Cell Regulation & Cancer Flashcards
Causes of anemia
hypoxia –> reduced erythropoietin response
nutritional deficiencies
bone marrow failure
iron deficiency
inflammation –> decreases erythropoietin synthesis
Cellular regulation
all functions carried out w/i a cell to achieve homeostasis
includes:
cellular response to extracellular signals (cytokines, hormones, neurotransmitters)
growth, proliferation, differentation
Growth
refers to physical growth of cells in terms of size
Proliferation
refers to increase in number of cells
Differentation
process of specialization wherein cells become functional through subsequent cell cycles
Cell adaptation
increases in growth and proliferation d/t increase in metabolic/functional demand
Ex: ventricular hypertrophy
Neoplasia
uncontrolled cell growth & proliferation
Apoptosis
programmed cell death of damaged, excess or old cells
Normal cell regulation
involves a balance between growth factors & growth controls
Factors promoting cell proliferation
growth factors
availability of open space in tissue
perfusion, oxygen and nutrients (requirements of cell growth)
Examples of growth factors
hormones
cytokines
growth actors (VGEF)
Growth factor MOA
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
Cell cycle
divided into four stages. presents the life cycle of a cell G1 S G2 M G0
G0
resting phase
cell is not actively dividing or preparing to divide
cell carrying out normal function in tissues
G1
physical growth –> cell duplicates organelles, produces proteins, molecules for division
growth & normal metabolism
S
DNA synthesis occurs –> cell duplicates DNA and condenses into a chromosome + duplicates the centrosome
G2
cell continues to grow producing proteins & organelles
growth & preparation for mitosis
M
mitosis phase –> cell divides and produces two daughter cells
Phases of mitosis
prophase
metaphase
anaphase
telophase
Cytokinesis
cytoplasm divides producing two new distinct cells
Factors inhibiting cell divison
growth inhibiting factors
contact inhibition
Contact inhibition
cells division depends on cell density
cells form intercellular junctions between cells –> intercellular contact inhibits cellular growth
contact blocks DNA replication & protein synthesis
Factors limiting cellular lifespan
apoptosis
telomeres
Telomeres
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
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
Senescence
functional cells that can no longer divide
Telomerase
enzyme that rebuilds telomeres
Cells containing telomerase
germ cells
stem cells
cancer cells** –> cancer cells are immortal
Neoplasia
uncontrolled cell proliferation that is permanent
Neoplasm
tumor made up of cancer cells
Types of tumors
benign
malignant
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
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
Stem cells
undifferentiated cells that can produce a variety of different cells
one daughter cell remains a stem cell
second daughter cell –> progenitor cell
Progenitor cells
committed but not fully differentiated cells
Oma suffix
benign tumor
Carcinoma suffix
malignant tumor
Sarcoma
malignant mesenchymal tumor
Polyp
growth projecting from a mucosal surface
Characteristics of tumors
characteristic of tumor cells
rate of growth
local invasion
ability to metastasize
Characteristics of normal tissue
specific morphology well-differentiated tight adherence to neighboring cells/ECM (anchorage) orderly, controlled proliferation euploidy (complete chromosomes
Clinical classification of tumors
Benign
Malignant
Histological classification of tumors
type of tissue
cell type
from which they arise
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
Mitotic index
ratio of actively dividing cells to resting cells
Factors causing cellular death
immune factors (WBC, antibodies, complement)
apoptosis
insufficient blood supply
Anaplasia
cells with poor differentiation “move backwards”
cells move backwards to an earlier more primitive state of cellular specialization
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
Tumor grading
histological and cellular characteristics of cancer cells
determines degree of differentiation
helps predict rate of growth & likelihood of metastasis
Tumor staging
extent and advancement of cancer
T = tumor size
N = lymph node involvement
M = metastasis
Colorectal cancer etiology
almost all start off as polyps
Polyp
growth projecting from mucosal surface –> grows into the lumen
benign tumor
Sessile polyp
flat
difficult to remove endoscopically
Pedunculated polyp
forms a stalk w/ mucosal surface
easy to remove
Most common type of colorectal cancer
adenocarcinoma
Cancer grading
G1 = well differentiated, slow growth G2 = moderately differentiated G3 = poorly differentiated G4 = undifferentiated, rapid growth
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
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
Direct tumor spread
tumor cells spread into local tissue
Mestasis spread
tumor cells break off from primary tumor and create a secondary tumor at a distal site
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
Secondary tumor characteristics
retain characteristics of the primary tumor despite being in a different anatomic region
**sometimes the secondary tumor is discovered first
Routes of metastasis
lymphatic spread
vascular spread
seeding
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
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
Vascular spread
cancer cells usually enter through the veins/capillaries
Common sites of metastasis
liver (hepatic portal vein)
lungs (pulmonary artery)
lymph nodes
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
S/S of bone cancer
pain
fractures
hypercalcemia
S/S of liver cancer
nausea
jaundice
RUQ pain
hepatomegaly
S/S of brain cancer
headache
seizures
S/S of lung cancer
SOB
cough
hemoptysis
