Neoplasia VII: Infection and Cancer Flashcards
(20 cards)
Cancer is a multi step process consisting of:
initiation–>selection–>angiogenesis–>invasion–>progression–>metastasis
- Bacterial infection can be an initiating event
How does infection promote cancer?
- uncouple normal regulatory mechanisms
- prevent apoptosis
- avoids the host immune response
H. pylori and gastric cancer
- uses flagella to make its way into stomach through mucosa layer where it can attach to lumen
- has adapted to survive low pH in lumen
- can have infection/inflammation for life and therefore increased cancer risk
MALT Lymphoma
- only cancer that can be cured with antibiotics
- most linked with H. pylori
MALT Lymphoma mech
- H. pylori lipopolysaccharides (mixed with autoantigens) activate immune cells (B cells) continually
- expansion of B cell clone + somatic mutations = MALT lymphoma–>DLBCL
Microbiota
the ecological community of commensal, symbiotic, and pathogenic microorganisms that share body’s space
Gut Microbiome and Colon Cancer
*
Microbiota and CRC
- dysbiosis–>bad bacteria invades epithelial layer, activate carcinogens, promote chronic inflammation, immune dysfunction, loss of cell cycle
- Driver bacteria (increased proliferation)–>overgrowth of passage bacteria (promote inflammation, overgrowth of bad bacteria)–>polyp forms–>carcinoma develops
- if persistently breaching barrier:
- alters balance of host cell proliferation and death
- alter immune system function
- alter host and microbial metabolism
Host microbia interactions
Dysbiosis<—>Inflammation<—>Barrier Failure
Human Cancer Viruses
Fates of Virus Infection
- Lytic infection
- latent infection (herpes)
- integration into the cell and cause transformation
Viral transformation
Rna viruses activate oncogenes
DNA viruses negate tumor suppressors
Oncogenes
arise from mutant proto oncogenes
stimulate unregulated proliferation
can be created by a single mutation
Tumor suppressor genes
slow cell division
repair DNA mistakes
stimulate apoptosis
need two active mutations to eliminate gene
Strategies of viruses
- introduction of oncogenes into host cell (HPV)
- modify viral oncogenes after integration into host cell (merkel)
- Chronic inflammatory damage (HBV, HCV)
- Modulation of apoptosis
- Immunse system avoidance/suppression (HIV)
- permanent activation of cell signaling cascades
- modulation of cell cycle (HPV)
Inactivation of p53
- SV40 T antigen stabilizes p53 in inactive state
- HPV E6 triggers degradation of p53
- adenovirus E1A blocks transcriptional activation function of p53
- H. pylori probably inactivates it too
HPV
- circular dsDNA
- infects basal epithelium (stem cells) effects genital, upper respiratory tract, skin
- integrates randomly into host genome
- E6, E7 maintained and expressed in all stages of infection through malignancy
- E6 binds and degrades p53
- E7 interacts with pRB to disrupt regulation of cell cycle transcription and increase genomic instability
- Cervix, anus, vagina, penis, vulva, oropharynx, oral cavity
HPV infection regression/progression
initial infection can lead to mild abnormalities, pap smears can pick up cervical cancer. if not caught can progress to cancer, not everyone will get cancer tho because of immune respnse
if cancer, precancerous lesion–>then invasion and development of cancer
Hepatocellular carcinoma
HBV, HCV
HBV,HCV infection–>blocks innate immunity–> Hepatitis (or asympomatic)–> fibrosis–>chirrosis–>changes in proliferation, genomic instability
