Inflammation And Cancer

Question 0

Karin suggests that NF-kB activation in cancer may be the result of either:

Answer 0

1) exposure to proinflammatory stimuli in the tumor microenvironment, or
2) mutational activation of upstream components in IKK-NFkB signaling pathways

Question 1

Oncogenic mutations that endow RelA, c-Rel or other NF-kB were to found rare and mainly limited to

Answer 1

Lymphoid malignancies

Question 2

With respect to tumor progression, NF-kB can:

Answer 2

1) Inhibit apoptosis
2) stimulate cell proliferation
3) Promote a migratory and invasive phenotype

Question 3

The first hint to a link between NF-kB and cancer had emerged with the cloning of RelA and the realization of its close kinship to

Answer 3

The viral oncoprotein v-Rel and its cellular homolog c-Rel

Question 4

Colitis-associated cancer (CAC) appears in patients suffering from

Answer 4

Ulcerative colitis

Question 5

The mouse model for CAC, mice are given

Answer 5

azoxymethane (AOM) that can give use to oncogenic mutations such activation of B catenin

Question 6

B-catenin is the most commonly activated oncogene in

Answer 6

Colon cancer

Question 7

Azoxymethane (AOM) alone produce a small number of large bowel adenomas, which can be strongly augmented through colonic inflammation by repeated administration of the irritant

Answer 7

Dextrane sulfate sodium (DSS)

Question 8

In the mice model using AOM and DSS and conditional disruption of IKKB, make them found that IKKB driven NF-kB activation in intestinal epithelial cells (IEC) is essential for the development of

Answer 8

Colonic adenomas

Question 9

The oncogenic role of NFkB appears to be mediated through its

Answer 9

Antiapoptotic functions, mainly through induction of Bcl-Xl

Question 10

In addition to anti apoptosis function IKKB driven NFkB contribute to CAC by stimulating the proliferation of malignant IEC through

Answer 10

The secretions of growth factors by myeloid cells, most likely within lamina propia macrophages.

Question 11

During CAC development, IL6 is mainly produced by

Answer 11

Lamina propia macrophages and dendritic cells.

Question 12

IL6 have effects both

Answer 12

Proliferative and the survival of IEC

Question 13

Proliferative and the survival effect of IL6 on IEC are mediated through activation of

Answer 13

STAT3 transcription factor

Question 14

Ablation of STAT3 in IEC dramatically compromised IEC survival and greatly reduced CAC growth, which suggest that some of protumorigenic effects of NFkB activation in myeloid cells could by caused by

Answer 14

Paracrine signaling to STAT3 in IEC

Question 15

In addition to IL6 other cytokines contribute to Proliferative and prosurvival effects of myeloids cells NFkB on premalignant IEC:

Answer 15

IL-22, IL-11, IL-12 IL 23 and EGF family members.

Question 16

Hageman 2008 found that inhibition of NFkB activity in tumor associated macrophages (TAM) through the conditional delection of IKKB:

Answer 16

Re-educated these immunosuppressive and protumorigenic cells to acquire a cytotoxic, antitumorigenic phenotype.

Question 17

Another tumor promoting function exerted by IKKB and NFkB in TAM is the maintenance of a tumor suppressive phenotype characterized by

Answer 17

Low levels of inducible NO synthase (iNOS) and IL12 expression, and high levels of IL-10, TNF alpha, and arginase-1

Question 18

Inhibition of NFkB in TAM result in

Answer 18

Up regulation of iNOS and IL-12, leading to elevated production of tumoricidal NO and enhanced activation of NK cell-mediated antitumorigenic immunity, respectively.

Question 19

Hepatocelular carcinoma (HCC) is the most common form of liver cancer. It develops in context of

Answer 19

Chronic viral hepatitis, either HBV or HCV

Question 20

Mices don’t develop HBV or HCV infection. Mice model Mdr2 -/- knockout mouse develops

Answer 20

Hepatoesteatosis caused by defective phospholipid and bile acid export, which leads to low grade hepatitis, and eventually HCC.

Question 21

There are two mechanism by which NFkB exert its tumor promoting function in Mdr2 -/- mice:

Answer 21

1) the mayor mechanism is suppression of apoptosis

2) A role of hepatocyre NFkB in the maintenance of chronic inflammation

Question 22

If procarcinogenic dyethylnitrosamine (DEN) is injected into two weeks old mice, it acts as carcinogenic without inflammation. However, DEN induced HCC requires NFkB activation in

Answer 22

Myeloids cells, in this case Kupffer cells, the resident liver macrophages

Question 23

As found in CAC, DEN induced HCC requires the NFkB dependent production of

Answer 23

IL-6 by Kupffer cells and activation of STAT3 by IL-6 in hepatocytes

Question 24

DEN induced HCC is strongly enhanced by activation in hepatocytes through the targeted delection of

Answer 24

IKKB. It’s also seen upon the conditional delection of hepatocytes IKKy/NEMO (in this case spontaneous develop hepatosteatosis, hepatitis, liver fibrosis and HCC without any injection of carcinogen.

Question 25

Enhanced chemical hepatocarcinogenic was also observed in hepatocyte-specific p38alpha knockout mice. Mice lacking IKKB or p38alpha exhibit greatly enhanced accumulation of

Answer 25

Reactive oxygen species (ROS) in zone 3 after DEN exposure.

Question 26

The major cause of enhanced HCC in IKKy, p38, IKKy knockout mouse is

Answer 26

The compensatory proliferation, driven by circles of injury and regenerations, rather than low grade chronic inflammation.