Path: Carcinogenesis 1 Flashcards Preview

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Flashcards in Path: Carcinogenesis 1 Deck (33):
1

Describe carcinogenic basis of UVB light.

UVB light from the sun causes pyrimidine dimer formation which is repaired by nucleotide excision, but sometimes this repair process is faulty - mutations accumulate and result in cancer

2

Pyrimidine dimer formation typically occurs between which two pyrimidines?

adjacent thymidines

3

Exposure to UV rays derived from the sun, particularly in fair-skinned individuals, is associated with an increased incidence of what 3 cancers?

squamous cell carcinoma, basal cell carcinoma, and melanoma of the skin

4

The degree of cancer risk during UVB light exposure depends on what?

- type of UV rays
- intensity of exposure
- quantity of light-absorbing melanin in the skin

5

what type of UV exposure are each of the following associated with?:
- nonmelanomas
- melanomas

total cumulative UV exposure; intense intermittent exposure

6

Why can't people with xeroderma pigmentosa go out in the sun unprotected?

they have defective nucleotide excision repair, therefore they are ever more susceptible to developing a cancer from UVB light exposure

7

Describe the classic microscopic pathology of the most common type of melanoma.

- Single cells or small clusters
- large round cells
- moderate amount of lightly basophilic cytoplasm, often with granules of brown melanin pigment
- large nuclei
- prominent nucleoli

8

If you are among the rocky mountain miners or survivors of the atomic bombings, what kind of radiation is causing your cancers?

Electromagnetic and particulate radiation

9

True or False: children who get 5-10 CT scans have a threefold higher risk of leukemia.

False - it only takes 2 or 3 CT scans to increase the risk of leukemia to threefold; 5-10 CT scans increase the risk of brain tumors by threefold*
*but that risk is 1 in 10,000 over 10 yrs

10

Epidemiologic studies strongly suggest a close association between hepatitis B/C virus infection and the occurrence of ____ cancer. Explain this.

liver - while the mode of tumorigenesis is not fully understood, the dominant effect seems to be chronic inflammation, hepatocyte death, and cell regeneration with activation of the NF-κB pathway leading to proliferation and genomic damage.

11

In Western countries the incidence of hepatocellular carcinoma is rapidly increasing, largely owing to what epidemic?

the hepatitis C epidemic

12

One key molecular step in hepatocellular injury seems to be activation of the ____ pathway; activation of which blocks ____ and allows the dividing hepatocytes to incur genotoxic stress and to accumulate mutations.

NF-κB; apoptosis

13

The HBV genome contains genes that may directly promote the development of cancer; name one and describe its activity.

an HBV gene known as HBx can activate a variety of transcription factors and several signal transduction pathways which is involved in the pathogenesis of virus-induced hepatocellular carcinoma

14

In addition to chronic liver cell injury and compensatory regeneration, the
HCV ____ ____ may have a direct effect on tumorigenesis,.

core protein

15

Is hepatitis C virus infection treatable to prevent the hepatocellular carcinomas it causes?

Yes

16

What is the primary etiologic agent, aka environmental factor, that causes gastric cancer?

Helicobacter pylori bacterium

17

What is H. pylori?

- spiral shaped, Gram negative bacterium
- has unique unipolar flagellae adapted to living in the human stomach
- primary etiologic agent of gastric cancer

18

What is CagA?

pathogenicity island of H. pylori that enters gastric epithelial cells and initiates signaling that mimics unregulated growth factor stimulation (Ras/Raf/Mek/Erk pathways)

19

Describe the process of developing gastric adenocarcinoma in the background of chronic inflammation, related to H. pylori infection.

over decades: initial development of chronic gastritis, followed by gastric atrophy, then intestinal metaplasia of the lining cells, then dysplasia, and finally cancer

20

If H. pylori is noninvasive, how does it cause intracellular changes that mimic unregulated growth factor stimulation?

CagA penetrates into gastric epithelial cells via a molecular syringe mechanism; once there it initiates the Ras/Raf/Mek/Erk signaling cascade

21

Histological visualization of goblet cells in the gastric surface mucosa indicates what condition?

intestinal metaplasia

22

Is Helicobacter pylori infection treatable to prevent the gastric carcinomas it causes?

You betcha.

23

How can tumor antigens stimulate T cells?

either by expressing altered gene products on the tumor cell surface via the MHC Class I pathway; or by APCs presenting antigen via MHC Class II pathway after taking up pieces of dead tumor cells

24

Describe the patterns of tumor antigen presentation.

1. overexpression/aberrant expression
2. expression in tumor cells that are derived from cells where that protein is not normally expressed

25

Where is the MAGE-1 antigen expressed?

on 37% of melanomas and some lung, liver, stomach, and esophageal carcinomas

26

Tumor antigens produced by human papilloma virus (HPV) and Epstein-Barr virus (EBV) are recognized by what type of T cells?

cytotoxic T cells

27

How are oncofetal antigens useful in the diagnosis and clinical management of cancer? Name 2 example oncofetal proteins used for this purpose.

oncofetal antigens expressed at high levels on cancer cells and can serve as markers that aid in tumor diagnosis and clinical management. The two most thoroughly characterized are carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP).

28

What are CA-125 and CA-19-9 and why are they significant?

they are mucins expressed on ovarian carcinomas and other types of carcinoma; useful for guiding course of treatment

29

Describe MUC-1 and what it is used for.

MUC-1 is a TM protein expressed on some ovarian and breast carcinomas, but is normally expressed only in breast ductal epithelium;
in breast ductal carcinomas it can be used as a target for mouse mAbs

30

What are some molecules secreted by tumors that may serve to downregulate host immune response? How do they downregulate the T cell response?

TGF-beta, IL-10, PGE2, tryptophan metabolites, and VEGFs - they inhibit the diapedesis of T cells from vasculature into tumor bed

31

What is CD20 and what is it good for?

it's a transmembrane protein expressed on the surface of normal mature B cells, and it's useful as a drug target because Abs against it have broad cytocidal activity against mature B-cell lymphomas and leukemias

32

How do tumor cells inhibit effector T cells?

They downregulate the expression of co-stimulatory molecules on APCs (that would bind CD28) and instead get them to bind/stimulate CTLA4; they also upreglate expression of PD-L1 and PD-L2 that bind PD-1 on T cells to initiated apoptosis and inhibit their effector functions

33

What is the "checkpoint blockade" treatment paradigm?

it's the idea that treatments that remove the “brakes” imposed by tumors on host anti-tumor immune responses can be highly effective in treating cancer; examples include Anti-CTLA4 and anti-PD-1 antibodies