Term
____ neoplasms are called cancer
____ neoplasms are NOT called cancer |
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Definition
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Term
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Definition
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Term
proto-oncogene:
oncogene:
tumor suppressor gene: |
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Definition
- a gene that promotes entrance into or progression through the cell cycle
- a mutated proto-oncogene that performs its duty without suppression
- gene that prevents entry or continuity through the cell cycle |
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Term
| at what phase in the cell cycle does RB work? |
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Definition
prevents entry into the G1-S phase.
RB binds to E2F in its hypophosphorylated state and prevents E2F's TF activity. CDK 4,6/Cyclin D phosphorylate RB and deactivate it. |
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Term
name a protein or proteins responsible for each of these important functions a tumor must gain before becoming malignant:
- Self-sufficiency in growth signals
- Insensitivity to antigrowth signals
- Evasion of apoptosis
- Sustained angiogenesis
- Limitless replication
- Ability to invade basement membrane, blood vessels, adhere to foreign tissue and metastasize |
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Definition
- (Ras activation, overexpression of growth factor receptors)
- (Rb inactivation)
- (loss of p53 function)
- (increase VEGF, FGF’s)
- (telomerase upregulation)
- (E-cadherin inactivation, proteases, homing signals to other organs) |
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Term
| increase in cell prolif, mutations or epigenetic events activating protooncogenes or inactivating tumor suppressors, and anything that generates free radicals are basis for what? |
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Definition
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Term
These are all examples of what?
Chronic burn injury or osteomyelitis; chronic viral hepatitis, H. pylori gastritis |
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Definition
things that cause chronic inflammation and possibly neoplastic growth.
chronic inflammation upregulates certain TFs. NF-kB is a really important one. |
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Term
| HPV, Epstein-Barr, and plyoma are what and do what? |
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Definition
| they are all viruses that can cause cancer by activating proto-oncogenes |
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Term
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Definition
| a toxin produced by aspergillus that causes major damage to human cells. It is implicated in neoplastic transformation |
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Term
| what are the two cell-cycle checkpoints? |
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Definition
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Term
| centrosome alterations can result in: |
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Definition
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Term
| suppressing terminal differentiation causes |
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Definition
| immortal cell and possibly cancer |
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Term
| carcinoma associate myofibroblasts are? |
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Definition
| cells stimulated by some cancers (particularly those of epithelial origin) that release growth factors and help the cancer survive and possibly aid in invasion and metastasis |
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Term
| _______ activation stimulates a host of cytokines, growth factors, apoptotic inhibitors and angiogenic factors and activation of proteases |
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Definition
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Term
| TP53 is unique for a tumor suppressor gene, because it acts as a dominant ______ |
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Definition
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Term
| ____ is found in over 50% of malignant neoplasms |
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Definition
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Term
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Definition
it is activated (phosphorylated) by ATM, which causes it to suppress transcription of Bcl-2, which represses BAX (an activator of apoptosis). Increase of pro-apoptotic proteins cause the cell to apoptose.
It also causes transcription of p21 and GADD45. The former is a CDK inhibitor, the latter is a DNA repair protein. |
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Term
| In an ironic twist, phagocytosis of ___ ____ can lead to ___ ____. |
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Definition
| apoptotic bodies; genomic instability |
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Term
| euchromatin is responsible for... |
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Definition
| it's the transcriptionally active portion of DNA |
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Term
| how do you tell if a cell is differentiated? |
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Definition
| size and shape of cytoplasm |
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Term
| name some features of benign, non-neoplastic cells. |
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Definition
- uniform in appearance, nuclear size & shape
- maintain nuclear polarity
- orderly arrangement
- cell-cell cohesion
- uniform heterochromatin distribution
- no abnormal mitoses |
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Term
| some light microscopic features of aneuploidy are: |
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Definition
- variations in nuclear size/shape
- irregularities in the nuclear membrane
- increased and/or decreased heterochromaitn and euchromatin |
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Term
| most malignant neoplasms have ___ alterations and abnormal ___ content and therefore abnormal nuclei |
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Definition
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Term
| cytoplasm of malignancies... |
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Definition
| show decreased level of differentiation: less cytoplasm, loss of cilia and decreased mucin produciton are just some examples. |
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Term
| HPV types 16 and 18 have certain proteins that do what during mitosis? |
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Definition
| uncouple centrosome duplication from cell division giving strange mitotic figures (tri/quadripolar) |
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Term
define:
polyp
papilloma
villous papilloma |
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Definition
- a neoplastic or non-neoplastic protrusion above flat surface
- polyp with finger like projections
- a papilloma with thin, leaf-like fonds |
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Term
name where these types of cancers usually spread:
- breast carcinoma
- bronchogenic carcinoma
- neuroblastoma |
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Definition
- breast-->bone
- bronchogenic --> adrenals and brain
- neuroblastomas-->liver and bones
skeletal muscle and spleen are rare sites of metastasis |
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Term
| what happens in burkitt lymphoma? |
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Definition
| the MYC gene on chromosome 8 gets translocated behind the IG gene promotor on chromosome 14 in B-cells |
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Term
| what happens in chronic myelogenous leukemia |
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Definition
| the ABL oncogene on chromosome 9 gets translocated to the BCR locus on chromosome 22 creating a constitutively active BCR-ABL, receptor independent tyrosine kinase |
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Term
| name some regulators in the B-catenin APC system. |
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Definition
WNT receptor sends signals to break up APC and release B-catenin (which binds TCF, a transcription factor).
