Expression characteristics of heparanase in colon carcinoma and its close relationship with cyclooxygenase-2 and angiogenesis.

BACKGROUND/AIMS: Heparanase (HPA) influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. Cyclooxygenase-2 (COX-2) was strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in colon carcinoma. The aim of this study was to determine whether the expression of HPA is related to the angiogenesis in colorectal cancer and whether it could be involved in clinical behaviour of colon carcinoma. METHODOLOGY: HPA and COX-2 was analyzed with Immunohistochemistry and Western blot. Microvessels in colon carcinoma were examined by using anti-CD34 antibody. Statistical analysis was applied to test for the prognostic and diagnostic associations. RESULTS: Immunohistochemistry revealed that HPA was expressed at low level in normal colonic mucosa (4/78, 5.1%), but at higher level in tumor tissues (63/78, 80.7%) and closely correlated with tumor lymph node metastasis (p < 0.05). This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high HPA expression demonstrated high COX-2 expression and high MVD (microvesseldensity) labelled with CD34. In addition, mortality was higher in patients with HPA+ phenotype and HPA was an independent predictor of overall survival (p < 0.05). CONCLUSIONS: Our findings indicated that HPA might be an important biomarker for malignant transformation and be involved in promoting colon carcinoma metastasis by increasing angiogenesis.

Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRas(G12D) mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia (PanIN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of PanIN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching PanIN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.

[Expression of human pituitary tumor transforming gene 1 in colorectal cancer detected with real-time fluorescent quantitative PCR and its clinical significance].

BACKGROUND & OBJECTIVE: Although human pituitary tumor transforming gene 1 (hPTTG1) is overexpressed in malignant tumors such as colorectal cancer, its correlation to clinicopathologic parameters and its value in diagnosis and prognosis prediction of colorectal cancer are still not clear. We investigated the expression of hPTTG1 in colorectal cancer tissues, and elucidated its correlation to some clinicopathologic parameters of colorectal cancer. METHODS: The expression of hPTTG1 in 60 specimens of colorectal cancer and corresponding noncancerous tissues were examined with real-time fluorescent quantitative polymerase chain reaction, and its correlation to seven clinicopathologic parameters were analyzed. RESULTS: The mRNA level of hPTTG1 was significantly higher in colorectal cancer tissues than in corresponding noncancerous tissues (0.42+/-0.07 vs. 0.03+/-0.01, P<0.001), significantly higher in colorectal cancer tissues with serum CEA level of > 5 ng/mL than in those with CEA of < 5 ng/mL (22.79+/-7.42 vs. 9.34+/-2.61, P<0.001), significantly higher in colorectal cancer tissues with diameter of > or = 3.5 cm than in those with diameter of < 3.5 cm (15.80+/-8.80 vs. 10.91+/-5.22, P<0.05), significantly lower in Dukes'A, B tumors than in Dukes' C, D tumors (9.03+/-0.35 and 9.58+/-2.93 vs. 15.88+/-8.09 and 25.69+/-7.67, P<0.001), and significantly higher in colorectal cancer tissues with lymph node metastasis (17.63+/-8.47), liver metastasis (31.07+/-4.10) and other organ metastasis (22.78+/-6.39) than in those without metastasis (11.15+/-6.65) (P<0.001). hPTTG1 expression had no relationship with patients' age, sex and histological type (P>0.05). CONCLUSIONS: hPTTG1 is overexpressed in colorectal cancer. It is closely related to the progression of colorectal cancer, and may be helpful for prognosis prediction of colorectal cancer.