Chapter 10 - Biology of Cancer Flashcards
what is cancer?
leading cause of suffering and death in developed word.
what caused cancer?
specific and often age-related accumulation of genetic and epigenetic alterations
___, ___, and ____ interact to modify risk of developing cancer and response to treatment
environment, heredity and behavior
what is the study of how behaviors and environment causes changes that affect gene function
epigenetic
what does karinoma mean?
crab
what is tumuor?
new growth or neoplasm (new/abnormal growth)
cells and tissues structures that are like normal tissues and tend to grow and spread slowly?
well-differentiated
made up of cells that look very abnormal and often grow and spread quickly
poorly differentiated or undiffrentiated
True or False: well-differentiated and undifferentiated are both tumuors
True
which type of tumour progresses to cancer?
malignant
loss of cellular differentiation; aka hallmark of cancer
anaplasia
what is pleomorphic? which type of tumour is this associated?
variability in size and shape; malignant
the most deadly characteristic of malignant tumuors
metastasis
what is metastasis?
ability to spread far beyond tissue of origin
these are cancers arising from epithelial tissue
carcinomas
cancers arising from ductal or glandular structures
adenocarcinomas
T or F: CIS is not considered malignant.
True
what is CIS?
preinvasive epithelial tumours of glandular or squamous cells origin
three fates of CIS?
remains stable for long time (1)
progress to invasive/metastatic cancers (2)
regress and disappear (3)
CIS vary from ___ grade to ____ grade dysplasia
low; high
which grade lesions having highest likelihood of becoming invasive carcinoma
high grade
Cancer is a predominantly a disease of ____
aging
T or F: Single mutations required before cancer can develop/
false; multiple mutations
result of multiple mutations?
decreased need for growth factors to multiply (1)
lack of contact inhibition (2)
anchorage independence to disseminate through body (metastasis) (3)
immortality - no apoptosis (4)
2 fundamental concepts of cancer:
cancer is a ___ (1) disease arising from ____ (2) mutations.
tumour environment is a ____ (3) of cells (cancerous and benign) as well as their secretions
genetic (1); multiple (2); mixture (3)
the three stages of cancer:
(1). tumour ___
(2). tumour ___
(3). tumour ___
initiation; promotion; progression
what is tumour initiation?
- first stage of cancer dev
- dependent on specific mutations
- producing initial cancer cell
what is tumour promotion?
- pop of cancer cell expands with diversity of phenotypes
- additional mutations
what is tumour progression?
- metastasis
- more mutations and changing microenvironments
small-scale changes: ___ mutations
large-scale changes: ___
point; translocations
two types of small-scale:
driver mutations (1)
passenger mutations (2)
what is point mutations?
alteration of one or few nucleotide base pairs
what is driver mutations?
mutations that drive progression of cancer.
what is passenger mutations?
random events; mutations that don’t contribute to malignant phenotype.
two types of large-scale mutation?
chromosome translocation & gene amplification
what is chromosome translocations?
- large change in chromosome structure
- section of one chromosome is translocated to another chromosome
what is gene amplification?
instead of normal 2 copies of gene, tens or even hundreds of copies are present.
E.g., gene expression of HER2 proteins
selective advantage cancer cell has over neighboring cells
clonal proliferation model (CPM)
In CPM, cancer cells can replicate ___ than nonmutant neighbors
faster
increasingly __ cell division and ____ DNA repair mechanisms of cancer cells. This continues the accumulation of ___ throughout progression to most aggressive metastatic lesion.
