Nanostructured titanium(IV) oxide was used for the destructive adsorption and photocatalytic degradation of mitoxantrone (MTX), a cytostatic drug from the group of anthracycline antibiotics. During adsorption on a titania dioxide surface, four degradation products of MTX, mitoxantrone dicarboxylic acid, 1,4-dihydroxy-5-((2-((2-hydroxyethyl)amino)ethyl)amino)-8-((2-(methylamino)ethyl)amino)anthracene-9,10-dione, 1,4-dihydroxy-5,8-diiminoanthracene-9,10(5H,8H)-dione and 1,4-dihydroxy-5-imino-8-(methyleneamino)anthracene-9,10(5H,8H)-dione, were identified. In the case of photocatalytic degradation, only one degradation product after 15 min at m/z 472 was identified. This degradation product corresponded to mitoxantrone dicarboxylic acid, and complete mineralization was attained in one hour. Destructive adsorbent manganese(IV) oxide, MnO2, was used only for the destructive adsorption of MTX. Destructive adsorption occurred only for one degradation product, mitoxantrone dicarboxylic acid, against anatase TiO2.

• MeSH
• adsorpce MeSH
• antracykliny chemie   MeSH
• katalýza MeSH
• mitoxantron chemie   MeSH
• nanočástice chemie   MeSH
• oxidy chemie   MeSH
• sloučeniny manganu chemie   MeSH
• titan chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antracykliny MeSH
• manganese dioxide MeSH Prohlížeč
• mitoxantron MeSH
• oxidy MeSH
• sloučeniny manganu MeSH
• titan MeSH
• titanium dioxide MeSH Prohlížeč

BACKGROUND: This study evaluates mitoxantrone (MX) therapy in patients with relapsing remitting and secondary progressive multiple sclerosis (MS). OBJECTIVES: Evaluation of the disability progression and side effects of MX. METHODS: There were studied 33 patients (10 males, 23 females), average age 48.5+/-9.9 SD) with relapsing remitting and secondary progressive MS. The disability was evaluated using Expanded Disability Status Scale (EDSS). Time period from the onset to secondary progressive course of the disease was 9.3 years. Patients, whose disability progression increased by one or more EDSS point per one year, and not responding to other therapy, were treated with mitoxantrone. Patients were treated once monthly with intravenous administration of mitoxantrone 12 mg/m2, not exceeding the maximum cumulative dose of 14 mg/m2 and Solu-Medrol 1000 mg. Six pulses were done in each patient. EDSS score was measured at the beginning of the treatment and after twelwe month. Disability progression was evaluated. Nonparametric Wilcoxon matched pair test was used for statistical analysis. (Tab. 1, Fig. 3, Ref: 5.)

• MeSH
• chronicko-progresivní roztroušená skleróza farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitoxantron škodlivé účinky   terapeutické užití   MeSH
• progrese nemoci MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• mitoxantron MeSH

INTRODUCTION: Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. METHODS: Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m2, Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts. RESULTS: A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87-1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72-1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade ≥3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043). CONCLUSIONS: Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered.

• Klíčová slova
• Antineoplastics, Metastatic, Mitoxantrone, Monoclonal antibodies, Olaratumab, Platelet-derived growth factor alpha, Prostate cancer, Receptor,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• míra přežití MeSH
• mitoxantron aplikace a dávkování   MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   patologie   MeSH
• následné studie MeSH
• prednison aplikace a dávkování   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• mitoxantron MeSH
• monoklonální protilátky MeSH
• olaratumab MeSH Prohlížeč
• prednison MeSH

• MeSH
• chromatografie na tenké vrstvě MeSH
• elektrochemie MeSH
• indikátory a reagencie MeSH
• lidé MeSH
• mitoxantron moč   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• indikátory a reagencie MeSH
• mitoxantron MeSH

