Y2B1 Path - Neo

Front 1

Malignant tumors - exception to the rule ending in oma

Back 1

1. Lymphoma
2. Melanoma
3. Mesothelioma
4. seminoma

Front 2

differentiation

Back 2

extent to which the tumor cells resemble the corresponding normal cells
(feature of benign)

Front 3

Anaplasia

Back 3

lack of differentiation
they exhibit:
- pleomorphism
- Abnormal nuclear morphology
- Atypical mitotic figures
- Tumor giant cells
- Loss of Polarity
(feature of malignancy)

Front 4

Carinoma in situ

Back 4

when dysplastic changes involve the full thickness of the epithelium

Front 5

Pathways of Metastatic spread?

Back 5

1. Seeding
2. Lymphatic - most common
(mostly seen in carcinomas)
3. Hematogenous
(mostly in sarcomas)

Front 6

The 3 features that characterize familial cancers include

Back 6

1. Early age at onset of cancer
2. Cancer arising in two or more close relatives
3. Sometimes multiple or bilateral tumors

Front 7

cystitis can cause

Back 7

bladder carcinoma

Front 8

Ulcerative Colitis

Back 8

Colorectal carcinoma

Front 9

Reflux esophagitis cause

Back 9

esophageal carcinoma

Front 10

Gastritis cause

Back 10

gastic carinoma and MALT lymphoma

Front 11

Linchen Sclerosis

Back 11

vulvar carcinoma

Front 12

Point mutation in RET proto-oncogene will cause

Back 12

medullary thyroid carcinoma
(on C cells on the thyroid to release Ca+2 )

Front 13

ERBB1 is overexpressed in up to 80% of

Back 13

squamous cell carcinoma of the lung

Front 14

ERBB2(aka HER-2/NEU)
is amplified in 25% of

Back 14

breast cancers

Front 15

Point mutation of ______ genes is the MC abnormality of proto-oncogenes in human tumors

Back 15

RAS family

Front 16

The over expression of normal Myc is commonly found in

Back 16

- many different carcinomas
- Burkitts lymphoma

Front 17

The RB protein has a key role in regulating the __- __ checkpoint of the cell cycle

Back 17

G1-S

Front 18

when RB protein is in its active HYPOphosphorylated state it bind E2F and

Back 18

BLOCKS! entry into S phase

Front 19

when is RB in its inactive form?

Back 19

when it is in it's inactive HYPERphosphorylated state and it releases E2F which will allow entry into S-phase

Front 20

___ is the most common target for genetic alteration in human tumors

Back 20

P53

Front 21

Li-Fraumeni syndrome

Back 21

inherit 1 mutant P53 allele
develop a wide variety of malignant tumors

Front 22

will chemo or radiation work in a patient with malignant neoplasms which have p53 mutations?

Back 22

NO
- the drugs work by inducing apoptosis and p53 initiates apoptosis in response to DNA damage

Front 23

APC gene's main function is to

Back 23

down-regulate growth-promoting signals

Front 24

APC is a component of what pathway?

Back 24

WNT

Front 25

Loss of APC -->

Back 25

accumulation of B-catenin--> proliferation --> tumor formation

Front 26

TGF-B is a potent

Back 26

inhibitor of proliferation

Front 27

PTEN acts as a tumor suppressor by

Back 27

serving as a brake on the P13K/AKT pathway

(PTEN cleaves PO4 from PIP3)

Front 28

What are the 4 ways apoptosis is avoided by tumors

Back 28

1. Decrease Fas Expression
(renders tumor cells less susceptible to apoptosis by cytotoxic Tcells)
2. Increase FLIP production
(inhibit cleavage of pro-caspase-8)
3. Overexpression of Bcl-2
(seen in B-cell lymphomas due to t(14;18)translocation)
4. P53 mutation --> decrease BAX expression

