Shen-Nien Wang

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established. Aim: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development. Methods: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival. Results: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan–Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups. Conclusions: The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Potential role of leptin expression in hepatocellular carcinoma

Background: Obesity is associated with hepatocellular carcinoma (HCC). The association may result from the aberrant expression of adipokines. Aim: To explore the potential biological effect and prognostic value of leptin, one of the adipokines, in HCC. Methods: Immunohistochemistry was used to evaluate the expression of leptin in 68 patients with HCC. The expression of Ki-67 and microvessel density (MVD) of tumorous lesions in HCC were also analysed. The result of leptin expression was further correlated with Ki-67 expression, intratumour MVD, clinicopathological characteristics, overall survival and the postoperative use of medroxyprogesterone acetate (MPA). Results: High leptin expression was seen in 60.3% of patients with HCC and was significantly correlated with intratumour MVD (high v low; 59.2 (standard deviation 3.2) v 44.2 (19.5), p = 0.004), but not with Ki-67 expression. No marked correlation was seen between leptin expression and clinicopathological characteristics. However, using a multivariate Cox’s proportional hazards model, leptin expression was a predictor for improved overall survival of patients with HCC (odds ratio 0.16; 95% confidence interval 0.03 to 0.87; p = 0.033). In addition, the Kaplan–Meier survival curve showed that high leptin expression was associated with a better survival in patients with HCC, treated postoperatively with MPA (p = 0.008, log rank test). Conclusion: High leptin expression was associated with an increased intratumour MVD and thus may be associated with HCC development. In addition, high leptin expression was a predictor for improved survival of patients with HCC, treated postoperatively with MPA.

Decreased microRNA-221 is associated with high levels of TNF-α in human adipose tissue-derived mesenchymal stem cells from obese woman.

Aim: The present study aimed to investigate the regulation and involvement of miR-221 in the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). The relationships between miR-221 and pro-inflammatory markers and adipokines were also explored. Methods: Eight adipose tissues were obtained from four obese (mean body mass index (BMI) =31.7 kg/m2) and four lean (mean BMI= 21.5 kg/m2) women. hASCs were induced to differentiate, and the related gene expression were measured in the hASC-differentiated adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). Results: During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR-221 levels were lower in hASC-differentiated adipocytes from obese subjects than in the corresponding adipocytes from lean subjects. Higher TNF-α mRNA levels were associated with lower levels of miR-221. In addition, the miR-221 levels in the adipocytes were inversely correlated with BMI. Conclusion: Our results support the link between miR-221 and obesity development as well as obesity related inflammatory status.

Potential prognostic value of leptin receptor in hepatocellular carcinoma

Background: Obesity is associated with several human malignancies, including hepatocellular carcinoma (HCC). This association may result from the deregulated expression of adipokines. Aims: To explore the potential role and the prognostic value of leptin receptor (Ob-R) in HCC. Methods: 66 patients with pathologically confirmed HCC were included in this study. Immunohistochemistry was used to evaluate the expression of Ob-R, microvessel density (MVD) and Ki-67 index in these patients. Eventually, the profiles of Ob-R expression, obtained by a semiquantitative scoring system, were further correlated with Ki-67 expression, intratumour MVD, clinicopathological characteristics and overall survival. Results: High Ob-R expression was seen in 53% of patients with HCC and was significantly correlated with intratumour MVD (high v low; 59.4 ?3.2) v 44.7 ?3.7); p = 0.004), but not with Ki-67 expression. In addition, Ob-R expression was inversely correlated with vascular invasion (p = 0.037), but not with other known clinicopathological characteristics. The Kaplan–Meier survival curve showed that high Ob-R expression was associated with a better overall survival (p = 0.027). Meanwhile, multivariate analysis showed that Ob-R expression was a significant determinant for HCC (odds ratio 0.02, 95% confidence interval 0.01 to 0.85; p = 0.041). Conclusion: Ob-R expression may have a potential role in the carcinogenesis of HCC. The positive association of Ob-R expression in the cancerous lesions of HCC with the survival outcome can be explained by its inverse correlation with vascular invasion, and may have prognostic value in HCC.

