Pathology - Neoplasia 5

Front 1

What is HER2?

Back 1

Human Epidermal growth factor Receptor 2

Front 2

In which cancer is HER2 present 15-20% of the time?

Back 2

Approximately 15-20% of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product.

Front 3

Herceptin

Back 3

Trastuzumab - a humanized monoclonal antibody that acts on the HER2/neu (erbB2) receptor. It acts as an anti-cancer therapy in breast cancer in patients whose tumors over-express HER2.

Front 4

Nm 23

Back 4

Tumor suppressor gene.
Breast carcinoma.

Front 5

KAI-1

Back 5

Tumor suppressor gene.
Prostate cancer.

Front 6

KISS-1

Back 6

Tumor suppressor gene.
Malignant melanoma.

Front 7

Binding of the GF to tyrosine kinase receptors causes (first step):

Back 7

Receptor dimerization and autophosphorylation of tyrosine residues.

Front 8

After dimerization of receptor and autophosphorylation, attachment of adapter proteins couples the receptor to what?

Back 8

Inactive RAS. RAS cycling between active/inactive form is regulated by GAP.

Front 9

Activated RAS interacts with and activates ____.

Back 9

RAF - also known as MAP kinase kinase kinase

Front 10

After activation by RAS, RAF then phosphorylates ____, which then phospohorylates ____.

Back 10

MEK - or, MAP kinase kinase
ERK - or MAP kinase

Front 11

Activated MAP kinase (ERK) phosphorylates what? And this leads to what?

Back 11

Nuclear transcription factors, generating cellular responses.

Front 12

What is RAS? Relationship to cancer?

Back 12

A signal transduction protein, meaning that it communicates signals from outside the cell to the nucleus. Sometimes a DNA mutation turns the signal permanently on, which leads to unlimited cell growth and cancer. RAS is a thus a proto-oncogene.

Front 13

What is a double minute?

Back 13

Small fragments of extra-chromosomal DNA seen in cancer.
They are a manifestation of gene amplification during the development of tumors, which give the cells selective advantages for growth and survival.
They frequently harbor amplified oncogenes and genes involved in drug resistance.

Front 14

In which type of cancer have double minutes most notably been identified? And which gene is amplified in this case?

Back 14

Neuroblastomas
N-MYC gene

Front 15

Burkitt's lymphoma

Back 15

A cancer of the lymphatic system associated with c-myc gene translocation. Certain segment of chromosome is transposed to a different area, which brings various genes in close association that are not usually so close. This abnormal positioning in genes brings about collaborative action, producing chimeric proteins.

Front 16

Philadelphia chromosome translocation is a highly specific test for which cancer?

Back 16

chronic myelogenous leukemia

Front 17

What is microchimerism?

Back 17

The presence of a small number of cells that are genetically distinct from those of the host individual.

Front 18

What is the most common form of microchimerism?

Back 18

The most common form is feto-maternal microchimerism (or fetal chimerism) whereby cells from a fetus pass through into the mother. Fetal cells have been documented to persist in maternal circulation for as long as 38 years.

Front 19

A male cell in the liver of a woman is evidence of what?

Back 19

Fetus-to-mother cell transfer.

Front 20

T/F Mother-->child and fetus-->mother transfer have both been found in several disorders.

Back 20

True. Fetus-->mother has also been found in breast and cervical cancer.

Front 21

Bcl-2

Back 21

Bcl-2 is the prototype for a family of genes that govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro-apoptotic (Bax, BAD, Bak and Bok among others) or anti-apoptotic (including Bcl-2 proper, Bcl-xL, and Bcl-w, among an assortment of others).

Hint 21

think apoptosis

Front 22

Bax

Back 22

Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.
The Bax gene contains a small promoter element that complements a binding domain on the multi-faceted p53 tumor suppressor.

Hint 22

think apoptosis

Front 23

T/F The balance between Bcl-2 and Bax is crucial.

Back 23

True. They can bind themselves or each other, which determines whether the cell lives or dies.

Front 24

T/F Anti-oncogenes are involved in carcinogenesis.

Back 24

True

Front 25

T/F The risk of contracting colon cancer is 1000x higher in a 70-yr-old than in a 20-yr-old.

Back 25

True

Front 26

What is the ACP gene?

Back 26

Well, APC and beta-catenin are components of WNT signaling pathway. In a resting cell, b-catenin and ACP form a complex, which leads to destruction of beta-catenin. When WNT signals, this destruction complex is deactivated, and beta-catenin in cytoplasm increases. It translocates to the nucleus, where it binds TCF, thereby activating genes involved in cell cycle. If APC is mutated or missing, the destruction of beta-catenin cannot occur, so it keeps promoting the cell cycle.

Hint 26

beta-catenin
WNT
TCF

Front 27

T/F Natural selection has the ability to prevent cancer.

Back 27

False. For the most part, anyway. Natural selection may have a limited ability to prevent cancer, but this just tends to delay the disease until later in life. Additionally, evolutionary forces have apparently favored some genes that can contribute to cancer's development or aggressiveness.

Front 28

What does epigenetic mean?

Back 28

Heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence, rather non-genetic factors cause the organism's genes to behave differently

Front 29

What is Zolinza?

Back 29

Histone deacetylase inhibitor with a broad spectrum of epigenetic activities.

Hint 29

The Z is capitalized.

Front 30

What are the eight essential alterations for malignant transformation?

Back 30

1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Defects in DNA repair
5. Limitless replicative potential
6. Sustained angiogenesis
7. Ability to invade and metastasize
8. Evasion of the immune system

Hint 30

They gotta grow. Think about what they need to do that.

Front 31

Turning on telomerase is an example of which acquired capability in metastasis?

Back 31

Limitless replicative potential.

Hint 31

and there ain't stoppin' me noooooow

Front 32

Losing Rb suppressor is an example of which acquired capability?

Back 32

Insensitivity to anti-growth signals.

Hint 32

jolly green giant

Front 33

Producing IGF survival factors is an example of which acquired capability?

Back 33

Evading apoptosis

Hint 33

you ain't bustin' no cap in my ass!

Front 34

Producing the VEGF inducer is an example of which acquired capability?

Back 34

Sustained angiogenesis

Hint 34

oh bloody hell

Front 35

The inactivation of E-cadherin and production of proteases is an example of which acquired capability?

Back 35

Tissue invasion and metastasis

Front 36

Activation of the H-ras oncogene is an example of which acquired capability?

Back 36

Self-sufficiency in growth signals.

Hint 36

you knows i don't need you