Cell Regulation & Cancer Flashcards
1
Q
Causes of anemia
A
hypoxia –> reduced erythropoietin response
nutritional deficiencies
bone marrow failure
iron deficiency
inflammation –> decreases erythropoietin synthesis
2
Q
Cellular regulation
A
all functions carried out w/i a cell to achieve homeostasis
includes:
cellular response to extracellular signals (cytokines, hormones, neurotransmitters)
growth, proliferation, differentation
3
Q
Growth
A
refers to physical growth of cells in terms of size
4
Q
Proliferation
A
refers to increase in number of cells
5
Q
Differentation
A
process of specialization wherein cells become functional through subsequent cell cycles
6
Q
Cell adaptation
A
increases in growth and proliferation d/t increase in metabolic/functional demand
Ex: ventricular hypertrophy
7
Q
Neoplasia
A
uncontrolled cell growth & proliferation
8
Q
Apoptosis
A
programmed cell death of damaged, excess or old cells
9
Q
Normal cell regulation
A
involves a balance between growth factors & growth controls
10
Q
Factors promoting cell proliferation
A
growth factors
availability of open space in tissue
perfusion, oxygen and nutrients (requirements of cell growth)
11
Q
Examples of growth factors
A
hormones
cytokines
growth actors (VGEF)
12
Q
Growth factor MOA
A
binds to a membrane receptor triggering an intracellular pathway –> cell enters the cell cycle
message is carried towards the nucleus causing transcription factors to bind to DNA
13
Q
Cell cycle
A
divided into four stages. presents the life cycle of a cell G1 S G2 M G0
14
Q
G0
A
resting phase
cell is not actively dividing or preparing to divide
cell carrying out normal function in tissues
15
Q
G1
A
physical growth –> cell duplicates organelles, produces proteins, molecules for division
growth & normal metabolism
16
Q
S
A
DNA synthesis occurs –> cell duplicates DNA and condenses into a chromosome + duplicates the centrosome
17
Q
G2
A
cell continues to grow producing proteins & organelles
growth & preparation for mitosis
18
Q
M
A
mitosis phase –> cell divides and produces two daughter cells
19
Q
Phases of mitosis
A
prophase
metaphase
anaphase
telophase
20
Q
Cytokinesis
A
cytoplasm divides producing two new distinct cells
21
Q
Factors inhibiting cell divison
A
growth inhibiting factors
contact inhibition
22
Q
Contact inhibition
A
cells division depends on cell density
cells form intercellular junctions between cells –> intercellular contact inhibits cellular growth
contact blocks DNA replication & protein synthesis
23
Q
Factors limiting cellular lifespan
A
apoptosis
telomeres
24
Q
Telomeres
A
short nucleotide sequences found at the end of chromosomes
shorten each cell cycle –> when telomeres become too short cell division shortens
cells become senescence or chromosomes break apart –> cell dies
25
Apoptosis process
cell shrinks
enzymes released that digest proteins & DNA
nucleus fragments
cell breaks down into small membrane bound fragments
fragments are digested by phagocytosis
26
Senescence
functional cells that can no longer divide
27
Telomerase
enzyme that rebuilds telomeres
28
Cells containing telomerase
germ cells
stem cells
cancer cells** --> cancer cells are immortal
29
Neoplasia
uncontrolled cell proliferation that is permanent
30
Neoplasm
tumor made up of cancer cells
31
Types of tumors
benign
| malignant
32
Characteristics of benign tumors
slow, progressive growth
encapsulated by connective tissue capsule
grow by expansion --> compress adjacent tissue
well-differentiated --> maintain normal tissue function
resemble local tissue cells
localized --> not capable of metassis
33
Characteristics of malignant tumors
rapid cell proliferation
poor differentiation --> look different/function differently from local tissue cells --> impaired tissue function
infiltrate/invade local tissue --> lack well-defined borders
compress blood vessels --> ischemia, necrosis
can secrete hormones, cytokines, toxins
can metastasize --> enter lymph/blood
34
Stem cells
undifferentiated cells that can produce a variety of different cells
one daughter cell remains a stem cell
second daughter cell --> progenitor cell
35
Progenitor cells
committed but not fully differentiated cells
36
Oma suffix
benign tumor
37
Carcinoma suffix
malignant tumor
38
Sarcoma
malignant mesenchymal tumor
39
Polyp
growth projecting from a mucosal surface
40
Characteristics of tumors
characteristic of tumor cells
rate of growth
local invasion
ability to metastasize
41
Characteristics of normal tissue
```
specific morphology
well-differentiated
tight adherence to neighboring cells/ECM (anchorage)
orderly, controlled proliferation
euploidy (complete chromosomes
```
42
Clinical classification of tumors
Benign
| Malignant
43
Histological classification of tumors
type of tissue
cell type
from which they arise
44
Do malignant cells divide faster than benign cells?
