Wyniki wyszukiwania - Biblioteka Nauki

1

Cytotoxicity and inhibitory properties against topoisomerase II of doxorubicin and its formamidine derivatives

100%

Kik K. , Studzian K. , Wąsowska-Łukawska M. , Oszczapowicz I. , Szmigiero L.

Acta Biochimica Polonica

|

2009

|

tom 56

|

nr 1

135-142

EN

This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. Conclusion: DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.

2

Aromatic indolinic aminoxyls as antioxidants in cardiac sarcoplasmic reticulum lipid and protein oxidation.

100%

Kulawiak-Gałąska D. , Woźniak M. , Greci L.

Acta Biochimica Polonica

|

2002

|

tom 49

|

nr 1

43-49

EN

The results presented demonstrate the influence of aromatic indolinic aminoxyls: 1,2-dihydro-2-ethyl-2-phenyl-3H-indole-3-phenylimino-1-oxyl (IA-C2) and 1,2-dihydro-2-octadecyl-2-phenyl-3H-indole-3-phenylimino-1-oxyl (IA-C18) on oxidation of lipids and proteins of cardiac sarcoplasmic reticulum membranes. We have used doxorubicin and t-butyl hydroperoxide as agents inducing oxidative stress in isolated rat cardiac sarcoplasmic reticulum membrane system. Carbonyl groups were measured as the end product of membrane protein oxidation, and thiobarbituric acid reactive substances were assessed as a marker of lipid peroxidation. Inhibition of peroxidation of certain membrane components depends on the length of acyl chain. Aminoxyl IA-C2 inhibits the lipid peroxidation process while IA-C18 is an efficient protector against protein oxidation.

3

Early diagnostics and prevention of anthracycline-induced cardiomyopathy – the role of cardiologist

100%

Chazova I. E. , Ovchinnikov A. G. , Ageev F. T.

OncoReview

|

2015

|

tom 5

|

nr 4

A169-176

EN

Anticancer antibiotics, anthracyclines, may cause severe left ventricle systolic dysfunction that is associated with poor clinical prognosis. In this review, we discuss the mechanisms and risk factors of anthracycline-induced cardiotoxicity and cardiomyopathy, among which the cumulative administered dose of anthracyclines and concurrent cardiovascular diseases are the most important. We also present strategies for primary and secondary prevention of anthracycline-induced cardiotoxicity via rigorous assessment of early signs of left ventricular dysfunction.

4

Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affects growth of B16-F10 tumors

100%

Mitrus I. , Sochanik A. , Cichoń T. , Szala S.

Acta Biochimica Polonica

|

2009

|

tom 56

|

nr 1

161-165

EN

The study aimed to check the effectiveness of anticancer therapy combining a vascular-disruptive drug (combretastatin phosphate, CA4P) and a liposomal formulation of a chemotherapeutic (doxorubicin). CA4P was synthesized in our laboratory according to a previously described procedure. The antivascular drug and long-circulating doxorubicin-loaded liposomes were used to treat B16-F10 murine melanoma experimental tumors. Seventy-four hours after drug administration, a decrease in the number of tumor blood vessels was apparent and necrotic areas within tumors were visible. Combination therapy consisting of alternate administrations of CA4P and liposomal doxorubicin yielded greater inhibition of tumor growth than monotherapies alone. The best therapeutic results were obtained with the antivascular drug administered intratumorally every second day at 50 mg/kg body mass. In the case of combined therapy, the best results were obtained when the vascular-disruptive agent (CA4P) and the antineoplastic agent (liposomal doxorubicin) were administered in alternation.

5

The influence of proteasome inhibitor on the expression of cardiomyocytes damage markers after incubation with doxorubicin

100%

Tereszkiewicz S. , Matysiak W. , Mandziuk S. , Korga A. , Oleksiejuk M. , Hejna M. , Korobowicz-Markiewicz A. , Iwan M. , Dudka J.

