JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Marked therapeutic efficacy of a novel polyethylene glycol-SN38 conjugate, EZN-2208, in xenograft models of B-cell non-Hodgkins lymphoma.
Haematologica
PUBLISHED: 10-02-2009
Show Abstract
Hide Abstract
Examination of the clinical utility of SN38 (10-hydroxy-7-ethyl-camptothecin), the active metabolite of CPT-11, has not been possible to date due to poor solubility of SN38. Here we evaluated the activity of EZN-2208, a water-soluble polyethyleneglycol-SN38 conjugate, in pre-clinical models of Burkitts non-Hodgkins lymphoma (NHL) (Raji and Daudi), and follicular NHL (DoHH2). In vitro, the IC50 of EZN-2208 ranged from 3-24 nM, which was 30- to 45-fold lower than CPT-11 or 2.5- to 3.5-fold higher than SN38. In both an early-disease Raji model and an advanced-disease Daudi model, treatment with multiple doses of EZN-2208 resulted in 90% and 100% cures of animals, respectively (cure defined as no sign of tumors by gross observations at the termination of study). The activity of EZN-2208 was dramatically superior to that of CPT-11 in all three models. The excellent therapeutic efficacy of EZN-2208 in several B-cell NHL xenograft models merits its evaluation in the clinic for lymphoid malignancies.
Related JoVE Video
Stromal platelet-derived growth factor receptor ? (PDGFR?) provides a therapeutic target independent of tumor cell PDGFR? expression in lung cancer xenografts.
Mol. Cancer Ther.
Show Abstract
Hide Abstract
In lung cancer, platelet-derived growth factor receptor ? (PDGFR?) is expressed frequently by tumor-associated stromal cells and by cancer cells in a subset of tumors. We sought to determine the effect of targeting stromal PDGFR? in preclinical lung tumor xenograft models (human tumor, mouse stroma). Effects of anti-human (IMC-3G3) and anti-mouse (1E10) PDGFR? monoclonal antibodies (mAb) on proliferation and PDGFR? signaling were evaluated in lung cancer cell lines and mouse fibroblasts. Therapy studies were conducted using established PDGFR?-positive H1703 cells and PDGFR?-negative Calu-6, H1993, and A549 subcutaneous tumors in immunocompromised mice treated with vehicle, anti-PDGFR? mAbs, chemotherapy, or combination therapy. Tumors were analyzed for growth and levels of growth factors. IMC-3G3 inhibited PDGFR? activation and the growth of H1703 cells in vitro and tumor growth in vivo, but had no effect on PDGFR?-negative cell lines or mouse fibroblasts. 1E10 inhibited growth and PDGFR? activation of mouse fibroblasts, but had no effect on human cancer cell lines in vitro. In vivo, 1E10-targeted inhibition of murine PDGFR? reduced tumor growth as single-agent therapy in Calu-6 cells and enhanced the effect of chemotherapy in xenografts derived from A549 cells. We also identified that low expression cancer cell expression of VEGF-A and elevated expression of PDGF-AA were associated with response to stromal PDGFR? targeting. We conclude that stromal PDGFR? inhibition represents a means for enhancing control of lung cancer growth in some cases, independent of tumor cell PDGFR? expression.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.