Test 2 Guide Questions

Front 1

1. No matter the carcinogen, what area of the cell is altered and therefore will triggerthe changes necessary for cells to become cancerous?

Back 1

1. The DNA (i.e., genes)

Front 2

2. What is lag time? Why does lag time suggest that cancer is a multi-step processinvolving a series of genetic mutations?

Back 2

2.

-The period between exposure and onset of cancer;

-A prolonged period of time is generally required for the multi-step processthat initiates a series of genetic mutations to cause cancer.

Front 3

3. What is the purpose of “checkpoints” within the cell cycle?

Back 3

3. Checkpoints prevent cell cycle progression at specific points, allowingidentification of any DNA damage and repair of DNA damage. The cell cannotproceed to the next phase until checkpoint requirements have been met.

Front 4

4. Where are the two main “checkpoints” in the cell cycle?

Back 4

4. G1/S checkpoint and G2/M checkpoint.

Front 5

5. Why is the molecule p53 called “the guardian of the genome”? Include“checkpoints” in your answer.

Back 5

5. It plays an important role in triggering the control mechanisms (i.e. determine ifcell cycle can proceed) at both G1/S and G2/M checkpoints.

Front 6

6. What two things can p53 do if there is DNA damage? Why is p53 called a“tumor suppressor gene”?

Back 6

6.

-p53 either 1) allows time for DNA damage to be repaired and thus allows the cellto continue through the cell cycle; or 2) if the DNA is damaged beyond repair,p53 will activate apoptosis;

-p53 plays a crucial role in the prevention of tumor development

Front 7

7. What 4 types of proteins (specific names) are involved in the cell’s typicalgrowth-control pathway?

Back 7

7. Growth factors, growth factor receptors, signaling enzymes, transcriptions factors

Front 8

8. Using Ras, explain oncogenes in relationship to proto-oncogenes

Back 8

8. Oncogenes arise from the mutation of proto-oncogenes (i.e., genes that areinvolved in “controlled” growth) and code for an altered version (or excessivequantities) of these growth-control proteins, thereby disrupting the cell’s growthsignal. Ras (a family of protein kinases) is a central player in signal transductionand is mutated to an oncogene in about a third of all human cancers.

Front 9

9. Genetically, are oncogenes dominant or recessive over proto-oncogenes?

Back 9

9. Oncogenes are usually dominant over the proto-oncogene.

Front 10

10. Are tumor suppressor genes dominant or recessive? What does this mean interms of cancer development?

Back 10

10. The tumor suppressor gene is dominant (S) and a defective copy is recessive (s).Therefore, both tumor suppressor genes must be lost from the cell or inactivated bymutations to inactivate the tumor suppressing activity of the cell.

Front 11

11. What two deadly characteristics do malignant cancers have that benign tumors donot?

Back 11

11. Malignant cancer cells invade adjacent tissue, enter blood vessels or lymphvessels, and travel to other areas of the body (metastasize). A benign tumor is atumor that lacks invasive properties and the ability to metastasize.

Front 12

12. Give an example of a benign tumor that is harmless and one that causes noncancerrelated complications.

Back 12

12. Warts are benign tumors that are not dangerous (i.e., in terms of cancer) but areremoved because they either are unsightly or cause discomfort. Fibroids arebenign tumors that cause complications in that they are a common cause of heavy,prolonged menstrual bleeding and pelvic pain and pressure.

Front 13

13. Distinguish between hyperplasia and dysplasia in terms of cell division, structure,and arrangement. How is cervical dysplasia identified?

Back 13

13.

-Hyperplasia refers to tissue growth based on an excessive rate of cell division,leading to a larger than usual number of cells. Nonetheless, cell structure and theorderly arrangement of cells within the tissue remain normall;

-Dysplasia is excessive cell proliferation characterized by loss of normal tissuearrangements and cell structure;

-Cervical dysplasia can be identified with a pap smear.

Front 14

14. Define angiogenesis and how does it allow cancer in situ to become invasive?What are four factors that could be released by cancer cells that would promoteangiogenesis?

