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N-cyclohexylacrylamide (NCA), the synthesized compound, was evaluated for their cytotoxic activities against HeLa cancer cell line. Also, the current study has been analyzed by the use of molecular docking as protein-ligand interactions play a vital role in drug design. The docking study of NCA was performed with BCL-2, BCL-W, MCl-1, AKT, BRAF, CDK2, VEGFR, EGFR PARP1, CDK6 proteins. The 3D structures of proteins were obtained from the protein data bank and 3D structure of NCA compounds using GAUSSIAN. The in silico molecular docking results indicated that NCA compound can inhibit cancer-related proteins and can play a role as potential lead compounds for developing new drugs for cancer therapy with chemical modification.
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BACKGROUND: Chemotherapeutics have been commonly used in cancer treatment. OBJECTIVE: In this study, the effects of Cisplatin, 5-fluorouracil, Irinotecan, and Gemcitabine have been evaluated on two-dimensional (2D) (sensitive and resistance) cell lines and three dimensional (3D) spheroid structure of MDA-MB- 231. The 2D cell culture lacks a natural tissue-like structural so, using 3D cell culture has an important role in the development of effective drug testing models. Furthermore, we analyzed the ATP Binding Cassette Subfamily G Member 2 (ABCG2) gene and protein expression profile in this study. We aimed to establish a 3D breast cancer model that can mimic the in vivo 3D breast cancer microenvironment. METHODS: The 3D spheroid structures were multiplied (globally) using the three-dimensional hanging drop method. The cultures of the parental cell line MDA-MB-231 served as the controls. After adding the drugs in different amounts, we observed a clear and well-differentiated spheroid formation for 24 h. The viability and proliferation capacity of 2D (sensitive and resistant) cell lines and 3D spheroid cell treatment were assessed by the XTT assay. RESULTS: Cisplatin, Irinotecan, 5-Fu, and Gemcitabine-resistant MDA-MB-231 cells were observed to begin to disintegrate in a three-dimensional clustered structure at 24 hours. Additionally, RT-PCR and protein assay showed overexpression of ABCG2 when compared to the parental cell line. Moreover, MDA-MB-231 cells grown in 3D showed decreased sensitivity to chemotherapeutics treatment. CONCLUSION: More resistance to chemotherapeutics and altered gene expression profile were shown in 3D cell cultures when compared with the 2D cells. These results might play an important role to evaluate the efficacy of anticancer drugs to explore the mechanisms of MDR in the 3D spheroid forms.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Irinotecano/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Desoxicitidina/química , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/química , Humanos , Irinotecano/química , Proteínas de Neoplasias/genética , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , GencitabinaRESUMO
SARS-Cov-2(Covid-19) is a new strain of coronavirus and was firstly emerged in December 2019 in Wuhan, China. Now, there is no known specific treatment of Covid-19 available. COVID-19 main protease is a potential drug target and is firstly crystallised by Liu et al (2020). In the study, we investigated the drug potential of molecules that the components of an important medicinal plant Passiflora by using molecular docking, molecular dynamic and drug possibility properties of these molecules. Docking performances were done by Autodock. Chloroquine, hydroxychloroquine were used as standarts for comparison of tested ligands. The molecular docking results showed that the Luteolin, Lucenin, Olealonic acid, Isoorientin, Isochaphoside, Saponarin, Schaftoside etc. ligands was bound with COVID-19 main protease above -8,0 kcal/mol binding energy. Besides, ADME, drug-likeness features of compounds of Passiflora were investigated using the rules of Lipinski, Veber, and Ghose. According to the results obtained, it has been shown that compounds of Passiflora have the potential to be an effective drug in the COVID-19 pandemic. Further studies are needed to reveal the drug potential of these ligands. Our results will be a source for these studies.
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The novel human coronavirus was firstly emerged in December 2019 in Wuhan, China, and has spread rapidly around the world. There is no known specific effective treatment of COVID-19. The most commonly used agents against this disease both in Turkey and around the world include chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir, and remdesivir. In the study, we investigated the drug potential of molecules that the components of an important medicinal plant Hypericum perforatum by using molecular docking and drug possibility properties of these molecules. The molecular docking results showed that the most stable complex was obtained with COVID-19 main protease and hypericin/isohypericin ligands with - 11 kcal/mol binding energy. Furthermore, ADMET, drug-likeness features of compounds of H. perforatum were investigated using the rules of Lipinski, Veber, and Ghose. According to the results obtained, it has been shown that H. perforatum has the potential to be an effective drug in the COVID-19 pandemic. In the next stage, it is necessary to carry out the clinically necessary reliability studies of these components. It is thought that it can be used for the treatment of COVID-19 if our molecular docking results are found to be in high correlation with clinical studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s40495-021-00254-9.
