Jan Poleszczuk

• PhD in Mathematics, PhD in Biocybernetics and Biomedical Engineering
• Professor (Associate) at Institute of Biocybernetics and Biomedical Engineering

Background: Triple Negative Breast Cancer (TNBC) is one of the subtypes of breast cancer, lacking the expression of the estrogen (ER), progesterone (PgR) and HER2 receptors. TNBC accounts for 10-15% of all breast cancer (BC) cases, but is responsible for approximately 40% of BC deaths. Significant advances in therapeutic approaches have been noted...

Machine learning algorithms that integrate multiple biomarkers are increasingly used in disease detection, yet economic considerations are often overlooked. Medial vascular calcification (mVC), a pathology associated with elevated cardiovascular risk in chronic kidney disease (CKD), requires cost-effective diagnostic approaches. This pilot study ev...

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost redu...

Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters...

Triple-negative breast cancer (TNBC) poses a serious therapeutic challenge due to the occurrence of frequently aggressive, heterogenic, and metastatic tumours. The absence of therapeutic targets for traditional therapies is a hindrance to establishing a standardised therapy for TNBC. There is limited TNBCs epidemiological and real-world data about...

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid malignancies, including non-small-cell lung cancer. However, immunotherapy resistance constitutes a significant challenge. To investigate carbonic anhydrase IX (CAIX) as a driver of resistance, we built a differential equation model of tumor–immune interactions. The mode...

Immune checkpoint inhibitors (ICIs) are revolutionary cancer treatments. However, the mechanisms behind their effectiveness are not yet fully understood. Here, we aimed to investigate the role of the pH-regulatory enzyme carbonic anhydrase IX (CAIX) in ICI success. Consequently, we developed an in silico model of the tumour microenvironment. The hy...

Background: We investigated whether an incidental diagnosis (ID) of bladder cancer (BC) was associated with improved survival. Methods: We retrospectively reviewed data of consecutive patients with no prior diagnosis of urothelial cancer who underwent a primary transurethral resection of bladder tumor (pTURBT) between January 2013 and February 2...

Antibodies against programmed cell death protein-1 or its ligand (PD-(L)1) are a standard of care in melanoma; however, this treatment may cause immune-related adverse events. The aim of this study was to evaluate the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy and analyze their influence on the overall survival rates in...

Proton radiotherapy has been implemented into the standard-of-care for cancer patients within recent years. However, experimental studies investigating cellular and molecular mechanisms are lacking, and prognostic biomarkers are needed. Cancer stem cell (CSC)-related biomarkers, such as aldehyde dehydrogenase (ALDH), are known to influence cellular...

Introduction: Selected patients with locally advanced or metastatic soft tissue and bone sarcomas (STBS) may benefit from intensive local treatment, such as stereotactic radiotherapy (SRT). This study aimed to summarize the utilization and outcomes of SRT in STBS and to identify predictive factors for progression and survival. Materials and method...

Classical mathematical models of tumor growth have shaped our understanding of cancer and have broad practical implications for treatment scheduling and dosage. However, even the simplest textbook models have been barely validated in real world-data of human patients. In this study, we fitted a range of differential equation models to tumor volume...

Haemodialysis (HD) and peritoneal dialysis (PD) are the main kidney replacement therapies for patients with end-stage renal disease. Both of these life-sustaining therapies replace the key functions of the failing kidneys, i.e. the removal of the excess body water and waste products of metabolism as well as the restoration of fluid-electrolyte and...

Classical mathematical models of tumor growth have shaped our understanding of cancer and have broad practical implications for treatment scheduling and dosage. However, even the simplest textbook models have been barely validated in real world-data of human patients. In this study, we fitted a range of differential equation models to tumor volume...

Rationale: Hypoxic regions (habitats) within tumors are heterogeneously distributed and can be widely variant. Hypoxic habitats are generally pan-therapy resistant. For this reason, hypoxia-activated prodrugs (HAPs) have been developed to target these resistant volumes. The HAP evofosfamide (TH-302) has shown promise in preclinical and early clinic...

Background: Due to the rarity of osteosarcoma and limited indications for radiotherapy (RT), data on RT for this tumor are scarce. This study aimed to investigate the utilization of RT for osteosarcomas in the recent 20 years and to identify factors related to patients’ response to radiation. Methods: We performed a retrospective analysis of patien...

Background: Traumatic brain injury is often associated with cardiac dysfunction, which is the consequence of the "brain-heart cross-talk". Sub-endocardial viability ratio (SEVR) is an estimate of myocardial perfusion. The aim of this study was to analyse the changes in SEVR in patients with severe TBI without previous cardiac diseases. Methods:...

