question

Overall cancer death rates continued to ___ in the United States among both _____ and ____, among all major racial and ethnic groups, and for all of the most common cancer sites, including ____________.

answer

decline; men and women lung, colon and rectum, female breast, and prostate.

question

Death rates continued to ____ during the latest time period (2000 through 2009) for _____ (among men only) and for cancers of the ___________.

answer

increase melanoma of the skin liver, pancreas, and uterus

question

Most human cancers are _____ because there is no identifiable inherited gene involved, but the cancers developed as a result of _________ (carcinogens such as cigarette smoke) that randomly induced mutations in cells that led to uncontrolled growth.

answer

"sporadic" environmental factors

question

Environmental factors are encountered throughout life and act over ______; hence, most _____ occur in ____ .

answer

a long period of time sporadic cancers adults

question

Most affected persons have _____, and that site is where you would expect most cancers to be (breast, lung, prostate, colon, etc.)

answer

one primary site

question

Sporadic Cancer is a ________ of a specific cancer in _____. It is _____ and a _______ in paired organs. It has a ______ of onset, starting with a ____________.

answer

Single occurrence the family Monoclonal Unilateral tumor Later age Single primary tumor

question

In sporadic cancer, _____ generally not at increased risk. It is rarely seen in ________.

answer

Relatives 'wrong' sex. (breast cancer in females)

question

Cancer has a misregulation of cell cycle. What mechanisms cause this?

answer

1. Activation of growth activation pathways 2. Loss of function mutations in growth inhibitors • Both mechanisms account for multistep hypothesis of cancer progression

question

Benign - X - Metastatic

answer

X = Malignant

question

Types of Proto-Oncogenes

answer

1. Secreted growth factors 2. Cell surface receptors 3. Intracellular signal transducers (Ras) 4. DNA-binding nuclear proteins, including transcription factors (Myc) 5. Cell cycle regulators - cyclins, cyclin dependent kinases

question

Ras proteins are molecular switches controlled by GTPase and nucleotide exchange

answer

Normal: Ras G12 "Activated": RasG12V Glycine to Valine mutation caused constitutively active state of Ras protein. This locks Ras in the activated state because the inhibitor of Ras cannot bind. This increases cell proliferation. HUGE in pancreatic cancer.

question

Drugs targeting Ras Pathways

answer

Drugs try to block all Ras pathways, depending on where the mutation is. You need to know where the molecular defect is to know if it is up or downstream. Ex Herceptin is upstream.

question

Histology slides of neuroblastoma shows:

answer

-Neuro-rosettes -Neuropil cells -Stage IV disease -Multiple bony metastasis -Bone marrow involvement

question

Neuroblastoma

answer

cancer of nerve cells (neurons) usually appearing in the embryo or shortly after birth in adrenal cortex

question

Neuro-rosettes? Neuropil cells (neuropile cells)?

answer

(or neural rosettes) rosette-like cluster of neural progenitor cells. (top) synaptically dense region with mostly unmyelinated axons, dendritic cells and glial cells.

question

Degree of oncogenic expression correlates with:

answer

stage of disease at diagnosis response to treatment prognosis

question

Greater than _____ of _______ is associated with amplification of N-Myc oncogene.

answer

One third neuroblastoma

question

_____ amplification is one mechanism of activation of cancer. If you increase the copies of it, you get _________. If you decrease the copies, you get ____.

answer

N-myc diagnosis of cancer at an earlier age diagnosis of cancer at a later age

question

Prognostic factors of Neuroblastoma

answer

predicting disease outcome based on: -patient's age at diagnosis stage of disease at diagnosis -ploidy level of tumor -presence/absence of N-Myc -gene amplification

question

Good outcome of Neuroblastoma

answer

-Infants -Hyperdiploid (;46) or near-triploid (69) chromosome number -No amplification of N-Myc gene

question

Poor outcome of Neuroblastoma

answer

-Age ;1 year -Near diploid (~46) or near-tetraploid (92) chromosome number -Amplification of N-Myc gene

question

Oncogenes- dominant oncogenes via 3 ways.

answer

1. Growth Activators- many steps 2. Mutational Activation (Ras, example) 3. Amplification (myc, example)

question

Knudson's Two Hit Hypothesis:

answer

A tumor ensues when two events occur in the same cell lineage, both copies of the gene need to be "hit" a "reminder" that dominance and recessiveness are properties of phenotype, not of genes or mutations

question

Familial tumor:

answer

individual born with mutation already so every cell susceptible only one additional mutation needed to develop the tumor family susceptibility inherited as a dominant trait whereas the the need for a second hit is a recessive pattern

question

Sporadic tumor:

answer

two events in same founder cell, likely to be rare

question

Retinoblastoma (Rb) tumor suppressor gene

answer

-Most common eye tumor in children -Occurs in heritable and non-heritable forms

question

Tumor Suppressor Genes

answer

Genes whose normal activity is to restrain cell growth and activity

question

______ in tumor suppressor genes, creates forms that lose their ____ function

answer

Loss of function mutations inhibitory

question

The TSG mutation converts the function of a normal tumor suppressor gene into a _________.

answer

cancer promoting function

question

G1-S checkpoints:

answer

genes should not be able to start replicating their DNA until all DNA damage has been repaired Unrepairable genes are triggered to undergo apoptosis

question

S phase checkpoint:

answer

operates whilst DNA is being synthesized. Different replication origins become active at different times during S phase

question

G2-M checkpoint:

answer

prevents cells from initiating mitosis when there is unrepaired DNA damage

question

_______ control Checkpoints.

answer

Tumor Suppressors

question

Function of recessive oncogenes

answer

-Encode growth inhibitors (brakes on cell cycle) -Requires loss of both alleles for cancer phenotype Examples Rb and p53

question

Multi-step nature of tumor genesis; What are 3 things needed for tumor genesis?

answer

1. Cancer progression requires a series of mutations 2. Gain of function (activators) and loss of growth inhibitors 3. Mutations that alter cell cycle increase subsequent mutation rates.

question

Familial Adenomatous Polyposis

answer

-Clinically defined as: at least 100 adenomatous polyps -often thousands of polyps present throughout the colon with early age of onset average ~16 yrs, range 8-34 yrs

question

Mutations in ____ Gene are Responsible for Familial Adenomatous Polyposis (FAP).

answer

APC

question

APC is a ____ gene. Mutations in the APC gene ____ account for ~95% cases of FAP.

answer

tumor suppressor 5q21

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