Lower serum CA125 level, negative vascular invasion, and wild BRAF were strongly associated with better 2-year disease-free survival in patients with stage III colorectal cancer who received adjuvant chemotherapy.

BACKGROUND: Adjuvant chemotherapy plays important role in the comprehensive treatment of patients with stage III colorectal cancer. However, there is few molecular markers for predicting the therapeutic effect. OBJECTIVE: To identify factors that could predict adjuvant chemotherapy benefits in patients with stage III colorectal cancer. METHODS: The medical records of 294 patients were reviewed and analyzed using the Kaplan-Meier method and Cox analysis. RESULTS: Lower CA125 (⩽ 35 u/ml, P= 0.0015) serum levels, stage IIIa (P= 0.0027), 1-3 positive lymph nodes (P= 0.0256), negative vascular invasion (P= 0.0215), lower CA199 (⩽ 27 u/ml, P= 0.0038) serum levels, and wild-type BRAF status (P= 0.0125) were significantly associated with a higher 2-year DFS rate in patients with stage III colorectal cancer. However, in multivariate COX analysis, the association remained significant only for CA125 levels (vs. ⩽ 35 u/ml group, HR 3.341; 95% CI, 1.198-9.316; P= 0.0212), vascular invasion (vs. negative vascular invasion, HR, 2.349; 95% CI, 1.227-4.499; P= 0.01), and BRAF (V600E) (vs. wild Braf, HR, 7.794; 95% CI, 1.867-32.531; P= 0.0049). CONCLUSION: Lower CA125 serum levels, negative vascular invasion, and wild-type BRAF status were significantly associated with improved 2-year DFS rates among patient with stage III disease who received adjuvant chemotherapy.

Zoledronic acid inhibits growth of hepatocellular carcinoma cells in vitro and in vivo.

BACKGROUND: Growing preclinical evidence shows that zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo. METHODS: Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection (s.c.) and H22-intraperitoneal injection (i.p.) mice model. RESULTS: ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo. CONCLUSION: ZOL inhibits growth of HCC cells in vitro and in vivo.

Twist expression associated with the epithelial-mesenchymal transition in gastric cancer.

This study aimed to investigate the expression of Twist in gastric cancer tissues and its correlation between Twist and the epithelial-mesenchymal transition (EMT). By means of RT-PCR and Western blot, the mRNA and protein expressions of Twist, E-cadherin, and Vimentin in 61 gastric cancer tissues and adjacent normal tissues were detected. The positive rates of Twist, E-cadherin, and Vimentin mRNA expression in gastric cancer tissues were 73.9. 40.6, and 60.9 %, respectively; compared to the expression of these genes in adjacent normal tissues (2.9, 75.4, and 27.5 %), the differences were significant (p < 0.05). The E-cadherin protein expression level in gastric cancer tissues was significantly lower than that in the adjacent normal tissues (p < 0.05). After the transfection of Twist siRNA into the MKN45 cells, the protein expression of Twist was significantly reduced (p < 0.05), the protein expression of E-cadherin was significantly increased, and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). Twist may be associated with the epithelial-mesenchymal transition in gastric cancer and the tumorigenesis, invasion, and metastasis of gastric cancer.

[Construction of adenovirus expressing anti-vascular endothelial growth factor hairpin ribozyme and its inhibition of growth of colorectal cancer HT-29 cells].

BACKGROUND AND OBJECTIVE: Oversexpression of vascular endothelial growth factor (VEGF) is correlated to poor prognosis of colorectal cancer. This study was to construct replication deficient adenovirus carrying anti-VEGF hairpin ribozyme and investigate its inhibitory effects on VEGF expression and growth of colorectal cancer HT-29 cells. METHODS: Anti-VEGF hairpin ribozyme was cloned into the transfer vector pAdTrack-CMV, and recombined with adenoviral backbone vector pAdEasy-1 in BJ5183 bacteria. The recombinant plasmids were packaged and amplified in 293 cells (named Ad-Rz). The expression of anti-VEGF ribozyme in HT-29 cells was examined by RT-PCR. Inhibition of Ad-RZ on VEGF mRNA and protein expressions were detected by real-time PCR and ELISA, respectively. Inhibition of cell growth was measured by MTT assay. HT-29 cell xenografts were established in nude mice and the microvessel density (MVD) was determined by CD34 staining. RESULTS: The anti-VEGF ribozyme was successfully inserted into the adenoviral vector. Anti-VEGF ribozyme was effectively expressed in HT-29 cells. After infection by Ad-RZ, the relative expression of VEGF mRNA was decreased to about(45+/-0.01)% of that of PBS control group in HT-29 cells (P<0.05); the amount of VEGF protein in the supernatant of Ad-Rz treated cells [(OD=(0.46+/-0.35)/million cells] was lower than that of PBS treated cells [(OD=(0.80+/-0.35)/million cells] (P<0.05). Although Ad-Rz did not significantly inhibit cell growth of HT-29 cells (P>0.05), it significantly inhibited tumor angiogenesis of HT-29 cell xenografts in nude mice, compared with PBS group (P<0.05). The proliferation rate of xenografts treated by Ad-Rz was lower than that treated by PBS, but the difference was not significant (P>0.05). CONCLUSION: Anti-VEGF hairpin ribozyme mediated by adenovirus could inhibit the expression of VEGF and the tumor angiogenesis in colorectal cancer HT-29 cells.