Cancer

1. Cancer Source:http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.4259

2. The Cells of Multicellular Organisms operate according to ecological principles The multicellular organism is an ecosystem of individual cells, reproducing by cell division and organized into collaborative tissues and organs Ecological Processes at work: …Cell births …Cell deaths …Cellular habitats …Cellular territorial limitations …Maintaining cellular population sizes

3. But what about applying natural selection to the cells of multi-cellular organisms? What happens when the cells in a multi-cellular organism operate In a world owned by the principles of natural selection? In a healthy multi-cellular organism self-sacrifice (apoptosis)— as opposed to survival of the fittest— is the rule. But what if the rules of the cells emerged from natural selection, then, competition and mutation among somatic cells.

4. All somatic cell lineages are committed to die. Somatic cells leave no progeny. They dedicate their existence to support of the germ cells. The germ cells alone have a chance of survival. The body is a clone. The genome of the somatic cells is the same as that of the germ cells. By their self-sacrifice for the sake of the germ cells, the somatic cells help to propagate copies of their own genes.

5. Free-living bacteria compete to survive! The cells of a multicellular organism are committed to collaborate! To coordinate their behavior, the somatic cells send, receive, and interpret an elaborate set of signals that serve as social controls, telling each of them how to act! Each cell behaves in a socially responsible manner, resting, dividing, differentiating, or dying as needed for the good of the organism!

6. Molecular disturbances that upset this harmony mean trouble for a multicellular society. A human body has 1014 cells, billions of cells. These cells experience mutations every day, potentially disrupting the social controls. A mutation may give one cell a selective advantage, allowing it to divide more vigorously than its neighboring cells …to become a founder of a growing mutant clone

7. A mutation that gives rise to such ‘CELLfish’ behavior can jeopardize the future of the whole organism. If repeated rounds of mutation, competition, and natural selection operate within the population of somatic cells …then the basic ingredients of cancer spell a recipe of potential disaster. Individual mutant clones of cells prosper at the expense of their neighbors, but in the end destroy the whole cellular society.

8. Cancer is a microevolutionary process. The cancer process occurs on a time scale of months or years in a population of cells in the body, and it depends on the same principles of mutation and natural selection that govern the long-term evolution of all living organisms.

9. Evolutionary Principles • reproduce in defiance of • the normal restraints on cell division and • (2) invade and colonize territories • normally reserved for other cells.

10. If an isolated abnormal cell does not divide more than its normal neighboring cells, then it does no significant damage. But if cell division is out of control, it will give rise to a tumor, or neoplasm— a relentlessly growing mass of abnormal cells. If the neoplastic cells remain clustered in a single mass, the tumor is said to be benign. A complete cure can be achieved by surgically removing the mass.

11. A tumor is cancer, if it is malignant. If its cells have acquired the ability to invade surrounding tissue. Invasiveness centers on the cells’ ability to break loose, enter the bloodstream or lymphatic vessels, and form secondary tumors, called metastases, at other sites in the body.

12. Even when a cancer has metastasized, its origins can usually be traced to a single primary tumor, arising in an identified organ derived by cell division from a single cell that has undergone some heritable change to outgrow its neighbors. A tumor contains about a billion cells or more …initiated by genetic changes cancer cells have similar DNA abnormalities …chemical carcinogens …ionizing radiations such as x-rays …viruses

13. An estimated 1016 cell divisions take place in a normal human body in the course of a lifetime Every single gene is likely to undergo mutation on about 1010 separate occasions in any individual human being If a single mutation were enough to convert a typical healthy cell into a cancer cell that proliferates without restraint, we would not be viable organisms.

14. The genesis of a cancer requires that several independent, rare accidents occur in the lineage of one cell Cancer requires mutations in many genes—ten or more The incidence of leukemia in Hiroshima and Nagasaki did not show a marked rise until about 5 years after the explosion of the atomic bombs

15. Industrial workers exposed for a limited period to chemical carcinogens do not usually develop the cancers characteristic of their occupation until 10, 20, or even more years after the exposure Long incubation period, the prospective cancer cells undergo a succession of changes Tumors grow in fits and starts, as additional advantageous mutations arise those cells becoming the dominant clone in the developing lesion

16. Evolution of Cancer • the mutation rate, probability per gene • per unit time that any given member of the • population will undergo genetic change • (2) the number of individuals in the population • (3) the rate of reproduction, the average number • of generations of progeny produced per unit time • (4) the selective advantage of successful • mutant individuals, the ratio of the number • of surviving fertile progeny they produce • per unit time to the number of surviving • fertile progeny produced by nonmutant • individuals.

17. 1. They disregard the external and internal signals that regulate cell proliferation.2. They tend to avoid suicide by apoptosis.3. They circumvent programmed limitations to proliferation, escaping replicative senescence and avoiding differentiation.4. They are genetically unstable.5. They escape from their home tissues (that is, they are invasive).6. They survive and proliferate in foreign sites (that is, they metastasize).

18. The tissue and cell type classifies malignant cancers. Adenocarcinoma - originates in glandular tissue Blastoma–originates in embryonic tissue of organs Carcinoma–originates in epithelial tissue (i.e., tissue that lines organs and tubes) Leukemia–originates in tissues that form blood cells Lymphoma–originates in lymphatic tissue, BCell, TCell proliferations lymphomas Myeloma–originates in bone marrow, hemopoietic cells Chondroma—tumors of the cartilage Sarcoma–originates in connective or supportive tissue (e.g., bone, cartilage, muscle) 90% of human cancers are carcinomas

19. Grading CancerUnder a microscope, examining tumor cells obtained through biopsy Abnormality determines the grade of the cancer, increasing the grade, from 1 - 4. Cells that are well differentiated closely resemble mature, specialized cells. Cells that are undifferentiated are highly abnormal, immature and primitive. Grade 1 Cells slightly abnormal and well differentiated Grade 2 Cells more abnormal and moderately differentiated Grade 3 Cells very abnormal and poorly differentiated Grade 4 Cells immature and undifferentiated

20. Classify the extent of the cancer Stage 0 Cancer in situ (limited to surface cells) Stage I Cancer limited to the tissue of origin, evidence of tumor growth Stage II Limited local spread of cancerous cells Stage III Extensive local and regional spread Stage IV Distant metastasis