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The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a ...
This eighth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses in detail the classification of the CNS tumors as well as brain tumor imaging. Scientists and Clinicians have contributed state of the art chapters on their respective areas of expertise, providing the reader a whole field view of the CNS tumors and brain tumor imaging in Europe. This fully illustrated volume: Explains the genetics of malignant brain tumors and gene amplification using quantitative-PCR; Presents a large number of standard and new imaging modalities, including magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, amide proton transfer imaging, ...
The vertebrate brain contains neurons and 3 classical types of glia cells, astrocytes, oligodendrocytes and microglia. Astrocytes and microglia have mainly been studied in gray matter, whereas oligodendrocytes myelinate white matter tracts. Until recently microglial effects were considered mainly during pathological conditions, but is now known that microglia plays important roles also in normal brain function. All these 3 glial cell types and their collaboration with neurons are important for learning. The concept that glia cells are important for cognitive function is not new. A glial-neuronal theory of brain function was proposed by Galambos in 1961. Hyden and Egyhazi demonstrated glial R...
The invasive character of a primary cancer is greatly dependent on numerous interactions between tumor cells and their extracellular surroundings. Matricellular receptors are defined as (cell-surface) receptors that bind extracellular matrix (ECM) structural proteins and soluble factors dynamically acting on ECM homeostasis. Matricellular receptors mediate numerous signalings from the extracellular environment to cell nucleus and drive main biological functions that are cell growth, survival and migration. Numerous data from the last decade evidence that matricellular receptors are biosensors that allow to a tumor cell answering to microenvironmental variations, and in this sense they are im...
Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.
TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifier...
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