Classification tree analysis of second neoplasms in survivors of childhood cancer

Background  

Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population.     

Malignant lymphoma of the stomach in association with inflammatory myofibroblastic tumor of the spleen. A case report

We report on a case of a 40-year-old male patient who underwent a gastrectomy because of a biopsy-proven large B-cell lymphoma of the stomach. On surgery, a nodule in the spleen also was noted. Grossly and microscopically, the two lesions were different: the tumor of the stomach appeared white-gray on the cut surface and was a centroblastic variant of diffuse large B-cell lymphoma. Histologically, one perigastric lymph node was involved. Grossly, the splenic nodule was gray-yellow and had a histological appearance of an inflammatory myofibroblastic tumor (IMT). The association between malignant tumor and IMT is rare. In such an association, the latter lesion most often has been reported in the spleen. As EBV may be involved in the genesis of both lymphoma and IMT, we tested both lesions for its presence using in situ hybridization, but the tests were negative. It remains to be verified whether the association between lymphoma and IMT is more than fortuitous.     

No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43 - 5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29 - 3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate.     

Nanosecond Electric Pulses are Equally Effective in Electrochemotherapy with Cisplatin as Microsecond Pulses

BackgroundNanosecond electric pulses showed promising results in electrochemotherapy, but the underlying mechanisms of action are still unexplored. The aim of this work was to correlate cellular cisplatin amount with cell survival of cells electroporated with nanosecond or standardly used 8 × 100 μs pulses and to investigate the effects of electric pulses on cisplatin structure.Materials and methodsChinese hamster ovary CHO and mouse melanoma B16F1 cells were exposed to 1 × 200 ns pulse at 12.6 kV/cm or 25 × 400 ns pulses at 3.9 kV/cm, 10 Hz repetition rate or 8 × 100 μs pulses at 1.1 (CHO) or 0.9 (B16F1) kV/cm, 1 Hz repetition rate at three cisplatin concentrations. Cell survival was determined by the clonogenic assay, cellular platinum was measured by inductively coupled plasma mass spectrometry. Effects on the structure of cisplatin were investigated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.ResultsNanosecond pulses equivalent to 8 × 100 μs pulses were established in vitro based on membrane permeabilization and cell survival. Equivalent nanosecond pulses were equally efficient in decreasing the cell survival and accumulating cisplatin intracellularly as 8 × 100 μs pulses after electrochemotherapy. The number of intracellular cisplatin molecules strongly correlates with cell survival for B16F1 cells, but less for CHO cells, implying the possible involvement of other mechanisms in electrochemotherapy. The high-voltage electric pulses did not alter the structure of cisplatin.ConclusionsEquivalent nanosecond pulses are equally effective in electrochemotherapy as standardly used 8 × 100 μs pulses.Key words: electroporation, electrochemotherapy, nanosecond pulses, cisplatin     

Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings

The electrochemical behavior of polycrystalline TiO₂ anatase coatings prepared by a one-step hydrothermal synthesis on commercially pure (CP) Ti grade 2 and a Ti13Nb13Zr alloy for bone implants was investigated in Hank’s solution at 37.5 °C. The aim was to verify to what extent the in-situ-grown anatase improved the behavior of the substrate in comparison to the bare substrates. Tafel-plot extrapolations from the potentiodynamic curves revealed a substantial improvement in the corrosion potentials for the anatase coatings. Moreover, the coatings grown on titanium also exhibited lower corrosion-current densities, indicating a longer survival of the implant. The results were explained by considering the effects of crystal morphology, coating thickness and porosity. Evidence for the existing porosity was obtained from corrosion and nano-indentation tests. The overall results indicated that the hydrothermally prepared anatase coatings, with the appropriate morphology and surface properties, have attractive prospects for use in medical devices, since better corrosion protection of the implant can be expected.     

Binding site comparisons for target-centered drug discovery

Introduction: The success of binding site comparisons in drug discovery is based on the recognized fact that many different proteins have similar binding sites. Indeed, binding site comparisons have found many uses in drug development and have the potential to dramatically cut the cost and shorten the time necessary for the development of new drugs.

