Cancer Bio first quiz

carcinus

latin word for tumor, means crab

Galen

uses word oncus

4 types of fluid (green, red, yellow, black) when imbalanced cause disease

what fluid did galen say causes cancer

black

Andreas Vesalius

student of Galen but found no “black fluid”, opened up questioning to what cancer is

Rudolph Virchow

looked at cancer tumors under microscope, saw the differences and similarities between the cells, hypothesized about removing the bad cells

William Stewart Halsted

first to start removing tumors —> 70% still died

removed more tissue —> 45% died

invented radical mastectomy

metastasization was the cause of death in 90% of patients

radical mastectomy

removal of all muscles and lymph nodes leaving patients crippled, still practiced in rural hospitals until 50-40 years ago

metastecization

cancer spreads to other parts of the body through blood stream

sidney farber

worked on treatment for leukemia based on mustard gas

created aminopterin —> 80% of children with leukemia survived

variation of aminopterin (chemotherapy) cures 90% of children with leukemia

#1 cancer in men

prostate (27%)

#1 cancer in women

breast (31%)

#1 death rate (common and deadly)

lung

deadliest cancer (rare and deadly)

pancreatic

why are most people with pancreatic cancer diagnosed at stage 3

no biomarker to identify it

why do men die from cancer at higher rates

they’re less likely to seek treatment and genetics

why do many people die from lung cancer

hard to treat, lungs can’t be removed easily

Why did stomach cancer rates drop

invention of refrigeration —> salt not used to preserve food

use of nitrate as a preservative

antibiotics to fight H. pylori (bacteria causing cancer)

Why does lung cancer increase from 1945-1990

popularization of smoking after the prohibition

Why did colon cancer drop in 1980s, 2000s

colonoscopy became routine

vaccinations against hpv

what causes colon cancer

high fat diet with a lot of preservatives

doctors and smoking

doctors were paid to advertise smoking as good and relaxing

Everett Koop

Office of Surgeon General who mandated a warning on tobacco products for pregnant women

where did tobacco companies go after they went under in the US

south america and europe —> both currently have a smoking epidemic

vaping and lung cancer

200+ young healthy individuals who vaped died of lung diseases, but only anecdotal evidence because it hasn’t been around long enough yet

Risk factors for vaping

no high school degree

health disparity

a subset of the population that is suffering because of lack of insurance, education, proper healthcare facilities, income; give an example: cynthia and dee dee

Harold Freeman Patient Navigation Institue

clinics around the US in rural and urban areas that people can go to with abnormalities to help patients suffering from not having insurance

Dee Dee + timeline

very rich, was able to get mammogram, biopsy, and surgery within weeks. chemo within 3 months. because of the early detection and treatment, she was cancer free after one round of chemo

Cynthia + timeline

poor with no health insurance. took over twice as long as Dee Dee, months for a biopsy and surgery, cancer spread to liver and then to her bones. she died because it wasn’t treated soon enough

stage 1 vs stage 4 stats

breast + prostate 100 —> 15

lung 55 —> 0

melanoma 99.5 —> 0

prostate cancer from 1987-1996

huge peak and then drop

why was there a peak in prostate cancer diagnoses

more men would go in to get screened after the invention of the PSA blood test (prostate surface antigen). hated original testing procedure: DRE (digital rectal exam) (finger up butt)

What was the DRE? biopsy?

digital rectal exam; the biopsy was 18 specimens blindly taken with a needle + biopsy gun with only 90% accuracy

Patrick walsh

invented PSA test in 1986 so everyone would get their prostate screened, and conducted first radical retropubic prostatectomy

What factors can cause a falsely high PSA? what were the consequences

spicy food, sexual intercourse, benign prostate hyperplasia; people in rural areas would automatically get their prostate removed instead of retesting after a false positive

Why did 80% of patients become impitent and 90% become incontinent after prostate removal?

mesh of nerves around prostate were not visible on living patients

What was the prostate removal procedure changed to and what were the effects?

