Monday Review - neoplasia + epidemiology

Question 1

What % of malignant neoplasms are caused by environment?

Answer 1

80%

Very large correlation w/ geographical region!

Question 2

Malignant tumors need which 2 things?

Answer 2

Invasion and metastasis

Question 3

What does carcinoma in situ mean?

Answer 3

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

Question 4

Hallmarks enabling characteristics of pathogenesis

Answer 4

○ 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

Question 5

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

Answer 5

Intravasation

Question 6

Can any cell become malignant?

Answer 6

No, just stem cells.

Question 7

How do malignant cells start invading?

Answer 7

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

Question 8

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

Answer 8

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.

Question 9

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

Answer 9

E-cadherin decrease = facilitate detachment

Question 10

4 ways E cadherin mutation is lost

Answer 10

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

Question 11

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

-how?

Answer 11

snail
slug
twist
ZEB1/2

repress E cadherins

Question 12

How do MMPs regulate tumor invasion?

Answer 12

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.

Question 13

How is CD44 involved in tumor metastasis?

Answer 13

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

overexpressed in cancer

Question 14

Ultimate effects of METASTASIS leading to mortality

Answer 14

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

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

Question 15

Ultimat causes of mortality due to cancer

Answer 15

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

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

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

Answer 18

No: must be activated by CYP P450 liver enzyme

-> gain diol, or epoxide

Question 19

Which carcinogens are found when in:

1. Burnt stuff
2. Industrial/consumer products
3. preservatives (foods)
4. moldy grain, nuts, tropics, corn, turkey

Answer 19

1. Burnt stuff - Polycyclic aromatic hydrocarbons
2. Industrial/consumer products - aromatic amines
3. preservatives (foods) - nitrosamines
4. moldy grain, nuts, tropics, corn, turkey - aflatoxin

Question 20

Miller’s Theory of Carcinogenesis

Answer 20

• 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

Question 21

Ames test

Answer 21

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

+ = mutagen present

Question 22

How are cellular triggers of carcinogenesis inherited?

Answer 22

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

Question 23

Cancer develops through which two stages?

Answer 23

Initiation : effect of carcinogen

Promotion: non carcinogen enabler

Question 24

Are bile salts a tumor initiator or promoter? why?

Answer 24

Promoter -> promotes cancer in benign colon polyps

Question 25

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

Answer 25

No. needs initiation then promotion. always

Question 26

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

Answer 26

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.