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)

Despite multimodality treatment for thyroid cancer, including surgical resection, radioiodine therapy, thyrotropin (TSH)-suppressive thyroxine treatment, and chemotherapy/radiotherapy, survival rates have not improved over the last decades. Therefore, development and evaluation of novel treatment strategies, including gene therapy, are urgently needed. A variety of gene therapy approaches have been evaluated for the treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy (p53 restoration, expression of a dominant negative RET mutant), cytoreductive gene therapy (suicide gene/prodrug strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir, antiangiogenic therapy with endostatin) and immunomodulatory gene therapy (expression of interleukin (IL)-2 and IL-12). Furthermore, cloning of the sodium iodide symporter (NIS) gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on NIS gene transfer followed by the application of radioiodine therapy ((131)I). NIS gene delivery into medullary and follicular cell-derived thyroid cancer cells has been shown to be capable of establishing or restoring radioiodine accumulation and might therefore represent an effective therapy for medullary and dedifferentiated thyroid tumors that lack iodide accumulating activity. The data summarized in this review article clearly demonstrate that the currently available strategies represent potentially curative novel therapeutic approaches for future gene therapy of thyroid cancer. The combination of different therapeutic genes has been demonstrated to be very useful to enhance therapeutic efficacy and seems to have a promising role at least as part of a multimodality approach for advanced thyroid cancer.
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PMID:Gene therapy for thyroid cancer: current status and future prospects. 1524 69

There is growing evidence that combinations of antiangiogenic proteins with other antineoplastic treatments such as chemo- or radiotherapy and suicide genes-mediated tumor cytotoxicity lead to synergistic effects. In the present work, we tested the activity of two non-replicative herpes simplex virus (HSV)-1-based vectors, encoding human endostatin::angiostatin or endostatin::kringle5 fusion proteins in combination with HSV-1 thymidine kinase (TK) molecule, on endothelial cells (ECs) and Lewis lung carcinoma (LLC) cells. We observed a significant reduction of the in vitro growth, migration and tube formation by primary ECs upon direct infection with the two recombinant vectors or cultivation with conditioned media obtained from the vector-infected LLC cells. Moreover, direct cytotoxic effect of HSV-1 TK on both LLC and ECs was demonstrated. We then tested the vectors in vivo in two experimental settings, that is, LLC tumor growth or establishment, in C57BL/6 mice. The treatment of pre-established subcutaneous tumors with the recombinant vectors with ganciclovir (GCV) induced a significant reduction of tumor growth rate, while the in vitro infection of LLC cells with the antiangiogenic vectors before their implantation in mice flanks, either in presence or absence of GCV, completely abolished the tumor establishment.
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PMID:Antitumor effects of non-replicative herpes simplex vectors expressing antiangiogenic proteins and thymidine kinase on Lewis lung carcinoma establishment and growth. 1755 10

Herpes-mediated viral oncolysis alone is not sufficient to completely eradicate tumors. In this study we used a replication conditional, endostatin-expressing herpes simplex virus-1 mutant (HSV-Endo) in a murine lung cancer model. We hypothesized that the anti-angiogenic action of endostatin would improve upon the oncolytic effect of HSV-1. HSV-Endo was evaluated in a pulmonary metastases and orthotopic flank model, where there was significantly less tumor burden and reduced microvessel density compared to a control virus. Endostatin expression appears to improve the anti-tumor effect of HSV-1 in a lung cancer model.
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PMID:Angiogenesis inhibition using an oncolytic herpes simplex virus expressing endostatin in a murine lung cancer model. 2236 Mar 64

Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, the use of a herpes simplex virus carrying endostatin-angiostatin (VAE) as a novel therapeutic targeting strategy for glioblastoma-derived cancer stem cells was investigated. We isolated six stable GSC-enriched cultures from 36 human glioblastoma specimens and selected one of the stable GSCs lines for establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in GSCs and expressed endo-angio in vitro and in vivo 48 h and 10 d after infection, respectively; (b) compared with the control gliomas treated with rHSV or Endostar, the subcutaneous gliomas derived from the GSCs showed a significant reduction in microvessel density after VAE treatment; (c) compared with the control, a significant improvement was observed in the length of the survival of mice with intracranial and subcutaneous gliomas treated with VAE; (d) MRI analysis showed that the tumor volumes of the intracranial gliomas generated by GSCs remarkably decreased after 10 d of VAE treatment compared with the controls. In conclusion, VAE demonstrated oncolytic therapeutic efficacy in animal models of human GSCs and expressed an endostatin-angiostatin fusion gene, which enhanced antitumor efficacy most likely by restricting tumor microvasculature development.
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PMID:Enhanced antitumor efficacy of an oncolytic herpes simplex virus expressing an endostatin-angiostatin fusion gene in human glioblastoma stem cell xenografts. 2475 77