Term
| What gene is over expressed in 80% of squamous cell carcinomas of the lung? |
|
Definition
ERBB1
Part of the EGF receptor family |
|
|
Term
What EGF receptor
is amplified in 25% of all breast cancers? |
|
Definition
|
|
Term
| Name the common signal transducing oncoprotein gene family. What mutations in these genes cause cancer? |
|
Definition
RAS. They are the link between growth factor receptors and nucleus
mutated RAS has no autoGTPase activity so it remains constitutively active. |
|
|
Term
| the 9:22 ABL-BCR gene translocation is an example of a mutation of what>? |
|
Definition
| Non-receptor tyrosine kinase |
|
|
Term
| What is the most commonoly mutated trasncription factor in human tumors? |
|
Definition
|
|
Term
| What type of mutation causes MYC proto-oncogene to become oncogenic? |
|
Definition
| gain of function and consitutive expression |
|
|
Term
| c-MYC in a normal cell is induced by ____? |
|
Definition
|
|
Term
| What molecules are responsible for regulating progression through cell cycles? |
|
Definition
| cyclins and cyclin dependent kinases. |
|
|
Term
| how is the G1 --> S transition regulated? by what molecules is the process activated and inhibited? |
|
Definition
| CDK4 and CDK6 that phosphorylated Rb protein are activated by cyclin D and cyclin E. Inhibited by p15, p16 (aka CDKN2A), p18, and p19. |
|
|
Term
| Cancers associated with CDK4 amplification? |
|
Definition
| melanoma, sarcomas, and glioblastomas |
|
|
Term
| p15, p16, p18, and p19 are examples of what? |
|
Definition
|
|
Term
What is the two-hit hypothesis?
Example of this? |
|
Definition
states that there must be mutations in both alleles to produce the cancer effect.
Example is retinoblastoma. inherit one mutated form and acquire the second --> cancer. |
|
|
Term
|
Definition
|
|
Term
| does TGF-beta inhibit or promote G1->S transformation? |
|
Definition
|
|
Term
| Loss of p53 functionality is present in how much cancer? What part of the protein is effected? |
|
Definition
| almost all DNA binding domain. |
|
|
Term
| Li-Fraumeni syndrome. Cause? effects? |
|
Definition
| inherited mutation of p53 on one allele. gives 25 fold increase in chance of developing cancer before 50 and causes a wide array of cancers. |
|
|
Term
| if p53 mutation is so important in the developement of cancer, if you don't have a p53 mutation, how can you still develop cancer in some cases? |
|
Definition
| mutation of MDM2 which tags ubiquitin to p53 and catalyzes its destruction. Typical of sarcomas. |
|
|
Term
| how is p53 used in treatment of cancer? |
|
Definition
| irradiation and chemo cause DNA damage that upregulates p53 --> apoptosis. |
|
|
Term
| mutation in what gene causes familial adenomatous polyposis? What is the function of this gene? |
|
Definition
| APC gene. Functions to downregulate growth promoting signals by binding to beta-catenin (growth inducer) and mediate its degradation. If APC isn't around, beta-catenin rises, binds to TCF, and upregulates proliferation. |
|
|
Term
| Describe the funcion of INK4a/ARF genes. |
|
Definition
This gene can be alternatively spliced to produce the following:
p16/INK4a - blocks D-CDK4 and D-CDK6 mediated phosphorylation of Rb
p14/ARF - innhibits MDM2 to preventp53 degradation |
|
|
Term
| what is the mechanism of action of TGF-beta? |
|
Definition
| binds serine-threonin kinase -> phosphorylates R-Smads -> R-smads increase synthesis of CDKis, and decrease CDKs and c-MYC |
|
|
Term
| What is the role of the PTEN gene and protein? What mutation in this gene causes cancer and how? |
|
Definition
| PTEN is a membrane bound phosphatase that serves as a tumor suppressor gene by removing a phoshpate from the oncoprotein PIP3. Therefore, a loss of function mutation will predispose pt to cancer. |
|
|
Term
| What gene is over expressed in 80% of squamous cell carcinomas of the lung? |
|
Definition
ERBB1
Part of the EGF receptor family |
|
|
Term
| what growth factor forms an autocrine loop in cancer to perpetuate growth? Which cancer is it associated with? |
|
Definition
|
|
Term
| H. pylori infection causes chronic inflammatio of the gastric mucosa (gastritis). What cancer may develop from this? |
|
Definition
| Gastric carcinoma or MALT lymphoma |
|
|
Term
| define anaplasia and give a few characteristics of anaplastic cells? |
|
Definition
lack of differentiation
Pleomorphism - variation in size and shape of the cell
abnormal nuclear morphology - darkly staining
Atypical mitotic figures ***
Tumor giant cells
loss of polarity
