HIV hollow fiber SCID model for antiviral therapy comparison with SCID/hu model

Taggart, Barbara; Harrington, Paula; Hollingshead, Melinda G.

doi:10.1016/j.antiviral.2004.04.001

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…The HFA was developed by the NCI as a low cost, high-throughput, preliminary in vivo screening assay for the evaluation of anti-cancer agents (3). It has since been adapted for the evaluation of antiviral agents (4), and there is considerable scope for use in other medical fields.…”

Section: Introductionmentioning

confidence: 99%

“…SJG-136 is a recently synthesised pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) dimer currently undergoing phase I clinical trial in both the UK (CRUK) and USA (NCI). The pyrrolo[2,1c] [1,4]benzodiazepines are a family of tricyclic antitumour antibiotics which interact sequence selectively with purineguanine-purine motifs in the minor groove of DNA, reacting covalently with the exocyclic C 2 -NH 2 of the central guanine via their electrophilic imine moiety (13).…”

Section: Introductionmentioning

confidence: 99%

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The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare

Suggitt

Cooper²,

Shnyder³

et al. 2006

Int J Oncol

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We describe a modified hollow fibre assay (HFA) for investigating the potential of novel molecules as pharmaceutical agents. In particular the assay provides drug/target interaction data that can facilitate the selection of lead compounds for further evaluation in more sophisticated solid tumour models, whilst successfully implementing the 3Rs-the 'replacement' 'refinement' and 'reduction' of animals. This more ethical and rapid approach to early drug development does not compromise on the validity, sensitivity, predictivity or efficacy of preclinical evaluation. We present novel data using the standard cross-linker mitomycin C (MMC) as a positive control, and two investigational DNA interactive molecules (C1311/ SJG-136). Tumour cells were seeded in fibres and implanted into mice. Following treatment with an intraperitoneal injection, fibres were excised and cells retrieved for pharmacodynamic analysis using the comet assay/fluorescence microscopy. Microscopy results revealed nuclear uptake and localisation within cytoplasmic organelles of HT29 colorectal adenocarcinoma cells following treatment with C1311 (150 mg/kg). Following treatment with SJG-136 (0.3 mg/kg) a 27.3% (p<0.001) DNA cross-linking (s.c.) effect was observed in the HL60 acute promyelocytic leukaemia cell line. DNA cross-linking effects of 55% (i.p) and 50% (s.c.) (p<0.005) were observed in the A549 lung carcinoma cell line following administration of MMC (6 mg/kg). These data are consistent with previous activity defined using solid tumour models, and support the use of the HFA for in vivo pharmacodynamic investigation whilst significantly reducing animal numbers and the influence of tumour growth on the welfare of mice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare

Suggitt

Cooper²,

Shnyder³

et al. 2006

Int J Oncol

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show abstract

“…Three to five months later, exploratory surgery is performed to determine if the tissues grew to a minimum of 30 mm 3 , and if so, treatments are initiated and the transplanted tissues are injected with virus. 56 The HIV hollow fiber SCID mouse assay is much faster, requires fewer surgeries, and is simpler than the SCID/hu assay. Therefore, this model can be used as a pharmacologic gatekeeper to help separate active and inactive agents and select the best lead compounds for further animal model testing such as the SCID/hu assay.…”

Section: Additional Applications Of the Hollow Fiber Assaymentioning

confidence: 99%

“…Since HIV does not infect rodent cells, human hematolymphoid organs that can support HIV replication are implanted in immunodeficient hosts such as SCID mice. − In this model, about 1 mm 3 of human fetal thymus and liver tissue (or other tissue sources of hematopoietic progenitor cells) that can support HIV replication is implanted under the renal capsules of SCID mice. Three to five months later, exploratory surgery is performed to determine if the tissues grew to a minimum of 30 mm 3 , and if so, treatments are initiated and the transplanted tissues are injected with virus . The HIV hollow fiber SCID mouse assay is much faster, requires fewer surgeries, and is simpler than the SCID/hu assay.…”

Section: Additional Applications Of the Hollow Fiber Assaymentioning

confidence: 99%

Use of the in Vivo Hollow Fiber Assay in Natural Products Anticancer Drug Discovery

Pezzuto

Farnsworth

et al. 2009

J. Nat. Prod.

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The in vivo hollow fiber assay was developed at the National Cancer Institute (NCI) to help bridge the gap between in vitro cell-based assays and human tumor models propagated in immunodeficient mice. The goal was to develop an intermediate assay that could help predict which compounds found active in the 60-cell line panel would be active in a subsequent xenograft system. This was necessary due to the high cost of the traditional xenograft assay in terms of number of animals required, time for assay completion, and financial commitment necessary. To address this problem, investigators of the NCI Developmental Therapeutics Program designed a method of propagating human cancer cells in inert hollow fibers with pores small enough to retain the cancer cells but large enough to permit entry of potential chemotherapeutic drugs, including large proteins and other important substances. Fibers containing proliferating cancer cells are transplanted into the peritoneum or under the skin, the host mice are treated with a test agent and the fibers are subsequently retrieved for analysis of viable cell mass. The assay has been successful in helping investigators from around the world, including our own research group, prioritize compounds active in vitro for further testing in the traditional xenograft system.

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Models of HIV-1 disease: A review of current status

Stoddart

Reyes

2006

Drug Discovery Today: Disease Models

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HIV hollow fiber SCID model for antiviral therapy comparison with SCID/hu model

Cited by 7 publications

References 18 publications

The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare

The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare

Use of the in Vivo Hollow Fiber Assay in Natural Products Anticancer Drug Discovery

Models of HIV-1 disease: A review of current status

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