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BACKGROUND: Targeted drug delivery is one of the recent hot topics in cancer therapy. Because of having a targeting potential under the magnetic field and a suitable surface for the attachment of different therapeutic moieties, magnetic nanoparticles are widely studied for their applications in medicine. OBJECTIVE: Gemcitabine loaded polyhydroxybutyrate coated magnetic nanoparticles (Gem-PHB-MNPs) were synthesized and characterized for the treatment of breast cancer by the targeted drug delivery method. METHODS: The characterization of nanoparticles was confirmed by FTIR, XPS, TEM, and spectrophotometric analyses. The cytotoxicities of drug-free nanoparticles and Gemcitabine loaded nanoparticles were determined with cell proliferation assay using SKBR-3 and MCF-7 breast cancer cell lines. RESULTS: The release of Gemcitabine from PHB-MNPs indicated a pH-dependent pattern, which is a desirable release characteristic, since the pH of the tumor microenvironment and endosomal structures are acidic, while bloodstream and healthy-tissues are neutral. Drug-free PHB-MNPs were not cytotoxic to the SKBR-3 and MCF- 7 cells, whereas the Gemcitabine loaded PHB-MNPs was about two-fold as cytotoxic with respect to free Gemcitabine. In vitro targeting ability of PHB-MNPs was shown under the magnetic field. CONCLUSION: Considering these facts, we may suggest that these nanoparticles can be a promising candidate for the development of a novel targeted drug delivery system for breast cancer.
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Antimetabólitos Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos , Hidroxibutiratos/farmacologia , Nanopartículas de Magnetita/química , Poliésteres/farmacologia , Antimetabólitos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/química , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Hidroxibutiratos/química , Estrutura Molecular , Tamanho da Partícula , Poliésteres/química , Proibitinas , Relação Estrutura-Atividade , Células Tumorais Cultivadas , GencitabinaRESUMO
PURPOSE: The current study was designed to evaluate the toxicity of the secondary metabolites of Lactobacillus plantarum against the human breast cancer cell line (MCF-7) and the Drosophila melanogaster. METHODS: In this study, toxicity analyses of secondary metabolites of Lactobacillus plantarum were analyzed on breast cancer cells, and the Drosophila melanogaster. After application, in the MCF-7 cell line, expression levels of RRAS-2, TP53, BCL-2, APAF-1, CASP-3, FADD, CASP-7, BOK genes; in D. melanogaster; expression levels of RAS64B P53, BUFFY, DARK, DECAY, FADD, DRICE, and DEBCL genes were determined by RT-PCR. In addition, analysis of L. plantarum secondary metabolite was performed by GC-MS method and molecular binding poses of secondary metabolites and human enzymes were investigated in silico. RESULTS: Drosophila melanogaster being used as a model organism where some of the human genes were preserved. The IC50 value of the secondary metabolite in the MCF-7 cell line was determined to be 0.0011 mg/ml. Lethal concentration 50 (LC50) and 99 (LC99) values of secondary metabolites against fruit fly adults were 0.24 mg/ml and 0.54 mg/ml, respectively. The expression levels of BCL-2 and BUFFY genes which are anti-apoptotic in human and fruit flies have been reduced, and at the same time, increased expression of DECAY, FADD, RAS64B apoptotic genes in D. melanogaster. CONCLUSION: The substance detected in the secondary metabolite content and encoded as L13 (3-phenyl-1, 2, 4-benzotriazine) has been observed to have high binding affinity in the studied genes.
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Neoplasias da Mama/patologia , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica/efeitos dos fármacos , Lactobacillus plantarum/metabolismo , Metaboloma , Probióticos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/microbiologia , Proliferação de Células , Citotoxinas/farmacologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Drosophila melanogaster/microbiologia , Feminino , Humanos , Células MCF-7 , Modelos Animais , Simulação de Acoplamento MolecularRESUMO
In the last years, miRNAs have been associated with molecular pathways of cancer and other diseases. The change of expression level of miRNA has an inhibitory role in tumorigenesis. Nevertheless, the poor bioavailability of miRNA due to the rapid enzymatic degradation is a critical handicap in cancer therapy. In this study, we designed dextran-coated iron oxide-based nanoparticle for the delivery of miR-29a to breast cancer cells and analyzed its therapeutic efficacy in vitro. Results indicated that the presence of dextran-coated magnetic nanoparticles, loaded with miR29a, enhanced the selective delivery of miR-29a. Further, miR-29a complex nanoparticles caused down-regulation of anti-apoptotic genes. These results pave the way for further investigations into the possible use of miR-29a complex magnetic nanoparticles for breast cancer therapy.