radical retrpubic prostatectomy, 10% became impitent and 20% loss of urination, but that was mostly due to age

Current procedure for prostate cancer

retest PSA 3 times to see if it increases, then DRE, biopsy, and radical retropubic prostatectomy

everything in the cell is controlled by

DNA

cellular equilibrium

in normal cells, there is a balance between cell proliferation and apoptosis, for every cell that dies a new one is generated

typical order of cell life

proliferation as premature stem cells —> differentiation into cell types and carry out job —> cell dies; if any are disrupted, cellular equilibrium is disrupted

APC gene

biggest risk factor for colon cancer, mutation causes more cells to proliferate than die, leading to disruption of cell equilibrium and tumor

EGFR

epidermal growth factor receptor located on outside of cell, when triggered tell the cell to divide

3 important characteristics that keep a cell non-cancerous

1. few EGFR receptors

2. no autoregulation, requires EGFR be triggered from neighbor cell (paracrine)

3. contact inhibition - close proximity of other cells prevents the cell from growing

3 differences that create cancer cells

1. abundant EGFR receptors, so many chances to proliferate

2. autocrine signaling and the production of their own growth factors that triggers a feedback loop

3. no contact inhibition that causes cells to grow on top of each other

what is cancer?

cancer is the combination of many diseases characterized by uncontrolled growth and spread of abnormal cells (at least 100 types); can also be abnormal cell differentiation

neoplasia

abnormal cell proliferation

blue

goblet cells; nondividing

yellow

enterocyte cells; differentiating very fast; fast division over 12 hours

red

stem cells; renew and differentiate into other cell types; slow division over 24 hours

gray

paneth cells; nondividing differentiated cells; signal to cells to proliferate, differentiate, and die; maintain cellular equilibrium

how do cells move in the crypt

the cells proliferate at the bottom, differentiate, and get pushed up the crypt. when they reach the villus (top) they die

How do we know epithelial cell migration in the gut?

Brdu is radioactive and is used to label DNA. scientists watched labelled dna travel up the villa from the crypt to the tip of the villus; could also use green fluorescent protein to label cell

3 steps of cancer

1. initiation - first mutation of a proto oncogene that is involved in cell proliferation in a single cell

2. promotion - proliferation is promoted only in the mutated cells

3. progression - second set of mutations, typically tumor suppressors

all 3 must be met for it to be cancer

how was skin cancer caused in mice as an example of the 3 steps of cancer

(1) ear painted with initiating agent DMBA —> no change

• mutation in Ras gene (proto oncogene involved in cell proliferation)

(2) ear painted with proliferation agent TPA —> no change

(1 + 2) both DMBA and TPA —> papilloma (reversible if TPA stops)

• mutated Ras gene cells proliferated by TPA

(1 + 2 + 3) DMBA + TPA + DMBA —> carcinoma

• second DMBA triggers second mutation in TP53 (tumor suppressor)

oncogenic addiction

when treating cells with promoting agent, only mutated Ras cells are being proliferated because they have multiple receptors so they can receive the message much faster

DMBA

initiates first mutation of Ras, proto oncogene involved in proliferation

TPA

encourages proliferation in Ras mutated cells

TP53

tumor suppressor, 73% higher risk of developing cancer if gene is not working

Bert Vogelstein

colon cancer 4 stages, assessed the progression of colon cancer and what triggered each stage

colon cancer 4 stages and what triggers each stage

1. normal

   • loss of heterozygosity in chromosome 5q (APC gene)

2. early polyps

   • Ras activation

3. large polyps

   • chromosomes 18q (unknown) and 17p (TP53) were missing

4. cancer

metastases in liver after Mm23 deletion

why does colon cancer metastasize into the liver

all vessels from the colon feed into the liver

do tumors grow exponentially?

not at first because a lot of them die before reproducing and tumor suppressors are still active and cause apoptosis

