Lecture 24 Flashcards
what is hypertrophy
increase in cell size in reaction to physiological or pathological stimulus
occurs in cells unable to divide
reversible
give 2 exs of hypertrophy
skeletal muscle hypertrophy with training
increase in cell size in cardiac muscle
what is hyperplasia
increase in cell number in response to phsyio or patho stimuli
occurs in cells that can divide
reversible
give 2 exs of hyperplasia
hyperplasia of epithelial cells in female breast during pregnancy
liver regeneration – if resected = becomes hyperplastic and grows back
what is neoplasia
neoplasm = new growth
pathological disturbance of growth characterized by excessive and unceasing proliferation of cells
Independent of normal regulatory controls
irreversible
arise from genetic alterations
neoplasms may be benign or malignant
what is dysplasia
cells look abnormal under microscope
not cancer but are considered to be precancerous - can be mild moderate or severe, depends on how abnormal the cells look under a microscope and how much of the tissue or organ affected
may or may not become cancer and can be reversible
describe difference between hyperplasia and neoplasia
hyperplasia = cells are genoptypically and phenotypically normal
hyperplasia usually ends when stimulus ends - mammary epithelial hyperplasia - reversible
describe neoplasia - benign tumours
growth confined to a specific site within a tissue
gives no evidence of invading adjacent tissue
refers to epithelial growth that has not penetrated bm
most are harmless
can cause issues if release high levels of hormones or are in specific locations like brain
describe neoplasia - malignant tumours
Aggressive growth
shows evidence of being locally invasive and maybe even metastatic
90% of cancer related deaths are result of metastasis spawned from original primary tumours
describe Theoretical generations of cells forming a tumor mass
not real exponential growth
one cubic cm has about billion cells in it
plot assumes that each time cancer cells in a tumour divide, this cell population as a whole will double in size buttttt
cells divide and die
if not have enough mutations= selective pressure on them to not divide or spread, as get more mutations = spread out
what is tumorigenesis
multistep process - well documented in epithelia of intestine - high rate of turnover
describe actual tumour growth models
have to look at 20 years prior
ripple effect triggered by events decades ago
divides selectively - not exponential
describe intestinal tract
bm underlies basement membrane to which cells are anchored
Epithelial layer is site of most of pathological changes associated with development of colon carcinomas
describe pathway of colorectal cancer
normal intestinal epi
inactivation of apc tsg
dysplatic epithelium
early adenoma - benign
Activation of k ras oncogene
intermediate adenoma
inactivation of tsg on 18q
laste adenoma
inactivation of tp53 tsg= bypasss senescence
carcinoma - malignant but not breach bm so can be removed
Inactivation of other tsgs
metastatic colorectal cancer
many diff oncogenes acquired and tsgs lost
what do cells accumulate as tumour progression proceeds
genetic and epigenetic alterations
what is carcinoma in situ
not a benign neoplasm
a carcinoma - stage 0
how is carcinoma in situ similar to malignancy
has biological geno and phenotype of malignancy
how is carcinoma in situ different from malignancy
has not invaded bm
cannot metastasize in its current state
considered premalignant or pre cancerous
as long as completely removed or treated = patient will be cured
intact bms = 0% chance of malignancy
what is emt and describe
Epithelial to mesenchymal transition
cellular process = epithelial cells acquire mesenchymal phenotypes and behaviour following the downreg of epithelial features
cells display fibroblast like morphology and increased migratory capacity
occurs during gastrulation and also when cancer metastasizes
more fibroblast like morphology
increase capability of spreading out and invading and migrating
name and explain the 4 core emt changes
1 - cytoskeletal remodeling
2 - cell cell adhesion weakening = lose tj and polarity
3 - acquisition of cell motility
4 - bm invasion
Change in gene expression - certain genes now turned off and certain genes associated with mesenchymal cells turned on
describe malignant tumour invasion
infiltrate lymphatic system and blood vessels and transport out and invade other parts of body
name the 4 parts of the invasion metastasis cascade
1 - localized invasiveness enables in situ carcinoma cells to breach bm
2 - intravasation into lymphatic blood vessels
3 - blood vessels can transport caner cells to distant sites
4 - cancer cells colonize to form metastatic tumours
what is met and describe
mesenchymal to epithelial transition = process reversed to form metastasis
mesenchymal like cells may acquire apical-basal polarity, reorganize their cytoskeleton and exhibit increased cell cell adhesion, resulting in organized epithelium= for them to be able to colonize
describe metastatic cancer
can localize in diff places
can have cancer without symptoms for a long time
pancreatic cancer = silent killer
various metastatic tropisms
