<i>In Silico</i>Modelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

Marcu, Loredana G.; Harriss-Phillips, Wendy M.

doi:10.1155/2012/960256

Cited by 23 publications

(17 citation statements)

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“…Previous studies have also identified that the decrease in NCOA5 expression in esophageal squamous cell carcinoma (ESCC) tissue is associated with the differentiation status of the tumor and the TNM stage, while is not associated with age, sex, weight loss, tumor location or lymph node metastasis (26,27). In addition, the expression of NCOA5 in normal tissues was higher compared with that in tumor tissues.…”

Section: Discussionmentioning

confidence: 97%

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

Dong

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to investigate the association between the expression of nuclear receptor co-activator 5 protein (NCOA5) and the prognosis of postoperative patients with osteosarcoma. Human osteosarcoma samples were collected from 145 patients and normal bone tissues were collected from 100 individuals as controls. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were employed to measure the levels of NCOA5 protein in cases of human osteosarcoma. The results from the RT-PCR analysis demonstrated that the positive rate of NCOA5 mRNA expression in human osteosarcoma was 17.24% (25/145). The positive rate in normal bone tissues was 84.00% (84/100), which was significantly higher compared with that of human osteosarcoma tissues (χ 2 =33.166; P<0.001). IHC staining indicated that the positive rate of NCOA5 protein in the osteosarcoma samples was 26.21% (38/145). The positive rate in normal bone tissues was 82.00% (82/100), which was significantly increased compared with that of human osteosarcoma tissues (χ 2 =28.166; P<0.001). NCOA5 mRNA and protein expression levels were consistent in human osteosarcoma tissues, and were lower than in control tissues. The expression of NCOA5 was low in human osteosarcoma tissues, while it was high in normal bone tissues. These low NCOA5 expression levels were associated with postoperative survival of human osteosarcoma.

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Section: Discussionmentioning

confidence: 97%

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

Dong

et al. 2017

Oncol Lett

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“…3,[9][10][11] A complete review of in silico radiobiological models is given in Marcu and Harriss-Phillips. 12 Dionysius et al 9,10 introduced the notion of a "geometrical cell," an elementary cubic volume containing a quantity of biological cells, which can be transferred to neighboring geometrical cells in order to maintain cell density within the tumor. In their work, metabolic information from medical imaging can be assigned to the spatially distributed geometrical cells.…”

Section: Introductionmentioning

confidence: 99%

A voxel‐based multiscale model to simulate the radiation response of hypoxic tumors

2015

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The results obtained with the developed multiscale model are in accordance with expectations based on radiobiological principles and clinical experience. As the model is voxel-based, radiological imaging methods may help to provide the required 3D-characterization of the tumor prior to irradiation. For clinical application, the model has to be further validated with experimental and clinical data. If this is achieved, the model may be used to optimize fractionation schedules and dose distributions for the treatment of hypoxic tumors.

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“…Tumor treatment planning, especially in the case of radiotherapy, uses many different stochastic process calculations, relevant on different time scales, from femtoseconds to years, as reviewed in (16)(17)(18)(19) and in the online AAPS Supplement section S.4.1. The influence on IIV of stochastic fluctuations at the single cell level is considered (16,18); an approach similar to the statistical methods of population PK/PD is also used to analyze IIV [reviewed, e.g., in (20)].…”

Section: Pk/pd Modelingmentioning

confidence: 99%

“…Stochastic process calculations of tumor control probability by radiotherapeutic eradication of cancer cells [reviewed in (16,17,19)] suggested to us analogous analyses of drug dosing regimens: the main novelty in the present paper is transferring a mathematical stochastic process theory technique from radiobiological tumor treatment planning to a PK/PD model of neonatal gentamicin treatment. Differences due to the fact that drugs remain in the body during a period of hours or more had to be taken into account, as did the fact that typically a substantial fraction of bacteria are CFU whereas only a small minority of tumor cells are CFU.…”

Section: Previewmentioning

confidence: 99%

Stochastic Process Pharmacodynamics: Dose Timing in Neonatal Gentamicin Therapy as an Example

Radivoyevitch

Siranart

Hlatky

et al. 2015

AAPS J

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ABSTRACT. We consider dosing regimens designed to cure patients by eradicating colony forming units (CFU) such as bacteria. In the field of "population" pharmaco-kinetics/dynamics (PK/PD), interindividual variability (IIV) of patients is estimated using model parameter statistical distributions. We consider a more probabilistic approach to IIV called stochastic process theory, motivated by the fact that tumor treatment planning uses both approaches. Stochastic process PD can supply additional insights and suggest different dosing regimens due to its emphasis on the probability of complete CFU eradication and its predictions on "pure chance" fluctuations of CFU number per patient when treatment has reduced this integer to less than~100. To exemplify the contrast between stochastic process PD models and standard deterministic PD models, which track only average CFU number, we analyze, neglecting immune responses, neonatal intravenous gentamicin dosing regimens directed against Escherichia coli. Our stochastic calculations predict that the first dose is crucial for CFU eradication. For example, a single 6 mg/kg dose is predicted to have a higher eradication probability than four daily 4 mg/kg doses. We conclude: (1) neonatal gentamicin dosing regimens with larger first doses but smaller total doses deserve investigation; (2) in general, if standard PK/PD models predict average CFU number drops substantially below 100, the models should be modified to incorporate stochastic effects more accurately, and will then usually make more favorable, or less unfavorable, predictions for front boosting ("hit hard early"). Various caveats against over-interpreting the calculations are given.

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In SilicoModelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

Cited by 23 publications

References 100 publications

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

A voxel‐based multiscale model to simulate the radiation response of hypoxic tumors

Stochastic Process Pharmacodynamics: Dose Timing in Neonatal Gentamicin Therapy as an Example

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