BSC 422 Lecture Notes - Lecture 20: Angiogenesis, Collagenase, Metastasis

1.In 1971, Dr. Judah Folkman published the “angiogenic hypothesis” suggesting that a tumor cannot grow beyond 1–2 millimeters without the development of new blood vessels (angiogenesis) that provide access to oxygen and nutrients. During the 1990s, it was discovered that vascular endothelial growth factor (VEGF) stimulates migration and proliferation of the cells that form blood vessels, leading to the formation of new blood vessels. VEGF binds to receptor tyrosine kinases (RTKs) on the cell surface and causes the RTKs to dimerize and become active, thereby initiating an intracellular signaling cascade that stimulates cell division and inhibits apoptosis. Many cancer cells secrete high levels of VEGF and increased VEGF expression in a tumor is correlated with a poor medical outcome for the patient. You work for a biotechnology company that seeks to create anti-cancer drugs that prevent growth of tumors and/or cause tumors to shrink, while leaving normal cells relatively untouched. Your company has purchased the rights to therapeutic uses of VEGF derived proteins as anti-tumor drugs. You have found that the VEGF protein has 2 domains, one involved in receptor binding, the other is required for dimerization of VEGF. You propose to make mutant versions of the protein that will act as antagonists of the receptor to be given to patients as an IV treatment as a way to inhibit the endogenous VEGF secreted by the tumor.

a.Which of the 2 domains should you mutate (receptor binding or dimerization)?

b. How do you expect the introduction of the mutant protein into the bloodstream of patients to block tumor progression (in other words, why did you change the domain in part a)?

61) How areantiangiogenic drugs used in the treatment of

cancer?

A) These drugsstop the replication of DNA so cancer cells

cannot reproduce.

B) These drugsstop the growth of blood vessels into the

tumor, so the cells "starve" to death.

C) These drugsstop metastasis.

D) These drugsstimulate the immune system.

E) These drugsstimulate the production of free radicals,

which kill cancer cells.

62) Which of the

following is true regarding photodynamic therapy?

A) It involves the use

of light sensitive drugs to target a cancer.

B) It uses magnets to

attract beads coated with a chemotherapeutic drug to acancer.

C) It is presently used

for the treatment of cancers of the breast and ovary.

D) It inhibits

angiogenesis.

E) It involves the use

of antibodies to deliver treatments to a cancer.

63) Which ofthe following types of cancer kills the highest

percentage of people diagnosed with the condition?

A)lung

B)breast

C)prostate

D)skin

E)colon

64) A mutationin which of the following genes can lead to

breast cancer?

A) BT05

B) HeLa

C) BRCA1

D)BCG

E)BCG2

65) If angiogenesis

were not to occur, a tumor would reach the size of a ________and stop growing.

A) period on a

typewritten page (.)

B) baseball

C) grapefruit

D) pea

E) basketball

66) Not onlydoes smoking cause lung cancer, it also doubles

the risk of which of the following types of cancer?

A)stomach

B)prostate

C)bladder

67) For women with a

mutated BRCA gene, the risk of breast cancer is about 60%.However, detection

of the mutated gene can occur before cancer ever develops by

A) testing of a blood

sample.

B) screening

mammography.

C) taking a biopsy of

breast tissue.

D) a PET scan.

E) urinalysis.

68) In some cases, why

doesn%u2019t the immune system recognize and destroy acancer?

A) Cancer cells that

produce abnormal antigens sometimes shed them.

B) Cancer cells have

less surface receptors needed for proper activation of Tcells.

C) Cancer cells have

enough %u201Cself%u201D surface markers as to be identified asnormal cells.

D) Cancer cells develop

from normal cells that cannot regulate cell division.

E) all of the above are

correct.

69) Theultimate goal of the male reproductive system is to

A) ensure thatsperm is produced at the correct time,

coinciding with ovulation.

B) releasesperm into the female's reproductive system.

C) join spermwith an egg, in an environment that favors

fertilization.

D) producelarge numbers of sperm.

E) maintain thehomeostatic condition of the male's body.

70) Synthesisof new sperm cells occurs in the

A) ductusdeferens.

B)urethra.

C) prostategland.

D) epididymis.

