Monday Review - neoplasia + epidemiology Flashcards Preview

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Flashcards in Monday Review - neoplasia + epidemiology Deck (26):
1

What % of malignant neoplasms are caused by environment?

80%

Very large correlation w/ geographical region!

2

Malignant tumors need which 2 things?

Invasion and metastasis

3

What does carcinoma in situ mean?

epithelial cells have all the cytologic features of malignancy, but it hasn’t invaded basement membrane yet

4

Hallmarks enabling characteristics of pathogenesis

○ Capability to modify cellular metabolism in order to most effectively support neoplastic proliferation

○ Genetic instability endow cancer cells w/ genetic alterations that drive tumor progression

○ Inflammatory responses → meant to heal, but instead supports tumor growth

5

Process that malignant tumors gain access to the circulation by penetrating the vascular basement membrane

Intravasation

6

Can any cell become malignant?

No, just stem cells.

7

How do malignant cells start invading?

1. Changes “loosening up” of tumor cell-cell interactions:
2. Degradation of ECM (basement membrane and interstitial CT)
3. Attachment to ECM components
4. Migration (invasion) of tumor cells

8

4 major mechanism of metastasis (bias of how certain types of cancer -> certain organs)

1. Rare variant clones that develop in primary tumor

2. "metastatic signature" Gene expression pattern of most cells in primary tumor

3. Combination of 1 and 2

4. Tumor environment

also tumors have chemokine receptors! and the organ they like have the chemokines.

9

What proteins do tumor cells regulate to allow it to have an invasive phenotype? Should it increase or decrease for tumors?

E-cadherin decrease = facilitate detachment

10

4 ways E cadherin mutation is lost

1. LOH
2. Inactivating mutations (rare)
3. Silencing of gene expression (hypermethylation of promoter)
4. Transcriptional repressors

11

Name 4 transcriptional repressors that promote epithelial-> mesenchymal transition (EMT)

-how?

snail
slug
twist
ZEB1/2

repress E cadherins

12

How do MMPs regulate tumor invasion?

1) Remodeling ECM + release insoluble components of basement membrane

2) By releasing ECM-sequestered growth factors → cleavage products of collagen and proteoglycans have chemotactic, angiogenic, and growth-promoting effects.

13

How is CD44 involved in tumor metastasis?

T lymphocytes have CD44 adhesion molecule → migrate to selective sites in lymphoid tissue

overexpressed in cancer

14

Ultimate effects of METASTASIS leading to mortality

Direct:
- actual tumor mass -> interferes w/ function

Indirect:
- "paraneoplastic syndrome" symptom is consequence of cancer, but not due to local presence of cancer cells

15

Ultimat causes of mortality due to cancer

Infection 41.6%
Organ Failure 19.2%
Hemorrhage 8.8%
Thromboembolism 12.2%
Emaciation 7.7%

16

3 leading causes of new cases of cancer for males and females

• Men:
○ Prostate (26%)
○ Lung (14%)
○ Colon/Rectum (14%)
• Women:
○ Breast (29%)
○ Lung (13%)
○ Colon/Rectum (8%)

17

What are the 4 kinds of environmental chemicals that can be carcinogens?

1. Polycyclic aromatic hydrocarbons
2. aromatic amines
3. nitrosamines
4. aflatoxins

18

Are the 4 kinds of environmental chemicals that can be carcinogens always active? Describe why or why not.

No: must be activated by CYP P450 liver enzyme

-> gain diol, or epoxide

19

Which carcinogens are found when in:
1. Burnt stuff
2. Industrial/consumer products
3. preservatives (foods)
4. moldy grain, nuts, tropics, corn, turkey

1. Burnt stuff - Polycyclic aromatic hydrocarbons

2. Industrial/consumer products - aromatic amines

3. preservatives (foods) - nitrosamines

4. moldy grain, nuts, tropics, corn, turkey - aflatoxin

20

Miller's Theory of Carcinogenesis

• Chemical carcinogens are metabolized by CYP450 to chemically active forms

• Active metabolite is a strong electrophile

• Electrophilic species can chemically modify proteins, RNA, and DNA

21

Ames test

• A rapid and inexpensive test of chemicals/carcinogens for mutagens via Salmonella typhimurium that are His (-)

+ = mutagen present

22

How are cellular triggers of carcinogenesis inherited?

• The cellular triggers of carcinogenesis are stably inherited
○ Tumors are proliferations of clones of a malignant cell

23

Cancer develops through which two stages?

Initiation : effect of carcinogen

Promotion: non carcinogen enabler

24

Are bile salts a tumor initiator or promoter? why?

Promoter -> promotes cancer in benign colon polyps

25

Can tumor production be started with only the initator? Just the promoter? Why?

No. needs initiation then promotion. always

26

Compare and contrast differences between somatic and germline mutations that cause cancer and so-called “epigenetic” factors that cause cancer

Somatic: Can't be passed to offspring

Germline: Transmitted to offspring

Epigenetic: Not coded for in DNA, but a modification added to proteins or DNA (ie methylation) to repress a gene.