Prosthodontic management of acquired partial mandibulectomy discontinuity defects: a clinical report

Prosthetic rehabilitation of partial mandibulectomy defects without bony reconstruction is rarely presented. An in-depth understanding of the surgical and conventional prosthodontic principles is essential for prosthetic rehabilitation in this unique group of patients. Often, the application of modified prosthodontic principles is needed and success is not always possible. A clinical report is presented in this article.     

Rapid genotyping of the human renin (REN) gene by the LightCycler® instrument: identification of unexpected nucleotide substitutions within the selected hybridization probe area

Preeclampsia is a serious disorder affecting nearly 3% of all in the Western world. It is associated with hypertension and proteinuria, and several lines of evidence suggest that the renin-angiotensin system (RAS) may be involved in the development of hypertension at different stages of a preeclamptic pregnancy. In this study, we developed rapid genotyping assays on the LightCycler® instrument to allow the detection of genetic variants in the renin gene (REN) that may predispose to preeclampsia. The method is based on real-time PCR and allele-specific hybridization probes, followed by fluorescent melting curve analysis to expose a change in melting temperature (T_m). Ninety-two mother-father-child triads (n=276) from preeclamptic pregnancies were genotyped for three haplotype-tagging single nucleotide polymorphisms (htSNPs) in REN. All three htSNPs (rs5705, rs1464816 and rs3795575) were successfully genotyped. Furthermore, two unexpected nucleotide substitutions (rs11571084 and rs61757041) were identified within the selected hybridization probe area of rs1464816 and rs3795575 due to aberrant melting peaks. In conclusion, genotyping on the LightCycler® instrument proved to be rapid and highly reproducible. The ability to uncover additional nucleotide substitutions is particularly important in that it allows the identification of potentially etiological variants that might otherwise be overlooked by other genotyping methods.     

Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety

In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates [7-O-POM-Q, 3-O-POM-Q]. In the absence of stabilizer (ascorbic acid), the synthesized conjugates showed significantly increased stability in cell culture media [t(?) = 4 h, 52 h] compared with quercetin (t(?) < 30 min) and quercetin prodrug 1 (t(?) = 0.8 h). In addition, the quercetin conjugate 2 underwent efficient cellular uptake and intracellular levels of its hydrolysis product, quercetin, were maintained up to 12 h. Stability and intracellular accumulation of were demonstrated by its stabilizer-independent cytostatic effect and induction of apoptotic cell death. Even though was more stable than, it failed to penetrate cell membranes. However, the remarkable stability of warrants further investigation of quercetin conjugates with various promoieties at the 3-OH position.     

Umbilical cord monitoring of in utero drug exposure to buprenorphine and correlation with maternal dose and neonatal outcomes

Buprenorphine is under investigation in the U.S. as pharmacotherapy for opioid-dependent pregnant women. Buprenorphine and metabolites were quantified in umbilical cord specimens from women receiving daily buprenorphine doses. Correlations between maternal buprenorphine dose, buprenorphine and metabolite umbilical cord concentrations, and neonatal outcomes were investigated, as well as the ability to identify heroin and cocaine relapse during pregnancy. Umbilical cord concentrations were compared to those of matched umbilical cord plasma and meconium. Buprenorphine metabolites were detected in all cords, but buprenorphine itself was absent. Concentration ranges were 1.2-5.1 ng/g norbuprenorphine, 1.7-4.2 ng/g buprenorphine-glucuronide, and 8.3-23 ng/g norbuprenorphine-glucuronide. Cord concentrations were similar to those in plasma, and lower (16-210-fold), although statistically correlated, than those in meconium. Significant positive correlations were observed for buprenorphine-glucuronide concentrations in umbilical cord and mean maternal BUP daily dose throughout pregnancy and third trimester, but buprenorphine biomarker concentrations did not predict neonatal outcomes. Opiate concentrations were lower (200-fold) in umbilical cord than in meconium, and when cocaine was present in meconium, it was not identified in cord. Umbilical cord can serve as an alternative matrix for identifying prenatal drug-exposure, but is much less sensitive than meconium. Buprenorphine provided a controlled drug administration model for evaluating drug disposition in the maternal-fetal dyad.     

