Intro to Cancer Biology Exam 1

Intro to Cancer, History of Cancer part 1 and part 2

What is cancer?

Abnormal growth of cell, uncontrolled pathological cell division

Cancer is a

genetic disease

Clone

cells that share common genetic ancestor

Cancer is a what?

Clonal disease

Clonal Disease

Originates from one ancestral cell and gives rise to limitless descendants

Cancer is not

1 disease

Cancer:

Greek for “karkinos”- crab

first termed by Hippocrates

Hippocrates termed Cancer “karkinos”

Because tumor looked like a crab- reminded him of a crab dug in sand with legs spread in a circle

Other interpretations

• Hard matted surface of tumor reminded of crab shell

  • stab of pain of disease was like being caught in grip of crab’s pincher

Oncology

“Onko”- Greek for “mass” or “load”

Study of cancer

Tumor

Latin for swelling, bulging

Cancer

Latin for crab

Growth can occur in 2 ways

Hyperplasia, and Hypertrophy

Hyperloasia

Increasing cell numbers (division and replication)

Hypertrophy

Increasing cell size

Ex of Normal growth

Hyperplasia and Hypertrophy

What undergoes normal hyperplasia

liver, blood, gut and skin

What undergoes normal hypertrophy

fat and muscle tissue

Ex of Pathological Growth

Pathological Hyperplasia and Pathological Hypertrophy

Ex of pathological hyperplasia

Cancer

Ex of Pathological Hypertrophy

Heart Hypertrophy

Benign Tumor

“Well born”, “gentle”, do not metastasize or spread, can be life threatening if in a bad location

Malignant Tumor

Invade and metastasize, deadly- compromises normal organ function

Neoplasia

New growth

Malignant Characterisitics

Metastasis, cells escape the primary tumor and form distant small tumors in other places in the body

Carcinoma

Derived from epithelial cells, 85% of cancers

Adenocarcinoma

derived from glandular tissues

ex. pancreatic, exocrine, things that secreate things

Carcinogen

Agent or chemical that causes cancer

Ex of carcinogen

Asbestos, UV rays, tobacco, etc.

Sarcoma

• Derived from mesoderm

• Bone, muscle, etc.

• Not as common

• Don’t divide as much

Hallmarks of Cancer

Biological characteristics of the cancer at a cellular level

How many hallmarks are there

14- 6 original, 2 enabling, 2 emerging, 4 new from 2022

What are the 6 major hallmarks of cancer?

Sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis

Enabling

refers to characteristics that allow cancer cells to acquire the core hallmarks of cancer

Emerging

newly identified features that are increasingly recognized as important contributions to cancer development but may not be fully established as core hallmark yet

What are the 2 enabling hallmarks?

Genomic Instability and mutation, and tumor-promoting inflammation

What are the 2 emerging hallmarks?

Deregulating cellular energetics, and avoiding immune destruction

Enabling and emerging

proposed to be part of core hallmarks now

What are the 4 additional hallmarks proposed

Unlocking phenotypic plasticity, senescent cells, polymorphic microbiomes, non-mutational epigenetic reprogramming

Leading causes of death in the US

1. Heart Disease

2.

Cancer

Incidence

the number of new cases of cancer each year or over a defined period of time (rate)

Mortality

the number of deaths rom cancer each year, or a defined period of time (rate)

Prevalence

the number of total cases of cancer ( or other disease) in a defined population over a defined period of time

The 4 leading causes of cancer death in 2017

Lung, colorectal, breast, prostate… pancreas is in top 4 list now

Hippocrates

Greek physician, father of medicine (~400 BC), first described cancer as “karkinos” because tumor in the body resembled a crab

Humors

Human body made of 4 cardinal fluids

What are the 4 cardinal fluids

Blood, phlegm, yellow bile, black bile

What balanced all 4 of the fluids

Health

Claudius Galen

Greek doctor (~169 AD), linked actual diseases to the imbalance of the 4 fluids

Blood

Inflammation- red, hot, painful

Phlegm

Tubercules, pustules, lymph nodes

Yellow bile

Jaundice

Black bile

Cancer and depression

Cancer was

trapped black bile; congeals into mass

Treatment alternatives

arsenic extract, boar’s tooth, fox lungs, ground white coral, laxatives, etc.

Andreas Vesalius

Doctor, ~1533 Paris, wanted to detail anatomy of the human body, specimens included graves/cemetery or prisoners left hanging

Vesalius

published detailed anatomy drawings (arteries, veins, brain, etc.), sought to determine which way the fluids ran, in order to purge disease, couldn’t find black bile when dissecting

Matthew Baillie

Doctor, 1793 London, anatomists, published morbid anatomy- mapped and described body in diseased state, pathology as a science- black bile not found in Vesalis’’s anatomical maps, but tumors should have it

Baillie

Could not find black bile which disproved Galen’s theory, but now tumors could be removed

Edwin Smith

bough Egyptian papyrus which was a transcript of a manuscript from 2500 BC. They were the teachings of Imhotep

What did the papyrus have on it?