Supportive care in tumour chemotherapy is a subject of intensive research. The complications of cytostatic therapy are a cause of extensive research of their pharmacological interactions and side effects. The immunologic and biochemical changes accompanying tumours are the factor that is most responsible for the worsening of the physiology of the host. Regimens containing carnitine and it's acetyl-derivative are used in many cases, among others even for preventing hepatotoxicity. Our hypothesis was to verify the supporting metabolic effects of acetyl-L-carnitine hydrochloride (ALC) in combined therapy with mitoxantrone (MX) and hepatotoxic cytostatic drugs including alkylating agents. This present report describes the effect of ALC in combination with MX on DBA/2 male mice bearing a transplantable L1210 leukemia resistant to MX. The criterion for evaluation of effect was the length of survival time of experimental animals. The proportional-hazards model quadratic in the drug dose (7) was used for survival time evaluation and optimal dose calculation. The hazard functions and the index of relative hazard were determined using Weibull distribution after logarithmic transformation of the entered data in each particular group. The dose-response curve was represented by a second-degree polynomial without absolute term. The combination therapy revealed that the optimal dose of ALC was 186 mg/kg s.c. This relation is shown in Fig.1. A significant effect of ALC (s.c.) in combined therapy with MX (6 mg/kg i.v.) given to animals bearing an experimental form of leukemia L1210/MX resistant to MX was proven at a level of probability p < or = 0.001. The effect of ALC in monotherapy was not demonstrable.

• MeSH
• acylkarnitin terapeutické užití   MeSH
• chemorezistence MeSH
• leukemie L1210 farmakoterapie   MeSH
• mitoxantron terapeutické užití   MeSH
• myši inbrední DBA MeSH
• myši MeSH
• protinádorové látky terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acylkarnitin MeSH
• mitoxantron MeSH
• protinádorové látky MeSH

The fluorometric assay of DNA alkaline unwinding [15] was applied to murine tumor DNA after in vivo treatment. Mitoxantrone (MX) whose cytostatic effect has been extensively investigated was tested as DNA damaging compound. The single-strand breaks of DNA (SSB) in ascitic tumors (EAT. P388) and in solid tumors (B16a, B16) were detected after intraperitoneal administrations of 1 and 10 mg/kg MX in the course of 1 to 96 hours. The maximal number of SSB was measured after 1 to 6 hours and DNA damage outlasted 24 to 96 hours in dependence on the dose of MX and on the type of tumor. A dependence of DNA damage induced by MX on the route of tumor implantation was found. Ascitic tumor P388 and EAT were more than 5 times more sensitive to the effects of MX than solid melanomas. The SSB correlated well with the intracellular concentration of MX in the EAT cells.

• MeSH
• časové faktory MeSH
• experimentální nádory farmakoterapie   genetika   MeSH
• injekce intraperitoneální MeSH
• játra účinky léků   MeSH
• jednovláknová DNA účinky léků   MeSH
• ledviny účinky léků   MeSH
• mitoxantron aplikace a dávkování   terapeutické užití   MeSH
• myši MeSH
• poškození DNA * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• jednovláknová DNA MeSH
• mitoxantron MeSH

We have commenced a series of experiments to evaluate the effect of carnitine derivatives on the antineoplastic activity of mitoxantrone (MX) on various animal cancers. This report describes the therapeutic effect of MX in combination with l-carnitine (LCAR) on the growth of a solid form of Ehrlich tumour inoculated into mice. LCAR was administered subcutaneously at doses of either 200 or 100mgkg(-1) on day 6 and 13 after tumour inoculation, 1h prior to the treatment with MX. Mitoxantrone was administered intravenously at doses of 3 or 6mgkg(-1). We found that LCAR had no potentiating effect on the efficacy of MX, in terms of either slowing tumour growth or increasing the survival of mice. Nevertheless, therapeutic effects can be assumed at higher doses of both drugs based on values calculated from an index of relative hazards.