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Neoplasias da Mama/tratamento farmacológico , Dextranos/química , Compostos Férricos/química , MicroRNAs/administração & dosagem , MicroRNAs/química , Nanopartículas/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Células MCF-7RESUMO
OBJECTIVE: : Signet ring cell carcinoma is a rare subtype of colorectal carcinoma (CRC) with an associated BRAFV600E mutation. We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters. METHODS: : According to the presence of signet ring cell component, tumors were categorized into groups as follows: 0%-9%, 10%-24%, 25%-49%, and >50%. Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism. Eleven of 28 cases (39.3%) showed BRAFV600E mutation, which was also confirmed by Sanger sequencing. To elucidate the importance of existence of signet ring cell component at the molecular level, we separated cases into two groups with cut-off levels of 10% and 50%, which pertain to percentages of signet ring cells. RESULTS: : Seven of 19 cases (36.8%) under the threshold of 50% and four of nine cases (44.4%) over this threshold value demonstrated BRAF mutation. Three of 7 cases (42.8%) featuring <10% signet ring cell component and eight out of 21 cases (38.1%) showing >10% were BRAF mutated. CONCLUSIONS: : BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.
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Tumor-specific delivery of anticancer drugs by magnetic nanoparticles will maximize the efficacy of the drug and minimize side effects, and reduce systemic toxicity. The magnetic core of these nanoparticles provides an advantage for selective drug targeting as they can be targeted to the tumor site and accumulated in cancer cells by means of an external magnetic field. Magnetic nanoparticles can be coated with Polyamidoamine (PAMAM) dendrimer and loaded with drugs. However, biomedical applications of PAMAM dendrimers are limited due to their toxicity associated with their multiple cationic charges due to terminal NH2 groups. Modifying the positively charged end groups with negatively charged COOH groups, is a satisfactory strategy for obtaining less toxic PAMAM dendrimers. Gemcitabine being an analogue of deoxycytidine, is an effective anticancer drug. However, clinical benefits of Gemcitabine are limited due to its short biological half-life. The aim of this study was to obtain an effective, less toxic targeted delivery system for Gemcitabine. Half generations, between G4.5 and G7.5, of PAMAM dendrimer coated magnetic nanoparticles (DcMNPs) were synthesized and conjugated with Gemcitabine. TEM images showed nanoscale size (12-14nm) of the nanoparticles. The zeta-potential analysis indicated a decreased negativity of surface charge in drug bound dendrimer compared to the empty nanoparticles. Gemcitabine was effectively conjugated successfully onto the surface of half-generations of PAMAM DcMNPs. It was observed Gemcitabine did not effectively bind to Generations G4 and G5. The highest drug loading was obtained for DcMNPs with Generation 5.5. Empty nanoparticles showed no significant cytotoxicity on SKBR-3 and MCF-7 cells. On the other hand, Gemcitabine loaded nanoparticles were 6.0 fold more toxic on SKBR-3 and 3.0 fold more toxic on MCF-7 cells compared to free Gemcitabine. Gemcitabine loaded on Generation 5.5 DcMNPs showed a higher stability than free Gemcitabine. About 94% of the drug was retained over 6 weeks period, at pH 7.2. Due to their targetability under magnetic field, stability, size distribution, cellular uptake and toxicity characteristics the dendrimeric nanoparticles obtained in this study can be useful a delivery system for Gemcitabine in cancer therapy.
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Dendrímeros/química , Desoxicitidina/análogos & derivados , Nanopartículas de Magnetita/química , Antineoplásicos/química , Cátions/química , Linhagem Celular Tumoral , Desoxicitidina/química , Sistemas de Liberação de Medicamentos/métodos , Meia-Vida , Humanos , Células MCF-7 , Tamanho da Partícula , Poliaminas/química , GencitabinaRESUMO
Development of novel drug-delivery systems aims to specifically deliver anticancer drugs to tumor tissues and improve the efficiency of chemotherapy, while minimizing side effects of drugs on healthy tissues and organs. However, drug-delivery systems are confronted by membrane barriers and multiple drug resistance in cancer cells. In recent years, the obtained results indicate an important role of lipids, proteins and carbohydrates in apoptosis, drug transport and the process of cellular uptake of nanoparticles via endocytosis. This article discusses the hypothesis of the relationship between cell membrane structure and nanoparticles in cancer cells.
