癌生物学(biology+of+cancer)

What is required for Metastasis (轉移)?
Must be able to cross the basal lamina (express type IV collagenase) Must not adhere to neighbor cells
In classic cell culture, cells form a monolayer Neoplastic cells continue to grow
Differentiation
Death
Stem cells as the target of carcinogens
Stem cell
Post mitotic Differentiated
Normal senescent differentiated cell
Benign tumor Grade 2 malignancy Grade 3 or 4 malignancy
The cells are picking up additional mutations as they divide, accounting for the phenotypic difБайду номын сангаасerences
2b:Molecular Biology of Cancer 癌分子生物學
Oncogenes Tumor suppressor genes
Where are stem cells?
Finally, the cells accumulate additional mutations that allow them to break through the basal lamina and invade other tissues. While the dysplasic state often spontaneously regresses, the malignant state does not.
Sell and Pierce, Lab Invest. 70: 6-22, 1994
Anatomy of a cancer: the progression of uterine cervix carcinoma. The dysplasic state appears when neoplastic cells begin to replace the existing epithelium, yet they still divide rather slowly and do not show signs of malignancy. The carcinoma in situ, however, is more dangerous; neoplastic cells have completely replaced the epithelium.
Newer additions to the menagerie
Tumor-suppressor genes (抑癌基因): genes whose products prevent tumor formation; when mutant, tumors result Apoptotic genes (萎凋死亡基因): genes whose products normally induce apoptosis in damaged cells Checkpoint proteins that assess DNA damage in the cell
Must be able to migrate through interstitial fluid and bloodstream to new sites
This is, of course, the normal situation, in which cells of epithelia maintain contacts with the basal lamina…
…but metastatic cells often express collagenase, allowing them to break down the lamina. In addition, they stop expressing laminin receptors and have cytoskeletal alterations…
癌化過程中什麼基因改變了？
Figure 1 | Example of a protein signalling pathway. Nature Reviews Drug Discovery 1; 683-695 (2002) Clinical proteomics: translating benchside promise into bedside reality
Cancer onset correlates strongly with age. Sporadic (non-inherited) cancers are rare before 40 years of age, but the risk climbs dramatically after that. On a log-log plot like the one in part B, the relationship looks linear, but it is actually rising roughly as the fifth power.
2a: Cancer Biology
癌細胞生物學
Clone and clonal evolution
增生中的細胞
蜇伏的細胞
Properties of stem cells (幹細胞)
3. Self renewing 1. Proliferative potential
2. Gives rise to differentiated cells
Cancer: General Etiology and Pathogenesis
Cancer Molecular Pathways
Normally, a ligand binds and causes the TK receptor to dimerize, eliciting the downstream effects--But suppose the N-terminal region is deleted, allowing receptor dimerization whether the signal is there or not---then cells could respond inappropriately to a LACK of signal as if it was there!
Pap smears, unfortunately, are only as good as the people doing and interpreting them, but they represent a good first test to detect neoplasy before it gets worse
Note in part F, the brave cell busting through the basal lamina. This is very bad for the individual who has this happening, obviously…
…which is why the Pap smear is so important. A represents normal cells, B represents dysplastic cells that are in a variety of differentiated stages, and C represents invasive carcinoma; note the embryonic features of the cells (low nucleus/cytoplasm ratio is pretty classic)
Note that cancer results ONLY if the cell is exposed to a tumor promoter repeatedly AFTER an initiator. Note also that multiple initiators may result in cancer (bottom timeline)
…that lead to the ability to move past the basal lamina into underlying tissues and eventually the circulatory sytem.
Even though a tumor is clonal, all the cells are not alike; they differ in their ability to form metastases, as this experiment clearly demonstrates
Neoplastic proteins/Oncogenes (致癌基因)
Growth factors and related hormones serving as ligands for their receptors (EGF, TGF-β, PDGF, etc.) Growth factor receptors (TK receptors, Glinked receptors, Smad receptors, etc.) Intracellular transducers (G- proteins, SH2SH3 proteins, etc.) Intracellular receptors/transcription factors that realize the ultimate result of the signal Cell-cycle control proteins
Cancers are clonal; they arise from a single cell that becomes malignant.
Shown here is a neoplastic mass among normal cells. The trick used here is to examine which X has been inactivated in the cells by using a marker of some sort. The cells around the mass exhibit random inactivation of one or the other X, while the cells in the mass are all identical. Other markers can be used to definitively demonstrate that tumors are clonal entities.
2-naphthylamine causes bladder cancer, but only does so after several years. The point is that exposure to a carcinogen and the development of cancer can be years apart, pointing out how difficult it is to attach causation to cancers.
Cellular equilibrium (細胞平衡)
Proliferation Differentiation Death
Transit Renewing Proliferating Exiting
Cancer: disruption of cellular equilibrium
Proliferation