4 reasons tumors don’t grow exponentially

1. immune response

2. lack of oxygen

3. lack of nutrients

4. apoptosis

how does an immune response kill early tumor cells

immune cells recognize these cells have mutations and destroy them

in early stages cancer cells are missing PDL1 (receptor that allows immune cells to recognize them. Later on they have this, so B and T immune cells recognize the tumor as self

individuals with autoimmune diseases are more susceptible to cancer

how does lack of oxygen and nutrients kill early tumor cells

the tumor cells still require oxygen and nutrients, but they cant obtain enough to feed those cells and grow

as cancer progresses they don’t need oxygen and nutrients because they start making their own nutrients (glycolysis?), become hypoxic, and create their own growth factors

how does apoptosis kill early tumor cells

tumor suppressor genes are still active and will kill tumor cells

hoo long does it take for cancer to develop

colon - 20-35 years

lung - 20-30 years

prostate 35-45 years

dependent on genetics/family history

after becoming a carcinoma, how long before it kills you?

a few months

microscopic appearance of normal cells

regular, well organized, nucleus is small and round, specialized cell features dictated by shape

microscoping appearance of cancer cells

irregular, unorganized, nucleus is large in variably shaped, small cytoplasmic volume compared to nucleus, variation of cell size and shape within a tissue, loss of specialized cell features, disorganized arrangement of cells, poorly defined tumor boundary

hypertrophy definition

increase in cell size

hyperplasia definition

increase in cell number

atrophy definition

decrease in cell size or number

metaplasia definition

change of cell type

dysplasia definition

abnormal growth

mild dysplasia

disorganization and cell crowding, but still have basement membrane, same shape, same size (beginning of initiation)

severe dysplasia

a lot of abnormalities in cell types, mutations change properties of the cells —> precancerous or carcinoma insitu (stage 0-1)

everything that happens above the basement membrane = severe dysplasia

when does severe dysplasia become cancer

when it breaks the basement membrane = invasive carcinoma (stage 2-4)

no longer normal upon visual inspection, increased mitotic activity

basement membrane

similar to rest of tissue but stronger

break this and it becomes cancer

what is hyperplasia?

cells appear normal but are too plentiful, abnormal proliferation

reversible

benign prostate hyperplasia

island/lake of semen covered by cells, no large white spot

medicine returns it to normal after a few weeks

what is metaplasia?

replacement of one type of normal adult differentiated cell type by another type that belongs somewhere else

vitamin A deficiency - Columnar epithelium cells (elongated) —> squamous epithelium (flat), flat cells can’t secrete properly

reversible and noncancerous

what is dysplasia?

abnormal interaction of cells giving abnormal tissue development

mild is reversible, severe is not

what is neoplasia?

abnormal mass of tissue, growth of which is uncoordinated with that of normal tissue

benign neoplasia

non cancerous, encapsulated or contained to one area, doesn’t have the markers/ability to become invasive, few mitotic features, highly differentiated, no dysplasia, slow growth

malignant neoplasia

non-encapsulated, invasive, penetrated basement membrane, poorly differentiated, lots of mitotic activity, rapid growth, capable of metastasis

2 things to become cancer

1. must cross basement membrane

2. has the ability to invade

parenchyma

above basement membrane, almost all cancer initiates from this (above basement membrane

stroma

anything below basement membrane, invasive carcinomas break through the basement membrane into this area

vasculature

veins and arteries

• As soon as the tumor finds an artery or vein, it can travel in the blood stream and come out in a different tissue (metastasization)

entravasation

entry into vein

extravasation

exit into new tissue

VEGF

tumor secretes this to encourage vasculature to grow towards the tumor

ECM

extracellular matrix

• Holds the tissue together, ECM can become displaced

• The cells can start falling apart → tissue ends up in the boodstream

carcinoma

epithelial cell originated

1. squamous

2. glandular

squamous example

skin

glandular example

prostate, breast, colon, lung

sarcoma

soft tissue (muscles, heart, bone marrow)

leukemia

blood