Back 14

14.

-Angiogenesis is the growth of new blood vessels that supplies needed nutrients toan in situ tumor to rapidly expand and become invasive;

-Vascular endothelial growth factor (VEGF), angiopoietin (Ang), platelet derivedgrowth factor (PDGF), and fibroblast growth factor (FGF).

Front 15

15. What are matrix metalloproteinases and how do they allow tumor cells to invade?

Back 15

15. Matrix metalloproteinase are enzymes produced by the in situ cancer. Theseenzymes or proteases dissolve proteins and degrade the “glue” of the basal laminaallowing cancer cells to invade the surrounding tissue.

Front 16

16. What two factors reduce the chance of cancer cells, once entering the blood, tometastasized to other parts of the body?

Back 16

16.

-Tumor cells will be mechanically destroyed by the stress of bouncing againstblood vessel walls under high hydrostatic pressure;

-Will encounter NK cells or CD8 T cells and be destroyed through theperforin/granzyme system.

Front 17

17. How do cancer cells “select” the tissue to which it metastasizes? What site dometastatic prostate cancer commonly select?

Back 17

17.

-Specific interactions between molecules on the cancer-cell surface (selectinligands and integrin proteins) and molecules on the surface of the endothelial cells(selectins and integrin ligands) that line the blood vessels in the new host tissue;

-Prostate cancer has a high affinity to bone tissue.

Front 18

18. What is meant by a 5-year survival rate?

Back 18

18. The 5-year survival rate refers to the percentage of patients who live at least 5years after being diagnosed with cancer.

Front 19

19. Survival rates for breast cancer show a variation amongst the two economicclasses. What are they and what is the main reason for this fact?

Back 19

19. Survival rates are also affected by accessibility to medical support (e.g., medicalinsurance) and therefore economic status. The more affluent have a better chancein identifying cancer in the early states (Stage I and II) because they can affordscreening (Pap smear, mammogram). Cancer identified in the early stages has ahigher survival rate. The less affluent cannot afford the cost of screening andwill, therefore, seek help only when the cancer becomes symptomatic, which is inthe latter stages. Initiating cancer treatment in the later stages has a reducedsurvival rate.

Front 20

Match the following stages of breast cancer to the description/characteristics in questions20-33.

a. Stage 0

b. State I

c. Stage II

d. Stage III

e. Stage IV

20. Five year survival rate is 10%.

Back 20

E. Stage IV

Front 21

21. Breast tumor measures 2-5 cm and cancer has spread to two or more axillarylymph nodes.

Back 21

C. Stage II

Front 22

22. Ductal-carcinoma in situ.

Back 22

A. Stage 0

Front 23

23. The most advance form of breast cancer

Back 23

E. Stage IV

Front 24

24. Tumor is larger than 5 cm and has spread to axillary lymph nodes that areconnected as well to surrounding breast tissue.

Back 24

D. Stage III

Front 25

25. Inflammatory breast cancer.

Back 25

D. Stage III

Front 26

26. Breast tumor is more than 5 cm, but the cancer has not spread to the axillarylymph nodes

Back 26

C. Stage II

Front 27

27. Tumor is less than 2 cm in size, and has not spread to the lymph nodes nor outsidethe breast.

Back 27

B. Stage I

Front 28

28. Tumor is smaller than 5 cm but has spread not only to axillary lymph nodes butalso lymph nodes above the collar bone.

Back 28

D. Stage III

Front 29

29. Five year survival rate is 86% to 91%

Back 29

C. Stage II

Front 30

30. Known as locally or regionally advanced breast cancer.

Back 30

D. Stage III

Front 31

31. Cancer cells have spread to distance parts of the body (e.g., bones, lungs, liver)

Back 31

E. Stage IV

Front 32

32. The estimated five-year survival rate is 100%.

Back 32

B. Stage I

Front 33

33. Lobular-carcinoma in situ.

Back 33

A. Stage 0

Front 34

34. What is Prostate-specific antigen (PSA)? What elements are combined todetermine total serum (blood) PSA?

Back 34

34.

