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Comparison of simple models of periodic protocols for combined anticancer therapy.

ABSTRACT: Several simple ordinary differential equation (ODE) models of tumor growth taking into account the development of its vascular network are discussed. Different biological aspects are considered from the simplest model of Hahnfeldt et al. proposed in 1999 to a model which includes drug resistance of cancer cells to chemotherapy. Some of these models can be used in clinical oncology to optimize antiangiogenic and cytostatic drugs delivery so as to ensure maximum efficacy. Simple models of continuous and periodic protocols of combined therapy are implemented. Discussion on the dynamics of the models and their complexity is presented.

SUBMITTER: Dolbniak M

PROVIDER: S-EPMC3638653 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Comparison of simple models of periodic protocols for combined anticancer therapy.

Dołbniak Marzena M Swierniak Andrzej A

Computational and mathematical methods in medicine 20130407

Several simple ordinary differential equation (ODE) models of tumor growth taking into account the development of its vascular network are discussed. Different biological aspects are considered from the simplest model of Hahnfeldt et al. proposed in 1999 to a model which includes drug resistance of cancer cells to chemotherapy. Some of these models can be used in clinical oncology to optimize antiangiogenic and cytostatic drugs delivery so as to ensure maximum efficacy. Simple models of continuo ...[more]

PMID: 23653666

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Project description:Background: Studies have reported that advanced NSCLC benefits from celecoxib combined with systematic treatment. However, the optimal combination with different treatments remains unclear. A meta-analysis was conducted to explore treatment combinations. Methods: We searched the relevant literature via PubMed, EMBASE, the Cochrane Library and PMC. The data for the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse effects were obtained. Subgroup analysis was performed according to the treatment pattern. Statistical analyses were carried out using Review Manager 5.3 software. Results: A total of 18 eligible studies were included, with 1178 advanced NSCLC patients. Subgroup analysis revealed that celecoxib combined with chemotherapy or tyrosine kinase inhibitors (TKIs) significantly increased the ORR, with no significant difference between the two groups. Celecoxib combined with chemotherapy improved OS-6 (OR=0.65, 95% CI 0.59-0.71, P<0.001), while OS-6 was not changed with celecoxib combined with TKIs (OR=0.53, 95% CI 0.31-0.73, P=0.82). Differences were apparent between the chemotherapy and TKIs regarding OS-6 (P=0.0392). Celecoxib combined with chemotherapy significantly prolonged OS-12 (OR=0.39, 95% CI 0.33-0.45, P<0.001). In terms of OS-12, there was no significant improvement when celecoxib was combined with radiotherapy or TKIs. Celecoxib combined with chemotherapy or TKIs significantly improved PFS-6 and PFS-12, with no obvious difference in terms of PFS between the two groups. Additionally, celecoxib combined with chemotherapy or TKI treatment increased the incidence of adverse events, with no significant differences between the two groups. Conclusions: Celecoxib combined with chemotherapy or TKIs improved the ORR, with no significant differences between the two groups. In terms of OS, celecoxib combined with chemotherapy was superior to TKIs or radiotherapy. Accordingly, celecoxib combined with chemotherapy increased hematological toxicity and cardiovascular events.

Project description:BackgroundBacteria or cells receive many signals from their environment and from other organisms. In order to process this large amount of information, Systems Biology shows that a central role is played by regulatory networks composed of genes and proteins. The objective of this paper is to present and to discuss simple regulatory network motifs having the property to maximize their responses under time-periodic stimulations. In elucidating the mechanisms underlying these responses through simple networks the goal is to pinpoint general principles which optimize the oscillatory responses of molecular networks.ResultsWe took a look at basic network motifs studied in the literature such as the Incoherent Feedforward Loop (IFFL) or the interlerlocked negative feedback loop. The former is also generalized to a diamond pattern, with network components being either purely genetic or combining genetic and signaling pathways. Using standard mathematics and numerical simulations, we explain the types of responses exhibited by the IFFL with respect to a train of periodic pulses. We show that this system has a non-vanishing response only if the inter-pulse interval is above a threshold. A slight generalisation of the IFFL (the diamond) is shown to work as an ideal pass-band filter. We next show a mechanism by which average of oscillatory response can be maximized by bursting temporal patterns. Finally we study the interlerlocked negative feedback loop, i.e. a 2-gene motif forming a loop where the nodes respectively activate and repress each other, and show situations where this system possesses a resonance under periodic stimulation.ConclusionWe present several simple motif designs of molecular networks producing optimal output in response to periodic stimulations of the system. The identified mechanisms are simple and based on known network motifs in the literature, so that that they could be embodied in existing organisms, or easily implementable by means of synthetic biology. Moreover we show that these designs can be studied in different contexts of molecular biology, as for example in genetic networks or in signaling pathways.

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Comparison of simple models of periodic protocols for combined anticancer therapy.

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Comparison of simple models of periodic protocols for combined anticancer therapy.

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