Front 29

All forms of angiogenesis in tumors result in increase in

Back 29

bFGF (basic fibroblast growth factor)
and
VEGF

Front 30

expression of CD44 favors

Back 30

metastatic spread

Front 31

3 main factors that influence the sites of metastases

Back 31

1. Location of primary tumor
2. Adhesion molecules present on the tumor cells
3. Chemokine receptors expressed on the tumor cell

Front 32

Hereditary Nonpolyposis Colon Cancer Syndrome

Back 32

- DNA mismatch repair defect
- Increase risk of colon cancer
- results in variations in microsatellite length which causes a frame shift

Front 33

Hereditary Nonpolyposis Colon Cancer Syndrome germline mutation in 2 genes:

Back 33

MSH2 &MLH1

Front 34

Familial Breast Cancer causes a mutation in BRACA1 and 2 which is involved in

Back 34

homologous recombination repairs double-strand DNA breaks
and
repair of intrastrand and interstrand DNA cross-links

- inactivating mutation cause dicentric chromosomes and aneuploidy

Front 35

The Warburg Effect

Back 35

- Even with lots of O2 shift from oxidative phosphorlyation to aerobic glycolysis
Increase proliferation -->increase anabolic activity and increase glycolysis
- allows carbons to be used in anabolic pathways

*the principal metabolic factor limiting cell division is the number of available carbons...NOT ATP

Front 36

what two types of chromosomal rearrangements can activate proto-oncogenes?

Back 36

1. Translocation
2. Inversion

Front 37

Burkitt Lymohoma

Back 37

t(8;14)
MYC gene being contiguous to regulatory elements of the IgH gene--> MYC overexpression

Front 38

Follicular Lymphoma

Back 38

(aka- B-cell lymphoma)
t(14;18)
BCL2 gene being contiguous to regulatory elements of the IgH gene --> BCL2 overexpression

Front 39

Chronic Myeloid Leukemia

Back 39

t(9;22) "philadelphia chromosome"
- translocation resulting in a hybrid/fusion gene
-ABL-BCR fusion gene--> encodes a constitutively active tyrosine kinase --> cells receiving an unregulated growth signal

Front 40

chromosomal deletions are more common in what type of tumors

Back 40

chromosomal deletions
(loss of tumor suppressor genes)

Front 41

gene amplification of a _____ --> cancer

Back 41

proto-oncogene
(results in worse prognosis)

Front 42

examples of genes silenced by hypermethylation

Back 42

*VHL (renal cell carcinoma)
p16/INK4a
BRACA1(breast)
MLH1 (colorectal)

Front 43

EZH2 has been shown to be overexpressed in

Back 43

breast and prostate carcinomas
(due to histone modifications)

Front 44

decrease of certain miRNAs occur in some leukemias and lymphomas which leads to

Back 44

increase BCL2 expression

Front 45

decrease of certain miRNAs occur in some lung cancers which leads to

Back 45

increase RAS expression

Front 46

in some brain and breast tumors there is 5-100x greater expression of certain miRNAs -->

Back 46

decrease in tumor suppressors

Front 47

Nitrosamine is associated with

Back 47

stomach cancer

Front 48

Vinyl chloride is associated with

Back 48

angiosarcoma of the liver

Front 49

Aflatoxin B1 is associated with

Back 49

Liver Cancer

Front 50

Most known carcinogens are metabolized by

Back 50

cytochrome P-450 encodes the
- CYP1A1 gene
(encodes for enzyme involved in the metabolism of PAHs)

Front 51

Increase activation of PAHs -->

Back 51

increase risk of lung cancer in smokers

Front 52

what type of UV light is believed to be principally responsible for the causation of skin cancer

Back 52

UVB

Front 53

Most frequent malignancies induced by ionizing radiation in descending order of frequency

Back 53

1. Leukemia
2. Thyroid Carcinoma
3. Lung, Breast and salivary gland carcinomas

Front 54

Human T-cell Leukemia Virus Type 1 (HTLV-1)