-Prostate specific antigen (PSA) is a glycoprotein produced in the ducts of theprostate;

-Total PSA = free or unbound PSA (f-PSA) + bound (ACT or aMG) prostate.

Front 35

35. What is the most accurate predictor of the risk of prostate cancer across the entirerange of total PSA values?

Back 35

35. Low free PSA likely signals prostate cancer. Most men with prostate cancer havea free f-PSA/Total PSA ratio below 15%

Front 36

36. What is this ratio in most men with prostate cancer?

Back 36

36. If f-PSA/Total PSA ratio is below 7%, prostate cancer is most likely.

Front 37

37. A PSA test is used in combination with what to screen both asymptomatic andsymptomatic men for prostate cancer?

Back 37

37. The total PSA test and digital rectal exam (DRE).

Front 38

38. What characteristics of the prostate during digital rectal exam (DRE) wouldindicate abnormalities?

Back 38

38. Irregularities, which include lumps, jagged areas, coarse spots, enlargements, orfirm areas.

Front 39

39. If the PSA and DRE are found to be abnormal, what might be the follow upprocedures?

Back 39

39. Prostate biopsy and imaging tests, such as an ultrasound

Front 40

Using the TMN System, match the following stages of prostate cancer to thedescription/characteristics in questions 40-50.

a. T1

b. T2a or T2b

c. T3a or T3b

d. T4

e. N0

f. N1

g. Nx

h. M0

i. M1

j. Mx

40. Metastasis has not been assessed.

Back 40

J. Mx

Front 41

41. Tumor extends outside of the prostate, but has not spread to the seminal vesicles.

Back 41

C. T3a or T3b

Front 42

42. The cancer has not spread to the lymph nodes

Back 42

E. N0

Front 43

43. The cancer has spread to lymph nodes in the pelvis.

Back 43

D. T4, F. N1

Front 44

44. The cancer has spread to the bones and/or a distant part of the body

Back 44

D. T4, I. M1

Front 45

45. Tumor involves both the left and right sides of the prostate.

Back 45

B. T2a or T2b

Front 46

46. Tumor is confined to only the right or left side of the prostate

Back 46

B. T2a or T2b

Front 47

47. Tumor is confined to the prostate and is not detectable by digital rectal exam(DRE) or ultrasound.

Back 47

A. T1

Front 48

48. Tumor extends outside of the prostate, and has spread to the seminal vesicles.

Back 48

C. T3a or T3b

Front 49

49. The test to detect lymph nodes spread have not been assessed.

Back 49

G. Nx

Front 50

50. The cancer has not spread to other parts of the body.

Back 50

H. M0

Front 51

51. What is the strongest predictive factor for development of prostate cancer?

Back 51

51. Age, in that it is rarely found in men under 50 years of age

Front 52

52. What types of tumors can neither surgery or radiation therapy alone treat?

Back 52

52. Those that have matastasized

Front 53

53. The extent or amount of breast tissue that is removed during breast surgery isdependent on what characteristic of the tumor?

Back 53

53. The stage of the tumor

Front 54

For questions 54-60, match the breast surgical procedure with the description:

a. Lumpectomy and quadrantectomy

b. MammoSite 5-day targeted radiation therapy

c. Simple Mastectomy or Total Mastectomy

d. Modified Radical Mastectomy

e. Radical Mastectomy

54. It attempts to insure that all the tumors involving lymph nodes, muscles, fat andconnective tissue are removed.

Back 54

E. Radical Mastectomy

Front 55

55. This simple mastectomy combined with an additional procedure to remove alllymph nodes from under the arm and like the simple mastectomy it spares thepectoralis muscles

Back 55

D. Modified Radical Mastectomy

Front 56

56. Shortens radiation treatment length following lumpectomy.

Back 56

B. MammoSite 5-day targeted radiation therapy

Front 57

57. These combined with axillary-node dissection are the treatment of choice forearly-stage breast cancers (i.e.., Stage I).