Clinical and therapeutic relevance of PIM1 kinase in gastric cancer

Background

Gastric cancer is a leading cause of cancer-related mortality, and chemotherapeutic options are currently limited. PIM1 kinase, an oncogene that promotes tumorigenesis in several cancer types, might represent a novel therapeutic target in gastric cancer.

Methods

We studied the expression and genomic status of PIM1 in human primary gastric normal and tumor tissue samples by immunohistochemistry and array-based comparative genomic hybridization (aCGH). To ascertain whether PIM1 expression predicted susceptibility to PIM1 kinase-specific inhibition, the cytotoxic effect of a previously reported PIM1-specific small molecular inhibitor (K00135) was investigated in two gastric cancer cell lines with high (IM95) and undetectable (NUGC-4) PIM1 expression levels.

Results

PIM1 expression was exclusively nuclear in normal gastric epithelial cells, while aberrant expression/localization (decreased nuclear and/or increased cytoplasmic expression) was observed in 75.6% (68/90) of the human gastric cancer tissue samples, with a significant inverse correlation between nuclear and cytoplasmic expression levels. Clinicopathological analyses revealed that decreased nuclear PIM1 expression correlated with poorer survival and greater depth of tumor invasion, while increased cytoplasmic PIM1 expression correlated inversely with the presence of lymphovascular invasion. High-level PIM1 amplification was identified in 10.5% of gastric cancers by aCGH. K00135 impaired the survival of IM95, while it had no significant effect on NUGC-4 survival.

Conclusion

Our findings demonstrate the clinical and therapeutic relevance of PIM1 in gastric cancers, and suggest that PIM1 represents a potential therapeutic target.     

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.     

Corpus callosum morphology in children who stutter

Multiple studies have reported both functional and neuroanatomical differences between adults who stutter and their normally fluent peers. However, the reasons for these differences remain unclear although some developmental data suggest that structural brain differences may be present in school-age children who stutter. In the present study, the corpus callosum of children with persistent stuttering, children who recovered from stuttering and typically developing children between 9 and 12 years of age was compared to test if the presence of aberrant callosal morphology is implicated in this disorder. The total corpus callosum midsagittal area and area of each subsection consisting of the rostrum, anterior midbody, posterior midbody and splenium were measured using MIPAV (Medical Image Processing, Analysis, and Visualization). Voxel-based morphometry (VBM) was also used to compare white matter volume. No differences were detected in the corpus callosum area or white matter volume between children with persistent stuttering, children who recovered from stuttering and typically developing children. These results agree with dichotic listening studies that indicate children who stutter show the typical right ear advantage. Therefore, the neural reorganization across the midline shown in adults who stutter may be the result of long-term adaptations to persistent stuttering. LEARNING OUTCOMES: Educational objectives: After reading this article, the reader will be able to: (1) summarize research findings on corpus callosum development; and (2) discuss the characteristics of corpus callosum anatomy in stuttering.     

Salivary duct carcinoma: what is already known, and can we improve survival?

Salivary duct carcinoma is an aggressive malignancy with a high mortality rate, which phenotypically resembles high-grade breast ductal carcinoma. The parotid gland is the most common location. Standard treatment is surgery to the primary tumour together with post-operative radiotherapy. Despite this, there is a high rate of local recurrence, cervical nodal involvement and distant metastasis. Chemotherapy is currently considered only for end-stage, disseminated disease; however, current evidence indicates that chemotherapy used with radiotherapy may result in improved disease control and survival.Human epidermal growth factor receptor-2 is a proto-oncogene which is over-expressed in both breast ductal carcinoma and salivary duct carcinoma. Clinical studies of patients with metastatic breast cancer, using trastuzumab, a monoclonal antibody directed against human epidermal growth factor receptor-2, have shown significant efficacy in tumour response, resulting in improved survival. Such advances in immunohistochemistry, and in targeted immunotherapy for breast ductal carcinoma, should be applied to the treatment of salivary duct carcinoma.