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62 Cards in this Set
- Front
- Back
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What is the difference between cancer cells and normal cells? Name at least 5 differences |
Cancer cells -High proliferation rate ---18-24 hrs -Irregular shape -lose differentiation ---lose tissue specific functions -High mutation rate -extra chromosomes/deletions/insertions -resilient to adverse conditions ---pH, O2, nutrients, etc -may stinulate growth of new blood vessels (angiogenesis) -May detach from tissue (metastasis) Normal cells -proliferation rate varies due to cell type ---days, months -regular shape -retain differentiated state ---maintain tissue-specific functions -Mutation leads to apoptosis ---remain diploid and any damage---> death -Not resilient and require a "healthy environment ----won't divide or will die otherwise -Do not stimulate growth of blood vessels -maintain contact with tissue |
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What is angiogenesis? |
growth of new blood vessels |
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What is metastasis? |
cancer cells break away from where they first formed (primary cancer), travel through the blood or lymph system, and form new tumors (metastatic tumors) in other parts of the body. Themetastatic tumor is the same type of cancer as the primary tumor.
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What is the difference in cell signaling btwn cancer cells and normal cells? |
Cancer Cells Abnormal cell cycle signaling -ignore death signal -do not require survival signals -do not require mitogens to divide -do not respond to anti-mitogens Divide continuously -do not respond to control signals(population/contact inhibition) -overactive telomerase (extend telomores)-> immortal Normal cells Normal cell cycle signaling -respond to death signals -require survival signals -require mitogens to divide -respond to anti-mitogens Divide when necessary -respond to population control and contact inhibition signals -telomerase only active in stem cells/germ cells lines |
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Which has multilayer cells? Cancer or normal? |
cancer |
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What is neoplasia? |
aberrant cell growth |
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What is a tumor? |
Accumulation of cells that form a solid mass ---leukemias and lymphomas are termed "liquid cancers Tumors can be classified as benign or malignant |
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What is benign? |
neoplasia that is restricted to the proper tissue location |
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What is malignancy |
neoplasia that has invaded other tissues within an organ |
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What is the overall scheme of cancer staging? |
0= benign and localized ****morphology retained (differentiated) I= benign and localized, loss of morphology (less differentiated) II= locally invasive tumor (if solid) III= locally invasive throughout organ and spread to nearby lymph nodes IV=metastatic (spread to other organs) |
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How are cancers classified? |
by cell of origin |
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What is the cell of origin for carcinoma |
epithelial cell |
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What is the cell of origin for sarcoma
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connective tissue cell |
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What is the cell of origin for leukemia
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white blood cell (not lymphocyte) |
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What is the cell of origin for lymphoma
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lymphocyte |
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What is the cell of origin for adenoma
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epithelial cells form gland (usually benign) |
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What is the cell of origin for adenocarcinoma |
tumor in a gland |
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What is the cell of origin for chondroma, chondrosarcoma
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benign/malignant tumor of cartilage |
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What is the cell of origin for osteoma, osteosarcoma
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bone tumor |
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What is the initiation of cancer? |
Begins with a single cell that divides and becomes a "clonal" population |
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What is the progression of cancer |
-cell accumulates further mutation and aneuploidy -follows a natural selection model:mutations at random and the ones that increase survival/proliferation are favored -each "stage" can be categorized by "clonal generations" of mutations that form the tumor |
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What is aneuploidy |
abnormal chromosome number |
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Why do mutations happen? |
Normally a human experiences 10^11 cell divisions/day -tremendous complexity of cell division regulation -Average mutation rate(per gene) in 10^6 divisons ***cancer mutations are always happening -where the mutations occur is important ----mutations in DNA repair regiions or in genes that control proliferation |
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What are the types of mutations? |
1. Coding regions 2. Regulatory regions 3. Epigenetic changes 4. Chromosomal damage |
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What is cancer?
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Cancer is a diseased state, in which cells escape the normal controls on cell division and proliferate in an unregulated manner. These cells may invade and colonize neighboring tissues or travel to other sites in the body
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What is a tumor?
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A tumor is any abnormal proliferation of cells. It may be benign- the cells to do not invade other tissues or spread to other sites.
the tumor may become malignant, that is, it invades surrounding tissues and may spread to distant sites in the body. |
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How can a tumor spread to other sites in the body?
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Tumor cells may enter the blood or lymph and travel to other parts of the body, where they lodge and continue to proliferate. This process is called metastasis.
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Can tumors be removed surgically?
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Benign tumors are readily removed by surgery, since they are confined to a single site and have not invaded surrounding tissues. Malignant tumors are harder to remove completely, since it is difficult to determine the boundaries of the region into which they have infiltrated. If metastasis has occurred, then surgery at the original site cannot, for obvious reasons, eliminate the cancerous cells that have migrated to other sites.
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How does cancer develop?
