Search

The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to stratify the risk of colorectal advanced neoplasm (AN). We aimed to evaluate the performance of the APCS score combined with a stool DNA test used for colorectal cancer screening.A total of 2842 subjects who visited outpatient clinics or cancer screening centers were enrolled. Age, sex, smoking status, and family history were recorded and APCS scores were calculated in 2439 participants. A stool DNA test (SDC2 and SFRP2 tests) and fecal immunochemical test (FIT) were performed and colonoscopy was used as the gold standard among 2240 subjects who completed all study procedures. We used a threshold of 4.4 μg/g for the FIT, in addition to the manufacturer's recommended threshold of 20 μg/g to match the specificity of a stool DNA test.Based on the APCS score, 38.8% (946 of 2439) of the subjects were categorized as high risk, and they had a 1.8-fold increase in risk for AN (95% CI, 1.4-2.3) compared with low and moderate risk. The APCS combined with the stool DNA test detected 95.2% of invasive cancers (40 of 42) and 73.5% of ANs (253 of 344), while the colonoscopy workload was only 47.1% (1056 of 2240). The sensitivity for AN of APCS combined with stool DNA test was significantly higher than that of APCS combined with FIT (73.5% vs 62.8% with FIT cut-off value of 20 μg/g, and 73.5% vs 68.0% with FIT cut-off value of 4.4 μg/g; both P.01).The APCS score combined with a stool DNA test significantly improved the detection of advanced colorectal advanced neoplasms, while limiting colonoscopy resource utilization (Chictr.org.cn, ChiCTR-DDD-17011169).

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a component of the ubiquitin-mediated proteolysis, could bind SKP1-CUL1-F box protein complex and participate in beta-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer and renal cancer. However, the role of CacyBP/SIP in pancreatic cancer progression still remains unclear. Therefore, the aim of the present study was to investigate the expression and clinical significance of CacyBP/SIP in pancreatic cancer.Immunohistochemistry was carried out on paraffin-embedded sections of pancreatic cancer and normal pancreatic tissues. In addition, Western blot and semiquantitative RT-PCR were carried out to analyze mRNA and protein expression of CacyBP/SIP in 8 pairs of freshly resected pancreatic cancer and their adjacent nontumorous tissue.CacyBP/SIP expression was significantly increased in pancreatic cancer tissue (28/68 or 41.2%) and correlated with differentiation degree, higher TNM (tumor, node, metastasis) stage and distance metastasis. Also, mRNA and protein expression of CacyBP/SIP were found to be at higher levels in almost all cancer tissues compared to adjacent tissues.CacyBP/SIP protein might play an important role in the process of pancreatic carcinogenesis and high-level CacyBP/SIP expression might be related to the malignant potential of pancreatic cancer.

Angiogenesis plays a crucial role in tumor development and growth. The present study was carried out to investigate the potential involvement of the cyclooxygenase-2 (Cox-2) pathway in the regulation of angiogenesis in hepatocellular carcinoma (HCC). We inhibited Cox-2 expression in HCC cell line HuH-7 by selective Cox-2 inhibitor (SC-58635) or Cox-2 siRNA. Conditioned media (CMs) from HuH-7 cells were used in angiogenic assays in vitro and in vivo. Compared with CMs from untreated and negative siRNA treated HuH-7 cells, CMs from SC-58635 and Cox-2 siRNA treated HuH-7 dramatically suppressed the proliferation, migration, and differentiation of human umbilical vein endothelial cells (HUVECs) in vitro and neovascularization in vivo. These inhibitory effects could be partially reversed by the addition of exogenous PGE2 to CMs. Furthermore, Cox-2 inhibition by SC-58635 resulted in PGE2 reduction accompanied by the down-regulation of four PGE2 receptor (EP receptor) subtypes. Treatment with SC-58635 led to the down-expression of proangiogenic factors such as VEGF, HGF, FGF2, ANGPT1 and ANGPT2 in HCC. An approximately 78% reduction of VEGF level has been found in the CM from SC-58635 treated HuH-7. Our results suggest an involvement of Cox-2 in the control of HCC-associated angiogenesis. PGE2 as a vital angiogenic factor may act directly on endothelial cells to promote HuH-7-stimulated angiogenic process. Moreover, Cox-2/PGE2/EP/VEGF pathway possibly also contributes to tumor angiogenesis in HCC. This study provides the rationale for clinical studies of Cox-2 inhibitors on the treatment or chemoprevention of HCC.