14 research outputs found
Increased Expression of Cathepsin L: A Novel Independent Prognostic Marker of Worse Outcome in Hepatocellular Carcinoma Patients
<div><p>Objectives</p><p>To investigate the expression and role of Cathepsin L (CTSL) in Hepatocellular carcinoma (HCC) tissue and cell line (MHCC-97H), and to evaluate the clinical and prognostic significance of CTSL protein in patients with HCC.</p><p>Methods</p><p>The expression of CTSL was examined in HCC tissue and MHCC-97H cells by Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth curve assay and colony formation assay were used to verify the effect of CTSL on the proliferation and tumor progression ability of MHCC-97H cells. Tumor formation assay in nude mice was used to analyze the effect of CTSL on the tumorigenicity of MHCC-97H cells.</p><p>Results</p><p>The status of CTSL protein in carcinoma tissues is much higher than that in paracarcinoma tissues. The overall survival of the patients with high CTSL expression was significantly shorter than the low CTSL expression group. high CTSL expression was significantly correlated with advanced clinical staging, histological grade and tumor recurrence. In vitro experiments demonstrated that over-expression of CTSL in MHCC-97H cells promoted cell proliferation and tumor progression ability. Down-regulation of CTSL showed the opposite effects. Over-expression of CTSL increase the tumorigenicity of MHCC-97H cells by in vivo experiments. Moreover, multivariate analysis suggested that CTSL expression might be an independent prognostic indicator for the survival of HCC patients after curative surgery.</p><p>Conclusions</p><p>CTSL might involve in the development and progression of HCC as a oncogene, and thereby may be a valuable prognostic marker for HCC patients.</p></div
Association between the hyperuricemia and nonalcoholic fatty liver disease risk in a Chinese population: A retrospective cohort study
<div><p>Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease associated with high levels of serum uric acid (SUA). However, whether this relationship applies in obese subjects has been unclear, and no cohort study has previously been conducted in non-obese subjects. We therefore performed a retrospective cohort study among employees of seven companies in China to investigate whether hyperuricemia was independently associated with NAFLD in obese and non-obese subjects, respectively. A total of 2383 initially NAFLD-free subjects were followed up for four years, and 15.2% (363/2383) developed NAFLD. Hyperuricemia subjects had a higher cumulative incidence than did those with normouricemia (29.0% vs. 12.9%, <i>P</i><0.001). Cox proportional hazard regression analyses showed that baseline hyperuricemia was significantly associated with risk of developing NAFLD in non-obese subjects. This relationship was significantly independent of baseline age, gender, metabolic syndrome components, and other clinical variables (RR = 1.389, 95%CI: 1.051–2.099). However, this association did not exist in obese subjects (RR = 1.010, 95%CI: 0.649–1.571). The independent effect of hyperuricemia on NAFLD was stronger in females (RR = 2.138, 95%CI: 1.050–4.355) than in males (RR = 1.435, 95%CI: 1.021–2.018). In conclusion, further studies are needed to explore the different mechanisms between obese and non-obese subjects, and the reason hyperuricemia raises NAFLD risk in females more than in males.</p></div
Relationship between CTSL expression and clinicopathologic features of HCC patients.
<p>Δ: The largest dimension of the tumor specimen.</p><p>Relationship between CTSL expression and clinicopathologic features of HCC patients.</p
Univariate and multivariate relationships between baseline hyperuricemia and incidence of NAFLD (<i>n</i> = 2383).
<p>Univariate and multivariate relationships between baseline hyperuricemia and incidence of NAFLD (<i>n</i> = 2383).</p
Analysis of CTSL protein in tissues by immunohistochemistry.
<p>A and B, CTSL expression is negative in normal liver cells. C and D, CTSL expression is weak in well-differentiated HCC cells. E and F, CTSL expression is moderate in moderately differentiated HCC cells. G and H, CTSL expression is strong in poorly differentiated HCC cells. (A, C, E, G ×200; B, D, F, H ×400).</p
Univariate survival analysis of 82 patients with HCC.
<p>Δ: The largest dimension of the tumor specimen.</p><p>Univariate survival analysis of 82 patients with HCC.</p
Expression levels of CTSL in HCC tissues.
<p>A. Expression levels of CTSL protein in 13 paired HCC tissues by Western blotting. N, paracarcinoma (normal) liver tissues. T, HCC tissues. B. Quantitative analysis of CTSL protein in 13 paired HCC tissues. C. mRNA levels of CTSL in 13 paired HCC tissues by real-time PCR.</p
The effect of CTSL on the proliferation and tumor progression ability of MHCC-97H cells.
<p>A. Western blotting analysis of CTSL protein expression in HCC cell line (MHCC-97H), colorectal carcinoma cell lines (CaCO2 and LoVo), stably CTSL-expressed MHCC-97H cell line, stably CTSL-expressed CaCO2 cell line, empty vector stable cell lines (MHCC-97H-Con or CaCO2-Con), and MHCC-97H cell line transfected by CTSL-shRNA or Con-shRNA. B. Colony formation assay and MTT assay of MHCC-97H cells and CaCO2 cells with over-expression of CTSL. (Colony formation assay: MHCC-97H-Con (vector) vs MHCC-97H-CTSL, P = 0.0042; CaCO2-Con (vector) vs CaCO2-CTSL, P = 0.0072. MTT: MHCC-97H-Con (vector) vs MHCC-97H-CTSL, P = 0.012; CaCO2-Con (vector) vs CaCO2-CTSL, P = 0.035). C. Colony formation assay and MTT assay of MHCC-97H cells with down-regulated CTSL. (Colony formation assay: MHCC-97H-Con-shRNA vs MHCC-97H-CTSL-shRNA, P = 0.003; MTT: MHCC-97H-Con-shRNA vs MHCC-97H-CTSL-shRNA, P = 0.001. (**P<0.01 as compared to parental groups, *P<0.05 as compared to parental groups).</p
Baseline characteristics of subjects with and without hyperuricemia.
<p>Baseline characteristics of subjects with and without hyperuricemia.</p
Univariate and multivariate relationship between baseline hyperuricemia and incidence of NAFLD in non-obese subjects.
<p>Univariate and multivariate relationship between baseline hyperuricemia and incidence of NAFLD in non-obese subjects.</p