جستجوی مقالات مرتبط با کلیدواژه « Docetaxel » در نشریات گروه « پزشکی »

Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity.
In this study, nano-niosomes were introduced for improving therapeutic index of DXL.
In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments.
DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. 
Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Owing to the synergistic effects of omega-3 fatty acids with chemotherapeutic agents in boosting response rates in gastric cancer (GC) patients, they became a promising addition to cancer therapy. Due to microRNAs (miRNAs) involvement in various cellular functions, their alterations in response to therapeutic interventions can offer insight into the efficacy of treatments. Our objective was to investigate docosahexaenoic acid (DHA) effects in conjunction with docetaxel on miR-30a-5p and miR-126-5p expressions in the MKN-45 cell line.

The CancerMIRNome database was used to investigate miR-30a-5p and miR-126-5p expression changes, as well as their relation to diagnosis and survival in GC patients. Then, MKN-45 cells were treated with docetaxel, DHA, and their combination. Later, RT-qPCR was performed to measure miR-30a-5p and miR-126-5p expression levels.

It was discovered that miR-30a-5p and miR-126-5p expression were both decreased in GC patients and associated with GC diagnosis and survival, respectively. Following treatment with docetaxel and docetaxel-DHA, miR-30a-5p and miR-126-5p expression levels increased. Of course, the increase in miRNAs' expression observed in the combination form was not as strong as docetaxel alone. DHA alone decreased miR-30a-5p and miR-126-5p expressions.

miR-30a-5p and miR-126-5p have important roles in GC tumorigenesis, and response to docetaxel and DHA. Attenuating effects of DHA on miR-30a-5p and miR-126-5p expression levels appear to counteract the beneficial effects of docetaxel on these miRNAs. Therefore, even though there is evidence of the anti-cancer effects of DHA in GC, not all DHA effects are anti-cancer.

Autophagy is a conservative mechanism for cell survival as the main response of cells to stress conditions. The present study aimed to assess the effect of docetaxel on the survival, fertilization, and expression of autophagy-related genes in vitrified oocytes.  The study was conducted in 2018 at the Stem Cells Technology Research Center, Shiraz University of Medical Sciences (Shiraz, Iran). Denuded oocytes were randomly selected and assigned to five groups, namely control (n=133), docetaxel (n=136), docetaxel+cryoprotectants (n=146), docetaxel+vitrification (n=138), and vitrification (n=145). The effect of vitrification on the expression of autophagy-related gene 5 (ATG5) and Beclin-1 was determined using a real-time polymerase chain reaction. Data were analyzed using SPSS software (version 26.0) and GraphPad Prism 9. Survival and fertilization rates in each experimental group were significantly reduced compared to the control group (P=0.001). After in vitro fertilization of oocytes, the 2-cell formation rate was significantly reduced in the docetaxel+vitrification and vitrification groups compared to the control and docetaxel groups (P=0.001 and P=0.001, respectively). Pre-incubation of oocytes with docetaxel reduced gene expression levels of Beclin-1 and ATG5 in the docetaxel+cryoprotectants and docetaxel+vitrification groups (P=0.001 and P=0.019, respectively). The expression level of these genes was also reduced in the docetaxel group compared to the control group (P=0.001).  Incubation of mouse metaphase II oocytes with docetaxel prior to vitrification reduced the expression of autophagy-related genes and increased survival and fertilization rates compared to untreated oocytes.

Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemosensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on GC cells.

MTT test was applied to determine the IC50 of docetaxel and the combined effect of B7-H7 siRNA and docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony‑forming ability, wound healing assay and colony formation test were employed, respectively.

B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and docetaxel in MKN- 45 GC cells. Also, B7-H7 suppression alongside docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes.

B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating GC.

Breast cancer is a common term for a malignant tumor that arises from the epithelial component of the breast. Concurrent chemoradiotherapy’s efficacy and safety are controversial, considering the impact on patients' quality of life.

The aim of this study was investigating the efficacy and safety of concurrent chemoradiotherapy with docetaxel in locally advanced breast cancer who have received a modified radical mastectomy.

A cohort of 110 female patients with locally advanced breast cancer were included in the present study and divided by chemoradiotherapy mode into a concurrent chemoradiotherapy group (n=58) and a sequential chemoradiotherapy group (n=52). Docetaxel was administered concurrently during radiotherapy in the concurrent group, whereas the sequential group underwent adjuvant radiotherapy 1-3 weeks after chemotherapy. Then, the two groups were compared with respect to clinical efficacy, levels of tumor markers across vascular endothelial growth factor (VEGF) and Carcinoembryonic antigen (CEA), adverse reactions, and the 3-year overall survival (OS) rate.

