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1

Mathematical modeling of the neutrophil production process supported by administration of glycoprotein

Mika Barbara, Pelka Magdalena, Tkacz Ewaryst

Biocybernetics and Biomedical Engineering

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2021

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Vol. 41, no. 1

45--63

EN

Drugs administered in chemotherapy influence the patient's hematopoietic system. The side effects of chemotherapy can force changes in both the dose of drugs and the schedule of their administration, which in turn may adversely affect the patient's health. During chemotherapy treatment, there is a necessity to continuously monitor basic blood parameters, including the number of neutrophils and blood platelets, responsible for the patient's immunity. The aim of this paper is to study the behavior of the hematopoietic system, during chemotherapy, by means of a modified mathematical model of neutrophil production. We conducted simulations for children from 1–15 years old, suffering from neuroblastoma, who are undergoing chemotherapy treatment with Topotecan (TPT). The proposed model provides an effective tool for signaling the moment when the number of mature neutrophils, circulating in the blood, drops below the critical level, that is, 500 cells/mL. Such a nadir persisting over time may result in severe neutropenia and consequently require a halt or change to the established treatment schedule. In addition, we analyzed the process of neutrophil production during chemotherapy, supported by the application of glycoprotein as a growth factor of stem cells.

2

Regularized error function-based extended Kalman filter for estimating the cancer chemotherapy dosage: impact of improved grey wolf optimization

Mohite Utkarsha L., Patel Hirenkumar G.

Bio-Algorithms and Med-Systems

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2021

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Vol. 17, no. 1

41--54

EN

Objectives: The main aim of this work is to introduce a robust controller for controlling the drug dosage. Methods: The presented work establishes a novel robust controller that controls the drug dosage and it also carried out parameters estimation. Along with this, a Regularized Error Function-based EKF (REF-EKF) is introduced for estimating the tumor cells that could be adapted for different conditions. It also assists in solving the overfitting problems, which occur during the drug dosage estimation. Moreover, the performance of the adopted controller is compared over other conventional schemes, and the attained outcomes reveal the appropriate impact of drug dosage injection on immune, normal, and tumor cells. It is also ensured that the presented controller does a robust performance on the parameter uncertainties. Moreover, to enhance the performance of the proposed system and for fast convergence, it is aimed to fine-tune the initial state of EKF optimally using a new Improved Gray Wolf Optimization (GWO) termed as Adaptive GWO (AGWO). Finally, analysis is held to validate the betterment of the presented model. Results: The outcomes, the proposed method has accomplished a minimal value of error with an increase in time, when evaluated over the compared models. Conclusions: Thus, the improvement of the proposed REFEKF-AGWO model is proved from the attained results.

3

Szczęście i ciężka praca w opracowywaniu leków

Koroniak Łukasz

Wiadomości Chemiczne

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2020

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[Z] 74, 3-4

135--144

EN

Luck is one of the critical factors determining outcome of many activities we are involved in. In chemistry, and specifically in drug discovery a strike of luck can determine a successful study outcome leading to an approval of potentially blockbuster drug consequently offering a new treatment option for patients in need. On the other hand, lack of luck can often result in termination of activities, wasted resources and years of studies and often have negative impact on a fate of companies and its employees. In a similar fashion, hard work is critical for one’s success. It is not meant in a literal fashion, but rather from the perspective of “going the extra mile” in scientific research and development. It is meant as a proper approach to analysis of study outcome and understanding the reasons “why”, rather than accepting simply yes/no outcomes. Below article discusses two instances where certain level of luck and extra effort invested in understanding of widely available results led to development of two novel therapeutics in oncology field. Described stories deal with development of Abraxane, novel formulation of paclitaxel commercialized by Abraxis Bioscience as well as enzalutamid (Xtandi®) discovered at UCLA and developed and commercialized by Medivation and Astellas Pharma.

4

Robust controller for cancer chemotherapy dosage using nonlinear kernel-based error function

Mohite Utkarsha L., Patel Hirenkumar G.

