Cancer Flashcards
(47 cards)
1
Q
fraction americans that develop cancer and percent that die of cancer
A
1/3 of americans develop cancer
22% of americans die of cancer
2
Q
carcinoma
A
from epithelial cells (ducts, body cavity lining, visceral organ lining)
3
Q
sarcoma
A
from connective tissue
4
Q
lymphoma
A
blood born cancers
5
Q
most cancers are ____ (carcinoma, sarcoma, lymphoma)
A
carcinoma
6
Q
neoplasm
A
tumor
proliferative growth that leads to a mass of cells
7
Q
where do tumors typically originate?
A
typically originate in stem cells; rarely differentiated cells
8
Q
characteristics of benign growth
A
- non – invasive
- cell-cell interactions maintained
- confined to original location
- does not reach basal lamella
- can be invasive if bulky
9
Q
characteristics of cancerous growth
A
- “malignant” = threatening
- invasive and metastatic
- cell-cell interaction affected
- may de-differentiate
- may evade immune system
- cancer cells often exhibit altered surface molecules that are non-self
10
Q
Hanahan-Weinberg – The Defining Characteristics of Cancer
A
- self-suficiency in growth signals
- insensitivity to growth-inhibiting signals
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- tissue invasion and metastasis
- Warburg metabolism (change in glucose metabolism)
- evasion of immune system
11
Q
Warburg metabolism
A
changes in glucose metabolism to accommodate cancer cell’s obsession with glucose
- cancer cells and proliferating cells convert most glucose to lactate regardless of whether oxygen is present or not - -aerobic glycolysis
12
Q
cancer characteristic: Insensitivity of Growth-Inhibiting Signals
A
- cancer cells ignore contact inhibition
- cancer cells will growth past the point of confluent growth; will continue growing even if bottom of dish has a full layer of growth
13
Q
cancer characteristic: Evasion of Apoptosis (#3)
A
- cancer cells avoid undergoing apoptosis and are able to circumvent the apoptotic process
Limitless Replicative Potential (#4)
- cancer cells do not demonstrate a hayflick limit
- most normal cells have a limited potential to divide; cancer cells are immortal
14
Q
cancer characteristic: Sustained Angiogenesis (#5)
A
- cancer cells induce angiogenesis in order to keep tumor cells from becoming hypoxic
- all cells in the body are within a millimeter of a capillary; if cells in a tumor get more than a few millimeters from a capillary they will become hypoxic
15
Q
consequences of induced angiogenesis
A
- nutrients and oxygen are supplied to the tumor
- new blood vessels provide as easy way ou
16
Q
Angiogenesis stimulated by:
A
- endothelial cell development stimulated by: VEGF and FGF
17
Q
VEGF
A
VEGF: vascular endothelial growth factor
- ligand for VEGF-receptor (tyrosine kinase)
- produced by tumor cells and tumor-associated macrophages
- importance of VEGF tested by transporting tumor of one animal to another to check for growth of vasculature around tumor
18
Q
cancer characteristics: Tissue Invasion and Metastasis (#6)
A
- cancer cells are invasive
- able to breach borders
- seldom does a primary tumor kill a patient – it’s almost always a secondary tumor
19
Q
Seven Types of Proteins That Participate in Controlling Cell Growth and Proliferation
A
- extracellular signaling molecules
- signal receptors
- signal transduction proteins
- transcription factors
- cell-cycle-control proteins
- function to restrain cell proliferation - DNA-repair proteins
- apoptotic proteins
20
Q
tumor suppressor genes encode for:
A
cell-cycle-control proteins and DNA repair proteins
21
Q
mutations in two broad classes of genes have been implicated in the onset of cancer:
A
proto-oncogenes and tumor-suppressor genes
22
Q
proto-oncogenes
A
promote cell growth; mutations change them into oncogenes whose products are excessively active in growth promotion
23
Q
tumor suppressor genes
A
restrain growth; mutations that inactivate them allow inappropriate cell division
24
Q
caretaker genes
A
protect the integrity of the genome; when they are inactivated, cells acquire additional mutations at an increased rate
25
multi-hit hypothesis
in most cases, cancer is a result of multiple separate mutations; 5-6 mutations before cancer
26
multi-hit hypothesis experiment
myc alone and rasD alone each had some tumor development but combining the two led to far greater tumor development
27
Downstream Effects of Mutation and Vogelstein