Current Issues in Pharmacy and Medical Sciences

|

2014

|

tom 27

|

nr 2

88-91

EN

The aim of the study was to verify the thesis that the cardiotoxic effects of doxorubicin are connected with activation of the ubiquitin - proteasome pathway followed by protein degradation. The expression of myocardial damage markers - fatty acid binding protein (H-FABP) and brain natriuretic peptide (BNP) was evaluated in rat fetal cardiomyocytes simultaneously treated with doxorubicin and the proteasome inhibitor - bortezomib. The level of H-FABP and BNP protein under the influence of doxorubicin was decreased below the detection threshold with unchanged (H-FABP) or elevated (BNP) mRNA expression level. Against the expectations, the inhibitor of proteasome did not abolish this effect. The observed abnormal expression of BNP and H-FABP protein after doxorubicin treatment makes their diagnostic significance in anthracycline cardiotoxicity questionable.

6

BIODISTRIBUTION OF DOXORUBICIN-LOADED SUCCINOYL CHITOSAN NANOPARTICLES IN MICE INJECTED VIA INTRAVENOUS OR INTRANASAL ROUTES

100%

Zubareva A. , Shcherbinina T. , Varlamov V. P. , Svirshchevskaya E.

Progress on Chemistry and Application of Chitin and its Derivatives

|

2014

|

tom 19

145-154

EN

Chitosan (Chi) is an extremely promising natural biopolymer with remarkable potency for the development of drug and vaccine delivery nanosystems. Various Chi derivatives are used to form nanoparticles (NPs) with unique properties. However, the efficacy of the therapy delivered by Chi NPs depends significantly on NP biodistribution in the body. The aim of this study was the analysis of biodistribution of NPs formed by succinoyl Chi and loaded with doxorubicin (SCNPDOX). We compared the distribution of free DOX and SCNP-DOX after intravenous (i.v.) and intranasal (i.n.) delivery into tumour-bearing mice. Distribution of DOX and SCNP-DOX was comparable after i.v. injection while they differed significantly after i.n. instillation.

7

Mathematical optimization for liposomal doxorubicin in tumor

100%

Hrynyk R. , Langner M.

Cellular and Molecular Biology Letters

|

2005

|

tom 10

|

nr Suppl.

8

Role of biomarkers and electrocardiography assessment as individual predictors of anthracycline cardiotoxicity in lymphoma patients

88%

Długosz-Danecka M. , Jaroszyński A. , Jurczak W.

OncoReview

|

2018

|

tom 8

|

nr 4

99-104

EN

The significant progress in the treatment of non-Hodgkin lymphomas, translating into prolongation of overall survival results in the manifestation of long-term adverse events, like anthracycline-related cardiotoxicity. Despite the dose-dependent cardiac dysfunction and the presence of risk factors, the increasing probability of cardiotoxicity arises from individual predisposition. Identification of high- -risk patients gives the opportunity to implement the prevention strategies to reduce the incidence of cardiac complications. The study evaluated the utility of biomarkers: N-terminal B-type natriuretic peptide, troponin I and electrocardiography with spatial QRS-T angle assessment, as indicators of individual sensitivity of cardiomyocytes to doxorubicin resulting in myocardial damage. Thirty-five treatment-naïve patients at increased risk of cardiotoxicity, were subjected prospectively during (R)-CHOP treatment to echocardiographic assessment and analysis of biomarkers: TnI and NT-proBNP plasma level and spatial QRS-T assessment before and 24 hours after each cycle of chemotherapy. The analysis of QRS-T angle was consistent with the results of NT-proBNP assessment and allowed to identify, after the first cycle of chemotherapy, patients at increased risk of developing cardiovascular complications, who require thorough echocardiographic analysis and primary cardioprotection implementation. Our data did not reveal the role of TnI in the identification of cardiac events. Our findings, though promising, should be confirmed in a larger group of patients in real-life or clinical trials.

9

Sarcomatoid renal-cell carcinoma: treatment strategy, review of the literature and a case report

88%

Gębara-Puchniarz A. , Hryciuk B. , Stec R. , Szczylik C. , Grala B. , Kozłowski W.

