Cancer Flashcards
(126 cards)
1
Q
definition of tumor
A
purposeless overgrowth of any cellular component
2
Q
hyperplasia
A
physiological proliferative increase in number of cells
3
Q
dysplasia
A
change in phenotype (size, shape and organization of tissue
4
Q
neoplasia
A
abnormal proliferation, tumor
5
Q
hypertrophy
A
increase in cell size
6
Q
benign
A
tumors localized and of small size
Ex: warts
7
Q
WHat delineates the extent of a benign tumor?
A
fibrous capsule
8
Q
malignant
A
grow and divide more rapidly than normal, fail to die at the normal rate, or invade nearby tissue without significant change in proliferation rate
9
Q
incidence of epithelial origin of cancers
A
85%
10
Q
glandular (breast, colon, liver..)
A
adenoma, adenocarcinoma
11
Q
adenoma
A
glandular benign
12
Q
adenocarcinoma
A
malignant glandular
13
Q
covering (skin, lungs, cervix…)
A
squamous cell papilloma, squamous cell carcinoma
14
Q
squamous cell papilloma
A
benign covering
15
Q
squamous cell carcinoma
A
malignant covering
16
Q
epithelial b/m
A
oma/carcinoma
17
Q
supporting tissue b/m
A
oma/sarcoma
18
Q
bone (osteoblast)
A
osteoma/osteosarcoma
19
Q
osteoma
A
benign bone
20
Q
osteosarcoma
A
malignant bone
21
Q
Striated muscle
A
rhabdomyoma/rhabdosarcoma
22
Q
rhabdosarcoma
A
malignant striated muscle
23
Q
rhabdomyoma
A
benign striated muscle
24
Q
smooth muscle
A
leiomyoma/leiomyosarcoma
25
leiomyoma
benign smooth muscle
26
leiomyosarcoma
malignant smooth muscle
27
hematopoietic
/leukemia
28
erythrocytes
erythrocyte leukemia
29
erythrocyte leukemia
erythrocyte
30
Lymphocyte
Lymophocyte or lymphocytic
| leukemia
31
bone marrow
myeloma or myeologenous leukemia
32
no benign version
erythrocytes, lymphocytes, BM
33
astrocytes
astrocytoma/glioblastoma
34
astocytoma
astrocytes benign
35
glioblastoma
astrocyte malignant
36
melanocytes
mole/melanoma*
37
mole
benign melanocytes
38
melanoma
malignant melanocytes
39
micro-anatomical changes
1. lack of differentiation
2. abnormal nucleus
3. abnormal chromosome
40
anaplasia
dedifferentiation or lack of differentiation
41
pleomorphic
variation in size or shape
42
FISH
paints chromosome
43
Behaviorial characteristics of cancer cells
- ability to proliferate indefinitely
- resistance to apoptosis
- anchorage-independent growth
- loss of contact-inhibition
- decreased requirement for growth factors
- increased metabolism
- form tumor in lab animals
- loss of cell-cell adhesion
- invasion and metastasis
- escape from immune surveillance
44
PET scan
can see metabolism
45
monoclonal theory of cancer origin
arise from a single cell of origin
| any cell could create tumor
46
cancer stem cell theory of cancer origin
relies on the fact that a lot of tumors are heterogenous (vary by phenotype and functions)
ONLY CSC CAN CREATE TUMOR
47
both origin theories
clonal evolution regulated by cancer stem cells
48
tumor cells and stem cells
```
share many similarities
self-renewal
differentiation
active telomerase expression
anti-apoptotic
ability to migrate
```
49
evidence of monoclonality
X-chromosome inactivation patterns
Use of starch gel electrophorsis to resolve the two forms of G6PD showed that all of the cancer cells in a tumor arising in a G6PD heterozygous patient express one or the other
50
additional evidence of monoclonality
unusual translocation involves exchange of segments between two separate (nonhomologous) chromosomes - all of the cancer cells carry the identical rare translocation - > monoclonality
51
differences of incidence by area of the world
suggests strong environment involvement
52
What causes cancer?