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Cancer starts with a mutation in a single cell. This mutant cell begins to proliferate abnormally. This, in itself, is not enough to cause cancer, however. If additional mutations occur, some of which confer a selective advantage on the tumor cells, then these cells will begin to proliferate faster than normal cells, and eventually may result in malignancy. Usually, it takes several mutations to turn a normal cell into a cancer cell. This is fortunate, since we have mutations occurring in our DNA every time our cells replicate. Although DNA polymerase is very accurate, mammalian cells have several billion basepairs of DNA to copy, and a few mistakes are inevitable
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How do carcinogens (cancer-causing substances) act?
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Many carcinogens cause damage or mutations in DNA. As we noted earlier, all cancer starts with mutation in a single cell. Chemicals and radiation that cause mutations can, thus, be initiating agents in cancer.
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What are tumor promoters?
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Some chemicals contribute to cancer development by stimulating cells to divide, rather than by causing mutation. Such chemicals are called tumor promoters, since they do not initiate the tumor, but promote its growth. Even substances that are normally present in the body, such as hormones, can act as tumor promoters.
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What is an oncogene?
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The name 'oncogene' means a gene that promotes cancer. This name is a bit misleading, because oncogenes are actually just normal cellular genes that, when they are mutated, can cause cancer. The example above, where a normal gene is picked up from a host cell by a retrovirus, illustrates this.
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How does a proto-oncogene becomes a viral oncogene? |
The original normal gene in the host cell is required by the cell for its normal functioning, and is called the 'cellular oncogene' or proto-oncogene. When it is picked up by a virus, and mutated so that it becomes cancer-promoting, it is called the 'viral oncogene'.Important Note: The proto-oncogene, although it is called an oncogene, does not promote cancer, only the mutated form does
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What is the consequence of such mutations in proto-oncogenes?
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A well-studied example of such oncogenes is the ras family of genes. Mutations in the ras gene can lead to the production of mutant Ras proteins that are unable to hydrolyze GTP bound to them. As we have discussed earlier, the binding of GTP to Ras activates Ras, which in turn switches on a series of MAP kinases. The signal from Ras is then turned off by the hydrolysis of GTP. If Ras is unable to hydrolyze the GTP bound to it, it will be "stuck" in the active form indefinitely even in the absence of growth signals. This results in uncontrolled cell proliferation
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What are some examples of hybrid proteins found in cancer cells |
-One example is the result of the translocation of the gene for the PDGF receptor. The receptor for PDGF (platelet derived growth factor) is a receptor tyrosine kinase. As you know, receptor tyrosine kinases are activated by the binding of their signal (in this case, PDGF) to dimerize and undergo autophosphorylation
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What is the receptor for PDGF? |
receptor tyrosine kinases |
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What are tumor suppressor genes?
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Tumor suppressor genes encode proteins that normally inhibit cell division. An example is the p53 gene. You may recall that p53 is involved in preventing the cell from passing from the G1phase of the cell cycle to S phase if there is damage to the cell's DNA. The p53 protein thus, acts as a brake on the cell cycle, stopping it when necessary to repair damage to the cell's DNA, and preventing damaged or mutated DNA from being copied and passed on to the daughter cells.
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What happens if a tumor suppressor gene is mutated?
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If a tumor suppressor gene is mutated, the protein encoded by it is defective and permits cell division when it should not normally occur. Mutational inactivation of p53 allows cells to divide by removing the brakes on cell proliferation
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Can a tumor suppressor be inactivated without mutation of the tumor suppressor gene?
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Yes, in fact, this is what happens when cells are infected with certain DNA tumor viruses. These viruses produce proteins that bind and inactivate p53 proteins. So, although the cell has normal p53, it is inactivated by binding of the viral protein
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Are there other ill effects of inactivation of tumor suppressors?
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Unfortunately, yes. The p53 tumor suppressor protein is a prime example. In addition to stopping the cell cycle to repair damaged DNA, p53 is also involved in regulating apoptosis. If the damage to the DNA is too extensive to be fixed, then p53 signals the cell, telling it to undergo programmed cell death. Thus, if the p53 in a cell is inactivated, then that cell could continue to copy badly damaged DNA and proliferate, instead of either fixing the DNA or quietly committing suicide. The proliferation of cells with damaged or mutated DNA is an important step in the progression of cancer, and without functional p53, these processes are accelerated.
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What is signal/receptor step therapy? |
Many kinds of breast cancers overproduce receptors for EGF(epidermal growth factor). This results in abnormally high stimulation of the cells to grow. Two strategies used to battle such cancers are blocking the growth factor itself, and blocking the receptor. Antibodies against growth factor or receptor have been successful in treating some kinds of these cancers
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What is Ras signalling step therapy? |
The activation of Ras following growth factor stimulation of a receptor depends on the interaction of a signalling complex with membrane-bound Ras (Ras is inserted into the cytosolic face of the plasma membrane by means of a lipid attached to it). Blocking the enzyme that adds the lipid group to Ras prevents Ras from being attached to the plasma membrane, thus breaking the link in the signal transduction pathway.
