carcinogenesis

Question 1

what is cancer?

Answer 1

disease characterized by uncontrolled cellular growth

Question 2

what is transformation?

Answer 2

process of converting a normal cell into a cell having attributes of a cancer cell

Question 3

what is neoplasia?

Answer 3

growth of new tissue (benign)

Question 4

what is neoplasm/tumor?

Answer 4

abnormal grwoth of tissue forming a mass

Question 5

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?

Answer 5

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

Question 6

what is the difference between begin and malignant tumors?

Answer 6

benign: local growth without invading adjacent tissue, often harmless, complications possible

malignant tumors: infiltration of nearby tissue, metastases, cachexia, obstruction

Question 7

what leads to complications in benign tumors?

Answer 7

mass effect, hormone overproduction, malignant transformation

Question 8

what are the major classifications of malignant tumors?

Answer 8

epithelial tissue, non-epithelial tissue, other tumors

Question 9

what tumors are in epithelial tissue?

Answer 9

carcinoma

Question 10

what tumors are in non epithelial tissue?

Answer 10

sarcoma, leukemia, lymphoma, neuroectodermal tumors

Question 11

which system is used for the stagingof cancer and what does it stand for?

Answer 11

TNM: Tumor, Nodes, Metastases

Question 12

what is grading of tumors used for?

Answer 12

determination of cell anaplasia, degree of tumor aggressivness, pathology, nucleus to cytoplasm ratio, mitotic activity, atypical mitoses

Question 13

what is the aim of staging?

Answer 13

help to plan treatment and give an indication of prognosis

Question 14

what are the grading categories?

Answer 14

GX: cannot be assessed
G1: well differentiated
G2: moderately differentiated
G3: poorly differentiated
G4: undifferentiated (high grade= anaplastic)

Question 15

what is the relationship between tumor grade and prognosis?

Answer 15

High grade = cell grow more quickly, metastasis more frequently, less responsive to treatment –> poor prognosis

Question 16

what types of riskfactors are there and how much do they contribute?

Answer 16

parental inheritance: 10 %
environmental factors: 90 %

Question 17

what types of environmental riskfactors are there?

Answer 17

lifestyle, naturally occuring exposures, medical treatment, air pollution, workplace exposure

Question 18

is obesity a risk factor? how much does it contribute?

Answer 18

yes, obesity is associated to 40 % of all diagnosed cancers

Question 19

how is the correlation between cancer and age?

Answer 19

exponential

Question 20

what are benign precursors?

Answer 20

many carcinomas can develop from begnin precursors

Question 21

what are riskfactors for pancreatic cancer?

Answer 21

family history, diet, obesity, race, smoking, gender, age, diabetes, pancreatitis

Question 22

what types of clonal expansion of tumors are there?

Answer 22

monoclonal (rare) and polyclonal

Question 23

what types of intra-tumor heterogeneity exsists?

Answer 23

genetic level, morphological level, functional level

Question 24

name the two tumor propagation models and explain how they work

Answer 24

stochastic model: each cell can form a new tumor

hierachical model: only original stem cell can form new tumor

Question 25

how is the regenerative tissue organized?

Answer 25

hierachical: tissue stem cell --> progenitors --> specialized cells

Question 26

how is the stem cell micro environment built?

Answer 26

stem cell niche, supporting stem cell viability, regulating self-renewal and differentiation

Question 27

what are the characteristics of the stem cell niche?

Answer 27

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

Question 28

how can the stem cell niche act on a stem cell?

Answer 28

direct contact, soluable factors (cytokines, grwoth factors), intermediate cell

Question 29

which animal model can be used in cancer research? Why and for what?

Answer 29

c.elegans --> a lot of homology to humans, cheap can be used as a model for a germline stem cell niche

Question 30

into what cells can the interstinal stem cell differentiate?

Answer 30

absorptive cell, goblet cell, enteroendrocrine cell, paneth cell

Question 31

what method can be used to identify tumor initiating cells?

Answer 31

FACS: isolation of cancer cells from sample --> staining with fluorophore conjugated antibodies against surface protein markers --> cell sorting by FACS --> analysis

Question 32

what are the characteristics of cancer stem cells?

Answer 32

behave like stem cells self-renewal unlimited proliferation potential production of a large number of progeny

Question 33

how do cancer stem cells arise?

Answer 33

mutation in 1. stem cell 2. progenitor 3.differentiated cell dedifferentiates

Question 34

why is there resistance against radio- and chemotherapy? How can it be circumvented?

Answer 34

due to stemness induction: drug export ROS decrease high survival Quiescence solution: target cancer stem cells

Question 35

what are the six hallmarks of cancer? Give one example each.

Answer 35

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)

Question 36

What is the reductionism model and heterotypic model?

Answer 36

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

Question 37

Name two new emerging hallmarks and two enabeling characteristics

Answer 37

new hallmarks: deregulating cellular energetics and avoiding immune destruction enabling characteristics: genome instability/mutation and tumor promoting inflammation