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Antineoplásicos/administração & dosagem , Estruturas da Membrana Celular , Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias/tratamento farmacológico , HumanosRESUMO
Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine. CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nanoparticles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay. Gemcitabine loading was optimized as 30µM by spectrophotometric analyses. Drug release was highest (65%) at pH 4.2, while it was 8% at pH 7.2. This is a desired release characteristic since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4nm with uniform size-distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles. Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Quitosana/química , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Nanopartículas de Magnetita/química , Transporte Biológico , Linhagem Celular Tumoral , Quitosana/metabolismo , Desoxicitidina/química , Desoxicitidina/farmacologia , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Humanos , Células MCF-7 , Campos Magnéticos , GencitabinaRESUMO
APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compared expression levels with drug sensitive MCF-7 cell line. After RNAscope staining, slides were scanned and saved as digital images using Aperio scanner and software. Quantitative scoring utilizing the number of punctate dots present within each cell boundary was performed for the parameters including positive cell percentage and signal intensity per positive cell. In Doxorubicin and Etoposide resistant MCF-7 cell lines, APOBEC3B expression was approximately five-fold increased (23% and 24% respectively) with higher signal intensity (1.92 and 1.44 signal/cell, respectively) compared to drug sensitive MCF-7 cell line (5%, 1.00 signal/cell) with statistical significance. The increase of APOBEC3B expression in Docataxel resitant and Paclitaxel resistant MCF-7 cell lines was not very high. In conclusion, APOBEC3B expression was increased in some population of tumor cells of drug resistant cell lines. At least for some drugs, APOBEC3B expression may be related to drug resistance, subjecting to some tumor cells to frequent mutation.
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Neoplasias da Mama/metabolismo , Citidina Desaminase/metabolismo , Resistencia a Medicamentos Antineoplásicos , Antígenos de Histocompatibilidade Menor/metabolismo , Western Blotting , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Células MCF-7RESUMO
OBJECTIVE: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients. MATERIALS AND METHODS: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. RESULTS: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML. CONCLUSIONS: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.
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Interleucina-18/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Alelos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Leucemia Linfocítica Crônica de Células B/etnologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/etnologia , Risco , Turquia/epidemiologiaRESUMO
PURPOSE: X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far. The aim of this study was to investigate the association of XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNP), smoking and alcohol consumption with the risk of HNSCC in Turkish population and also to compare to these results with the ones from both Turkish and different populations in the literature. The frequencies of Arg194Trp and Arg399Gln SNPs were studied in 55 HNSCC and 69 healthy individuals. METHODS: Genomic DNA was isolated from peripheral blood and SNP was genotyped by PCR-RFLP method. RESULTS: The genotype and allele frequencies of both polymorphisms were not statistically different between the HNSCC and control groups. On the other hand, smoking and chronic alcohol consumption were associated with risk of HNSCC, but there was no association between Arg194Trp, Arg399Gln polymorphisms, smoking and alcohol consumption in HNSCC cases. CONCLUSION: These results indicate that both Arg194Trp and Arg399Gln polymorphisms were not associated with the development of HNSCC in Turkish population. In addition, the allele frequencies of polymorphisms were in line with other Turkish population results that were studied previously. However, compared to different populations, there were marked differences in allele frequencies.
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Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo de Nucleotídeo Único , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Frequência do Gene , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Turquia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population. The frequencies of Thr241Met SNP were studied in 58 laryngeal cancer cases (SSC) and 67 healthy individuals. Genomic DNA was isolated from peripheral blood samples of both controls and laryngeal cancer cases. Thr241Met SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of Thr241Met polymorphism were not statistically significant between the laryngeal cancer and control groups. Carrying mutant allele was not associated with the risk of laryngeal cancer. On the other hand, smoking and chronic alcohol consumption were associated with the risk of laryngeal cancer but there is no association between Thr241Met, smoking and alcohol consumption in laryngeal cancer cases. These results indicate that Thr241Met polymorphism was not associated with the development of laryngeal cancer in Turkish population. However, it should be kept in mind that the association of a polymorphism with cancer susceptibility can differ due to several factors such as cancer type, selection criteria, ethnic differences and size of the studied population.
