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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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. ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...