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Cancer is the result of the interaction between a person's __________ and three categories of external agents called ___________.
- genetic factors
what are carcinogens and what are the 3 categories of carcinogens?
- cancer causing agents; capable of inducing neoplastic growth
- 3 categories: chemicals, radiation, some viruses or bacteria
what are genes? what is it's function?
- inherited instructions that reside within chromosomes
- each gene instructs a cell how to build a specific product, a particular kind of gene.
what is genetic instability?
somatic cell mutation by carcinogenic agents
what are some other factors of carcinogenesis? (3)
- dietary habits
- alcohol consumption
Chemicals are commonly tested for carcinogenicity using what test?
what are some typical chemical carcinogens? (4)
- aflatoxin (mold)
- polycyclic aromatic hydrocarbons
what two viral carcinogens are responsible for about 80% virally-induced cancers?
hepatitis B and HPV
what is somatic mutations?
acquisition of mutations that convert a normal cell to a cancer cell
what is germline mutation?
inheritance of an alteration or mutation that will cause or predispose cancer
Types of DNA mutations: single base change. what is this mutation and what cancer can it cause?
- point mutation
- bladder cancer
Types of DNA mutations: larger sections of DNA through amplifications (3)
what is epigenetic changes? give an example.
- type of DNA mutation; reversible heritable non-mutational changes that result in altered gene activity
- BRCA1 activity in breast cancer
what is miRNA?
type of DNA mutation; small sequences of ssRNA that silence mRNA that can be silenced in cancer cells
chromosomal changes such as changes in number is called?
what chromosomal change created the Philadelphia chromosome and chronic myeloid leukemia (CML)?
- translocation of Bcr-Abl genes
- small piece of chromosome 9 and 22 break off and switch
What happens to a gene when it's mutated?
can produce dysfunctional proteins and cause a variety of effects
Cancer mutations usually occur in 2 types of genes, name and briefly describe each function.
- oncogenes: normal function is cell growth, gene transcription
- tumor suppressor genes: normal function is cell cycle control, DNA repair, cell death (apoptosis)
oncogenes are cancerous versions of __________________.
what mutation does oncogenes undergo? (3)
- "gain of function" mutations
- they do even more of what they normally do
- cause cells to divide more or die less
_____________ genes can also act as oncogenes.
what mutation does tumor suppressor genes undergo?
- undergo "loss of function" (has to be both copies)
- tumor suppressor genes usually act as inhibitors of cell replication
what is the function of the tumor-suppressor mutation and oncogene?
- tumor-suppressor mutation: lack of inhibition of the cell cycle
- oncogene: overactive stimulation of the cell cycle
_______________ are genes that correct errors in DNA replication
what is the function of p53? (2)
- apoptosis controllers
- halts the cell cycle and initiates DNA repair
what is the mutation gene that suppresses apoptosis?
Bcl-2 an oncogene
what is classic example of carcinogenesis in action?
describe the 4 steps in carcinogenesis?
- initiation: carcinogen produces a mutation in a cell
- promotion: some other factor encourages proliferation of the cell
- progression: transformed cells begin to grow autonomously
- cancer: invasion and metastasis
what is neoplasia?
a new growth of cancerous cells
what is anaplasia?
cells of the tumor are undifferentiated and resemble embryonic cells
growth and proliferation of endothelial cells that line the inner surface of existing blood vessels
why is cancer potentially dangerous?
their capacity to invade neighbouring tissues and colonize distant organs with their cells
direct migration and penetration of cancer cells into tissues
refers to the ability of cancer cells to enter the vasculature and migrate to distant sites
what are the 5 steps to the spread of malignant tumors?
- invasion of connective tissue matrix(stroma)
- invasion of blood and lymphatic vessels
- circulation of tumor cells
- invasion from blood vessels into tissues
Angiogenesis is ___________________.
needed for tumor survival
how do tumors destroys both the basement membrane and surrounding matrix which lies between the tumor and its path to metastasis?
tumors secrete cytokinesis and enzymes called proteases
what is metastatic cancer?
- malignant spread of tumor cells away from the primary lesion
- all malignant cells can metastasize
what 3 ways can metastatic cancer occur through?
- hematogenous spread (blood vessels)
- lymphatic spread (lymphatic vessels)
- direct seeding of body cavities/surfaces
briefly explain metastasis via blood vessels. (4)
- tumor embolus entering a vein is carried through larger and larger vessels to heart
- enters pulmonary circulation
- vessel size narrows in lungs, trapping embolus
- embolus begins to grow
why is the lung the most common site of secondary tumor growth?
capillaries and veins have thin walls which is easy to penetrate
what are the 2 organs that are common sites for secondary tumor growth?
how does a secondary tumor growth in the liver happen?
- many veins pass through liver
- liver sinusoids have small diameter which traps tumor emboli
why are arterial metastasis less common than venous?
arteries have thicker walls, so invasion's harder
what are the 3 steps in metastasis via lymph nodes?
- tumor cells get trapped in lymph node and start growing
- alternate routes of flow carry tumor cells to new sites
- lymph nodes also intersect with blood vessels
how is another way metastasis spreads through body cavities?
cells shed into the cavity and can establish masses in other regions of the cavity
what is metastasis spread by implantation?
spread/implantation facilitated by surgery
Bloodstream carries cancer cells all over the body. Each type of cancer preferentially metastasizes to particular locations depending on what 4 things?
- pattern of blood flow
- organ specific factors
- tumor progression
- immune system
how does organ specific factors factor into the decision of cancer cells to metastasize?
some tissues secrete growth factors that stimulate proliferation of cancer cells
Not all tumor cells that migrate via blood or lymph survive to set up new tumors, why is this?
low survival may be due to combination of turbulence in blood causing mechanical damage, and host defenses
what are the 5 Hallmarks of Cancer? briefly describe each.
- 1. Growth without Go signals: do this by producing their own growth factors, over-express or change growth factors
- 2. Failure to respond to STOP signals: cancer cells avoid the signals for anchorage dependent or density dependent growth
- 3.Unlimited number of cell divisions: cancer cells have the ability to divide endlessly
- 4. Avoidance of cell death: cancer cells that get past this have acquired the ability to avoid the cell death signals
- 5. Angiogenesis: release signals that result in growth of blood vessels towards and into the tumor supplying it oxygen and nutrients