Neoplasia 3 8-10-15

Question 1

What do carcinogenic agents do?

Answer 1

inflict genetic damage

-react with nucleic acids (RNA, DNA) and or proteins

Question 2

What are direct acting vs indirect acting chemical carcinogens?

Answer 2

1. direct acting
   - require no metabolic conversion
   - ex: cancer chemotherapeutics)alkylating agents)
2. 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

Question 3

What do promoters do to carcinogenicity?

Answer 3

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

Question 4

vinyl chloride

Answer 4

angiosarcoma of the liver

Question 5

Nitrosamine in smoked foods

Answer 5

stomach cancer

Question 6

asbestos

Answer 6

mesothelioma and bronchogenic carcinoma

Question 7

Arsenic

Answer 7

squamous cell carcinoma of the skin

Question 8

naphthylamine dyes

Answer 8

urothelial carcinoma of the bladder

Question 9

aflatoxin B

Answer 9

hepatocellular carcinoma (primary liver cancer)

Question 10

cigarette smoke

Answer 10

carcinoma of the oropharynx, lung, esophagus, kidney and bladder

Question 11

What are sources of radiation carcinogens?

Answer 11

• sunlight-ultraviolet radiation
• x-rays
• nuclear fusion/ionizing radiation
• fission by-products
• radionuclides

Question 12

What does ionizing radiation do?

Answer 12

results in chromosome breakage, translocations, point mutations, which leads to genetic damage and carcinogenesis

-associated with papillary carcinoma of the thyroid

Question 13

What does UV light do?

Answer 13

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

Question 14

Is radiation initiation reversible is continued exposure additive

Answer 14

• irreversible
• additive
• radiation carcinogenesis has a long latent period

Question 15

xeroderma pigmentosum

Answer 15

autosomal recessive syndrome of defective DNA repair

• defect in nucleotide excision repair pathway
• markedly increased predisposition to skin cancer

Question 16

What types of microbial things cause cancer?

Answer 16

1. RNA viruses
   - T-cell lymphotropic virus (HTLV-1)
   - ->T cell leukemia/ lymphoma
2. DNA viruses
   - HPV
   - –>benign warts and cervical cancer
   - Epstein Barr Virus
   - –>burkitt lymphoma, nasopharyngeal carcinoma
   - Hep B and C virus
   - ->hepatocellular carcinoma
3. Bacteria
   - Heliobacter pylori
   - Gastric adenocarcinoma, MALT lymphoma

Question 17

How do cancers evade immune system?

Answer 17

• 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

Question 18

What are 3 effects tumors have on the host?

Answer 18

1. compress adjacent tissue and ulcerate through surfaces
2. can produce hormones
3. cancer cachexia-loss of body fat, lean body mass, weakness, anorexia, anemia

Question 19

What is cancer cachexia? What cytokines mediate it? Is there treatment?

Answer 19

• loss of body fat, lean body mass
• weakness, anorexia, anemia

cytokine mediated

• TNF
• proteolysis inducing factor

-no satisfactory treatment-neoplasm cannot be removed

Question 20

Paraneoplastic Syndrom

Answer 20

symptoms complexes that cannot be readily explained by local or distant spread
-hormone elaboration not indigenous to tumor parenchyma

Question 21

What is grading based on?

Answer 21

cytologic differentiation of the tumor cells to estimate the aggressiveness of the tumor

1. degree of cellular differentiation
2. degree of cellular pleomorphism
3. degree of loss of normal architecture
4. mitotic index

Question 22

What is staging based (TNM system) on?

Answer 22

1. size of primary tumor (T1, T2, T3, T4)
2. Extent of spread to lymph nodes (NO, N1 (regional), N2, N3)
3. presence or absence of metastasis (M0 or M1)

Question 23

Which is of greater clinical significance grading or staging?

Answer 23

staging
exept
-prostate cancer, chondrosarcoma

Question 24

What are some methods that aid diagnosis?

Answer 24

1. histological and cytological examination (tissue vs cell)
2. histoimmunochemistry
3. biochemical studies
4. ultrastructural studies (electron microscopy)
5. molecular biology studies

Question 25

What do you use biochemical studies for?

Answer 25

detection of tumor associated markers

-know they had this type of cancer, check for recurrence

Question 26

What does Alpha fetoprotein determine?

Answer 26

• liver carcinomas
• tumor of yolk sac remnants
• gonadal tumors

Question 27

what does carcinoembryonic antigen determine?

Answer 27

colon, pancreas, lung, stomach, breast

Question 28

What does molecular analysis of tumors play a role in?

Answer 28

• *Diagnosis
• prognosis
• detection of minimal residual disease
• diagnosis of hereditary predisposition to cancer
• therapeutics