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  • American Association for Cancer Research (AACR)  (3)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 5127-5127
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 5127-5127
    Abstract: Background: Cancer cell culture has contributed with pivotal discoveries for cancer biology and pharmacology. However, cancer cells in culture have not provided a good test method for patient´s response to chemotherapy to a similar extent as antibiograms have been useful to predict response to antibiotics. Although the reason for this is multifactorial, some very common mistakes in cancer cell pharmacology are made in most studies that, if corrected, could improve the overall results. Methods: We systematically tested key conditions such as concentration, time of exposure and analysis, methods of analysis and number of cells analyzed in glioma cell lines. Results: We found that time of exposure to the drug and time of analysis have a large impact on the outcome, with some drugs producing in vitro “relapse” only after 20 days of analysis. Additionally, the initial number of cells plated is also central for the outcome, with resistance being uncovered only after a certain number of cells is treated. Finally, a direct comparison between the MTT viability assay with population doubling assay clearly indicates that the former is not suited for studying effective anticancer drugs and resistance due to its low sensitivity. By systematically analyzing concentration, time of exposure and analysis, number of initial cells and method of analysis we showed that for more meaningful in culture cancer pharmacology, drug exposure should mimic the patient´s exposure time, (5 days for gliomas), analysis should be for at least one treatment cycle (28 days for gliomas), the number of cells tested should be at least more than 15 thousand and the method for analyzing cell number should be repetitive direct counting instead of viability assays such as MTT. Conclusion: Despite not addressing other very fundamental issues in cancer cell culture such as medium, adhesion, 3D culture and presence of other cell types, these simple improvements should aid to produce more significant in culture cancer pharmacology. Financial support: FAPERGS, CNPq e CAPES. Citation Format: Guido Lenz, Andrew O. Silva. The most common mistakes in cancer cell pharmacology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5127. doi:10.1158/1538-7445.AM2015-5127
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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    detail.hit.zdb_id: 410466-3
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4 ( 2021-02-15), p. 1040-1051
    Abstract: Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. Significance: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 17 ( 2016-09-01), p. 5103-5114
    Abstract: Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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