Neoplasia 2

Question 1

What are the two categories of carcinogenic chemicals/agents?

Answer 1

1. Direct acting

2. Indirect acting

Question 2

Name two examples of direct acting agents.

Answer 2

1. Alkylating agents

2. Acylating agents

Question 3

What characterizes an indirect acting carcinogen? What is the consequence of this?

Answer 3

They require metabolic conversion to an ultimate carcinogen. Consequently, polymorphisms of enzymes like P450 can influence carcinogenesis.

Question 4

What are the two steps of clinical carcinogenesis?

Answer 4

Initiation and promotion.

Question 5

Is the damage incurred after initiation by a carcinogen reversible?

Answer 5

Nope

Question 6

Can carcinogenesis occur if exposure to a promoting carcinogen happens before exposure to an initiating carcinogen?

Answer 6

Nope

Question 7

Are the effects of chemical promoters reversible? Do they act directly on DNA? What do they do?

Answer 7

Yeah. They do not act directly on DNA. They promote cell proliferation.

Question 8

All initiating carcinogens are reacting _________ that react with ________ sites in the cell.

Answer 8

electrophiles that react with nucleophilic cellular sites

Question 9

Which particular UV ray type is most dangerous?

Answer 9

UV-B

Question 10

What causes melanomas? What causes determines risk for non-melanomas?

Answer 10

Melanomas are caused by intense intermittent exposure. Non-melanomas are a result of total cumulative exposure to UV radiation.

Question 11

What does UV radiation do to DNA?

Answer 11

Forms pyrimidine dimers (between adjacent cytosine nucleotides)

Question 12

By which two mechanisms can ionizing radiation cause mutations?

Answer 12

Directly on DNA or indirectly by hitting water or oxygen in the cell, generating free radicals, that can then damage DNA

Question 13

Name three oncogenic DNA viruses.

Answer 13

1. HPV
2. EBV
3. Hep B

Question 14

Name an oncogenic RNA virus.

Answer 14

Human T cell lymphotrophic virus

Question 15

Name an oncogenic bacteria. What does it cause?

Answer 15

H. pylori causes gastric adenocarcinoma and MALT lymphoma

Question 16

Which HPV types are considered high risk for cervical cancer and what genes in particular must integrate into the host chromosome?

Answer 16

Types 16 and 18 are high risk. E6 and E7 genes must integrate. E6 degrades p53 and E7 sequesters Rb.

Question 17

What is the only human retrovirus implicated in carcinogenesis?

Answer 17

Human T cell lymphotrophic virus type 1.

Question 18

What type of cancer does Human T cell lymphotrophic virus cause? In what parts of the world is it most common?

Answer 18

T cell leukemia-lymphoma. Most common in Japan and the Carribean basin.

Question 19

What is the mechanism of carcinogenesis of Human T cell lymphotrophic virus?

Answer 19

It encodes a viral transcription activation protein called TAX which turns on genes for cytokines and their receptors in T cells, causing an autocrine and paracrine signaling loop that results in cell proliferation. Further mutations can result in monoclonal T cell development.

Question 20

What is the first bacteria classified as a carcinogen? What is the pathogenesis to gastric cancer?

Answer 20

Heliobacter pylori. Chronic inflammation/gastritis –> gastric atrophy –> metaplasia –> dysplasia –> cancer

Question 21

What is the cellular origin of gastric lymphomas? Hint: they are found in MALT

Answer 21

B-cells

Question 22

What is the pathogenesis of MALT marginal zone associated B cell lymphoma?

Answer 22

T cells expand to fight H. pylori, causing polyclonal B cell proliferation –> B cell mutations –> monoclonal B cell tumor

Question 23

What chemicals are thought to play a large role in cancer cachexia?

Answer 23

Cytokines produced by the tumor and host in response to the tumor such as TNF from macrophages.

Question 24

What is a paraneoplastic syndrome? How common is it?

Answer 24

When tumors randomly synthesize compounds/hormones unexpectedly. Found in 10-15% of cancer patients.

Question 25

Name two endocrinopathies with ectopic hormone production and explain what they are.

Answer 25

1. Cushing syndrome - small cell lung carcinoma, pancreatic carcinoma, or neural tumor that secretes ACTH or an ACTH-like chemical. 2. Hypercalcemia caused by PTH-like secretions from squamous cell carcinoma of the lung, breast carcinoma, renal carcinoma, ovarian carcinoma, or T cell leukemia/lymphoma.

Question 26

How can cancer cause thombotic endocarditis? What is thrombotic endocarditis?

Answer 26

It is when blood clots mess up heart valves. Mechanism unknown but some advanced cancers can cause hypercoagulability and cause the endocarditis.

Question 27

Grading reflects ________ _________, whereas staging reflects ________ ____ _______.

Answer 27

grading reflects cellular characteristics whereas staging reflects the extent of spread

Question 28

Describe the system of staging.

Answer 28

``` T = site and extent of primary tumor N = regional lymph node involvement M = distant metastasis ```

Question 29

What four methods can be employed to diagnose cancer?

Answer 29

1. Histopathology 2. Flow cytometry 3. Molecular diagnostics 4. Tumor markers

Question 30

Which HPV types cause benign squamous papillomas? Which ones have a low malignant potential?

Answer 30

Benign squamous papillomas: 1, 2, 4, 7 Low malignant potential: 6 and 11

Question 31

Does Human T cell lymphotropic virus carry an oncogene?

Answer 31

No, the TAX protein is a viral protein and is not considered an oncogene because it doesn't integrate into the host genome to produce malignancy.

Question 32

Which infectious carcinogenic organism infects 50% of the world population while only 3% have cancer as a result?

Answer 32

H. pylori

Question 33

PSA testing is an example of which cancer diagnosis method?

Answer 33

Tumor markers