Oral health and related factors in a group of children with cystic fibrosis in Istanbul, Turkey

Background: Cystic fibrosis (CF) patients can be considered as high caries risk patients because they frequently consume sugar.rich food between meals and they have a high intake of sugar containing syrups, aerosols, and salivary flow reducing medication. Variable caries prevalences were reported in CF patients in previous studies. There are no studies related to CF and salivary thromboplastic activity, which can be presented as a marker of wound healing and bleeding tendency of oral cavity.Objective: The aim of this study was to compare oral health status and salivary pH, flow rate, and thromboplastic activity in children with CF and healthy controls.Materials and Methods: Asample of 35 children with CF (23 girls and 12 boys), and 12 healthy control subjects (6 girls and 6 boys) were selected. Caries experience, oral hygiene, and dental erosion were assessed. Salivary flow rate, pH, thromboplastic activity, and total protein content were determined. Differences between the groups were evaluated using Chi.square test with a significance level set at 0.05.Results: The differences between children with CF and healthy controls in tooth brushing frequency, use of fluoride tablets, caries experience, dental erosion index, oral hygiene index, salivary flow rate and total protein levels were not statistically significant (P > 0.05). Salivary thromboplastic activity of the CF group was significantly lower than the healthy controls (P < 0.01).Conclusion: Large population studies may be necessary to establish the role of salivary thromboplastic activity in children with CF considering our findings related to the decreased salivary thromboplastic activity, which  may indicate delayed oral wound healing process.Key words: Caries, children, cystic fibrosis, saliva, salivary thromboplastic activit

Castleman’s Disease presenting as a pleural mass in the thoracic cavity

A 61-year-old non-smoking Turkish woman presented with chest pain for 10 months. Computed tomography of the chest revealed a solitary, relatively well circumscribed, heterogeneous mass of 4 x 6 cm diameter in left posteriorlateral hemithorax. On thoracotomy, an extraparanchymal mass destructing the ribs was determined. Mass excision and partial chest wall resection were performed. On histopathologic examination, this mass showed features of the hyaline vascular type of Castleman’s Disease

Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer

PurposeAmplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that BET bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven NSCLC with BET inhibition.Experimental DesignWe performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cells lines harboring KRAS and/or LKB1 mutations. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. Effects of bromodomain inhibition on transcriptional pathways were explored and validated by expression analysis.ResultsWhile JQ1 is broadly active in NSCLC cells, activity of JQ1 in mutant KRAS NSCLC is abrogated by concurrent alteration or genetic knock-down of LKB1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1.ConclusionBromodomain inhibition comprises a promising therapeutic strategy for KRAS mutant NSCLC with wild-type LKB1, via inhibition of MYC function. Clinical studies of BET bromodomain inhibitors in aggressive NSCLC will be actively pursued

Kinase Domain Activation of FGFR2 Yields High-Grade Lung Adenocarcinoma Sensitive to a Pan-FGFR Inhibitor in a Mouse Model of NSCLC

Somatic mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) are present in 4-5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLC and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma though mouse models of FGFR driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade III/IV adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting

\u3cem\u3eLkb1\u3c/em\u3e Inactivation Drives Lung Cancer Lineage Switching Governed by Polycomb Repressive Complex 2

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours

Somatic LKB1 Mutations Promote Cervical Cancer Progression

Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence

Low-surface energy surfactants with branched hydrocarbon architectures

International audienceSurface tensiometry and small-angle neutron scattering have been used to characterize a new class of low-surface energy surfactants (LSESs), "hedgehog" surfactants. These surfactants are based on highly branched hydrocarbon (HC) chains as replacements for environmentally hazardous fluorocarbon surfactants and polymers. Tensiometric analyses indicate that a subtle structural modification in the tails and headgroup results in significant effects on limiting surface tensions γcmc at the critical micelle concentration: a higher level of branching and an increased counterion size promote an effective reduction of surface tension to low values for HC surfactants (γcmc 24 mN m-1). These LSESs present a new class of potentially very important materials, which form lamellar aggregates in aqueous solutions independent of dilution

Co-Clinical Trials Demonstrate Superiority of Crizotinib to Chemotherapy in ALK-Rearranged Non-Small Cell Lung Cancer and Predict Strategies to Overcome Resistance

To extend the results of a phase III trial in non-small cell lung cancer patients with adenocarcinomas harboring EML4-ALK fusion

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

<p>Abstract</p> <p>Background</p> <p>Expression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging.</p> <p>Methods</p> <p>We describe a method to identify the <it>trans-</it>acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed <it>co-regulatory expression quantitative trait locus </it>(creQTL) <it>mapping</it>-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping.</p> <p>Results</p> <p>Applying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNβ-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNβ-induced genes and the DNA damage response.</p> <p>Conclusions</p> <p>Because of the importance of IFNβ in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at <url>http://sites.google.com/site/kenkompass/</url>.</p