E) seminiferous tubules.

71) Externalgenitalia

of the male reproductive system include(s)

A) theejaculatory duct.

B) the urethraand scrotum.

C) the penisand scrotum.

D) thepenis.

E) the penis,urethra, and ejaculatory duct.

72) The releaseof LH in human males signals that

A) inhibin hasinhibited FHS secretion.

B) thehypothalamus has been stimulated to release inhibin.

C) spermproduction must be reduced.

D) the positivefeedback loop that regulates sperm production

is active.

E) blood levels of

testosterone are low

The Case of the Aging Surfer

Seth, a thirty-eight year-old white male of Scandinavian descent, has lived his entire life in Southern Florida. He is very concerned with maintaining a "healthy" appearance. Seth is very athletic and especially enjoys surfing. He has been surfing since the age of twelve and he started making surfboards while he was in high school. After obtaining a college degree in marketing Seth decided to start his own business making surfboards and giving surfing lessons for a local resort near his home. During a routine physical examination the physician assistant that Seth sees commented on the presence and appearance of a small growth (approximately 2-cm in diameter) above Seth's right eyebrow. This growth was shiny with a pearly border, a central ulcer and engorged surface blood vessels. The physician assistant was concerned that this might be a tumor and asked Seth a number of questions to aid in the diagnosis. Seth reported that he noticed this growth approximately six months ago but thought nothing about it since he often developed "pimples" when he was working on surfboards because of the heat and dust. Seth noticed that the growth would occasionally bleed, but he thought the bleeding most often occurred when he absently scratched above his eyebrows when he was working. Seth also reported that after bleeding the growth would "crust over" and appear to heal, but not disappear. Seth also thinks the lesion has increased in size, but he can't be certain.

The physician assistant asks Seth to come back in two days to visit with the attending physician and encourages Seth to be sure to use sunscreen whenever possible, especially when he is surfing or teaching surfing classes. Upon returning to see the physician, Seth is told that he probably has a basal cell carcinoma. This, the physician explains, is a cancer that while not benign, rarely metastasizes and grows very slowly. This type of cancer usually occurs in areas that have the greatest exposure to the sun (i.e. the face, head, and neck). While this cancer would probably not metastasize, the physician suggests surgical removal to minimize damage to any underlying tissues and a histological examination of the excised tissue to confirm the diagnosis.

Seth is concerned that if this is indeed cancer he will have to undergo radiation and/or chemotherapy and suffer from both hair loss and nausea like his mother did when she was being treated for breast cancer 10 years ago. The physician assures Seth that these treatments are not required for basal cell carcinoma and explains that this cancer usually remains localized to the specific area of the skin and does not usually spread to other tissues, so radiation and chemotherapy would not be necessary. Seth then asks why it is necessary to remove the tumor if it will not spread and is told that while the tumor does not spread to other body areas it will continue to grow and also invade deeper layers of the skin, such as the dermis, and destroy normal tissues. Seth agrees to the procedure and schedules a follow-up appointment to discuss the results of the biopsy the following week. At the follow-up appointment, Seth is told that the lesion was indeed a basal cell carcinoma. He is told that it will be important for him to try to use both sunscreens, specifically those containing para-aminobenzoic acid or PABA, and protective clothing as much as possible to minimize the effects of the ultraviolet (UV) rays of the sunlight. Seth is also told that while he should not be overly concerned, he should also pay close attention for similar lesions in the future, since a person with a single basal cell carcinoma is likely to develop additional basal cell carcinomas in the future.

http://emedicine.com/derm/topic47.htm

http://www.skincancer.org

The Case of the Aging Surfer:

Define the bold terms in the text.

How are benign and malignant tumors similar and different from each other?

Identify and briefly describe the three most common types of skin cancer and the risk to individuals who have developed each of them.

What are oncogenes and how are they believed to be related to cancer?.

Identify both the primary risk factors that Seth presents with and other risk factors that may or may not relate to Seth's case.

The procedure that Seth experiences is called the Mohs Surgery. What does it involve?

How do chemotherapy and radiation therapy act as treatments for cancer?

8) Explain why tanning booths are actually more dangerous than sunlight exposure in increasing the risk of developing some form of skin cancer.