جستجوی مقالات مرتبط با کلیدواژه "mitoxantrone" در نشریات گروه "پزشکی"

Conventional methods of cancer treatment include surgery, chemotherapy, radiation therapy, and immunotherapy. Chemotherapy, as one of the main methods of cancer treatment, due to the lack of targeted distribution of the drug in tumor tissues, is not able to destroy cancer cells and also affects healthy tissues and causes serious side effects in patients. Sonodynamic therapy (SDT) is a promising strategy for non-invasive treatment of deep solid cancer tumors. In this study, for the first time, the sono-sensitive activity of mitoxantrone was investigated and then mitoxantrone (MTX) was conjugated to hollow gold nanostructure (HGN) to improve the efficiency of in vivo SDT. 

Firstly, after the synthesis of hollow gold nanoshells and the PEGylation process, conjugation of MTX was performed. Then, after evaluating the toxicity of the treatment groups in vitro, in order to perform an in vivo study, 56 male Balb/c mice that had been tumorized by subcutaneous injection of 4T1 cells were divided into eight groups of breast tumor model. Ultrasonic irradiation (US) conditions including intensity of 1.5 W/cm2 (with a frequency of 800 kHz, 5 min), MTX concentration of 2 μM, and HGN dose of 2.5 mg/kg (unit of animal weight) were used.

The results show that administration of PEG-HGN-MTX caused a slight reduction in tumor size and growth compared with free MTX. Ultrasound also improved the therapeutic effect of the gold nanoshell in treated groups, and the HGN-PEG-MTX-US treated groups were able to significantly reduce and control tumor size and growth. 

The findings also show that MTX and HGN can be used as sonosensitizers in SDT. Also, HGN-PEG-MTX can act as a sono-chemotherapy agent for the combination of sonodynamic therapy and chemotherapy for in vivo breast tumors.

Mitoxantrone (MTX) is one of the most commonly used chemotherapeutic agents for treatment of different cancers. However, prolonged treatment with MTX results in unwanted side effects and drug resistant cancer cells. Combination therapies and exploiting of targeted nanoparticles have the potential of improving the efficiency of drug treatment as well as reducing the side effects. Curcumin (CUR) is a biological molecules with anticancer property. In this study, we investigated whether targeted PLGA (Poly Lactic-co-Glycolic Acid)–CUR nanoparticles (NPs) can reinforce the effect of MTX on breast cancer cells.

PLGA NPs containing CUR targeted with AS1411 aptamer were prepared by single emulsion evaporation method. Physicochemical properties of NPs were investigated. The cytotoxicity of non-targeted and targeted NPs along with MTX was evaluated on MCF7, 4T1 and L929 cell lines.

The results showed that PLGA-CUR NPs were synthetized with an average encapsulation efficiency of 66% with a mean size of 186±3.2 nm. The drug release of curcumin from these NPs within 72h was about 59% in neutral medium and 90% in acidic medium. Interestingly, the combined treatment with PLGA-CUR-Apt and MTX inhibited the cancer cell's proliferation significantly more than the non-targeted nanoparticles, CUR and MTX-treated group alone.

These results suggest that targeted PLGA-CUR nanoparticles may consider as a potential therapeutic contender in improving the efficacy of MTX in Breast cancer therapy.

Mitoxantrone is a chemotherapy anti-cancer drug, which can have side effects on healthy cells like secondary cancers. On the other side, Melatonin is a hormone that is responsible for the daily rhythm adjustment and has several properties to be anticancer and anti-inflammatory. Recently, it has been shown that all living cells produce ultraweak photon emission (UPE) spontaneously and continuously. The intensity of UPE is in the order of a few, up to 104 photon/(cm2 sec) (or 10−19 to 10−14 W/cm2) measurable by photodetectors. UPEs are produced from diverse natural oxidative and biochemical reactions, especially free radical reactions and the simple cessation of excited molecules. Also, it has been evidenced that UPE has a signaling role at a distance among different cell cultures.

Here, we investigate the effect of UPE among similar cells (i.e. “Autooptic effect”) by using mirrors around the cell plate(s).

In this experimental research, the HepG2 cells were co-treated by melatonin as a genoprotective and silver nanoparticles as a carrier against mitoxantrone’s genotoxicity. Our results are analyzed based on the Comet assay method, and the genoprotective effect of melatonin is investigated in presence of (and without) mirrors against the genotoxicity of mitoxantrone. Additionally, the autooptic effect is investigated in presence of Ag nanoparticles (NPs).

The results indicated that Ag NPs with lower concentrations of melatonin made more protection as genoprotective agent, and the same results obtained by increasing access’ cells to drug.

