Human lung cancer xenografts

In vivo studies were carried on the aziridinated cyclopent[Z ]indole quinone out before it was discovered that the aziridinyl ring did not participate in DNA alkylation. The results in Fig. 7.22 for the B16 melanoma syngraft model reveal that there was substantial reduction of tumor mass at 3 mg/kg. However, toxicity (animal deaths) became apparent at 5 mg/kg. On the other hand, human lung cancer xenografts in SCID (severe combined immunodeficient) mice were reduced to 50% mass with 3x1 mg/kg doses without any animal deaths. 

Radiation sensitization with irinotecan in two human lung cancer xenografts has been reported (42). In these experiments, CPT-11 was administered in nontoxic doses 1 h prior to a single dose of irradiation. In other reports radiation sensitization with CPT occurred during or after irradiation (43). 

Ma, Y. P. and A. L. Et. 1989. Prediction of responsiveness of human lung cancer xenografts to extracts of Fagopyrum cymosum (Trev) Meisn by SRC assay. Chin. J. Clin. Oncol. 16 309-312. 

Mattern J, Eichhorn U, Kaina B, Volm M (1998) 0 -Meth guanine-DNA methyl-transferase activity and sensitivity to cydophoshamide and dsplatin in human lung tumor xenografts. Int. ] Cancer 77 919-922... 

Tamura K, Takada M, Kawase I, et al. Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts. Jpn J Cancer Res 1997 88(2) 218—223. 

O Connor, R., et al. 2004. Increased anti-tumour efficacy of doxorubicin when combined with sulindac in a xenograft model of an MRP-1-positive human lung cancer. Anticancer Res 24 457. 

YC-1,3-(5 -hydroxymethyl-2 -furyl)-l-benzylindazole, a soluble guanylyl cyclase stimulator, has been shown in several xenograft cancer models to inhibit HIF-la protein expression and to have anti-angiogenic activity [212]. In addition, in an animal model of metastasis, YC-1 treatment dramatically reduced cell migration and metastatic burden [213]. Likewise, YC-1 treatment has been shown to decrease bone metastases derived from MDA-MD-231 breast cancer cells that were introduced into animals by intracardiac injection [214]. YC-1 was recently reported in a human lung cancer cell line to also reduce cell proliferation to block activation of matrix metalloproteinases (MMP-2 and MMP-9) and to reduce cyclin D1 expression [215]. However, to date no clinical trials using YC-1 have been initiated. 

Williams, S. S., Alosco, T. R., Mayhew, E., Lasic, D. D., Martin, F. J. and Bankert, R. B., Arrest of human lung tumor xenograft growth in severe combined immunode-ficient mice using doxorubicin encapsulated in sterically stabilized liposomes. Cancer Res., 53, 3964-3967 (1993). 

Figure 6.8 In vivo fluorescence imaging of human prostate cancer xenograft tumors. Mice were injected intravenously with GPI-functionalized QDs and observed for 4 h. (a) The prostate-specific membrane antigen (PSMA)-positive LNCaP tumor and PSMA-negative PC-3 tumor are indicated. Shown are representative images for animals in the prone position, (b) In situ (top row) and resected (bottom row) organs from a imaged at 4 h post-injection with color video and NIR fluorescence. (Ki, kidneys Du, duodenum Sp, spleen In, intestines Lu, lungs Li, liver Pa, pancreas Ab, abdominal wall Bl, bladder.) Reproduced by permission from Macmillan Publishers Ltd. Nat. Nanotechnol. Copyright (2009).

Ihle NT, Paine-Murrieta G, Berggren MI et al. (2005) The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther 4 1349-1357... 

Katiyar SK, Meeran SM, Katiyar N, Akhtar S (2009) p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol Carcinog 48 24-37... 

Shi J, Zheng D, Liu Y, Sham MH, Tam P, Farzaneh F, Xu R. Overexpression of soluble TRAIL induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. Cancer Res 2005 65 1687-1692. 

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