Cancer I

Question 1

cancer stats

Answer 1

• 1/5 will die of cancer
• 1/3 will contract cancer
• 1.3 mil new cancer cases/year
• about 50% of these new cases will die from their cancer (600,000)
• compare to 725,000 deaths from heart attacks

Question 2

what is the deadliest type of cancer? compare it to breast cancer

Answer 2

lung cancer is the deadliest; the different survival rate is due to the fact that you can remove tumor from breast but cannot remove it from the lung.

Question 3

** what are some properties of cancer cells?

Answer 3

cells grow out of control

become self-sustaining, do not need signals to grow

release autocrine growth factor signals

these cells should stop growing with anti-growth signals -but cancer cells ignore them

cancer cells ignore apoptosis signals

Question 4

info about cell growth, division, and cancer

Answer 4

cell growth is controlled by growth factors

growth factors produced by other cells stimulate target cells to divide (healing, growth)

cells do not divide unless told to do so

Question 5

what is erythropoeitin?

Answer 5

its a small protein growth factor that is produced by the kidneys when RBC is low

it stimulates bone marrow to produce more RBCs

Question 6

normal vs cancer cells

Answer 6

cancer cells require little growth factors

normal cells have a strong requirement for growth factors

cancer cells become independent of stimulation that is normally required by cells to proliferate

cancer cells have uncontrolled proliferation

Question 7

what are the two heritable properties of cancer cells?

Answer 7

1) they reproduce in defiance of normal restraints on cell division and cell growth
2) invade areas normally reserved for other cells

Question 8

how does cancer kill?

Answer 8

as tumor grows and spreads, it squeezes or destroys blood vessels, nerves - until organ can no longer do its job - death results

Question 9

what is the pathology of cancer?

Answer 9

an abnormal cell that grows (incr in mass) and proliferates (divides) out of control will give rise to a tumor or neoplastic growth

Question 10

what is a benign tumor?

Answer 10

if the neoplastic cell does not become invasive, then it is benign.

this means you can surgically remove local mass as cure

Question 11

when is it considered cancer?

Answer 11

if it is malignant - which means if cells have the ability to invade surrounding tissues

Question 12

what are some classifications of cancers?

Answer 12

carcinomas: from epithelial cells (most common)
sarcomas: from connective tissue and muscle tissue

leukemias and lymphomas - from white blood cells and their precursors

adenoma: benign epithelial tumor with glandular organization

Question 13

differentiate between basal-cell carcinoma vs melanoma:

Answer 13

BCC rarely metastasizes whereas malignant melanomas metastasize widely

Question 14

what is metastases?

Answer 14

invasiveness as a property of cancer

when a cancer cell breaks loose, enters the blood or lymph, and travels to a new area and forms a secondary tumor

this kills patients

Question 15

describe tumor development

Answer 15

it involves multiple mutational events

all tumors from a single ancestor

mutations confer a proliferative advantage

mutations allow cells to grow more rapidly than normal

Question 16

tumor development: colon cancer.

what gene is mutated?

Answer 16

APC gene, which is a tumor suppressor

Question 17

describe the APC gene mutation and cancer development

Answer 17

cells with an APC gene mutation gain an advantage in growth - they firm polyps. at this stage, still a benign tumor.

Question 18

what happens when a mutation in Ras occurs?

Answer 18

it becomes “cancer” gene

loss of other tumor suppressor - lose p53

tumor moves out into blood stream, gains capacity to invade, now malignant tumor

Question 19

where do most cancers derive from?

Answer 19

a single abnormal cell; a primary tumor

also, from a single cell that outgrows, out-divides and out-lives neighboring cells

Question 20

what evidence is there for cancer from a single heritable cell?

Answer 20

philadelphia chromosome (translocation between Car 9 + 22)

Philadelphia chromosome is smaller

Responsible for CML (chronic myelogenous leukemia)
all cancer cells have this same chromosomal aberration- not a spectrum of different defects

Question 21

what type of mutations do cancer cells contain?

Answer 21

somatic mutations

Question 22

what are two types of carcinogens?

Answer 22

chemical and radiation

Question 23

what is the best weapon against cancer?

Answer 23

early detection

Question 24

what is an example of tumor progression into cancer?

Answer 24

cervical cancer

Question 25

cancerous growth depends on what two things?

Answer 25

defective apoptosis

defective growth

Question 26

what are the steps in the process of metastasis?