No.
| malignant tumors have a higher # of cells that area actively dividing, less apoptosis and cells do not enter G0 phase
45
Mitotic index
ratio of actively dividing cells to resting cells
46
Factors causing cellular death
immune factors (WBC, antibodies, complement)
apoptosis
insufficient blood supply
47
Anaplasia
cells with poor differentiation "move backwards"
| cells move backwards to an earlier more primitive state of cellular specialization
48
When are benign tumors removed
cosmetic
symptomatic --> begin to impair local tissue function
risk of malignancy (colon polyps)
functional endocrine tumors oversecrete hormones
prevent organ injury (d/t growth by expansion)
reduce anxiety
49
Tumor grading
histological and cellular characteristics of cancer cells
determines degree of differentiation
helps predict rate of growth & likelihood of metastasis
50
Tumor staging
extent and advancement of cancer
T = tumor size
N = lymph node involvement
M = metastasis
51
Colorectal cancer etiology
almost all start off as polyps
52
Polyp
growth projecting from mucosal surface --> grows into the lumen
benign tumor
53
Sessile polyp
flat
| difficult to remove endoscopically
54
Pedunculated polyp
forms a stalk w/ mucosal surface
| easy to remove
55
Most common type of colorectal cancer
adenocarcinoma
56
Cancer grading
```
G1 = well differentiated, slow growth
G2 = moderately differentiated
G3 = poorly differentiated
G4 = undifferentiated, rapid growth
```
57
Growth properties of cancer cels
growth factor independence --> grow w/o being stimulated
loss of contact inhibition --> do not respond to inhibiting factors
loss of cohesiveness/adhesion --> allows shedding of cancer cells
anchorage independence --> grow w/o being bound to ECM
angiogenesis --> cancer develops its own vascular supply
activation of telomerase --> immortality
58
Anchorage dependence
normal cells do not grow unless attached to a solid surface i.e. the ECM/other cells
detached cells programmed to die via apoptosis
**prevents growth of cells outside of local region
59
Direct tumor spread
tumor cells spread into local tissue
60
Mestasis spread
tumor cells break off from primary tumor and create a secondary tumor at a distal site
61
Requirements of tumor motility
1) cancer cell becomes more loosely attached to ECM/other cells
2) cancer cells evade apoptosis after detachment (anchorage independence)
3) produce enzymes that degrade basement membrane --> invasion
62
Secondary tumor characteristics
retain characteristics of the primary tumor despite being in a different anatomic region
**sometimes the secondary tumor is discovered first
63
Routes of metastasis
lymphatic spread
vascular spread
seeding
64
Seeding
tumor cells can shed and enter body cavities
spread along serous membranes of body cavities
spread into other organs within the body cavity
*risk of cancer spread during surgical removal
65
Tumor cells in lymph nodes
1) destroyed by immune cells
2) pass thru lymph --> enter subclavian vein --> circulatory system
3) form a secondary tumor in the lymph node
66
Vascular spread
cancer cells usually enter through the veins/capillaries
67
Common sites of metastasis
liver (hepatic portal vein)
lungs (pulmonary artery)
lymph nodes
68
Bone metastases
occur in bones of high blood cell production (high in red bone marrow = higher blood supply)
ex: vertebrae, humerus, pelvis, ribs, femur, skull
69
S/S of bone cancer
pain
fractures
hypercalcemia
70
S/S of liver cancer
nausea
jaundice
RUQ pain
