Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
119 Cards in this Set
- Front
- Back
|
Choristoma
|
Normal tissue in abnormal location, i.e. etopic pancreatic tissue in ileum.
|
|
|
Semimoma
|
Malignant testicular tumor
|
|
|
Napkin-ring tumor
|
Adenocarcinoma that causes proliferation of connective tissues that obstructs the colon.
|
|
|
5 markers of anaplasia
|
1. Pleomorphism
2. Abnormal nuclear morphology 3. High mitotic activity 4. Loss of polarity 5. Formation of giant cells and necrosis |
|
|
6 ways tumors can affect host
|
1. Impingement on adjacent structures
2. Hormone Synthesis 3. Bleeding and secondary infections due to ulceration 4. Acute symptoms due to rupture or infarction 5. Cachexia-loss of fat/muscle 6. Paraneoplastic Syndromes |
|
|
What are paraneoplastic syndromes?
|
Symptom complexes that can't be explained by local/distant spread of tumor or by hormones from the tumor. i.e. ectopic hormone production.
Can mimic metastases (i.e. PTH causing hypercalcemia). |
|
|
What does tumor grading indicate?
|
Degree of aggressiveness.
|
|
|
What does tumor staging indicate?
|
Size of primary lesion, extent of spread to regional lymph nodes, presence of metastasis
|
|
|
Is grading or staging more clinically valuable?
|
Staging.
|
|
|
-oma
|
Suffix for benign tumor
|
|
|
-carcinoma or -sarcoma
|
Suffix for malignant tumor.
|
|
|
Multiple Myeloma
|
Malignant tumor of plasma cells. Is one tumor present in many locations.
|
|
|
Seminoma
|
Malignant testicular tumor.
|
|
|
Wilm's tumor
|
Carcinoma of kidney. 2nd most common tumor of childhood.
|
|
|
Dysgerminoma
|
Malignant tumor of ovary.
|
|
|
4 ways that tumors are spread
|
1. Lymphatics
2. Direct extension 3. Blood 4. Serosal surfaces. |
|
|
2 factors that distinguish malignant tumors.
|
1. Metastasis
2. Invasion |
|
|
What is Sturge-Weber Syndrome?
|
encephalotrigeminal angiomatosis. An external birthmark that is a sign of serious condition. Char by port-wine stains in distribution of trigeminal nerve and mental deficiency and seizures.
|
|
|
What is neveus flammeus?
|
Marker for malformation of blood vells in brain. Hemangioma.
|
|
|
What is meningioma?
|
Benign tumor of meninges of brain. Increased intracranial pressure can push brain out the foramen magnum.
|
|
|
Ulceration and obsruction are manifestation of what general types of tumors?
|
Both malignant and benign.
|
|
|
A lung tumor making PTH is an example of?
|
Paraneoplastic syndrome.
|
|
|
A kidney producing abudant light chain amyloid is an example of?
|
Paraneoplastic syndrome.
|
|
|
What is difference between ultimate carcinogen and procarcinogen?
|
* Ultimate: causes cancer while in its natural state or after forming a solution in water.
* Procarcinogen - can be converted to ultimate carcinogen by enzyme. Is stable in its natural state. |
|
|
Give 4 examples of procarcinogens.
|
1. Benz(a)pyrene.
2. Sassafras. 3. Aflatoxin B. 4. Cycasin, pyrrolizidine alkaloids. |
|
|
Describe the metabolism of polycyclic hydrocarbons.
|
Parent compound via MONO OXYGENASE to Epoxide.
Epoxide can covalently bind to nucleic acids and proteins and can mutation. |
|
|
Do all epoxides cause mutation?
|
No. Some are excreted through the liver, usually as conjugated metabolites.
|
|
|
What is the area of activation of polycyclic hydrocarbons called?
|
Bay Region. This is where the enzyme will react and expoxides will form.
|
|
|
Characteristic of procarcinogens that are not polycyclic.
|
Resonating bonds that makes then suceptible to breakage by enzymatic action.
|
|
|
Give an example of non-polycyclic hydrocarbon procarcinogen.
|
Methyl Nitrosyl Guanine (MNNG) which is converted into methyl carbonium ion (ultimate carcinogen) with forms adduct with DNA.
|
|
|
What is the role of p450 enzyme system in chemical carcinogenesis?
|
It resides in microsomal membrane fraction of liver and other cells. Activates oxygenases to form epoxides.
|
|
|
Describe some of the ways that carcinogens mutate DNA.
|
1. Makes DNA not good template for RNA.
2. Removal of purine. 3. Adding C chain. 4. Breaking strand. 5. Hydration of DNA strand. 6. Addition of Adduct. 7. Polyermization along the chain. 8. Cross-linking b/w DNA chains. |
|
|
What single factor effects chemical carcinogens ability to be carcinogenic?