1. chemical agents
2. radiation (UV, ionizing)
3. infectious agents (virus)
4. heredity
53
carcinogens vs mutagens
carcinogens are mutagens
54
test mutagens
Ames test
55
Ames test for gauging mutagenicity
liver is homogenized - releasing the enzymes that can metabolically activate a chemical to mutagenic form
- mixed with test compound
- add to Salmonella bacteria unable to grow w/o histidine in culture
- count colonies
56
Rous's protocol for inducing sarcomas in chickens
Removed sarcoma from breast muscle of chicken
- pass through fine pore filter
- filtrate into wing web of a young chicken
- sarcoma*
Therefore, VIRUS.
RSV
57
transformation
conversion of a normal cell into a tumor cell could be accomplished with RSV
58
three major types of viral proteins
env - glycoprotein spike (adsorb to cell surface)
gag - protein coat of core proteins
pol - specify reverse transcriptase molecules
59
temperature sensitive mutant and the maintance of transformation by RSV
- infected at permissive temp (transformed)
- shifted to non permissive (normal)
- back to permissive temp (transformed again)
Thus, temp sens viral protein must be active to transform cell.
60
viruses containing DNA molecules
are also able to induce cancer
61
Important discoveries of viruses and cancer
1. transformed cells integrate viral genome
2. Some viral genomes have genes that can transform cells (these have no function in viral replication)
3. transforming genes have counterparts in host cells
4. often viral oncogenes are mutated and hyperactive
5. cellular proto-oncogenes can also be activated by insertion of slowly transforming retrovirus lacking oncogenes (insertional mutagenesis)
62
nude mice in testing tumorigenicity
1. lack thymus/immunocompromised; receptive to engrafted cells
2. hairless - easy to monitor closely the progress of tumor formation
63
oncogenes
gene with the potential to cause cancer
| gain of function drives toward cancer
64
proto-oncogene
gene that can become an oncogene if mutated or expressed at high levels
65
insertional mutagenesis
cellular proto-oncogenes can also be activated by insertion of slowly transforming retrovirus lacking oncogenes
66
tumor supressor gene
loss of function
67
two categories of cancer-critical mutations
dominant (oncogene)/recessive (tumor suppressor gene)
68
conversion of protooncogene to oncogene
1. deletion or point mutation - hyperactive protein made in normal amounts
2. regulatory mutation - normal protein overproduced
3. gene amplification - normal protein overproduced
4. chromosome rearrangement
a. normal protein overproduced
b. hyperactive protein
69
Screening of oncogenes
transfection
- DNA extracted from cancer cells
- DNA uptake by cells
- if has oncogene, result in tumor formation
70
Cloning of transfected oncogenes
Southern blotting
Alu sequence probe, ones that were transfected successfully were oncogenes in the mouse
-genomic library and DNA clone could be identified
71
cloned proto-oncogene
no transfection
72
cloned oncogene
transfection
73
localization of an oncogene-activating mutation - point mutation - Ras
endonuclease with a protooncogene
| until you get a fragment that transfects the proto-oncogene
74
activating mutant of Ras...
