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Maciej Swat

Publications and source records attributed to Maciej Swat.

6 recordsLinked to original sources
arXiv2014

Investigating the development of chemotherapeutic drug resistance in cancer: A multiscale computational study

Chemotherapy is one of the most important therapeutic options used to treat human cancers, either alone or in combination with radiation therapy and surgery. Recent studies have indicated that intra-tumoural heterogeneity has a significant role in driving resistance to chemotherapy in many human malignancies. Multiple factors including the internal cell-cycle dynamics and the external microenvironement contribute to the intra-tumoural heterogeneity. In this paper we present a hybrid, multiscale, individual-based mathematical model, incorporating internal cell-cycle dynamics and changes in oxygen concentration, to study the effects of delivery of several different chemotherapeutic drugs on the heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics. The computational simulation results from the multiscale model are in good agreement with available experimental data and support the hypothesis that slow-cycling sub-populations of tumour cells within a growing tumour mass can induce drug resistance to chemotherapy and thus the use of conventional chemotherapy may actually result in the emergence of dominant, therapy-resistant, slow-cycling subpopulations of tumour cells. Our results indicate that the appearance of this chemotherapeutic resistance is mainly due to the inability of the administered drug to target all cancer cells irrespective of the stage in the cell-cycle they are in i.e. most chemotherapeutic drugs target cells in a particular phase/phases of the cell-cycle, and hence always spare some cancer cells that are not in the targeted cell-cycle phase/phases. The results also suggest that this cell-cycle-mediated drug resistance may be overcome by using multiple doses of cell-cycle, phase-specific chemotherapy that targets cells in all phases and its appropriate sequencing and scheduling.

q-bio.TO↗
arXiv2014

Bystander effects and their implications for clinical radiation therapy: Insights from multiscale in silico experiments

Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects such as DNA mutation or bystander effects affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this article, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses may play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model.

q-bio.QM↗
arXiv2005

Biological Profiling of Gene Groups utilizing Gene Ontology

Increasingly used high throughput experimental techniques, like DNA or protein microarrays give as a result groups of interesting, e.g. differentially regulated genes which require further biological interpretation. With the systematic functional annotation provided by the Gene Ontology the information required to automate the interpretation task is now accessible. However, the determination of statistical significant e.g. molecular functions within these groups is still an open question. In answering this question, multiple testing issues must be taken into account to avoid misleading results. Here we present a statistical framework that tests whether functions, processes or locations described in the Gene Ontology are significantly enriched within a group of interesting genes when compared to a reference group. First we define an exact analytical expression for the expected number of false positives that allows us to calculate adjusted p-values to control the false discovery rate. Next, we demonstrate and discuss the capabilities of our approach using publicly available microarray data on cell-cycle regulated genes. Further, we analyze the robustness of our framework with respect to the exact gene group composition and compare the performance with earlier approaches. The software package GOSSIP implements our method and is made freely available at http://gossip.gene-groups.net/

q-bio.GN↗
arXiv2003

Study of the $ηπ$ and $η'π$ spectra and interpetation of possible exotic $J^{PC}=1^{-+}$ mesons

We discuss a coupled channel analysis of the $ηπ$ and $η'π$ systems produced in $π^-p$ interactions at 18 GeV/$c$. We show that known $Q\bar Q$ resonances, together with residual soft meson-meson rescattering, saturate the spectra including the exotic $J^{PC}=1^{-+}$ channel. A possibility of a narrow exotic resonance at a mass near 1.6 GeV/$c^2$ cannot, however, be ruled out.

hep-ph↗
arXiv2001

Role of Photoproduction in Exotic Meson Searches

We discuss two production mechanisms of the $J^{PC}=1^{-+}$ exotic meson, hadroproduction, using pion beams and photoproduction. We show that the ratio of exotic to non-exotic, in particular the $a_2$, meson production cross sections is expected to be by a factor of 5 to 10 larger, in photoproduction then in hadroproduction. Furthermore we show that the low-t photoproduction of exotic meson is enhanced as compared to hadronic production. This findings support the simple quark picture in which exotic meson production is predicted to be enhanced when the beam is a virtual $Q\bar Q$ pair with a spin-1 (photon) rather then with a spin-0 (pion).

hep-ph↗