hepatomegaly
71
S/S of brain cancer
headache
| seizures
72
S/S of lung cancer
SOB
cough
hemoptysis
wheezing
73
S/S of lymph node cancer
enlarged (palpable) lymph nodes W/O pain
| pain usually indicates inflammation/infection
74
When does a polyp become malignant
genetic changes --> rapid growth
invasion thru GI tract wall alyers
spread to distant sites
75
Factors causing DNA damage
```
radiation (ionizing, UV)
chemical carcinogens
replication errors
viruses, bacteria
free radicals
```
76
G1/S checkpoint
detects DNA damage BEFORE replication begins
77
G2/M checkpoint
detects DNA replication errors BEFORE mitosis begins
78
Outcomes of DNA damage
cell dies via apoptosis
cell cycle stops --> error is corrected
mutation survives and becomes part of cellular DNA
79
Genetics of cancer
develops when control genes that regulate cell growth/proliferation become mutated
80
Genes involved in cancer
proto-oncogenes
tumor suppressor genes
apoptosis regulating genes
DNA repair genes
81
Proto-oncogenes
normal genes become PO when mutated
| code proteins that PROMOTE cell division --> growth factors, receptors, transcription factors, apoptosis inhibitors
82
Tumor suppressor genes
code for proteins that normally INHIBIT cell division
limits cell division
underactivity = uncontrolled proliferation
83
Carcinogenesis stages
Initiation
Promotion
Tumor progression
Metastasis
84
Initiation
cell exposed to carcinogen --> irreversible mutation
| *actively dividing cells most susceptible
85
Promotion
promoters enhance growth/proliferation of mutated cells
| new colony of cells containing original mutation
86
Tumor Progression
cells gain additional mutations
87
Factors stimulating cancer growth
increase in proto-oncogenes
decrease in tumor suppressor genes
decrease in apoptosis
88
Colorectal cancer RF
```
carcinogen exposure (smoking, alcohol, abdominal radiation)
advanced age >50
genetics
chronic irritation/inflammation (IBS)
weak immune function
lifestyle
obesity
```
89
Why is age (>50) a RF
longer exposure to carcinogens
time to accumulate mutations
decreased ability to fix replication errors
weakened immunity
90
Acquired mutations
occur throughout life
| more common
91
Inherited mutations
received from mother/father
92
Oncogenic viruses
```
HPV
Hep B/C
Esptein Barr (mono)
Herpesvirus 8
Human T-cell lymphotropic virus
```
93
Oncogenic bacteria
H. pylori
94
Immune surveillance
malignant cells have tumor-specific antigens --> marked for destruction by lymphocytes/antibodies
can cause spontaneous regression
95
Local Manifestations of cancer
palpable/visible lump
bleeding
obstruction
pain (mechanical compression)
96
Changes in organ function manifestation
loss of function
| hormonal effects
97
Systemic Manifestation of Cancer
```
anemia
anorexia/cachexia
non-specific
paraneoplastic syndrome
fatigue, sleep disorders
```
98
3 Endocrine syndromes assoc w/ cancer
SIADH
Cushing's
Hypercalcemia
99
S/S of colorectal cancer
```
change in bowel habits --> constipation, narrow stools, incomplete evacuation
abdominal pain
bloating
N/V
blood in stool (frank, fecal occult, melena)
palpable mass in rectum
fatigue
anorexia, weight loss
S/S of metastatic tumor
```
100
Goals of cancer therapy
cure --> remove all of cancer
control --> slow/stop spread
palliation --> relieve symptoms
prophylaxis --> individual high risk of cancer
101
Cancer treatments
surgery
radiation
chemotherapy
102
Radiation therapy
damages cellular DNA through the production of free radicals OR by breaking chemical bonds in DNA
