A novel strategy for the generation of angiostatic kringle regions from a precursor derived from plasminogen

Schmitz, Volker; Wang, L; Barajas, Miguel; Peng, Dacheng; Prieto, Jesús; Qian, Cheng

doi:10.1038/sj.gt.3301805

Cited by 16 publications

(11 citation statements)

References 24 publications

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“…Tubular formation on Matrigel was assayed as described previously 24 with a minor modification. Briefly, the 24-well plates were coated with 200 ml Matrigel.…”

Section: Tubular Formation Assaymentioning

confidence: 99%

Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy

et al. 2004

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Tumor-endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their ''crosstalk'' with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluated the in vitro and in vivo synergistic and/or additive effects of a combination of conditional oncolytic adenovirus plus an adenoviral-mediated antiangiogenic therapy. In the in vitro study, we demonstrated that human umbilical vein endothelial cells (HUVEC) and human C4-2 androgen-independent (AI) prostate cancer cells, when infected with an antiangiogenic adenoviral (Ad)-Flk1-Fc vector secreting a soluble form of Flk1, showed dramatically inhibited proliferation, migration and tubular formation of HUVEC endothelial cells. C4-2 cells showed maximal growth inhibition when coinfected with Ad-Flk1-Fc and Ad-hOC-E1, a conditional replication-competent Ad vector with viral replication driven by a human osteocalcin (hOC) promoter targeting both prostate cancer epithelial and stromal cells. Using a threedimensional (3D) coculture model, we found that targeting C4-2 cells with Ad-hOC-E1 markedly decreased tubular formation in HUVEC, as visualized by confocal microscopy. In a subcutaneous C4-2 tumor xenograft model, tumor volume was decreased by 40-60% in animals treated with Ad-Flk1-Fc or Ad-hOC-E1 plus vitamin D 3 alone and by 90% in a combined treatment group, compared to untreated animals in an 8-week treatment period. Moreover, three of 10 (30%) pre-established tumors completely regressed when animals received combination therapy. Cotargeting tumor and tumor endothelium could be a promising gene therapy strategy for the treatment of both localized and metastatic human prostate cancer.

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“…Tubular formation on Matrigel was assayed as described previously 24 with a minor modification. Briefly, the 24-well plates were coated with 200 ml Matrigel.…”

Section: Tubular Formation Assaymentioning

confidence: 99%

Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy

et al. 2004

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“…This approach would allow obtaining high concentration of the antiangiogenic molecule at the tumor site with reduced risk of systemic toxicity. Although soluble VEGF receptors (Goldman et al, 1998;Raskopf et al, 2005) and other antiangiogenic molecules, such as Tie2 receptor, angiostatin, endostatin and pigment epithelium-derived factor (PEDF) have shown antitumor activity in animal models of HCC (Lin et al, 1998;Griscelli et al, 1998;Schmitz et al, 2002;Folkman, 2003;Wang et al, 2003), clinical trials have not been initiated so far.…”

Section: Antiangiogenic Gene Therapymentioning

confidence: 99%

New therapies for hepatocellular carcinoma

et al. 2006

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“…Gene therapy is a new and promising therapeutic strategy that is based on the introduction of genetic material, for example natural genes, chimeric genes or subgenomic molecules, into cells in order to generate a beneficial effect against disease [31] . So far, a variety of gene therapy approaches have been designed to treat liver cancer, including the replacement of functional tumor suppressor genes [32] , inhibition of oncogenes [33] , selective prodrug activation within the tumor [34] , stimulation of antitumor immunity [35] and inhibition of tumor vascularization [36] , although encouraging results have been mostly only obtained in pre-clinical models.…”

Section: Hcc Biology and Targeted Therapiesmentioning

confidence: 99%

Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

Coradini

Speranza

2005

Acta Pharmacologica Sinica

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Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Surgical resection has been considered the optimal treatment approach, but only a small proportion of patients are suitable candidates for surgery, and the relapse rate is high. Approaches to prevent recurrence, including chemoemboliza-tion before and adjuvant therapy after surgery, have proven to have a limited benefit; liver transplantation is successful in treating limited-stage HCC because only a minority of patients qualify for transplantation. Therefore, new therapeutic strategies are urgently needed. Because in addition to the classical genetic mechanisms of deletion or inactivating point mutations, epigenetic alterations, such as hyperacetylation of the chromatin-associated histones (responsible for gene silencing), are believed to be involved in the development and progression of HCC, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In particular, pre-clinical results obtained using HA-But, an HDAC inhibitor in which butyric acid residues are esterified to a hyaluronic acid backbone and characterized by a high affinity for the membrane receptor CD44, indicated that this class of compounds may represent a promising approach for hepatocellular carcinoma treatment.

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A novel strategy for the generation of angiostatic kringle regions from a precursor derived from plasminogen

Cited by 16 publications

References 24 publications

Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy

Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy

New therapies for hepatocellular carcinoma

Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

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