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46 Cards in this Set

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What image regarding Oncogenes & their protein products did Gilbert ask us to memorize?
Robbins pg 294, Fig 7-31
What is the 2nd image regarding Growth factors & growth factor receptors that Gilbert wants us to understand - by looking at the explanation in the text?
Robbins pg 297, Fig 7-32
What is the age range with highest cancer diagnoses?
55-74 years old, but NO age group is spared
What are some common environmental factors with high cancer indicence?
Sun exposure - melenoma
Alchohol abuse - GI tract CA
Promiscuity/STDs- Cervical CA
What are some hereditary factors that affect cancer?
Autosomal dominant syndromes (familial retinoblastoma)
Familial cancers (breast, ovarian, colon)
Defective DNA repair, autosomal recessive syndroms (Xeroderma pigmentosum)
Why do you have to differentiate between hereditary and genetic factors for cancer?
ALL cancer is genetic - it's a problem that has occured in DNA

NOT all cancer if hereditary (inherited from parents)
List 4 inherited cancer cyndromes - Autosomal dominant
Retinoblastoma
Li-Fraumeni syndrome (various tumors
Melanoma
Familial adenomatous polyposis/colon cancer
P53 - what is it?
It's a tumor repressor gene ("brakes" for cell growth)
Mutation of this gene is associated with 50% of cancer diagnoses because it can no longer induce apoptosis of damaged cells
Which phrase regarding development of cancer do you need to have memorized?
METAPLASIA leads to DYSPLASIA, Carcinoma-in-situ and the CANCER

Memorize this!
Acquired PRE-neoplastic disorders:
List 2 that are chronic inflammatory diseases
Ulcerative colitis (required colectomy because it WILL become malignant)
Hepatitis
Acquired PRE-neoplastic disorders:
List 2 NON-neoplastic disorders
Salar keratosis (spots on hands, forehead, etc)
Leukoplakia (white placques, in oral cavity due to irritation like denture, pipe smoker)
What's the Molecular Basis of Cancer?

(Gilbert suggests NOT reading the text book on this, too tough!)
-Nonlethal genetic damage (ie UV radiation)
-Regulatory genes - something gets out-of-whack
*Proto-oncogenes promote growth
*Antioncogenes inhibit growth
*Apoptosis
*DNA repair gene
KNOW: Cardinogenesis is a multistep process @ phenotypic & genetic level
What are oncogenes?
Cancer-causing genes
Derived from protooncogenes (aka V-onc) that promote normal growth & differentiation
Spontaneously arising cancers will have oncogenes in DNA
Cell oncogenes (aka C-onc) can be formed from V-oncs by retroviral tranduction or by somether that alatered V-onc behavior in situ.
What are the 5 protein products of Oncogenes? Why are these clinically significant?
Growth factors
Growth factor receptors
Proteins in signal transduction
Nuclear regulatory proteins
Cell cycle regulators

*Significant because if we can block any of these, we can halt cancer
What is an example of a drug that interferes with a growth factor receptor?
Herceptin is a newer drug that attaches to HER2 growth stimulating receptors, blocking but not stimulating them.
HER2 receptors cause breast cancer when overexpressed.
Drug has only lengthened survival time by 4 mon
What is the "ras" gene?
Point mutation of the ras gene is the single most common cause of abnormality of dominant oncogenes in humans (affects Signal Transduction proteins)
How are oncogenes activated?
Either changes in structure of the gene
Or in the regulation of gene expression (Point mutations, chr rearrangements & gene ampl)
What happens in a translocation?
Overexpression of protoncogenes due to chromosomal rearrangement

Ex: Philadelpia chr- a movement of a chunk of Chr 9 exchanged with a chunk of Chr 22 - characteristic of chronic myeloid leukemia
What happens in gene amplification?
Overexpresson of Oncogenes from reduplication & manifold ampl of the genes's DNA seqence
May result of several hundred copies in tumor cell
How does gene amplification affect age on cancer onset?
When genes are prone to amplification, each generation will have a larger number of copies at birth.
These multiply in each generation, causing offspring to have a more copies of the gene at a younger age than the previous generation.
Ex. Onset of cancer for Gma=73, Mom=55, Daughter=39
How is age on onset related to cancer severity?
Younger onset usually means more agressive (possibly due to hormonal issues)
What are 3 tumor repressor genes that have to do with cell cycle regulation?
RB (retinoblastoma)
BRCA1 & BRCA2
p53
How does HPV cause cancer?
By phosphorylating (& thus activating) a cell cycle control gene, stimulating growth in the cervix & leading to cervical cancer
What is the role of Hypoxia in cancers?

