Neoplasia 3 8-10-15 Flashcards
What do carcinogenic agents do?
inflict genetic damage
-react with nucleic acids (RNA, DNA) and or proteins
What are direct acting vs indirect acting chemical carcinogens?
- direct acting
- require no metabolic conversion
- ex: cancer chemotherapeutics)alkylating agents) - Indirect
- require metabolic conversion to become ultimate carcinogens
- ex:
- polycyclic hydrocarbons:
a. benzo(a) pyrene formed in combustion of tobacco
b. animal fats
- aromatic amines, azo dyes
a. B-naphthylamine in dye and rubber industries
*some people have enzymes that are really robust
What do promoters do to carcinogenicity?
compounds which themselves are non tumorigenic however they
*facilitate the induction of cell proliferation
“initiation-promotion” sequence
-some chemical carcinogens may act in concert with viruses or radiation to induce neoplasms
vinyl chloride
angiosarcoma of the liver
Nitrosamine in smoked foods
stomach cancer
asbestos
mesothelioma and bronchogenic carcinoma
Arsenic
squamous cell carcinoma of the skin
naphthylamine dyes
urothelial carcinoma of the bladder
aflatoxin B
hepatocellular carcinoma (primary liver cancer)
cigarette smoke
carcinoma of the oropharynx, lung, esophagus, kidney and bladder
What are sources of radiation carcinogens?
- sunlight-ultraviolet radiation
- x-rays
- nuclear fusion/ionizing radiation
- fission by-products
- radionuclides
What does ionizing radiation do?
results in chromosome breakage, translocations, point mutations, which leads to genetic damage and carcinogenesis
-associated with papillary carcinoma of the thyroid
What does UV light do?
damages DNA by forming pyrimidine dimers-this process is repaired by the nucleotide excision repair pathway
-associated cancers-skin squamous cell carcinoma, basal cell carcinoma, melanoma
Is radiation initiation reversible is continued exposure additive
- irreversible
- additive
- radiation carcinogenesis has a long latent period
xeroderma pigmentosum
autosomal recessive syndrome of defective DNA repair
- defect in nucleotide excision repair pathway
- markedly increased predisposition to skin cancer
What types of microbial things cause cancer?
- RNA viruses
- T-cell lymphotropic virus (HTLV-1)
- ->T cell leukemia/ lymphoma - DNA viruses
- HPV
- –>benign warts and cervical cancer
- Epstein Barr Virus
- –>burkitt lymphoma, nasopharyngeal carcinoma
- Hep B and C virus
- ->hepatocellular carcinoma - Bacteria
- Heliobacter pylori
- Gastric adenocarcinoma, MALT lymphoma
How do cancers evade immune system?
- fail to express HLA class 1 and escape CTL(cytotoxic t lymphocytes) attack
- eliminate strong immunogenic subclone
- suppress the host immune responses–>secrete TGF B, Expressing FasL and inducing immune cell apoptosis; activating regulatory t cells
- producing a thicker coat of glycocalyx molecules blocking access to immune cells
What are 3 effects tumors have on the host?
- compress adjacent tissue and ulcerate through surfaces
- can produce hormones
- cancer cachexia-loss of body fat, lean body mass, weakness, anorexia, anemia
What is cancer cachexia? What cytokines mediate it? Is there treatment?
- loss of body fat, lean body mass
- weakness, anorexia, anemia
cytokine mediated
- TNF
- proteolysis inducing factor
-no satisfactory treatment-neoplasm cannot be removed
Paraneoplastic Syndrom
symptoms complexes that cannot be readily explained by local or distant spread
-hormone elaboration not indigenous to tumor parenchyma
What is grading based on?
cytologic differentiation of the tumor cells to estimate the aggressiveness of the tumor
- degree of cellular differentiation
- degree of cellular pleomorphism
- degree of loss of normal architecture
- mitotic index
What is staging based (TNM system) on?
- size of primary tumor (T1, T2, T3, T4)
- Extent of spread to lymph nodes (NO, N1 (regional), N2, N3)
- presence or absence of metastasis (M0 or M1)
Which is of greater clinical significance grading or staging?
staging
exept
-prostate cancer, chondrosarcoma
What are some methods that aid diagnosis?
- histological and cytological examination (tissue vs cell)
- histoimmunochemistry
- biochemical studies
- ultrastructural studies (electron microscopy)
- molecular biology studies