Back 57

A. Lumpectomy and quadrantectomy

Front 58

58. Are considered breast conserving surgery and/or partial mastectomy.

Back 58

A. Lumpectomy and quadrantectomy

Front 59

59. A procedure that removes all of the breast tissue of the affected breast, includingthe removal of the areola and nipple, but leaves the muscle under the breast intact.Although most of the axillary lymph nodes are left intact, a sentinel lymph nodemay be removed.

Back 59

C. Simple Mastectomy or Total Mastectomy

Front 60

60. Involves removing the entire breast, the axillary lymph nodes, and the pectoralismajor and minor muscles behind the breast

Back 60

E. Radical Mastectomy

Front 61

61. How does the “indirect interaction” of radiation therapy cause DNA damage?

Back 61

61. The x-ray ionize water adjacent to the DNA. The reactive species that are createdin this reaction (hydroxyl radicals, H2O2 and O-) interact secondarily with DNA,causing damage and DNA strand breakage

Front 62

62. Explain cancers in terms of radiosensitivity and radioresistant

Back 62

62. The response of a cancer to radiation is described by its radiosensitivity. Highlyradiosensitive cancer cells are rapidly killed by modest doses of radiation. Somecancers are only moderately radiosensitive, and require a significantly higher doseof radiation to achieve cure. Some types of cancers are notably radioresistant, inthat the dose necessary to produce a cure may be unsafe (i.e., destroys healthytissue that causes further patient deterioration) for clinical practice.

Front 63

For questions 63-69, match the radiation therapy procedure with the description;

a. Conventional external beam radiation therapy(2DXRT)

b. Stereotactic radiation therapy (SRT)

c. Brachytherapy

d. Radioisotope therapy (RIT)

63. Delivered by placing radiation sources (s), consisting of radioactive “seeds” or“pellets” inside or next to the area requiring treatment.

Back 63

C. Brachytherapy

Front 64

64. An example is the use of oral iodine-131 to treat thryoid cancer.

Back 64

D. Radioisotope therapy (RIT)

Front 65

65. With this type of therapy, high-dose treatments may be limited by the radiationtoxicity capacity on healthy tissues which lay close to the target tumor. Anexample of this problem is seen in radiation of the prostate gland.

Back 65

A. Conventional external beam radiation therapy(2DXRT)

Front 66

66. Uses multiple narrow radiation beams to target small, well-defined tumors withprecision and accuracy using extremely detailed imaging scans.

Back 66

B. Stereotactic radiation therapy (SRT)

Front 67

67. The optimal form of treatment for very small tumors in the brain or spine.

Back 67

B. Stereotactic radiation therapy (SRT)

Front 68

68. Consists of a single beam of radiation delivered to the patient from severaldirections: often front or back, and both sides.

Back 68

A. Conventional external beam radiation therapy(2DXRT)

Front 69

69. This therapy can be temporary (radioactive material placed near the tumor for aspecific amount of time then removed) or permanent (radioactive source remainsin place, but becomes inert as radioactive material decays).

Back 69

C. Brachytherapy

Front 70

70. Define the following chemotherapy strategies: remission, prolongation of life, andpalliation.

Back 70

70.

-Until remission means that treatment continues until all manifestations(e.g., leukemic cells in blood and bone marrow) of the cancer disappears:

-For prolongation of life means that it has been demonstrated in clinicalstudies that patients on this therapy will live longer (e.g., 1.5-3 years) thanwithout treatment;

-Palliative chemotherapy is given without curative intent but to decreasethe suffering by reducing tumor load.

Front 71

71. What are the four common side effects of chemotherapy?

Back 71

71.

-Immunosuppression due to decrease production white blood cells;

-Anemia due to decrease production of red blood cells;

-Mucositis, inflammation of the linining of the digestive tract;

-Alopecia-hair loss

Front 72

72. Why is it important to determine the patient’s performance status beforechemotherapeutic treatment?

Back 72

72. Because of these side effects in answer #71, all chemotherapy regimens requirethat the patient be sufficiently healthy or capable of undergoing treatment.

