Neoplasia VII: Infection and Cancer

Question 1

Cancer is a multi step process consisting of:

Answer 1

initiation–>selection–>angiogenesis–>invasion–>progression–>metastasis

• Bacterial infection can be an initiating event

Question 2

How does infection promote cancer?

Answer 2

1. uncouple normal regulatory mechanisms
2. prevent apoptosis
3. avoids the host immune response

Question 3

H. pylori and gastric cancer

Answer 3

• 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

Question 4

MALT Lymphoma

Answer 4

• only cancer that can be cured with antibiotics
• most linked with H. pylori

Question 5

MALT Lymphoma mech

Answer 5

• H. pylori lipopolysaccharides (mixed with autoantigens) activate immune cells (B cells) continually
• expansion of B cell clone + somatic mutations = MALT lymphoma–>DLBCL

Question 7

Microbiota

Answer 7

the ecological community of commensal, symbiotic, and pathogenic microorganisms that share body’s space

Question 8

Gut Microbiome and Colon Cancer

Answer 8

*

Question 9

Microbiota and CRC

Answer 9

• 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

Question 10

Host microbia interactions

Answer 10

Dysbiosis<—>Inflammation<—>Barrier Failure

Question 11

Human Cancer Viruses

Question 12

Fates of Virus Infection

Answer 12

• Lytic infection
• latent infection (herpes)
• integration into the cell and cause transformation

Question 13

Viral transformation

Answer 13

Rna viruses activate oncogenes

DNA viruses negate tumor suppressors

Question 14

Oncogenes

Answer 14

arise from mutant proto oncogenes

stimulate unregulated proliferation

can be created by a single mutation

Question 15

Tumor suppressor genes

Answer 15

slow cell division

repair DNA mistakes

stimulate apoptosis

need two active mutations to eliminate gene

Question 16

Strategies of viruses

Answer 16

• 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)

Question 17

Inactivation of p53

Answer 17

• 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

Question 18

HPV

Answer 18

• 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

Question 19

HPV infection regression/progression

Answer 19

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

Question 20

Hepatocellular carcinoma

Answer 20

HBV, HCV

HBV,HCV infection–>blocks innate immunity–> Hepatitis (or asympomatic)–> fibrosis–>chirrosis–>changes in proliferation, genomic instability