high nuclear:cytoplasm ratio (1:1 bad) |
|
|
Term
| define metaplasia and give two examples |
|
Definition
changing of one cell type to another
Barret's esophagus is a metaplastic change of the lower esophagus epithelium from squamous to columnar
respiratory epithelium may change to stratified squamous in smokers |
|
|
Term
| dysplasia that takes up the whole epidermis is known as? |
|
Definition
|
|
Term
| name 3 factors (identify the most important of the three) of rates of tumor growth |
|
Definition
doubling time of cells
fraction of tumor cells in proliferative pool ***
Rate at which cells shed or die |
|
|
Term
| do benign tumors tend to have a fibrous capsule? |
|
Definition
| yes. think since they are benign, they must be separated from other tissues since they aren't invasive. |
|
|
Term
| What tumor generally doesn't metastisize? |
|
Definition
|
|
Term
| name three pathways of metastatic spread? |
|
Definition
1. seeding of body cavities (ovarian cancer)
2. lymphatic spread (most common dissemination path for carcinomas)
3. hematogenous spread (sarcomas) |
|
|
Term
| what is the major contributor to most cancer formation? |
|
Definition
|
|
Term
| exposure to benzine predisposes you to what cancer? |
|
Definition
| leukemia and hodgkin's lymphoma |
|
|
Term
define the term "marker phenotype"
give two examples |
|
Definition
| clinical manifestation that readily indicates they have another disease. in this case the other disease is cancer. Ex is hundreds of colon polyps indicate familial adenomatous polyposis or cafe au lait spots indicating neurofibromatosis. |
|
|
Term
hereditary nonpolyposis colon cancer (HNPCC) is an example of what gene mutation
? |
|
Definition
|
|
Term
| Bcl-2 and Bcl-x are what? They acheive their function by doing what? |
|
Definition
| cell regulators of apoptosis. They promote cell survival. Block cytochrome c from leaking out of the mito and inducing apoptosis |
|
|
Term
| BH3 proteins cause what? by what mechanisms? |
|
Definition
| cause apoptosis by binding and inhibiting Bcl-2 and Bcl-x. Also BH3 proteins activate Bax and Bak which allow cyt c out of mito -> caspase 9 activation |
|
|
Term
|
Definition
| open up mito channels for cyt c release and activation of caspase 9. |
|
|
Term
| What happens when Fas binds to FasL? |
|
Definition
| Three of more Fas are brought together and cytoplasmic death domains form to generate caspase 8 -> apoptosis |
|
|
Term
| What protein inhibits the extracellular apoptotic pathway? what part of the pathway is it involved with? |
|
Definition
| FLIP binds to pro-caspase 8 and prevents in proteolytic cleavage into its active form. |
|
|
Term
| Mechanisms employed by cancer to avoid apoptosis? 4 ways |
|
Definition
decrease Fas expression
increase FLIP expression
Increase BCL-2 expression (common in B-Cell lymphomas)
decrease p53 mutations. |
|
|
Term
| what enzyme activated in cancer gives limitless replicative potential? |
|
Definition
|
|
Term
| In the absence of checkpoints, DNA-repair pathways are inappropriately activated, leading to the formation of dicentric chromosomes. During anaphase the dicentric chromosomes are pulled apart, generating random double-stranded breaks, which then activate DNA-repair pathways, leading to the random association of double-stranded ends and the reformation of dicentric chromosomes. Cells undergo numerous rounds of this bridge-fusion-breakage cycle, which results in marked chromosomal instability and numerous mutations. If cells fail to express telomerase, they eventually undergo mitotic catastrophe and death. Expression of telomerase allows cells to escape the bridge-fusion-breakage cycle, thus promoting their survival resulting in malignancy. |
|
Definition
| straight from the lecture. no other way |
|
|
Term
| define mitotic catastrophe |
|
Definition
| apoptosis resulting in mitosis from attempted asymmetric segregation of chromosomes |
|
|
Term
| what do tumors need in order to get bigger than 2 mm? |
|
Definition
|
|
Term
| name the two major angiogenesis inducing factors and where they are located |
|
Definition
basic fiberblast growth factor - located in the ECM
VEGF - induced by hypoxia (HIF1a) and located in the cell. |
|
|
Term
| what are the two steps of the metastatic cascade? |
|
Definition
| invasion of the ECM and vascular dissemination, homing, and colonization |
|
|
Term
| what molecules does cancer frequently down regulate in order to begin metastisis and invade the ECM? |
|
Definition
e-cadherin - holds cells together.
