Objective To investigate the crosstalk between Wnt signaling pathway and TGF-? signaling pathway in prostate cancer cell line PC-3. Methods Luciferase report assay and RT-PCR methods were used to explore the crosstalk between two pathways. Results Wnt signaling pathway activated TGF-? responsive CAGA-luciferase reporter activity. ?-catenin(WT), TCF-4(WT), GSK3? (KM) activated while TCF-4(DN) inhibited CAGA reporter activity. ?-catenin(WT), TCF-4(WT) synergized to activate TGF-? signaling while TCF-4(DN) had converse effect.TGF-? signaling pathway activated LEF-1 luciferase activity through a Smad3-dependent manner.Smad7 activated LEF-1 luciferase activity,Smad3 and Smad4 also synergically activated LEF-1 reporter activity.?-catenin(WT),TCF-4(WT) cooperated with each other to the activity of cyclinD1 promoter luciferase while Smad3 inhibited cyclinD1 promoter activity.The inhibitory effect of Smad3 on cyclinD1 promoter could be partially reversed by co-transfecting ?-catenin(WT),TCF-4(WT).TGF-? induced the expression of VEGF in PC-3 cells and this effect was enchanced by LiCl addition. Conclusions Wnt signaling pathway and TGF-? signaling pathway can activate each other in prostate cancer cell line PC-3.Two pathways have crosstalk and this might be important for the development and progression of prostate carcinoma.

Objective To assess hepatitis B virus(HBV)and hepatitis C virus(HCV)infections in different anatomic location of cholangiocarcinoma(CC)and relationship with abnormal p53 expression.Methods A total of 411 CC samples including intrahepatic cholangiocarcinoma(ICC 312 cases);perihilar cholangiocarcinoma(PHC,73 cases)and distal cholangiocarcinoma(DC,26 cases)underwent serologic test for HBsAg and anti-HCV using microparticle enzyme immunoassay.Abnormal p53 expression was detected in formalin-fixed.paraffin-embedded CC tissues by immunohistochemistry.Results Seropositivity for HBsAg and anti-HCV were found in 48.4%(151/312)and 2.9%(9/312)of ICC cases,and in 10.9%(8/73)and zero of PHC,and in 7.7%(2/26)and zero of DC,respectively.Abnormal p53 expression was detected in 30.1%(94/312)of ICC cases.23.3%(17/73)of PHC cases and 19.2%(5/26)of DC cases.There was no correlation between seropositivity of HBsAg and anti-HCV and p53 overexpression among three groups of CC. Conclusions HBV but not HCV infection may be associated with the development of ICC.p53 abnormality may not play a significant role in HBV-associated carcinogenesis of ICC.

Objective To evaluate the techniques and the effects of resection of giant hepatic tumors in the caudate lobe of the liver. Methods The clinical data of 33 patients with primary liver carcinoma or benign tumor (>10 cm) in the caudate lobe of the liver surgically treated in our hospital from January 2000 to January 2007 were retrospectively analyzed. Results The total of 33 huge liver tumors with a median diameter of 12.3 cm (10.2-15.3cm) were successfully resected. The types of the hepatectomies conducted were as follows:isolated total caudate lobectomy in 7cases, partial cau-date lobectomy in 8, caudate lobectomy plus other extended hepatectomy in 18. The median operative time was 218 min (120-360 min) and the median intraoperative blood loss 958 ml (400-7000 ml),with operative mortality and morbidity being 0 and 27%, respectively. The postoperative 1-, 3- and 5-year survival rates for the patients with primary liver cancer were 76 %,52% and 24%, respectively. Con-clusion The hepatic tumors of caudate lobe, when larger than 10 cm in diameter, frequently involves all the hepatic portal,hepatocaval confluence and retrohepatic IVC. Though it is sophisticated in tech-nique, surgical resection of this kind of tumor is safe, effective and of the first choice.

Objective To examine the effects of a peroxisome proliferator-activated receptor γ ligand troglitazone on the proliferation and differentiation of HepG2 cells. Methods After the pretreatment of HepG2 cells with troglitazone, MTT and flow cytometry were used to analyze the proliferation and cell cycle of HepG2 cells, respectively. Immunocytochemistry, bromocresol green dye-binding method and chemiluminessence immunosorbent assay was used to determine E-cadherin, albumin and AFP, respectively. The expression of cyclin D1 and c-myc protein were detected by Western blot. Results Troglitazone inhibited the proliferation of HepG2 cells in a concentration-dependent manner and arrested HepG2 ceils at the G0>/G1> phase. After pretreated with troglitazone, HepG2 cells showed E-cadherin expression, a decreased expression of cyclin D1 and c-myc protein, a reduction of AFP level and a dramatic increase of albumin level. Conclusions Troglitazone inhibits proliferation and induces differentiation of HepG2 cells, the mechanism of which might be attributable to the down-regulation of cyclin D1 and c-myc expression.

Objective:To investigate the effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life.Methods:Healthy and sexually mature C57BL/6J mice were paired according to the female to male ratio of 2∶1. After confirmation of pregnancy, female mice were randomly divided into control (drinking double distilled water), low- (0.5 mg/L) and high- (5.0 mg/L) dose arsenic exposure groups, 10 mice in each group. The exposure time of arsenic in drinking water ranged from day 0 of pregnancy to day 28 after birth. At the end of arsenic exposure, female offspring (10 mice in each group) were sacrificed and mammary glands were dissected for whole tissue staining to evaluate the development of mammary glands and quantitative analysis of mammary gland development indexes. The expression of proliferating cell associated antigen Ki67 was detected by immunohistochemistry.Results:There were no significant differences in body weight and organ coefficients of liver, kidney and mammary glands between female offspring in low- and high-dose arsenic exposure groups and control group ( F=1.018, 1.033, 1.764, 0.199, P > 0.05). Compared with control group, low- and high- dose arsenic exposure groups showed more terminal end buds (TEB) and ductal branches as well as stronger longitudinal growth ability in mammary gland morphological analysis. Quantitative analysis results showed that the numbers of TEB in the low- and high-dose arsenic exposure groups (11.83 ± 4.40, 11.00 ± 3.74) were significantly higher than that in the control group (4.00 ± 1.83, P < 0.05). The ductal lengths in the low- and high-dose arsenic exposure groups [(6.43 ± 1.08), (6.08 ± 1.74) mm] were also significantly longer than that in the control group [(3.71 ± 0.61) mm, P < 0.05]. The distance of leading edge of ducts to the midpoint of lymph nodes in the low- and high-dose arsenic exposure groups [(0.58 ± 1.12), (- 0.02 ± 1.57) mm] was significantly shorter than that in the control group [(- 2.67 ± 0.87) mm, P < 0.05]. The mean maximum area of TEB in the low-dose arsenic exposure group [(0.04 ± 0.01) mm 2] was significantly larger than that in the control group [(0.02 ± 0.01) mm 2, P < 0.05]. Immunohistochemistry staining indicated strong staining of Ki67 within TEB in the low- and high-dose arsenic exposure groups. Conclusion:Early life inorganic arsenic exposure promotes the development of TEB, ductal extension and cell proliferation within TEB in female mice, indicating that early life arsenic exposure alters mammary gland development.