Xenograft

Few studies in the past 10 years have mentioned xenograft due to its high level of complications and bad publicity. Recently, Stone et al. transplanted immu-nochemically modified porcine patellar tendon using the two-bone tunnels technique in ten patients with ACL-defident knees and followed them up for 24 months without any immunosuppressive treatment. At the time of publication, five of them were still in place. Only one was removed for a bone plug loosening at 15 months. No one had any knee effusion and everyone went back to their previous level of activity with a stable knee. They were able to demonstrate the process of ligamentization of the xenograft with the explanted implants (two sports accidents). They concluded that this modified porcine implant could be considered an option for patients with a ruptured ACL. 

With a goat model, some authors developed an artificial biological ligament with a porcine tendon treated with epoxy-crosslinking fixation. This process produces a passive-degrading material only when tissue regeneration is 

Olson EJ, Kang JD, Fn FH, Georgescn HI, Mason GC and Evans CH. The biochemical and histological effects of artificial ligament wear particles in vitro and in vivo stndies. Am J Sports Med. 1988 16 558-570. 

Bolton CW and Bmchman WC.The Gore-Tex expanded polytetrafluoroethyl-ene prosthetic ligament. An in vitro and in vivo evaluation. Clin Orthop Relat Res. 1985 196 202-213. 

Dnthon VB, Barea C, Abrassart, Easel JH, Fritschy and Menetrey J. Anatomy of the anterior cruciate ligament. Knee Surg Sports TraumatolArthros. 2006 14 204-213. 

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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). 

DABROSiN c, CHEN J, WANG L and THOMPSON L u (2002) Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett. 185 (1) 31-7. 

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. 

Berin MC, Eckmann L, Broide DH, Kagnoff MF. Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts. Am J Respir Cell Mol Biol 2001 24(4) 382-389. 

FIGURE 4.12 Experimental 2D-PAGE map of a neuroblastoma xenograft implanted in mice. The circles indicate the spots identified by MS analysis. Reproduced from Campostrini et al. (2005) with permission from Wiley-VCH Verlag GmbH. 

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

Chen X, Conti PS, Moats RA (2004) In vivo near-infrared fluorescence imaging of integrin av(33 in brain tumor xenografts. Cancer Res 64 8009-8014... 

Kawato Y, Furuta T, Aonuma M et al. Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. Cancer Chemother Pharmacol 1991 28 192-198. 

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. 

ATM-deficient cell lines were found to be sensitive to olaparib [53]. In xenograft studies using ATM-deficient Granta-519 cells, olaparib was shown to decrease tumor growth and prolong overall survival by 42%. 

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