1998
DOI: 10.1023/a:1006140513233
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Abstract: Rapid evaluation of new cytotoxic agents and biological response modifiers for therapy of cancer and elucidation of their mechanisms of action require the use of relevant animal models. It is well established that the faithful reproduction of the tumor microenvironment that allows the emergence of subpopulations of tumor cells with the biological and metastatic properties observed in clinical cancer occurs with orthotopic tumor models (transplantable and transgenic). This review summarizes the evidence that ph… Show more

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Cited by 378 publications
(123 citation statements)
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“…The same could be true for their infiltration of tumors, and we do detect fewer macrophages infiltrating tumors growing in integrin-or selectin-deficient mice, although the numbers of circulating monocytes͞macrophages do not differ among the strains of mice (15). Macrophages have been suggested to be tumoricidal (36)(37)(38)(39), although other reports have suggested that they also can contribute to tumor growth (40-42); they probably have both effects (42)(43)(44)(45)(46).…”
Section: Discussionsupporting
confidence: 50%
“…The same could be true for their infiltration of tumors, and we do detect fewer macrophages infiltrating tumors growing in integrin-or selectin-deficient mice, although the numbers of circulating monocytes͞macrophages do not differ among the strains of mice (15). Macrophages have been suggested to be tumoricidal (36)(37)(38)(39), although other reports have suggested that they also can contribute to tumor growth (40-42); they probably have both effects (42)(43)(44)(45)(46).…”
Section: Discussionsupporting
confidence: 50%
“…Tumors growing subcutaneously may show unnatural reactions to experimental drugs [37, 42], possibly because the expression profile of multidrug resistance (mdr) genes is altered [49, 50]. Thus, therapeutic results obtained in a subcutaneous tumor model should always be followed by studies in an orthotopic implantation model, preferably one in which metastases develop [51]. …”
Section: Implantation Modelsmentioning
confidence: 99%
“…Indeed, significant evidence exists demonstrating the same tumor cell line has an improved response to chemotherapy when the cells are implanted subcutaneously compared with orthotopic implantation of cells. 34 Thus, for proper evaluation of novel therapies, it is critical to implant cancer cells in the appropriate environment. Furthermore, in a clinical setting, patients are often being treated for advanced metastatic disease, while s.c. xenograft models are treated within 1-14 d of tumor inoculation and rarely develop metastases.…”
Section: Evaluation Of a Reductively Activated Duocarmycin Prodrug Agmentioning
confidence: 99%
“…35 Thus, orthotopic tumor models are more clinically relevant for assessing drug efficacy, as they more accurately represent the clinical growth characteristics of primary tumor and metastatic disease. 34,[36][37][38] To further advance BocNHO as a clinical candidate, we examined this novel prodrug for activity against breast, prostate and lung solid tumor cell lines in a series of in vitro experiments and then selected one type of cancer for an in vivo orthotopic tumor efficacy study. Herein, we reveal the potent anti-cancer properties of the BocNHO prodrug against solid tumor cell lines in vitro and demonstrate superior in vivo efficacy in an aggressive orthotopic non-small cell lung cancer model.…”
Section: Evaluation Of a Reductively Activated Duocarmycin Prodrug Agmentioning
confidence: 99%