The Synergistic Anticancer Traits of Graphene Oxide Plus Doxorubicin Against BT474 and MCF7 Breast Cancer Stem Cells In Vitro.

Breast cancer is among the leading causes of death due to cancers around the globe. Current therapeutic approaches towards healing of breast cancer have been associated with poor outcomes. Graphene and its derivatives have a two-dimensional flat structure, which is characterized by the ability to carry drugs and modify the surface, low cytotoxicity, and high biocompatibility. This study was performed on MCF7 and BT474 human breast cancer cells. Different concentrations of doxorubicin (DOX), graphene oxide (GO), and graphene oxide plus doxorubicin (GO-DOX) were subjected to both cell lines at specified intervals. At the end of the treatments, MTT test was applied to determine the viability of cells, and then flow cytometry, colony formation, and spheroid tests were implemented in both cell lines treated with DOX, GO, and GO-DOX components. We used DLS and TEM to confirm the GO properties. According to the MTT test results, 1 µL of DOX at 10 mg/ml (equivalent to 0.1 mg/ml) caused 50% survival of MCF7 cells at 24 h. In both cell lines, an increase in apoptosis occurred after incubation with GO and DOX. Although a rate of mortality of MCF-7 cells was due to necrosis, the BT474 cell death was merely through the apoptosis. Furthermore, the results of the colony formation test outlined an enhancing inhibitory effect in the presence of GO-DOX as a comparison to the control. Additionally, spheroids formed following treatment with GO-DOX exhibited a significant decrease compared to their control group, with an increase in the number of spheroids in BT474 cells compared to those in the MCF-7. The decreasing effect of compounds against the migration and cell invasion potential was also observed, being higher in MCF7 than BT474 cells. The effects of cytotoxic GO were observed at higher concentrations.

Proteomics analysis of human oligodendroglioma proteome.

Proteomics analyses enable the identification and quantitation of proteins. From a purely clinical perspective, the application of proteomics based on innovations, may greatly affect the future management of malignant brain tumors. This optimism is based on four main reasons: diagnosis, prognosis, selection of targeted therapy based on molecular profile of the brain tumor and monitoring therapeutic response, or resistance. We extracted the proteins of tumor and normal brain tissues, and then evaluated the protein purity by Bradford test. In this study, we separated the proteins by two-dimensional (2DG) gel electrophoresis methods. Then spots were analyzed, compared using statistical data and specific software and were identified by pH isoelectric, molecular weights and data banks. The protein profiles were determined using 2D gel electrophoresis and MALDI TOF/TOF mass spectrometry approaches. Simple statistical tests were used to establish a putative hierarchy in which the change in protein level was ranked according to a cut-off point with p<0.05. The 2D gel showed a total of 1328 spots among which 157 spots were under-expressed and 276 spots were overexpressed. Most proteins are subjects to post-translational modifications, where amino acid residues may be chemically modified or conjugated by small proteins like ubiquitin. Proteomics is a powerful way to identifying multiple proteins which are altered following a neuropharmacological intervention in a CNS disease.

Cluster and Principal Component Analysis of Human Glioblastoma Multiforme (GBM) Tumor Proteome.

BACKGROUND: Glioblastoma Multiforme (GBM) or grade IV astrocytoma is the most common and lethal adult malignant brain tumor. Several of the molecular alterations detected in gliomas may have diagnostic and/or prognostic implications. Proteomics has been widely applied in various areas of science, ranging from the deciphering of molecular pathogen nests of discuses. METHODS: In this study proteins were extracted from the tumor and normal brain tissues and then the protein purity was evaluated by Bradford test and spectrophotometry. In this study, proteins were separated by 2-Dimensional Gel (2DG) electrophoresis method and the spots were then analyzed and compared using statistical data and specific software. Protein clustering analysis was performed on the list of proteins deemed significantly altered in glioblastoma tumors (t-test and one-way ANOVA; P< 0.05). RESULTS: The 2D gel showed totally 876 spots. We reported, 172 spots were exhibited differently in expression level (fold > 2) for glioblastoma. On each analytical 2D gel, an average of 876 spots was observed. In this study, 188 spots exhibited up regulation of expression level, whereas the remaining 232 spots were decreased in glioblastoma tumor relative to normal tissue. Results demonstrate that functional clustering (up and down regulated) and Principal Component Analysis (PCA) has considerable merits in aiding the interpretation of proteomic data. CONCLUSION: 2D gel electrophoresis is the core of proteomics which permitted the separation of thousands of proteins. High resolution 2DE can resolve up to 5,000 proteins simultaneously. Using cluster analysis, we can also form groups of related variables, similar to what is practiced in factor analysis.

The Study of "Dihydropyrimidinase Related Proteins (DRPs)" Expression Changes Influence in Malignant Astrocytoma Brain Tumor.

BACKGROUND: Dihydropyrimidinase Related Proteins (DRPs) have known homologous to the Collapsing Response Mediator Proteins (CRMPs). The DRP gene family has comprised four members, DRP 1, 2, 3, and 4, all out of which have considered to be involved in axonal outgrowth and path-finding. METHODS: The protein has extracted from tumor, normal brain tissues, and then the protein purity has evaluated by Bradford test and spectrophotometric methods. In this study, proteins has separated by Two-Dimensional Gel (2DG) electrophoresis method and then spots have analyzed and compared using statistical data and specific software (Progenesis Same Spots).Spots have identified by pH isoelectric, molecular weights and data banks. RESULTS: The 2D gel has shown 800 spots totally. Two spots have reported for DRP2, and one spot has reported for DRP3 in the human brain proteome, that have differed in pH isoelectric, and Molecular Weights values. CONCLUSION: This protein family has involved in neuronal differentiation and axonal guidance, and abundantly influenced in the developing brain, but their expression persisted into adulthood. DRP2 has regulated by phosphorylation, Glycogen synthase kinase 3, regulate phosphorylation of DRP2 an inactive from, and induced neuronal polarity.

The investigation of changes in proteins expression (Apolipoprotein A1 and albumin) in malignant astrocytoma brain tumor.

OBJECTIVE: Angiogenesis performs a critical role in the development of cancer. Angiogenesis research is a cutting-edge field in cancer research. Proteomics is a powerful tool in identifying multiple proteins that are altered following a neuropharacological intervention in a disease of the central nervous system. Diagnostic oncoproteomics is the application of proteomic techniques for the diagnosis of malignancies. MATERIALS AND METHODS: We extracted proteins of tumor and normal brain tissues and then evaluated the protein purity by Bradford test and spectrophotometery method. In this study, we separated proteins by two-dimensional (2D) gel electrophoresis method and the spots were then analyzed and compared using statistical data and specific software, after providing three-dimensional images of spots alteration. Spots were identified by pH isoelectric, molecular weights, and data banks. RESULTS: Simple statistical test were used to establish a putative hierarchy in which the change in protein level were ranked according a cutoff point with P < 0.05. Apolipoprotein A1 (apo A1) protein and albumin were consistently upregulated in astrocytoma brain tumors. CONCLUSION: The vascular microenvironment of glioma play a major role in determining the pathophysiological character is tics of the tumor. apo A1 and albumin are very significant due to their functional consequences in glioma tumor growth, migration and angiogenesis.