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Uncontrolled Proliferation (uncontrolled + proliferation)

Distribution by Scientific Domains
Life Sciences80%

Selected Abstracts

PERSPECTIVE: EMBEDDED MOLECULAR SWITCHES, ANTICANCER SELECTION, AND EFFECTS ON ONTOGENETIC RATES: A HYPOTHESIS OF DEVELOPMENTAL CONSTRAINT ON MORPHOGENESIS AND EVOLUTION

EVOLUTION, Issue 5 2003
Kathryn D. Kavanagh
Abstract The switch between the cell cycle and the progress of differentiation in developmental pathways is prevalent throughout the eukaryotes in all major cell lineages. Disruptions to the molecular signals regulating the switch between proliferative and differentiating states are severe, often resulting in cancer formation (uncontrolled proliferation) or major developmental disorders. Uncontrolled proliferation and developmental disorders are potentially lethal defects in the developing animal. Therefore, natural selection would likely favor a tightly controlled regulatory mechanism to help prevent these fundamental defects. Although selection is usually thought of as a consequence of environmental or ecological influences, in this case the selective force to maintain this molecular switch is internal, manifested as a potentially lethal developmental defect. The morphogenetic consequences of this prevalent, deeply embedded, and tightly controlled mechanistic switch are currently unexplored, however experimental and correlative evidence from several sources suggest that there are important consequences on the control of growth rates and developmental rates in organs and in the whole animal. These observations lead one to consider the possibility of a developmental constraint on ontogenetic rates and morphological evolution maintained by natural selection against cancer and other embryonic lethal defects. [source]

Brain engraftment and therapeutic potential of stem/progenitor cells derived from mouse skin

THE JOURNAL OF GENE MEDICINE, Issue 4 2006
Patrizia Tunici
Abstract Skin stem/progenitor cells (SKPs) derive from the dermis and in culture can generate mesodermal and neural progenies. To investigate their potential for the treatment of brain diseases, we first injected SKPs into the brain of syngeneic mice. Brain histology indicated that most SKPs remained undifferentiated and clustered at the injection site, while, in vitro, 17% of SKPs expressed neural markers, as assessed by flow cytometry. After labeling with magnetodendrimers, murine and human SKPs were detected by magnetic resonance imaging even 5 months after brain injection. To evaluate their therapeutic potential on malignant gliomas, IL-4 SKPs (i.e. SKPs transduced by a lentiviral vector carrying the cDNA of the anti-glioma cytokine interleukin-4) were injected into GL261 experimental gliomas. IL-4-SKPs prolonged significantly the survival of tumor-bearing mice: furthermore, GL261 gliomas attracted SKPs originally injected into the contralateral hemisphere. Thus, prolonged survival, capacity for transgene expression, and lack of uncontrolled proliferation suggest that SKPs warrant further consideration as therapeutic tools for brain tumors and, possibly, other neurological disorders. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Inhibition of protein kinase CK2 leads to a modulation of androgen receptor dependent transcription in prostate cancer cells

THE PROSTATE, Issue 2 2007
Claudia Götz
Abstract BACKGROUND The androgen receptor (AR) mediates the biological responses of androgens in the prostate gland. In prostate cancer, this pathway is often deregulated and causes an uncontrolled proliferation. METHODS The current study focuses on the effects of an inhibition of protein kinase CK2 on the AR-mediated transcription in LNCaP prostate cancer cells. We used chemical inhibitors of CK2 as well as dominant-negative kinase mutants to downregulate the CK2 activity. We determined the effects of the inhibition by Western blot analysis of endogenous target genes of the AR as well as by reporter assays. RESULTS We found that inhibition of CK2 led to a downregulation of the AR-dependent transcription. Moreover, the amount of the AR protein decreased significantly. CONCLUSION According to the fact that AR pathways are involved in the development and progression of prostate cancer, the ability to modulate AR function should provide an alternative basis for the development of new cancer therapies. Prostate © 2006 Wiley-Liss, Inc. [source]

The theoretical basis of cancer-stem-cell-based therapeutics of cancer: can it be put into practice?

BIOESSAYS, Issue 12 2007
Isidro Sánchez-García
In spite of the advances in our knowledge of cancer biology, most cancers remain not curable with present therapies. Current treatments consider cancer as resulting from uncontrolled proliferation and are non-specific. Although they can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but recent developments indicate that different types of cells contribute to the tumour structure, and that the tumour's cellular organization would be analogous to that of a normal tissue, with a main mass of differentiating cells sensitive to anti proliferative agents, together with a small percentage of quiescent, resistant stem cells responsible for replenishing the tumour: the Cancer Stem Cells (CSCs). Anti-CSCs targeted therapeutic agents would prevent tumour regeneration. New mouse models tailored to exploit this novel concept will be critical to develop CSC-based anti-cancer therapies. Here we review the biological basis and the therapeutic implications of the stem-cell model of cancer. BioEssays 29:1269,1280, 2007. © 2007 Wiley Periodicals, Inc. [source]