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)

Uveal melanoma is the most common primary ocular malignancy, although it is rare in children, and patients presenting with metastatic disease have a median survival of only 2 to 5 months. The tumor is generally unresponsive to systemic chemotherapy, but immunotherapy may be effective in selected patients. This report describes an 8-year-old girl with metastatic uveal melanoma treated with high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide. She tolerated treatment well and initially responded with stable disease in the liver and pancreas for 23 months. New pulmonary metastases developed and she was re-treated with high-dose IL-2, resulting in regression of her liver lesions and stable pulmonary disease for more than 18 months. These results suggest that IL-2 at high doses, and in combination with thalidomide, may be useful for uveal melanoma with tolerable side effects in children. Further study of this combination in children with immune-responsive tumors is warranted.
 ...
PMID:Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide. 1221 99

The dose of radiation that can be safely delivered to cancers residing in sensitive areas such as the lungs is limited by concern for normal tissue damage. Therapies that target tumor vasculature have potential to enhance the efficacy of radiotherapy, with minimal risk for toxicity. We constructed a unique plasmid, pXLG-mEndo, containing the mouse endostatin gene. A significantly greater anti-tumor effect was obtained against Lewis lung carcinoma (LLC) in mice when pXLG-mEndo was combined with radiation compared to radiation alone. Here we report results of cellular and cytokine assessments performed one day after treatment. These analyses were done to obtain baseline data on leukocytes that affect angiogenesis, as well as anti-tumor immunity, and to detect possible treatment-related toxicities. White blood cell counts were dramatically elevated in blood and spleens of untreated tumor-bearing mice, primarily due to granulocytosis. Overall, the effect of radiation was more evident than that of the plasmids (pXLG-mEndo and parental pWS4); radiosensitivity of specific lymphocyte subsets was variable (B > T > NK; CD8+ Tc > CD4+ Th). Tumor presence resulted in dramatically elevated interleukin-2 (IL-2) and decreased tumor necrosis factor-alpha (TNF-alpha) in supernatants of activated splenocytes, but had no significant effect on interferon-gamma (IFN-gamma). Administration of pXLG-mEndo, radiation, or both modified the tumor-induced aberrations in IL-2 and TNF-alpha; IFN-gamma production was decreased by radiation. Red blood cell counts, hemoglobin, and hematocrit were low in tumor-bearing mice, but there were no treatment-related differences among groups. Platelet counts were reduced, whereas their volumes were increased in tumor-bearing mice; both parameters were only slightly affected by either pXLG-mEndo or control plasmid injection, however. The data demonstrate in the Lewis lung carcinoma model that tumor-localized endostatin gene therapy and radiation had significant effects on cells and cytokines that can influence angiogenesis, tumor growth, and immune status.
 ...
PMID:Radiation and endostatin gene therapy in a lung carcinoma model: pilot data on cells and cytokines that affect angiogenesis and immune status. 1655 Nov 33

There is a great demand for the improvement of mammalian cell production systems such that they can compete economically with their prokaryotic counterparts. Of a number of parameters that need to be explored to accomplish this we have tested the effects of different signal peptides on the synthesis and secretion of Gaussia princeps luciferase in mammalian cells. A series of plasmids were transfected into CHO cells where the coding region for the marine luciferase was fused to the signal peptide coding regions derived from different sources. Both cell extracts and medium samples were analysed for luciferase activity. When the native Gaussia luciferase signal sequence in the vector was substituted by that from human interleukin-2 or albumin then the amount of active recombinant protein produced was substantially reduced, both in transiently and stably transfected cells. Western blotting showed that enzyme activity and protein levels mirrored one another. The major decrease in luciferase activity was shown not to be a result of decreased mRNA levels, indicating the involvement of a post-transcriptional event. When the coding region of human endostatin was fused to that of the Gaussia luciferase signal peptide then an elevated level of secreted endostatin was observed compared to when that of the albumin signal peptide was used. Stable transfection of HepG2 cells with the different signal peptide constructs gave essentially the same results as seen in CHO cells. The overall results indicate that the choice of signal peptide can be imperative to ensure an optimal synthesis and secretion of a recombinant protein in a mammalian cell culture system.
 ...
PMID:The level of synthesis and secretion of Gaussia princeps luciferase in transfected CHO cells is heavily dependent on the choice of signal peptide. 1731 61

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.
 ...
PMID:Therapeutic efficacy of Bifidobacterium longum-mediated human interleukin-2 with endostatin or TRAIL in transplanted tumors in mice. 2296 15