Areas covered: The authors review recent methods for comparing protein binding sites and their use in drug repurposing and polypharmacology. They examine emerging fields including the use of binding site comparisons in precision medicine, the prediction of structured water molecules, the search for targets of natural compounds, and their application in the development of protein-based drugs by loop modeling and for comparison of RNA binding sites.

Expert opinion: Binding site comparisons have produced many interesting results in drug development, but relatively little work has been done on protein–protein interaction sites, which are particularly relevant in view of the success of biological drugs. Growth of protein loop modeling for modulating biological drugs is anticipated. The fusion of currently distinct methods for the comparison of RNA and protein binding sites into a single comprehensive approach could allow the search for new selective ribosomal antibiotics and initiate pharmaceutical research into other nucleoproteins.     

Animal and human dentin microstructure and elemental composition

Animal teeth are a common model in studies on dentin adhesive materials. The aim of this study was to compare microstructural parameters (density and diameter of dentinal tubules (DT), peritubular dentin (PTD) thickness, PTD and intertubular dentin (ITD) surface area) and chemical characteristics of canine, porcine, equine, and human root dentin. The middle layers of dentin were harvested just below a cemento-enamel junction from incisors and investigated by means of scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDXS). SEM evaluation of the specimens revealed, that porcine dentin shared most similarities with human dentin. When comparing the density of DTs, canine dentin was also found to be similar to human dentin. Elemental composition of the root dentin did not differ significantly in porcine, equine and human dentin, but in canine dentin higher magnesium value in PTD compared to ITD was found. It is known that microstructural and chemical characteristics affect the strength of the adhesive bonds created among restorative materials and dentin. According to the results of this study, porcine dentin seems to be the most appropriate model to study dental materials to be used in human restorative dentistry.     

The Effect of Court Location and Available Time on the Tactical Shot Selection of Elite Squash Players

No previous research in squash has considered the time between shots or the proximity of the ball to a wall, which are two important variables that influence shot outcomes. The aim of this paper was to analyse shot types to determine the extent to which they are played in different court areas and a more detailed analysis to determine whether the time available had an influence on the shot selected. Ten elite matches, contested by fifteen of the world’s top right handed squash players (age 27 ± 3.2, height 1.81 ± 0.06 m, weight 76.3 ± 3.7 kg), at the men’s World Team Championships were processed using the SAGIT/Squash tracking system with shot information manually added to the system. Results suggested that shot responses were dependent upon court location and the time between shots. When these factors were considered repeatable performance existed to the extent that one of two shots was typically played when there was limited time to play the shot (< 1.20s). For example, it was clear that when players did not have a lot of time to hit the ball (low time i.e. < 1.06s, and mid time i.e. 1.06 - 1.20s) in the front left corner close to the side wall, the crosscourt lob was used frequently (44.30% and 36.31% respectively) whereas when there was more time this shot was seldom used (13.64%). Consequently variant and invariant behaviour were shown to exist in elite squash although for the first time it was suggested that the availability of time to play a shot contributed to which of these behaviours was evident. This analysis could be extended by adopting a case study approach to see how individual differences in strategy and tactics affect shot selections.

Key points

• Previous research has suggested that a playing strategy, elements decided in advance of the match, may be evident for elite players by examining court location and preceding shot type, however these parameters alone are unlikely to be sufficient predictors.
• At present there is no known analysis in squash, or indeed in any of the racket sports, that has quantified the time available to respond to different shot types. An understanding of the time interval between shots and the movement characteristics of the player responding to different shots according to the court positions might facilitate a better understanding of the dynamics that determine shot selection.
• Some elements of a general playing strategy were evident e.g. predominately hitting to the back left of the court, but tactical differences in shot selection were also evident on the basis of court location and time available to play a shot.

Key words: Strategy, tactics, SAGIT, invariant behaviour.