Molecular biology of mantle cell lymphoma: From profiling studies to new therapeutic strategies

Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols. The hallmark genetic alteration of MCL is the t(11;14)(q13;32) chromosomal translocation that leads to the overexpression of cyclin D1. Recently, new molecular alterations of major importance in the pathogenic mechanisms of this disease have been discovered, and have revealed the biological heterogeneity of MCL. The first section of our review discusses our current understanding of the molecular biology of this entity according to recent information from comparative genomic hybridization (CGH) and expression profiling studies, which are leading to the identification of several druggable targets. In the second section we revise new therapeutic strategies based on new drug families that target key molecular pathways of major relevance in this malignancy. We analyze emerging agents that are already producing significant results in different models of human cancers, including MCL. Based on the current knowledge and recent studies, we suggest that the encouraging results described here should provide a rationale platform for the design of new treatments that may overcome the resistance of this aggressive lymphoma to conventional therapy and improve patient prognosis.     

Effect of repeated torque/mechanical loading cycles on two different abutment types in implants with internal tapered connections: an in vitro study

Objectives: Internal tapered connections were developed to improve biomechanical properties and to reduce mechanical problems found in other implant connection systems. The purpose of this study was to evaluate the effects of mechanical loading and repeated insertion/removal cycles on the torque loss of abutments with internal tapered connections.
Material and methods: Sixty-eight conical implants and 68 abutments of two types were used. They were divided into four groups: groups 1 and 3 received solid abutments, and groups 2 and 4 received two-piece abutments. In groups 1 and 2, abutments were simply installed and uninstalled; torque-in and torque-out values were measured. In groups 3 and 4, abutments were installed, mechanically loaded and uninstalled; torque-in and torque-out values were measured. Under mechanical loading, two-piece abutments were frictionally locked into the implant; thus, data of group 4 were catalogued under two subgroups (4a: torque-out value necessary to loosen the fixation screw; 4b: torque-out value necessary to remove the abutment from the implant). Ten insertion/removal cycles were performed for every implant/abutment assembly. Data were analyzed with a mixed linear model ( P ≤0.05).
Results: Torque loss was higher in groups 4a and 2 (over 30% loss), followed by group 1 (10.5% loss), group 3 (5.4% loss) and group 4b (39% torque gain). All the results were significantly different. As the number of insertion/removal cycles increased, removal torques tended to be lower. It was concluded that mechanical loading increased removal torque of loaded abutments in comparison with unloaded abutments, and removal torque values tended to decrease as the number of insertion/removal cycles increased.     

Evaluation of the adaptation interface of one-piece implant-supported superstructures obtained in Ni-Cr-Ti and Pd-Ag alloys

Several formulations of alternative alloys have been proposed for the substitution of gold-based alloys used in Dentistry. Recently, a Ni-Cr-Ti-based alloy has been introduced. The purpose of this work was to verify the marginal adaptation obtained with one-piece superstructures for implant-supported prostheses obtained in Ni-Cr-Ti alloy, compared to a semi-noble alloy Pd-Ag. Eight superstructures for each alloy were produced over 4 implants in the anterior region of the mandible. The superstructures were placed in a torquemeter and the fixation screw of implant #1 was tightened with a 20 Ncm load with the others loosened (Sheffield test). The unfitness (in mm) was measured using a three-dimensional optical measurer in each implant, in the buccal and lingual aspects. The obtained data were submitted to statistical analysis by the analysis of variance and Tukey's test at 5% level. Significant differences were found for the factors material (p<0.05), with Ni-Cr-Ti pieces better than Pd-Ag ones, and implants (p<0.01). There were no significant differences for the factor position and interactions among factors (p>0.05). Based on the analysis of the data, it is possible to conclude that the Ni-Cr-Ti alloy makes possible the obtainment of one-piece implant-supported superstructures with a smaller misfit compared to the one obtained in Pd-Ag alloy, traditionally indicated for this situation. Additional tests may verify the superiority of the Ni-Cr-Ti alloy.     

The effect of protein or energy restriction on the biodistribution of Na99TcmO4 in Wistar rats

The effect of malnutrition on the biodistribution of radiopharmaceuticals is not known. We studied the biodistribution of 99Tcm-labelled sodium pertechnetate (Na99TcmO4) in two rat models of malnutrition. Three groups of 2-month-old rats were separated according to their diets: (1) control diet, 23% protein (C); (2) protein-restricted, receiving 8% protein (PR), both ad libitum; and (3) energy-restricted, receiving 60% of control diet (ER). After 21 days of the diet, 99Tcm was injected and the animals were killed after 30 min. The organs were isolated, their weight determined and the absolute per cent (%ID) and the per cent per gram injected dose (%ID x g(-1)) calculated. The %ID and %ID x g(-1) had a similar pattern, increasing in stomach and brain and decreasing in the thyroid, but did not change significantly in kidney, lung, liver, bone or testis in PR rats, except in the heart where the increase was only observed in the %ID x g(-1). In the ER group the %ID x g(-1) was decreased in the bone only, and did not change in the other organs. It is suggested that when using Na99TcmO4 scintigraphy in malnourished patients, the different patterns of distribution must be kept in mind.     

Angiographic effects of indocyanine green photobleaching by the diode laser.

BACKGROUND AND OBJECTIVE: To investigate the cause of hypofluorescent spots detected by indocyanine green (ICG) videoangiography in areas subjected to ICG-enhanced transpupillary thermotherapy in pigmented rabbits. MATERIALS AND METHODS: In 6 eyes, two similar areas were treated with transpupillary thermotherapy. A standard dose of ICG (0.5 mg/kg) was injected intravenously before treatment of the second area. Red-free photographs without further injection of ICG (first ICG videoangiography) were then performed. The first area was re-irradiated using the same parameters. Red-free photographs and a second ICG videoangiography, still without further injection of ICG, were performed. ICG was then re-injected and a third ICG videoangiography was obtained. Finally, fluorescein angiography was performed. RESULTS: The first ICG videoangiography demonstrated hyperfluorescence of the first area and normofluorescence of the second area. The second ICG videoangiography demonstrated hypofluorescence of the first area. The third ICG videoangiography showed hyperfluorescence of both areas. CONCLUSIONS: Hypofluorescence detected after re-irradiation is probably related to ICG photobleaching.