Term
| Define hyperplasia, dysplasia, neoplasia. |
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Definition
| Increased proliferation, morphologic abnormalities and loss of architecture without invasion, new tissue growth either benign or malignant |
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Term
| Which of these 3 are reversible and which is a point of no return mutation: hyperplasia, dysplasia, neoplasia? |
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Definition
| Hyper/dysplasia reversible, neoplasia no return |
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Term
| Distinction between benign and malignant neoplasms? |
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Definition
| Malignant are invasive and metastatic |
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Term
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Definition
| Tumor that grows and LOCALLY invades through basement membrane or through other tissue barriers |
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Term
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Definition
| Cells detach from primary tumor and travel via lymphatic or venous system, multiplying at distant sites. |
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Term
| Why is it important to understand the molecular basis of invasion and metastasis? |
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Definition
| Determines diagnoses/therapy/prognosis; tumor cell heterogeneity necessitates multiple therapies, invasion and metastasis are the features responsible for the lethality of cancer |
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Term
| Since metastatic cells are a result of tumor progression in a stepwise fashion, why can those small percentage of cells (<.01%) move? |
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Definition
| Because they have a selective advantage for metastasis among tumor cells. |
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Term
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Definition
| Cellular movement based on chemical concentrations/affinities in their environment |
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Term
| What are the first four steps required for both invasion and metastasis? |
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Definition
| Detachment of tumor cells from one another, adhesion to the basement membrane, protelytic dissolution of the basement membrane, locomotion of cells across the extracellular matrix |
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Term
| After the first 4 steps required for invasion and metastasis, what are the last 8 steps needed for successful metastasis? |
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Definition
| Intravasation (enter blood vessel/lymp), detach endothelium, attach at distant endothelium, extravasation, attach ECM distant site, distant site growth, angiogenesis, evasion of immune response |
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Term
| What are the 3 clinical approaches to cancer therapy? |
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Definition
| Surgery removes primary tumor, radiation kills micrometastases, chemo kills metastases but limited by bioavailability and vascular access |
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Term
| True or False: The types of targets drugs will attack for controlling metastasis are anti-adhesion molecules, protease inhibitors, anti-growth factors, anti-angiogenic factors. |
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Definition
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Term
| Why is it important to always use combinatorial approaches in cancer therapy? |
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Definition
| Tumor cell heterogeneity and high mutation rate |
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Term
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Definition
| Agents that induce a cell in a G-0 state to G1 and progress through the cycle |
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Term
| During what phases of a cells cycle does the DNA content double and half? |
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Definition
|
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Term
| True or False: a flow microflourimeter is used to determine cancer metastasis. |
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Definition
| False, determines DNA content of individual cells |
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Term
| Why is there a great increase in G2-M histone kinase activity at the end of G2 cell cycle? |
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Definition
| Because when histones are created in S phase, they are then subject to post-translation phosphorylation in preparation for M phase. |
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Term
| At the cell cycle restriction point G1/S, which transcription factor repressor must become phosphorylated to activate transcription factors to get past this point? |
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Definition
| Restriction boundary protein, it must be dephosphorylated to before the restriction point in the next cell cycle |
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Term
| If you want to synchronize cells at the G1/S point what can you add to a group of cells? |
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Definition
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Term
| What does cell fusion data using heterokaryons indicate about transitions between cell phases? |
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Definition
| That there are distinct controls and regulator activities that mediate the cell in different stages. |
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Term
| The most famous protein kinase regulating cell cycles is cdc2 kinase, what type of kinase is it and what regulates it? |
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Definition
| It is a cyclin-dependent protein kinase, and it is regulated by cyclin and phosphorylation at 2 sites. |
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Term
| Since CDK can phosphorylated twice, what does each one do to the CDK/Cyclin complex? |
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Definition
| One activates its enzymatic activity, and the other inactivates it. |
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Term
| True or false: Cyclins are are absent in G1, synthesized in S-phase, accumulate in G2, destroyed in mitosis. |
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Definition
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Term
| How are cyclin proteins destroyed and how are proteins repaired? |
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Definition
| A ubiquitination mechanism that marks the cyclins or proteins with a protein called ubiquitin to be degraded or corrected in a proteosome. |
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Term
| A distinct CDK is required for a cell to pass which cell cycle check points? |
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Definition
| G1/S to phosphorylate restriction boundary protein, DNA synthesis at S-phase, and G2/M |
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Term
| True or False: The cdc2/cyclin B complex is a poor histone kinase. |
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Definition
| False, it is a potent kinase for histones. |
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Term
| In regards to the cell cycle, what 3 states do cells exist? |
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Definition
| Postmitotic, cycling, non-dividing but able to respond to mitogenic signals |
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Term
| Briefly, what happens to G-0 cells following mitogenic stimulation to go past the G1/S restriction boundary? |
