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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

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.

3

Chemotherapy-induced fatigue estimation using hidden Markov model

Ameli Sina, Naghdy Fazel, Stirling David, Naghdy Golshah, Aghmesheh Morteza

Biocybernetics and Biomedical Engineering

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2019

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Vol. 39, no. 1

176--187

EN

Chemotherapy-induced fatigue undermines the physical performance and alter gait behaviour of patients. In clinics, there is not a well-established method to objectively assess the effects of chemotherapy-induced fatigue on gait characteristics. Clinical trials commonly use 6 Minute Walking Tests (6MWT) to assess patients' gait. However, these studies only measure the distance that patients can walk. The distance does not provide comprehensive information about variations in ambulatory motion characteristics and body postural behaviour which can more appropriately describe the fatigue effects on general physical performance. Gait characteristics provide a manifestation of relationships between muscular and cardiovascular fitness status and physical motions. Hence, an assessment of gait characteristics provides more appropriate information about the effects of chemotherapy-induced fatigue on gait behaviour. A novel approach is proposed to objectively assess the impacts of chemotherapy-induced fatigue on cancer gait by analysing the gait characteristics during 6MWT. The joint angles of the lower body segments are measured by inertial sensors and modelled through a Hidden Markov Model (HMM) with Gaussian emissions. A Gaussian clustering method classifies the joint angles of first gait cycle to determine the six gait phases of a normal gait as initial training values. A comparison of gait characteristics before and after chemotherapy-induced fatigue determines the gait abnormalities. The method is applied to four cancer patients and outcomes are benchmarked against the gait of a healthy subject before and after running program-induced fatigue. The results indicate a more accurate quantitative-based tool to measure the effects of chemotherapy-induce fatigue on gait and physical performance.

4

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*.

5

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.

6

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.

7

Optimal strategy in chemotherapy for Malthusian model of cancer growth

Maroński R.

Acta of Bioengineering and Biomechanics

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2017

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Vol. 19, no. 1

63--68

EN

Purpose: The problem of optimal strategy in cancer chemotherapy is reconsidered. Two incompatible goals should be completed: the number of cancer cells in the patient’s body should be reduced and the toxic effect of the therapy should be minimized. Such problem may be formulated in optimal control. The control function is the amount of the drug administered in the time unit. Methods: The Malthusian model of cell population growth is employed where the rate of increase of the number of cancer cells is proportional to the number of cells in population and an intrinsic rate that usually is assumed to be constant. The performance index is the amount of the drug cumulated in the patient’s body and it is minimized. A non-standard method of optimal control is used – method of Miele. Results: The optimal solutions are obtained for three cases: constant intrinsic rate, monotonically increasing/decreasing intrinsic rate and for periodic intrinsic rate. The optimal control is ununique for the first case – the result is irrespective of the strategy. Such result has been known earlier. The optimal control is unique for other cases and it is of bang-bang type. Conclusions: The ununique solution for constant intrinsic rate is surprising, therefore a mechanical analogy is given. The optimal strategy is in accordance with clinical experience for decreasing intrinsic rate. The optimal control is a periodic function of time for the intrinsic rate of sin/cos type – the drug should be administered, as its value is relatively high.

8

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.

9

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.

10

Radiobiologia w służbie medycyny

Grądzka I., Szumiel I.

Postępy Techniki Jądrowej

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2009

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z. 1

7-11

11

Optimal strategy in chemotherapy for a Gompertzian model of cancer growth

Maroński R.

Acta of Bioengineering and Biomechanics

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2008

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Vol. 10, nr 2

81-84

EN

The problem of optimal cancer chemotherapy is reconsidered. For the assumed result of the therapy the cumulative negative toxic effect of the drug is minimized. The unknown function to be optimized is the time-dependent dose of the drug. The Gompertzian model of cell population growth is employed. The formulated problem of the calculus of variations is solved using the method of Miele (the method of extremization of linear integrals via Green’s theorem). The optimal solution is unique and of “bang-bang” type with one switching point.

