Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness

Britten, Richard A.; Evans, Andrew; Allalunis-Turner, M. J.; Franko, Allan J.; Pearcey, R.

doi:10.1016/0167-8140(96)01719-7

Cited by 50 publications

(38 citation statements)

References 36 publications

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“…This ensures conditions for clonogenic cells that do not necessarily reflect the in vivo conditions regarding nutrition, space and oxygen level. Furthermore, the accuracy of measured tumour-specific radiosensitivity has been questioned in the light of tumour heterogeneity and the risk that it only represents a small proportion of a tumour [24]. Nevertheless, the results of this study indicate that individual results from clonogenic assays lead to better correlations with outcome than average parameters.…”

Section: -Specificitymentioning

confidence: 52%

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Hedman¹,

Björk‐Eriksson²,

Brodin³

et al. 2013

BJR

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Objective: The aim of this study was to compare patient-specific radiobiological parameters with population averages in predicting the clinical outcome after radiotherapy (RT) using a tumour control probability (TCP) model based on the biological effective dose (BED).Methods: A previously published study of 46 head and neck carcinomas with individually identified radiobiological parameters, radiosensitivity and potential doubling time (T pot ), and known tumour size was investigated. These patients had all been treated with external beam RT, and the majority had also received brachytherapy. The TCP for each individual based on the BED using patient-specific radiobiological parameters was compared with the TCP based on the BED using average radiobiological parameters (a50.3 Gy 21 , T pot 53 days).Results: 43 patients remained in the final analysis. There was only a weak trend for increasing local tumour control with increasing BED in both groups. However, when the TCP was calculated, the use of patientspecific parameters was better for identifying local control correctly. The sensitivity and specificity for tumour-specific parameters

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Section: -Specificitymentioning

confidence: 52%

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Hedman¹,

Björk‐Eriksson²,

Brodin³

et al. 2013

BJR

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“…4 Tumor progression has been associated with decreased genomic stability, oncogene and tumor suppressor gene expression changes, and loss of DNA repair mechanisms within the cells. [5][6][7][8] Existence of multiple cell subpopulations was shown to be correlated with the process of tumor growth and sensitivity to chemotherapy, 9 radiation therapy, 10 immunotherapy, 11 and hormone therapy. 12 Tumor heterogeneity is modulated by the microenvironment with regard to hypoxia, metabolism, and nutrient supply limitations.…”

mentioning

confidence: 99%

Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery

Vamvakidou

Mondrinos

Petushi³

et al. 2007

SLAS Discovery

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Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can be used in drug resistance and drug delivery investigations. Breast cancer cell lines of different phenotypes (MDAMB231, MCF7, and ZR751) were cocultured in a rotating wall vessel bioreactor to form a large number of heterogeneous tumoroids in a single cell culture experiment. Cells in the rotating vessels were labeled with CellTracker fluorescent probes to allow for time course fluorescence microscopy to monitor cell aggregation. Histological sections of tumoroids were stained with hematoxylin and eosin, progesterone receptor, E-cadherin (E-cad), and proliferation marker ki67. In vitro tumoroids developed in this study recapture important features of the temporal-spatial organization of solid tumors, including the presence of necrotic areas at the center and higher levels of cell division at the tumor periphery. E-cad-positive MCF7 cells form larger tumoroids than E-cad-negative MDAMB231 cells. In heterogeneous tumors, the irregular surface roughness was mainly due to the presence of MDAMB231 cells, whereas MCF7 cells formed smooth surfaces. Moreover, when heterogeneous tumoroids were placed onto collagen gels, highly invasive MDAMB231 cell-rich surface regions produced extensions into the matrix, whereas poorly invasive MCF7 cells did not. The fact that one can form a large number of 1-mm tumoroids in 1 coculture attests to the potential use of this system at high-throughput investigations of cancer drug development and drug delivery into the tumor. (Journal of Biomolecular

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“…Histopathology analysis also revealed similar type of pathology for the cancerous tissues involved in this study. Further, literature evidence also reveals low levels of intra-tumoral heterogeneity for cervical tumors compared to other tumors like glioblastomas [11].…”

Section: Resultsmentioning

confidence: 99%

Interfacial properties as predictors of radioresistance in cervical cancer

Anand

Huilgol

Banerjee

2007

Journal of Colloid and Interface Science

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Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness

Cited by 50 publications

References 36 publications

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Heterogeneous Breast Tumoroids: An In Vitro Assay for Investigating Cellular Heterogeneity and Drug Delivery

Interfacial properties as predictors of radioresistance in cervical cancer

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