The autooptic effect could increase the genoprotective effect of melatonin.

Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α. Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results. Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α. Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.

Context:

 Mitoxantrone (MTX) is an antracyclin drug that is used for treatment of patients with chronic refractory multiple sclerosis (MS). Congestive heart failure (CHF) is a rare complication of this drug that may occur early, during therapy, or late, months or years after termination of therapy.

The aim of this study is to evaluate the long‑term adverse effect of MTX on cardiac function.

The study involved 49 MS patients on MTX therapy because of their disease was refractory to other treatments (18 men and 31 women). They were treated in two canters related to Esfahan University of Medical Sciences. The mean age was 34.65 ± 9.56 years. Systolic and diastolic left ventricular (LV) functions were measured by echocardiography. The baseline echocardiographic data were collected from patients’ file. Echocardiography was repeated by a single cardiologist in 2016.

After MTX therapy, one patient’s ejection fraction (EF) reduced below 50% (2%). In spite of their normal diastolic function before therapy, two patients developed diastolic dysfunction (4%). Nonparametric binominal analysis reveals that MTX therapy increased the probability of developing systolic dysfunction, early or late P < 001.

MS patients treated with MTX are at increased risk of developing early and late‑LV dysfunction, so all patients on MTX therapy must be periodically evaluated for these late complications.

DNA topoisomerase II alpha (Top2-α) enzyme is an important target for many anticancer drugs. A variety of TOP2A genomic variants has been found associated with the development of drug resistance to this enzyme. Here, we have characterized 2 non-synonymous single nucleotide polymorphisms (nsSNPs) including rs762022284 and rs764177670 in TOP2A gene, which could affect its response to Amsacrine and Mitoxantrone as important inhibitors of the enzyme. The nsSNPs were genotyped in the Iranian population and the data were analyzed, using PLINK and PICcalc programs. Genotyping data indicated the allele frequency of 0.30 (PIC = 0.42) and 0.05 (PIC = 0.09) for rs762022284 and rs764177670, respectively. The data suggested that the presence of rs762022284 and rs764177670 nsSNPs could affect Top2-α response to Amsacrine and Mitoxantrone, indicating the necessity of consideration of population-dependent genotypes in cancer chemotherapy, using these drugs.

  Mitoxantrone (MX) has been introduced as a photosensitizer drug. However, due to some side effects, the widespread use of this drug has been confronted with some limitations. Hollow gold nanoshells (HGN) have attracted considerable attention due to their interesting photochemical features that can use as nanocarrier. In this paper, the thermal response of MX and the use of this property for thermal effects during the photodynamic process by MX-conjugated HGN were investigated.
Material and After optimizing the synthesis of ultimate nanostructure, the characteristics of pharmacological agents including MX, HGN, methoxy polyethylene glycol (mPEG)-HGN, and MX-mPEG-HGN were determined. Then, the thermal response of MX was determined at 0-50°C. Finally, by applying light irradiation with a non-coherent source at a wavelength of 670 nm and exposures of 0 to 50 j/cm2, the profile release and temperature variation in MX-mPEG-HGN were determined. The zeta potentials of HGN and MX were negative, which resulted in electrostatic repulsion between them. In order to solve this challenge, the surface modification of HGN with mPEG was performed, resulting in the chemical bonding of the drug with the nanostructures and increasing the stability of the final nanostructure. With increasing temperature, the optical density of the drug at 660 nm significantly increased, which is an effective induction of photodynamic effect. In this study, we used mPEG-HGN as the nanocarrier for MX. Also, the thermal behavior of MX was recognized as an important factor in increasing temperature that could improve the photodynamic process

Mitoxantrone (MXT) is a drug for cancer therapy and a hazardous pharmaceutical to the environment which must be removed from contaminated waste streams. In this work, the removal of MXT by the electro-Fenton process over heterogeneous and homogenous catalysts is reported.
The effects of the operational conditions (reaction medium pH, catalyst concentration and utilized current intensity) were studied. The applied electrodes were carbon cloth (CC) without any processing (homogenous process), graphene oxide (GO) coated carbon cloth (GO/CC) (homogenous process) and Fe3O4@GO nanocomposite coated carbon cloth (Fe3O4@GO/CC) (heterogeneous process). The characteristic properties of the electrodes were determined by atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM) and cathode polarization. MXT concentrations were determined by using ultraviolet-visible (UV-Vis) spectrophotometer.
In a homogenous reaction, the high concentration of Fe catalyst (>0.2 mM) decreased the MXT degradation rate. The results showed that the Fe3O4@GO/CC electrode included the most contact surface. The optimum operational conditions were pH 3.0 and current intensity of 450 mA which resulted in the highest removal efficiency (96.9%) over Fe3O4@GO/CC electrode in the heterogeneous process compared with the other two electrodes in a homogenous process. The kinetics of the MXT degradation was obtained as a pseudo-first order reaction.
The results confirmed the high potential of the developed method to purify contaminated wastewaters by MXT.

