The hollow fiber assay for drug responsiveness in the Ewing’s sarcoma family of tumors

Bridges, Esther; Bibby, Michael C.; Burchill, Susan A.

doi:10.1016/j.jpeds.2006.02.042

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Several papers have examined the efficacy of hollow fibre assays and find a high degree of correlation between hollow fibre and xenograft assays (e. g. Mi et al 2002, Bridges et al 2006, with the added advantages that more than one cell type can be tested at the same time, and thus comparison between different cell types is better controlled. Hollow fibre methodology has been adopted by the National Cancer Institute of the US as a wholly reliable primary in vivo assay for anti-cancer activity.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

Anti-cancer actions of a recombinant antibody (R6313/G2) against the angiotensin II AT1 receptor

Redondo-Müller¹,

Stevanovic-Walker²,

Barker³

et al. 2008

Endocrine Related Cancer

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Although several tumour types express both AT1 and AT2 angiotensin II receptors, and angiotensin II stimulates cell proliferation, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not effective anti-cancer agents. Development of a biologically active monoclonal antibody (6313/G2) against the AT1 receptor prompted the testing of a recombinant short-chain variable fragment form (R6313/G2) against breast cancer cells in vitro and in vivo. Cell lines MCF-7, MDA-MB-231 and T47D all expressed both receptor subtypes. In vitro, R6313/G2 suppressed cell proliferation in the presence of 100 nM angiotensin II, with IC50s of 30 nM, 153 nM and 2.8 mM for the three cell types respectively; in contrast, the AT1 receptor blocker losartan was effective only in T47D cells, at 25 mM. Studies on MCF-7 and T47D cells showed R6313/G2 also opposed the angiotensin II-induced inhibition of caspase-3/7 activity. In vivo, hollow fibres containing the cell lines were implanted in nu/nu balb-c mice at two sites, s.c. and i.p. Treatments of R6313/G2 at 2.5 nmol/kg and 25 nmol/kg twice per day for 7 days dose dependently reduced cell numbers for all three cell lines, but here MCF-7 cells responded most sensitively and MDA-MB-231 cells least. Although T47D cells were refractory at the s.c. site, growth was inhibited at the i.p. location, and otherwise results were similar at the two sites. In xenografts, MCF-7 cell tumours were dose dependently reduced by R6313/G2, and 13 and 27 nmol/kg R6313/G2 twice/day gave means of 74 and 76% tumour regression after 7 days. The data suggest that the anti-cancer action of R6313/G2 is considerably more effective than AT1 antagonists.

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Section: Endocrine-related Cancermentioning

confidence: 99%

Anti-cancer actions of a recombinant antibody (R6313/G2) against the angiotensin II AT1 receptor

Redondo-Müller¹,

Stevanovic-Walker²,

Barker³

et al. 2008

Endocrine Related Cancer

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“…The hollow fiber assay has been incorporated into the drug discovery programs of many laboratories around the world including Argentina,69 Austria,70 France,71 Germany,72 India,73Italy,74–78 New Zealand,79 Poland,80,81 Spain,82,83 Sweden,84 and the United Kingdom 85–89…”

Section: Discussionmentioning

confidence: 99%

“…The hollow fiber assay has been incorporated into the drug discovery programs of many laboratories around the world including Argentina, Austria, France, Germany, India, Italy, − New Zealand, Poland, , Spain, , Sweden, and the United Kingdom. − Laboratories that focus on chemical synthesis or on natural product isolation and structure elucidation usually choose to have their compounds tested by the NCI rather than have the assay set up in their own laboratories. This underscores the multidisciplinary and collaborative nature of drug discovery and emphasizes the important role that the NCI plays in the drug discovery efforts of academic laboratories.…”

Section: Discussionmentioning

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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“…Tumor biopsy evaluation with fine‐needle aspirations or tissue dissections is confounded by intracellular and nonspecific staining, and is limited by low quantitative capability of immunohistochemistry (IHC). Alternative strategies, at least in animal studies, include performing surrogate RO on encapsulated cells implanted subcutaneously 62, 63 or direct bioluminescent tissue imaging using intravenous injected fluorescence‐labeled, receptor‐specific antibodies in live animals 64, 65. In addition, the most plausible route to tissue‐based RO assays may be based on advances in the coupling of immunocytochemical methods with high‐resolution laser ablation linked mass cytometry, such as CyTOF mass cytometry imaging 66.…”

Section: Future Perspectivesmentioning

confidence: 99%

Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development

Liang¹,

Schwickart²,

Schneider³

et al. 2015

Cytometry Part B Clinical

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Receptor occupancy (RO) assays are designed to quantify the binding of therapeutics to their targets on the cell surface and are frequently used to generate pharmacodynamic (PD) biomarker data in nonclinical and clinical studies of biopharmaceuticals. When combined with the pharmacokinetic (PK) profile, RO data can establish PKPD relationships, which are crucial for informing dose decisions. RO is commonly measured by flow cytometry on fresh blood specimens and is subject to numerous technical and logistical challenges. To ensure that reliable and high quality results are generated from RO assays, careful assay design, key reagent characterization, data normalization/reporting, and thorough planning for implementation are of critical importance during development. In this article, the authors share their experiences and perspectives in these areas and discuss challenges and potential solutions when developing and implementing a flow cytometry‐based RO method in support of biopharmaceutical drug development. © 2015 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.

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The hollow fiber assay for drug responsiveness in the Ewing’s sarcoma family of tumors

Cited by 5 publications

References 31 publications

Anti-cancer actions of a recombinant antibody (R6313/G2) against the angiotensin II AT1 receptor

Anti-cancer actions of a recombinant antibody (R6313/G2) against the angiotensin II AT1 receptor

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

Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development

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