Bio-Algorithms and Med-Systems

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2020

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Vol. 16, no. 4

art. no. 20190056

EN

It is well-known that chemotherapy is the most significant method on curing the most death-causing disease like cancer. These days, the use of controller-based approach for finding the optimal rate of drug injection throughout the treatment has increased a lot. Under these circumstances, this paper establishes a novel robust controller that influences the drug dosage along with parameter estimation. A new nonlinear error functionbased extended Kalman filter (EKF) with improved scaling factor (NEF-EKF-ISF) is introduced in this research work. In fact, in the traditional schemes, the error is computed using the conventional difference function and it is deployed for the updating process of EKF. In our previous work, it has been converted to the nonlinear error function. Here, the updating process is based on the prior error function, though scaled to a nonlinear environment. In addition, a scaling factor is introduced here, which considers the historical error improvement, for the updating process. Finally, the performance of the proposed controller is evaluated over other traditional approaches, which implies the appropriate impact of drug dosage injection on normal, immune and tumor cells. Moreover, it is observed that the proposed NEF-EKF-ISF has the ability to evaluate the tumor cells with a better accuracy rate.

5

Procedury ochrony personelu narażonego w pracy na działanie czynników chemicznych w postaci leków cytostatycznych

Karkowski Tomasz A., Król Halina, Czarny-Działak Małgorzata, Szpringer Monika, Florek-Łuszczki Magdalena, Dziechciaż Małgorzata, Gworek Barbara, Karkowska Dorota, Chmielewski Jarosław

Przemysł Chemiczny

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2019

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T. 98, nr 10

1623--1628

PL

Omówiono polskie i międzynarodowe przepisy określające standardy bezpieczeństwa i higieny pracy z lekami cytostatycznymi oraz działania prewencyjne podejmowane w celu ochrony personelu medycznego narażonego w pracy na działanie tych czynników chemicznych.

EN

A review with 65 refs.

6

Antiradical properties of chemo drug, carboplatin, in cooperation with ZnO nanoparticles under UV irradiation in putative model of cancer cells

Pairoj Suttirak, Damrongsak Pattareeya, Damrongsak Badin, Jinawath Natini, Kaewkhaw Rossukon, Leelawattananon Tanaporn, Ruttanasirawit Chinnapat, Locharoenrat Kitsakorn

Biocybernetics and Biomedical Engineering

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2019

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Vol. 39, no. 3

893--901

EN

The main objective of this study was to assess the antiradical properties of zinc oxide (ZnO) nanoparticles upon exposure to ultraviolet radiation with carboplatin, an anti-proliferative drug used in the treatment of retinoblastoma. For the purpose of this study, the decomposition of 2,2(diphenyl-1-picryhydrazyl) radical (DPPH*) was used to assess the free radical capacity of antioxidants and was followed by MTT measurements. To test the antiradical capacity, the effective concentration, antiradical power, stoichiometry, and number of reduced DPPH* were investigated. DPPH* has a peak absorbance at a wavelength of 515 nm, which disappears upon the introduction of the antiradical agents. Four agents were reacted with DPPH* and represented the possible reaction kinetic categories. ZnO nanoparticles and carboplatin-loaded ZnO nanoparticles reacted more strongly with DPPH* and approached a saturation state at 420 min. The remaining two antiradical agents, ZnO nanoparticles under UV radiation and carboplatin-loaded ZnO nanoparticles under UV radiation, reacted a bit slower with DPPH* and approached a steady state at 1440 min. Among the different four antiradical agents, carboplatin-loaded ZnO nanoparticles under UV light had the highest antiradical response with the lowest effective concentration value to the reduced DPPH* molecules. ZnO nanoparticles alone were found to be poor antiradical agent. Possible mechanisms were attributed to the number of hydroxyl groups available to decrease the number of DPPH*.

