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Cited by 278

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.

Acquired multicellular-mediated resistance to alkylating agents in cancer.

Open access
Kobayashi, H, Man, S, Graham, C H, Kapitain, S J, Teicher, B A, Kerbel, R S·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.8.3294
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Abstract

EMT-6 murine mammary tumor sublines highly resistant to cyclophosphamide, cis-diamminedichloro-platinum(II), or N,N',N"-triethylenethiophosphoramide were generated in vivo by sequential treatment of tumor-bearing mice with the respective drugs. Previous studies demonstrated the drug-resistant phenotypes of the sublines were not expressed in vitro when the cells were grown as monolayer cultures. We now show that expression of drug resistance--including patterns of cross-drug resistance observed in vivo--can be fully recapitulated in vitro when the cells are grown under in vivo-like, three-dimensional conditions--namely, as multicellular tumor spheroids. Moreover, the spheroids generated from all of the drug-resistant sublines manifested a much more compact structure. Immediate drug-sensitivity testing of single cells released by trypsin treatment from compact drug-resistant spheroids revealed that such cells lost much of their drug-resistant properties. The results suggest a possible mechanism of acquired drug resistance in tumors based on the response of a cell population (i.e., multicellular or tissue resistance) as opposed to classic (uni)cellular resistance mechanisms.

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Metadata

Authors
Kobayashi, H., Man, S., Graham, C. H., Kapitain, S. J., Teicher, B. A., & Kerbel, R. S.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
1993-04-15
Volume
90
Issue
8
Pages
3294-3298
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.90.8.3294
OpenAlex
W2023300542
Cited by
278
References
22
FWCI
3.12
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Acquired multicellular-mediated resistance to alkylating agents in cancer. https://app.cochat.ai/papers/10.1073/pnas.90.8.3294
The paper
Kobayashi, H., Man, S., Graham, C. H., Kapitain, S. J., Teicher, B. A., & Kerbel, R. S. (1993). Acquired multicellular-mediated resistance to alkylating agents in cancer. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.8.3294

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.