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Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Laríngeas/genética , Polimorfismo de Nucleotídeo Único , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Humanos , Neoplasias Laríngeas/epidemiologia , Fumar/epidemiologia , Turquia/epidemiologiaRESUMO
PURPOSE: The purpose of this study was to evaluate the relationship between -174G/C interleukin-6 (IL-6) gene promoter polymorphism and susceptibility to chronic lymphocytic (CLL), chronic myelogenous (CML) and acute myelogenous leukemia (AML) in Turkish patients. METHODS: The frequencies of -174G/C polymorphism were studied in 23 unrelated CLL, 25 CML and 17 AML patients and 30 healthy individuals. Single nucleotide polymorphisms (SNPs) were genotyped by the PCR-RFLP method. RESULTS: A higher prevalence of the C allele was found in CLL, CML and AML patients. However, there were no statistically significant differences regarding either the genotype or the allelic frequencies of the -174G/C polymorphism between CLL, CML and AML cases. CONCLUSIONS: These results indicate that C allele is associated with risk of CLL, CML and AML susceptibility in Turkish patients.
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Predisposição Genética para Doença , Interleucina-6/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide/genética , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Genótipo , Humanos , Risco , TurquiaRESUMO
Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500µg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/administração & dosagem , Idarubicina/administração & dosagem , Nanopartículas de Magnetita/administração & dosagem , Antineoplásicos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Feminino , Ácido Fólico/metabolismo , Humanos , Idarubicina/metabolismo , Células MCF-7RESUMO
The ends of chromosoms, telomeres are bound with a number of proteins which protect and stabilize telomeres against degredation, end to end fusion and aberrant recombinations. Telomeric DNA is bound of two groups of proteins, which are double-stranded telomeric DNA bindings proteins, and single stranded telomeric binding proteins. Among telomere binding proteins, protections of telomere 1 protein is a single stranded telomere binding proteins and suggested to be a significant player for telomere elongation and has an association with an enzyme called as telomerase which is an intrinsic reverse transcriptase. Telomerase synthesizes hexameric telomeric repeats onto the chromosomes thereby compansating telomere loss in immortal cells, such as tumor cells, whereas telomeres are shorthened with each division in normal cells. PCR-based TRAP (telomeric repeat amplification protocol) assay is a very sensitive assay for the detection of enzymatic activity of telomerase even if a few numbers of cancerous cells are available. The association between telomerase activity and hPOT1 expression in colorectal cancer is still unclear. Protein extraction was performed from specimens of matched normal and colorectal cancer specimens. Protein concentrations were determined by Bradford assay. Optimized protein concentrations were used for TRAP Assay. TRAP products were seperated by vertical gel electrophoresis on 12.5% polyacrylamide gels and visualized by silver staining. Gene expression of hPOT1 was determined by qPCR analysis. The results demonstrated that all tumor tissues were telomerase positive whereas all corresponding normal tissue was telomerase negative. Among clinicopathological findings, telomerase activity was found to be associated with stage, histology, localization, distant metastasis and lymph node metastasis of tumor in the current study. Although all of the clinicopathological findings differed in the expression of hPOT1 compared to normal tissues, they did not differ from each other significantly, except side of tumor and lymph node metastasis. Telomerase activity and hPOT1 gene expression may serve as a promising tumor marker for colorectal cancer and there is a close association between the enzymatic activty of telomerase and the expression of human protection of telomere 1 gene.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Expressão Gênica/genética , Proteínas de Ligação a Telômeros/genética , Adulto , DNA/genética , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Complexo Shelterina , Telomerase/genéticaRESUMO
In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs) were prepared by coprecipitation of iron salts (Fe and Fe) by ammonium hydroxide. Characterizations of PHB-coated MNPs were performed by Fourier transform infrared spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric analysis, vibrating sample magnetometry, and transmission electron microscopy analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at different pHs were studied under in vitro conditions. The most efficient drug loading concentration was found about 87% at room temperature in phosphate-buffered saline (pH 7.2). The drug-loaded MNPs were stable up to 2 months in neutral pH for mimicking physiological conditions. The drug release studies were performed with acetate buffer (pH 4.5) that mimics endosomal pH. Doxorubicin (60%) released from PHB-MNPs within 65 hours. Doxorubicin-loaded PHB-MNPs were about 2.5-fold more cytotoxic as compared with free drug on resistant Michigan Cancer Foundation-7 (human breast adenocarcinoma, MCF-7) cell line (1 µM doxorubicin) in vitro. Therefore, doxorubicin-loaded PHB-MNPs lead to overcome the drug resistance.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Hidroxibutiratos/química , Nanopartículas de Magnetita , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Proibitinas , Fatores de TempoRESUMO
Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure - stellate cells - simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.