7

Zespół przewlekłego zmęczenia u chorych na raka płuca w trakcie chemioterapii : badanie wstępne

Lampart Gabriela, Górecki Michał, Karczmarek-Borowska Bożena

Problemy Nauk Stosowanych

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2018

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T. 9

159--170

PL

Wprowadzenie: Zespół przewlekłego zmęczenia to stan ciągłego uczucia osłabienia, który może być związany z obecnością procesu nowotworowego jak również wystąpić w trakcie leczenia. Jedną z metod oceny natężenia zmęczenia jest zastosowanie kwestionariusza Brief Fatigue Inventory (BFI). Celem pracy jest ocena zespołu przewlekłego zmęczenia u chorych poddanych chemioterapii. Materiał i metody: W badaniu uczestniczyło 24 pacjentów z rozpoznanym rakiem płuca leczonych chemioterapią w Klinice Onkologii Klinicznej Podkarpackiego Centrum Onkologii w Rzeszowie. Chorzy otrzymywali chemioterapię 3 dniową w odstępach co 21 dni. Przed każdym kursem chemioterapii wypełniali ankietę zawierającą dane demograficzne i pytania dotyczące zmęczenia, kwestionariusz BFI, oceniano stan sprawności chorego wg Karnofsky’ego oraz stopień zaawansowania nowotworu. Wyniki: Wśród badanych było 7 kobiet (29,2%) oraz 17 mężczyzn (70,8%). Średnia wieku badanych wynosiła 65 lat. Wyniki poddano analizie statystycznej. Poziom zmęczenia przed I kursem chemioterapii uznano za umiarkowany u 15 chorych (62,5%), zaś u 9 badanych (37,5%) za łagodny. W związku z zastosowanym leczeniem po jego zakończeniu odnotowano u większej liczby chorych umiarkowany poziom zmęczenia w porównaniu do łagodnego, odpowiednio: 22 osoby - 91,7% vs 2 osoby - 8,3%. Według kwestionariusza BFI stwierdzono zwiększenie średniego ogólnego poziomu zmęczenia przed każdym z kolejnych 4 kursów, odpowiednio: 4,0, 4,5, 5,4, 5,0. Subiektywnie pacjenci ocenili III kurs jako nasilenie uczucia zmęczenia w trakcie chemioterapii - 11 (45,8%). Wnioski: W trakcie chemioterapii stwierdzono zwiększenie uczucia zmęczenia. Zaawansowanie choroby oraz ocena w skali Karnofsky’ego nie wpłynęła na uczucie zmęczenia. Wiek u badanych nie miał wpływu na uczucie zmęczenia w trakcie kolejnych cykli chemioterapii. Odnotowano różnicę w odczuciu zmęczenia w zależności od płci w różnych cyklach chemioterapii. Stwierdzono, że utrata wagi ciała nie wpłynęła na poziom zmęczenia. Wskazane dalsze prowadzenie badań na większej liczbie chorych.

EN

Introduction: Cancer related fatigue is a chronic feeling of tiredness, which can be associated with malignancy as well as its treatment result. One of the methods of rating the intensity of tiredness is the Brief Fatigue Inventory (BFI) questionnaire. The aim of this thesis is the evaluation of cancer related fatigue in patients receiving chemotherapy. Material and methods: 24 patients with diagnosed lung cancer who have been receiving chemotherapy at the Oncology Clinic in Rzeszow Oncology Centre have participated in the research. These patients have been receiving 3-day chemotherapy every 21 days. Before each chemotherapy course they filled in a questionnaire with demographical data, answered questions about tiredness and BFI questionnaire. Patients’ efficiency has been scored using Karnofsky’s scale and stage of cancer. Results: There were 7 women (29,2%) and 17 men (70,8%) among the evaluated patients. The average age of subjects was 65 years old. The results have been statistically analyzed. The rate of fatigue before the 1st course has been classed as moderate with 15 patients (62,5%), and as mild with 9 of them (37,5%). In relation to the treatment received, moderate fatigue level has been identified with a higher number of patients compared to a mild one, post-treatment: 22 people - 91,7% vs 2 people - 8,3%, consequently. According to the BFI questionnaire an increased fatigue level has been observed in each of the chemotherapy courses: 4,0, 4,5, 5,4, 5,0 accordingly. Patients have subjectively rated the 3rd course as intensification of the fatigue level during chemotherapy treatment - 11 (45,8%). Conclusions: A higher level of fatigue has been observed during chemotherapy treatment. The stage of disease or evaluation based on Karnofsky’s scale has not influenced the fatigue. The age of the patients has not had any impact on fatigue rate in any of the treatment courses. A difference in experiencing fatigue by gender has been identified in various chemotherapy cycles. The loss of weight has not had any effect on fatigue level. Further research on an increased number of patients is advised.