- Vogelstein: worked on colon cancer
- able to get tissue from really early stages of abnormal growth in the colon
- genetically examined the tissue and found that as one gene went mutant another would, and then another would – domino effect of mutation
- numerous studies show that colon cancer arises from a series of mutations that common occur in a well-defined order, providing strong support for the multi-hit model
28
sis oncogene
- encodes a type of PDGF (platelet derived growth factor)
29
EGF and cancer
* orange: a mutation that alters a single amino acid in the transmembrane regions of the Her2 receptor causes dimerization of the receptor, even in the absence of the normal EGF-related ligand
* blue: a deletion that causes loss of the extracellular ligand-binding domain in the EGF receptor leads to constitutive activation of the kinase activity of the resulting oncoprotein ErbB
30
c-myc
transcription factor responsible for expression of proteins involved with cell division
31
Burkitt’s lymphoma
result of a translocation between chromosomes the c-myc gene is placed adjacent to the gene for part of the antibody heavy chain, leading to the overproduction of the Myc transcription factor in lymphocytes and hence their growth into a lymphoma
32
effect of loss of TGF-B signaling
in the absence of effective TGF-B signaling owing to either a receptor mutation or a SMAD mutation, cell proliferation and invasion of the surrounding extracellular matrix (ECM) increase
33
p15 and lack of it
leads to transcription of gene encoding cell-cycle inhibitory; example of how a problem can arise from a lack of a transcription factor; lack of p15 leads to proliferation
34
cyclin D, p16 and Rb role in cancer
overproduction of cyclin D, a positive regulator, or loss of the negative regulators p16 and Rb commonly occurs in human cancers
35
CycD, p16, and CDK4 pathway
36
G1 Arrest in Response to DNA Damage
- loss of p53 abolishes the DNA damage checkpoint
- the kinase activity of ATM is activated in response to DNA damage due to various stresses (like UV radiation and heat); activated ATM then triggers three pathways leading to arrest in G1
- ATM activates p53
- p53 is a transcription factor; leads the cell into cell cycle arrest responsible for turning on the machinery for DNA repair
- if cell damage is beyond repair then apoptosis will be induced
37
Cancer and Apoptosis and examples of mutated proteins that have been found to be related to disrupted apoptosis
- typically if you cannot do apoptosis then there will be an accumulation of damaged cells or mutated cells
- many chemotherapeutic agents work to induce apoptosis
examples: BAX, APAF1, Fas/APO1, Bcl-2
38
visualizing metastasis in the body
- can visualize metastasis in the body by looking at where glucose is accumulating; viewed on PET scan; patient intakes non-digestible form of glucose
- metastases measured by the amount of cancer cells in a lymph node
39
The Steps in Metastasis
1. Detachment of tumor cells; cadherins are surface glycoproteins involved in cell-cell adhesion; down regulation of cadherin production has been identified in several carcinomas.
2. Attachment to matrix components allow tumor cells to adhere to ECM components
3. Degradation of extracellular matrix; after attachment tumor cells secretion of matrix proteolytic enzymes particularly type IV collagenases (basement membrane collagen) is correlated with metastatic capability.
40
cancer cell motility
cancer cells demonstrate different motility
41
Molecular Changes Required for Metastasis
- Loss of cadherins is detected in all tumors.
- Metastatic cells produce high concentrations of MMPs (matrix-metalloproteinases)
42
Human Cancer-Associated Viruses
- Viruses can contribute to but not be the sole cause of human cancer
- However, up to 15% of all cancers have a viral association
43
examples of cancer-associated viruses
Papillomaviruses HPV 16 and 18,
hepatitis B virus,
Epstein-Barr virus,
Human T-cell leukemia
44
SV40
make proteins which are going to lead the cell into S
- inhibits apoptosis
- inhibits Rb function
- many of these viral proteins lead the cell into S; want to get the - -machinery in place to replicate their own DNA and proteins
45
most common cancer for men and women
men: prostate
women: breast
46
top death cancer for men and women
men: lung
women: lung
47
men and women: who will have cancer at some point
1 in 2 men
1 in 3 women