E-cadherins, when bound to an adjacent protein, sequester B-catenin and keep it inactive same way APC does. |
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Term
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Definition
FASL binds FAS-->activates caspase8-->activates BID and Caspase3-->caspase3 initiates apoptosis
BID is an activator of BAX/BAK which liberate cytochrome c. Cytochrom C dimerizes and activates caspase 9 which continues the sequence to the apoptosome. |
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Term
| list a proposed sequence of events that a invasive epithelial cell has to undergo to become metastatic. |
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Definition
| loose intercellular junctions --> produce collagenase (IV) --> attach to membrane and migrate using autocrine motility factors. |
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Term
| Name, in order, the sequence of events that can lead to metastatic colon adenomas. |
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Definition
| loss of single APC-->double hit on APC leaves B-catenin free to act as a TF-->K-RAS constitutively active-->p53 mutation-->telomerase expression |
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Term
| what causes burkitt's lymphoma? |
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Definition
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Term
| name some ways the immune system can detect tumor cells |
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Definition
- mutated gene
- overexpressed gene
- oncogenic virus |
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Term
| how can tumor cells evade the immune system? |
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Definition
- loss of tumor-specific antigen
- MHC1-deficient tumor
- Immunosuppressive cytokines (TGF-B) |
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Term
name the mechanisms used by cancers to overcome these barriers:
- self-sufficiency in growth signals
- insensitivity to antigrowth signals
- limitless replication
- sustained angiogenesis
- ability to invade |
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Definition
- RAS activation or growth factor production
- RB inactivation
- telomerase upregulation
- VEGFs, FGFs
- E-cadherins, proteases, homing signals to other organs |
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Term
| what is the maximum size a tumor can grow without angiogenesis? |
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Definition
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Term
| inflammatory response is a way that tumors can get vasculature. what is an important cytokine in this process? |
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Definition
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Term
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Definition
accumulation of fluid in the peritoneal cavity
seeding of tumor cells in the peritoneal cavity can cause this |
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Term
| how can cancers cause pleural and pericardial effusions? |
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Definition
| seeding of tumor cells cause inflammation |
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Term
| What are probably the two most important metastatic changes that occur. |
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Definition
| ability to produce angiogenic factors and attach & degrade (manipulate) extracellular matrix. |
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Term
| carcinoma associated fibroblasts (CAFs) do what? |
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Definition
they provide growth factors for the tumor cells:
Called also: tumor-associated fibroblasts (abbr. TAF). These types of fibroblasts or myofibroblasts were described originally as carcinoma-associated fibroblasts (abbr. CAF) Olumi et al (1999). These authors observed that fibroblasts associated with prostatic carcinomas (stromal fibroblasts), but not fibroblasts from normal prostate, stimulate growth, alter the histology of epithelial cells, and stimulate tumor progression of initiated non-tumorigenic epithelial cells in vivo and in vitro. Carcinoma-associated fibroblasts do not affect the growth of normal human prostatic epithelial cells under identical conditions. Thus, the stromal microenvironment of a tumour can be a critical determinant of benign versus malignant growth (Cunha et al, 2003). San Francisco et al (2004) have shown that expression of TGF-beta-1 and colony formation in soft agar differentiate prostate carcinoma-associated fibroblasts from normal prostate fibroblasts. |
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Term
| sarcomas general spread how? |
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Definition
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Term
| how do lung melanomas spread? |
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Definition
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Term
| an exfoliative histological sample is... |
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Definition
| sputum, body fluids, washings |
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Term
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Definition
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Term
| what is romanowsky stain good for? |
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Definition
| microorganisms and hematopoietic lesions. |
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Term
| what are the determining factors for type of chemotherapy treatment in breast cancer? |
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Definition
- Tumor size (if greater than 1cm, give chemo)
- ER & PR status (give estrogen modulator?)
