2009年1月10日星期六

Principles of cancer biology

Principles of cancer biology
Dramatic technical advances in the areas of molecular biology, eukaryotic cell biochemistry, cellular immunology, virology, cytogenetics, cell culture, and animal models of multistage carcinogenesis have provided significant new insights into the molecular basis of cancer biology. This understanding already has opened new doors to the treatment of cancer.
One such advance is a novel treatment based on the construction of a monoclonal antibody targeted against a specific cancer cell gene product (e.g., an aberrant cell growth factor receptor) to treat certain forms of aggressive breast cancer. Other advances include progress in the use of steroid hormone antagonists, such as tamoxifen, not only to treat existing breast cancer but also to prevent the emergence of new breast cancers in highrisk women.
1. Cellular nature of cancer biology
1.1 Cell structure
On the use of normal cells transformed in vitro by viruses, irradiation, or chemical carcinogens have allowed the identification of cellular features that distinguish the cell biology of cancer cells from that of normal cells. cancer cells in cell cultures show an increased nucleus-to-cytoplasm ratio characterized by increased nuclear size, enlarged nucleoli, and irregular chromatin distributions. Cancer cells in cell culture also appear to be more rounded in overall shape in contrast to noncancerous cells, which appear flattened along the growth surface. The rounded appearance is linked to changes in the structural organization of actin polymers in the cell cytoskeleton.
1.2 Loss of Contact Inhibition During Cell Proliferation
Typically, cancer cells fail to stop proliferating when cell density reaches that of a monolayer of cells in contact with one another (i.e., loss of contact inhibition). The loss of contact inhibition is correlated with the loss of signaling between cells by small-molecule movement through gap junctions between adjacent cells. As a result, cancer cells overgrow and form multicell layers called foci.
2. Molecular nature of cancer biology (GENE EXPRESSION IN CANCER CELLS)
Understanding cancer at the molecular level has advanced rapidly because of expanded knowledge about how select sets of regulatory genes control cell proliferation and cell differentiation. Now accepted is that human tumors arise largely through a sequence of multiple alterations in specific families of cell regulatory genes. Generally, the gene families have been classified either as altered genes (termed oncogenes) in which functional activation in the cell was tied strongly to cancer causation or as altered genes (termed tumor suppressor genes) in which functional loss in the cell strongly supported cancer development. Characteristically, activation of oncogenes increases cell proliferation, whereas inactivation of tumor suppressor genes increases cell proliferation by abrogation of their normal function of blocking cell proliferation.
Fundamentally, cancer is a genetic disease resulting from mutations affecting genes that control normal cell function (proto-oncogenes and tumor suppressor genes) or from polymorphic gene activity governing enzyme systems that either activate or detoxify environmental carcinogens ( phase I and phase II enzyme reactions).
Knowledge of the cellular and molecular basis of cancer has contributed to marked advances in the diagnosis and treatment of this disease. Advances in understanding the molecular characteristics of cancer have led to a number of new strategies for cancer treatment that offer the advantages of being more specific in impeding the growth and development of cancer without general toxicity.

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