Author Archives: poljan86

I’ve just added a new post on my ComputeCancer blog. This time I wrote about estimating minimal time on PD-1/PD-L1 inhibitors for successful tumor regression.

Link: https://computecancer.wordpress.com/2017/10/27/estimating-minimal-time-on-pd-1pd-l1-inhibitors-for-successful-tumor-regression/

And here is a brief intro:

“In todays post, I will adopt a mathematical model that was introduced by Kuznetsov and colleagues back in 1994 (Kuznetsov et al., Bull Math Biol, 1994) to investigate the effects of anti-PD-1/PD-L1 therapy depending on the pretreatment tumor characteristics. The way in which the model was formulated more than two decades ago allows for elegant and straightforward incorporation of such a treatment. I will show how the variability in the observed response dynamics is explained by the model and how can we estimate the minimal time on PD-1/PD-L1 treatment required for a therapeutical success.”

Despite the fact that the local immunological microenvironment shapes the prognosis of colorectal cancer, immunotherapy has shown no benefit for the vast majority of colorectal cancer patients. A better understanding of the complex immunological interplay within the microenvironment is required. In this study, we utilized wet lab migration experiments and quantitative histological data of human colorectal cancer tissue samples (n=20) including tumor cells, lymphocytes, stroma and necrosis to generate a multi-agent spatial model. The resulting data accurately reflected a wide range of situations of successful and failed immune surveillance. Validation of simulated tissue outcomes on an independent set of human colorectal cancer specimens (n=37) revealed the model recapitulated the spatial layout typically found in human tumors. Stroma slowed down tumor growth in a lymphocyte-deprived environment but promoted immune escape in a lymphocyte-enriched environment. A subgroup of tumors with less stroma and high numbers of immune cells showed high rates of tumor control. These findings were validated using data from colorectal cancer patients (n=261). Low-density stroma and high lymphocyte levels showed increased overall survival (hazard ratio 0.322, p=0.0219) as compared with high stroma and low lymphocyte levels. To guide immunotherapy in colorectal cancer, simulation of immunotherapy in pre-established tumors showed that a complex landscape with optimal stroma permeabilization and immune cell activation is able to markedly increase therapy response in silico. These results can help guide the rational design of complex therapeutic interventions which target the colorectal cancer microenvironment.

The whole article can be found under the link: http://cancerres.aacrjournals.org/content/early/2017/09/16/0008-5472.CAN-17-2006

Impairments in decision-making are frequently observed in neurodegenerative diseases, but the mechanisms underlying such pathologies remain elusive. In this work, we study, on the basis of novel time-delayed neuronal population model, if the delay in self-inhibition terms can explain those impairments. Analysis of proposed system reveals that there can be up to three positive steady states, with the one having the lowest neuronal activity being always locally stable in nondelayed case. We show, however, that this steady state becomes unstable above a critical delay value for which, in certain parameter ranges, a subcritical Hopf bifurcation occurs. We then apply psychometric function to translate model-predicted ring rates into probabilities that a decision is being made. Using numerical simulations, we demonstrate that for small synaptic delays the decision-making process depends directly on the strength of supplied stimulus and the system correctly identifies to which population the stimulus was applied. However, for delays above the Hopf bifurcation threshold we observe complex impairments in the decision-making process; that is, increasing the strength of the stimulus may lead to the change in the neuronal decision into a wrong one. Furthermore, above critical delay threshold, the system exhibits ambiguity in the decision-making.

The whole article can be found under the link: https://www.hindawi.com/journals/complexity/2017/4391587/

After 3 years in making, 10 months of 3 rounds of reviews, our paper “Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival” has been finally published in Breast Cancer Research.

In the paper we assessed overall and cancer-free survival of 250,195 early-stage breast cancer patients in the SEER database who received either adjuvant or neoadjuvant radiotherapy (RT).  The hazard ratio (HR) of developing a second tumor after neoadjuvant compared with adjuvant RT was 0.64 (95% confidence interval (CI), 0.55-0.75; P < 0.0001) for estrogen receptor-positive women who underwent partial mastectomy, without jeopardizing the excellent overall survival (HR = 1; P = 0.95).  Neoadjuvant RT also resulted in lower HR for second primary cancer for estrogen receptor-positive patients who underwent mastectomy compared with adjuvant RT (HR = 0.48, CI = 0.26-0.87; P = 0.0162).

We conclude that neoadjuvant RT may significantly improve disease-free survival without reducing overall survival, especially for estrogen receptor-positive patients with early-stage breast cancer. This finding warrants further exploration of potential long-term benefits of neoadjuvant radiotherapy for early-stage breast cancer in a controlled, prospective clinical trial setting, with correlative studies done to identify potential mechanisms of superiority.

The whole article can be found under the link: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-017-0870-1

Our abstracts entitled “INFLUENCE OF HEMODIALYSIS ASSOCIATED CARDIOVASCULAR COMPLICATIONS ON PULSE WAVE ANALYSIS: MODELING-BASED APPROACH” and “IMPACT OF SOLUTE EXCHANGE BETWEEN ERYTHROCYTES AND PLASMA ON HEMODIALYZER CLEARANCE” just got accepted for 54th ERA-EDTA Congress, which will be organised in Madrid, Spain (June 3-6, 2017). Come and visit us in the Poster Area of the IFEMA Feria de Madrid (North Congress Center) on Monday, June 5 2017 (poster numbers MP514 and MP596, respectively).

Our abstract entitled “Co-registration of multi-parametric MRI and histology to study breast cancer habitats in a preclinical model.” just got accepted for 25th Annual Meeting & Exhibition of International Society for Magnetic Resonance in Medicine. The meeting will take place between 22-27th of April this year in Honolulu. Unfortunately I won’t make it there, but if anyone is interested our talk will be at 16:15 on April 24th.

I’ve just launched simulations in which pressure profiles predicted by 1D blood flow model in 55 elastic arterial segments are being fitted to the clinical data from applanation tonometry (180 patients in total). I’m using 180 CPUs in total and more than 240 Gb of RAM memory. Hopefully simulations will be done by the end of next week…

Back in April 2015 I was presenting my joint work with Heiko Enderling on evolution and phenotype selection of cancer stem cells (Poleszczuk et al., PLOS Comp Bio, 2015) at MBI during the emphasis workshop “Stem cells, Development, and Cancer”.

Below is the link to the recorded video (>40 min, consider yourself warned…) from that event:

https://mbi.osu.edu/video/player/id=3493&title=Evolution+and+phenotypic+selection+of+cancer+stem+cells