Curcumol is the major component extracted from root of Rhizoma Curcumae. Recent studies have shown that curcumol exerts therapeutic effects against multiple conditions, particularly cancers. However, the therapeutic role and mechanism of curcumol against cholangiocarcinoma cells are still unclear. In our current research, we tested the effect of curcumol in cholangiocarcinoma cells, and using two-dimensional electrophoresis, proteomics and bioinformatics, we identified cyclin-dependent kinase like 3 (CDKL3) as a potential target for curcumol. We have demonstrated that curcumol can evidently suppress growth and migration of cholangiocarcinoma cells. Furthermore, curcumol could significantly block the cell cycle progression of the cholangiocarcinoma cells. These effects could be largely attributed to the inhibition of CDKL3 by curcumol. Further studies have recapitulated the oncogenic role of CDKL3 in that knockdown of CDKL3 by lentiviral mediated transfection of shRNA against CDKL3 also led to a significant inhibition on cell proliferation, migration, invasion, and cell cycle progression. Given the high level of CDKL3 expression in human cholangiocarcinoma tissues and cell lines, we speculated that CDKL3 may constitute a potential biological target for curcumol in cholangiocarcinoma.

Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444 462 participants between the ages of 40 and 69 years from the UK Biobank, followed up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow‐up of 6.6 years, 2033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable‐adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5 mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI] = 0.75‐2.29) in males and 1.26 (95% CI = 1.03‐1.55) in females. The HRs in the highest uric acid groups (>8.4 mg/dL) were 1.16 (95% CI = 0.83‐1.63) in males and 2.00 (95% CI = 1.02‐3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95% CI = 1.15‐4.23) in males and 0.98 (95% CI = 0.66‐1.45) in females. The HRs in the highest uric acid groups were 1.35 (95% CI = 0.82‐2.23) in males and 3.81 (95% CI = 1.38‐10.56) in females. In conclusion, SUA showed a U‐shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects.

Background & Aims: Cholangiocarcinoma (CCA) patients have poor outcomes since the late diagnosis limits the benefits of surgery therapy and curative treatment options. The present study was designed to screen the biomarkers for CCA patients. Methods: Quantitative iTRAQ proteomic analysis was used to identify differentially expressed proteins between CCA and pericarcineous tissue. We examined the expression profile of PRDX2, BGN, LUM, and PPP3CA in CCA tissue using immunohistochemistry. We further investigated the correlation between PPP3CA expression and the survival of CCA patients (n=91). Results: 2,886 confidential proteins were identified by using the iTRAQ technique, 233 of which were differentially expressed. PRDX2, BGN, PPP3CA, and LUM were expressed in CCA tissue, whereas they were not expressed in choledocal cyst tissue except for LUM. PPP3CA was expressed in the cytoplasm of carcinoma cells in 22 cases (24.2%) of 91 CCA patients. Patients with PPP3CA-positive expression showed a significantly shorter survival period than did non-expressing patients ( P = 0.030). The univariate analysis showed that tumor size ( P = 0.002), vascular invasion ( P = 0.001), histological grading ( P = 0.011), and PPP3CA expression ( P = 0.033) were statistically significant risk factors affecting the prognosis of CCA patients. The multivariate analysis demonstrated PPP3CA expression ( P = 0.009) and vascular invasion ( P = 0.012) were statistically significant independent risk factors of CCA patients. Conclusions: The results suggested that the expression of PPP3CA in CCA patients is a new independent factor for poor prognosis and a useful prognostic predictor for patients with CCA.

BACKGROUND Uric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear. AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer. METHODS In this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders. RESULTS In total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed ( P -nonlinear = 0.03). CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.