An inbred colony of oncogene transgenic mice: diversity of tumours and potential as a therapeutic model

Thomas, Hilary; Hanby, Andrew M.; Smith, Roy C.; Hagger, P.; Patel, Keyur; Raikundalia, B.; Camplejohn, R. S.; Balkwill, Frances R.

doi:10.1038/bjc.1996.12

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…A transplantable breast carcinoma, originated from a colony of BALB/c c-neu transgenic mice (Thomas et al, 1996) was used as a solid epithelial tumour model. This breast carcinoma was passaged every 14 to 16 days to BALB/c mice.…”

Section: Tumourmentioning

confidence: 99%

See 1 more Smart Citation

Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model

Dias¹,

Thomas

Balkwill³

1998

Int. J. Cancer

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Section: Tumourmentioning

confidence: 99%

“…The breast tumour originated in a colony of c-neu transgenic mice previously described (Thomas et al, 1996) and is an invasive, angiogenic, comedo-type, metastatic breast carcinoma. It grows as a solid mass around a central area of necrosis.…”

mentioning

confidence: 99%

Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model

Dias¹,

Thomas

Balkwill³

1998

Int. J. Cancer

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“…Physiological differences associated with factors such as diet (164), environment (139), and maternal in uences (39,85,86) may require investigation of apparent phenotypes under a variety of husbandry conditions. In addition, phenotypes may be altered by background strain (29,57,134) and genetic drift (113,142,143). Therefore, the genetic milieu of GEMs and their wild-type controls must be identical-ideally by backcrossing to a constant genetic background.…”

Section: Confounding Phenotypesmentioning

confidence: 99%

“…For example, differences in the level of transgene expression of certain cytokines in the central nervous system results in the development of either acute (high expression) or chronic progressive (low expression) disease associated with a spectrum of clinical, physiologic and pathologic manifestations (17 ). Phenotypes may decline or become enhanced in later generations (142).…”

mentioning

confidence: 99%

Use of Genetically Engineered Mice in Drug Discovery and Development: Wielding Occam's Razor to Prune the Product Portfolio

Bolon

Galbreath

2002

Int J Toxicol

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Genetically engineered mice (GEMs) that either overexpress (transgenic) or lack (gene-targeted, or "knock-out") genes are used increasingly in industry to investigate molecular mechanisms of disease, to evaluate innovative therapeutic targets, and to screen agents for efficacy and/or toxicity. High throughput GEM construction in drug discovery and development (DDD) serves two main purposes: to test whether a given gene participates in a disease condition, or to determine the function(s) of a protein that is encoded by an expressed sequence tag (EST, an mRNA fragment for a previously uncharacterized protein). In some instances, phenotypes induced by such novel GEMs also may yield clues regarding potential target organs and toxic effects of potential therapeutic molecules. The battery of tests used in phenotypic analysis of GEMs varies between companies, but the goal is to define one or more easily measured endpoints that can be used to monitor the disease course--especially during in vivo treatment with novel drug candidates. In many DDD projects, overt phenotypes are subtle or absent even in GEMs in which high-level expression or total ablation of an engineered gene can be confirmed. This outcome presents a major quandary for biotechnology and pharmaceutical firms: given the significant expense and labor required to generate GEMs, what should be done with "negative" constructs? The 14th century philosophical principle known as Occam's razor-that the simplest explanation for a phenomenon is likely the truth-provides a reasonable basis for pruning potential therapeutic molecules and targets. In the context of DDD, Occam's razor may be construed to mean that correctly engineered GEMs lacking obvious functional or structural phenotypes have none because the affected gene is not uniquely essential to normal homeostasis or disease progression. Thus, a "negative" GEM construct suggests that the gene under investigation encodes a ligand or target molecule without significant therapeutic potential. This interpretation indicates that, at least in a market-driven industrial setting, such "negative" projects should be pruned aggressively so that resources may be redirected to more promising DDD ventures.

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“…MHC class I and rat HER-2 expression was confirmed by flow cytometry. The HTH-K tumor cell line was obtained from F. Balkwill (Imperial Cancer Research Fund, London, U.K.) (35). HTH-K expresses rat HER-2 and grows progressively in BALB/c and BALB/c ϫ MMTV-c-neu F 1 hybrids.…”

Section: Mice Cell Lines and Tumor Challengesmentioning

confidence: 99%

HER-2 DNA and Protein Vaccines Containing Potent Th Cell Epitopes Induce Distinct Protective and Therapeutic Antitumor Responses in HER-2 Transgenic Mice

Renard¹,

Sonderbye²,

Ebbehøj³

et al. 2003

The Journal of Immunology

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Overexpression of the growth factor receptor HER-2 (c-erbB-2, neu) has transforming potential and occurs in ∼20–30% of breast and ovarian cancers. HER-2 is a self Ag, but Abs and T cells specific for HER-2 have been isolated from cancer patients, suggesting HER-2 may be a good target for active immunotherapy. We constructed rat HER-2 DNA and protein vaccines containing potent Th cell epitopes derived from tetanus toxin and studied their potency in two strains of mice transgenic for the rat HER-2 molecule. Vaccination with HER-2 DNA protected nontransgenic mice from tumor challenge, but induced only moderate protection in one of the tumor models. However, vaccination with the modified HER-2 protein resulted in almost complete protection from tumor challenge in both tumor models. This protection could be mediated by Abs alone. In addition, protein vaccination efficiently eliminated pre-established tumors in both models, even when vaccination occurred 9 days after tumor implantation. These data demonstrate the potential of HER-2-based vaccines as therapeutic agents for the treatment of cancers overexpressing HER-2.

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An inbred colony of oncogene transgenic mice: diversity of tumours and potential as a therapeutic model

Cited by 9 publications

References 22 publications

Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model

Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model

Use of Genetically Engineered Mice in Drug Discovery and Development: Wielding Occam's Razor to Prune the Product Portfolio

HER-2 DNA and Protein Vaccines Containing Potent Th Cell Epitopes Induce Distinct Protective and Therapeutic Antitumor Responses in HER-2 Transgenic Mice

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