ArticleProceedings of the National Academy of Sciences of the United States of America1995
Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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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.
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Who cites it
24 citing papers in PubMed, 111 citations in OpenAlex.
- Article
- The effect of phosphorylation efficiency on the oncogenic properties of the protein E7 from high-risk HPV.Virus research · 2024Article
- Anti-cancer efficacy including Rb-deficient tumors and VHL-independent HIF1α proteasomal destabilization by dual targeting of CDK1 or CDK4/6 and HSP90.Scientific reports · 2021Article
- MicroRNA-1226-3p has a tumor-promoting role in osteosarcoma.Oncology letters · 2021Article
- Review
- Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies.International journal of molecular sciences · 2020Review
- Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance.MedChemComm · 2019Review
- Article
- A versatile drug delivery system targeting senescent cells.EMBO molecular medicine · 2018Article
- Linker Histone H1.2 Directs Genome-wide Chromatin Association of the Retinoblastoma Tumor Suppressor Protein and Facilitates Its Function.Cell reports · 2017Article
- Testis specific Y-like 5: gene expression, methylation and implications for drug sensitivity in prostate carcinoma.BMC cancer · 2017Article
- CCND1 G870A polymorphism is associated with toxicity of methotrexate in childhood acute lymphoblastic leukemia.International journal of clinical and experimental pathology · 2015Article
- Pharmacogenetics of methotrexate in acute lymphoblastic leukaemia: why still at the bench level?European journal of clinical pharmacology · 2014Review
- Tumour suppressor genes in chemotherapeutic drug response.Bioscience reports · 2012Review
- Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell leukemia Jurkat cells.Cancer science · 2010Article
- Sister telomeres rendered dysfunctional by persistent cohesion are fused by NHEJ.The Journal of cell biology · 2009Article
- RB activity alters checkpoint response and chemosensitivity in lung cancer lines.The Journal of surgical research · 2007Article
- Article
- From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates.Investigational new drugs · 2006Review
- Discrete signaling pathways participate in RB-dependent responses to chemotherapeutic agents.Oncogene · 2004Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectively, than for the HT-1080 (fibrosarcoma) cell line, which has wild-type pRB. These Rb-/- cell lines exhibited a 2- to 4-fold increase in both dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzyme activities as well as a 3- to 4-fold increase in mRNA levels for these enzymes compared to the HT-1080 (Rb+/+) cells. This increase in expression was not due to amplification of the DHFR and TS genes. Growth inhibition by MTX and FdUrd was increased and DHFR and TS activities and expression were correspondingly decreased in Rb transfectants of SaOS-2 cells. In contrast, there was no significant difference in growth inhibition among these cell lines for the nonantimetabolites VP-16, cisplatin, and doxorubicin. A gel mobility-shift assay showed that parental SaOS-2 cells had increased levels of free E2F compared to the Rb-reconstituted SaOS-2 cells. These results indicate that pRB defective cells may have decreased sensitivity to growth inhibition by target enzymes encoded by genes whose transcription is enhanced by E2F proteins and suggest mechanisms of interaction between cytotoxic agents and genes involved in cell cycle progression.
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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.