ArticleProceedings of the National Academy of Sciences of the United States of America1993
Acquired multicellular-mediated resistance to alkylating agents in cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 278 citations in OpenAlex.
- PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.Scientific reports · 2025Article
- Long-Term Survival of Cellulose Sulphate-Encapsulated Cells and Metronomic Ifosfamide Control Tumour Growth in Pancreatic Cancer Models-A Prelude to Treating Solid Tumours Effectively in Pets and Humans.Life (Basel, Switzerland) · 2023Article
- In Vitro Models of Head and Neck Cancer: From Primitive to Most Advanced.Journal of personalized medicine · 2023Review
- Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography.Scientific reports · 2023Article
- Multi-Omics Analysis of NCI-60 Cell Line Data Reveals Novel Metabolic Processes Linked with Resistance to Alkylating Anti-Cancer Agents.International journal of molecular sciences · 2023Article
- Three-Dimensional Spheroids for Cancer Research.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 3D Multicellular Tumor Spheroids in a Microfluidic Droplet System for Investigation of Drug Resistance.Polymers · 2022Article
- Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.International journal of molecular sciences · 2022Article
- Challenges of applying multicellular tumor spheroids in preclinical phase.Cancer cell international · 2021Review
- CAFs affect the proliferation and treatment response of head and neck cancer spheroids during co-culturing in a unique in vitro model.Cancer cell international · 2020Article
- Generation of immune cell containing adipose organoids for in vitro analysis of immune metabolism.Scientific reports · 2020Article
- Review
- Emerging trends in modeling human liver diseaseAPL bioengineering · 2019Article
- Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model.Scientific reports · 2019Article
- Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery.Scientific reports · 2016Article
- Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.PloS one · 2016Article
- Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer.Clinical Medicine Insights. Oncology · 2016Review
- Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors.International journal of molecular sciences · 2015Review
- Mass spectrometry imaging of therapeutics from animal models to three-dimensional cell cultures.Analytical chemistry · 2015Review
- Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review.Cancers · 2015Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
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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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.