Background and aims Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, detection of biomarkers in stool, blood or serum, including fecal immunochemical test (FIT), ColoGuard, pro Epicolon and PolypDx have recently been advanced. We aimed to identify characteristics of theoretical, highly e...

Introduction There is no standard treatment for marginally resectable soft tissue sarcomas (STS) of the extremities and trunk wall, and current approaches give unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5x5 Gy hypofractionated radiotherapy may generate a higher ratio of limb-sparing...

Background/aim: Follicular lymphoma (FL) relapse within 24 months of the first immunochemotherapy (POD24) indicates more precisely poor overall survival and high risk of death. The aim of the study was to assess the potential value of POD24 in FL and describe the enhancer of zeste homolog 2 (EZH2) expression profile, in correlation with clinical/hi...

Hypoxic regions (habitats) within tumors are heterogeneously distributed and can be widely variant. Hypoxic habitats are generally pan-therapy resistant. For this reason, hypoxia-activated prodrugs (HAPs) have been developed to target these resistant volumes. The HAP evofosfamide (TH-302) has shown promise in preclinical and early clinical trials o...

Available epidemiological reports on follicular lymphoma (FL) often highlight a significant discrepancy between its high and low incidence rates in Western and Eastern Europe, respectively. The reasons behind that difference are not fully understood, but underreporting is typically presumed as one of the main factors. This study aimed to assess FL...

Tumor habitats are phenotypically and spatially distinct intratumoral regions. Hypoxic habitats are associated with reduced accessibility of chemotherapeutics, resulting in resistance. Hypoxia targeted prodrugs (HAPs) may overcome this resistance. However, in a phase III clinical trial, the HAP evofosfamide (TH-302) did not improve survival of sarc...

Background and Aims Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD) due to complex processes in the uremic milieu linked to CKD - mineral and bone disorders (CKD-MBD). These processes alter structure and function of heart and vasculature e.g. by causing ectopic calcification that makes vessels stiffer thu...

Follicular lymphoma (FL) is a well-studied microenvironment-dependent hematological malignancy, but the crosstalk between various involved cell subtypes is still not fully understood. Recent promising results of immunotherapy in recurrent FL warrant the need for an in-depth analysis of the expression and role of immune system-related proteins in th...

e23554 Background: CCS is a rare aggressive sarcoma with melanocytic differentiation and specific genetic background of EWSR1/ATF1 or EWSR1/CREB1 translocations. It typically localizes in the tendons, fascia, and aponeuroses. The role of lymph node dissection (LND) remains to be elucidated in this sarcoma, although it was indicated to have a high r...

e23503 Background: Ewing Sarcoma is a rare type of aggressive tumor that occurs in bones or in the soft tissue around the bones. The multidisciplinary approach chemotherapy (CHT), radiotherapy (RTH) and surgery (S) is the standard of care. The aim of our study was to analyze prognostic factors and treatment results in patients with Ewing Sarcoma. M...

Despite high initial efficacy, targeted therapies eventually fail in advanced cancers, as tumors develop resistance and relapse. In contrast to the substantial body of research on the molecular mechanisms of resistance, understanding of how resistance evolves remains limited. Using an experimental model of ALK positive NSCLC, we explored the evolut...

Introduction Histopathological examination and immunohistochemistry (IHC) with a crucial role of CD10 expression remain a standard diagnostic tool in follicular lymphoma (FL). The results of IHC CD10 detection with different primary antibodies are not fully reproducible, but some reports show that flow cytometry (FCM) can be a reliable method of CD...

In a typical setting, mathematical biologists develop models with a certain number of free parameters, either to be calibrated with experimental data, or to be evaluated numerically to explore a variety of model behaviors.

Back in 2013 our group made an attempt to bring additional insight into the process of carcinogenesis by using the tools of mathematical modeling [1], an approach being at the very core of theoretical biology.

Background: A significant drop of serum phosphate and calcium removal or loading during hemodialysis induce reactions in mineral and bone remodeling that may inversely affect phosphate and calcium removal during dialysis. Objectives: We aimed to analyze the interdependencies between biomarkers of mineral and bone metabolism and removal of phosph...

It is well-recognized that solid tumors are genomically, anatomically, and physiologically heterogeneous. In general, more heterogeneous tumors have poorer outcomes, likely due to the increased probability of harboring therapy-resistant cells and regions. It is hypothesized that the genomic and physiologic heterogeneity are related, because physiol...

Purpose: Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and disease-free survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced antitumor immunity...

The standard theory of mass transport in dialyzer for water solutions was extended for solutes distributed in both plasma (PW) and erythrocyte intracellular (EW) water. Blood flow was divided into two separate flows of PW and EW with the diffusive exchange of solutes across cellular membrane (CM). Diffusive permeability of CM for urea and creatinin...