|
Must induce change that is minor enough to allow replication, but major enough to be critical.
|
|
|
How specific is single carciogenic chemical?
|
Most mutagens react with one specific site on the DNA.
|
|
|
Describe 5 properties of transformed cells
|
1. Production of malignancy.
2. Immortality. 3. Growth in soft agar. No need for stroma. Don't have to attach to plate in order to grow. 4. Growth on glass independent of serum factors. 5. Features such as abnormal cell junctions, abnormal reaction to hormones, altered matrix, chromosome alterations) |
|
|
4 stages of carcinogenesis
|
1. Initiation
2. Reversible promotion 3. Irreversible promotion. 4. Tumor progression. |
|
|
Describe function of tumor promoter.
|
Are either mutagenic or carcinogenic; promote tumor formation when applied repeatedly after a sub-carcinogenic dose of carcinogen.
|
|
|
If a promoter is applied spread out over a period of time after the initiator, will tumor form?
|
No. There is sufficient time for repair to take place.
|
|
|
Provide an example of a tumor promotor
|
TPA. Component of croton oil. Has differential effects on different cell types.
|
|
|
Which cell type is affected by carcinogens?
|
Stem cells.
|
|
|
What is epigenetics?
|
Study of processes that establish somatically inheritable states of gene expression w/o altering DNA sequences.
|
|
|
Name 4 targets assoc with molecular basis of cancer.
|
1. Protooncogenes.
2. Tumor suppressor genes. 3. Apoptosis. 4. DNA repair. |
|
|
7 fundamental changes in cell physiology that determine malignant phenotype.
|
1. Can proliferate w/o external stimuli.
2. Insensitivity to growth inhibitory signals. 3. Evasion of apoptosis. 4. Defects in DNA repair. 5. Immortality. 6. Sustained angiogenesis. 7. Ability to invade/metastasize. |
|
|
What is an oncogene?
|
Genes that promote autonomous cell growth.
|
|
|
What role does TGF-beta play in tumors?
|
It inhibits cell proliferation.
|
|
|
What is the major role of p53?
|
Cell cycle arrest in late G1, initiation of apoptosis if damage, and induction of DNA repair genes.
|
|
|
What is required for autosomal dominant inherited cancer syndromes to manifest themselves?
|
Loss of heterozygosity. (Both alleles need to be mutated, but they are inherited in autosomal dominant manner).
|
|
|
4 Examples of autosomal dominant inherited cancer syndromes and their genes.
|
1. Retinoblastoma -Rb
2. Familial adenomatous polyposis - APC. 3. Breast/Ovarian - BRCA1/2 4. Li-Fraumeni syndrome-p53 |
|
|
What change in Rb is assoc with retinoblastoma?
|
Rb is phos by cyclin/CDK and releases E2F. Unbound Rb leads to gene transcription.
|
|
|
How does mutation in APC lead to familial adenomatous polyposis?
|
APC fails to degrade beta-catenin. Beta-catenin leads to transcription.
|
|
|
Name 3 Autosomal Recessive Syndromes of DNA repair
|
1. Xeroderma pigmentosum
2. Ataxia-telangectasia 3. Fanconi anemia. |
|
|
How many cell doublings is required for clinically detected mass in lung?
|
30. (10 to 9th or 1gram)
|
|
|
How many mutated alleles for tumor suppressor genes is neede for cancer?
|
2 mutated alleles.
|
|
|
List 6 proteins involved in cell growth (mutation of any can lead to tumor growth).
|
1. Growth factors.
2. GF receptors 3. Intracellular signal transducers. 4. Nuclear transcription factors. 5. Cell-cycle proteins (cyclin/CDK) 6. Apoptosis |
|
|
Describe two ways in which self-sufficiency in growth signals can occur.
|
1. overexpression of GF.
2. Receptors always ON even w/o ligand binding. |
|
|
What is the role of Cyclin-CDKs in regulating the cell cycle?
|
Is one of 1st points to be deregulated. Inactive CyclinD/CDK is phosphor. This activates it and it allows G1-S transition.
