Prognostic Value of Brain Metastasis-Free Interval in Patients with Breast Cancer Brain Metastases

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins

Flavonoids are associated with multiple biological and pharmacological activities, including anti-enterovirus activity. An internal ribosomal entry site (IRES) required for viral protein translation is a potential drug target for enterovirus 71 (EV71). Regulation translation initiation requires the interaction of IRES specific trans-acting host factors with viral IRES element. By evaluation of 12 flavonoids against EV71 infection, we found that (a) 7,8-dihydroxyflavone, kaempferol, quercetin, hesperetin and hesperidin exhibited more than 80% of cell survival and inhibition of EV71 infection; however, no anti-oxidative effects were noted from these flavonoids; (b) among them, only 7,8-dihydroxyflavone, kaempferol and hesperetin showed 40% of viral IRES activity; (c) kaempferol interfered with EV71 virus replication and pseudotyped virus production; and (d)FUBP1, FUBP3, HNRPD, HNRH1 and HNRPF proteins are associated with EV71 5'-UTR as shown using RNA affinity pull-down assay coupled with LC-MS/MS analysis. We firstly found that kaempferol may change the composition of these IRES associated trans-acting factors, and affect IRES function and EV71 virus replication. These studies help not only to understand the IRES function but also the mechanism by which drug induced cellular proteins are acting against EV71 infection. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved

IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan

Objective The genetic control of Interleukin-10 (IL-10) and Tumour necrosis factor-alpha (TNF-alpha) production and the possible interaction between the two cytokines in influencing SLE susceptibility as well as clinical features has not been completely evaluated in the Taiwanese population. Methods We investigated the association of IL-10 and TNF-alpha promoter polymorphisms (-1082, -819 and -592 for IL-10 gene; -308 for TNF-alpha gene) with SLE in a total of 172 Taiwanese patients and 215 controls. Results Our results indicate that IL-10 A/T/A-A/T/A genotype was associated with Taiwanese SLE, whereas no significance was observed between TNF-alpha genotype and SLE. Furthermore, the TNF-alpha G allele frequency of the polymorphism at -308 was significantly decreased in patients with oral ulcers. The combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly increased in SLE patients. In addition, the combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly decreased in patients with oral ulcers. Conclusion These results suggest a significant correlation of the combined IL-10 and TNF-alpha genetic polymorphisms contribute to SLE susceptibility and clinical features in the Taiwanese population

Subtype switching in breast cancer brain metastases: a multicenter analysis

Background. Breast cancer (BC) brain metastases (BM) can have discordant hormonal or human epidermal growth factor receptor 2 (HER2) expression compared with corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in BM.Methods. BCBM patients seen at 4 tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed.Results. In BM from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen, 25.2% for progesterone, and 10.4% for HER2. Because estrogen and progesterone were considered together for hormonal status, 50 (22.8%) patients switched subtype as a result; 20 of these switches were HER2 based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by estrogen loss (hazard ratio = 1.80, P= 0.03). Patients gaining HER2 status (n =8) showed a nonsignificant tendency toward improved survival (hazard ratio = 0.64, P= 0.17).Conclusions. In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie