[Changes in the incidence and mortality rates of malignant melanoma in the Seine-Maritime region over a 20-year period]. / Évolution de l'incidence et de la mortalité du mélanome en Seine-Maritime sur une période de 20ans.

BACKGROUND: The aim of this study was to assess changes in the incidence and mortality rates of malignant melanoma (MM) over a 20-year period in a region without a cancer registry. METHODS: All cases of MM studied were collected retrospectively from the databases of six private and three hospital-based histopathology laboratories in the Seine-Maritime region covering three 24-month periods each 10years apart: 1988-1989, 1998-1999 and 2008-2009, The incidence and mortality rates were estimated based on data provided by French National Institute for Statistics and Economic Studies (Insee) and French National Institute of Health and Medical Research (Inserm). RESULTS: Over the 20-year period, the incidence of MM increased from 8.6 to 21.2/100,000inhabitants per year (+147%, P<0.0001) while the mortality rate rose from 1.3 to 2.8/100,000inhabitants per year (+115%, P=0.0003). The incidence of invasive MM increased by +110%, while the incidence of MM in situ increased by +456%. The incidence and overall mortality rate of invasive MM increased particularly during the first 10-year period: +62% (P<0.0001) and +77% (P=0.01) respectively, and to a much lesser extent during the last 10-year period: +30% (P=0.0007) and +22% (P=0.22) respectively. This slowdown in the incidence of invasive MM and in overall mortality rates was even more pronounced in women over the last 10years (+17 and +9%), whereas these rates continued to increase in men (+49% and +35%, respectively). In contrast, the incidence of MM in situ increased above all during this same period (+257%). CONCLUSION: This study shows that while the incidence and mortality rate of invasive MM has increased little over the last 10years in the Seine-Maritime region, the incidence of MM in situ continues to rise sharply.

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells.

The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1-expressing cells, by inactivating NF-kappaB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation.