Evaluation of the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.

Dietary intake of n-3 fatty acids and colorectal cancer risk: a meta-analysis of data from 489 000 individuals.

Preclinical studies have suggested an anti-colorectal cancer effect of n-3 fatty acids, yet epidemiological studies have reported mixed results. The goal of the present meta-analysis was to examine the association between the dietary intake of n-3 fatty acids and colorectal cancer risk by conducting a meta-analysis of prospective cohort studies. We searched the PubMed database up to February 2012 to identify eligible studies. Either a fixed- or random-effects model was used to obtain a pooled relative risk (RR) comparing the highest intake of n-3 fatty acids with the lowest. We conducted subgroup analyses according to sex, geographic region, length of follow-up, cancer site and type of n-3 fatty acids. We included seven prospective studies in the meta-analysis, comprising 489 465 participants and 4656 incident cases. The pooled RR of colorectal cancer in relation to n-3 fatty acids was 0·98 (95 % CI 0·88, 1·09). The results from subgroup analysis indicated a significant reduced risk of colorectal cancer in relation to n-3 fatty acids among men (RR 0·87, 95 % CI 0·75, 1·00; n 4). No significant association was observed in other subgroups. There was no evidence of publication bias as suggested by Begg's test (P = 0·76) and Egger's test (P = 0·66). The present meta-analysis showed insufficient evidence of a protective effect of n-3 fatty acids on colorectal cancer risk. However, a reduced risk observed in men warrants further investigation.

Enhancement of radiosensitivity in human esophageal carcinoma cells by fenofibrate and its potential mechanism.

AIMS AND BACKGROUND: Fenofibrate is a specific agonist of PPARα, and is characterized by relatively low systemic toxicity. Recent studies have revealed that fenofibrate suppresses the growth of several cancer lines in vitro, but the exact relation between fenofibrate and irradiation has not been explored. The purpose of this study was to investigate the radiosensitivity enhancement effects of fenofibrate combined with radiation on the human esophageal carcinoma cell lines Eca-109 and TE1, and the potential mechanism underlying these effects. METHODS AND STUDY DESIGN: The Eca-109 and TE1 cell lines were tested by the CCK-8 assay for cell proliferation. The multitarget click model was used to delineate the survival curve and radiosensitivity was determined after cells were treated with fenofibrate and/or x-ray radiation. Flow cytometry was used to examine the effect of fenofibrate and radiation on the cell cycle. The expression of vascular endothelial growth factor (VEGF) protein was detected by Western blot analysis. RESULTS: When given alone, fenofibrate had a time- and concentration-dependent cytotoxic effect on cells. The dose-enhancement ratio for combined fenofibrate and radiation increased markedly compared with fenofibrate alone. Further, the ratio of cells in the G2/M phase after fenofibrate and radiation was higher than that after fenofibrate or irradiation alone. The expression of VEGF protein was suppressed after treatment with fenofibrate alone or fenofibrate plus radiation. CONCLUSIONS: Fenofibrate can enhance the radiosensitivity of human esophageal carcinoma cells by increasing G2/M phase arrest. Modulation of VEGF expression could contribute in vivo to a favorable interaction.

Bortezomib induces protective autophagy through AMP-activated protein kinase activation in cultured pancreatic and colorectal cancer cells.

BACKGROUND: Bortezomib, a selective and potent inhibitor of the proteasome, has demonstrated broad anti-tumor activities in many malignancies. In the current study, we aimed to understand the potential resistance factor of bortezomib in cultured pancreatic and colorectal cancer cells. RESULTS: We observed that bortezomib-induced protective autophagy in cultured PANC-1 pancreatic cancer cells and HT-29 colorectal cancer cells. Inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine enhanced bortezomib-induced apoptosis and cytotoxicity in both PANC-1 and HT-29 cells. Activation of AMP-activated protein kinase (AMPK) was required for bortezomib-induced autophagy induction in PANC-1 and HT-29 cells, and AMPK inhibition by its inhibitor compound C (CC) or RNAi-depletion suppressed bortezomib-induced autophagy, while dramatically enhancing cancer cell apoptosis/cytotoxicity. Meanwhile, significant AMPK activation and autophagy induction were observed after bortezomib stimulation in primary cultured pancreatic cancer cells derived from a patient's tumor tissue. Both CC and 3-MA facilitated bortezomib-induced cytotoxicity in primary cultured pancreatic cancer cells. CONCLUSIONS: In conclusion, our data here suggest that bortezomib induces protective autophagy in pancreatic and colorectal cancer cells through activating AMPK-Ulk1 signalings. AMPK or autophagy inhibitors could be developed as an adjunct or chemo-sensitizer for bortezomib.

FAM9C plays an anti-apoptotic role through activation of the PI3K/Akt pathway in human hepatocellular carcinoma.

The function of FAM9C encoding a testis-exclusively expressed and nuclear-localized protein remains unknown. In the present study, we evaluated the role of FAM9C in human hepatocellular carcinoma. We found that among three FAM9 family members, only FAM9C was frequently upregulated in HCC specimens compared with that in corresponding adjacent non-cancer liver tissues. FAM9C was located in the nucleus of HCC cells, as shown by both western blotting and immumofluorescence assays. Significantly, FAM9C overexpression promoted proliferation, clonogenicity in an anchorage-dependent manner, in vivo tumorigenicity of YY-8103, and Huh-7 cells. In contrast, FAM9C knockdown suppressed proliferation, anchorage-dependent colony formation and in vivo tumorigenicity of QGY-7703, and BEL-7404 cells. However, FAM9C had no significant effects on cell cycle progression when FAM9C was stably overexpressed in Huh-7 cells or knocked down in BEL-7404 cells. Most importantly, FAM9C regulated activation of Akt and UV-induced apoptosis in HCC cells. FAM9C overexpression increased the phosphorylation levels of Akt and anti-apoptotic ability of Huh-7 cells, whereas endogenous FAM9C knockdown reduced the phosphorylated levels of Akt and anti-apoptotic ability of BEL-7404 cells. Furthermore, the anti-apoptotic function of FAM9C could be prevented when the PI3K-Akt pathway was in a loss-of-function caused by RNA interference against Akt or PI3K inhibitor LY294002 in HCC cells. Taken together, our data demonstrate that FAM9C as a novel cancer testis gene plays an anti-apoptotic role in human hepatocellular carcinoma through activating the PI3K/Akt signaling pathway, and serves as a promising target for HCC therapy.