The promoting effect of adiponectin in hepatocellular carcinoma

Adipokines may explain the newly established association of obesity with hepatocellular carcinoma (HCC). This study investigated if adiponectin levels in HCC patients differed from healthy controls and their potential effect in the development of HCC.

Efficacy of sorafenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative surgery: A pilot study

Until now, no effective adjuvant therapy to prevent early recurrence of hepatocellular carcinoma (HCC) after curative treatment has been reported. The aim of this study is to evaluate the clinical benefit of sorafenib as adjuvant treatment in subjects with HCC after hepatic resection.

Association of circulating insulin‐like growth factor 1 with hepatocellular carcinoma: one cross‐sectional correlation study

Deregulation of insulin‐like growth factor‐1 (IGF‐1) has been implicated in the pathogenesis of several malignancies. This study aimed to investigate the association of changes in circulating IGF‐1 with hepatocellular carcinoma (HCC). The radioimmunoassay was used to analyze serum IGF‐1 levels of 65 HCC patients and 165 healthy subjects. Serum IGF‐1 levels were significantly decreased in the HCC patients as compared with the healthy subjects (158.46±105.07 vs. 247.63±149.96 ng/mL, P<0.001). Furthermore, insulin resistance was significantly higher in the HCC patients than the healthy subjects (P=0.027). In addition, the significant correlations of serum IGF‐1 levels with age and insulin resistance in the healthy subjects were not noted in the HCC patients. Intriguingly, individuals with hepatitis C virus (HCV), not hepatitis B virus, had remarkably decreased IGF‐1 levels in both groups of the HCC patients and healthy subjects. Moreover, in the HCV subgroup, serum IGF‐1 levels were significantly reduced in the HCC patients than the healthy subjects (113.14±71.28 vs. 172.42±74.02 ng/mL, P=0.003). In conclusion, decreased serum IGF‐1 levels were associated with HCC and the decrease was remarkably noted in those patients concomitant with chronic hepatitis C. J. Clin. Lab. Anal. 24:195–200, 2010.

The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes

Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world. The effect of preoperative transarterial chemoembolization (TACE) for resectable HCC is still controversial and cost‐associated treatments are unknown.

Phosphorylated p38 and JNK MAPK proteins in hepatocellular carcinoma

Eur J Clin Invest 2012; 42 (12): 1295–1301

Urinary cell-free DNA as a potential tumor marker for bladder cancer

The objective was to assess the possibility of measuring urine creatinine (UCr)-adjusted urinary cell-free (ucf) DNA concentration as a noninvasive screening tool for bladder cancer. Using PicoGreen-based detection, the ucf-DNA/UCr concentration was quantified in urine supernatant specimens from 46 bladder cancer patients and 98 controls and compared to 400-bp real-time PCR-based detection, which detected the amplification of 400-bp beta-actin (named 400-bp ucf-DNA/UCr). The mean concentrations for both PicoGreen and 400-bp ucf-DNA (ng/mL)/UCr (mg/dL) were significantly higher in bladder cancer patients than in controls: 15.28 vs 6.68 (p<0.001, t-test) and 14.98 vs 1.07 (p<0.001), respectively. Among different stages and grades, no significant difference was found between these two methods. The areas under the ROC curves of PicoGreen and 400-bp ucf-DNA/UCr were 0.571 (95% confidence interval, 0.451-0.692) and 0.805 (95% confidence interval, 0.713-0.896), respectively. In 400-bp ucf-DNA/UCr, the best sensitivity and specificity were 86.1% and 72.0% at the cutoff value of 0.0645. These data indicated that 400-bp ucf-DNA/UCr is more reliable for bladder cancer detection than PicoGreen. In conclusion, our results suggest that ucf-DNA/UCr can be used as a potential tumor marker for bladder cancer, especially for detecting longer DNA fragments.