COMPLETE SOLUTIONS GRADED A++
Hallmark 3
Unstable DNA
-this is an enabling hallmark that is required for tumor progression
-Lead to drug resistance
DNA becomes unstable = Genetic instability
Hallmark 7
Angiogenesis
-Growth of new blood vessels from pre-exsisting ones
Hallmark 8
Inflammation
-Heat, redness, swelling, pain, loss of function
-Innate and Adaptive immune responses are in play.
Hallmark 9
Evasion of the Immune System
-Cancer cells frequently arise in the body
-Immune system effectively eliminates these cells
-Tumor escape from anti-cancer immune response
---Altering their characterisitcs
,---Suppressing the immune response
---Hiding the immune response
---Exploiting the immune system's ignorance
---Outpacing immune response
Tumor antigens
Tumors can display two types of antigens
1) Tumor specific antigens
-Protein that does not get expressed in a normal cell. Unique tumor cells do not occur
on normal cells
-Usually results from mutation in tumor cells that generate altered cellular proteins or
expression of viral proteins
Tumor associated antigens
Not unique to tumor cells
-Normal antigens (Self) expressed at the wrong time and in a wrong way
-Most tumor antigens are not specific to tumor cells but are also present in normal cells
ex. Oncofetal proteins and overexpression of proteins
Oncofetal proteins
Expression of oncofetal proteins
Found on normal fetal cells
Appear early in embryonic development, before the immune system becomes mature
If on cancer cells, they are recognized as Non-Self and induce an immune response.
Ex.
,Alpha-fetoprotein (AFP) - Liver cancer
Carcinoembryonic antigen (CEA) - Colorectal cancer
Overexpression of Proteins
-Protein/Oncogene overexpression
-----Several growth factors are overexpressed in tumor cells. These serve as tumor-
associated antigens.
-----EGFR 100X overexpression
-----Transferrin receptor - Normal cell expression <8000 molecules. Melanoma cells
express 50,000-500,000 molecules of transferrin per cell.
Hallmark 10: Immortality
Can divide infinitely
Germ cells
Stem cells -=-> Regeneration of tissue
Normal cells have a biological clock
Normal cells have a biological clock
-Normal cells have a finite number of replications before they become senescent or die.
-Telomere length at the end of chromosomes dictates the number of replications a cell
can undergo -> Biological clock.
Telomerase: Overcoming the clock
-Telomerase is an enzyme that KEEPS TELOMERE LONG.
, -Telomerase is present in 85% of cancer cells, and almost all somatic cells are
telomerase negative
Carcinogenesis
Genotoxic -the ability of harmful substances to damage genetic information
Non-Genotoxic Cause long-term inflammation
High fiber diet reduces carcinogens
Cancer caused by Tobacco
PAH: Polycyclicaeromatic hydrocarbon
NNK: Nicotine Mutagen
Carcinogen/DNA Interaction - Apoxide turns into alcohol. Alcohols and Apoxide interact
with the DNA, which alters it.
Proteins become mutagenic at high heat.
Carcinogen testing
Carcinogen testing
In vivo: testing for tumors in mice and rats
In Vitro:
-Ames Test:
1. Most commonly used to cause DNA mutations
2. Tests ability to cause DNA mutations
3. It uses a unique strain of bacteria