Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous study, we have shown that vector pBV22210 containing a chloramphenicol resistance and a cryptic plasmid pMB1 from Bifidobacterium longum strain could stably replicate and did not significantly affect the biological characteristics of B. longum. In this study, B. longum was transfected by electroporation with pBV22210 encoding the extracellular domain of TRAIL (B. longum-pBV22210-TRAIL) and its carbohydrate fermentation and growth curve were determined, and its location and inhibitory effect on tumor xenografts in mice were also examined. The results further proved that gene transfection did not change the main biochemical characteristics of B. longum. The results also showed that B. longum-pBV22210-TRAIL resulted in selective location in tumors and exhibited a definite antitumor effect on S180 osteosarcoma. In addition, when a low dosage of Adriamycin (5 mg kg(-1)) or B. longum-pBV22210-endostatin was combined, the antitumor effect was significantly enhanced. The successful inhibition of S180 tumor growth suggested a stable vector in B. longum for transporting anticancer genes combined with low-dose chemotherapeutic drugs or other target genes is a promising approach in cancer gene therapy.
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PMID:Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth. 1922 87

This study examined the effects of TRAIL-endostatin-based gene-radiotherapy on cellular growth, apoptosis and cell cycle progression in human vascular endothelial cells ECV304 in vitro. The expression of TRAIL and endostatin protein in ECV304 cells was detected by ELISA after the transfection of recombinant plasmid pshuttle-Egr1-shTRAIL-shES and X-ray irradiation. Then MTT assay was used for determining the cellular proliferation, and flow cytometry (FCM) plus Annexin V and propidium iodide (PI) double-staining or PI single-staining were employed for the detection of apoptosis and cell cycle progression. The results showed that expression of TRAIL and endostatin protein exhibited a time- and dose-dependent change in ECV304 cells after pshuttle-Egr1-shTRAIL-shES transfection in conjunction with irradiation. In the TRAIL-endostatin-based single- or double-gene-radiotherapy, the cell viability declined in a time- and dose-dependent manner, the percentage of cells at G(2)/M phase and apoptotic rate was increased, and the percentage of cells at G(0)/G(1) phase was lowered as compared with those receiving radiotherapy alone. Moreover, TRAIL-endostatin-based double-gene-radiotherapy demonstrated better effects on growth inhibition, promotion of apoptosis and induction of cell cycle arrest in ECV304 cells than single-gene-radiotherapy.
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PMID:Enhanced effects of TRAIL-endostatin-based double-gene-radiotherapy on suppressing growth, promoting apoptosis and inducing cell cycle arrest in vascular endothelial cells. 2252 15

Interleukin-2 (IL-2), as an important cytokine in immune response, has been demonstrated to have therapeutic activity in several cancer models. In our previous study, we showed that the pBV22210 vector containing a chloramphenicol resistance gene and the cryptic plasmid, pMB1, from the Bifidobacterium longum (B. longum) strain could stably replicate and did not significantly affect the biological characteristics of B. longum. In this study, B. longum was transfected by electroporation with pBV22210 containing IL-2 (B. longum-pBV22210-IL-2), its growth curve was determined, and its inhibitory effect on tumor xenografts in mice was examined. The results showed that B. longum-pBV22210-IL-2 reduced the tumor size and prolonged the survival time of H22 tumor-bearing mice. In addition, when cyclophosphamide (CTX), B. longum-pBV22210-endostatin, or B. longum-pBV22210-TRAIL was combined with B. longum-pBV22210-IL-2, the antitumor effect was significantly enhanced. The survival times of the mice in the combination groups of B. longum-pBV22210-endostatin or B. longum-pBV22210-TRAIL were longer than those of the mice in the B. longum-pBV22210-IL-2 alone group. However, when CTX was added, the survival times of the mice showed no statistically significant difference compared with those of the mice in the dextrose-saline solution group. These results suggest that B. longum-pBV22210-IL-2 has potent antitumor effects that could be enhanced when combined with chemotherapeutic drugs or other antitumor genes.
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PMID:Therapeutic efficacy of Bifidobacterium longum-mediated human interleukin-2 with endostatin or TRAIL in transplanted tumors in mice. 2296 15

A previous study reported that combinatorial human endostatin and soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL) gene transfer suppresses human hepatocellular carcinoma (HCC) growth and angiogenesis using the pVAX1 plasmid vector. The current study investigated the antitumor efficacy in HCC through adenovirus-mediated combination gene therapy. Human endostatin and sTRAIL (114 to 281 AA) genes were amplified and cloned into the Adeno-X expression vector. The recombinant adenoviruses (Ad-E and Ad-T) were packaged, amplified in the HEK 293 cells and used to infect human umbilical vein endothelial cells (HUVECs) and HepG2 cells, respectively. The results revealed that a significant cell growth inhibition was observed in the two types of cells using a cell viability assay. Intratumoral administration with Ad-E and Ad-T revealed a significant enhanced regression of the tumors compared with treatment with either recombinant adenovirus alone. Histology and immunohistochemistry examination further indicated that the inhibition of tumor growth appeared to result from increased apoptosis and reduced angiogenesis in tumor xenografts. In conclusion, these data further confirm the enhancement of antitumor efficacy through combined endostatin and TRAIL gene therapy and provide a promising application prospect by virtue of adenovirus-mediated anti-angiogenic and pro-apoptotic cancer gene therapy.
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PMID:Adenovirus-mediated combined anti-angiogenic and pro-apoptotic gene therapy enhances antitumor efficacy in hepatocellular carcinoma. 2325 47

One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is gene-radiotherapy, i.e. a combination of radiation therapy and gene therapy. It is to choose certain exogenous radiation-inducible regulatory genes, for example, early growth response-1 (Egr-1), and transcript its downstream tumor-therapeutic genes under ionizing radiation so as to kill the tumor cells synergistically by the expressed gene products together after transfection and irradiation exposure. In this study, we engineered a plasmid encoding both TRAIL and endostatin under the control of the radiation-inducible Egr-1 promoter, and evaluated its anti-tumor efficacy in combination with radiotherapy. Our plasmid showed significant efficacy in up-regulating the levels of TRAIL and endostatin proteins after transfected into breast cancer cells and exposed to X-ray irradiation. The detected cellular effects in vitro manifested that TRAIL-endostatin-based gene therapy could enhance radiosensitizing effects in breast cancer cells in terms of tumor cell growth inhibition, promoting apoptosis and the induction of cell cycle arrest. In summary, our results suggest that TRAIL-endostain-targeting approach might be a promising method to sensitize solid tumors to radiation therapy.
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PMID:Radiosensitization of breast cancer cells by TRAIL-endostatin-targeting gene therapy. 2390 95