Front 73

73. Compare the sensitivity of chemotherapy on cancers with high growth fractionscompared to cancers with a slow growth rate.

Back 73

73. Tumors with high growth fractions are more sensitive to chemotherapy becausethey have a large proportion of the targeted cells undergoing mitosis. However,malignancies with a slower growth rate (i.e., less targeted cells undergoingmitosis), tend to have a modest response to chemotherapy.

Front 74

74. What is the relationship between cancer resistance and ABC multidrugtransporters?

Back 74

74. Cancer cells that become resistant to chemotherapy treatments develop ABCmultidrug transporters on their cell membrane. These drug transporters pump thechemotherapeutic drug out of the cytoplasm, thus preventing them from damagingtheir DNA.

Front 75

For questions 75-81, match the Chemotherapy strategies with the descriptions.

a. Combined Modality Chemotherapy

b. Neoadjuvant Chemotherapy

c. Adjuvant Chemotherapy

d. Combination chemotherapy

75. Treating a patient with a number of different chemotherapeutic drugssimultaneously.

Back 75

D. Combination chemotherapy

Front 76

76. This chemotherapy strategy is also known as postoperative treatment because it isused after surgery in which the surgeon believes all the observable canceroustissue was removed, but is concerned with the risk of recurrence.

Back 76

C. Adjuvant Chemotherapy

Front 77

77. With this therapy, the drugs will differ in their mechanism and side effects, butthis strategy carries with it the advantage of minimizing the chances of resistancedeveloping to any one chemotherapeutic agent.

Back 77

D. Combination chemotherapy

Front 78

78. This strategy initially involves surgically removing or irradiate the tumors that arevisible together with chemotherapy for those small tumors that are not visible orhave metastasized

Back 78

A. Combined Modality Chemotherapy

Front 79

79. Commonly known as preoperative treatment because the patient is givenchemotherapy before surgery or radiotherapy.

Back 79

B. Neoadjuvant Chemotherapy

Front 80

80. This strategy involves the combined use of chemotherapeutic drugs with othercancer treatments, such as radiation therapy or surgery.

Back 80

A. Combined Modality Chemotherapy

Front 81

81. This chemotherapy strategy is design to shrink the primary tumor, therebyrendering surgery or radiotherapy less destructive or more effective.

Back 81

B. Neoadjuvant Chemotherapy

Front 82

For questions 82-87, match the chemotherapeutic drug to the description of its action?

a. Alkylating agents

b. Antimetabolites

c. Plant alkaloids

d. Topoisomerase inhibitors

82. As a group, these chemotherapeutic drugs prevent the formation of DNA andRNA by blocking the formation of their building blocks, purines and pyrimidines.

Back 82

B. Antimetabolites

Front 83

83. A class of enzymes that alter the supercoiling of DNA, preventing the DNA helixfrom unwinding and thus blocking DNA transcription and replication

Back 83

D. Topoisomerase inhibitors

Front 84

84. These chemotherapeutic drugs blocks the formation of microtubules from tubulin,thus preventing cells from forming the spindle fibers necessary for mitosis.

Back 84

C. Plant alkaloids

Front 85

85. Purine or pyrimidine analogues that prevent these bases from becomingincorporated into DNA during the S phase of the cell cycle, thus stopping normaldivision.

Back 85

B. Antimetabolites

Front 86

86. Attaches to the negatively charged sites on the DNA (oxygen, nitrogen,phosphorous and sulfur atoms). By binding to the DNA, steps (replication,transcription, and base pairing) leading to duplication of the cell's genetic materialare significantly altered.

Back 86

A. Alkylating agents

Front 87

87. This chemotherapeutic bind and inhibit the enzyme dihydrofolate reductase(DHFR), and thus prevents the formation of an intermediate, tetrahydrofolate.Tetrahydofolate is essential for purine and pyrimidine synthesis and its deficiencycan lead to inhibited production of DNA and RNA.

