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Anti-epidermal growth factor receptor (EGFR) therapy has established efficacy in metastatic colorectal cancer, but a significant number of patients do not respond to such treatment. Recently, various biomarkers were reported to be useful in predicting resistance to anti-EGFR. All the potential biomarkers predicting resistance to anti-EGFR are reviewed herein from five aspects. First, upstream molecules, including epiregulin (EREG) and amphiregulin (AREG), might play different roles according to their abnormal levels in tumor tissue and serum. Second, the EGFR amplification and distinct polymorphisms may have roles in identifying patients for initial anti-EGFR mAbs therapy, while rare EGFR mutations have limited predictive values. Third, among the downstream molecularly related factors, rat sarcoma viral oncogene (Ras) has been identified as a successful predictor, while B-Raf proto-oncogene (BRAF) is considered as a prognostic factor rather than a predictor. Fourth, among the molecular bypass pathway components, phosphatidylinositol 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) may be potential biomarkers in the future, while activation of hepatocyte growth factor (HGF)/c-Met signaling confers resistance to anti-EGFR therapy. Fifth, many microRNAs and additional molecular biomarkers are promising in predicting the efficacy of anti-EGFR therapy. Applications of multiple biomarkers are more effective than the use of a single biomarker in selecting patients who might benefit from cetuximab- or panitumumab-based treatments. Comprehensive molecular analyses of the EGFR signaling pathways should be considered in the future. Subsequent prospective trials will be required to further confirm the clinical utility of these biomarkers.

Many foreigners enter Taiwan for the purpose of marriage or study, or as dependants or relatives of Taiwanese citizens. The aim of this study was to investigate the proportions of these immigrants infected with intestinal parasites. A total of 2875 foreigners from 39 countries or regions underwent stool examination in our hospital within the study period, and the merthiolate iodine formaldehyde method was used to diagnose intestinal parasite infections. In total, 214 foreigners (7.4%) were found to be infected, and hookworm was identified as the most prevalent intestinal parasite (2.92%). Infection was most prevalent in the Vietnamese foreigners (46.3%), followed by the Chinese (38.8%), and was more prevalent in females (92.3%) than in males. Among the intestinal parasites identified, hookworm (2.92%), Trichuris trichiura (1.18%), and Blastocystis hominis (1.14%) were the three most prevalent. Infection was most prevalent in the foreign brides group (11.9 %), hookworm and Trichuris trichiura being the two most common species of intestinal parasite in the foreign brides and foreign dependants/relatives of Taiwanese citizens, while the proportion of foreign students infected was lower. Most foreigners enter Taiwan for the purpose of marriage or study, or as dependants/relatives of Taiwanese citizens, and originate from countries or regions in which public health is poorer than in Taiwan. Therefore, close monitoring and examination of these foreigners continue to be indicated.

Curcumin has been shown to possess potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism involved in curcumin's ability to suppress prostate cancer cell invasion, tumor growth, and metastasis is not yet well understood. In this study, we have shown that curcumin can suppress epidermal growth factor (EGF)- stimulated and heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment significantly resulted in reduced matrix metalloproteinase 9 activity and downregulation of cellular matriptase, a membrane-anchored serine protease with oncogenic roles in tumor formation and invasion. Our data further show that curcumin is able to inhibit the induction effects of androgens and EGF on matriptase activation, as well as to reduce the activated levels of matriptase after its overexpression, thus suggesting that curcumin may interrupt diverse signal pathways to block the protease. Furthermore, the reduction of activated matriptase in cells by curcumin was also partly due to curcumin's effect on promoting the shedding of matriptase into an extracellular environment, but not via altering matriptase gene expression. In addition, curcumin significantly suppressed the invasive ability of prostate cancer cells induced by matriptase overexpression. In xenograft model, curcumin not only inhibits prostate cancer tumor growth and metastasis but also downregulates matriptase activity in vivo. Overall, the data indicate that curcumin exhibits a suppressive effect on prostate cancer cell invasion, tumor growth, and metastasis, at least in part via downregulating matriptase function. Cancer Prev Res; 6(5); 495–505. ©2013 AACR.

Detection and quantification for hepatitis B virus (HBV) DNA has been an essential tool in the clinical setting. We aimed to assess clinical performance of the RealArt HBV TM PCR (RealArt) assay and the COBAS TaqMan HBV (COBAS) assay. Serum levels of HBV DNA in 146 treatment-naïve chronic HBV (CHB) Taiwanese patients (118 males, 47 HBeAg + ; mean age, 34.7+/-13.0 y) were determined by both assays. The detection rate by the RealArt assay was 85.6% (125/146), which was not significantly different from the COBAS assay (89.7%, 131/146). The detection rate was also not significantly different between both assays irrespective of HBeAg seropositivity. The 2 assays were also comparable regarding quantification rate (92.8%, 116/125 vs 93.1%, 122/131). There was a positive correlation in the 109 specimens measurable by both assays (r=0.94,p0.001). The mean HBV DNA level measured by the COBAS assay was significantly higher than the RealArt assay (5.24+/-1.83 vs 4.79+/-2.09 log IU/ml, p0.001). This study demonstrated that both RealArt and COBAS assays were comparable regarding clinical performance in HBV DNA measurement.