Integrins - holds cells to ECM |
|
|
Term
| what cell surface marker is used by metastatic cancer cells to adhere to distant sites and to what receptor? |
|
Definition
| CD44 is cancer adhesion molecule that binds to hyaluronic acid on the surface of host cells. |
|
|
Term
|
Definition
| chemokine receptor implicated in the metastases of breast cancer. |
|
|
Term
| HNPCC results from what defect? Characteristic DNA features? |
|
Definition
| DNA mutation of DNA mismatch repair. possess lots of CACA microsatellites |
|
|
Term
| BRCA1 and BRCA2 genes are used for what? |
|
Definition
| homologous recombination DNA repair of INTRASTRAND AND INTERSTRAND DNA CROSS LINKS |
|
|
Term
| Define the Warburg Effect |
|
Definition
| in the presence of ample oxygen, cancercells shift glucose metabolism away from OxPhos to aerobic glycolysis |
|
|
Term
| What is the explanation for the Warburg Effect |
|
Definition
| Halting oxidation of glucose as pyruvate increases carbon availability for anabolic use. The limit for cell division is carbon availability, not ATP availability |
|
|
Term
| most chromosomal abnormalities are seen in what type of malignancies? What are the types of chromosomal abnormaliteis seen? |
|
Definition
lymphoma and leukemias.
translocations (most common)
inversions |
|
|
Term
What genetic abnormality is seen in Burkitt's lymphoma
? |
|
Definition
t(8;14) translocation
results in MYC gene moved next to IgH gene -> MYC overexpression |
|
|
Term
| What genetic abnormality causes follicular lymphoma? |
|
Definition
| t(14;18) that places Bcl-2 gene next to IgH gene -> overexpression of Bcl-2 |
|
|
Term
| What genetic abnormality is presend in CML (chronic myeloid leukemia)? |
|
Definition
the "philidelphia chromosome".
t(9;22)
ABL-BCR fusion gene -> overactive tyrosine kinase
causes 90% of myeloid leukemia. |
|
|
Term
| Chromosomal deletions leading to cancer are more common in what kind of tumors? |
|
Definition
non-hematopoeitic solid tumors
ex. is retinoblastoma deletion of 13q14 |
|
|
Term
define epigenetics
What are the effects of methylation and histone modification? |
|
Definition
heritable reversible changes to DNA without mutation
Methylation silences genes
Histone acetylation unwids DNA and upregulates expression. |
|
|
Term
| 2 examples of genes silenced by hypermethylation |
|
Definition
p16/INK4a
BRCA1
VHL (renal cell carcinoma)
MLH1 (colorectal cancer) |
|
|
Term
| name the enzyme that modifies histones to silence the tumor suppressor gene p21. what cancer it is indicated in? |
|
Definition
| EZH2 and breast/prostate carcinoma. |
|
|
Term
| Chemical carcinogenesis occurs by two steps |
|
Definition
Inititiation - initial DNA damage
Promotion - initiated cell is stimulated to proliferate |
|
|
Term
| What enzyme system is involved in the conversion of pro-carcinogens into carcinogens? |
|
Definition
|
|
Term
| Which spectrum of light is considered to be most carcinogenic? |
|
Definition
| UVB forming pyrimidine dimers |
|
|
Term
| The three most typically malignancies induced by radiation are what? |
|
Definition
| leukemia, thyroid carcinoma, lung/breast/salivary carcinoma |
|
|
Term
HTLV-1 (human T Cell Leukemia Virus Type 1)
What does it do to pass the G1-S transition? |
|
Definition
| virus that infects CD4 cells. Encodes tax gene that inhibits p16/INK4a and upregulates cyclin D formation. |
|
|
Term
HPV
