carcinogenesis Flashcards
what is cancer?
disease characterized by uncontrolled cellular growth
what is transformation?
process of converting a normal cell into a cell having attributes of a cancer cell
what is neoplasia?
growth of new tissue (benign)
what is neoplasm/tumor?
abnormal grwoth of tissue forming a mass
what are the attributes of normal cells vs cancer cells regarding cell proliferation, number of cell devisions, contact inhibition, dependency on growth factors, tumor formation?
normal cell: controlled cell proliferation, 50 cell cycles, monolayer culture (contact inhibition), dependency on grwoth factors, no tumor formation
cancer cell: uncontrolled cell proliferation, immortality, multilayer culture (no contact inhibition), no dependency on growth factors, tumorigenic
what is the difference between begin and malignant tumors?
benign: local growth without invading adjacent tissue, often harmless, complications possible
malignant tumors: infiltration of nearby tissue, metastases, cachexia, obstruction
what leads to complications in benign tumors?
mass effect, hormone overproduction, malignant transformation
what are the major classifications of malignant tumors?
epithelial tissue, non-epithelial tissue, other tumors
what tumors are in epithelial tissue?
carcinoma
what tumors are in non epithelial tissue?
sarcoma, leukemia, lymphoma, neuroectodermal tumors
which system is used for the stagingof cancer and what does it stand for?
TNM: Tumor, Nodes, Metastases
what is grading of tumors used for?
determination of cell anaplasia, degree of tumor aggressivness, pathology, nucleus to cytoplasm ratio, mitotic activity, atypical mitoses
what is the aim of staging?
help to plan treatment and give an indication of prognosis
what are the grading categories?
GX: cannot be assessed
G1: well differentiated
G2: moderately differentiated
G3: poorly differentiated
G4: undifferentiated (high grade= anaplastic)
what is the relationship between tumor grade and prognosis?
High grade = cell grow more quickly, metastasis more frequently, less responsive to treatment –> poor prognosis
what types of riskfactors are there and how much do they contribute?
parental inheritance: 10 %
environmental factors: 90 %
what types of environmental riskfactors are there?
lifestyle, naturally occuring exposures, medical treatment, air pollution, workplace exposure
is obesity a risk factor? how much does it contribute?
yes, obesity is associated to 40 % of all diagnosed cancers
how is the correlation between cancer and age?
exponential
what are benign precursors?
many carcinomas can develop from begnin precursors
what are riskfactors for pancreatic cancer?
family history, diet, obesity, race, smoking, gender, age, diabetes, pancreatitis
what types of clonal expansion of tumors are there?
monoclonal (rare) and polyclonal
what types of intra-tumor heterogeneity exsists?
genetic level, morphological level, functional level
name the two tumor propagation models and explain how they work
stochastic model: each cell can form a new tumor
hierachical model: only original stem cell can form new tumor
how is the regenerative tissue organized?
hierachical: tissue stem cell –> progenitors –> specialized cells
how is the stem cell micro environment built?
stem cell niche, supporting stem cell viability, regulating self-renewal and differentiation
what are the characteristics of the stem cell niche?
secreted factors: chemokines, hormones, wnt
inflammation: macrophages, T cells
extracellullar matrix: integrins, fibronectin/collagen, basement membrane
physical factors: elasticity/stiffness, topography
hypoxia and metabolism
cellular components: blood vessels, nerve cells, tissue specific cells
how can the stem cell niche act on a stem cell?
direct contact, soluable factors (cytokines, grwoth factors), intermediate cell
which animal model can be used in cancer research? Why and for what?
c.elegans –> a lot of homology to humans, cheap
can be used as a model for a germline stem cell niche
into what cells can the interstinal stem cell differentiate?
absorptive cell, goblet cell, enteroendrocrine cell, paneth cell
what method can be used to identify tumor initiating cells?
FACS: isolation of cancer cells from sample –> staining with fluorophore conjugated antibodies against surface protein markers –> cell sorting by FACS –> analysis
what are the characteristics of cancer stem cells?
behave like stem cells
self-renewal
unlimited proliferation potential
production of a large number of progeny
how do cancer stem cells arise?
mutation in
1. stem cell
2. progenitor
3.differentiated cell dedifferentiates
why is there resistance against radio- and chemotherapy? How can it be circumvented?
due to stemness induction:
drug export
ROS decrease
high survival
Quiescence
solution: target cancer stem cells
what are the six hallmarks of cancer? Give one example each.
1.self sufficiency in growth signals (activation of H-Ras oncogene)
2.insensitivity to anti-growth signals (loss of retinoblastoma suppressor)
3.tissue invasion and metastasis (production of IGF survival factor)
4.limitless replicative potential (turn on telomerase)
5.sustained angiogenesis (production of VEGF inducer)
6.evading apoptosis (inactivation of E-cadherin)
What is the reductionism model and heterotypic model?
reductionist: cancer is a disease of cells and the phenotype of cancer cells can be understood by examining genes and proteins within them
heterotypic: neoplastic cells are in continous communication with their non-neoplastic neighbor cells within the tumor mass/microenvirnonment
Name two new emerging hallmarks and two enabeling characteristics
new hallmarks: deregulating cellular energetics and avoiding immune destruction
enabling characteristics: genome instability/mutation and tumor promoting inflammation