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Definition
| Mitogen stims a Cdk complex which phosphors a restriction boundary protein which is on a transcription factor, this releases Rb and allows the trans factor to create genes needed for the G1/S transition. |
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Term
| What is a dominant oncogene? |
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Definition
| Oncogenes that gain an autonomous function and can drive the cell into division |
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Term
| What is a tumor suppressor gene? |
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Definition
| Gene who’s loss of function enables the expression of cancer phenotype. |
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Term
| What is a proto-oncogene and why is it relevant to RNA tumor retroviruses? |
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Definition
| A normal gene that is captured and mutation by virus, this leads to the insertion of the modified oncogene back into the human genome where it causes cancer. |
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Term
| Give a basic overview of how the cellular Ras signal molecule affects gene expression and mitotic division. |
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Definition
| Ligand binds receptor, receptor phosphors, Grb2/GNEF binds receptor, binds Ras and activates with GTP, active Ras bind protein kinase cascade (Raf/MAPK), MAPK phosphors transcription factors |
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Term
| What is the difference between a normal cellular Ras signal molecule and a mutated one that causes cancer? |
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Definition
| Ras needs to be inactivated by GTPase Activating Proteins(GAP), mutated one can’t bind to GAP so it is always on. |
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Term
| True or False: The mutated Ras oncogene is a dominant oncogene, therefore it cannot caused by a single point mutation in its gene. |
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Definition
| False, single point mutations can cause changes in the Ras protein giving it inability to deactivate. |
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Term
| What are the three ways dominant oncogenes are activated? |
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Definition
| Point mutations, chrome translocations (either unregulated DNA expression or fusion proteins with transforming properties), gene amplification |
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|
Term
| What is a tumor suppressor gene? |
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Definition
| Genes who’s loss of function allows cell to express cancer phenotype |
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Term
| What is the most commonly mutated human cancer gene and what does it do? |
|
Definition
| P53 prevents cells with damaged DNA to continue to replicate instructing the cells to fix DNA or apoptosis; it is a trans factor that expresses a Cdk inhibitor |
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Term
| True or False: Genes involved in cell control - Cyclin D, Rb gene, Cdk Inhibitors - are all altered in different human cancers. |
|
Definition
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|
Term
| What is a better predictor of cancer patient survival, gene profiling of cancer cells or traditional clinical data? |
|
Definition
|
|
Term
| True or False: Cancer rates are relatively linear as you age. |
|
Definition
| False, they increase exponentially around 40-50 yrs old. |
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Term
| True or False: Cancer is a multigenic, multistage process. |
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Definition
| True, it requires mutations in multiple oncogenes to intiate, promote, and progress cancer. |
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Term
| What is the role of PET scans in cancer treatment? |
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Definition
| PET scans analyze whether the imaging molecule FDG is being changed by Hexokinase activity which indicates cancer activity and therefore the size and spread of cancer. |
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Term
| What is the role of PTEN phospholipids phosphotase in tumor progression? |
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Definition
| If PTEN is missing then the AKT/PKB kinase has greater activity on TOR (targets of Rapamycin) substrates increasing cell proliferation, promoting migration, preventing apoptosis. |
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Term
| What drug can bind to TOR, targets of Rapamycin, to limit kinase activity when the PTEN regulator protein is missing? |
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Definition
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|
Term
| True or False: Only 20-30% of cancers have an environmental causation. |
|
Definition
|
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Term
| In cancer development, which one of these is genotoxic: initiators or promoters? |
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Definition
| Initiators, promoters are non-genotoxic |
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Term
| What is an iniator carcinogen? |
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Definition
| It is a carcinogen that is genotoxic that usually require metabolic activation by phase 1 enzymes (CYP450) making it electrophilic and able to mutate DNA, ie - PAH, benzopyrene, alflatoxin B1 |
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Term
| What is the ultimate carcinogen? |
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Definition
| Benzopyrene, BPDE, it attaches to guanine residues in DNA to pair with A instead of C, it has long half life, resistant to metabolism. aflatoxin B1 is also very potent iniator. |
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Term
| True or False: All carcinogenic initiators require metabolism before they become active. |
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Definition
| False, some are directly acting alkylating agents. |
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|
Term
| Define a carcinogenic promoter. |
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Definition
| An non-mutagenic agent that binds to cellular receptors preferentially stimulating the growth of intiated cells |
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Term
| Briefly, how do the promoters TPA and Dioxin function? |
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Definition
| TPA mimics DAG and activates PKC and is therefore a mitogen with a long half-life, Dioxin binds to Ah receptor and stimulates growth and also has a long half-life |
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|
Term
| What are the targets of genotoxic carcinogens? |
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Definition
| Protooncogenes, tumor suppressor genes, and DNA repair genes |
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Term
| How is it that diet can protect against cancer? |
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Definition
| Certain foods(broccoli, resveratrol) modulate metabolism of carcinogens, for example either inhibiting the amount of phase 1 CYP metabolites formed or stimulating phase 2 enzymes to quickly remove metabolites |
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|
Term
| For reference what are the normal levels of hematocrit for women, men, and what is the critical value? |
|
Definition
|
|
Term
| Elaborate on the complete cell cycle without the details of mitosis. |
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Definition
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