Post Term Test 2 - Cancer Flashcards
how do neoplastic cells BEHAVE BADLY (6)
expansion
tissue injury
pain
invasion
metastasis
secretion
Hyperplastic vs Benign vs Malignant - Cellular Differentiation
Hyperplastic: normal gradient/cells
Benign: usually well differentiated
Malignant: poorly differentiated, anaplastic
Hyperplastic vs Benign vs Malignant - Mitotic Activity
Hyperplastic: variable; typically low
Benign: usually low
Malignant: often high
Hyperplastic vs Benign vs Malignant - Rate of growth/Reversible or irreversible
Hyperplastic: reversible
Benign: slow, irreversible
Malignant: rapid, irreversible
Hyperplastic vs Benign vs Malignant - Necrosis
Hyperplastic: none
Benign: usually minimal
Malignant: often high
Hyperplastic vs Benign vs Malignant -Tissue demarcation
Hyperplastic: blends with normal
Benign: expansive, discrete
Malignant: poorly demarcated; locally invasive
Hyperplastic vs Benign vs Malignant - Heterogeneity
Hyperplastic: none
Benign: minimal
Malignant: more
Hyperplastic vs Benign vs Malignant - Aneuploidy
Hyperplastic: none
Benign: low
Malignant: more
Hyperplastic vs Benign vs Malignant - paraneoplastic syndrome
Hyperplastic: none
Benign: variable
Malignant: variable
Hyperplastic vs Benign vs Malignant - recurrence after removal
Hyperplastic: none
Benign: rare
Malignant: frequent
Hyperplastic vs Benign vs Malignant - Propensity to progress if not removed
Hyperplastic: none
Benign: low
Malignant: high
name some examples of local injury
ulceration, infection, perforation, hemmorrhage, nerve damage, restricted motion
T/F invasion and local spread is always malignant
T
what is one way that cancerous cells can change phenotype and why is it beneficial
epithelial to mesenchymal -> the latter has fewer cell-cell junctions/contact inhibition and more ECM matrix adhesion/protease expression -> better invasion
what is the fertile soil concept of tumor metastasis
going from one region of the organ to another because it can grow well there (ex. from one ovary to the other via the peritoneal cavity)
Uterine carcinoma tends to produce what characteristic that can be appreciated grossly
Secretes growth factors (ex. TGFβ) that induce fibrosis; tumors are schirrhous
what is paraneoplastic syndrome
when tumours produce excessive amounts of functional proteins in an unregulated manner (think endocrine disease-causing tumours)
what is elevated with some paraneoplastic syndromes and can indicate neoplasia
elevated Ca2+
What underpins neoplastic behaviour on a molecular level (7)
- activated oncogenes
- functional harmful molecules
- matrix proteinases
- angiogenic factors
- ECM factors (ex. TGFβ -> scarring)
- cell adhesion molecules
- resistance factors
T/F necrotic tumors are easier to kill than non-necrotic tumours
F
a tumor that outgrew its own blood supply takes on what gross appearance
umbilicated; has a central, red depression
name two examples of angiogenic growth factors
VEGF, bFGF
Sutent (Sunitinib) does what
inhibits angiogenesis
what are the 6 hallmarks of cancer
sustained proliferative signalling
evade growth suppressors
activate invasion and metastasis
evade cell death
induce angiogenesis
enable replicative immortality
what are two enabling characteristics of cancer
genome instability and mutation
tumor promoting inflammation
oncogenes are __________ in cancers whereas TSGs are _____________in cancers
activated; inactivated
oncogenes
mutated genes that produce proteins with increased growth stimulatory or cell survival functions
tumor suppressor genes
genes typically involved in genomic stability and apoptosis, or that counteract oncogenes, that become mutated
what is c-kit
a membrane receptor for growth factors; targeted in some cancer therapies
what are two examples of oncogenes
mutated c-kit; mutated tyrosine kinase receptors
Herceptin (Trastumuzab) targets
ErbB2 receptor (tyrosine kinase)
Lapatinib targets
downstream tyrosine phosphorylation of the ErbB2 receptor
