neoplasias Flashcards
basic components of all tumors
- neoplastic cells (parenchyma)
- supporting stroma
supporting stroma of tumor cells
- CT
- blood vessels
- adaptive/ innate immunity cells
tumor microenviornment
- hematopoietic cells
- cells with mesenchymal origin
- non-cellular components
heatompoietic cells in tumor microenviornment
- cells arise in bone marrow
- consist of T and B cells, NK cells, macrophages, and neutrophils
cells with mesenchymal origin in tumor microenviornment
- fibroblasts
- myofibroblasts
- mesenchymal stem cells
- adipocytes
- endothelial cells
non-cellular components of microenviornment
- ECM
- proteins
- glycoproteins
- proteoglycans
significance of tumor microenviornment
- protects cancer cells
- important influence on malignancy outcome and treatment responses
differentiation
- how closely tumor cells histologically and functionally resemble their normal cell counterpart
- lack of differentiation= anaplasia
metaplasia
replacement of one cell type with another cell type
dysplasia
loss of ceulluar uniformity and architectural organization
carcinoma in situ
marked dysplastic changes involving the entire thickness of epithelium
invasive carcinoma
basement membrane is not intact so abnormal cells can escape and metastasize
local invasion of neoplasms
- most benign tumors don’t invade locally
- malignant tumors cause local invasion
metastasis of neoplasms
- single most important features distinguishing benign from malignant
- can metastasize due to dislodged cells
pathways of tumor spread
- seeding of body cavities and surfaces
- lymphatic spread
- hematogenous spread
what tumors commonly spread hematogenously
- sarcoma
- some carcinomas
what tumors commonly spread in lymphatics
carcinomas
tropism
- tumors tendency to metastasize to specific organs
- indicates ability to adopt and colonize
mechanisms of tumors tropisms
- adhesion molecules with preferential expression of ligands in specific organs
- chemokine receptors in particular organs
- microenviornment of organ might not be suitable
where is the primary site of metastasize for colon cancer and why?
- metastasizes to liver
- due to portal vein drainage from colon directly to liver
environmental factors in cancer
- infectious agent
- smoking
- alcohol consumption
- diet
- obesity
- reproductive history
- environmental carcinogens
- age
acquired predisposing factors in cancer
- chronic inflammation
- precursor lesions
- immunodeficiency states
hallmarks of cancer
- sustaining proliferative signaling
- avoiding immune destruction
- evading growth suppressors
- enabling replicative immortality
- tumor promoting inflammation
- activating invasion and metastasis
- genomic instability
- inducing angiogenesis
- resisting cell death
- deregulating cellular energetics
normal cell proliferation
- growth factor binding to cell surface receptor
- activation of signal transduction proteins
- initiating DNA transcription
oncogenes
promote autonomous/ abnormal cell growth
tyrosine kinase
- family of receptors that phosphorylate target protein using ATP
- causes cellular growth, apoptosis, and cell migration
tyrosine kinase mutations
- cause inappropriate activation of signaling pathways
- leads to neoplastic growth
MYC oncogene
- most commonly involved in human tumors
- causes over-expression of growth factor receptors
main cause of MYC oncogene mutation
- causes burkitt lymphoma
- is an aggressive b cell lymphoma
tumor suppressor genes
- slow cell divisions
- repair DNA mistakes
- activate apoptosis
- cancer arises due to inactivation
- i.e. RB and P53
loss of heterozygosity
- mutation of both alleles of tumor suppressor genes needed for carcinogenesis
RB
- tumor suppressor gene
- causes persistent cell cycling
- mutation causes pathogenesis of childhood tumor retinoblastoma
P53 gene
- normally prevents growth of genetically defective cells
- senses DNA damage
- if DNA can be repaired, cell undergoes S phase
- if DNA cant be repaired, induces apoptosis
- mutated in more than 50% of all cancers
cell mediated immunity
- cytotoxic T cells (CD8+)
- NK cells
- macrophages
role of telomeres
- protect end of chromosomes
- when shorten, cell undergoes senescence and/or apoptosis
- telomerase builds telomeres
role of telomerase in tumor cells
- is active in tumor cells
- prevents apoptosis
metastatic cascade
- invasion of ECM
- vascular dissemination and homing of tumor cells
invasion of ECM
- detachment and loosening of intracellular junctions
- ECM degraded by proteases
- migration of tumor cells
theories about how metastasis occurs
- clonal evolution model -> rare variant clones
- metastasis signature
- metastatic variants exist in a tumor with metastatic signature
- role of tumor stroma
genomic instability
- DNA repair pathways act indirectly by correcting spontaneous DNA errors
- inherited mutations increase risk of carcinogenesis
mutations that cause breast cancer
- BRCA1
- BRCA2
mutations that cause ovarian, prostate, pancreas and stomach cancers
mutations in BRCA2
angiogenesis
- creation of new blood vessels
- stimulates tumor growth through endothelial cell production of GF
- influences metastatic potential
result of hypoxia in tumorgenesis
- causes upregulation of VEGF
- leads to angiogenesis
proapoptotic proteins
- considered primed for apoptosis
- occurs in normal cells
antiapoptotic proteins
- considered unprimed for apoptosis
- occurs in tumor cells
do cancer cells utilize aerobic or anaerobic metabolism?
- anaerobic respiration
- able to complete anaerobic respiration 100 times faster than aerobic respiration
steps involved in chemical carcinogenesis
- initiation
- promotion
initiation of chemical carcinogenesis
- induction of irreversible changes/ mutations in the genome
- direct acting agents- no metabolic conversion
- indirect acing agents- metabolic conversion
promotion of chemical carcinogenesis
- can induce tumors in previously initiated cells by stim cell proliferation
- short lived, reversible and nontumorigenic
UVA radiation
- creates ROS
- gets through all clothes and sunscreen
UVB radiation
- most prominent UV damage
- causes t dimers
- t dimers distort DNA
radiation carcinogenesis
- damage the nucleotides or DNA sugar moieties
- strand breaks in DNA
- indirect DNA damage by increasing ROS
benign and malignant tumors can cause problems due to:
- location
- functional activity like hormones produced
- bleeding and infection
- sx from tumor rupture or infection
- cachexia
cachexia
- profound muscle loss
- possible fat loss
- staged as precachexia, cachexia, refractor cachexia
pathophys of cachexia
- cytokines, inflammation and hypermetabolic state
- lipolysis and lipid mobilization
- genomics
- cancer treatments
- reduced dietary intake or absorption