The results showed that the mean age, operation, evaluation of Post treatment VEGF (pg / mg) and Post treatment CEA (/g / L), effectiveness of treatment in two sequential and concurrent treatment groups was not significant The results showed that the amount of Prior treatment VGEF (pg / mg) and Post treatment VGEF (pg / mg) in the two groups were statistically significant difference. Which shows the positive effect of this treatment before and after the intervention. Comparison of survival time in the two groups did not show a significant difference.

The chemotherapy protocol with a combination of cyclophosphamide, fluorouracil and epirubicin with concurrent docetaxel presented higher efficacy and prolonged the overall survival in locally advanced breast cancer patients who had undergone a radical mastectomy, while it did not significantly increase the toxicity.

To investigate the clinical efficacy and safety of docetaxel in combination with cisplatin in comparison of standard methods of in treatment of platin-sensitive ovarian cancer regimens and in addition to radiotherapy for whole abdomen radiotherapy in platin-sensitive recurrent ovarian cancer and the effect on the levels of VEGF and MMP-2.

We recruited a total of 160 platin-sensitive recurrent ovarian cancer patients between April 2017 and April 2020 who were treated in this hospital, and assessed them based on the treatment chemotherapy and radiotherapy regimens to control, the docetaxel+cisplatin, and Whole abdomen radiotherapy groups. Patients in the control group received the co-medication of paclitaxel and carboplatin, while those in the docetaxel+cisplatin group received the docetaxel in combination with cisplatin. Following treatment, we compared the clinical efficacy, levels of vascular endothelial growth factor (VEGF) and MMP-2 and safety of these three methods between two groups.

the total effectiveness rate of the docetaxel+cisplatin group was 69.09%, significantly higher than 16.36% in the control group and 24% in WAR group (P<0.05). Besides, it was found that treatment in the docetaxel+cisplatin group decreased the levels of VEGF and MMP-2 in serum of patients more evidently than those in the control and whole abdomen radiotherapy groups (P<0.05).

docetaxel in combination with cisplatin performs well, with significant decreases in the levels of VEGF and MMP-2 and reliable safety; while there was a high rate of adverse reactions in patients undergoing whole abdomen radiotherapy.

Cancer is still a serious disease with high incidence over the past decades. Many anticancer drugs are discovered and used to treat cancer, among them, taxanes such as paclitaxel and docetaxel have high lipophilicity and low aqueous solubility which is further magnified considering the strong need for administering them by intravenous infusion. Currently, the poor water-solubility of taxanes is improved by prodrug formation, conjugation, inclusion complexation, micellar solubilization and liposome-based formulations. Recent achievements for solubilization of taxanes are reviewed and critically discussed regarding their pharmaceutical and chemical applications.

Combination therapy with powerful and new components is presented as an effective method in treating breast cancer against conventional approaches. Here, we tried to evaluate the implementation of rosmarinic and thymoquinone on the tumor growth inhibition and apoptotic induction of docetaxel on MDA-MB231 breast cancer cells.

The drug interaction between rosmarinic acid, thymoquinone, and docetaxel, as the chemotherapeutic drug, was analyzed using the Chou-Talalay method along with CompuSyn. To understand the number of cell proliferation of MDAMB231 breast cancer, a tetrazolium-based colorimetric assay (MTT assay) was investigated. DAPI and the flowcytometric assay were harnessed to evaluate the morphology and the percentage of apoptosis, respectively. Real-time polymerase chain reaction (PCR) was used to recognize the association between the NF-κB pathway and program cell death signal.

The IC50 values for docetaxel, rosmarinic, and Thymoquinone were 2.6 ± 0.62 nM, 15.6 ± 2.4 µM, and 35.5 ± 3.4 μM, respectively. MDA-MB231 breast cancer showed combination index value following three combination recipes; rosmarinic acid + docetaxel, thymoquinone + docetaxel, rosmarinic acid + thymoquinone + docetaxel was 0.26, 0.55, and 0.08, which designated a remarkable synergistic effect. The cultivation of the tumor cells under the exposition of docetaxel and rosmarinic, as well as thymoquinone, discovered a substantial upsurge in the anti-proliferative manner of docetaxel from 60% to 82%, along with a double-fold surge in the number of dead cells. mRNA levels exhibited a noticeable decline in IκB-α as an indicator of NF-κB activation and the decline of survivin and Bcl-2 escorted by a surge in pro-apoptotic Bad mRNA levels (P<0.05).