• MeSH
• algoritmy MeSH
• Ehrlichův tumor farmakoterapie   patologie   MeSH
• fixní kombinace léků MeSH
• injekce intravenózní MeSH
• injekce subkutánní MeSH
• karnitin terapeutické užití   MeSH
• mitoxantron terapeutické užití   MeSH
• myši MeSH
• přežití MeSH
• protinádorové látky terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fixní kombinace léků MeSH
• karnitin MeSH
• mitoxantron MeSH
• protinádorové látky MeSH

The relationship between signal pathways MEK1/2-ERK1/2 and ATM-p53 in the response to DNA damage is not well understood. The aim of our study was to investigate the effect of mitoxantrone and two protein kinase inhibitors - caffeine (inhibitor of ATM kinase) and U0126 (inhibitor of MEK1/2 kinase) - on MOLT-4 and Jurkat leukaemic cell lines. In this work we show that the inhibition of MEK1/2 is associated with an increased mortality of cells after mitoxantrone treatment. Inhibition of ATM by caffeine delayed mitoxantrone-induced cell death in MOLT-4 cells. Mitoxantrone itself induced cell-cycle arrest and accumulation of the cells in late S and G2/M phase. Inhibition of ATM, but not of MEK1/2, abrogated mitoxantrone-induced cell-cycle arrest. Inhibition of MEK1/2 did not change mitoxantroneinduced up-regulation of p53 and p21, but inhibition of ATM markedly decreased up-regulation of p53 and p21, and p53 phosphorylation on serine 15 and serine 392. It can be concluded that: 1) mitoxantrone- induced phosphorylation of p53 on serine 15 and serine 392 is ATM dependent and MEK1/2-ERK1/2 independent. 2) ATM inhibition by caffeine prevents G2 cell arrest and in p53-positive cells MOLT-4 delays the onset of mitoxantrone-induced cell death. 3) Inhibition of MEK1/2-ERK1/2 cascade potentiates the cytostatic effect of mitoxantrone regardless of the p53 status.

• MeSH
• apoptóza * MeSH
• ATM protein MeSH
• buněčný cyklus MeSH
• butadieny farmakologie   MeSH
• DNA vazebné proteiny antagonisté a inhibitory   genetika   MeSH
• G2 fáze účinky léků   MeSH
• Jurkat buňky MeSH
• lidé MeSH
• mitogenem aktivovaná proteinkinasa 1 antagonisté a inhibitory   MeSH
• mitogenem aktivovaná proteinkinasa 3 antagonisté a inhibitory   genetika   MeSH
• mitoxantron farmakologie   MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny antagonisté a inhibitory   genetika   MeSH
• nitrily farmakologie   MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   genetika   MeSH
• proteiny buněčného cyklu antagonisté a inhibitory   genetika   MeSH
• protinádorové látky farmakologie   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ATM protein, human MeSH Prohlížeč
• ATM protein MeSH
• butadieny MeSH
• DNA vazebné proteiny MeSH
• mitogenem aktivovaná proteinkinasa 1 MeSH
• mitogenem aktivovaná proteinkinasa 3 MeSH
• mitoxantron MeSH
• nádorové supresorové proteiny MeSH
• nitrily MeSH
• protein-serin-threoninkinasy MeSH
• proteiny buněčného cyklu MeSH
• protinádorové látky MeSH
• U 0126 MeSH Prohlížeč