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

Tuberkulostatyczne chemioterapeutyki

Nowak K., Suryło P., Kowalski P.

Wiadomości Chemiczne

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2003

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[Z] 57, 9-10

877--906

EN

At the present time tuberculosis is completely treatable. However, it[MS1] is still a major cause of morbidity and mortality among the poorest people. Tuberculosis is the main source of death from among infectious diseases worldwide. In turn, infectious diseases remain the leading cause of death in the world today, greater than cardiovascular disease or cancer. According to the data provided by World Health Organization (WHO), one-third of the world's population is infected with Mycobacterium tuberculosis. In contrary to general expectation, the incidence of mycobacterial disease has significantly increased since 1990 worldwide. This problem has been aggravated by the human immunodeficiency virus (HIV) pandemia and the recent increase in incidences of microbial resistance to antibiotics. Another problem is the lack of the viable research program to develop the new range of the antituberculosis drugs. Since the mid 90’s no new drugs have been introduced, with the exception of a few minor modifications of existing formulas. This review presents history and current summary of the developments in the application and synthesis of tuberculostatic chemotherapeutics. One of the first type of drugs used were salts of heavy metals, which were discontinued quickly due to the high degree of their toxicity. However pirazinamide(2), introduced in 1936 is still being used today. Modern antituberculosis therapies started in 1944 with the Waksman’s discovery of the streptomycin (12). From among modern drugs the most popular are: PAS (15), INH (18), and EMB (34). Schemes 7, 8 and 14, 15 show the methods of synthesis of these compounds. Similarly, schemes 9?11 show the same for the cycloserine (22) antibiotic, and figures 2, 3 and 4 present the structures of the kanamycin 33 cyclic polipeptide 38 and ansamycin 39 antibiotics. Furthermore, detailed description of the methods of synthesis of fluorochinolones 44, 45 and 46 (introduced in 80’s) can be found in schemes 19, 20 and 22. In this article there is also information about the direction of the new research trends taking place in the field of the new antituberculosis agents.

15

Optimal Control for a Class of Compartmental Models in Cancer Chemotherapy

Świerniak A., Ledzewicz U., Schättler H.

International Journal of Applied Mathematics and Computer Science

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2003

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Vol. 13, no 3

357-368

EN

We consider a general class of mathematical models P for cancer chemotherapy described as optimal control problems over a fixed horizon with dynamics given by a bilinear system and an objective which is linear in the control. Several two- and three-compartment models considered earlier fall into this class. While a killing agent which is active during cell division constitutes the only control considered in the two-compartment model, Model A, also two three-compartment models, Models B and C, are analyzed, which consider a blocking agent and a recruiting agent, respectively. In Model B a blocking agent which slows down cell growth during the synthesis allowing in consequence the synchronization of the neoplastic population is added. In Model C the recruitment of dormant cells from the quiescent phase to enable their efficient treatment by a cytotoxic drug is included. In all models the cumulative effect of the killing agent is used to model the negative effect of the treatment on healthy cells. For each model it is shown that singular controls are not optimal. Then sharp necessary and sufficient optimality conditions for bang-bang controls are given for the general class of models P and illustrated with numerical examples.

16

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.

17

An Application of Optimal Control Theory to the Design of Theoretical Schedules of Anticancer Drugs

Boldrini J. L., Costa I. S.

International Journal of Applied Mathematics and Computer Science

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1999

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Vol. 9, no 2

387-399

EN

A system of differential equations for the control of tumor growth cellsin a cycle non-specific chemotherapy is analyzed. Spontaneously acquired drug resistance is taken into account by means of a mutation rate non-decreasingly dependent on time and the drug kill rate is supposed to depend on the growth rate of sensitive cells. For general tumor growth and drug kill rates the optimal treatment consists in maximizing the allowable drug concentration throughout.