fails to hydrolyze GTP
75
Sos
Ras GEF
76
Grb2
bridging protein of Sos to ligand-activated growth factor receptors due to two SH3 domains
bind to proline rich domains of Sos
77
Two bridging proteins of Sos
Grb2 and Shc
78
Ras/Raf/MAP kinase pathway
Ras->Raf->MEK->ERK (MAPK)
| - Fos and Jun Tx factors, associate with one another to form AP-1, found in hyperactive cancer cells
79
translocation
fuse a region from one chromosome with another region from a second, unrelated chromosome
80
ongenic activation of myc
1. gene amplification
2. insertional mutagenesis (WT mys locus, but under foreign promoter
3. chromosomal translocation
81
myc driven under
IgH promoter - Burkitt's lymphoma
82
truncated growth factor receptor causing
deregulated firing
| Ex: truncated EGF receptor in breast
83
structural changes in protein
can also lead to oncogene activation
84
conceptualized existence of tumor suppressor genes by
cell fusion
- tumorigenic - dominant
- not - recessive
85
Rb (retino blastoma)
first identified tumor suppressor gene
86
genetic mech that cause Rb
hereditory - every one has one missing
| nonhereditory - all cells contain functional...both are lost or inactivated
87
elimination of WT Rb gene copies
LOH
88
loss of heterozygosity
from mitotic recombination/crossing over
89
p53
tumor suppressor
| suppresses Ras induced transformation of fibroblasts
90
mutant p53
has dominant negative function
91
accumulation of p53
cell-cycle arrast, DNA repair, block angiogenesis, apoptosis
92
p53 controlled by
Mdm2 - causes p53 proteolysis
93
p53 targets
p21 (cell cycle inhibitor)
| PUMA (pro-apoptotic)
94
ARF
binds to Mdm2 and blocks p53 degradation
95
loss of p53 function
excessive proliferation, inhibition of apoptosis and DNA damage repair
96
loss of function of tumor suppressor genes caused by
genetic and epigenetic factors
| methylation!
97
How do you search for tumor suppressor genes?
LOH analyses by RFLP (restriction fragment length polymorphism)
rationale: chromosomal region flanking tumor-suppressor gene is likely to undergo LOH
98
Tumor Progression
growth and dissemination
99
new blood vessel generation...
is critical for primary tumor growth
100
hypoxic cells
die
101
distance from blood vessel
100-200 mm
102
hypoxia triggers
angiogenesis
103
angiogenesis aids...
survival of tumor cells
104
metastatic dissemination requires
new blood vessel generation
105
leaky tumor vasculature promotes
intravasation
106
metastatic colonization requires
angiogenesis
107
4 ways to recruit blood vessels to tumors
1. sprouting angiogenesis (predominant)
2. vasculogenesis
3. vascular mimicry
4. Csc differentiation
108
sprouting angiogenesis
new vessel generation from pre-existing vessels
109
VEGF signaling promotes
- junctional disruption
- proliferation
- survival
- migration
- recruitment of EPCs
110
VEGF upregulation
in cancer
111
major triggers of VEGF
hypoxia, oncogenic signaling
112
H1F1-alpha
regulated by oxygen
113
major oncogenic signaling
```
PI3K, Ras
PI3K mutation
Activated EGFR
AKT mutation
PTEN loss
RAS activation
```
114
multicellular interactions in the tumor microenvironment
promote tumor angiogenesis
115
key players in tumor angiogenesis
tumor cells, EC, matrix remodeling, secretion of pro-angiogenic factors, myeloid cells (macrophages ECM deg)
116
block VEGF signaling
block progenitor cell recruitment
117
vascular mimicry
channel formation
118
CSC differentiation into
Endothelial cells
119
epithelial to mesenchymal transition
promotes tumor invasion
| E-cad staining (loss of E-cadherin)
120
reciprocal stimulation
promotes tumor invasion/intravasation
121
macrophages and fibroblasts secrete
mmps
122
Treatments
surgery
radiation
chemotherapy
adjuvants
123
chemotherapy treatments
1. antimetabolite (analogs)
2. microtuble stabilizing (taxol)
3. DNA cross-linking agents (cisplatin)
4. antibiotics (doxorubicin
5. hormone therapy (tamoxifen)
124
adjuvent
anti-angiogenic drug (VEGF antibody)
| growth-factor receptor blocker (EGFR antibody)
125
Problems with therapy
- side effects
- delivery issues
- redundancy of mol players and pathways (single line adjuvant therapy is not often sufficient)
- increased drug resistance (over expression of transporter proteins)
- resistance offered by cancer stem cell
126
Tumor vessels are abnormal
1. leaky
2. tortuous
3. heterogeneous
4. poor pericyte coverage
5. thin basement membrane