Dexrazoxane (DEX) selectively blocks the development of irreversible diffuse myocardial toxicity induced by anthracyclines and related antitumor agents, such as mitoxantrone (MTX). Therefore, daunorubicin (DNR) should not be administered to patients with cumulative DNR doses higher than 550 to 700 mg/m2, which we used for remission induction and consolidation therapy in patients with acute myeloid leukemia (AML). To administer further doses of anthracyclines without risks in seven relapsed AML patients and in one patient with impaired heart functions receiving consolidation therapy, we used DEX as a cardioprotective agent. Patients received DEX 30 minutes before DNR 45 mg/m2 or MTX 10 mg/m2 in doses eight to 13 times higher (DNR) or 30 to 60 times higher (MTX) in the treatment cycle with 10 high doses (2,000 mg/m2/12 hr) of cytosine arabinoside plus two doses of DNR or MTX on the fourth and fifth day. When this cycle was used as reinduction therapy, complete remission was achieved in all five cases. A cycle of MTX and etoposide was given three times with DEX as consolidation. Myelotoxicity of the treatment cycles with DEX was similar to the cycles without it. Two patients received cumulative anthracyclines doses corresponding to more than 1,300 and 1,000 mg/m2 of DNR, respectively; the remaining five relapsed patients received 550 to 850 mg/m2 of DNR, all without signs of cardiac toxicity. Delayed administration of DEX after cumulative doses of DNR 500 mg/m2 in AML patients at relapse provides cardioprotection against DNR or MTX in combination with high doses of cytosine arabinoside. This type of chemotherapy seems to be effective for remission induction in relapsed, heavily pretreated AML patients or in patients with impaired heart functions.

• MeSH
• akutní myeloidní leukemie farmakoterapie   MeSH
• daunomycin aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• kardiovaskulární látky aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitoxantron aplikace a dávkování   škodlivé účinky   MeSH
• nemoci srdce chemicky indukované   prevence a kontrola   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• razoxan aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• daunomycin MeSH
• kardiovaskulární látky MeSH
• mitoxantron MeSH
• razoxan MeSH

The aim of the present study was to investigate the subcellular localization of proteins participating in the double-strand break response pathway - p53, Mdm2, p21 and Chk2. MOLT-4 cells were pre-treated with mitoxantrone in concentrations 1 nmol/l and 5 nmol/l. The trypan blue technique was used to determine cell viability and proliferation. Western blotting was used to evaluate changes in p53, Mdm2 and Chk2 protein expression and sandwich ELISA was used to evaluate changes in the p21 protein amount. After 1 nmol/l mitoxantrone cells did not die, but their ability to proliferate was decreased. The p53 protein was activated and phosphorylated at serines 15 and 392 and accumulated in the nucleus after 24 and 48 h. The Mdm2 protein was present in the cytoplasm with its maximal level after 8 and 16 h. The p21 protein was detected in the nucleus after 24 and 48 h. Increased levels of phosphorylated Chk2 at threonine 68 were observed in the cytoplasmic fraction after 24 and 48 h of mitoxantrone treatment. We used mitoxantrone as an inducer of double-strand breaks to bring new data about the subcellular distribution of proteins responding to DNA damage. In MOLT-4 cells, the p53 protein was activated. p53 was phosphorylated at serines 15 and 392 and accumulated in the nucleus. The Mdm2 protein was activated in advance to p53 and occurred in the cytoplasm. The p21 protein was present in the nucleus. Chk2 kinase was activated by the phosphorylation at threonine 68 and we observed increased levels of this protein in the cytoplasmic fraction.

• MeSH
• akutní lymfatická leukemie patologie   MeSH
• buněčné dělení účinky léků   MeSH
• checkpoint kinasa 2 MeSH
• cytoplazma chemie   MeSH
• dvouřetězcové zlomy DNA * MeSH
• fosforylace MeSH
• inhibitor p21 cyklin-dependentní kinasy analýza   MeSH
• lidé MeSH
• mitoxantron toxicita   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny analýza   MeSH
• nádorový supresorový protein p53 analýza   MeSH
• oprava DNA * MeSH
• posttranslační úpravy proteinů MeSH
• protinádorové látky toxicita   MeSH
• protoonkogenní proteiny c-mdm2 MeSH
• subcelulární frakce účinky léků   MeSH
• transport proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN1A protein, human MeSH Prohlížeč
• checkpoint kinasa 2 MeSH
• CHEK2 protein, human MeSH Prohlížeč
• inhibitor p21 cyklin-dependentní kinasy MeSH
• MDM2 protein, human MeSH Prohlížeč
• mitoxantron MeSH
• nádorové proteiny MeSH
• nádorový supresorový protein p53 MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny c-mdm2 MeSH
• TP53 protein, human MeSH Prohlížeč