Infection and Cancer

Question 1

Cancer is a milti step process

Answer 1

Initiation (often viral or bacterial agent)

Selection

Angiogenesis

Invasion

Progression

Metastasis

Question 2

How does infection promote cancer?

Answer 2

Carcinigenic mircoorganisms put oncoproteins in cells, cells become infected. Infected cells lead to immune response. Cytokine production promotes survivial and proliferation of cancer

Question 3

How organisms induce uncontrolled cell proliferation

Answer 3

1) organism must uncouple normal regulatory mechanisms controlling progress of cell cycle and cell division
2) The organisms must prevent the host cells from undergoing apoptosis, a normal cellular response to viral indiced injury
3) In vivo proliferating cell (usually with surface Ag expression) must avoid the host immune system

Question 4

H pylori and gastric cancer

Answer 4

About half of world pop infected

10% develop ulcers

1% infected develop gastric carcinoma

cancer of chronic inflammation

Question 5

MALT lymphoma

Answer 5

MALT- mucosa-associated lymphoid tissue

MALTomas: extranodal manifestations of marginal-zone lumphomas

~80% associated with H pylori

ONLY NEOPLASM KNOWN TO BE ELIMINATED WITH ANTIBIOTICS

Question 6

Only neoplasm known to be eliminated by abx

Answer 6

MALT lymphoma

Question 7

MALT Lymphoma hypotheatical model

Answer 7

LPS from H pylori (lipopolysaccharide layer) activates B cells which lead to exmansion of single B cell clone, somatic mutaion happens, and then MALT lymphoma

Question 8

Gastric carcinoma

Answer 8

Caused by H pylori 80% of the time

Second deadliest cancer worldwide

Question 9

Answer 9

Factors promoting gastric cancer

Note CagA on H pylori. Can promote epithelial cell proliferation. Linked with cancer

Question 10

Steps in normal gastric mucosa to cancer

Answer 10

Normal gastric muscosa

superficial gastritis

chronic inflammation

atrophic gastritis

intestinal metaplasia

dysplasia

carcinoma

Question 11

Microbiota

Answer 11

the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space

Question 12

microbiota places

Answer 12

skin, gut, vaginal tact

Commensals

most are not patjogenic

vaginal tract

enzymes secreted by commensal bacteria keeps low pH to inhinit growth of pathogens

Question 13

Microbiota and colorectal cancer (CRC)

Answer 13

Dysbiosis happens in CRC

In the dysbiotic microbiota

Adherent/invasive species

loss of protective species

activation of carcinogens

In the host

Loss of barrier function

Inflammation and immune dysfunction

DNA damage and genetic changes

Loss of cell cycle control

Question 14

Colorectal cancer

Answer 14

Bacterial driver model.

Driver bacteria hanging out in the intestinal lumen. Passenger bacteria comes along. Overgrowth of passenger bacteria increases inflammation. Overgroth of passenger bacteria

Question 15

CRC assocaited microbiome

Answer 15

Increased:

Fusobacterium

Decreased:

lostridium

Roseburia

Ruminococcaceae

Question 16

What can we do with the microbiota information

Answer 16

Which are the best pathobionts assocatioed with the development of adenoma?

Is the microbiota a factor in the progression of adenoma to cancer?

Can we stratify pts with CRC and optimize their tx based on their microbiota profiles>

Can we use probiotics to improve the pts quality of like in the later stages of CRC?

Question 17

Answer 17

microbiota and CRC

Question 18

Answer 18

Host-microbiota interactions

Question 19

Human cancer viruses

Answer 19

Major cause of liver and cervical cancer

Question 20

Viruses that cause cancer in humans

Answer 20

Hep C

Hep B

HPV

Question 21

RNA viruses…

Answer 21

activate oncogenes

Question 22

DNA viruses…

Answer 22

negate tumor suppressors

Question 23

Cancer is primarily caused by…

Answer 23

mutatuons in growth and growth-inhibiting factor genes, and pathways that inhibit the normal sequence of events associated with apoptosis

Question 24

Oncogenes

Answer 24

arise from mutant proto-oncogenes

Oncogenes are more active than normal or active at inappropriate times and stimulate unregulated cell proliferation

Question 25

Tumor suppressor genes

Answer 25

are normal genes that slow down cell division, repair DNA mistakes, or tells cells whento die (a process known as apoptosis or programmed cell death

Question 26

How do oncogenes work

Answer 26

Single mutation even

Question 27

How do tumor suppressor genes work

Answer 27

loss of function mutations

two hit situation

loss of one genes has no effect

eliminaiton of tumor suppressor leaging to cell prolifetaion

Question 28

Viral inactivation of P53 function

Answer 28

SV40 large T anitgen stabilizes P53 in inactive state

HPV E6 triggers degredation of P53

Adenovirus E1A blocks transcriptional activation function of P53

Question 29

Human Papillomavirus (HPV)

Answer 29

Infects basal epithelium of genital tract, skin, and UR tract

Transmitted by break in epithelium

HPV genome may integrate randomly into host genome

Both E6 and E7 are maintained and expressed in all stages of malignancy

E6 binds and degrades tumor suppressor p53

E7 interacts with tumor suppressor pRB to disrupt regulation of host cell cycle and transcription thus increases genomic instability

Question 30

What is expressed in all stages of infection through malignancy in HPV

Answer 30

E6 and E7

Question 31

E6

Answer 31

binds and degrades tumor suppressor P53

Question 32

E7

Answer 32

interacts with tumor suppressor pRB to disrupt regulation of host cell cycle and transcription thus increases genomic instability