KIN enhances stem cell-like properties to promote chemoresistance in colorectal carcinoma.

Chemotherapy is widely used in colorectal cancer (CRC) treatment, especially in advanced stage patients. However, it is inevitable to develop chemoresistance. Recently, cancer cells acquired stem cell-like properties or cancer stem cells (CSC) were proved to attribute to chemoresistance. Here, we found that KIN protein was elevated in CRC cell lines and tissue specimens as compared to normal controls. Upregulation of KIN positively correlates with the metastatic status of CRC patients. Patients with high KIN expression showed poor prognosis and were with a short survival time. Overexpression of KIN enhanced, while silencing KIN impaired, chemoresistance to oxaliplatin (Ox) or 5-fluorouracil (5-FU) in CRC cell lines. Further investigation demonstrated that overexpression of KIN rendered CRC cells enriching CSC markers and CSC phenotype, and silencing KIN reduced CSC markers and CSC phenotype. Our findings suggest that the KIN level may be a suitable marker for predicting chemotherapy response in CRC, and silencing KIN plus chemotherapy may be a novel therapy for CRC treatment.

Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

BACKGROUND: Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. METHODS: We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. RESULTS: The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. CONCLUSIONS: Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

Correlation between neutrophil/lymphocyte ratio and cognitive impairment in cerebral small vessel disease patients: A retrospective study.

Background and objective: The blood neutrophil/lymphocyte ratio (NLR) is an objective and convenient parameter of systemic inflammation. Elevated NLR is associated with an increased risk of mild cognitive impairment (CI) in the elderly. However, few data are available on the impact of the NLR on CI in patients with cerebral small vessel disease (CSVD). Methods: A total of 66 CSVD subjects with CI and 81 CSVD subjects without CI were evaluated in this study. Clinical, laboratory, radiological, and cognitive parameters were collected. The NLR was obtained with the absolute neutrophil count being divided by the absolute lymphocyte count in fasting blood samples. Logistic regression analysis was performed to evaluate the factors associated with CI. Receiver operating characteristic curves were illustrated to predict factors associated with CI in patients with CSVD. Results: The NLR of the CI group was significantly higher than that of subjects without CI (2.59 vs. 2.21, P = 0.003). In multivariate analysis, NLR was positively correlated to the CI (OR: 1.43, 95% CI: 1.05-1.96, P = 0.024). It was suggested that the optimum NLR cutoff point for CI was 1.89 with 69.7% sensitivity and 59.3% specificity. Subjects with NLR ≥ 1.89 showed higher possibilities of CI compared to those with NLR < 1.89 (OR: 3.38, 95% CI: 1.62-7.07). Conclusions: Correlations were found between NLR and CI. Patients with CSVD who have higher NLR might have an increased risk of CI.

N-3 PUFAs have antiproliferative and apoptotic effects on human colorectal cancer stem-like cells in vitro.

The n-3 polyunsaturated fatty acids have been shown to inhibit the induction and progression of many kinds of tumor and to increase the therapeutic effects of numerous chemotherapeutics, but their anticancer effect on cancer stem cells from colorectal cancer has not been described previously. In the present study, we cultivated spheres from the SW620 cell line in serum-free medium and evaluated the features of the spheres by immunofluorescence, cell cycle distribution, resistance to chemotherapeutics and soft agar clone formation, and the spheres were shown to be cancer stem-like cells through tumorigenicity in athymic nude mice. Reverse transcriptase polymerase chain reaction analysis of pluripotency genes, such as Sox-2, Oct-4 and Bmi-1, showed that the spheres were generated by dedifferentiation of SW620 cells. The study explored the use of n-3 polyunsaturated fatty acids (PUFAs) in spheres, which were treated with two n-3 PUFAs [docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA)]. Treatment of the spheres with DHA and EPA alone or in combination for 72 h led to apoptosis and the progressive loss of viability and DNA fragmentation and an increase in annexin V expression. DHA and EPA can enhance the chemotherapeutic sensitivity effect of 5-Fu and mitomycin C, especially DHA combined with EPA. Taken together, these results provide evidence that n-3 PUFAs exert a direct anticancer action that may contribute to their antiproliferative and proapoptotic effect on the cancer stem-like cells.