Human tumor xenografts

At the in vivo assay level, the classic ip-ip (iateraperitoneal) in vivo model has been replaced as a selection criteria for advancement of new dmg candidates to clinical trial. More stringent alternative models iaclude subcutaneous or subrenal capsule implantation of tumor followed by iatravenous dmg dosiag (7) and the human tumor xenograft models ia aude mice (8). 

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Needham D, Anyarambhatia G, Kong G, Dewhirst MW. A new temperature-sensitive liposome for use with mild hyperthermia characterization and testing in human tumor xenograft model. Cancer Res 2000 60 1197-1201. 

S. Aharinejad, D. Abraham, P. Paulus, H. Abri, M. Hoffmann, K. Grossschmidt, R. Schaefer, E. R. Stanley, and R. Hofbauer, Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor xenografts in mice. Cancer Res. 62(18), 5317-5324 (2002). 

Hemiasterlin (206) Oligopeptide E7974 (207) Oncology Tubulin assembly inhibition Phase I (against a variety of human tumor xenografts) Eisai 944... 

Activity of 4-Deacetylvinblastine HvDRAZiDE-MoAb Conjugates against Human Tumor Xenografts... 

Plumb, J.A., Finn, P.W., Williams, R.J., Bandara, M.J., Romero, M.R., Watkins, C.J. et al. (2003) Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXDIOI. Molecular Cancer Therapeutics, 2, 721-728. 

The most potent PDKl kinase inhibitor reported to date is UCN-01 (compound 16 Fig. 4 IC50 = 6 to 33 nM) [101], a staurosporine analogue isolated from the culture broth of Streptomyces sp. Originally developed as an inhibitor of calcium-dependent PKC, UCN-01 has the capacity to inhibit a broad spectrum of kinases [102], including other members of the AGC subfamily of kinases (e.g., IC5o = 491nM for PKB) [103]. UCN-Ol-induced PDKl inhibition has also been observed in in vivo murine and human tumor xenografts [101]. 

The group at Millennium Pharmaceuticals has claimed MLN-8054 (97) to be the first kinase inhibitor selective for Aurora-A over Aurora-B, which gives robust inhibition of human tumor xenografts [228-230]. Treatment of cultured human tumor cells with 97 resulted in the accumulation of mitotic cells with spindle abnormalities, a phenotype consistent with selective Aurora-A inhibition. In a pharmacodynamic model the time-dependent accumulation of... 

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Cohen-Jonathan E, Muschel RJ, Gillies McKenna W, et al. Famesyltransferase inhibitors potentiate the antitumor effect of radiation on a human tumor xenograft expressing activated HRAS. Radiat Res 2000 154 125-132. 

Goldstein NI, Prewett M, Zuklys K, et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995 1 1311— 1318. 

Kozin SV, Boucher Y, Hicklin DJ, et al. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res 2001 61 39 14. 

Fig. 8. Combined effect of fractionated NS-398 and radiotherapy on the tumor growth delay of H460 (A) and HCT-116 (B) human tumor xenografts in nude mice. Day 0 is defined as the first day of treatment. Tumors were treated with vehicle (DMSO) or 36 mg/kg NS-398 on d 1 through 7. Radiation fractions (2 Gy) were given 2 h after drug administration starting d 2, for 5 consecutive days. Error bars represent the SE from 8-9 mice. (O), vehicle treatment alone ( ), NS-398 treatment alone ( ), radiation plus vehicle treatment ( ), radiation plus NS-398 treatment.

L.D. Stegman, A. Rehemtulla, B. Beattie, E. Klevit, T.S. Lawrence, R.G. Blasberg, J.G. Tjuvajev, B.D. Ross, Noninvasive quantitation of cytosine deaminase transgene expression In human tumor xenografts with in vivo magnetic resonance spectroscopy, Proc. Natl. Acad. Scl. USA 96 (1999) 9821-9826. 

Yuan, E, M. Lennig, S.K. Huang, D.A. Berk, D. Papahadjopoulos, and R.K. Jain, Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res, 1994.54(13) 3352-6. 

Yuan, F., M. Dellian, D. Fukumura, M. Leunig, D. A. Berk, V. P. Torchilin, and R. K. Jain. 1995. Vascular permeability in a human tumor xenograft molecular size dependence and cutoflsizssr Res55 3752-3756. 

Berk, D.A., Yuan, F., Leunig, M. and Jain, R.K. (1997) Direct in vivo measurement of targeted binding in a human tumor xenograft. Proc. Natl. Acad. Sci. USA, 94,1785-1790. 

In a human tumor xenograft model, Kong et al.21 compared the antitumor effect of doxorubicin encapsulated in three types of liposome formulations, a nonthermosensitive liposome (NTSL), a traditional thermosensitive liposome (TTSL), and a low-temperature-sensitive liposome (LTSL). All three liposomes are sterically stabilized with PEG grafted on their surface. All the liposomes have a long circulation time and can accumulate selectively in tumor tissue. However, the lipid compositions of the three formulations are different. The NTSL was composed of saturated long-chain lipids such as hydrogenated soybean... 

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