OncoReview

|

2016

|

tom 6

|

nr 4

A184-187

EN

Introduction: Sarcomatoid renal-cell carcinoma is a very rare cancer characterised with aggressive course of disease and poor prognosis. At present there are no standards of care for this histologic subtype of renal cell carcinoma resistant to various forms of systemic treatment. Methods: The study describes a case of 58 year old woman after left nephrectomy for clear cell carcinoma with sarcomatoid component and after resection of right-kidney tumour for synchronous clear cell carcinoma who received first-line bevacizumab and temsirolimus under the clinical trial, and then second-line chemotherapy based on gemcitabine and doxorubicin and ifosfamide-based third-line chemotherapy. The patient underwent pulmonary metastasectomy twice, and once a metastasectomy for liver metastases. Conclusions: Surgery (including metastases treatment) followed by the systemic chemotherapy seems to be correct option of treatment in patients with renal cell carcinoma with sarcomatoid features. The development of optimum method of systemic treatment requires further prospective randomised trials.

10

Methylxanthines (caffeine, pentoxifylline and theophylline) decrease the mutagenic effect of daunomycin, doxorubicin and mitoxantrone

88%

Piosik J. , Gwizdek-Wiśniewska A. , Ulanowska K. , Ochociński J. , Czyż A. , Węgrzyn G.

Acta Biochimica Polonica

|

2005

|

tom 52

|

nr 4

923-926

EN

Previously performed experiments showed that methylxanthines, especially caffeine, may protect cells against cytostatic or cytotoxic effects of several aromatic compounds. One of the proposed mechanisms of this protection is based on stacking interactions between π electron systems of polycyclic aromatic molecules. In this work, we demonstrate that caffeine and other methylxanthines - pentoxifylline and theophylline - significantly decrease mutagenicity of the anticancer aromatic drugs daunomycin, doxorubicin and mitoxantrone. The spectrophotometric titration of these aromatic compounds by methylxanthines indicated formation of mixed aggregates. The concentrations of free active forms of the drugs decreased when the concentrations of methylxanthines increased in the mixture. Therefore, likely methylxanthines may play a role of scavengers of the free active forms of daunomycin, doxorubicin and mitoxantrone.

11

Effect of iodothyronine hormone status on doxorubicin related cardiotoxicity

88%

Dudka J. , Mandziuk S. , Madej-Czerwonka B. , Sierocinska-Sawa J. , Walczyna B. , Korga A. , Cendrowska-Pinkosz M. , Burdan F.

Folia Morphologica

|

2013

|

tom 72

|

nr 4

EN

The anthracycline anticancer agent doxorubicin has been recognised to induce a dose-dependent cardiotoxicity. The chronic form of such complication is characterised by an irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be multifactorial, the pivotal role has been attributed to reactive oxygen species formation. Because redox equilibrium in cardiomyocytes may be regulated via iodothyronine hormones, the aim of the study was to appraise the effect of hypothyroidism on heart damages induced by doxorubicin. The rats received methimazole in drinking water (0.001 and 0.025%) after doxorubicin administration (2.0, 5.0 and 15 mg/kg). The cardiac morphology and blood biochemical markers of heart damage were assessed. Decreased levels of iodothyronine hormones had not significant impact on cardiac morphological changes and no effect on the level of B-type natriuretic peptide in rats receiving doxorubicin. Lower hormonal levels had sporadic, diverse effect on blood transaminases, lactate dehydrogenase and creatine kinase levels, but any relation to time, doxorubicin doses and hypothyroid status was found. Hypothyreosis leads to increase in fatty acid binding protein in rats receiving higher dose of doxorubicin. Hypothyreosis had no effect on heart stretching and on necrosis at morphological level, but caused biochemical symptoms of cardiomyocyte necrosis in rats receiving doxorubicin. (Folia Morphol 2013; 72, 4: 340–348)

12

The effect of one-electron reduced drugs on hepatic aconitase activity and triglycerides level

88%

Wnukowska M. , Mandziuk S. , Korga A. , Jodlowska-Jedrych B. , Matysiak W. , Halasa J. , Burdan F. , Iwan M. , Gieroba R. , Dudka J.

