HSP70s: From Tumor Transformation to Cancer Therapy

Heat shock proteins (HSPs) are a defined set of chaperones for maintaining proper functions of proteins. The HSP70 family, one of the most inducible families in response to stress, protects cells from stress-induced cell death. It has been documented that HSP70s are highly expressed in various types of cancer cells and make the cells resistant to adverse microenvironments, such as hypoxia and glucose starvation, which are common features in malignant progression. Over-expression of HSP70s is thus associated with tumor transformation and eventually results in a decrease of chemotherapy efficacy. Notably, the distribution of HSP70s is deregulated in cancer cells. It has been reported that HSP70s localize distinct organelles or are exported to humoral circulation during cancer development. Either surface or exported HSP70s play danger signals and trigger immune response to destroy the tumor cells. In this review, we lay out recent advances in the HSP70s-mediated cancer diagnosis and therapy. This review would be enlightening for clinical cancer medicine

Association of p53 Codon 72 Polymorphism with Risk of Hypopharyngeal Squamous Cell Carcinoma in Taiwan

Backgroundp53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit.MethodsGenomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism.ResultsPatients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04).ConclusionThis study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer

The Design and Implementation of Collaborative Filtering in Data Mining

Data mining is the process of discovering explicit knowledge from large amounts of data stored in database, data warehouse or other repositories. There have been many studies about models of data mining such as association rule, sequential pattern and so on. Collaborative filtering is one of data mining models. In this paper, we propose two approaches to solving the mining process of collaborative filtering. Finally, collaborative filtering mining is applied to Knowledge Management system

IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection

Antipsychotic Prescription Trends, Patterns and Associated Factors in Taiwanese Children and Adolescents

This study evaluated the prescription trends, patterns and associated factors of antipsychotic medication in children and adolescents. We conducted a retrospective study by using the database of outpatient health insurance files of a psychiatric center in Northern Taiwan from 2004 to 2013. A total of 173,209 outpatient health insurance files were included. The average age of the study patients was 11.3 (±3.9) years. Of all visits of the patients, 13.4% were prescribed antipsychotics. The prescription rate of all antipsychotic medication types in all the outpatients aged ≤18 years increased yearly by 0.6%. The prescription rate of first-generation antipsychotics decreased with an estimated average annual percent change of 5.6% (p < .001). By contrast, the prescription rate of second-generation antipsychotics increased with an estimated average annual percent change of 3.4% (p <.001). Multiple logistic regression analysis was performed to examine clinical factors (age, sex and diagnosis) associated with antipsychotic prescription. After adjusting for other variables, antipsychotic prescription was found to be increased by 1.31 times every year with age and by 1.06 times in the male patients. The patients with diagnoses other than schizophrenia appeared less likely to be prescribed antipsychotics. Antipsychotic medications are being increasingly prescribed to children and adolescents in recent years. T he efficacy and safety of antipsychotics in children and adolescents warrant clinical attention

Sensitivity of Deep-Towed Marine Electrical Resistivity Imaging Using Two-Dimensional Inversion: A Case Study on Methane Hydrate

Uncertain physical properties of methane hydrate (MH) above a bottom simulating reflector should be estimated for detecting MH-bearing formations. In contrast to general marine sediments, MH-bearing formations have a relatively high electrical resistivity. Therefore, marine electrical resistivity imaging (MERI) is a well-suited method for MH exploration. The authors conducted sensitivity testing of sub-seafloor MH exploration using a two-dimensional (2D) inversion algorithm with the Wenner, Pole-Dipole (PD) and Dipole-Dipole (DD) arrays. The results of the Wenner electrode array show the poorest resolution in comparison to the PD and DD arrays. The results of the study indicate that MERI is an effective geophysical method for exploring the sub-seafloor electrical structure and specifically for delineating resistive anomalies that may be present because of MH-bearing formations at a shallow depth beneath the seafloor

Influence of Socioeconomic Factors, Gender and Indigenous Status on Smoking in Taiwan.

The indigenous Austronesian minority of Taiwan is heavily affected by health disparities which may include suffering from a greater burden of the tobacco epidemic. While a lack of representative data has historically precluded an investigation of the differences in smoking between Taiwanese ethnicities, these data have recently become available through an annual population-based telephone survey conducted by the Health Promotion Administration, Ministry of Health and Welfare (previously known as the Bureau of Health Promotion (BHP), Department of Health). We used the BHP monitoring data to observe the prevalence of smoking and environmental tobacco smoke exposure among indigenous and non-indigenous Taiwanese surrounding a tobacco welfare tax increase in 2006, investigate ethnic differences in smoking prevalence and environmental tobacco smoke exposure each year between 2005 and 2008, and perform multiple logistic regression to estimate measures of association between potential risk factors and smoking status. Despite significant ethnic and gender differences in smoking prevalence, smoking status was not found to be significantly associated with ethnicity after controlling for socioeconomic and demographic factors

Recombinant VP1, an Akt Inhibitor, Suppresses Progression of Hepatocellular Carcinoma by Inducing Apoptosis and Modulation of CCL2 Production

BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC), one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC

TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells

<p>Abstract</p> <p>Background</p> <p>Eosinophilic granulocytes are important for the human immune system. Many cationic proteins with cytotoxic activities, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), are released from activated eosinophils. ECP, with low RNase activity, is widely used as a biomarker for asthma. ECP inhibits cell viability and induces apoptosis to cells. However, the specific pathway underlying the mechanisms of ECP-induced cytotoxicity remains unclear. This study investigated ECP-induced apoptosis in bronchial epithelial BEAS-2B cells and elucidated the specific pathway during apoptosis.</p> <p>Results</p> <p>To address the mechanisms involved in ECP-induced apoptosis in human BEAS-2B cells, investigation was carried out using chromatin condensation, cleavage of poly (ADP-ribose) polymerase (PARP), sub-G1 distribution in cell cycle, annexin V labeling, and general or specific caspase inhibitors. Caspase-8-dependent apoptosis was demonstrated by cleavage of caspase-8 after recombinant ECP treatment, accompanied with elevated level of tumor necrosis factor alpha (TNF-α). Moreover, ECP-induced apoptosis was effectively inhibited in the presence of neutralizing anti-TNF-α antibody.</p> <p>Conclusion</p> <p>In conclusion, our results have demonstrated that ECP increased TNF-α production in BEAS-2B cells and triggered apoptosis by caspase-8 activation through mitochondria-independent pathway.</p