ABSTRACT
AIM: To investigate relationship between activity of matrix metalloproteinases - 2 ( MMP - 2, 72 kD) and invasion, metastasis of breast cancer. METHODS: Useing zymography and computer software assisted analysis, the activitive levels of MMP- 2 (72 kD) in tissues from breast cancer were measeured. RESULTS: Mean activitive levels of MMP- 272 kD (13.93 + 3.60) in breast cancer were lower than those in benign disease (21.43 + 8.31), P < 0.05. There was no difference (P > 0.05) in MMP - 2 62 kD + 72 kD of benign and malignant dis ease, but MMP - 262 kD ( 13.83 + 4.53) and MMP - 262 kD/62 kD + 72 kD (0.48) respectively were significantly higher in malignant disease (P < 0.01). It was also found that MMP- 262 kD/62 kD + 72 kD were apparently higher in invasive carcinomas (0.48) and lymph node metastases (0.61), P < 0.01, respectively. CONCLUSION: These results demonstrated that a clear relationship between MMP - 2 activity and the invasion and metastasis of breast carcinoma.
ABSTRACT
AIM: To investigate relationship between activity of matrix metalloproteinases-2 ( MMP-2, 72 kD) and invasion, metastasis of breast cancer. METHODS: Useing zymography and computer software assisted analysis, the activitive levels of MMP-2 (72 kD) in tissues from breast cancer were measeured. RESULTS: Mean activitive levels of MMP-2 72 kD (13.93?3.60) in breast cancer were lower than those in benign disease (21.43?8.31), P0.05) in MMP-2 62 kD+72 kD of benign and malignant disease, but MMP-2 62 kD (13.83?4.53) and MMP-2 62 kD/62 kD+72 kD(0.48) respectively were significantly higher in malignant disease (P
ABSTRACT
It was an important strategy in cancer gene therapy that transferring foreign gene to fibroblasts to express synthetic protein to exert antitumor effect. But most of studies regarded the foreign gene-modified fibroblasts as a by-stander, only a delivery source of synthetic protein, and neglected their irnmunological characters. In this paper, human primary dermal fibroblasts were modified by human IL-2 gene by retrovirus vector and induced by human IFN-?. The results showed that the MHC- I , MHC- II and CD40 expression on the surface of IFN-? induced fibroblasts were up-regulated significantly in comparison with those of non-induced cells. The IL-2, IL-1, IL-6 secretion were detected as a increased level in supematants of the IFN-?-induced, IL-2 gene modified fibroblasts. Because these molecules and cytokines play important roles in antigen presentation and effector activation, it can be inferred that the IFN-y induced, IL-2 gene modified fibroblasts could be used as antigen presenting cells in addition to delivery cells to activated the effector cells.
ABSTRACT
Antitumor effect of combined transfer of suicide gene and cytokine gene was evaluated in the present study. Adenoviruses expressing E. coli. cytosine deaminase (AdCD) and adenoviruses expressing murine interleukin 2 (AdTL2) were used for the treatment of tumor-bearing mice. The mice were inoculated s. c. with FBL-3 leukemia cells and 3 days later received intratumoral injection of AdCD in the presence or absence of AdIL2 followed by intraperitoneal 5-fluorocytosine (5FC) administration. The results demonstrated that tumor-bearing mice treated with AdCD/5FC in combination with AdTL2 showed more .potent inhibition of tumor growth and survived much longer as compared with mice treated with AdCD/5FC, AdEL2, AdlacZ/5FC or PBS. It was illustrated that the tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD4+ and CD8+ T cells infiltrated into the tumor after combined therapy. The splenic NK and CTL activities increased significantly in mice after combined transfer of CD gene and EH gene. Our results demonstrated that combined transfer of suicide gene and IL-2 gene could inhibit the growth of established tumor in mice significantly and induce antitumor immunity of the host efficiently.
ABSTRACT
Adenoviruses harboring E. coli cytosine deaminase gene (AdCD) were used to transfect murine FBL-3 ery-throleukemia cells in vitro. FBL3 cells infected with AdCD were more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus AdLacZ. Further study indicated that this combination therapy (AdCD and 5-FC) killed tumor cells by inducing apoptosis of FBL-3 cells. The supematants from FBL-3 cells treated with AdCD/5-Fc were transferred on the culture system of uninfected (wild - type) FBL-3 cells, the result indicated that only 6.25% of the supernatant could induce significant cytotoxicity on wild type FBL3 cells. The results demonoustrated that bystander effect plays an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into established subcutaneous FBL3 tumor in mice followed by daily intraperitoneal injection of 5-FC for 10 days was found to inhibit tumor growth significant-
ABSTRACT
Escherichia coli cytosine deaminase ( CD) gene was transfected into murine B16F10 melanoma cells by recombinant adenovirus AdCD in vitro . The tumor cells infected with AdCD were more sensitive to 5-fluorocytosine (5FC) than cells infected with a control adenovirus AdLacZ. The supernatant from B16F10 cells treated with AdCD/5FC was transferred to uninfected cells, and we found that only 6. 25 % of the supernatant could significantly inhibit the growth of wild type B16F10 cells. When AdCD was directly injected into established subcutaneous B16F10 tumors in mice followed by intraperitoneal injection of 5FC for 10 days, a significant reduction in tumor size and prolongation of survival period were observed. These studies not only explored the cytotoxic effects of AdCD/5FC on B16F10 melanoma cells in vitro and in vivo but also elucidated the mechanisms of its bvstander effect.