Back 87

B. Antimetabolites

Front 88

For questions 88-95, match the following types of hormone therapy to description of itsaction:

a. Orchiectomy

b. Luteinizing hormone-releaing hormone-analogs

c. Selective estrogen receptor modulator (SERMs)--tamoxifen

d. Aromatose inhibitors

e. Anti-androgens

88. The effect of this drug is to inhibit the action of 5α-reductase

Back 88

E. Anti-androgens

Front 89

89. This treatment involves the removal of the testes to eliminate the source oftestosterone.

Back 89

A. Orchiectomy

Front 90

90. This drug blocks the action of the estrogen in the breasts.

Back 90

C. Selective estrogen receptor modulator (SERMs)--tamoxifen

Front 91

91. This drug prevents the pituitary from releasing a hormone that stimulates thetestes to release testosterone.

Back 91

B. Luteinizing hormone-releaing hormone-analogs

Front 92

92. This drug will stimulate bone cells, reducing the risk of osteoporosis, yet maystimulate the endometrium of the uterus, increasing the risk for uterine cancer.

Back 92

C. Selective estrogen receptor modulator (SERMs)--tamoxifen

Front 93

93. This drug is used by postmenopausal women to block the production of estrogen.

Back 93

D. Aromatose inhibitors

Front 94

94. The action of this drug can prevent the binding of dihydrotestosterone (DHT) to aDNA receptor which in turn would stimulate the growth of prostate cancer.

Back 94

E. Anti-androgens

Front 95

95. This drug is used against breast cancer and prevents androgens, released mostlyfrom the adrenal gland, from being converted to estrogen. The latter takes placemostly in fat cells.

Back 95

D. Aromatose inhibitors

Front 96

For questions 96-100, match the type of monoclonal antibody to the description:

a. Murine mAb

b. Chimeric mAb

c. Humanized mAb

d. Human mAb

96. Composed of murine antigen sequence region fused onto human sequence regionsresulting in mAb that are approximately 65% human, thus reducing the patient’simmune response against the mAb and increasing the serum half-life.

Back 96

B.Chimeric mAb

Front 97

97. Approximately 95% human origin and therefore with a longer half-life

Back 97

C. Humanized mAb

Front 98

98. Produced by transferring human immunoglobulin genes into the murine genome,after which the transgenic mouse is vaccinated against a desired cancer antigen.

Back 98

D. Human mAb

Front 99

99. Historically, these were the initial therapeutic antibodies obtain from hybridomatechnology but have been plagued with clinical failures because of a short half-liein vivo due to type III hypersensitivity reaction (immune complex formation afterrepeated administration clears murine mAb before it can target cancer).

Back 99

A. Murine mAb

Front 100

100. Produce by grafting the murine antigen determinant region into the Fab portionhuman antibodies.

Back 100

C. Humanized mAb

Front 101

For questions 101-104, match the therapeutic use of mAb with the description.

a. Complement Dependent Cytotoxicity

b. Antibody-Dependent Cell-Mediated Cytoxicity

c. Radioimmunotherapy

d. Antibody-Drug Conjugates (ADCs)

101. Bind to the target cell (tumor) antigen, are trafficked into the cell where they arerelease and usually result in the activation of apoptosis

Back 101

D. Antibody-Drug Conjugates (ADCs)

Front 102

102. It recruits natural killer (NK) cells which, via the porferin/granzyme process, killsthe B cells.

Back 102

B. Antibody-Dependent Cell-Mediated Cytoxicity

Front 103

103. Targeted α-particle, 213Bi, therapy offers the potential for higher biologicaleffectiveness and more specific tumor cell kill with less damage to surroundingnormal tissues compared with the more conventional high-dose external beamradiation.

Back 103

C. Radioimmunotherapy

Front 104

104. End result will be the formation of the membrance attack complex (MAC) thatwill cause lysis and death to the cell.

Back 104

A. Complement Dependent Cytotoxicity