUNEL assay, and by flow cytometry detecting FITC-conjugated annexin-V. RESULTS: Desferrioxamine and deferiprone induced a time- and dose-dependent inhibition of SiHa and HeLa cell growth. The inhibition of cell growth was associated with a decrease in the expression of both stable and total PCNA and Ki-67, a proliferation marker whose expression may predict survival in uterine cervical carcinoma. TUNEL assay, flow cytometry with annexin-V-fluorescein, and morphological analysis indicated that iron chelation also induced a time- and dose-dependent apoptosis of both cell lines. This apoptotic effect was prevented by the addition of exogenous iron. CONCLUSION: These results show that iron chelation inhibits the growth and induces the apoptosis of HPV-positive carcinoma cells. This suggests that iron chelators may represent a potential therapeutic approach for the management of cervical carcinoma.

Apoptosis↗
PubMed2002

Expression of the fibroblast/macrophage marker 1B10 by spindle cells in Kaposi's sarcoma lesions and by Kaposi's sarcoma-derived tumor cells.

BACKGROUND: Kaposi's sarcoma (KS) is a tumor whose ontogenic origin remains a matter of contention. KS tissues are characterized by predominant expression of endothelial markers, while KS-derived cell cultures are usually characterized by expression of mesenchymal non-endothelial cell markers. AIMS: In order to clarify the ontogenic origin of KS cells, we investigated the expression of the fibroblast/macrophage marker 1B10 in KS tissues (AIDS-associated KS, n = 9; classic KS, n = 6; iatrogenic KS, n = 6) and in KS-derived cell cultures. RESULTS: 1B10 was expressed by loosely distributed spindle-shaped cells in early 'patch-stage' KS and by a variable proportion of spindle cells in late 'plaque- and nodular-stage' KS. Using immunohistochemistry and immunoblot analysis, we found that, in vitro, reactivity for 1B10 was uniformly evidenced in fibroblasts and in KS-derived spindle cell cultures, irrespective of their histological or epidemiological setting. By contrast, vascular smooth muscle cells and endothelial cells were negative for 1B10. CONCLUSIONS: These results suggest that the KS spindle cells isolated in vitro may represent a particular subpopulation of the KS spindle cell compartment.

Antigens, Surface↗