Tumor models, variety

From the above described antitumor and emesis studies, JM216 was selected on the basis of possessing both good oral antitumor activity against a variety of murine and human ovarian tumor models, a low emesis score in the ferret and favourable physico-chemical properties. 

Lactam-based analogs of epothilones were conceived by the BMS group as metabolically more stable alternatives to the lactone-based natural products (which exhibit limited metabolic stability in rodent plasma). It is worth noting, however, that despite its short plasma half-life in rodent species, Epo B shows potent antitumor activity in a variety of nude mouse human tumor models,and the same is tme for Epo D (vide infra). In addition, Epo D has subsequently been demonstrated to... 

Poly(glutamic acid) Paclitaxel Ester A variety of tumor models in mice Phase... 

The anticancer drugs delivered by liposomes include many small molecule drugs such as DOX, daunoru-bicin, platinates, taxanes, camptothecin, etc. The most successful development is DOX-encapsulated pegylated liposomes, with a trade name of Doxil in the U.S. market or Cylax in the European market. Doxil has shown significant clinical advantages over free DOX and conventional DOX liposomes.f Enhanced tumor accumulation of Doxil has been demonstrated in numerous preclinical studies over a variety of tumor models. Similar effects were also observed in clinical uses. 

The Combretastatin A-4 analogues, containing a variety of heterocyclic moieties, such as imidazoles, thiazoles and tetrazoles, not only display efficient inhibition of tubulin polymerization but also exert potent cellular growth inhibition in different cancer lines including MDR cancer cells. It is worthy to note that some of Combretastatin A-4 analogues, such as imidazole-based Combretastatin A-4 exhibited oral availability leading to solid tumor regression in vivo tumor models. 

IL-12 has been shown to exert striking therapeutic effects at nontoxic doses in mouse tumor models and in mouse models of a variety of infectious diseases and airway inflammation. In mouse tumor models, the therapeutic effects of IL-12 have been shown to result from its immu-noenhancmg activity, which requires both T cells and IFNy. In some models, administration of IL-12 can result in antiangiogenic effects, which may also contribute to its antitumor activity. Tumor cell-induced angiogenesis is... 

The antitumor activity of saffron was also evaluated against a variety of murine tumor models. Ascites tumors were induced by i.p. transplantation of one million cells in mice and appeared in 7-14 days depending on the type of tumor cells used [82], Saffron was administered... 

Poly(ADP-ribose) polymerases (PARPs) are a family of abundant nuclear enzymes that play a critical role in DNA repair mechanism triggered by DNA damaging agents or radiation. Inhibition of PARPs that often over-express in a variety of tumors, would retard this intracellular DNA repair and maximize the antitumor effects of radiation or cytotoxic agents. We have developed ABT-888, an orally efficacious PARP inhibitor currently being evaluated in several human phase I clinical trials. Herein, we disclose our discovery of another series of highly potent and orally efficacious PARP inhibitors. The SAR, structural characterization, and in vivo evaluation of this series of PARP inhibitors in a number of rodent tumor models in combination with temozolomide (TMZ) will be presented. 

Correlation of Certain Proteases with Metastatic Potential in Model Tumor Systems. A variety of different proteases have been found to correlate with metastatic potential in model tumor systems. Many of these early studies were carried out with B16 mouse melanoma cells. Variants of these cells with different metastatic potential have been selected. In separate experiments, total PA activity, CB activity, and collagenase IV activity have all been found to correlate with metastatic potential in these cells (A4, D6). More recently, levels of mRNA for CB have also been found to correlate with metastasis in these melanoma cells (Ql). Correlations also exist between levels of specific proteases and metastatic ability in a number of other model systems see Table 2 (D6). 

However, similar changes in hpid conposition are possible using a variety of other cell types (Bums and Wagner, 1993) such as an adenocarcinoma (Awad and Specter, 1976), and hepatoma (Wood et al, 1975). The dietary fatty acid modification is not limited to tumor cells, since many tissues of the host are affected (Bums et al., 1983). However, different tissues are modified to varying extents, and because of this it will likely be possible to develop protocols that provide therapeuhc selechvity by producing greater or lesser enrichment of the neoplashc cells with a particular type of fatty acid as compared to normal tissues. We have also demonstrated that L1210 leukemia cells that were fatty acid modified in vivo and then placed into tissue culture maintain their experimentally-induced fatty acid composition for up to 4 days (Bums et al, 1980). Therefore, this is a versahle model. 

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