miR-211 regulates the expression of RRM2 in tumoral metastasis and recurrence in colorectal cancer patients with a k-ras gene mutation.

Colorectal cancer (CRC) ranks as the third-leading cause of cancer-associated mortalities in Taiwan. The expression of ribonucleotide reductase M2 (RRM2) and p53R2 is associated with tumoral malignancy and progression in several types of cancer. The aim of the present study was to determine the association of p53R2/RRM2 with the upstream expression of microRNA (miR)-211 and the association of expression levels of p53, APC and k-ras with clinical outcomes in patients with CRC. The study consisted of 192 tumor tissue samples obtained from patients with CRC. Immunohistochemistry and direct sequencing of DNA were performed to analyze p53R2/RRM2 protein expression and p53/APC/k-ras gene mutations in these samples. The expression level of miR-211 was detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the expression of p53R2 was lower and that of RRM2 was higher in patients with lymph node metastasis, distant metastasis, and late-stage CRC compared with patients without lymph node metastasis, distant metastasis and early-stage CRC. A high expression of RRM2 in patients had a negative effect on overall survival (OS) and disease-free survival (DFS) in CRC. Positive expression of RRM2 was detected in tumor tissues, and expression associated with the presence of k-ras gene mutation. Furthermore, it was detected that the upstream miR-211 expression was negatively associated with RRM2 expression in tumor tissues of patients with CRC. miR-211 expression was associated with survival and tumoral recurrence in patients with k-ras mutations. The present authors suggest that the downregulation of miR-211 and overexpression of RRM2 in tumor tissues of patients with CRC could be used to predict metastases and disease prognosis, particularly in patients with k-ras gene mutations.

MicroRNA expression profiling in PBMCs: a potential diagnostic biomarker of chronic hepatitis C.

The expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 in PBMCs were significantly higher in CHC patients compared with healthy controls and significantly different between CHC patients with HCV genotype 1 (GT-1) and non-genotype-1 (non-GT-1). Multivariate logistic regression analysis also showed that patients with high expression levels of the six target miRNAs had an approximately 7.202-fold risk of CHC compared with those with low expression levels of the target miRNAs. We concluded that the expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 target miRNAs in PBMCs of CHC may act as significant risk biomarkers for the development of CHC.

Assessment of health-related quality of life in antiviral-treated Taiwanese chronic hepatitis C patients using SF-36 and CLDQ.

BACKGROUND: Interferon (IFN) therapy can cause significant side effects in chronic hepatitis C (CHC) patients; however, the health-related quality of life (HRQOL) of antiviral-treated CHC patients has not been established in Taiwan. This study evaluated domains and the degree to which antiviral treatment affects the HRQOL in CHC patients and identifies factors associated with variations between patients. METHODS: Health-related quality of life (HRQOL) was assessed using the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) in 108 antiviral-treated CHC patients. Eight scales and two summary scales of the SF-36 were compared with 256 age- and gender-matched population norms and 64 age- and gender-matched CHC patients without antiviral therapy. Descriptive statistic measures, one-way ANOVA, and regression analysis were used for data analysis. RESULTS: (1) CHC patients receiving antiviral treatment displayed significantly lower scores in six scales, the Physical Component Summary (PCS), and the Mental Component Summary (MCS) of the SF-36, when compared to the population norms and patients without antiviral therapy (p < 0.05). (2) The mean CLDQ score of antiviral-treated patients was lower than that of patients without antiviral therapy, including subscales of 'fatigue', 'systemic symptoms', and 'role emotion'. (3) All SF-36 subscales significantly correlated with all CLDQ subscales, with the greatest correlation coefficients shown between fatigue and vitality and mental health of SF-36. (4) Antiviral therapy had a greater negative impact on females in the CLDQ, on all patients during treatment weeks 9-16 in the PCS and on patients with a monthly income of less than NT$10,000 in the CLDQ, PCS, and MCS. CONCLUSIONS: This study highlighted impairments in the quality of life of chronic hepatitis C patients treated with IFN-based therapy. The significant factors associated with HRQOL include gender, income, and treatment duration. The results of this study might provide nurses with a comprehensive understanding of HRQOL and its determining factors in antiviral-treated CHC patients. The findings can serve as a useful reference for nursing personnel in developing instructions for upgrading the care of CHC patients.

Safety and efficacy of adefovir therapy for lamivudine-resistant hepatitis B virus infection in renal transplant recipients.

BACKGROUND/PURPOSE: The emergence of lamivudine (LAM)-resistant mutants after prolonged LAM therapy may reduce its therapeutic effects against hepatitis B virus (HBV). Adefovir dipivoxil (ADV) is an effective treatment of LAM-resistant HBV infections. However, only limited data are available regarding the safety and efficacy of ADV for treating HBsAg-positive renal transplant recipients. METHODS: Fourteen HBsAg-positive patients who underwent renal transplantation and developed the YMDD mutation after prolonged LAM therapy were retrospectively analyzed. Five patients were administered ADV monotherapy, while nine patients received ADV plus LAM combination therapy. Data on age, gender, duration of previous LAM treatment, pre-LAM HBV DNA and liver enzyme levels, duration of LAM treatment prior to the emergence of mutations, duration of ADV rescue therapy, and the clinical outcomes of treatment (i.e., normalization of alanine transaminase (ALT) and undetectable HBV DNA levels) were analyzed. RESULTS: The mean age of the patients was 46.8 ± 11.5 years. Males were predominantly studied. The mean follow-up duration of rescue therapy was 38.2 ± 18.3 months. At the beginning of rescue therapy, the mean serum ALT level was 142.2 ± 99.8 IU/mL, while the median serum level of HBV DNA was 7.85 log(10) copies/mL. Patients who received combination therapy tended to demonstrate undetectable serum HBV DNA levels, but no significant differences in terms of clinical outcomes were observed between patients who received ADV monotherapy and patients who received combination therapy. After 12 months of treatment, 13 patients (92.8%) developed normalized ALT levels. Five (35.7%) and six (42.8%) patients achieved undetectable serum HBV DNA levels after 12 months and 24 months of treatment, respectively. No virological breakthroughs were observed. Twenty-nine percent of the patients developed moderate to severe renal insufficiency. CONCLUSION: Although no statistical difference was noted, ADV plus LAM combination therapy tended to demonstrate a higher therapeutic efficacy than ADV monotherapy for treating LAM-resistant HBV infection in renal transplant recipients. Renal function should be closely monitored in order to ameliorate nephrotoxicity.