7. Neoplasia VII- Infection And Cancer Flashcards
Understand how some bacteria are linked to cancer (objective)
Answer later
Become familiar with the potential role of microbiota in cancer (objective)
Answer later
Understand how viruses are linked to cancer (objective)
Answer later
Gloval Infection-Related Cancer Data
92% of infections (H. Pylori, hep b/c, hpv)
2 million cancer cases
Gastric, liver, cervix/uteri
Damage to DNA causes
Chemicals, radiation, viral or bacterial infection
How does infection promote cancer?
Virus can bring oncogenes to cells
Virus can induce inflammation (which provides microenvironment for cancer progression)
How Organisms Induced Uncontrolled Cell Proliferation
- Uncouple normal regulatory mechanisms of cell cycle and division
- Prevent apoptosis
- Avoid host immune system
- Bacteria and Cancer (table)
H. Pylori and gastric cancer
H. Pylori and Gastric MALT lymphoma
Salmonella enterica and gallbladder cancer
H. Pylori reduces risk for oesophageal cancer
H. Pylori
- Spiral shaped
- Gram negative
- long flagella (to get to mucosa layer of stomach)
- can buffer to survive low pH (can be lifetime, low level of chronic inflammation)
H. Pylori and Gastric Cancer
Over 50% of world infected
-cancer of chronic inflammation (immune and cytokine response)
MALT Lymphoma
80% associated with H. Pylori
Only neoplasm known to be eliminated with antibiotics
LPS (lipopolysaccharide) from H pylori and autoantigen from damaged cells lead to expansion of a single B cell clone leading to MALT lymphoma (with more mutations becomes DLBCL, diffused large B cell lymphoma)
Factors promoting Gastric Cancer (third deadliest form of cancer worldwide)
CagA proteins on H. Pylori are linked to cancer
High salt consumption, cigarette smoking
Immune response, reactive oxygen species, increased proliferation, bacterial overgrowth, low acidity also promote gastric cancer.
- Microbiota and Cancer
Healthy vs. Dysbiotic Microbiota in (Gut Microbiome and Colon Cancer Balancing Act)
Healthy microbiota: balanced community, short chain fatty acids, liberation of vitamins and nutrients
Dysbiotic microbiota: adherent/invasive species, loss of protective species, activation of carcinogens)
Gut Microbiome and CRC Development
Bacterial driver-passenger model of CRC:
Driver bacterium initiates bad hyper-proliferation, passenger promotes inflammation (not initially but makes worse later and outcompetes driver bacteria from benign to malignant change)
Ex. Fusobacterium- passenger
Host Microbiota Interactions
Dysbiosis
Inflammation
Barrier Failure
These three are interrelated
- Human Cancer Viruses
Major cause of liver and cervical cancer
-cancer is a side effect of host response or host-viral replication
Fates of Viral Infection
- Lytic infection: increase machinery, destroys cell and leaks viral contents
- Latent infection: lie dormant and can be reactivated
- Abortive Lytic Infection: expression of early viral genes, integrate into cell
Generalization about viral transformation
- RNA viruses activate oncogenes (HIV, HCV)
2. DNA viruses negate tumor suppressors (HBV, HPV)
Strategies
Introduction of oncogenes (HPV) Modified viral oncogenes Chronic inflammatory damage (HBV/HCV) Modulation of apoptosis (HPV) Virus induced immunosuppression (HIV) Permanent activation of signal transduction cascades Modulation of cell cycle (HPV)
Viral Inactivation of p53 Function
HPV E6: triggers degradation of p53
Human Papillomavirus (HPV)
Circular double-stranded DNA
Degrades p53, transmitted by close contact via breaks in epithelium
Infects basal epithelium (stem cells) of genital tract, skin, and upper respiratory tract (cutaneous HPV 1/5/8; genital/mucosal HPV 6/11/16/18)
E6 and E7 maintained and expressed in all stages of infection through malignancy
E6 binds and degrades p53
E7 interacts with pRB to disrupt host cell cycle and transcription
Contribution of HPV-Infections to Cancer
Persistent infections required for cancer progression
Cofactors include tobacco, long term oral contraceptive use.
HPV and Cervical Cancer
Pap smear picks up mild abnormalities to catch early.
Slide 42
Hepatocellular carcinoma- HBV and HCV
60% HBV
25% HCV
HBV
Causes liver cancer
Transmission: perinatal, sexual, blood transfusion, IV drug use
HBV and HCV
Both can be resolved and cleared
HBV- fails to trigger innate immunity
HCV- blocks innate immunity
Both can lead to liver cancer