rapid; impaired; mutations
a process by which a normal cell becomes a cancer cell
transformation
___ ____ that do not accumulate a critical set of mutations lose to competition and die
cancer cells
T or F: each cancer develop its own set of mutations
true
Transformation is directed by ___ accumulation of ____ ____ that ____ basic nature of cell and drive it to ____
progressive; genetic changes; alter; malignancy
Cancer development is similar to ____ _____
wound healing
initial cancer cell proliferation triggers a typical ______ response by itself and ____ nonmalignant cells
proinflammatory; adjacent
wound healing, mediators recruit:
- inflammatory or ____ cells (e.g., T cells, B cells and macrophages)
- cells associated with ___ repair like (f____, adipocytes, m____ stem cells and e____ cells
immune; tissue; fibroblasts, mesenchymal, endothelial
stroma cells make up ___% of tumour mass
90%
extensive _____ signaling among stromal and cancer cells affect both population:
(1) ____, & (2) _____
paracrine; secretory cell (1); adjacent target cell (2)
In Ab wound healing, recruited cells form a _____ (tumour microenvrionment
stroma
In ab wound healing, effect:
cancer cells ____ proliferation
becomes more ____ (diverse)
increase; heterogenous
In ab wound healing, process,
- great deal of cancer cell ___
- surviving cells are more ____
- many take on _____ phenotype
death; aggressive; metastatic
what is the first hallmark of cancer?
uncontrolled cellular proliferation
Normal cells generally only enter proliferative phases in response to ____ factors
growth
what is proto-oncogenes?
normal genes that direct protein synthesis and cellular growth
what are oncogenes?
mutated proto-oncogenes cells
_____ produce oncogenes, which allows uncontrolled growth
mutations
oncogenes are ____ of normal regulatory mechanisms
independent
____ can cause excessive and inappropriate production of oncogenes
translocations
translocation changes normal chromosomes into _____ lymphoma
Burkitt
what does Burkitt lymphoma produces?
Abnormal B lymphocytes
how do cancer cells evade growth suppressors?
mutation of tumour suppressor genes
what does normal tumour suppression genes do?
- inhibit proliferation
- stop cell division when cells are damaged
- prevent mutations
Tumour suppressor genes (which are called ____-_____) must be _____ for cancer proliferation to occur.
anti-oncogenes; inactivated
What is the classic tumour-suppressor gene?
tumour-protein P53
another name for tumour protein P53
guardian of the genome
what does P53 do?
- monitor cellular stress and activates caretaker genes to repair genetic damage
- also controls cellular apoptosis
Inactivation of P53 requires at least ___ mutations
two
what is Hayflick Limit?
the limit on cell replication imposed by shortening of telomeres in each division.
What are the protective caps on each chromosome?
telomeres.
when most cells proliferate, ______ caps ____ with each cell division
telomeres; shorten
T or F: When telomeres run out, cell can no longer divide, thus cells dies.
True
what is the enzyme that maintains telomeres, which don’t decrease in number with cell division
telomerase
Telomerase – usually active only in _____ and ____ (germ cells) and ____ cells
ovaries; testes; stem
T or F: cancer cells deactivate telomerase = unlimited telomeres
False; activate telomeres
what is the result of cancer cells activating telomerase?
unlimited proliferation which = to immortality.
what is angiogenesis?
production of new blood vessels – activated by cancer cells
what happens if angiogenesis occurs?
vessels are more porous = prone to hemorrhage
irregular branching from existing capillaries
allow passage of tumour cells int vascular system = metastasize
advanced cancers secrete ____ factors
angiogenic
normal cells use ____ metabolism with O2
aerobic
with limited O2, normal cells use ____ and produce ____ acid
glycolysis; lactic
cancer cells use only ______ even in presence of O2. What effect is this called?
glycolysis; Warburg
Warburg effect = _____ glycolysis
aerobic
what is the cancer benefit of Warburg effect?
shift to glycolysis which allows continual production of lactate
what pathway is relatively dormant until death receptor is activated. What death receptor is needed?
extrinsic; BAK
T or F: The activation of both extrinsic and intrinsic pathways = T cells and NK cells induce apoptosis
true
Apoptotic pathways are ______ in cancers
dysregulated
T or F: Cancer cells do not undergo programmed apoptosis
True
Metastasis is the defining characteristic of cancer and the major cause of _____ from cancer.
death
T or F: Cancer that has not mestastized can often be cured by a combination of surgery, chemotherapy and radiation
true
T or F: Same therapies are frequently effective againts metastasized cancer
False; ineffective against metastasized
How do cancer cells develop ability to metastasize?
epithelial-mesenchymal trasition (EMT)
To metastasize, cancer cells must dissociate from _____
ECM
Carcinomas originate from highly _____ _____ cells that form structured sheets stabilized by multiple adhesions to neighboring cells.
differentiated epithelial
EMT – achieved with a programmed transition from a ____ epithelial- like carcinoma to a more _______ mesenchymal-like carcinoma.
