Cancer I Flashcards
cancer stats
- 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
what is the deadliest type of cancer? compare it to breast cancer
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.
** what are some properties of cancer cells?
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
info about cell growth, division, and cancer
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
what is erythropoeitin?
its a small protein growth factor that is produced by the kidneys when RBC is low
it stimulates bone marrow to produce more RBCs
normal vs cancer cells
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
what are the two heritable properties of cancer cells?
1) they reproduce in defiance of normal restraints on cell division and cell growth
2) invade areas normally reserved for other cells
how does cancer kill?
as tumor grows and spreads, it squeezes or destroys blood vessels, nerves - until organ can no longer do its job - death results
what is the pathology of cancer?
an abnormal cell that grows (incr in mass) and proliferates (divides) out of control will give rise to a tumor or neoplastic growth
what is a benign tumor?
if the neoplastic cell does not become invasive, then it is benign.
this means you can surgically remove local mass as cure
when is it considered cancer?
if it is malignant - which means if cells have the ability to invade surrounding tissues
what are some classifications of cancers?
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
differentiate between basal-cell carcinoma vs melanoma:
BCC rarely metastasizes whereas malignant melanomas metastasize widely
what is metastases?
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
describe tumor development
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
tumor development: colon cancer.
what gene is mutated?
APC gene, which is a tumor suppressor
describe the APC gene mutation and cancer development
cells with an APC gene mutation gain an advantage in growth - they firm polyps. at this stage, still a benign tumor.
what happens when a mutation in Ras occurs?
it becomes “cancer” gene
loss of other tumor suppressor - lose p53
tumor moves out into blood stream, gains capacity to invade, now malignant tumor
where do most cancers derive from?
a single abnormal cell; a primary tumor
also, from a single cell that outgrows, out-divides and out-lives neighboring cells
what evidence is there for cancer from a single heritable cell?
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
what type of mutations do cancer cells contain?
somatic mutations
what are two types of carcinogens?
chemical and radiation
what is the best weapon against cancer?
early detection
what is an example of tumor progression into cancer?
cervical cancer
cancerous growth depends on what two things?
defective apoptosis
defective growth
what are the steps in the process of metastasis?
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
what is the most deadly aspect of cancer?
metastasis - can’t eradicate by surgery or irradiation
what is angiogenesis?
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)
what is neovascularization?
the formation of new blood vessels basically from scratch
differentiate the two
angiogenesis is when the blood vessels sprout from pre-existing blood vessels vs neovascularization is the formation of new blood vessels basically from scratch
what are some more properties of cancer cells?
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
what is the Ames test?
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
what other viruses and infections contribute to human cancer?
AIDS: HIV causes Kaposi’s sarcoma
Ulcers and Helicobacter pylori - can cause stomach cancers
what is the most environmental cause of cancer?
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
what are two general genetic causes of cancer?
oncogenes and tumor suppressor gene
what are cancer critical genes?
genes who alteration frequently result in cancers
what is a third group that may cause cancer?
DNA maintenance genes (subset of TSG)
mutations involve inactivation of caretaker genes that create genomic stability
include DNA repair genes, checkpoint genes
discuss retroviruses and oncogenes
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
what are transformed cells?
small colonies of proliferating cells caused by oncogene
what does transcformation of RSV depend on?
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)
what is the first human oncogene?
Ras
Ras is a monomerc GTPase for signal transduction
Ras oncognes: cannot shut off by hydrolyzing GTP to GDP
overactivity leads to cancer
what are some ways to activate oncogenes?
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))
what other situations cause cancer?
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
speak on Bcl2 oncogene
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