wheezing
S/S of lymph node cancer
enlarged (palpable) lymph nodes W/O pain
pain usually indicates inflammation/infection
When does a polyp become malignant
genetic changes –> rapid growth
invasion thru GI tract wall alyers
spread to distant sites
Factors causing DNA damage
radiation (ionizing, UV) chemical carcinogens replication errors viruses, bacteria free radicals
G1/S checkpoint
detects DNA damage BEFORE replication begins
G2/M checkpoint
detects DNA replication errors BEFORE mitosis begins
Outcomes of DNA damage
cell dies via apoptosis
cell cycle stops –> error is corrected
mutation survives and becomes part of cellular DNA
Genetics of cancer
develops when control genes that regulate cell growth/proliferation become mutated
Genes involved in cancer
proto-oncogenes
tumor suppressor genes
apoptosis regulating genes
DNA repair genes
Proto-oncogenes
normal genes become PO when mutated
code proteins that PROMOTE cell division –> growth factors, receptors, transcription factors, apoptosis inhibitors
Tumor suppressor genes
code for proteins that normally INHIBIT cell division
limits cell division
underactivity = uncontrolled proliferation
Carcinogenesis stages
Initiation
Promotion
Tumor progression
Metastasis
Initiation
cell exposed to carcinogen –> irreversible mutation
*actively dividing cells most susceptible
Promotion
promoters enhance growth/proliferation of mutated cells
new colony of cells containing original mutation
Tumor Progression
cells gain additional mutations
Factors stimulating cancer growth
increase in proto-oncogenes
decrease in tumor suppressor genes
decrease in apoptosis
Colorectal cancer RF
carcinogen exposure (smoking, alcohol, abdominal radiation) advanced age >50 genetics chronic irritation/inflammation (IBS) weak immune function lifestyle obesity
Why is age (>50) a RF
longer exposure to carcinogens
time to accumulate mutations
decreased ability to fix replication errors
weakened immunity
Acquired mutations
occur throughout life
more common
Inherited mutations
received from mother/father
Oncogenic viruses
HPV Hep B/C Esptein Barr (mono) Herpesvirus 8 Human T-cell lymphotropic virus
Oncogenic bacteria
H. pylori
Immune surveillance
malignant cells have tumor-specific antigens –> marked for destruction by lymphocytes/antibodies
can cause spontaneous regression
Local Manifestations of cancer
palpable/visible lump
bleeding
obstruction
pain (mechanical compression)
Changes in organ function manifestation
loss of function
hormonal effects
Systemic Manifestation of Cancer
anemia anorexia/cachexia non-specific paraneoplastic syndrome fatigue, sleep disorders
3 Endocrine syndromes assoc w/ cancer
SIADH
Cushing’s
Hypercalcemia
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
Goals of cancer therapy
cure –> remove all of cancer
control –> slow/stop spread
palliation –> relieve symptoms
prophylaxis –> individual high risk of cancer
Cancer treatments
surgery
radiation
chemotherapy
Radiation therapy
damages cellular DNA through the production of free radicals OR by breaking chemical bonds in DNA
*most effective against actively dividing cells
Neoadjuvant therapy
shrink before BEFORE first-line therapy
stimulates cells to move from G0 –> cell cycle increasing effectiveness of radiation
Adjuvant therapy
destroy cancer cells remaining AFTER first-line therapy
Concurrent therapy
chemo & radiation used at the same time
Types of radiation therapy
External = radiation beam Internal = brachytherapy & systemic radiation
Brachytherapy
sealed radioactive source inserted into tumor or nearby tumor –> temporary or permanent
“radioactive seeds”
Systemic radiation
small radioactive isotopes with short half life given by mouth/injected into tumor site
External beam
x-rays
gamma rays
delivered in smaller, fractionated doses to minimize damage to healthy cells & allow for healing
Chemotherapy
use of cytotoxic drugs to destroy cancer cells or slow growth
*systemic side fx
Types of chemotherapy drugs
cell-cycle specific
non-cell cycle specific
*diff drugs can be combined d/t diff MOA, onset, etc.
Cell-cycle specific drugs
act on a specific stage of the cell cycle
Non-cell cycle specific
act on all stages of the cell cycle –> works on resting/dividing cells
cause DNA damage –> apoptosis
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
Chemotherapy hematologic side fx
decreased RBC –> anemia
decreased platelets –> bleeding
decreased WBC –> infection
Chemotherapy GI side fx
anorexia nausea/vomiting (CTZ stimulation) diarrhea mouth sores changes in taste
Chemotherapy skin side fx
alopecia
hair loss
Chemotherapy reproductive side fx
changes in menstruation
amenorrhea
reduced sperm count, no sperm
teratogenic fx
Secondary screening for colorectal CA
fecal immunochemical test (FIT)
Diagnostics for colorectal cancer
colonoscopy
biopsy
Biopsy
microscope examination of a tissue sample
used to grade tumors
Tests to check metastasis
chest xray - lung metastasis
abdominal CT scan - liver metasis
Tumor marker for colorectal cancer
carcinoembryonic antigen (CEA) -> produced by cancer cells measured in the blood
PET scan
positron emission tomography
detects changes in cellular metabolism `
Cellular adapation
occurs in response to cellular stress –> hypertrophy, hyperplasia, metaplasia
reversible change in cells
if cells cannot adapt –> cell injury occurs
Permanent cells
skeletal muscle cells
cardiac cells
neurons
Permanent cells & hyperplasia
permanent cells DO NOT DIVIDE
these cells adapt by increasing in size (hypertrophy)
Types of cellular adaptation
atrophy
hypertrophy
hyperplasia
metaplasia
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
Causes of atrophy
decreased functional demand
decreased stimulation
inadequate nutrition/perfusion
Dysplasia
disordered cell growth
non-adaptive cellular change
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