Background It is typically assumed that within short time-frames, patient-specific peritoneal membrane characteristics are constant and do not depend on the initial fluid tonicity and dwell duration. The aim of this study was to check whether this assumption holds when membrane properties are estimated using the 3-pore model (3PM). Methods Thirty-...

Despite high initial efficacy, therapies that target abnormal kinase activities, including those directed against the oncogenic EML4-ALK fusion product, eventually fail in advanced, metastatic cancers. This failure in the initially responsive tumors is the direct result of the evolution of drug resistance under therapy-imposed selective pressures....

Background: Ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overa...

Valuable information about cardiovascular system can be derived from the shape of aortic pulse wave being the result of reciprocal interaction between heart and vasculature. Pressure profiles in ascending aorta were obtained from peripheral waveforms recorded non-invasively (SphygmoCor, AtCor Medical, Australia) before, during and after hemodialysi...

Parameters of pulse wave derived before, during and after hemodialysis performed after 3-day and 2-day interdialytic intervals. (DOCX)

The synergy of radiation and the immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong anti-tumor immune responses. It remains unclear, however, what are the best radiation fractionation protocols to maximize the therapeutic benefits of this synergy. Here, we...

The purpose of this work was to compare dose distributions between two radiosurgery modalities, single‐isocenter volumetric modulated arc therapy (VMAT), and GammaKnife Perfexion (GK), in the treatment of a large number (≥7) of brain metastases. Twelve patients with 103 brain metastases were analyzed. The median number of targets per patient was 8...

Risk of cardiovascular associated death in dialysis patients is the highest among all other co-morbidities. Improving the identification of patients with the highest cardiovascular risk to design an adequate treatment is, therefore, of utmost importance. There are several non-invasive cardiovascular state biomarkers based on the pulse (pressure) wa...

Description of the model with upper and lower arm arteriovenous fistula. (PDF)

Impact of the arteriovenous fistula on radial-to-aortic transfer function. For each individual from the control group we calculated the radial-to-aortic transfer function before and after AV fistula creation. Shown is the average modulus and phase of the transfer function in the frequency domain. (TIF)

Interdependence of the clinical and pulse wave-derived characteristics in healthy individuals. Color coded are the Spearman correlation coefficients for four different pulse wave measurement moments. Font color encodes the type of the parameter, i.e. whether it is model-derived (red), SphygoCor derived (black), or it is a basic clinical characteris...

Impact of the arteriovenous fistula on the model-predicted pressure profiles. AV fistula was introduced into the modeled arterial tree for each individual from the control group. Average peripheral (A) and aortic (B) blood pressure profiles show that creation of AV fistula results mostly in decreased pressure values while the shape of the wave rema...

Changes in estimated parameters values when fitting the model without fistula to the profiles generated by the model with incorporated fistula. Shown are percent changes between true parameters, i.e. those used for generating radial profiles from the model with AV fistula, and those estimated by fistula-free model. Asterisks indicate statistical si...

Ability of the fistula-free model to approximate the profiles generated by the model with upper or lower arm fistula. The model considered in the main text of the manuscript, i.e. the model without fistula, was fitted to radial pressure profiles generated by the model with AV fistula for each individual from control population. Shown are boxplots o...

Five randomly selected recorded radial pressure profiles. (TIF)

Synergy of radiation and immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong antitumor immune responses. It remains unclear, however, what are the best radiation fractionation protocols to maximize the therapeutic benefits of this synergy. Here, we present a...

Solid tumors are rich ecosystems of numerous different cell types whose interactions lead to immune escape and resistance to immunotherapy in virtually all patients with metastatic cancer. Here, we have developed a 3D model of human solid tumor tissue that includes tumor cells, fibroblasts, and myeloid and lymphoid immune cells and can represent ov...

This work demonstrates the efficacy of voxel‐based 90Y microsphere dosimetry utilizing post‐therapy SPECT/CT imaging and applies it to the prediction of treatment response for the management of patients with hepatocellular carcinoma (HCC). A 90Y microsphere dosimetry navigator (RapidSphere) within a commercial platform (Velocity, Varian Medical Sys...

Complex interactions occur between tumor and host immune system at each site in the metastatic setting, the outcome of which can determine behavior ranging from dormancy to rapid growth. An additional layer of complexity arises from the understanding that cytotoxic T cells can traffic through the host circulatory system. Coupling mathematical model...

Cardiovascular diseases are the leading cause of death worldwide. Pulse wave analysis (PWA) technique, which reconstructs and analyses aortic pressure waveform based on non-invasive peripheral pressure recording, became an important bioassay for cardiovascular assessment in a general population. The aim of our study was to establish a pulse wave pr...