This step is initiation of _____-mesenchymal transition process
partially; undifferentiated; epithelial
EMT occurs normally in ____ development and wound ____ healing
embryonic; wound
what happens to normal cells when separated from their ECM?
normal cells undergo Anoikis – induction of apoptosis in cell’s loss of ECM
T or F: Cancer cells avoid anoikis by entering circulation and spread
True
what are the three steps of EMT?
(1) Intravasation - entry of tumor cells into circulation
(2) extravasation – exit of tumor cells from circulation to host tissue
(3) survival in circulation – platelets coat tumor = provide protection
what does platelets coat tumor do? and what stage of EMT you can find them?
provide protection; aka cancer clot. Stage 3 of EMT: survival in circulation
In terms of survival in new loc, only a ____ cancer cells required to establish a tumour in new loc.
few
what do you call to cancer cells establish in new location?
tumour initiating cells (TIC) or cancer stem cells
T or F: metastasis does guarantee proliferation.
FALSE; it doesnt guarantee.
what is dormancy?
a stable non-proliferating state that is reversible.
how many of the breast cancer deaths occur after a 5 year disease-free interval?
2/3
T or F: studies of deceased individuals with no history of cancer have dormant cancer cells.
True
what are the viruses associated with cancer?
HPV, EBV, & Hepatitis B and C
what is a new cancer therapy?
dev of oncolytic viruses that specifically attack cancer cells
cancer cells avoid immune detection and destruction using 3 mechanisms:
failure to produce tumor antigen (1), mutation in MHC genes (2) & production of immunosuppressive proteins or expression of inhibitory cell surface proteins
T or F: normal immune system protects against cancer
true
T or F: immunosuppression fosters cancer
True
Ways on how immunosuppression fosters cancer?
(1) Non-hodgkin’s lymphoma (10x)
(2) Kaposi sarcoma (1000X)
(3) Release of immunosuppressive factors into tumour microenvironment increases resistance of tumour to chemo and radiotherapy
What are the different phenotypes of macrophages?
M1, M2 & TAM
What is M1?
classic macrophage (M1) responds to inflammatory stage to perform phagocytosis
during healing, what does M2 produces? And what does it do?
anti-inflammatory mediators, which suppress inflammation
what does TAM (tumour-associated macrophages) do?
perform like M2; TAM block T cells and NK cells and produce cytokines advantageous to tumour growth and spread
what are the 4 stages based on presence of metastasis?
Stage 1: no metastasis
Stage 2: local invasion
Stage 3: spread to regional structures
Stage 4: distant metastasis
what are some cancer treatment?
surgery, radiation & chemotherapy
what is paraneoplastic syndromes?
group of rare disroders that are triggered by an ab immune system response to a cancerous tumour.
____ or ____ pain is associated with early stages of malignancy
little; no
weakness and wasting of body due to severe chronic illness
cachexia syndrome
what is cachexia syndrome?
most severe form of malnutrition (1)
includes anorexia, early satiety, weight loss, anemia, asthenia, taste alteration, altered protein, lipid and carbo metabolism
what is asthenia?
weakness; lack of energy and strength
What causes when there is a direct tumour invasion of bone marrow?
leukopenia and thrombocytopenia
what is leukopenia?
reduced WBC in blood
what is thrombocytopenia?
blood platelet count too low
its a risk that increases when absolute neutrophil and lymphocyte counts fall
infection
