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Neck hybrid schwannoma/neurofibromas are uncommon and classified as peripheral nerve sheath tumors (PNSTs). PNSTs develop from soft tissues, of which schwannoma, perineurioma, and neurofibroma are the most common. Hybrid PNSTs consist of more than 1 type of PNST, such as hybrid schwannoma/neurofibromas. The exact epidemiology and pathogenesis of these tumors are still largely unknown because of the limited studies on this topic. Such tumors can spread over the soft tissues, although most cases reported involve the subcutaneous layer or dermis. Some studies have suggested that hybrid schwannoma/neurofibromas may be associated with neurofibromatosis. We present a case of a 51-year-old female patient with a neck hybrid schwannoma/neurofibroma diagnosed by histopathology and immunohistochemistry. The patient was referred to the neurology department for neurofibromatosis screening, which reported negative results. After 12 months, the patient showed no evidence of tumor recurrence.

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Naphthalimide derivatives have multiple biological activities, including antitumour and anti-inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5-10 µM) inhibited collagen- and convulxin- but not thrombin- or U46619-mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases.

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The non-structural protein 5A (NS5A) is a hepatitis C virus (HCV) protein indispensable for the viral life cycle. Many prior papers have pinpointed several serine residues in the low complexity sequence I region of NS5A responsible for NS5A phosphorylation; however, the functions of specific phosphorylation sites remained obscure. Using phosphoproteomics, we identified three phosphorylation sites (serines 222, 235, and 238) in the NS5A low complexity sequence I region. Reporter virus and replicon assays using phosphorylation-ablated alanine mutants of these sites showed that Ser-235 dominated over Ser-222 and Ser-238 in HCV replication. Immunoblotting using an Ser-235 phosphorylation-specific antibody showed a time-dependent increase in Ser-235 phosphorylation that correlated with the viral replication activity. Ser-235 phosphorylated NS5A co-localized with double-stranded RNA, consistent with its role in HCV replication. Mechanistically, Ser-235 phosphorylation probably promotes the replication complex formation via increasing NS5A interaction with the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein. Casein kinase Iα (CKIα) directly phosphorylated Ser-235 in vitro. Inhibition of CKIα reduced Ser-235 phosphorylation and the HCV RNA levels in the infected cells. We concluded that NS5A Ser-235 phosphorylated by CKIα probably promotes HCV replication via increasing NS5A interaction with the 33-kDa vesicle-associated membrane protein-associated protein.

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Polymorphisms in DNA repair genes may be associated with differences in repair capacity of DNA damage and may thereby influence an individual's susceptibility to lung cancer. We investigated the association between the -93G-->A polymorphism in the mismatch repair hMLH1 gene for its role in the susceptibility and survival of non-small cell lung cancer (NSCLC) patients. Using a case-control study design, 165 NSCLC patients and 193 controls with similar range for age, gender and smoking habit distributions were subjected to genotype analysis. The risk of lung cancer was estimated by logistic regression analysis. The Kaplan-Meier method was used to estimate the probability of survival and the log-rank test was used to assess the significance of the difference between survival probabilities. The homozygous variant A/A genotype was associated with a significantly increased risk for lung cancer compared with the other genotypes (Crude analysis P=0.003, Adjusted analysis P=0.011, using the logistic regression model). The patients with a homozygous variant A/A genotype had a trend toward poorer prognoses compared with other patients, especially smoking (P=0.05, by log-rank test), male (P=0.06), or squamous carcinoma (P=0.08) patients. This is the first case-control study to show a significant association between the hMLH1-93G-->A polymorphism and the susceptibility to and prognosis of lung cancer. The results herein may be useful for risk assessment and disease monitoring of NSCLC.

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Genetic polymorphisms at the genes involved in mismatch repair may determine individual's susceptibility to cancer initiation and progression. However, the prognostic significance of hMSH2 gIVS12-6T>C polymorphism (T-C substitution at the -6 intronic splice acceptor site of exon 13) in non-small cell lung cancer (NSCLC) remains unclear. Therefore, we investigated the frequency of hMSH2 gIVS12-6T>C polymorphism in 156 NSCLC patients and 235 cancer-free individuals matched for age, gender and smoking habit. The correlations between hMSH2 genotypes and protein expression and survival of the patients were also analyzed. The frequencies of hMSH2 genotypes T/T, T/C, and C/C were 37.4%, 43.0%, and 19.6%, respectively, and the variant (C) allele was represented at a significantly higher frequency in the general Taiwanese population than in non-Asian populations (P<0.0001, chi(2) test). No significant difference in hMSH2 genotype distribution was found between NSCLC patients and cancer-free controls (P=0.255, multivariate logistic regression). However, the homozygous wild-type T/T genotype was significantly associated with a poor prognosis (P=0.007, log-rank test). Our study showed that the frequency of the variant C allele was significantly higher in the general Taiwanese population than in non-Asian populations and the T/T genotype of hMSH2 gIVS12-6T>C polymorphism was a poor prognostic factor in NSCLC patients.

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