Flashcards in Monday Review - neoplasia + epidemiology Deck (26)
What % of malignant neoplasms are caused by environment?
Very large correlation w/ geographical region!
Malignant tumors need which 2 things?
Invasion and metastasis
What does carcinoma in situ mean?
epithelial cells have all the cytologic features of malignancy, but it hasn’t invaded basement membrane yet
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
Process that malignant tumors gain access to the circulation by penetrating the vascular basement membrane
Can any cell become malignant?
No, just stem cells.
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
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.
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
4 ways E cadherin mutation is lost
2. Inactivating mutations (rare)
3. Silencing of gene expression (hypermethylation of promoter)
4. Transcriptional repressors
Name 4 transcriptional repressors that promote epithelial-> mesenchymal transition (EMT)
repress E cadherins
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.
How is CD44 involved in tumor metastasis?
T lymphocytes have CD44 adhesion molecule → migrate to selective sites in lymphoid tissue
overexpressed in cancer
Ultimate effects of METASTASIS leading to mortality
- actual tumor mass -> interferes w/ function
- "paraneoplastic syndrome" symptom is consequence of cancer, but not due to local presence of cancer cells
Ultimat causes of mortality due to cancer
Organ Failure 19.2%
3 leading causes of new cases of cancer for males and females
○ Prostate (26%)
○ Lung (14%)
○ Colon/Rectum (14%)
○ Breast (29%)
○ Lung (13%)
○ Colon/Rectum (8%)
What are the 4 kinds of environmental chemicals that can be carcinogens?
1. Polycyclic aromatic hydrocarbons
2. aromatic amines
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
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
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
• A rapid and inexpensive test of chemicals/carcinogens for mutagens via Salmonella typhimurium that are His (-)
+ = mutagen present
How are cellular triggers of carcinogenesis inherited?
• The cellular triggers of carcinogenesis are stably inherited
○ Tumors are proliferations of clones of a malignant cell
Cancer develops through which two stages?
Initiation : effect of carcinogen
Promotion: non carcinogen enabler
Are bile salts a tumor initiator or promoter? why?
Promoter -> promotes cancer in benign colon polyps
Can tumor production be started with only the initator? Just the promoter? Why?
No. needs initiation then promotion. always