Human leukocyte antigens (HLAs) may play a role in the clinical evolution of hepatitis C virus (HCV) infection. The present study was aimed at elucidating the association between the HLA loci and responses to combination therapy with pegylated interferon-alpha 2a (PEG-IFN) and ribavirin in Taiwanese. We enrolled a total of 208 treatment-naïve Taiwanese chronic hepatitis C (CHC) patients treated with combination therapy. Patients with sustained virological response (SVR) had a significantly higher frequency of genotype non-1b infection, lower pretreatment HCV RNA levels and a higher frequency of mild hepatic fibrosis (fibrosis score: F: 0-2). The HLA A24 and B40 alleles were significantly associated with SVR after adjusted for the other three confounding factors including HCV genotype, hepatic fibrosis and pretreatment serum HCV RNA levels. Haplotypes (B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, and Cw1- DRB1*9) were significantly associated with SVR to combination therapy. For 167 patients with genotype 1b infection and viral loador =5.6 logIU/ml or genotype non-1b infection, the B46 was significantly associated with sustained response with OR (odds ratio) [95% CI (confidence interval) of 0.047 (0.168-0.988)]. Haplotypes B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, Cw1- DRB1*9 and DQB1*3- DRB1*9 were found to be associated with SVR to PEG-IFN/ribavirin therapy with OR (95% CI) of 0.179 (0.032-0.989), 0.313 (0.107-0.918), 0.350 (0.145-0.845), 0.282 (0.105-0.759) and 0.412 (0.174-0.978), respectively. We concluded that the virological and the host immunogenetic factors may possibly predict the response to combination therapy in CHC patients.

Background: Polymerase chain reaction (PCR) methods play an essential role in providing data relating to diagnosis, monitoring and treatment of hepatitis C virus (HCV) infection. The real-time reverse transcription PCR (RT-PCR) assay is an established and promising tool in terms of quantifying HCV RNA for clinical application. This study aimed to evaluate the performance characteristics of a real-time RT-PCR-based test in a clinical setting. Methods: Validation and reproducibility tests were performed using a standard panel. Sera from 197 chronic HCV patients were analyzed by the real-time RT-PCR assay and the results were compared with the Versant bDNA3.0 assay (bDNA3.0). Results: The real-time RT-PCR assay showed an acceptable linear response (r 2 =0.989-0.995) in the serial dilutions regarding genotypes 1b, 2a, 2b and 1b+2a. HCV viral loads were quantifiable in all 197 patients (100%) by the real-time RT-PCR assay and in 194 (98.5%) by the bDNA3.0. HCV RNA quantification values measured by the real-time RT-PCR and bDNA3.0 assays were positively correlated (Pearson's correlation coefficient r=0.734, p

Curcumin has been shown with potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism how curcumin suppresses prostate cancer cell migration and invasion is not well understood. In this study we showed that curcumin could significantly suppress prostate cancer PC3 cell migration and invasion. Moreover, our data also showed that curcumin was able to suppress EGF- or heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment resulted in not only significant reductions on MMP-9 and MMP-2 activities, but also on activated level of matriptase which is a membrane-bound serine protease and has been proposed to play important roles in tumor invasion and malignancy. Matriptase is synthesized as a full length zymogen, which is rapidly stepped into the maturation process, mature form through a cleavage within the SEA domain to from a latent matriptase. Our data further showed that curcumin can inhibit the latent matriptase formation in the maturation process to affect matriptase activity. Furthermore, the reduction of activated matriptase by curcumin was also partly due to curcumin promoting the shedding of activated matriptase into extracellular environment, but not due to curcumin effect on matriptase gene expression. In addition, we established the stable pools of CWR22Rv1 cells with matriptase overexpression and found that expression of matriptase in CWR22Rv1 cells enhanced their invasive ability. With curcumin treatment, the invasive ability induced by matriptase overexpression was significantly suppressed. In summary, the data indicated that curcumin exhibits a suppressive effect on prostate cancer cell invasion, at least in part by down-regulating matriptase activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2000. doi:1538-7445.AM2012-2000

We evaluated the performance of a hepatitis C virus (HCV) antigen/antibody combination test [Murex HCV Antigen/Antibody Combination Test (Murex Ag/Ab test)] by comparing it with the current third-generation HCV antibody enzyme immunoassay (anti-HCV). A total of 403 serum samples were consecutively collected from four patient groups: healthy controls ( n =100); HCV-infected patients (HCV group, n =102); Human immunodeficiency virus (HIV)/HCV-infected patients (HIV/HCV group, n =100); and patients with uremia (uremia group, n =101). Performances were evaluated for the Murex Ag/Ab, anti-HCV, and HCV RNA in the HIV/HCV and uremia patient groups. In the HCV group, all 102 samples showed concordant positive and negative results for anti-HCV, Murex Ag/Ab, and HCV RNA tests. In the HIV/HCV group, all 100 samples were positive for both anti-HCV and Murex Ag/Ab tests, whereas 88 patients (88%) were HCV RNA positive. In the uremia group, 14 (69.0%) of the 23 anti-HCV-positive patients were HCV RNA positive, whereas 14 (77.8%) of the 18 Murex Ag/Ab–positive patients were HCV RNA positive. None of anti-HCV-negative or Murex Ag/Ab–negative patients were HCV RNA positive. Based on the HCV RNA assay, the sensitivities for both anti-HCV and Murex Ag/Ab assays were 100%, whereas the specificities of these two assays were 89.7% and 95.4%, respectively. With good sensitivity and specificity, the Murex Ag/Ab assay could be a useful alternative diagnostic tool, especially in immunocompromised populations, such as patients with uremia or those infected with HIV.