- Her2 status (used to mean a poor prognosis, now there are targeted drugs)
- Age (people over 65 do better with hormonal therapy than chemotherapy)
- Proliferative index (Ki-67) |
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Term
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Definition
Selective Estrogen Receptor Modulators
example: tamoxifen as antagonist for breast cancers; raloxifen (basically same); toremifene (bc) |
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Term
| aromatase inhibitors are typically used on who? |
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Definition
| post-menopausal women with breast cancer |
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Term
| type 1 aromatase inhibitors |
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Definition
False substrate, converted by aromatase to reactive intermediate that binds to enzyme inactivating it. “Suicide inhibition”
*Breast cancer |
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Term
| type 2 aromatase inhibitors |
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Definition
“non steroidal”
Competitive aromatase inhibitors, bind to the heme of cyto P450
type 2s are used more currently
*Breast cancer |
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Term
| How long can you typically use tamoxifen (SERM) before become resistant or dependent? |
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Definition
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Term
| Name some benefits and some toxicities of tamoxifen (SERM) |
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Definition
Benefits:
-increase HDL/LDL ratio;
-reduction in bone loss;
-decrease cardiovascular defects
Toxicities:
- endometrial cancer
- thromboembolism
- hot flashes and vaginal/urinary problems
*Breast cancer |
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Term
| a 'triple negative' tumor is: |
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Definition
PR- ER- Her2-
there is very little treatment for this tumor. prognosis is worse if Ki-67 is high.
*Breast cancer |
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Term
| Ki-67 is a measure of what? |
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Definition
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Term
| if you have a high Ki-67 positive tumor, what type of therapy are you likely to respond to? |
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Definition
Cytotoxic chemo (which attacks dividing cells)
Ki-67 is a marker for proliferative index (PI) |
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Term
| Adriamycin (doxorubicin) and cyclophosphamide: what are they and what do they do? |
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Definition
cytotoxic chemo drugs
Adriamycin: inhibits DNA synthesis by intercalation (topoisomerase II action). side effects: causes decreased oxidative phosphorylation activity of mitochondria and ROS damage of cardiac muscle by interaction with iron compounds
cyclophosphamide: inter and intrastrand cross-linking. Hemorrhagic cystitis (enlargement of the bladder and hematuria/hemorrhage) is a side effect.
*Breast cancer |
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Term
| after surgery/chemo, what is the normal course of treatment (for breast cancer?) and when can't you do this? |
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Definition
5 years on a SERM; when you have ER- PR-
*Breast cancer |
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Term
| What treats Her2+ cancers? |
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Definition
trastuzumab (herceptin) is a MAB against Her2
*Breast cancer |
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Term
| Paclitaxel (Taxol) does what? |
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Definition
It's a mitotic inhibitor: stabilizes microtubules thus disrupting normal centrosome action.
it was first isolated from the bark of a yew tree. it is now synthetically made.
*Breast cancer |
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Term
| what are the factors to determine chemo in a colon cancer? |
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Definition
- not size, but depth of invasion
- lymph node involvement
- metastasis (liver)
- perforation (to abdomen)
- obstruction (bowl pressure may cause tumor cells to get pushed out of the into the surrounding area) |
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Term
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Definition
Folinic acid + 5 flurouricil + oxaliplatin combined therapy for colon cancer.
Folinic acid: protective. readily converted to folic acid derivatives (THF) without dihydrofolate reductase, thus allowing for some nucleotide synthesis. It is used to save bone marrow from destruction during methotrexate therapy.
5-flurouricil is a pyrimidine analog that is incorporated into DNA and RNA and eventually causes apoptosis because the cell can't replicate
oxaliplatin - inhibits DNA synthesis. may have some specific effects on colon cancers. |
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Term
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Definition
| same as FOLFOX, but with Irinotecan (a topoisomerase 1 inhibitor) |
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Term
| Bevacizumab (avastin) does what? |
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Definition
| MAB that blocks VEGF-A and thus angiogenesis |
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Term
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Definition
| MAB against EGFR. has no effect against kRAS mutations |
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Term
stage 3 lymphoma is located _______
stage 4 lymphoma is located _______ |
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Definition
both sides of diaphram
bone marrow |
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Term
| on a CT scan for lymphoma, what do you look for? |
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Definition
| how many bulky lymph nodes there are and where they are located |
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Term
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Definition
| MAB that targets CD20. treatment for B-cell lymphoma |
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Term
| If TTF1 is positive, you most likely have... |
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Definition
lung cancer
TTF = thyroid transcription factor. found in thyroid, lung, and diencephalon. |
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Term
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Definition
cytokeratin: protein of keratin containing intermediate filaments found in epithelial cells
CK7 and CK20 are usually positive in colon cancer |
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Term
| small cell carcinomas grow ___ and respond ___ to chemotherapy. |
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Definition
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Term
| gemcitabine, vinorelbine, docetaxel, and paclitaxel are ___ generation drugs that are used in concert with ____ for treatment of ____. |
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Definition
| Third; platinum chemo drugs; non small cell lung carcinoma (NSCLC). this is called a 'platinum doublet' |
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Term
| what is a problem with using Avastin with NSCLC |
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Definition
| hemorrhage. you have to know if the cancer is adeno or squamous. squamous cancers will BLEED about 3% of the time. |
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