Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells.

Cancer cells are characterized by the Warburg effect, a shift from mitochondrial respiration to oxidative glycolysis. We report here the crucial role of cyclin D1 in promoting this effect in a cyclin-dependent kinase (CDK)4/6-independent manner in multiple myeloma (MM) cells. We show that the cyclin D1 oncoprotein targets hexokinase 2 (HK2), a major glycolysis regulator, through two original molecular mechanisms in the cytoplasmic and nuclear compartments. In the cytoplasm, cyclin D1 binds HK2 at the outer mitochondrial membrane, and in the nucleus, it binds hypoxia-inducible factor-1α (HIF1α), which regulates HK2 gene transcription. We also show that high levels of HK2 expression are correlated with shorter event-free survival (EFS) and overall survival (OS) in MM patients. HK2 may therefore be considered as a possible target for antimyeloma therapy.

Pelvic fracture in multiple trauma: A 67-case series.

INTRODUCTION: Severe pelvic trauma remains associated with elevated mortality, largely due to hemorrhagic shock. OBJECTIVE: The main study objective was to test for correlation between fracture type and mortality. The secondary objective was to assess the efficacy in terms of mortality of multidisciplinary management following a decision-tree in multiple trauma victims admitted to a level 1 trauma center. MATERIAL AND METHODS: Between July 2011 and July 2013, 534 severe trauma patients were included in a single-center continuous prospective observational study. All patients with hemorrhagic shock received early treatment by pelvic binder. Patients with active bleeding on full-body CT or persisting hemorrhagic shock underwent arteriography with or without embolization. Pelvic trauma was graded on the Tile classification. The principle end-point was mortality. RESULTS: Median age was 40 years (range, 26-48 years), with a 79% male/female sex ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12 (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock. Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and 12.1%, respectively; P=0.001). CONCLUSION: Vertical shear fracture (Tile C) was associated with greater mortality from hemorrhagic shock. LEVEL OF EVIDENCE: IV, case series.

[Supernumerary teeth]. / Dents surnuméraires.

Through a study of 68 patients, presenting 84 supernumerary teeth all together and, after a thorough survey of the literature, we can now state accurately about the frequency, location, surgery, X-Ray and heredity involved. After recalling and discussing the various pathological theories already set up, a theory has been put forward, more specifically intent on the explanation of frequent supernumerary teeth in the upper front teeth area. Nevertheless, the theories of extra growth and the overgrowth of the external layer remain worth while to explain some other locations.