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 experime...

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...

Background: Gastric cancer is typically diagnosed at a late stage, leading to poor prognoses. Helicobacter pylori is responsible for 70% of gastric cancers globally, and patients with this bacterial infection often present with early stages of the carcinogenic pathway such as inflammation or gastritis. Although many patients continue to progress t...

Background: Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier fo...

Radiation is commonly used in cancer treatment. Over 50% of all cancer patients will undergo radiotherapy (RT) as part of cancer care. Scientific advances in RT have primarily focused on the physical characteristics of treatment including beam quality and delivery. Only recently have inroads been made into utilizing tumor biology and radiobiology t...

Despite decades of effort, most disseminated cancers remain incurable, and progression from localized to metastatic disease is largely responsible for cancer-related mortality. In metastatic disease, an ongoing battle between tumor and host occurs at each site; tumor-associated antigens, stress proteins, and danger-associated molecular patterns can...

Background: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients. Methods: We used the Surveillance, E...

The potential for local radiation therapy to elicit systemic (abscopal) anti-tumor immune responses has been receiving a significant amount of attention over the last decade. We recently developed a mathematical framework designed to simulate the systemic dissemination of activated T cells among multiple metastatic sites. This framework allowed the...

Radiation Oncology treatment planning requires compromises to be made between clinical objectives that are invariably in conflict. It would be beneficial to have a 'bird's-eye-view' perspective of the full spectrum of treatment plans that represent the possible trade-offs between delivering the intended dose to the planning target volume (PTV) whil...

Introduction: The human immune system is complex, dynamic, and highly effective with system tools ranging from simplistic barrier formation to innate and adaptive cellular responses. In turn, the organisms subject to the immune response can evolve a number of different adaptive strategies. Here we examine these evolutionary dynamics in host immune...

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Tumors grow within a host tissue that both facilitates progression by supplying nutrients and growth factors, and inhibits it through physical constraints and immune surveillance. Transformed cancer cells are confronted with this innate and adaptive immune surveillance...

Background/aims: Various body-regulating mechanisms try to counteract rapid changes in serum phosphate levels during hemodialysis (HD). Neither recently proposed nor other existing standard compartment models are able to capture clinically observed intradialytic serum phosphate rebound. Methods: Phosphate serum concentration was frequently measu...

The poor immunogenicity of pancreatic tumors makes them particularly difficult to treat. Standard chemotherapies and single agent immunotherapies have had notoriously little success in this arena. Oncolytic virus therapy has the potential to enhance the penetration of immunotherapeutically-delivered CAR T cells into the tumor and improve treatment...

It is estimated that about 10% of new prostate cancer (PCa) cases are lymph node-positive (LN+). We have previously discussed the role of the inflection point (IP) of an inverse Gompertzian survival curve as a surrogate for disease incurability. In this study, we aimed to stratify curability of different patient cohorts with pathologically positive...

Figure S1. (A) Estimated relative survival curves for LN+ stratified cohorts. (B) Derivatives of fitted curves together with calculated inflection points (circles).

Computational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated by in vitro assays, and e...

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 fema...

It remains unclear how localized radiotherapy for cancer metastases can occasionally elicit a systemic antitumor effect, known as the abscopal effect, but historically, it has been speculated to reflect the generation of a host immunotherapeutic response. The ability to purposefully and reliably induce abscopal effects in metastatic tumors could me...

Computational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated by in vitro assays, and e...

It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughl...

Multi-scale agent-based models are increasingly used to simulate tumor growth dynamics. Simulating such complex systems is often a great challenge despite large computational power of modern computers and, thus, implementation techniques are becoming as important as the models themselves. Here we show, using a simple agent-based model of tumor grow...

Background: The combination of radiotherapy and immunotherapy for cancer treatment has regained momentum since the recent remarkable clinical success in immune checkpoint strategies. The attraction comes from the concept that radiation-induced tumor cell death will release tumor antigens capable of activating dendritic cells to establish long term...

Introduction and Objectives: Radiation-induced abscopal effects are characterized by regression of tumor nodules outside the local radiation treatment field. Abscopal effects have been reported in metastatic lymphoma, melanoma, lung and breast cancer as well as renal cell carcinoma amongst others. Radiotherapy causes a perturbation to the local imm...

Background: Although altered protocols that challenge conventional radiation fractionation have been tested in prospective clinical trials, we still have limited understanding of how to select the most appropriate fractionation schedule for individual patients. Currently, the prescription of definitive radiotherapy is based on the primary site and...

Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialy...

It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughl...