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

Both chemotherapy and chimeric anti-CD20 monoclonal antibodies are effective agents against B-cell non-Hodgkin lymphoma (NHL). However, patients achieving remission are at risk of relapse. To evaluate the effect of the antiangiogenic drug endostatin used alone and after the administration of cyclophosphamide (CTX) or the anti-CD20 antibody rituximab, we generated a new model of human NHL by transplanting Namalwa cells intraperitoneally into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. First, we determined the most effective treatment schedule for the drugs assessed. When administered alone, CTX (3 courses of 75 mg/kg of body weight given intraperitoneally), rituximab (3 courses of 25 mg/kg given intraperitoneally), and endostatin (5 courses of 50 microg given subcutaneously) delayed tumor growth, and CTX was the most effective in controlling bulky disease. When given after chemotherapy or immunotherapy, endostatin effectively induced tumor stabilization. When mice given CTX or rituximab on days 3, 5, and 7 after transplantation were randomly assigned to receive endostatin or phosphate-buffered saline on days 15 to 19, tumor growth was prevented in endostatin-treated mice as long as the drug was administered. Furthermore, administration of endostatin on days 25 to 29 after tumor regrowth still induced significant tumor regression, whereas CTX and rituximab were not effective. The specific antiangiogenic action of endostatin was confirmed by in vitro and in vivo studies indicating that the drug inhibited proliferation and induced apoptosis of endothelial (but not of NHL) cells. In conclusion, sequential administration of chemotherapy and endostatin seems promising for treating bulky NHL, and the less toxic sequential administration of rituximab and endostatin is promising for treating limited disease. (
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PMID:Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma. 1089 63

Granulocyte colony-stimulating factor (GCSF) is frequently used as an adjunctive agent in tumor chemotherapy. Bifidobacterium longums (B. longum) attracted researchers' interests due to its enhancement of immunity and selective location in solid tumors. B. longum-pBV22210-endostatin (Endo) was proved to have a definite inhibitive effect on tumor growth in our previous study. In the present study, we evaluated the effects of B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with cyclophosphamide (CTX) on H22 and S180 tumor-bearing mice. Based on our previous work, the plasmid pBV22210-GCSF was constructed and transformed by electroporation into B. longum. The B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with CTX were applied to treat H22 and S180 tumor-bearing mice. A leukocyte count was carried out and the tumor inhibition rate was calculated after treatment. In our study, CTX combined with B. longum-pBV22210-GCSF significantly raised the leukocyte level of tumor-bearing mice, while combined with B. longum-pBV22210-GCSF alone or B. longum-pBV22210-Endo alone combinations with CTX inhibited tumor growth by over 65%. The results showed that B. longum-pBV22210-GCSF had an effective antagonistic effect on bone marrow inhibited by CTX and could inhibit tumor growth when it was combined with B. longum-pBV22210-Endo and CTX. Our results provide an enhanced understanding of B. longum and GCSF as well as their potential as an adjunctive approach in cancer gene therapy.
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PMID:Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors. 1967 23

One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.
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PMID:Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs. 1974 37

Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable beta-subunit human choriogonadotropin (beta-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment.
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PMID:Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma. 2023 20

EMT-6/Parent and EMT-6/CDDP and EMT-6/CTX in vivo alkylating agent resistant cells were grown as spheroids or as monolayers and their response to cis-diamminedichloroplatinum(II) or 4-hydroperoxycyclophosphamide exposure for 1 h alone or in combination with TNP-470 or SR-4233 was determined. When grown as spheroids, each of the three cell lines were less responsive to cis-diamminedichloroplatinum(II) and 4-hydroperoxycyclophosphamide exposure than when the cells were grown and drug-treated in monolayer. The hypoxic cell selective cytotoxic agent SR-4233 was additive in cytotoxicity with the antitumor alkylating agents in both the monolayer and spheroid cultures as determined by isobologram analysis. The antiangiogenic agent TNP-470 was synergistic in cytotoxicity in combination with cis-diammedichloroplatinum in each of the three cell lines when the cells were grown in monolayer and was additive in cytotoxicity with cis-diamminedichloroplatinum(II) when the cells were grown as spheroids. The combination of TNP-470 and 4-hydroperoxycyclophosphamide resulted in additive cytotoxicity toward both monolayer cultures and spheroids. Thus, co-exposure with TNP-470 or SR-4233 increased the cytotoxicity of the antitumor alkylating agents in both the parental and drug resistant cells grown as monolayers or spheroids.
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PMID:Combinations of tnp-470 or sr-4233 with antitumor alkylating-agents in emt-6 spheroids and monolayers. 2155 3

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

Our previous study suggests that heme oxygenase-1 (HO-1) may play an important role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in peritoneal metastasis of gastric cancer (PMGC) and explored the potential mechanism. We established animal model of PMGC by orthotopic implantation into nude mice of human gastric cancer cell line GC9811-P with high peritoneal metastasis potential. The mice were injected intraperitoneally with saline, CTX or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was determined by immunohistochemistry, and vascular endothelial growth factor (VEGF) level was determined by ELISA. We found that the number, volume, weight of peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg) group decreased remarkably compared with control group. MVD value and VEGF level of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased significantly, while the survival rate and survival time of the mice were higher than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species production and ERK phosphorylation in human umbilical vein endothelial cells. In conclusion, our results suggest that HO-1 plays an important role in PMGC and ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC.
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PMID:ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic activity. 2596 Feb 43