Neoplasia Ii

Front 1

4 phases of malignant tumor growth?

Back 1

malignant transformation, growth of transformed cell, local invasion, distant metastasis

Front 2

agents that induce neoplastic change?

Back 2

chemical carcinogens, radiant energy, oncogenic microbes (viruses chiefly)

Front 3

describe initiation in chemical carcinogenesis

Back 3

exposure to inappropriate dose of a carcinogenic agent (initiator) thus altering cell, rendering it likely to give rise to a tumor, however, it alone cannot give rise to a tumor. rapid, irreversible, has memory, permanent mutation to the DNA.

Front 4

describe promotion in chemical carcinogenesis

Back 4

can induce tumors in initiated cells but are non tumorgenic by themselves. effect is reversible and unlikely that they affect the DNA

Front 5

direct vs indirect carcinogenesis?

Back 5

direct requires no metabolic conversion while indirect does

Front 6

describe the chemistry of the direct acting carcinogens and ultimately formed carcinogens that allows them to react with DNA, RNA, and protein

Back 6

highly reactive electrophiles (have electron deficient atoms) and can react with nucleophilic (electron rich) sites in the cells (ie DNA, RNA, and proteins with DNA being the main target)

Front 7

most carcinogens are metabolized by what?

Back 7

cytochrom p450 dependent mono oxygenase. note that metabolism can lead to detox of the procarcinogen/carcinogen or activation of it

Front 8

what must happen for the change in DNA to become fixed and permanent?

Back 8

it must undergo one replication cycle

Front 9

what specefic gene mutation is frequently noted in chemically indued cancers?

Back 9

RAS gene mutations

Front 10

describe the characteristics of promoters of carcingoenisis and give some examples

Back 10

non electrophillic, do not damage DNA. phorbol esters, phenols, hormones, drugs (phenobarbital). TPA is most widely used tumor promoter, it activates PKC that pis cell proliferating and diferentiating molecules

Front 11

describe the action of direct acting alkylating agents in carcinogenesis

Back 11

releatively weak, exs are cyclophosphamide, chlorambucil, busulfan, melphalan. induce lymphomas, leukemias, and others, interaction with and damage to the DNA renders them therapeutic and carcinogenic

Front 12

describe the action of polycyclic aromatic hydrocarbons.

Back 12

indirect carcinogens, activated by p450, most potent carcinogen, formed during combustion of tobacco with cig smoking, contribute to lung and bladder cancer

Front 13

describe the action of aromatic amines and azo dyes

Back 13

metabolized in liver via cyt p450 and excreted in urine. act on transitional epi of bladder, B naphthylamine implicates a 50 fold increase in bladder CA

Front 14

describe the action of aflatoxin B1.

Back 14

produced by aspergillus flavus, from corn, rice, peanuts, causes hepatocellular carcinoma

Front 15

describe the actions of nitrosamines and amides

Back 15

carcinogen formed in GI tract in humans, implicated in CA of the stomach, from preservatives and are converted to nitrites by bacteria

Front 16

cancers caused by asbestos?

Back 16

bronchogenic carcinoma, mesothelioma, GI cancer

Front 17

CA caused by vinyl chlorides?

Back 17

hemangiosarcomas of liver

Front 18

cancer caused by estrogens?

Back 18

endometrial carcinoma in post menopausal women

Front 19

describe the acylating agents as carcinognes

Back 19

dimethylcarbamyl chloride, do not need metabolic conversion and are weal carcinogens,many are also therapeutic agents

Front 20

degree of cancer risk from UV exposure depends upon?

Back 20

type of rays, intensity of exposure, quantity of melanin

Front 21

effects of UV light on cells?

Back 21

inhibition of cell division, inactivation of enzymes, induction of mutation, cell death

Front 22

carcinogensis from UV is attributed to what? damage is repaired by?

Back 22

pyrimidine dimers repaired by nucleotide excision repair. note mutations in oncogenes and tumor suppressors especially RAS and p53 have been notes

Front 23

initiation in UV damage? promotion?

Back 23

UV light IS the initiating mechanism and CMI changes is the promoter

Front 24

what disease is especially likely to induce skin cancer and why?

Back 24

xeroderma pigmentosum from a defect in the nucleotide excision repair of DNA

Front 25

what are some types of ionizing radiation that are carcinogenic and give the specefic CA caused by each

Back 25

X rays cause skin cancer. uranium miners have increase in lung cancer. atom bomb survivors of fallout got AML, CML after 7 years and some got thyroid, breast, colon, and lung Ca, after longer pds. thorotrast is used as a radiologic imaging contrast material and can cause angiosarcoma. therapeutic irradiation is carcinogenic - 9% of head and neck radiation in infacny and child hood developed thyroid cancer

Front 26

how do DNA oncogenic viruses cause CA on a molecular level?

Back 26

genomes of the oncogenic DNA viruses integrate into and form stable associations with the host genome

Front 27

what types of HPV are responsible for squamous cell cancer of the cervix?

Back 27

85% from types 16, 18. less frequently by 31, 33, 35, and 51.

Front 28

HPV that causes benign squamous papillomas (warts)?

Back 28

1,2,4, and 7. note 6 and 11 cause warts with low malignant potential

Front 29

describe aspects of integration and other carcinogenic activities of HPV.

Back 29

integration site is clonal (site of integration is identical in all cells of a given cancer), viral DNA is interrupted at E1/E2 ORF, in 16 and 18 viral protein E6 binds and facilitates the degradation of p53 while E7 binds tumor suppressor protein pRb

Front 30

EBV is seen in what cancers?

Back 30

african burkitts, B cell lymphoma, hodgkins lymphoma, nasopharyngeal carcinoma

Front 31

molecule that allows infection of nasopharynx epithelium and B lymphocytes to be infected with EBV.

Back 31

CD21 molecules

Front 32

common genetics of Burkitt's lymphoma?

Back 32

t (8;14) or less common variant translocation that leads to dysregulated expression of the c-myc oncogene

Front 33

how does hep B virus cause hepatocellular cancer?

Back 33

not sure- genome does not encode oncoproteins and pattern of integration is not constant. liver injury and regenerative hyperplasia increases the risk for genetic mutation