Effects of natural and recombinant hirudin on superoxide dismutase, malondialdehyde and endothelin levels in a random pattern skin flap model.

We have assessed the anti-inflammatory, anti-oxidative and anti-coagulant effects of locally applied natural and recombinant hirudin in a random skin flap rat model. Thirty Wistar rats with venous congested skin flaps were randomly divided into two treatment groups and a control group to receive subcutaneous injections of natural hirudin (6 U), recombinant hirudin (6 U) or physiological saline, respectively. Superoxide dismutase, malondialdehyde and endothelin levels as well as flap survival rates of the skin flaps were measured after surgery. Compared to the control group, the treatment groups had significant higher superoxide dismutase levels and lower malondialdehyde and endothelin levels in the skin flaps. The surviving areas of the flaps were larger in the treatment groups than the control group. Our results demonstrated that hirudin could improve skin flap survival through its anti-inflammatory, anti-oxidative and anti-coagulant activities.

In vivo short hairpin RNA interference of vascular endothelial growth factor on drug-resistant tongue cancer cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the in vivo interference effects of vascular endothelial growth factor (VEGF) short hairpin RNA (shRNA) on xenografts of drug-resistant tongue cancer cells.</p><p><b>METHODS</b>Drug-resistant tongue caner cells Tca/Cisplatin (DDP) were injected subcutaneously into nude mice to establish xenograft models, which were randomly divided into non-transfected group, mock control group, control group transfected with scrambled sequence plasmid, interference group transfected with VEGF-shRNA expression plasmid. Liposome-mediated plasmid transfection was done in the latter three groups every three days. Xenografts were observed and tumor growth curve was measured. After the 10th transfection, tumors were anatomized and weigh. Microvessel density was detected by immunohistochemical staining. In situ hybridization assay was used to test VEGF mRNA, and immunohistochemistry to test VEGF, P-glycoprotein (P-gp), B cell lymphoma/leukemia-2 (bcl-2) and extracellular signal-regultaed kinase 2 (ERK-2) protein.</p><p><b>RESULTS</b>Tumor growth in VEGF-shRNA interference group was significantly slow. Tumor weight was (0.4781 ± 0.0860) g, microvessel density (7.35 ± 1.31)/view, VEGF mRNA (0.0767 ± 0.0234), VEGF protein (0.1301 ± 0.0433), P-gp (0.1517 ± 0.0184), bcl-2 (0.1218 ± 0.0251) and ERK-2 protein (0.1178 ± 0.0291) in VEGF-shRNA interference group; all of them were less than those in the other three groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Inhibition targeting VEGF may become a potential therapy for drug-resistant tongue cancer.</p>

Nerve growth factor and vascular endothelial growth factor: retrospective analysis of 63 patients with salivary adenoid cystic carcinoma.

AIM: To detect the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in salivary adenoid cystic carcinoma (SACC) tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. METHODOLOGY: Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox's proportional hazard regression model were applied to assess predictors of survival. RESULTS: NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues (P < 0.05), and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high-expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates (P < 0.05). CONCLUSION: NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent

Tyrosine kinase A and vascular endothelial growth factor receptor 2 in the invasion and metastasis of salivary adenoid cystic carcinoma / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To determine the effect of tyrosine kinase A (TrkA) and vascular endothelial growth factor receptor 2 (VEGFR2) in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC).</p><p><b>METHODS</b>The expression of TrkA and VEGFR2 were detected by immunohistochemical staining in 47 cases of SACC of salivary glands. Clinical data were reviewed by multivariate prognostic analysis.</p><p><b>RESULTS</b>The positive rate of TrkA and VEGFR2 in SACC was 87.23% (41/47) and 85.11% (40/47) respectively. Express of TrkA and VEGFR2 in perineural invasion and recurrence group were higher than non-perineural invasion and non-recurrence group. Significant difference was found in microvessel density (MVD) and VEGFR2 expression within different groups (P < 0.05). MVD in perineural invasion group (25.14 +/- 2.83) was significantly higher than that in none perineural invasion group (18.81 +/- 1.33) (P < 0.05). MVD in recurrence or metastasis group (26.58 +/- 2.38) was significantly higher than that (19.06 +/- 1.39) in none recurrence nor metastasis group (P < 0.05).</p><p><b>CONCLUSION</b>Positive correlation between expression of TrkA, VEGFR2 and nerve invasion and vessel metastasis of SACC indicate that TrkA and VEGFR2 play important roles in the invasion and metastasis of SACC. It is possible that TrkA and VEGFR2 could be an aid for evaluating the prognosis of SACC patients.</p>

Vasoactive intestinal peptide expression and its clinical significance in gastric adenocarcinoma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression of vasoactive intestinal peptide (VIP) in gastric adenocarcinoma, and to evaluate the correlation of VIP level with clinical pathologic parameters.</p><p><b>METHODS</b>The level of VIP in sera from gastric adenocarcinoma patients and healthy people was investigated by ELISA. Moreover, the differential gene expression between gastric adenocarcinoma, gastric dysplasia, and the corresponding normal gastric mucosa were determined by RT-PCR. Western Blot was also used to measure the expression of VIP in the gastric adenocarcinoma and the normal gastric mucosa.</p><p><b>RESULTS</b>The serum level of VIP was (5.794 +/- 0.014) ng/ ml in normal control and was (14.437 +/- 0.825) ng/ml in gastric adenocarcinoma patients, showing significant difference (P < 0.05). Meanwhile,the V/B of gastric adenocarcinoma tissues was greater than that of gastric dysplasia and the corresponding normal gastric mucosa (P <0.01), the values of V/B were 1.5261 +/- 0.3028, 0.9334 +/- 0.2872,and 0.9051 +/- 0.2794, respectively. The values of V/B between normal gastric mucosa and gastric dysplasia were not different significantly (P > 0.05). There were significantly negative correlation between the VIP mRNA expression of the differentiation degree of tumor (P < 0.05). The VIP mRNA expression was higher in gastric adenocarcinoma with lymph node metastasis than that without lymph node matastsis (P < 0.05). The VIP protein expression of the gastric adenocarcinoma tissues was greater than that of normal control.</p><p><b>CONCLUSION</b>This findings provide a direct evidence to support the possibility that VIP play a cofactor role in the pathogenesis of gastric adenocarcinoma.</p>

Combining of TNP-470 and 5-Fu in inhibition of adenoid cystic carcinoma in nude mice model / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).</p><p><b>METHODS</b>Acc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.</p><p><b>RESULTS</b>TNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.</p><p><b>CONCLUSION</b>Since ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.</p>