**Gilbert says he always tests on this
Hypoxia induces mutations in p53, preventing DNA repair & allowing proliferation of cancer cells
What percent of breast cancer is caused by BRCA1 or 2?
5-10% are due to these genes, the rest are "spontaneous" cancers - not inherited
what is APC and what does it lead to?
APC is ademomatus polyposis coli gene - (means colon polyps)
LOSS/mutation of APC is a step in evolution of colorectal cancer.
A Signal Transduction regulator - APC slows down proliferation of cells
What is neurofibromatosis?
"Lumps and Bumps" - tumors formed. Location determines severity. Can lead to brain tumors. Gene (NF-1) regulates signal transduction
Name 3 cell surfacr recptors that are associated with cancer
TGF-G (growth inhibitory factor, upregulates transcription of growth-inhib genes)
Cadherins - "glue" holding tissue together, when lost, favors local invasion/metastases
DCC - Deleted in Colon Carcinoma
Name 2 genes that inibit cell death
bcl-2
bcl-xl
Name 3 genes that favor apoptosis
bax
bad
bcl-xS
How does normal p53 affect the bax gene and what is the result?
p53 upregulates bax to cause apoptosis.
What's the molecular basis of mutistep carcinogenesis?
*Multiple steps in initiation & promotion
*Activation of several oncogenes & loss of 2+ cancer-suppessor genes
*"gatekeeper" genes directly regulate growth of tumors
*"caretaker" genes affect genomic stability
Steps of specific morphologic & molecular change in colon cancer development
Start with normal epithelium.
Loss/mutation of APC leads to metaplasia
Loss of DNA methylation leads to early dysplasia
Mutation of ras gene leads to intermed dysplasia
Loss of tumor suppressor on 18q leads ot late dysplasia
Loss of p53 leads to carcinoma-in-situ
Which leads to cancer
List 4 karyotypic changes found in tumors
Translocations
Deletions
Gene amplification
Whole chromosomes may be lost or gained
What is involved in tumor growth?
Doubling time - growth rate
Angiogenesis - can't grow over 2mm w/out own blood supply
Tumor progression & heterogeneity - invasiveness, metastatic ability, etc
How many "doubling times" for a tumor to be detectable?
30 doubling times to form a 1 g tumor, the smallest detectable via CT
Just 10 more doubling times could give a 2.2 lb tumor
Describe tumor angiogenesis
Newly formed endothelial cells produce growth factors such as:
VEGF - Vascular Endothelial Growth Factor
bFDF - basic Fibroblast Growth Factor
Tumor progression & heterogeneity - what does term this mean?
Most malignant tumors are monoclonal (all from one cell) but cells are heterogeneous (cell subpopulations have different characteristics)
What differentiates carcinoma in -situ from metastasis?
Tumor is carcinoma-in-situ UNTIL a basment membrane is breached by altered cells.
How does a tumor cell invade extracellular matrix?
1) Detachment of tumor cells from each other - attachments loosen up
2) Attach to matrix components (laminin)
3) Degradation of extracellular matrix (collagenase)
4) Migration of tumor cells through basement membrane
Describe vascular dissemination and homing of tumor cells
-Tumor cells in circulation are vulnerable to immune defenses
F-ormation of platelet-tumor aggregates seem to enance tumor cell survival & implantability
**It appears some organs have chemoattractants that recruit tumor cells to that organ (ie adrenals) OR that there are stimulating factors for cancer that travel to areas that already have pre-cancerous cells
What is an initiator?
A carcinogenic agen that causes permanent DNA damage
Most are metabolized by cytochrome P-50 enzymes
What is a promoter?
Something that induces cell growth, & thus tumors, in INITIATED cells. Does NOT cause tumors in uninitiated cells so is nontumorigenic by itself
Examples of initiators?
Chemotherapy drugs
Immunosuppressive Rx
Hydrocarbons from burning (ie tobacco)
Hep B birus
Nitrates (preservative
Asbestos, chromium, nickel, etc
Examples of promoters?
Cigarette smoke
Viral infections
Estrogens
Bile salts
High levels of dietary fat
How does UV light effect carcinogenesis?
UVB causes pyrimidine dimers in DNA - thus it is an initiator