Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin

AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice. Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ± 52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.

Value of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: A prospective evaluation

AIM: Gastrografin is a hyperosmolar water-soluble contrast medium. Besides its predictive value for the need for operative treatment, a potential therapeutic role of this agent in adhesive small bowel obstruction has been suggested. This study aimed at evaluating the effectiveness of gastrografin in adhesive small bowel obstruction when conservative treatment failed.METHODS: Patients with adhesive small bowel obstruction were given trial conservative treatment unless there was fear of bowel strangulation. Those responded in the initial 48 h had conservative treatment continued. Patients who showed no improvement in the initial 48 h were given 100 mL of gastrografin through nasogastric tube followed by serial abdominal radiographs. Patients with the contrast appeared in large bowel within 24 h were regarded ashaving partial obstruction and conservative treatment wascontinued. Patients in which the contrast failed to reachlarge bowel within 24 h were considered to have completeobstruction and laparotomy was performed.RESULTS: Two hundred and twelve patients with 245episodes of adhesive obstruction were included. Fifteenpatients were operated on soon after admission due tofear of strangulation. One hundred and eighty-six episodesof obstruction showed improvement in the initial 48 h andconservative treatment was continued. Two patients hadsubsequent operations because of persistent obstruction.Forty-four episodes of obstruction showed no improvementwithin 48 h and gastrografin was administered. Sevenpatients underwent complete obstruction surgery. Partialobstruction was demonstrated in 37 other cases, obstruction resolved subsequently in all of them except one patient who required laparotomy because of persistent obstruction. The overall operative rate in this study was 10%. There was no complication that could be attributed to the use of gastrografin.CONCLUSION: The use of gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment is safe and reduces the need for surgical intervention.