Had 48 case reports of medical cases described by Imhotep

In Case 45

stated that there was a “bulging mass in the chest”; made it the first written document of cancer

Herodotus

440 BC Greek Historian, considered 1st historian, Wrote the book Histories, In the book it talked about the story of Atossa

Atossa

Queen of Persia, found a bleeding lump in her breast because of that she hid for the rest of her life and quarantined because of the breast lump, a Greek slave named Democedes surgically excised the tumor

Historical Physical Evidence of Cancer

Atacama Desert- Peru and Chile, 1000 year old grave sites in Peru, mummified remains of Chiribaya Tribe

Dr. Arthur Aufderheide

He was a professor at the University of Minnesota, Duluth, he’s a paleopathologist (autopsy mummies), he found one mummy (a woman in her 30s) with a bulbous mass

That mummy had a

Osteosarcoma- malignant bone tumor- easily preserved compared to other tumors

Other mummies

Abdominal cancer- Dakhlen, Egypt 400 AD

1914 Egyptian mummy tumor invading pelvic bone

In 2011

Scientists found metastatic prostate cancer in Egyptian mummy

Cancer is a

age-related disease, Breast cancer- 1 in 400 for 30 year olds, 1 in 9 for 70 years olds

People

in most ancient societies did not live long enough to develop cancer

Civilization did not cause cancer, per se, it “unveiled” cancer

• Extended human life span

Ex. death of child from leukemia in 1850s would have been blamed on infection

Leukemia

Weiss Blut: German term for white blood; White blood was used to describe Leukemia

John Bennett

Scottish Physician; In Case Report 1845: the patient’s blood was full of white blood cells-though it was pus and from an infection, the source of the infection could not be found, it was said that the blood has spoiled “Suppuration of Blood” and spontaneously turned into infection

Rudolf Virchow

German Physician; could not believe in suppuration of blood; he called it Weiss Blut and then changed the name to Leukemia; “Leukos” is Greek for white; Cancer in liquid form

John Hill

MD, London, 1761, thought tobacco was an environmental chemical of cancer; tobacco snuff could cause lip, mouth and throat cancer, he was a joke to his peers and his warnings were dismissed

Scrotal Cancer

Percivall Pott, MD, surgeon, England, he noticed a rise in scrotal cancer (1775), it was seen in young boys- chimney sweeps (worked with very little clothing); there was a sore on the scrotum- it was thought to be an STI at first but it was only seen in pre-puberty boys and only in one trade; soot was lodged chronically in the skin which was decided was the most likely cause of scrotal cancer, took almost 100 years to ban this practice

Carcinogen that Pott discovered

Soot; occupational hazard linked to cancer

Environmental Carcinogens

Tobacco, smoke, radium, UV rays, etc.

Environmental carcinogens still

don’t explain all cases of cancer, occupational hazards not the cause of most cancers, there must be another cause

Hereditary Cancer

Hilario de Gouvea, MD, in 1872 it was noticed that retinoblastoma was passed down in families, suggested some factor lived in genes and caused cancer

Retinoblastoma

tumor in the eye- derived from retina

Walther Flemming

1879Prague, Cell Division in Salamander Eggs, stained eggs with aniline dye, discovered chromosomes

Chromosomes

highlighted blue, threadlike substance in nucleus that condensed and brightened just before division, Chromosomes- colored bodies, cells from every species had distinct number of chromosomes, they are duplicated during cell division and equally divided between daughter cells

David Paul von Hansemann

Former assistant to Virchow, studied human cancer cells, examined cancer cells stained with aniline dyes, proposed the abnormal structure and chromosome issues were probably responsible

Chromosomes in cancer cells:

had split, frayed, disjointed and broken/rejoined, triplets, and quadruplets

Theodor Boveri

Another assistant of Virchow, studied eggs from sea urchins, forced fertilized 2 sperm in one egg- “Chromosomal Chaos”, he came up with “Chromosomal theory of cancer”, published a pamphlet called “Concerning the Origin of Malignant Tumors” in 1914

Wrong Combination

of chromosomes when dividing caused death- according to Boveri

Chromosomes must

carry important vital information for proper development and growth of cells- Boveri

Boveri came up with:

Chromosomal theory of cancer, said chromosomal abnormalities may be cause of cancer

Form of internal chromosomal chaos

unitary cause of carcinoma

Hermann Joseph Muller

1928, student of Thomas Morgan, found that x-rays could greatly increase rate of mutation in fruit flies, produced hundreds of mutant flies over the months, asked could cancer be a disease of mutations

Thomas Morgan

Discovered that mutations were genes that could be passed down from studying fruit flies (Drosophila)

Muller’s Theory

Could genetic alterations be the “unitary cause of cancer”- yes!

Peyton Rous, 1911

Chicken virologist, Chicken cancer- sarcoma, could inject the tumor from one chicken to another, strained and filtered the tumor, and injected and still saw tumor growth, called it Rous Sarcoma Virus (RSV)

Rous Sarcoma Virus Figure 1

Remove tumor → chop tumor → inject tumor pieces →tumor grew and can be transplanted

RSV Figure 2

Remove tumor → chop tumor → filter tumor in strained liquid (supernatant) → inject tumor filtrate → tumor grew, substance in the liquid (non-tumor cells) caused growth- VIRUS

Howard Temin

1956 (Dulbecco’s lab as a PhD student), added RSV to plate of normal cells, cells grew- did not die as a result of viral infection, RSV incorporated into cell’s DNA, viral gene caused increased growth of cells

What was the viral gene from RSV that kept the cells growing?

Src