Multiple sclerosis (MS) is a central nervous system disorder with periods of recurrence and recovery. Mitoxantrone has been approved for secondary progressive MS (SPMS) treatment but data lacks the role of corticosteroid pulse therapy in SPMS.. To evaluate the role of corticosteroid pulse therapy in patients with SPMS receiving mitoxantrone..Patients and A double blind randomized controlled clinical trial was performed on 71 patients with SPMS referred to Shahid Sadoughi Hospital (Yazd, Iran) for receiving mitoxantrone in two groups. The first group (35 patients) received 20 mg mitoxantrone plus 500 mg methylprednisolone monthly for six months. The second group (36 patients) received the same dosage of mitoxantrone plus 100 CC of 5% dextrose water monthly for six months. Expanded disability status scale (EDSS), MRI plaques in both groups before and after the treatment completion and six months after the end of trial were compared together.. 28 men and 43 women enrolled in the study. MRI plaques number reduced in groups significantly (2.29 vs. 2.17) without significant difference between the groups (P = 0.782). Six months after trial completion, plaques number increased in groups without significantly difference (0.72 vs. 0.77, P = 0.611). The mean value of EDSS showed significant reduction at the end of treatment in groups (0.79 and 0.53) without significant difference between the groups (P = 0.953). Six months after trial completion, EDSS increased in groups without significant difference (0.35 vs. 0.43, P = 0.624).. Corticosteroid pulse therapy in SPMS was effective in inflammatory process, but could not postpone or decline the neurodegenerative process and besides the imposing side effects could not result in significant improvement in EDSS and MRI plaques number in long term..

Although mitoxantrone inhibits lipopolysaccharide induction of many immunological factors, but the mechanism of action somewhat remains to be more understood.. This preliminary study was designed to investigate the evidence-based mitoxantrone therapy results in patients with multiple sclerosis (MS)..Patients and This cross-sectional study on 71 patients with MS was carried out between 2010 and 2012, in an Iranian population. Demographic and pharmacological variables were recorded in d-Base. Statistical analyses were performed using SPSS for Windows.. The females/males sex ratio within the study population was 3.17: 1. The mean age of females was 32.2 years old (range 20 - 45 years) and the mean age of males was 52.7 years old (range 45 - 64 years). Out of the total population studied, 20% received both methylprednisolone (MP) pulse therapy and mitoxantrone on at least on one occasion. The mean frequency of dose received by each individual was two, with a range of one to five.. To prevent the serious adverse effects of mitoxantrone, such as acute leukemia and secondary hematologic cancers, pharmacotherapy outcome, using disease modifying drugs, should focus on rate and severity of relapses within Iranian pateints with MS..

Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy. Anticancer effects of MTX, siRNA, and LY alone and in combination were evaluated in MCF7 cells using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. MTT and apoptosis assays showed that both MTX and LY inhibited cell proliferation and induced apoptosis in MCF7 cells. Results indicated that inhibition of BCRP by siRNA or PI3K/Akt signaling pathway by LY significantly increased sensitivity of MCF7 cells to antiproliferation and apoptosis induction of MTX. Furthermore, MTX showed G2/M arrest, whereas LY induced G0/G1 arrest in cell cycle distribution of MCF7 cells. Combination of siRNA or LY with MTX chemotherapy significantly increased accumulation of MCF7 cells in the G2/M phase of cell cycle. Combination of MTX chemotherapy with BCRP siRNA and PI3K/Akt inhibition can overcome MDR in breast cancer cells. This study furthermore suggests that novel therapeutic approaches are needed to enhance anticancer effects of available drugs in breast cancer.

The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS) is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Forty patients with aggressive relapsing remitting MS were randomly put into two groups. The first group underwent monthly plasma exchange for three successive months, followed by 12 mg/m2 mitoxantrone at the end of each course and two more doses of 6 mg/m2 mitoxantrone in 3-month intervals. The second group received the same doses of mitoxantrone only without plasma exchange. At the end of 8 months treatment course, clinical reassessment and neuroimaging was performed and treatment was continued with interferon-b. At the end of induction therapy, Expanded Disability Status Scale score was significantly improved in both groups (P < 0.001). Number of demyelinating and gadolinium-enhancing plaques in brain magnetic resonance imaging (MRI) was prominently reduced in group 2 (P £ 0.05), but the changes were not statistically significant in group 1, except for juxtacortical plaques. Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.