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What is protein kinase cascade step therapy |
A variety of protein kinase inhibitors have been designed to block these steps. Unfortunately, it is difficult to block protein kinases without causing many normal pathways to shut down as well. More specificity of inhibition can be achieved by using antisense RNAs directed at particular protein kinases, but these technologies are still in the experimental stage and limited by the difficulty of getting the RNAs into the target cells.
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What is tumor suppressor step therapy |
Most cancer cells have a defect in their tumor suppressor genes, so they often lack functional p53. This fact has been used to devise an elegant strategy to kill cancer cells without affecting normal cells. In this method, a mutant cold virus is used to attack the cancer cells.
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What is a coding region mutation? |
proto-oncogene always ON or tumor suppressor gene always OFF |
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What are regulatory regions mutations |
promoter/enhancers/introns; can up/down regulate gene or disrupt normal TF function |
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What is epigenetic changes of mutations |
Dna methylation to silence genes |
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What is chomosomal damage |
aneupolidy, deletions rearrangements, overamplificaiton ***example philadelphia chromosome (c9/c22) causes CML (chronic myeloid lukemia) |
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what is dna methylation |
an epigenetic mechanism used by cells to control gene expression. A number of mechanisms exist to control gene expression in eukaryotes, but DNA methylation is a commonly used epigenetic signaling tool that can fix genes in the “off” position.
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What is p53? |
-A transcription factor with many targets, coded by the TP53 gene - Normal cell: not expressed during the normal cell cycle |
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The correct concept of a gene is:
a) a DNA segment that obligatorily carries information for protein synthesis b) a DNA segment whose primary transcription is an RNA c) any DNA segment, regardless of its containing information for RNA or protein d) the whole DNA base sequence |
c |
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According to the "central dogma of molecular biology", what can NOT happen?
a) RNA synthesis from DNA b) DNA synthesis from RNA c) Protein synthesis from RNA d) Protein synthesis directly from DNA |
b |
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The action of oncogenes in the development of tumors occurs by:
a) DNA damage repair; b) Cell growth promotion ;c) Blocking of cell cycle progression; d) Leading cells to death (apoptosis). |
b |
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Genetic mutations can confer to cells certain characteristics which are important in the development of cancer. These characteristics can be represented by:
a) Reduction in proliferation capacity, evasion of apoptosis, ability to generate metastases, and loss of response to growth inhibition factors b) Loss of response to growth inhibition factors, reduction of angiogenesis, evasion of apoptosis, reduction in proliferation capacity c) Increase of apoptosis, greater response to growth inhibition factors, ability to generate metastases d) Increase in proliferation capacity, evasion of apoptosis, ability to generate metastases, and loss of response to growth inhibition factors |
a |
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The action of proto-oncogenes in tumor growth is due to:
a) Activation during the embryonic phase taking advantage of the cellular vigor of young organisms b) Direct action on the activation of apoptosis, besides keeping protein RAS activated c) As they are transformed into oncogenes, they express themselves by signaling uncontrolled cell multiplication d) They are genetically dominant over the tumor suppressor genes |
b |
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In the process named translation,
a) mRNA is translated into proteins in the ribosome b) rRNA transforms mRNA into proteins c) DNA is processed into proteins d) tRNA is translated into proteins in the ribosome |
b |
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What does p53 trans-activate when there is DNA damage |
-DNA repair, metabolism, angiogenesis -Temporary cell cycle arrest (mainly p21 inhibitor of Cyclin-CDKs)
-Apoptosis (Bax, Bak, and PUMA) -Permanent cell cycle arrest |
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What happens when the p53 gene is in a cell that is under stress? |
If p53 is produced:
--- it is constantly made and quickly degraded (half-life ~< 20 min) ------mdm2 protein (aka hdm2) “tags” p53 with ubiquitin -> disassembled If prolonged stress ->p53 may become stabilized -----It can trans-activate its target genes AND TP53 (to cause feed forward activation) -----Recent research (Ano Bom et al. 2012) ----------- P53 can act like prions ----------- Form protein aggregates around DNA |
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what is a prion? |
Prions are bits of misfolded protein that have the ability to spread by making other proteins misfold.
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What is ubiquitin? |
a small protein that is found in almost all cellular tissues in humans and other eukaryotic organisms, which helps to regulate the processes of other proteins in the body.Through a process known as ubiquitination or ubiquitylation, an ubiquitin molecule can bind to a substrate protein, changing the way it functions.
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What is angiogenesis? |
the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels.
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What are some of the angiogenesic factors |
VEFG PIGF PDGF |
