CUL4A promotes proliferation and inhibits apoptosis of colon cancer cells via regulating Hippo pathway.

OBJECTIVE: The aim of this study was to investigate the effect of cullin 4A (CUL4A) on the proliferation and apoptosis of colon cancer (CC) cells, and to elucidate its regulatory relationship with the Hippo pathway. PATIENTS AND METHODS: Paired CC tissues and adjacent normal tissues were obtained from patients. CC cells were isolated and cultured in vitro. CUL4A was interfered by small interfering ribonucleic acid (siRNA) (siR-CUL4A group) or overexpressed by overexpression vector (CUL4A-Vector group), with negative control (NC)-CUL4A or CUL4A -NC as the control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of CUL4A in CC tissues and cells. The proliferative ability of cells was detected by cell counting kit-8 (CCK-8) assay. Flow cytometry was applied to measure the apoptosis of cells in each group. Western blotting (WB) was conducted to determine the protein expression of CUL4A. In addition, the proliferative ability was examined in vivo through subcutaneous injection of cells into nude mice. RESULTS: QRT-PCR showed that CUL4A was highly expressed in 66.67% of CC samples (p<0.01). In vivo and in vitro proliferative ability was significantly reduced in siR-CUL4A group (p<0.01), whereas the apoptosis rate was promoted (p<0.01). However, in vivo and in vitro proliferative ability increased significantly in CUL4A-Vector group (p<0.01), while the apoptosis rate was reduced (p<0.01). The protein expressions of MST1, LATS1 and p-YAP were significantly up-regulated in siR-CUL4A group (p<0.01), while they were remarkably down-regulated in CUL4A-Vector group (p<0.05, p<0.01). CONCLUSIONS: CUL4A is highly expressed in CC and promotes the proliferation and inhibits the apoptosis of CC cells by regulating the Hippo pathway.

Tegafur gimeracil oter combined with oxaliplatin for advanced colorectal cancer.

OBJECTIVE: To analyze the therapeutic actions of tegafur gimeracil oteracil combined with oxaliplatin for treating patients with advanced colorectal cancer, and its effects on the K-ras gene mutation and the CK20 mRNA. PATIENTS AND METHODS: Forty-one patients with advanced colorectal cancer from our hospital, from October 2013 to October 2014, were enrolled in this study. After obtaining consent from the hospital Ethics Committee and the patients as well as their relatives, all 41 patients were divided into two groups. The control group, which consisted of 20 cases, were treated with capecitabine combined with oxaliplatin. The study group, which comprised of 21 cases, were treated with tegafur gimeracil oteracil combined with oxaliplatin. Both groups were followed-up after six months to evaluate the treatment outcomes. RESULTS: The survival rate in the observation group was higher than that in the control group. The progression-free survival time (PFS) in the observation group was longer than that in the control group. The objective response rate (ORR) and disease control rate (DCR) were higher for the observation group. The differences had statistical significance (p < 0.05). The proportion of K-ras gene mutation in the observation group was substantially superior to that in the control group. The positive expression rate of CK 20 mRNA in the observation group was significantly lower than that in the control group. The differences had statistical significance (p < 0.05). The incidence of adverse reaction in the observation group was lower than that of the control group, and the differences had statistical significance (p < 0.05). CONCLUSIONS: Tegafur/gimeracil/oteracil combined with oxaliplatin therapy had better treatment outcomes than capecitabine combined oxaliplatin for advanced colorectal cancer. This maybe related to K-ras gene mutation and the reduction of CK20 mRNA expression.

Double primary malignancy in colorectal cancer patients--MSI is the useful marker for predicting double primary tumors.

BACKGROUND AND AIMS: The incidence of double primary malignancies (DPM) is known to be higher in colorectal cancer patients than the general population. And, the role of microsatellite instability (MSI) in DPM has been previously studied. We evaluated the clinical features and association between MSI and colorectal cancer patients with DPM. MATERIALS AND METHODS: From September 1994 to May 2004, we reviewed 2,301 colorectal cancer patients with regard to secondary primary malignancies. A subgroup analysis was performed for MSI after January 2003. RESULTS: One hundred forty-five patients (6.3%) had a DPM identified. In DPM group, 57 patients had a synchronous DPM (39.3%), and 88 patients had a metachronous malignancy (60.7%). Male gender (p<0.001) and colon cancer (p<0.001) were the factors related with the development of the DPM. Most of the second malignancies occurred within 3 years after the primary operation. The common second malignancies were stomach (58 patients, 40%) and lung (21 patients, 14.5%). In the subgroup analysis, there was a higher frequency of DPM in the MSI group when compared to the microsatellite stable group (p=0.021). CONCLUSIONS: The careful pre- and postoperative evaluation should be paid for detecting DPM as well as for detecting recurrence in colorectal cancer patients. The results of this study suggest that MSI might be a useful marker for the detection of DPM in colorectal cancer patients.