*most effective against actively dividing cells
103
Neoadjuvant therapy
shrink before BEFORE first-line therapy
| stimulates cells to move from G0 --> cell cycle increasing effectiveness of radiation
104
Adjuvant therapy
destroy cancer cells remaining AFTER first-line therapy
105
Concurrent therapy
chemo & radiation used at the same time
106
Types of radiation therapy
```
External = radiation beam
Internal = brachytherapy & systemic radiation
```
107
Brachytherapy
sealed radioactive source inserted into tumor or nearby tumor --> temporary or permanent
"radioactive seeds"
108
Systemic radiation
small radioactive isotopes with short half life given by mouth/injected into tumor site
109
External beam
x-rays
gamma rays
delivered in smaller, fractionated doses to minimize damage to healthy cells & allow for healing
110
Chemotherapy
use of cytotoxic drugs to destroy cancer cells or slow growth
*systemic side fx
111
Types of chemotherapy drugs
cell-cycle specific
non-cell cycle specific
*diff drugs can be combined d/t diff MOA, onset, etc.
112
Cell-cycle specific drugs
act on a specific stage of the cell cycle
113
Non-cell cycle specific
act on all stages of the cell cycle --> works on resting/dividing cells
cause DNA damage --> apoptosis
114
Chemotherapy drug classifications
antimimotics --> M phase prevents formation of the mitotic spindle
antimetabolites --> S phase prevents replciation
antibiotics --> S/G phases --> inhibits replication & protein synthesis
alklylating --> any phase
115
Chemotherapy hematologic side fx
decreased RBC --> anemia
decreased platelets --> bleeding
decreased WBC --> infection
116
Chemotherapy GI side fx
```
anorexia
nausea/vomiting (CTZ stimulation)
diarrhea
mouth sores
changes in taste
```
117
Chemotherapy skin side fx
alopecia
| hair loss
118
Chemotherapy reproductive side fx
changes in menstruation
amenorrhea
reduced sperm count, no sperm
teratogenic fx
119
Secondary screening for colorectal CA
fecal immunochemical test (FIT)
120
Diagnostics for colorectal cancer
colonoscopy
| biopsy
121
Biopsy
microscope examination of a tissue sample
| used to grade tumors
122
Tests to check metastasis
chest xray - lung metastasis
| abdominal CT scan - liver metasis
123
Tumor marker for colorectal cancer
```
carcinoembryonic antigen (CEA) -> produced by cancer cells
measured in the blood
```
124
PET scan
positron emission tomography
| detects changes in cellular metabolism `
125
Cellular adapation
occurs in response to cellular stress --> hypertrophy, hyperplasia, metaplasia
reversible change in cells
if cells cannot adapt --> cell injury occurs
126
Permanent cells
skeletal muscle cells
cardiac cells
neurons
127
Permanent cells & hyperplasia
permanent cells DO NOT DIVIDE
| these cells adapt by increasing in size (hypertrophy)
128
Types of cellular adaptation
atrophy
hypertrophy
hyperplasia
metaplasia
129
Metaplasia
reversible conversion of one cell type to another
causes loss of function in original tissue
ex; smoking causes epithelium to convert from ciliated pseudostratified --> stratified squamous
130
Causes of atrophy
decreased functional demand
decreased stimulation
inadequate nutrition/perfusion
131
Dysplasia
disordered cell growth
| non-adaptive cellular change
132
Characteristics of dysplasia
```
cells vary in size, shape, organization
caused by persistent, severe irritation
primarily occurs in epithelial tissue & metaplastic squamous epithelium
may be reversible
precursor to neoplasia
```
