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前沿科技及其它

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Examination of CYP3A and P-Glycoprotein-Mediated DrugDrug Interactions Using Animal Models

With the advent of polytherapy for cancer treatment it has become prudent to minimize, as much as possible, the potential for drug–drug interactions (DDI). Toward this end, the metabolic and transporter pathways involved in the disposition of a drug candidate (phenotyping) and potential f ...

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Immunosuppressors as Multidrug Resistance Reversal Agents

Multidrug-resistance (MDR) is the major reason for failure of cancer therapy. ATP-binding cassette (ABC) transporters contribute to drug resistance via ATP-dependent drug efflux. P-glycoprotein (Pgp), which is encoded by MDR1 gene, confers resistance to certain anticancer agen ...

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Multidrug Resistance in Cancer

It is becoming increasingly clear that the proliferation of human tumours is driven by a small proportion of cells, termed tumour stem cells, which have the properties of self-renewal. On analogy with stem cells for normal tissues, there are likely to be multiple mechanisms, involving both intr ...

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Overcoming Multidrug Resistance by RNA Interference

The ATP-binding cassette (ABC)-transporter P-glycoprotein (Pgp, also known as ABCB1) is the best characterized factor involved in multidrug resistance (MDR) of cancer cells. Pgp, which is encoded by the MDR1 gene, acts as a membrane-embedded drug extrusion pump for multiple structural ...

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Circumventing Tumor Resistance to Chemotherapy by Nanotechnology

Patient relapse and metastasis of malignant cells is very common after standard cancer treatment with surgery, radiation, and/or chemotherapy. Chemotherapy, a cornerstone in the development of present day cancer therapy, is one of the most effective and potent strategies to treat mali ...

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Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets

Resistance of tumor cells to several structurally unrelated classes of natural products, including anthracyclines, taxanes, and epipodophyllotoxines, is often referred as multidrug resistance (MDR). This is associated with ATP-binding cassette transporters, which func ...

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Molecular Mechanisms of Drug Resistance in Single-Step and Multi-Step Drug-Selected Cancer Cells

Multidrug resistance (MDR) remains one of the key determinants in chemotherapeutic success of cancer patients. Often, acquired resistance is mediated by the overexpression of ATP-binding cassette (ABC) drug transporters. To study the mechanisms involved in the MDR phenotype, inv ...

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Mechanisms of Multidrug Resistance in Cancer

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activat ...

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Studying Drug Resistance Using Genetically Engineered Mouse Models for Breast Cancer

The generation of genetically engineered mouse models (GEMMs) that mimic breast cancer in humans provides new tools to investigate mechanisms of drug resistance in vivo. The advantages are manifold: inbred mice do not have the genomic heterogeneity seen in patients; mammary tumors are su ...

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Pharmacogenetics of ATP-Binding Cassette Transporters and Clinical Implications

Drug resistance is a severe limitation of chemotherapy of various malignancies. In particular efflux transporters of the ATP-binding cassette family such as ABCB1 (P-glycoprotein), the ABCC (multidrug resistance-associated protein) family, and ABCG2 (breast cancer resista ...

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Manual Microdissection

The new opportunities of modern assays of molecular biology can only be exploited fully if the results can be accurately correlated to the tissue phenotype under investigation. This is a general problem of non-in situ techniques, whereas results from in situ techniques are often difficult to ...

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A Decade of Cancer Gene Profiling: From Molecular Portraits to Molecular Function

Cancer gene profiling has greatly profited from the progress in high-throughput technologies including microarray-, sequencing-, and bioinformatics-based methods. The flood of data generated during the last decade has provoked a panel of “-omics” fields that significantly cha ...

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Mining Expressed Sequence Tag (EST) Libraries for Cancer-Associated Genes

Originally established in the beginning of the 1990s as a direct route to gene finding, expressed sequence tags (ESTs) still lend themselves as a means to analyze gene expression in almost all human tissues. The type of questions that can be addressed using public EST libraries ranges from tissue- ...

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Automated Fluorescent Differential Display for Cancer Gene Profiling

Since its invention in 1992, differential display (DD) has become the most commonly used technique for identifying differentially expressed genes because of its many advantages over competing technologies such as DNA microarray, serial analysis of gene expression (SAGE), and subt ...

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Manual Microdissection Combined with Antisense RNALongSAGE for the Analysis of Limited Cell Numbers

Establishing a gene expression profile of defined subtypes of cells within an organ is still challenging because it frequently requires microdissection and subsequent amplification of the limited amount of messenger RNA (mRNA) isolated from the microdissected tissue in order to be ...

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Quantitative DNA Methylation Profiling on a High-Density Oligonucleotide Microarray

Recently, the analysis and functional elucidation of CpG island methylation has become a focus area of genomic research. Deviations from the normal parental imprinting pattern have been shown to cause developmental defects associated with serious symptoms. Aberrant DNA methyla ...

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Epigenetic Regulation of Multidrug Resistance 1 Gene Expression: Profiling CpG Methylation Status Using Bisulphite Sequencing

Methylation of CpG dinucleotides is one of the major epigenetic processes involved in the regulation of gene expression. Catalyzed by DNA methyltransferases, hypermethylation of CpG islands in promoter regions is typically associated with gene silencing. DNA methylation plays ...

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Targeted Chemotherapy in Drug-Resistant Tumors, Noninvasive Imaging of P-Glycoprotein-Mediated Functional Transport in Cancer, and Emerging Role of Pg

Multidrug resistance (MDR) mediated by overexpression of P-glycoprotein (Pgp) is one of the best characterized transporter-mediated barriers to successful chemotherapy in cancer patients and is also a rapidly emerging target in the progression of neurodegenerative disorde ...

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Flow Cytometric Evaluation of Multidrug Resistance Proteins

There are several ways to detect proteins on cells. One quite frequently used method is flow cytometry. This method needs fluorescently labeled antibodies that can attach selectively to the protein to be investigated for flow cytometric detection. Flow cytometry scans individual cel ...

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Detection and Genotyping Analysis of Human Papillomavirus Isolates from Liquid-Based Cervical Cytology Specimens

The detection of oncogenic subtypes of human papillomavirus (HPV) from exfoliated cervical cells collected in liquid-based preservative fluid at the time of the annual Pap test can be accomplished using PCR-based amplification methods. DNA sequence analysis of the L1 open reading fra ...

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