By considering our results, the co-administration of docetaxel, rosmarinic, and thymoquinone can be figured out as a promising adjuvant therapy besides other treatment protocols.

MicroRNAs are involved in response to therapeutic agents and have the ability to regulate the expression level of the targets associated with cancer growth and progression. As a dangerous signal in tumor cells, increased expression level of MHC class I chain-related protein A (MICA) could activate the immune system and induce responses to tumor cells. We conducted the present research to study the effect of linoleic acid (LA) and docetaxel alone or in combination with miR-106b, miR-20a, and MICA expression level in metastatic gastric cancer (GC) cell line MKN-45.
The study was an in vitro study using the gastric cancer cell line MKN- 45, which was cultured and treated with docetaxel and LA. Subsequently, the expression level of miR-106b, miR-20a, and MICA were assessed with quantitative real-time polymerase chain reaction.
MiR-106b decreased in LA and LA/docetaxel (P < 0.0001 and P = 0.002),and increased in docetaxel alone (P = 0.01). Meanwhile, miR-20a significantly decreased in docetaxel and LA/docetaxel (P < 0.0001), increased in LA treatment (P = 0.02). Regarding MICA, it significantly decreased in all the treated cells (P < 0.0001, P<0.0001, and P=0.0002 for docetaxel, LA and docetaxel/LA, respectively) but with different reduction intensities.
Using LA or docetaxel alone had a different effect on miR-106b, miR-20a, and MICA expression level, yet in a simultaneous treatment, their positive effects were intensified. LA enhanced the effect of docetaxel concerning the expression level of miR-106b, miR-20a, and MICA and vice versa, which suggested that LA could be employed as an effective complementary agent in GC along with docetaxel.

Paclitaxel (PTX) and docetaxel (DTX) belong to the family of taxanes drugs which have been employed for treatment of ovarian, breast, lung, head, neck, gastric, pancreatic, bladder, prostate and cervical cancer. Controlled drug release systems improve the effectiveness of drug therapy by modifying the release profile, biodistribution, stability and solubility, bioavailability of drugs and minimize the side effects of anticancer drugs. So, the purpose of the present study was to synthesize the modified nanocomposite for the controlled releases of these drugs.

Magnetic magnesium iron oxide nanoparticles were synthesized via the co-precipitation chemical method and then composited with graphene oxide and modified by polyvinyl alcohol. The physicochemical characterization of the prepared nanocomposites was investigated by scanning electron microscope (SEM),  X-ray powder diffraction (XRD) , Fourier-transform infrared spectroscopy and vibrating-sample magnetometer.

Specific characteristics such as adsorption capacity, monodispersity, stability and hydrophilicity of magnetic nanomaterials were studied in the controlled release of anticancer drugs. Drug loading content and drug loading efficiency and release rate of drugs were investigated in vitro at different pH with ultraviolet-visible spectroscopy (UV-Vis). DLE and DLC of PTX and DTX in the modified magnetic nanocomposites were calculated  as 85.2 ± 2.7% and 7.74 ± 0.24% , 89.4 ± 1.2% and 8.12 ± 0.11% of, respectively. The cumulative release amount of PTX and DTX from magnetic modified nanocomposites at pHs 5.8, 7.4 over 100 h were 58 % and 40 % and 54 % and 37 %, respectively.

The potential of modified nanocomposite in drug delivery systems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of modified nanocomposite generated by different surface coatings. The generally sustained and controlled release profile of DTX (or PTX) facilitates the application of modified nanocomposite for the delivery of anticancer drugs.

Docetaxel is widely used in the treatment of metastatic breast cancer. However, its effectiveness is limited due to chemoresistance and its undesirable side effects. The combination of chemotherapeutic agents and natural compounds is an effective strategy to overcome drug resistance and the ensuing inevitable toxicities. Quercetin is a natural flavonoid with strong antioxidant and anticancer activities. This study aimed to evaluate the cytotoxic and modulatory effects of combined docetaxel and quercetin on the MDA-MB-231 human breast cancer cell line. The cell viability was assessed by MTT assay. The induction of apoptosis was examined using flow cytometry. The role of p53 in the apoptotic process was evaluated via qRT-PCR. The levels of BAX, BCL2, ERK1/2, AKT, and STAT3 proteins were measured by Western blot analysis. The results showed that the single-agent treatment with docetaxel or quercetin leads to a decrease in the viability of the MDA-MB-231 cells at 48 h. Furthermore, the combination of docetaxel (7 nM) and quercetin (95 μM) displayed the greatest synergistic effects with a combination index value of 0.76 accompanied by up regulation of p53 and a significant increase in BAX level, as well as decreases in the levels of BCL2, pERK1/2, AKT, and STAT3 proteins (P < 0.05). The concomitant use of docetaxel and quercetin leads to the cell growth inhibition associated with the induction of apoptosis and inhibition of cell survival. Therefore, this study provides a promising therapeutic approach to enhance the efficacy of docetaxel in a less-toxic manner.

