Neoplasia Flashcards
Epidemiology
Men vs. Women
Men
30% Prostate
Women
31% Breast
Lung and bronchus
Colon and rectum
The risk of cáncer from environmental causes is found to be
65%
The principal targets for genetic damage:
Prooncogens (RAS)
Tumor supressor genes (TP53, Rb)
Genes that regulate apoptosis
Six hallmarks of cancer
- Evading apoptosis
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasión and metástasis
- Limitless replicative potential
- Sustained angiogénesis
Tell me about RAS
Activated RAS recruits RAF-1 and stimulates the MAP-kinase pathway to transmit growth-promoting signals to the nucleus. The mutant RAS protein is permanently activated because of inability to hydrolyze GTP, leading to continous stimulation
Cáncer asociado: Colon, vejiga
Tell me about the Retinablastoma Protein
Regulates G1 -> S
P = inactivated -> S
Activated RB prevents cell replication by binding to E2F family transcription factors
GF > higher D, 4, 6, E, 2 > P of Rb
Tell me about TGF
Growth factor inhibitor
Arrest cell cycle at G1
Tell me about theADENOMATOUS POLYPOSIS COLI-B-CATENIN PATHWAY
In resting cells (not exposed to WNT) B-catenin forms a macromolecular complex containing the APC protein. This complex leads to the destrucción of catenin B.
When cells are stimulated by secreted WNT molecules, the destrucción complex is deactivated, B-catenin degradation does not occur. B-catenin translocates to the nucleus where it binds to TcF, a transcription factor that activates several genes involved in the cell cycle. (Cyclin D1 and MYC)
Tell me about the TP53 gene
Antiproliferative efects
Regulates apoptosis
TP53 + MDM2 -> destrucción of TP53
Stressed cell -> TP53 is released from MDM2 and is activated as a transcription factor.
Activated TP53 induces the transcription of genes that cause cell cycle arrest, and those that cause apoptosis. (BAX)
Arrest by p21. -> prevents the P of RB -> no pass g1-> s
If DNA damage is repaired TP53 upregulates transcription of MDM2
If DNA damage cannot be repaired -> apoptosis
TP53 = guardian of the genome
Hypoxia activates TP53
How does FAs evade apoptosis?
FAS L (CD95L) + FAS (CD95)
->FADD + caspase 8 -> a Caspase 3 -> cell death
caspase 8 upregulates BID
How does tumor cells prevent apoptosis?
- Loss of TP53 -> reduced CD95
- High levels of FLIP (binds death-inducing signals, and prevent a C8)
- Overexpression of BCL2
- Loss of APAF-1 -> blocking the mitochondrial-cytochrome c pathway
The metastatic cascade
- Clonal expansion, growth, diversification, angiogenesis
- Metastatic subclone
- Adhesion to and invasion of basement membrane
- Passage through extracellular matrix
- Intravasation
- Interaction with host lymphoid cells
- Tumor cell embolus
- Adhesion to basement membrane
- Metastatic deposit
- Angiogenesis
- Growth
Invasion of extracellular matrix
- Detachment of tumor cells from each other
- Loosening of intercellular junctions (cadherins) - Attachment of tumor cells to matrix components
- laminin and fibronectin receptors - Degradation of ECM
Type IV collagenase and plasminogen activator - Migration of tumor cells
MAYOR CHEMICAL CARCINOGENS
Direct-acting carcinogens Alkylating agents: anticancer drugs Acylating agents: 1-acetyl-imidazole, Dimethylcarbamyl chloride Procarcinogens that require metabolic activation Aromatic hydrocarbons Aromatic amines, amides, azo dyes Natural plant and microbial products: aflatoxin B1, Griseofulvin, Betel nuts Others - nitrosamine and amides - Vinyl chloride, nickel, chromium - Insectides, fungicides - Polychlorinated bihenyls (PCBs) - Arsenic - Asbestos
VIRAL AND MICROBIAL ONCOGENESIS
RNA ONCOGENIC VIRUSES - Human T-cell leukemia virus type 1 DNA ONCOGENIC VIRUSES - HPV - Epstein-Barr virus (EBV) - Human herpesvirus 8 (HHV-8) - HBV
Human papilloma virus
E7 protein - Binds to the RB and displaces the E2F - Inactivates p21 and p27 - Activate cyclins E and A E6 protein - Inactivates TP53 - Degrades BAX - Activates telomerase Summary: Loss of tumor suppressor genes, activation of cyclins, inhibits apoptosis and combats cellular senescence.
G1->S
CD CDK4, CDK6
S->G2
CA + CDK1 y CDK2
G2 -> M
CB + CDK1
Epstein Barr virus
Herpes virus 4Infectious mononucleosis (glandular fever) Hodkin´s lymphoma Burkitt´s lymphoma Gastric cancer Nasopharyngeal carcinoma Human immunodeficiency virus (HIV) -> hairy leukoplakia, CNS lymphomas Autoimmune diseases: - Dermatomyositis - Systemic lupus erythematosus - Rheumatoid arthritis - Sjogren´s syndrome - Multiple sclerosis
Smooth muscle cell tumor
Leiomyoma
Desmoplasia
producción excesiva de tejido conectivo
Produccion of fibrous or epithelial tissue
Papiloma
un tumor benigno que se forma en las papilas de la piel o de las mucosas
Teratoma
– originate from totipotenitial cells (ovary and testis). Have the capacity to differentiate into any of the cell types found in the adult body
– When all the component parts are well differentiated = benign (mature) teratoma