Current Issues in Pharmacy and Medical Sciences

|

2015

|

tom 28

|

nr 1

5-7

EN

The redox cycle triggered by one electron reduction of doxorubicin and tirapazamine - both anticancer agents - leads to superoxide production. This superoxide production itself removes one iron atom from the [4Fe-4S] cluster, being an active center of aconitase. In addition, the incurred changes in cell redox equilibrium may affect lipid metabolism. The aim of the study was to evaluate a concomitant effect of both drugs on hepatic aconitase activity and triglycerides level. In our study, doxorubicin (1.8 mg/kg b.w.) was administered intraperitoneal (i.p.) six times, once a week, within male Wistar rats, to achieve a cumulative dose of 10.8 mg/kg b.w. Two hours before every doxorubicin administration, tirapazamine in the dose of either 5 or 10 mg/kg b.w. was also i.p. injected. A week after withdrawing drug administration, the liver was taken for biochemical analysis. Therein, an increase in aconitase activity and a decrease in triglycerides level was seen in all groups exposed to doxorubicin. Our work demonstrated that tirapazamine administration had no influence on both tested parameters, but its higher dose rate normalized aconitase activity affected by doxorubicin.

13

The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

88%

Czuba B. , Fituch M. , Mandziuk S. , Jodlowska-Jedrych B. , Matysiak W. , Halasa J. , Burdan F. , Korga A. , Iwan M. , Luszczewska-Sierakowska I. , Dudka J.

Current Issues in Pharmacy and Medical Sciences

|

2014

|

tom 27

|

nr 4

220-223

EN

The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS) in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.

14

CARDIOPROTECTIVE EFFECT OF GREEN TEA EXTRACT ON DOXORUBICIN-INDUCED CARDIOTOXICITY IN RATS

88%

KHAN G. , HAQUE S. E. , ANWER T. , AHSAN M. N. , SAFHI M. M. , ALAM M. F.

Acta Poloniae Pharmaceutica - Drug Research

|

2014

|

tom 71

|

nr 5

861-868

EN

The in vivo antioxidant properties of green tea extract (GTE) were investigated against doxorubicin (DOX) induced cardiotoxicity in rats. In this experiment, 48 Wistar albino rats (200ñ250 g) were divided into eight groups (n = 6). Control group received normal saline for 30 days. Cardiotoxicity was induced by DOX (20 mg/kg i.p.), once on 29th day of study and were treated with GTE (100, 200 and 400 mg/kg, p.o.) for 30 days. Aspartate aminotransferase (AST), creatinine kinase (CK), lactate dehydrogenase (LDH), lipid peroxidation (LPO), cytochrome P450 (CYP), blood glutathione, tissue glutathione, enzymatic and non-enzymatic antioxidants were evaluated along with histopathological studies. DOX treated rats showed a significant increased levels of AST, CK, LDH, LPO and CYP, which were restored by oral administration of GTE at doses 100, 200 and 400 mg/kg for 30 days. Moreover, GTE administration significantly increased the activities of glutathione peroxidase (GPX), glutathione reductase (GR), glutathione s-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), in heart, which were reduced by DOX treatment. In this study, we have found that oral administration of GTE prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels to the normal levels.

15

Annamycin, a novel liposomally formulated anticancer agent

88%

Priebe W. , Booser D. , Perez-Soler R.

Cellular and Molecular Biology Letters

|

1999

|

tom 04

|

nr 2

16

Imatinib inhibits the renewal and tumorigenicity of CT-26 colon cancer cells after cytoreductive treatment with doxorubicin

75%

Przybyszewska M. , Miloszewska J. , Kotlarz A. , Swoboda P. , Pysniak K. , Szczepek W. , Kaczmarek L. , Markowicz S.

Archivum Immunologiae et Therapiae Experimentalis

|

2017

|

tom 65

|

nr 1

17

Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affetcs growth of B16-F10 tumors

75%

Mitrus I. , Sochanik A. , Cichon T. , Szala S.