The purpose of the current study was to prepare and characterize the targeted solid lipid nanoparticles(SLNs) containing docetaxel (DTX) for prostate cancer treatment. The goal has been achieved by locating anisamide (Anis) ligand on the surface of SLNs, which can interact with the overexpressed sigma receptor on the prostate cancer cells. DTX loaded SLNs were prepared by high shear homogenization and ultra-sonication method and optimized by applying experimental design. The average particle size and the entrapment efficiency of the optimum DTX-SLN were 174 ± 9.1 nm and 83 ± 3.34%, respectively. The results of differential scanning calorimetry showed that DTX had been dispersed as amorphous in the nanocarriers. Scanning electron microscopy (SEM) images confirmed the nanoscale size and spherical shape of the nanoparticles. The cytotoxicity studies have demonstrated that IC50 of free drug, DTX-SLN and DTX-SLN-Anis was 0.25 ± 0.01, 0.23 ± 0.02, 0.12 ± 0.01 nM on PC3 cell line and 20.9 ± 3.89, 18.74 ± 7.43, and 14.68 ± 5.70 nM on HEK293 cell line, respectively. Targeted DTX-SLN-Anis was acted more effectively on prostate cancer cells in comparison to DTX-SLN and free drug. The results of this study have depicted that the anti-cancer drug loaded in targeted SLNs can be a promising way for cancer treatment. In addition, performing in-vivo studies will be complementary to these findings.

Docetaxel is a chemotherapeutic agent commonly used for treatment of many cancers, including esophageal squamous cell carcinoma. Docetaxel induces G2/M phase cell cycle arrest and ultimately cell death. In this study, we aimed to assess the effects of docetaxel on YM1 cells considering exposure time and dose.

After calculating the doubling time of YM1 cells, the anti-proliferative effect of different concentrations of docetaxel () [A1]  after 24, 48 and 72 hours was assessed by the standard colorimetric assay. In addition, the effect of docetaxel on cell cycle was evaluated by flow cytometry.

The results showed that docetaxel toxicity was not significant until 24 hours at the tested concentrations (P>0.05). In addition, the effect of docetaxel on the cells was time-dependent at all tested concentrations. Overall, the duration of exposure to docetaxel had more significant role in docetaxel toxicity in YM1 cells compared to concentration.

Our findings suggest that the cytotoxicity of docetaxel on YM1 cells is time-dependent.

Poor solubility, low bio-stability, and the high toxicity of docetaxel medicine result in limited consumption, common side effects, and low efficacy. The current commercial form of the product, Taxotere®, with intravenous administration caused hypersensitivity due to hemolysis by separating hemoglobin and red blood cells. In addition, the patient suffers from a severe treatment regime through prolonging medicine injection. The most important advantages of medicine in cancer treatment are to consider patients' comfort, and acceptance during treatment, as well as to choose the most effective medicine to achieve the highest improvement in cancer cells. Following our previous study, in this study stabilized docetaxel loaded nanomicelles were used for the treatment of mice with C26 colon carcinoma. The synthesized nanomicelles have satisfying results on animal trials and adequate characters such as an oral form of medicine, particle size of less than 15 nm, proper PDI, sufficient zeta potential for physical stability and maintaining particle size, non-toxicity of career, and high efficacy than the commercial product Taxotere®. In addition, lower side effects of synthesized oral form medicine on the treatment of C26 colon carcinoma can be named as the other advantage of this study.

The stimulator of interferon genes (STING) agonist (cGAMP) kills the cancer cells through the activation of the innate immune system. PC3 cells are high in BTK and low in STING. In this study, the effect of adding STING agonist, cGAMP, to docetaxel investigated.

 PC3 cells were treated with docetaxel, cGAMP, and a combination of the docetaxel and cGAMP. Cell toxicity was evaluated by MTT assay, and changes of STING, IRF3, BTK, and DDX41 genes’ expression were quantified by the real-time PCR. STING protein was also detected by Western blotting.

