H pylori status and angiogenesis factors in human gastric carcinoma

AIM： To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density （MVD）, thymidine phosphorylase （TP）, vascular endothelial growth factor receptor-1 （VEGF-R1）, p53 and circulating VEGF levels. METHODS： Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin （vacA） and the cytotoxin-associated gene （cagA） amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS： A total of 69% of patients were positive for circulating IgG antibodies against Hpylori. cagA-positive H pylor/strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA （P = 0.0001）. MVD was significantly correlated with both tumor VEGF expression （r = 0.361, P = 0.009） and serum VEGF levels （r = -0.347, P = 0.041）.Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level （P = 0.026）. CONCLUSION： H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib(Iressa^(TM))and to the antiangiogenic agent ZD6474:Cytotoxic and biomolecular effects

AIM： To analyze the biological effects of prolonged in vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib （Iressa^TM）, an inhibitor of epidermal growth factor receptor （EGFR） activity, and ZD6474, an inhibitor of both KDR and EGFR activities. METHODS： Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent （4 d of drug exposure followed by 3 d of washout each week） schedule. RESULTS： In both cell types, prolonged exposure （up to 14 d） to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erkl/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. CONCLUSION： We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.