Angiogenesis and vascular malformations:Antiangiogenic drugs for treatment of gastrointestinal bleeding

Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler’s disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specif ic drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.

Effects of resistin-like molecule β over-expression on gastric cancer cells in vitro

AIM: To investigate the effects of resistin-like molecule β (RELMβ) over-expression on the invasion, metastasis and angiogenesis of gastric cancer cells. METHODS: Human RELMβ encoding expression vec tor was constructed and transfected into the RELMβ lowly-expressed gastric cancer cell lines SGC7901 and MKN-45. Gene expression was measured by Western blotting, reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR. Cell proliferation was measured by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetry, colony formation and 5-ethynyl-20-deoxyuridine incorporation assays. The in vitro migration, invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenic capabilities of cancer cells were measured by tube formation of endothelial cells. RESULTS: Transfection of RELMβ vector into SGC-7901 and MKN-45 cells resulted in over-expression of RELMβ, which did not infl uence the cellular proliferation. However, over-expression of RELMβ suppressed the in vitro adhesion, invasion and metastasis of cancer cells, accompanied by decreased expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Moreover, transfection of RELMβ attenuated the expression of vascular endothelial growth factor and in vitro angiogenic capabilities of cancer cells. CONCLUSION: Over-expression of RELMβ abolishes the invasion, metastasis and angiogenesis of gastric cancer cells in vitro, suggesting its potentials as a novel therapeutic target for gastric cancer.

Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection

AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC resection.METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

Preliminary assessing no-surgical treatment response in bronchogenic carcinoma with changes in enhancement pattern

Objective： The aim of this study was to evaluate the efficacy of changes in enhancement pattern in assessing no-surgical treatment response in bronchogenic carcinoma preliminarily. Methods Thirty-three patients with bronchogenic carcinoma underwent two-phase contrast material-enhanced computed tomography prior to and after stopping no-surgical treatment more than one-month respectively. Two spiral CT scans were obtained at 25 and 90 s respectively after nonionic contrast material was administrated via the antecubital vein at a rate of 3 mL/s by using an autoinjector. The sum of the tumor longest diameters （LD） prior to treatment, after treatment and the sum of the post-treatment tumor enhancement area LD on the images obtained at 90 s after injection of contrast medium were recorded, Precontrast and postcontrast attenuation on every scan was recorded and peak height was calculated. The significance of the difference among groups was analyzed by means of ANOVA, student t test and chi-square test. Results： The sum of the tumor LD prior to treatment, that of after treatment and the sum of the post-treatment tumor enhancement area LD on the images obtained at 90 s after injection of contrast medium were （4.49 ± 1.32）, （4.05 ± 1.63）, （3.36 ± 1.22） cm respectively and there were statistically significant dif- ferences among them （f= 5.467, P = 0.006）. The sum of the tumor LD prior to treatment was significantly higher than that of the post-treatment tumor enhancement area （P = 0.001）. No statistically significant difference in the sum of the tumor LD was found between the pre- treatment and the post-treatment （P = 0.207）. There was no statistically significant difference between the sum of the tumors LD and that of tumor enhancement area after treatment （P = 0.086）. The response rate （RR） （21.21%） according to changes in sum of the tumor LD was significantly lower than that （30.30%） according to changes in the sum of the post-treatment tumor enhancement area LD （x2 = 15.12, P 〈 0.05）, and the progressive diseases （PD） rate （21.21%） was significantly higher than that （12.12%; X2 = 14.12, P 〈 0.05）. No statistically significant difference was found between precontrast attenuation prior to treatment [（41.77±7.03） HU] and that after treatment [（41.89 ± 7.63） HU; t = 0.335, P = 0.740 〉 0.05]. Peak height of bronchogenic carcinoma prior to treatment [（36.50 ± 11.21） HU] were significantly higher than that after treatment [（29.91 ± 10.35） HU; t = 10.081, P = 0.001]. Conclusion： Therapeutic effect may be underestimated with use of changes in sum of the tumor LD. The changes in sum of tumor enhancement area LD in addition to peak height is suggested to be used in assessing no-surgical.treatment response in bronchogenic carcinoma.