Acta Biochimica Polonica

|

2009

|

tom 56

|

nr 1

161-165

EN

The study aimed to check the effectiveness of anticancer therapy combining a vascular-disruptive drug (combretastatin phosphate, CA4P) and a liposomal formulation of a chemotherapeutic (doxorubicin). CA4P was synthesized in our laboratory according to a previously described procedure. The antivascular drug and long-circulating doxorubicin-loaded liposomes were used to treat B16-F10 murine melanoma experimental tumors. Seventy-four hours after drug administration, a decrease in the number of tumor blood vessels was apparent and necrotic areas within tumors were visible. Combination therapy consisting of alternate administrations of CA4P and liposomal doxorubicin yielded greater inhibition of tumor growth than monotherapies alone. The best therapeutic results were obtained with the antivascular drug administered intratumorally every second day at 50 mg/kg body mass. In the case of combined therapy, the best results were obtained when the vascular-disruptive agent (CA4P) and the antineoplastic agent (liposomal doxorubicin) were administered in alternation.

18

Doksorubicyna i jej kompleksy w terapiach nowotworów

75%

Filipiuk D. , Lewandowski W. , Świsłocka R. , Świderski G.

Przemysł Chemiczny

|

2018

|

tom T. 97, nr 12

2173--2179

PL

Przedstawiono przegląd literaturowy na temat wykorzystania doksorubicyny i jej kompleksów z metalami jako leków w terapii nowotworów.

EN

A review, with 67 refs.

19

Modulation of Doxorubicin Cytotoxicity by Isoliquiritin and Cynarin Combination on Different Cancer Cell Lines

75%

Al-AdamI S. G. , Al-Khateeb E. H. , NUMAN N. A. , ABBAS M. M. , Tawfiq F. A. , Shakya A. K.

Acta Poloniae Pharmaceutica - Drug Research

|

2020

|

tom 77

|

nr 3

475-484

EN

Natural polyphenolic compounds produced by plant exhibit many pharmacological effects including antioxidant, chemopreventive as well as anticancer properties. This study was conducted to investigate the effect of cynarin ( from Artichoke, Cynara scolymus) and isoliquiritin (from Licorice, Glycyrrhiza uralensis) on doxorubicin (positive control) cytotoxicity in different cell lines including normal (Fibroblasts MCR-5 and Myoblasts H9c2) and cancer (colorectal HCT-116 and hepatocellular HEP-G2) cell lines. The cytotoxic effect of doxorubicin, isoliquiritin and cynarin alone or in different combination was studied on cancer cell lines as well as normal cell lines. The results obtained indicated that both cynarin and isoliquiritin enhance the cytotoxicity of doxorubicin. Both cynarin and isoliquiritin also reduce the cardiotoxicity of doxorubicin on normal cardiac cell lines. The combination of the three compounds (cynarin, isoliquiritin and doxorubicin) result in decrease the cytotoxicity of doxorubicin, which may indicate the presence of interaction and/or antagonism effect between cynarin and isoliquiritin. Cynarin was found to enhance the growth of (HCT-116 and HEP-G2) this might suggest avoiding use of Artichoke in subjects’ susceptibility for these cancers. All results were evaluated using statistical path and showed significant findings. The mechanism of enhanced doxorubicin’s cytotoxicity by cynarin or isoliquiritin also require further investigation to explain the increasing and/or the decreasing effect of these polyphenolic compounds on cytotoxicity of doxorubicin. The current finding can help to start with safe minimum dose of two or three combination of compounds in the context of clinical trials and practice.

20

Cytotoxicity and inhibitory properties against topoisomerase II of doxorubicin and its formamidine derivatives

75%

Kik K. , Studzian K. , Wasowska-Lukawska M. , Oszczapowicz I. , Szmigiero L.

Acta Biochimica Polonica

|

2009

|

tom 56

|

nr 1

135-142

EN

This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. Conclusion: DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.