8

A multi-layered incremental feature selection algorithm for adjuvant chemotherapy effectiveness/futileness assessment in non-small cell lung cancer

Naftchali R. E., Abadeh M. S.

Biocybernetics and Biomedical Engineering

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2017

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Vol. 37, no. 3

477--488

EN

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; and is one of the leading causes of death in the world. Surgery combined with chemotherapy is the recommended treatment for NSCLC. Since chemotherapy is an expensive treatment for either medical staff or patients suffering from pain, this study attempts to construct an intelligent predictive model to predict the adjuvant chemotherapy (ACT) effectiveness/ futileness in the patients, in order to help futile cases for unnecessary applications. There is a 2-step method: preprocessing and predicting. First a purposefully preprocessing tech-nique: chi-square test, SVM-RFE and correlation matrix, were employed in NSCLC gene expression dataset as a novel multi-layered feature selection method to defeat the curse of dimension and detect the chemotherapy target genes from tens of thousands features, based on which the patients can be classified into two groups, with NB classifier at second step. 10-Fold cross-validation was found with accuracy of 68.93% for 2 genes, TGFA (205015_s_at) and SEMA6C (208100_x_at), which is preferable compared to earlier studies, even though more than 2 input features are employed for the prediction. According to the results found in this study, one can concludes that the multi-layered feature selection approach has increased the classification accuracy in terms of finding the fitted patient for receiving ACT by reducing the number of features and has significant power to be used in medical datasets with small train samples and large number of features.

9

Cytotoxic surfaces for regional chemotherapy

Krukiewicz K., Cichy M., Turczyn R., Jarosz T., Zak J. K., Bednarczyk-Cwynar B., Ruszkowski P.

Engineering of Biomaterials

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2016

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Vol. 19, no. 138 spec. iss.

78

10

Chemioterapia raka piersi - efekty uwarunkowane genetycznie

Pamuła-Piłat J., Tęcza K.

Laboratorium - Przegląd Ogólnopolski

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2014

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nr 3-4

32--36

PL

Efekty chemioterapii raka piersi mogą zależeć od modyfikacji w genach białek uczestniczących w biotransformacji i transporcie leków, a także w genach związanych z naprawą DNA oraz apoptozą. Badania molekularne tych genów mogą być pomocne w selekcji pacjentów, którzy odniosą korzyść ze stosowanej terapii, lub pacjentów zagrożonych wysoką toksycznością leczenia.

EN

The efficacy of chemotherapy depends on the genetic variations in genes encoding proteins crucial for drugs biotransformation, transport, DNA repair and apoptosis. Pharmacogenetic analyses in drugmetabolizing enzymes and transporters genes could be useful for the distinction between responders and non-responders to the treatment and also the patients who are at risk of developing severe toxicity.

11

Kardiotoksyczność w leczeniu raka piersi

Wittych J., Wachowicz M., Banatkiewicz P., Mitura S., Gisterek I.