Type of virus? High risk types? oncoproteins produced by HPV |
|
Definition
| DNA virus. High risk types are 16 and 18. HPV E6 and E7 are the oncoproteins |
|
|
Term
| Role of HPV viral oncoproteins E6 and E7. |
|
Definition
| blocks p53, p21, cyclin D, and Rb. |
|
|
Term
| Epstein-Barr Virus (EBV) Member of what family? Infects what cells? Causes which cancers? |
|
Definition
| herpes family B Cells, and epithelial cells Burkitt Lymphoma (overexpress LMP and EBNA2) B-Cell lymphoma (immunocompromised) Nasopharyngeal carcinoma |
|
|
Term
| Name the two genes of EBV and what they do? |
|
Definition
LMP-1 - transmembrane which functions as a CD40 receptor (survival signal)
EBNA2 - transcription factor that upregulates cyclin D |
|
|
Term
what is Burkitt Lymphoma?
Caused by what?
Associated with what infection? |
|
Definition
| neoplasm of B lymphocytes. Endemic disease is associated w/ EBV. possess t(8;14) translocation |
|
|
Term
| what causes 70-85% of hepatocellular carcinomas? |
|
Definition
|
|
Term
| first bacterium classified as a carcinogen? |
|
Definition
|
|
Term
| What gene in H. Pylori is associated with increased risk of adenocarcinoma? |
|
Definition
| CagA - activates growth factor signal transduction |
|
|
Term
| Examples of tumor antigens |
|
Definition
1. products of mutated genes
2. overexpressed cellular proteins
3. Ags made by oncogenic viruses
4. Oncofetal proteins
5. Altered cell surface glycolipids or glycoproteins
6. Cell type specific antigens |
|
|
Term
| Mechanisms for evading immune serveillance |
|
Definition
1. selective outgrowth of antigen negative variants
2. loss or reduced expression of mHC molecules
3. lack of costimulation
4. immunosuppression
5. apoptosis of cytotoxic T Cells |
|
|
Term
|
Definition
loss of body fat and lean body mass, weakness, anemia.
Not caused by the demands of the tumor or the induced anorexia.
Caused by cytokines, proteolysis inducing factor, lipid mobilizing factor. |
|
|
Term
| define paraneoplastic syndrome |
|
Definition
| symptoms or signs of cancer that cannot be explained by local invasion or distant spread of tumor. |
|
|
Term
| What causes paraneoplastic syndromes? |
|
Definition
| tumor secreting substances such as hormones and cytokines as well as the host immune response to the tumor. |
|
|
Term
name cancer associated with the following paraneoplastic syndromes. Cushings Syndrome
Hypercalcemia
Polycythemia
Trousseau Syndrome (migratory thrombophlebitis)
Autoimmune hemolytic anemia
Acanthosis Nigricans |
|
Definition
cushings -> small cell carcinoma of the lung
hypercalcemia -> squamous cell carcinoma of the lung Polycythemia ->renal cell carcinoma
Trousseau Syndrome -> pancreatic adenocarcinoma Autoimmune Hemolytic anemia -> lymphoma Acanthosis Nigricans -> adenocarcinoma of GI |
|
|
Term
| Grading of tumors is based on what? |
|
Definition
histologic appearance
Degree of anaplasia
Architectural features
Mitotic index |
|
|
Term
| Staging of tumors is based on what? |
|
Definition
TNM system
T - primary tumore
N - lymph node involvment
M - metastases |
|
|
Term
Tumor markers are defined as what?
Useful for what purpose? |
|
Definition
tumor markers are products secreted by tumors that can be assay for in the pt's blood or other fluids
Used for detection, determining efficacy of treatment, and monitoring for recurrence |
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