T/F oncogenes may undergo translocations to become activated
T
what is the classic example of oncogene translocations in cancer
chronic myeloid/myelogenous leukemia (CML)
what goes Gleevec (imatinib) target (3)
tyrosine kinase domain of abl, c-kit, and PDGF-R
what is a classic tumor suppressor gene product
p53 (involved in cell cycle checkpoints and initiation of apoptosis)
patients with DNA mismatch repair defects are susceptible to
colon polyps -> cancer
how does heterozygosity play a role in oncogenesis
if people are born heterozygous for a TSG allele and then lose that copy, they are more prone to progress to malignancy
how does PTEN work as a TSG
it dephosphorylates tyrosine kinase receptors (ex. c-Met), which inhibits downstream signalling
what is a key factor for combating colon carcinogenesis
remove the polyp before it becomes malignant; if malignant you will leave cells behind
transition of a large colon adenoma to a carcinoma is mediated by what molecular factor
p53 mutation and loss of 18q
___________heterogeneity leads to ____________ heterogeneity
genotypic; phenotypic
heterogeneity leads to what practical problems (4)
diagnostic markers
chemotherapeutic regimens (drug resistance)
mutation-specific drugs
evasion of immune system
how can we identify poorly differentiated tumors? how can this be a problem?
immunohistochemistry; can be an issue if the tumor is heterogeneous for expression of markers
what is an endothelial cell marker
CD31
what are the two ways that cancer cells can sustain proliferative signalling
- do not require GF for signalling
- make their own GF
what is a marker for cancer stem cells
CD133
T/F tumours require cancer stem cells to form a new tumour
T
what are 2 key factors that make cancer stem cells hard to treat
- low proliferation rate
- low uptake of drugs
Consequence: drug and radiation resistant
T/F cancer stem cells express unique stem cell markers
F; often express normal markers
how can giving anti-oxidants actually increase the incidence of cancer
cancer cells produce high ROS, which can kill them; antioxidants produced by the cell deal with this but only partially balance the oxidative stress, which means the cancer cells survive and have more ROS-mediated mutagenic events
most cancer mortality is due to
metastasis
T/F for some cancers there are primary tumor gene expression signatures that can predict their likelihood to metastasize
T
what is the term for spread into body cavities by entering the pleural, peritoneal, pericardial or subarachnoid spaces
transcelomoic
what are the 8 steps in the metastatic cascade
- detach (from primary tumor)
- invade (local stroma)
- intravasate (go into local lymphatics/bvs)
- survive (in circulation)
- arrest (in capillaries or venules)
- extravasate (go into parenchyma)
- adapt to or subvert (environment)
- proliferate (to form new tumor)
why is inflammation associated with cancer (4)
- cytokines
- angiogenic factors
- high proliferation
- produce ROS - predisposes to mutation
how do cancer cells avoid immune destruction (3)
- stop producing antigen in a subset of cells (immuno-editing)
- mutate or stop expressing MHC
- produce immunosuppressive cytokines
list whether the following factors increase or decrease the risk of cancer:
- decreasing age
- high calorie, low fibre diets
- obesity
- reproductive status (spayed/neutered)
- exposure to chemical carcinogens
- ionizing and UV radiation
- decreases
- increases
- increases
- decreases
- increases
- increases
what are 4 oncogenic viruses
papillomaviruses
herpesviruses
hepadnaviruses
retroviruses
avian leukosis virus causes
bursa lymphoma
marek’s disease (herpesvirus) causes
lymphoma infiltrate in liver
T/F there can be transmission of live neoplastic cells
T (can occur in tasmanian devils, in dogs)
T/F after a tumor has undergone treatment, it cannot be reliably graded but can be reliably staged
F; cannot be reliably graded OR staged