Inżynier i Fizyk Medyczny

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2014

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Vol. 3, nr 4

209--213

PL

Rak piersi jest w Polsce najczęstszym nowotworem złośliwym rozpoznawanym u kobiet. Kardiotoksyczność uzupełniającego leczenia pooperacyjnego u kobiet chorych na raka piersi staje się na całym świecie coraz większym problemem terapeutycznym. Zarówno radioterapia, jak i chemioterapia stosowane jako metody leczenia powodują kardiologiczne powikłania. W przypadku połączenia obydwu technik leczenia ryzyko wystąpienia kardiotoksyczności znacznie wzrasta. Zaburzenia i uszkodzenia kardiologiczne zaliczane są do wczesnych i późnych powikłań po radioterapii. Powikłania wczesne (kardiotoksyczność ostra) najczęściej ujawniają się w ciągu kilku tygodni (do roku) po zakończeniu leczenia promieniowaniem jonizującym. Powikłania te dotyczą głównie osierdzia oraz zastawek serca. Natomiast uszkodzenia późne (kardiotoksyczność przewlekła) to przede wszystkim choroby naczyń wieńcowych, ale również mięśnia sercowego czy układu przewodzącego serca. Pojawiają się zwykle w ciągu 10-15 lat po napromienianiu. Wraz z rozwojem technik radioterapii dawka, jaką otrzymuje serce, uległa znacznej minimalizacji. Również postęp w chemioterapii powoduje zmniejszenie powikłań kardiologicznych. Nadal jednak zaburzenia i uszkodzenia serca stanowią znaczną część skutków ubocznych leczenia onkologicznego.

EN

Breast cancer is one of the most popular and frequent cancer in women. Cardiac toxicity is often observed side effect of the adjuvant therapy and this is a big therapeutical problem. Both radiotherapy and chemotherapy used as anti-cancer therapy cause the cardiac complications. In the case of combined radiotherapy and chemotherapy the risk of cardiac toxicity increase. Cardiotoxic side effects after radiotherapy are divided into acute and late complications. The acute side effects (acute cardiac toxicity) may occur during the therapy or to one year after radiotherapy. These complications mainly affect the pericardium and the heart valves. The late side effects (late cardiac toxicity) may occur more than one year, generally 10-15 years after the end of the treatment. The complications were located mostly in the pericardium and in the coronary vessels, but it also can involve the myocardium and the conducting system of the heart. The development of radiotherapy techniques gives the possibility of minimalizing the heart dose. Moreover, the progress in chemotherapy also reduces the risk of cardiac injury. But still the cardiac complications and injuries are the significant part of the side effect of anti-cancer therapy.

12

Optimal strategy in cancer chemotherapy for exponential model of cell population growth

Maroński R.

Zeszyty Naukowe Katedry Mechaniki Stosowanej / Politechnika Śląska

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2006

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z. 26

231-234

EN

The problem of optimal cancer chemotherapy is reconsidered. The cumulative negative toxic effect of the drug is minimized for the assumed destruction result at the end of the therapy. The control function to be optimized is time-dependent dose of the drug. A exponential model of growth of the cancer cell population is employed. It is known that for constant intrinsic rate the solution of the problem is ununique - different strategies give the same result of the therapy. If intrinsic rate is a variable monotonic function of time the solution of the problem is unique and it is of "bang-bang" type with one switching point. The method of extremization of linear integrals via Green's theorem is applied.

13

Finite dimensional models of drug resistant and phase specific cancer chemotherapy

Ledzewicz U., Schättler H., Świerniak A.

Journal of Medical Informatics & Technologies

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2004

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Vol. 8

IP5--14

EN

The problem of modelling drug resistance and phase specificity of cancer chemotherapy using finite dimensional models were considered. We formulate optimal control problems arising in protocol design for such models and discuss research issues resulting from these formulations.

14

Kontrolowane uwalnianie leków : nowa strategia w chemoterapii

Jedliński Z., Juzwa M.

Inżynieria Biomateriałów

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2002

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R. 5, nr 22

12-16

15

Identification problems of temperature field parameters in human body by cyclic therapy

Kącki E., Małolepszy A., Janaszewski M.

Journal of Applied Computer Science

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2000

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Vol. 8, nr 1

93-100

EN

The paper deals with modelling of temperature fields created in human body at cyclic therapy and with identification of the field parameters. The paper contain also description of artificial neural network applied to investigations of modeled temperature fields. To train a network, training and testing sets obtained by solving a boundary problem for a partial differential equation of parabolic type under cyclic constraint have been used. The paper shows the results of a computer experiment and points at some possibilities of exploitation of the elaborated software to modelling of phenomena occuring at cyclic therapy.