M. Agopiantz

Thyroid side effects prophylaxis in front of nuclear power plant accidents

The better knowledge of the mechanisms of nuclear incidents and lessons learned from accidents in the recent past to improve the effectiveness of measures taken following a nuclear accident exposure to fallout of radioactive iodine isotopes. Thus, immediate, passive measures, such as containment, and stopping consumption of contaminated products are paramount. The earliest possible administration of stable iodine as potassium iodide (KI) reduces significantly (up to 90% if taken at the same time of the accident) thyroid radioactive contamination. These tablets should be given in priority to children and pregnant women. The side effects are minor. KI is not recommended for persons aged over 60 years, or for adults suffering from cardiovascular disorders.

Neurotensin receptor 1 antagonist SR48692 improves response to carboplatin by enhancing apoptosis and inhibiting drug efflux in ovarian cancer

Purpose: The high affinity receptor 1 (NTSR1) and its agonist, neurotensin (NTS), are correlated with tumor cell aggressiveness in most solid tumors. As chemoresistance and tumor aggressiveness are often related, we decided to study the role of the NTSR1 complex within platinum-based chemotherapy responses. In an ovarian model, we studied carboplatin because it is the main standard of care for ovarian cancer. Experimental Design: Experimental tumors and in vitro studies were performed using SKOV3 and A2780 cells treated with carboplatin, with or without a very specific NTSR1 antagonist, SR48692. We measured the effects of these treatments on cell apoptosis and apoptosis-related proteins, platinum accumulation in the cell and nucleus, and the expression and localization of platinum transporters. NTS and NTSR1 labeling was measured in patients with ovarian cancer. Results: SR48692 enhanced the response to carboplatin in ovarian cancer cells and experimental tumors. When SR48692 is combined with carboplatin, we noted a major improvement of platinum-induced DNA damage and cell death, as well as a decrease in tumor growth. The relationship of these results to clinical studies was made by the detection of NTS and NTSR1 in 72% and 74% of ovarian cancer, respectively. Furthermore, in a large series of high-grade ovarian cancer, NTSR1 mRNA was shown to correlate with higher stages and platinum resistance. Conclusions: This study strongly suggests that the addition of NTSR1 inhibitor in combination with platinum salt–based therapy will improve the response to the drug. Clin Cancer Res; 23(21); 6516–28. ©2017 AACR.

McCune–Albright syndrome, natural history and multidisciplinary management in a series of 14 pediatric cases

BACKGROUND McCune-Albright syndrome is a rare disorder characterized by endocrine disorders, café-au-lait spots and fibrous dysplasia of bone that occurs early in life. METHODS A series of 14 pediatric cases were followed between 1994 and 2013 by the competence center for rare endocrine diseases and constitutional bone diseases at CHU de Nancy (France). The diagnosis is based on the presence of at least two symptoms. RESULTS The mean follow-up was 6 years (1-17 years). The sex ratio was six girls per boy. The incidence was 0.28 cases/million population/year. Mean age at diagnosis was 6 years. A mutation in the GNAS gene was found in 33% of patients tested. Gonadal involvement (13/14 cases), including early peripheral puberty and ovarian cysts in girls (82%) occurred on average at 4 years of age. Bone involvement (10/14 cases) appeared on average at 5 years of age and was most often multiple (80%) with fracture risk, and the skull, with a neurosensory risk. CONCLUSION Clinical definition and methods of screening and monitoring can be improved to allow for an earlier intervention. It must be multidisciplinary and take into account the disability and quality of life of the patient.

An adult patient with 49, XXXXY syndrome: further clinical and biological delineation

49, XXXXY syndrome is a rare sex chromosome aneuploidy occurring in 1:80 000-1:100 000 male births. Data on this aneuploidy in adulthood are limited, with most of the literature data based on paediatric patients. We report a new male patient whose 49, XXXXY diagnosis was formally made at the age of 54 years. So far, no medical follow-up was performed specifically for his condition. This man presented with facial features (epicanthus, hypertelorism, up-slanting palpebral fissures), microorchidism and features of chronic hypoandrogenism with muscular weakness, sparse body hair, dry skin with abnormal healing of skin wounds. Endocrine evaluation confirmed a hypergonadotropic hypogonadism. He had moderate intellectual deficiency with more affected verbal skills. A recent deep vein thrombosis was diagnosed in his left leg. Unusually, in addition to moderate deafness, he developed progressively a severe vision impairment leading to blindness. There have been very few reports of adult individuals with 49, XXXXY syndrome and this kind of report may contribute to improved management of prospective medical healthcare associated with this condition in older individuals.