Note: the complex phos Rb and plays role in retinoblastoma. |
|
|
Role of CDK inhibitors and significance of p53.
|
Inhibitors serve as checkpoints. p53 upregulates p16 and p21 CDK inhibitors. p53 can stop cycle at G1 to S phase and at G2 to mitosis.
|
|
|
List 5 types of oncogenes
|
1. Growth Factors
2. Growth FActor Receptors 3. Signal TRansduction Pathways 4. Nuclear Regulatory Proteins 5. Cell Cycle Regulators. |
|
|
Which particular proto-oncogene is oveproduced in many tumors?
|
SIS, which encodes for beta-chain of PDGF. These tumors also receptor for PDGF (autocrine stimulation loop)
|
|
|
What molecular modification occurs in GF receptor oncogenes?
|
Receptors are constitutively dimerized and are activated without bound GF.
|
|
|
What is Herceptin?
|
A monoclonal antibody for HER2 receptors which are amplified in 25% of breast ca.
|
|
|
What is RAS?
|
A signal transduction protein product of oncogenes which results in increased GF and GF stimulators (TGF=alpha).
|
|
|
What transcription factor alteration is mnost common in cancers?
|
Myc, a potent transcription activator.
|
|
|
What happens if myc is produced without a growth signal?
|
Apoptosis. Usually you have grwoth signal, then myc production, then increased transcription.
|
|
|
Name 2 conditions associated with myc gene chromosomal translocation.
|
1. Burkitt Lymphoma - translocation onto chromosome 14. Overexpression of Ig (heavy).
2. Chronic Myelogenous Leukemia - persistently active tyrosine kinase. |
|
|
Explain 2 hit hypothesis.
|
2 events necessary for tumor formation:
1. Genetic change inherited from parent. 2. 2nd mutation, resulting in recessive cancer gene. Loss of heterozygosity. |
|
|
What is Li-Fraumen syndrome?
|
inheritance of one mutant p53 allele.
|
|
|
How does p53 affect chemotherapy?
|
Tumors with normal p53 respond better to chemo because they allow treatment to induce DNA damage and then undergo apoptosis.
|
|
|
What does beta-catenin allow>
|
Persistent cell proliferation.
|
|
|
What down=regulated beta=catenin?
|
APC. Adenomatous polyposis coli.
|
|
|
How is APC implicated in colon cancer?
|
homozygous loss of APC results in failure to down-regulate beta-catenin, resulting in persistent cell proliferation.
|
|
|
What does bcl-2 do?
|
Protects cell from apoptosis.
|
|
|
Describe 3 types of DNA repair defects.
|
1. Mismatch repair (hereditary nonpolyposis cancer syndrome)
2. Nucleotide excision repair (UV light causing crosslinking of pyrimidines, xeroderma pigmentosum) 3. Recombination repair (BRCA1/2) |
|
|
Role of telomerase in tumors.
|
90% of cancerous tumors have persistent telomerase activity. Maintains length of telomere, so can continue replicating.
|
|
|
Name 2 important checkpoints where inhibitors play role and name them.
|
1. G1-S. Regulated by phos of Rb. (phos-proceed)
2. G2-M. Cyclin DK. |
|
|
List 7 types of endogenous DNA damage.
|
1. Depurination
2. Depyrimidination 3. Deamination of Cytosine 4. Single Strand Breaks 5. SSB after depurination 6. 8-Hydroxyguanine 7. O6-Methylguanine |
|
|
List 5 types of DNA repair.
|
1. Base excision
2. Nucleotide Excision 3. Direct Reversal 4. Mismatch Repair 5. Recombination Repair |
|
|
What is base excision repair?
|
aberrant bases are removed. i.e. Bases modified by oxidative damage are repaired by base excision.
|
|
|
What is nucleotide excision?
|
Bulky damages create alterations in DNA helical structure and can lead to altered replication. Are cute out and DNA is ligated. i.e. pyrimidine dimers and DMBA-induced damage.
|
|
|
What is direct reversal repair?
|
Direct reversal back to normal by specific enzymes. i.e. photolyase breaking pyrimidine dimer or alkyltransferase converting oxidated guanine to guanine.
|
|
|
What disease is associated with mismatch repair deficiency?
|
Hereditary Non-Polyposis Colon Cancer (HNPCC)
|
|
|
What is recombination repair?
|
Putting double strand DNA break back together.
|
|
|
What specific genes are involved in recombination repair?
|
BRCA-1 and BRCA-2
|
|
|
What aberration has been found in 100% of lung cancer patients?
|
Aberrant methylation of p16 or O6-methyl-guanine-DNA methytransferase (repair genes)
|
|
|
What mechanism is responsible for Xeroderma Pigmentosum?
|
Mutation in 1 of the 8 nucleotide excision repair genes which repair pyrimidine dimers.
|
|
|
At what wavelength does DNA maximally absorb light?
|
260 nm. (most sunlight is 320 nm)
|
|
|
UVA vs. UVB radiation
|
UVA - 315-400 nm. (some melanoma)
UVB -280-315. (melanoma, sunburn) |
|
|
What is role of melanin in skin cancer?
|
It is a photosensitizer, meaning that it absorbs all wavelengths. (Hypothesis: activation causes oxidative damage to DNA)
|
|
|
How does amt of melanin influence cancer development?
|
High melanin, lower non-melanoma skin cancer.