Answer 26

normal cells grow as benign tumor in epithelium

cells become invasive and enter capillary

adhere to blood vessel wall in liver

escape from blood vessel to form micro metastasis

colonize liver forming full-blown metastasis

Question 27

what is the most deadly aspect of cancer?

Answer 27

metastasis - can’t eradicate by surgery or irradiation

Question 28

what is angiogenesis?

Answer 28

formation of new blood vessels

tumors must get oxygen and nutrients like normal cells, cancer cells release factor to induce new blood vessels formation

*antiogenesis is a target of cancer therapy (Folkman)

Question 29

what is neovascularization?

Answer 29

the formation of new blood vessels basically from scratch

Question 30

differentiate the two

Answer 30

angiogenesis is when the blood vessels sprout from pre-existing blood vessels vs neovascularization is the formation of new blood vessels basically from scratch

Question 31

what are some more properties of cancer cells?

Answer 31

more self-suffiecient

insensitive to anti-proliferation signals from outside cell

less prone to undergo apoptosis

defective in cell cycle control mechanisms to stop cell cycle

gets help from stromal cells (fibroblasts and WBCs)

induces angiogenesis

invasive to other tissues

do not show replicative-senescence (stop dividing after a # of divisions) but are immortal

Question 32

what is the Ames test?

Answer 32

a test that uses bacteria to test whether certain chemicals can cause mutations in DNA; eg: bacteria needing histidine. salmonella will not grow histidine, unless mutated DNA

Question 33

what other viruses and infections contribute to human cancer?

Answer 33

AIDS: HIV causes Kaposi’s sarcoma

Ulcers and Helicobacter pylori - can cause stomach cancers

Question 34

what is the most environmental cause of cancer?

Answer 34

Tobacco

90% of people with lung cancer smoked

last year 20% of people who died - was due to smoking (600K) - heart disease, emphysema, cancer

13% of lung cancer victims survive

Question 35

what are two general genetic causes of cancer?

Answer 35

oncogenes and tumor suppressor gene

Question 36

what are cancer critical genes?

Answer 36

genes who alteration frequently result in cancers

Question 37

what is a third group that may cause cancer?

Answer 37

DNA maintenance genes (subset of TSG)

mutations involve inactivation of caretaker genes that create genomic stability

include DNA repair genes, checkpoint genes

Question 38

discuss retroviruses and oncogenes

Answer 38

Rous sarcoma virus (RSV) can cause cancer in chickens

this retrovirus contains an RNA genome which upon enfection of host cell is reverse-transcribed into DNA that is integrated into host genome - get transformed cells

Question 39

what are transformed cells?

Answer 39

small colonies of proliferating cells caused by oncogene

Question 40

what does transcformation of RSV depend on?

Answer 40

v-src oncogene

the virus hijacks c-src (normal cell gene) and makes a mutation so c-src is activated like crazy

retroviruses hijack porto-oncogenes and activate them by either over-expression or cause mutations of porto-oncogene into oncogene (via Ras)

Question 41

what is the first human oncogene?

Answer 41

Ras

Ras is a monomerc GTPase for signal transduction

Ras oncognes: cannot shut off by hydrolyzing GTP to GDP

overactivity leads to cancer

Question 42

what are some ways to activate oncogenes?

Answer 42

1) deletion or point mutation in coding sequence - makes hyperactive protein (eg: Ras codon 12 Gly to Val: keeps Ras protein in active state)
2) regulatory mutation - produce more normal protein - promotor mutation
3) gene amplification - several copies instead of 1 copy - normal protein overproduced
4) chromosomal rearrangement - brings new regulatory sequence that causes over production OR creates overactive fusion protein (eg: EGF receptor - rearrangement removes extracellular domain, truncated EGF receptor - becomes active without ligand. receptor fools cell to divide –> glioblastoma (brain tumor))

Question 43

what other situations cause cancer?

Answer 43

too many ligands

too many receptors

transcription factors (too many)

over production of cell cycle proteins

proteins that inhibit apoptosis - like Bcl2 (promotes cell survival despite DNA damage) - overproduction allows cancerous cells to survive and grow

Question 44

speak on Bcl2 oncogene

Answer 44

this is an example of rearrangement mutation

in cancer cells Bcl2 locus on Chr18 undergoes a reciprocal translocation with part of Chr14

this places Bcl2 gene under control of new enhancer that induces greater expression (Ab heavy chain gene) - very active in B cells

this results in over-expression of Bcl2 in B cells

so this prevents apoptosis of damaged cells - gets DNA damage and cell proliferation and development of B cell lymphoma