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前沿科技及其它

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Human Recombinant Fab Antibodies with T-Cell Receptor-Like Specificities Generated from Phage Display Libraries

In this chapter we describe efficient procedures for the construction, expression and screening of comprehensive libraries of human Fab antibody fragments displayed on the surface of filamentous phage. Phagemid vectors are used for placing randomly paired light (L) and heavy (H) chain ...

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Humanization of Monoclonal Antibodies by CDR Grafting

The discovery of the process for making rodent monoclonal antibodies (MAbs) 26 years ago by Kohler and Milstein has led to a revolution in the treatment of over 50 major diseases, and has borne an industry whose products today represent 6% of total biotechnology sales. The full potential of this indus ...

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Immunohistochemical Analysis of 8-Nitroguanine, A Nitrative DNA Lesion, in Relation to Inflammation-Associated Carcinogenesis

Chronic inflammation is induced by various infectious/infected agents and by many physical, chemical and immunological factors. Many malignancies arise from areas of infection and inflammation. Reactive oxygen species and reactive nitrogen species are considered to play the k ...

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Molecular Analysis of Genetic Instability Caused by Chronic Inflammation

Genetic instability is a hallmark of human cancers. It is the driving force for tumor development as it facilitates the accumulation of mutations in genes that regulate cell death and proliferation and therefore promotes malignant transformation. Chronic inflammation is a common und ...

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Obesity Provides a Permissive Milieu in Inflammation-Associated Carcinogenesis: Analysis of Insulin and IGF Pathways

Current dogma suggests that the positive correlation between obesity and cancer is driven by white adipose tissue that accompanies obesity, possibly through excess secretion of adipokines. However, recent studies in fatless A-Zip/F-1 mice, which have undetectable adipokine lev ...

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Detecting and Modulating the NF-kB Activity in Human Immune Cells: Generation of Human Cell Lines with Altered Levels of NF-B

NF-κB plays a pivotal role in immunity and inflammation and is considered to be a promising candidate for drug development. However, global suppression of NF-κB may have undesirable side-effects. Our data and the results of others suggest that each of the five NF-κB subunits may have a specific fun ...

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Inflammation-Related Aberrant Patterns of DNA Methylation: Detection and Role in Epigenetic Deregulation of Cancer Cell Transcriptome

It is now apparent that epigenetic abnormalities, in particular altered DNA methylation, play a crucial role in the development and progression of human cancers. DNA hypermethylation at promoter CpG islands is now recognized as a third mechanism by which inactivation of tumor suppress ...

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cDNA Microarray Analysis of Inflammatory Breast Cancer Signatures

Global gene expression profiling studies conducted over the last couple of years have shown that molecular profiling of breast cancers can be used to identify clinically and genetically significant subtypes of breast carcinomas and subgroups of patients with different prognosis or ...

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Induced Nitric Oxide Synthase as a Major Player in the Oncogenic Transformation of Inflamed Tissue

Nitric oxide (NO) is a free radical that is involved in the inflammatory process and carcinogenesis. There are four nitric oxide synthase enzymes involved in NO production: induced nitric oxide synthase (iNOS), endothelial NO synthase (eNOS), neural NO synthase (nNOS), and mitochondrial ...

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Analysis of the TLR/NF-B Pathway in Antigen-Presenting Cells in Malignancies Promoted by Inflammation

Activation of the transcription factor, nuclear factor of κB (NF-κB), has recently emerged as the critical link between inflammation and cancer. NF-κB is activated by many signals including DNA damage and microbial pathogen recognition. Although microbial infections account for an e ...

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The NF-B Transcription Factor Pathway as a Therapeutic Target in Cancer: Methods for Detection of NF-B Activity

NF-κB transcription factors marshal innate and adaptive immunity and inflammation. NF-κB also counters programmed cell death (PCD) induced by the proinflammatory cytokine tumor necrosis factor (TNF)α, and this activity of NF-κB is crucial for organismal physiology, chronic infl ...

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Inhibiting Proinflammatory NF-B Signaling Using Cell-Penetrating NEMO Binding Domain Peptides

Nuclear factor kappa B (NF-κB) is an inducible transcription factor that regulates the expression of many genes involved in normal immune and inflammatory responses. NF-κB activation is normally a rapid and transient response to pro-inflammatory stimuli however dysregulated con ...

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Quantitative Measurement of Cytokine Expression in Synoviocytes Derived from Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by pain, swelling and progressive destruction of synovial joints. The synovial membranes of the affected joints markedly increase in size due to infiltration of several cell types, of which macrophages, lym ...

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Molecular Characterization of Inflammation-Induced JNK/c-Jun Signaling Pathway in Connection with Tumorigenesis

Tumor cells recruit inflammatory cells to the tumor site and transform them into tumor-supportive cells which in turn release numerous cytokines, including Transforming Growth Factor-β that enhances tumor proliferation, invasion, angiogenesis and induces immune paralysis. ...

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Inflammation and Tumor Progression: A Lesson from TNF--Dependent FAK Signaling in Cholangiocarcinoma

Focal Adhesion Kinase (FAK) is implicated in a wide array of cellular processes and also involved in the production of matrix metalloproteinases (MMPs) which degrade extracellular matrix (ECM). We have shown that FAK plays a critical role in MMP-9 production and subsequent invasion of the ch ...

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Molecular Characterization of STAT Signaling in Inflammation and Tumorigenesis

The Janus kinases (JAK) and signal transducer and activator of transcription (STAT) signaling are strongly activated in many tumors. STAT proteins are activated by phosphorylation at the tyrosine residue, then dimerize, translocate to the nucleus and bind DNA, initiating the transcr ...

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Cyclooxygenase Inhibitors Induce Colon Cancer Cell Apoptosis Via PPAR 14-3-3 Pathway

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) induce cancer cell apoptosis via several signaling pathways. There is evidence that they induce colon cancer cell apoptosis by suppressing peroxisome proliferat ...

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PPAR/ Agonist Increases the Expression of PGE2 Receptor Subtype EP4 in Human Lung Carcinoma Cells

Lung carcinoma remains one of the most common malignant tumors in the world despite recent advancements in the development of new chemotherapeutic agents for its treatment. Therefore, novel approaches for drug target discovery play an important role in the effort to help extend its dismal 5 ...

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Investigating Macrophage and Malignant Cell Interactions In Vitro

Within most human and murine cancers there is an abundant macrophage population, attracted to the tumor microenvironment by cytokines and chemokines such as CSF-1 (M-CSF) and CCL2 (MCP-1) (Cell 124:263–266, 2006). Despite their intrinsic antitumor activity there is usually, but not alway ...

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Cellular Magnetic Resonance Imaging Using Superparamagnetic Anionic Iron Oxide Nanoparticles: Applications to In Vivo Trafficking of Lymphocytes and C

In current cancer research, the application of cytotoxic T lymphocytes with specificity to tumor antigens is regarded as a real therapeutic hope. The objective of imaging is to provide a follow-up of these killer cells in real time, in order to gain a better understanding of the mechanisms and action ...

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