intro to carcinogenesis (neoplasm 1) Flashcards
carcinoma
malignant tumor originates in epithelium
sarcoma
malignant tumor originates in mesechyme
merkel cell carcinoma
neuroendocrine tumor of skin
osteoma
benign tumor of bone
where is BRCA 1 located on chromosomes
17
where is BRCA 2 located on a chromosme
13
where is cancer mestastases to bone most common
vertebral column
pelvis
how do. pro-carcinogens get converted to carcinogens
by cytochrome P450
How can extrinsic factors for cancers be categorised
Behavioural
environmental
How can reproductive history in a women be related to cancer
History of long term exposure of oestrogen that is unopposed by progesterone can increase risk of cancer
E.g. later pregnancies
How does epstein barr virus act as a carcinogen
Infect B lymphocytes and promotes cell survival and proliferation
How does HIV act as a carcinogen
Indirectly lowers immunity allowing other carcinogenic infections to occur
How many alleles must be inactivated in tumour suppressor genes for neoplastic growth
2
How many alleles of proto-oncogenes need to be activated for neoplastic growth
1
In what stages of carcinogenesis are chemicals involved in
Initiation and promotion
Neoplasm
Abnormal growth of cells, persists after the initial stimulus is removed
Radiation therapy causes single and double stranded
DNA breaks
What advantages do germline mutations have in carcinogenesis
The germline mutation allows for neoplastic cells to have a head start in carcinogenesis
What are examples of indirect infectious carcinogens
Hepatitis B and C
Parasitic flukes
Helicobacter pylori
What are some behavioural factors associated with causes of cancer
High BMI
Low fruit and vegetable intake (Colorectal cancers)
Lack of physical activity
smoking
Alcohol use
What are some enviromental factors associated with causes of cancer
Chemicals
Radiation
viruses
What are some intrinsic factors for causes of cancer
Age-Older age more at risk
Gender-Related to hormones
Heredity
What are the 2 categories of neoplasm
Benign
Malignant
What are the 2 methods in which infections can cause carcinogenesis
Directly by affecting genes that control cell growth
Indirectly by causing chronic tissue damage resulting in regeneration
What are the 2 pathways in cell signalling pathways for carcinogenesis
Mutation in Ras
Lack of pRb
What are the 3 general stages of neoplasia
Initiation
Promotion
progression
What are the 6 hallmarks of cancer
1.self-sufficiency in growth signals;
2.resistance to growth stop signals;
3.no limit on the number of times a cell can divide (cell immortalisation);
4/sustained ability to induce new blood vessels (angiogenesis);
5.resistance to apoptosis;
6.the ability to invade and produce metastases
What are the different classifications of mutagenic chemical carcinogens
Polycyclic aromatic hydrocarbons - cigarette smoke
aromatic amines - cigarette smoke
N-nitroso compounds - smoked foods
Alkylating agents -
natural products - asbestos, aspergillus
What can asbestos act as in regards to carcinogenesis
Initiator and promotor
What cancer(s) are associated with Asbestos?
mesothelioma
bronchogenic carcinoma
What do proto-oncogenes code for
Growth factors
Growth factor receptors
Plasma membrane signal transducers
Intracellular kinases
Transcription factors
Cell cycle regulators
Apoptosis regulators
What does E6 inhibit
p53
What does E7 inhibit
pRB
What is a complete carcinogen
Carcinogen that is a initiator and promotor
What is a pro-carcinogen
substance that is transformed into a carcinogen by metabolism
What is an example of a molecular alteration for growth indefinitely in cancer
Telomerase gene activation
What is an example of a molecular alteration for induction of new blood vessels in cancer
Activation of VEGF expression
What is an example of a molecular alteration for invasion and production of metastases in cancer
E-Cadherin mutation
What is an example of a molecular alteration for resistance to anti-growth signals in cancer
CDKN2A gene deletion
What is an example of a molecular alteration for resistance to apoptosis in cancer
BCL2 gene translocation
What is an example of a molecular alteration for self sufficient growth signals in cancer
HER2 gene amplification
What is an example of infection that is direct carcinogen
HPV
What is anaplastic tissue?
poorly differentiated tissue
What is desmoplastic tissue?
Fibrous tissue made in response to neoplasm.
What is genetic instability
high frequency of mutations within genome of cellular lineage
What is required for malignant neoplasm
Multiple mutations
What is the Ames test
method that uses bacteria to test if a given chemical can cause mutations in DNA.
What is the approximate number of mutations needs for malignant neoplasm
10 or less
What is the function of BRCA1 and BRCA2
Repair double strand DNA breaks
What is xeroderma pigmentosa due to
Mutations in one of 7 genes that effects DNA nucleotide excision repair
What occurs in direct DNA damage
Altered bases
Single/double strand DNA breaks
What occurs in indirect DNA damage
Free radical production
What proteins does human papilloma virus express
E6
E7
What type of carcinogen is epstein barr virus
indirect
What type of condition is hereditary non-polyposis colon cancer syndrome
Autosomal dominant
What type of genetic condition is xeroderma pigmentosa
autosomal recessive
When do initiation and promotion lead to neoplasms
When proto-oncogenes and tumour suppressor genes affected
Which 2 angiogenic growth factors are commonly produced by tumour cells?
FGF
VEGF
Which cyclin-CDK complex functions to phosphorylate Rb bound to E2F?
CyclinD/CDK4
allows E2F to be free drive the transition into the S-phase cell cycle.
Rb mutation allows for constitutively active E2F and uncontrolled cell growth.
Which neoplasm is associated with Actinic Keratosis?
Squamous cell carcinoma of the skin
Which of the BRCA genes is involved with Male Breast Cancer?
BRCA2
Which transition point in the cell cycle is regulated by p53?
G1 to S
Which transition point in the cell cycle is regulated by Rb (retinoblastoma protein)?
G1 to S
protein upregulated by tumour suppressor p53 that functions to disrupt Bcl2, thereby causing apoptosis.
BAX
decreased BCL2 leads to increase cytochrome c leakage from mitochondria and activates caspases
benign tumour of cartilage.
chondroma
what function of p53
tumour suppressor gene that upregulates BAX if DNA damage cannot be repaired.
what is the function of Rb
tumour suppressor protein that “holds” the E2F transcription factor needed for the transition into S-phase.
what is telomerase
enzyme involved with DNA replication that is often upregulated in cancer, thereby resulting in neoplastic cells having preserved telomeres.