 The IC50 of docetaxel was 31.1 nM, and cGAMP did not change it significantly but decreased docetaxel toxicity about 30%. Docetaxel increased IRF3, BTK, and DDX41 gene expression significantly, and STING protein about 5 folds. By adding cGAMP to docetaxel STING, IRF3, and BTK, expression decreased several folds.

 In this in vitro study, cGAMP potentiated docetaxel’s effects and alleviated it.

To investigate the effects of docetaxel combined with icotinib on tumor markers in serum and quality of life of patients with advanced non-small cell lung cancer (NSCLC).

Overall, 121 patients with advanced NSCLC, admitted to the Third Affiliated Hospital of Shandong First Medical University, China from 2017- 2018 were selected as subjects. Among them, 58 patients treated with docetaxel combined with icotinib for chemotherapy were considered as study group, and 63 patients treated with paclitaxel combined with carboplatin as control group. The clinical efficacy, adverse reactions, and ECOG scores of the two groups were observed. CEA, CA125, and SCC (Tumor markers) levels of the two groups before and after treatment were detected by chemiluminescence immunoassay (CLIA).

The leukopenia, oral mucosa ulcer and mild numbness in the control group were significantly higher than those in the study group (P<0.05). After treatment, ECOG scores of both groups decreased (P<0.05), and the ECOG score of the study group was significantly higher than that of the control group (P<0.05). The serum CEA, CA125 and SCC levels of the study group and the control group after treatment decreased significantly compared with that before treatment (P<0.05).

Application of docetaxel combined with icotinib for chemotherapy of patients with advanced NSCLC can effectively reduce the serum levels of CEA, SCC, and the CA125. Docetaxel combined with icotinib can significantly reduce adverse reactions and better improve the quality of life of patients compared with paclitaxel combined with carboplatin, which is worthy of clinical promotion.

Combination chemotherapy with new adjuvants has been introduced as an innovative method of treating various types of cancer. The aim of this study was to investigate potential synergistic effect of quinacrine on the anti-proliferative and anti-apoptotic activity of docetaxel in A549 lung cancer cells. 

Cell viability and apoptosis percentage were evaluated with MTT assay and annexin V staining. To understand the mechanisms through which quinacrine modulates expression of pro-apoptotic and anti-apoptotic genes, expression of Bcl-2, Bcl-xl and Bax genes were investigated using real-time RT-PCR.

The half maximal inhibitory concentration values for docetaxel and quinacrine was 3.16±1.5 nM and 4.4±0.58 μM, respectively. The combination index value of docetaxel and quinacrine was 0.66 against A549 cells, indicating strong synergism. The expression of anti-apoptotic genes Bcl-2 and Bcl-xl reduced significantly, while the expression of the pro-apoptotic gene Bax increased significantly after co-treatment with docetaxel and quinacrine (P<0.05). Treatment of cells with a combination of quinacrine and docetaxel significantly increased the inhibitory effect of docetaxel (reduced proliferation by 50%) and the percentage of apoptotic cells.  

Our findings suggest that the combination of quinacrine and docetaxel can be considered as a promising strategy for the treatment of patients with lung cancer.

A simple, rapid, and sensitive reversed-phase high performance liquid chromatography (RP-HPLC) method based on liquid-liquid extraction was developed and validated for
determination of docetaxel (DTX) in plasma and homogenate tissues of tumor-bearing mice. Experimental approach: Samples were spiked with celecoxib as the internal standard and separation was achieved on a μ-Bondapak C18 HPLC column. The mobile phase consisted of a mixture of acetonitrile/water (40/60 v/v) at flow rate of 1.2 mL/min and the effluent was monitored at 230 nm.

Calibration curves were linear over the concentration range of 0.1-10 μg/mL of DTX in plasma and 0.25-50 μg/mL in tissue homogenates with acceptable precision and accuracy. The mean recoveries of the drug from plasma extraction was 94.6 ± 1.44% while those of tissue homogenates ranged from 73.5 ± 3.2 to 85.3 ± 2.8% depending on the type of tissues examined. DTX was stable in biological samples with no evidence of degradation during 3 freeze-thaw cycles and two months of storage at -70 ± 15 °C.
The developed HPLC method was applied to quantify DTX in the mouse plasma and tissues after intravenous administration of 7.5 mg equivalent DTX/kg dose of DTX-loaded folic acid-polyethylene glycol-heparin-tocopherol (FA-PEG-HEP-CA-TOC) micelle formulation to female Balb/c mice.

A simple, sensitive, rapid, accurate, and prudent RP-HPLC method was developed, validated, and applied for DTX determination in plasma and tissues.