Necrotizing Sialometaplasia Accompanied by Adenoid Cystic Carcinoma on the Soft Palate

Necrotizing Sialometaplasia (NS) is a benign, self-limiting inflammatory disease of the mucus-secreting glands, and this illness mainly involves the minor salivary glands. The significance of NS resides in its clinical and histopathological resemblance to malignancy. We present here a case of necrotizing sialometaplasia on the soft palate, and this was accompanied by adenoid cystic carcinoma. We report here on this case to draw attention to the difficulty for deciding the extent of resecting a malignancy, and especially when the malignancy is simultaneously accompanied by necrotizing sialometaplasia

Simultaneous detection and subtyping of porcine endogenous retroviruses proviral DNA using the dual priming oligonucleotide system

The purpose of this study was to develop a multiplex PCR that can detect porcine endogenous retrovirus (PERV) proviral genes (pol, envA, envB, envC) and porcine mitochondrial DNA, using a dual priming oligonucleotide (DPO) system. The primer specifically detected the PERV proviral genes pol, envA, envB, envC, and porcine mitochondrial DNA only in samples of pig origin. The sensitivity of the primer was demonstrated by simultaneous amplification of all 5 target genes in as little as 10 pg of pig DNA containing PERV proviral genes and mitochondrial DNA. The multiplex PCR, when applied to field samples, simultaneously and successfully amplified PERV proviral genes from liver, blood and hair root samples. Thus, the multiplex PCR developed in the current study using DPO-based primers is a rapid, sensitive and specific assay for the detection and subtyping of PERV proviral genes

EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers

The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLC) to tyrosine kinase inhibitors (TKIs) has been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. To understand the role of microRNAs in TKI-resistant NSCLC, we examined TK receptor-mediated microRNA changes. Here we report that miR-30b/c and miR-221/222, modulated by both EGF and MET receptors, and miR-103, -203, controlled only by MET, play important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition (EMT) of NSCLC cells, in vitro and in vivo, by inhibiting the expression of Bim, APAF-1, PKC-ε and SRC genes. The finding suggests that modulation of specific microRNAs may provide a therapeutic approach for future treatment of NSCLC

A Case of Aortopulmonary Fistula Caused by a Huge Thoracic Aortic Aneurysm

Aortopulmonary fistula is an uncommon but often fatal condition resulting as a late complication of an aortic aneurysm. The most common cause is erosion of a false aneurysm of the descending thoracic aorta into the pulmonary artery, resulting in the development of a left-to-right shunt and leading to acute pulmonary edema and right heart failure. We report an our experience with aortopulmonary fistula as a rare complication associated with thoracic aortic aneurysm and high output heart failure

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Methods Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. Results The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. Conclusion P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement

Clinical Features Reflect Exon Sites of EGFR Mutations in Patients with Resected Non-Small-Cell Lung Cancer

The aim of the current study was to determine the clinical significance according to the subtypes of epidermal growth factor receptor (EGFR) mutations and presence of KRAS mutations in operable non-small-cell lung cancer (NSCLC). We sequenced exons 18-21 of the EGFR tyrosine kinase domain and examined mutations in codons 12 and 13 of KRAS in tissues of patients with NSCLC who had undergone surgical resection. EGFR mutations were more frequent in never-smokers than smokers (33% vs. 14%, respectively; p=0.009) and in females than in males (31% vs. 16%, respectively; p=0.036). Mutations in exon 18-19 and 20-21 were found in 10 and 22 patients, respectively. Never-smokers and broncho-alveolar cell carcinoma features were positively associated with a mutation in exon 18-19 (p=0.027 and 0.016, respectively). The five-year survival rate in patients with a mutation in exons 18-19 (100%) was higher than that in patients without such mutation (47%; p=0.021). KRAS mutations were found in 16 patients (12%) and were not related to the overall survival (p=0.742). Patients with an EGFR mutation in exons 18-19 had better survival than patients without such mutation. Subtypes of EGFR mutations may be prognostic factors in patients undergoing curative resection