Back 54

-retrovirus implicated in causing cancer
-infects CD4+ Tcells
- TAX gene ( which increase proliferation, inactivates p16/INK4a and enhances cyclinD activation, interferes with DNA repair and upreg anti-apoptotic genes)

Front 55

Low risk HPV

Back 55

-type 6 and 11
-cause genital warts
-doesnt integrate HPV genome into host genome

Front 56

High risk HPV

Back 56

- type 16 and 18
- cause carcinoma of the cervix and vulva
- HPV genome is integrated into the host genome

Front 57

Integration of HPV genome into the host genome--> loss of HPV E2 -->

Back 57

overexpression of HPV E6 and E7 (oncoproteins)

Front 58

EBV infects _ cells

Back 58

B cells(and some epithelial)

Front 59

What are 3 neoplasms that are caused by EBV virus

Back 59

1. Burkitt lymphoma
2. B-cell lymphomas in immunosuppressed ppl
3. Nasopharyngeal carcinoma

Front 60

two gene products that are largely responsible for the transforming effects of EBV

Back 60

1. LMP-1
- transmembrane protein which functions as a constitutively active CD40 receptor(on surface of B-cells and macrophages)
2. EBNA2
- acts as a transcription factor, upreg cyclin D
(oncoproteins)

Front 61

B-cell lymphomas in immunosupressed patients

Back 61

- Express LMP-1 and EBNA2
- may regress if patients immune status improves

Front 62

Nasopharyngeal Carcinoma

Back 62

- Express LMP-1 and EBNA2
- 100% of these carcinomas contain EBV DNA

Front 63

Does Burkitt Lymphoma express LMP-1 and EBNA1?

Back 63

NO!
Endemic cases are associated with EBV but not sporadic cases
- EBV is not directly oncogenic here but acts as a B-cell mitogen which leads to mutations and lymphomas

Front 64

How does HepB and C virus cause hepatocellular carcinomas?

Back 64

NOT! by encoding any definite oncoproteins

they cause hepatocellular injury --> chronic inflammation and compensatory proliferation of hepatocytes--> mutations-->cancer

Front 65

H. Pylori infection is implicated in the genesis of

Back 65

Gastric adenocarcinoma
Gastric lymphoma (MALT lymphoma or MALToma)

Front 66

H. Pylori strains that have the ___ gene are associated with increase risk of adenocarcinoma

Back 66

CagA gene
(continuously activates a growth factor signal transduction pathway--> proliferation)

Front 67

Proposed mechanism of of MALT lymphoma

Back 67

H. Pylori infection --> reactive Tcells--> stim. polyclonal B-Cell proliferation
Mutations--> monoclonal proliferation of B-cells (MALToma)
-at this stage eradication of H. Pylori by antibiotic Rx is often curative

- additional mutations t(11;18)--> constitutive activation of NF-kB--> autonomous proliferation and capacity for distant spread

Front 68

what is the major immune defense mechanism against tumors?

Back 68

CD8+

Mutated proteins synthesized in the cytoplasm can enter the class I MHC antigen-processing pathway --> activation of CD8+ Tcells --> apoptosis of tumor cells

Front 69

What is the important role of NK cells?

Back 69

they eliminate tumors that do NOT express class I MHC molecules

Front 70

4 ways tumors evade immune surveillance

Back 70

1. Selective outgrowth of antigen-negative variants
2. Loss or reduce expression of MHC molecules
(have to express class I MHC to be recognized by CD8+ Tcells)
3. Lack of co-stimulation
(therefore T cells aren't activated)
4. Immunosupression
5. Apoptosis of cytotoxic T cells
(some neoplasms express FasL)

Front 71

How does cachexia differ from starvation?

Back 71

weight loss from equally from loss of fat AND lean muscle (@the same time)
- basal metabolic rate is increased (in starvation it decreases)

Front 72

Flow cytometry

Back 72

- measure the DNA content of individual cells
- detect the presence of specific surface antigens on individual tumor cells
- commonly used to assist in diagnosis and classification of lymphomas and leukemias