Xenograft models

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). 

Miller, F. R. (2000). Xenograft models of premalignant human breast disease. J. Mammary Gland Biol. 5, 379-391. 

ABT-888 (22) shows limited activity as monotherapy however, it strongly potentiates the activity of multiple DNA-damaging agents in preclinical models [39]. ABT-888 potentiated TMZ in a glioma model in a dose-dependent manner, with maximal efficacy achieved at 50 mg/ kg, which reduced tumor volume by 63%, 44% better than TMZ alone. In the MX-1 breast xenograft model, ABT-888, at 5 mg/ kg/ day in combination with cisplatin, caused sustained regressions in 8/9 mice compared to 3/9 for cisplatin monotherapy. 

PD-325901 is another analog of CI-1040 that is also a potent, selective and ATP non-competitive inhibitor of MEK1/2 [23]. The compound inhibited MEK1 with Ki — 1.1 nM, MEK2 with K — 0.79 nM and pERK in C26 cells with IC50 = 0.43 nM. PD-325901 is efficacious in a number of xenograft models and is currently in Phase I/n trials in cancer patients. 

ARRY-142886 (AZD6244) is another potent, selective and ATP non-competitive MEK1/2 inhibitor with IC50 = 12 nM. This compound inhibited cellular pERK with an ICYn < 10 nM and tumor growth in a number of xenograft models and is reported to be in Phase II clinical trials in cancer patients [25]. 

Ciomei M, Croci V, Ciavolella A, Ballinari D, Pesenti E. Antitumor efficacy of edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model. Clin. Cancer Res. 2006 May 1 12(9) 2856-61. 

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. 

Tardi P, Choice E, Masin D, Redelmeier T, Bally M, Madden TD. Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. Cancer Res 2000 60 3389. 

Harrington KJ, et al. Targeted radiosensitisation by pegylated liposome-encapsulated 3, 5 -0-dipalmitoyl 5-iodo-2 -deoxyuridine in a head and neck cancer xenograft model. Br J Cancer 2004 91 366. 

Sapra P, Moase EH, Ma J, et al. Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab fragments. Clin Cancer Res 2004 10 1100. 

Messerer CL, Ramsay EC, Waterhouse D, et al. Liposomal irinotecan formulation development and therapeutic assessment in murine xenograft models of colorectal cancer. Clin Cancer Res 2004 10(19) 6638. 

Jackson T, Chougule MB, Ichite N, Patlolla RR, Singh M. (2008) Antitumor activity of noscapine inhuman non-small cell lung cancer xenograft model. Cancer Chemother Pharmacol 63 117-126. 

Kelner MJ, McMorris TC, Estes L, Wang W, Samson KM, Taetle R. (1996) Efficacy of HMAF (MGI-114) in the MV522 metastatic lung carcinoma xenograft model nomesponsive to traditional anticancer agents. Invest New Drugs 14 161-167. 

In human colon, prostate, and breast cancer cells, SFN has demonstrated inhibition of HDAC activity.In xenograft models of prostate cancer and osteosarcoma, SFN has inhibited HDAC activity, increased acetylation levels of H3 and H4, and a slowing of growth." " In vivo results confirm that SFN is an effective chemoprotective... 

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