Melanin absorbs UVA light mainly. Also lower melanoma b/c contribution of UVA filtering. |
|
|
What type of UV light inhibits the immune system?
|
UVA
|
|
|
Do melanocytes protect against melanoma?
|
Melanocytes without melanin (albinos) result in more basal and squamous cell carcinoma, but low melanoma. Empty melanocytes are more resistant than keratinocytes to malignant transformation.
|
|
|
At what wavelength does DNA maximally absorb light?
|
260 nm. (most sunlight is 320 nm)
|
|
|
UVA vs. UVB radiation
|
UVA - 315-400 nm. (some melanoma)
UVB -280-315. (melanoma, sunburn) |
|
|
What is role of melanin in skin cancer?
|
It is a photosensitizer, meaning that it absorbs all wavelengths. (Hypothesis: activation causes oxidative damage to DNA)
|
|
|
How does amt of melanin influence cancer development?
|
High melanin, lower non-melanoma skin cancer.
Melanin absorbs UVA light mainly. Also lower melanoma b/c contribution of UVA filtering. |
|
|
What type of UV light inhibits the immune system?
|
UVA
|
|
|
What is a superman cell?
|
Rare cancer cells within a primary tumor that acquire metastatic capabilites through somatic mutation.
|
|
|
What structural change is required in order for metastasis to occur?
|
Breach in the basement membrane.
|
|
|
What is a genetic profile of tumor cells?
|
A profile that matches primary and metastatic cells. Poor prognosis.
|
|
|
What role do matrix metalloproteinases (MMPs) play in metastasis?
|
MMPS degrade basement membranes by cleaving collagen, laminin ( and other substrates in the ECM.)
|
|
|
What role do Plasminogen Activators play in metastasis?
|
uPA and tPA are serine proteases which can activate MMPs.
|
|
|
What do metalloproteinases require in order to work?
|
Zinc.
|
|
|
List 2 types of MMPs.
|
1.MT-MMP - connected to PM. Impo in tumor proliferation
2.MT1-MMP - |
|
|
Describe the process by which the basement membrane is broken down in metastasis.
|
Ca cells have EMMPRIN, glycoprotein, on their surface. EMMPRIN stimulates fibroblasts to make MMPs which cause BM to break down.
|
|
|
What is EMMPRIN?
|
Extracellular Matrix Metalloproteinase Inducer, on surface of CA cells which induces fibroblasts to produce MMPs.
|
|
|
What positive role do MMPs play?
|
Regeneration and wound repair.
|
|
|
What role do cell-cell adhesion play in metastasis?
|
Must be broken for metastasis to occur.
|
|
|
What cell adhesion molecules are abnormal in metastasis and invasion?
|
1. Loss of E-cadherin function. (link cells)
2. Catenin (which link intercellular domain). 3. Integrins (link to ECM) |
|
|
What motility factors are associated with metastatis?
|
1. Autocrine motility factor.
2. Scatter factor/hepatocyte GF 3. Insulin-like GF 4. Chemokines 5. Epithelial-Mesenchymal Transition |
|
|
What chemokine receptor is upregulated in breast ca?
|
CXCR4 (ligand is SDF-1)
|
|
|
What are anti-metastatic genes?
|
1 Maspin
2. MIM 3. KISS 4. Nm23B |
|
|
What 3 roles does cancer stroma play in cancer:
|
1. Produce GF ad proteases that facilitate cell growth.
2. Harbor mutations, like p53 3. Inflammatory cells (T/B) can enhance or interfere with tumor progression. |
|
|
4 mechanisms behind tumor dormancy?
|
1. Immune suppresion.,
2. Lack of neoangiogenesis. 3. Natural inhibitors of angiogenesis. 4. Proteases (Plasminogen activator, MMPs) |
|
|
What growth factors are involved in angiogenesis?
|
Veg-F and angiopoietin families.
|
|
|
Describe 4 steps involved in tumor angiogenesis:
|
1. Secretion of angiogenic factors by tumor.
2. Destruction of ECM of vessel. 3. Endothelial prolif and migration. 4. New capillary sprout. |
|
|
What types of metabolic stress turn on angiogenesis?
|
1. Low pO2
2. low pH 3. low glucose |
|
|
Name 2 general classes of vascular growth factors.
|
1. Endothelium-specific (VEGF, Angiopoietin, Ephrins)
2. Non endothelium-specific (PDGF, TGF-beta) |
|
|
2 roles VEGF-A plays in angiogenesis.
|
1. Endothelial proliferation
2. Vascular leak permeability. Subsequently, angiopoietins and ephrins are involved. |
|
|
How does MMP affect VEGF?
|
MMPs cleave matrix-bound VEGF. There fragments promote capillary dilatation.
|
