biology, clinical manifestations, and treatment of cancer

Question 0

malignant tumors

Answer 0

• rapid growth rates
• loss of differentiation and absence of normal tissue organization
• anaplasia (loss of cellular differentiation)
• pleomorphic (size and shape)
• large darkly stained nuclei
• mitotic cells are common
• lack a capsule and grow to INVADE nearby blood vessels, lymphatics, and surrounding structures
• have the ability to SPREAD far beyond tissue of origin (metastasis)

Question 1

benign tumors

Answer 1

• not cancerous
• well-differentiated cells and well-organized stroma
• DO NOT INVADE BEYOND CAPSULE
• mitotic cells are very rarely present

Question 2

carcinoma in situ (CIS)

Answer 2

• abnormal growths in epithelial tissues with atypical cells
• localized to epithelium and have not yet penetrated or invaded surrounding stroma
• not malignant
• can remain stable, metastasis, or disappear
• often removed instead of “waiting”

Question 3

carcinomas

Answer 3

-cancers arising in epithelial tissue

Question 4

adenocarcinomas

Answer 4

-cancers arising from of form ductal or glandular structures

Question 5

lymphomas

Answer 5

-cancers of lymphatic tissue

Question 6

sarcomas

Answer 6

-cancers arising from mesenchymal tissue (connective tissue, muscle, and bone)

Question 7

leukemias

Answer 7

cancers of blood-forming cells

Question 8

tumor markers

Answer 8

• include hormones, enzymes, genes, antigens, and antibodies
• liver and germ cell tumors secrete a protein known as ALPHA FETOPROTEIN (AFP) into the blood
• prostate tumors secrete PROSTATE SPECIFIC ANTIGEN (PSA) into the blood

Question 9

3 ways that tumor markers are used

Answer 9

1. to screen and identify individuals at high risk for cancer
2. to help diagnose the specific type of tumor in individuals with clinical manifestations relating to their tumor, as in adrenal tumors or enlarged liver or prostate
3. to follow the clinical course of a tumor

Question 10

difference in cancer cells from normal cells

Answer 10

• sometimes described as transformed cells (can be created from normal cells)
• they lack contact inhibition- they continue to crowd and pile up on each other
• often anchorage independent- continue to divide even when suspended in a soft agar gel
• cancer cells are immortal- unlimited life span and continue to divide for years under appropriate lab conditions

Question 11

some ways that heritable changes in cells can contribute to cancer

Answer 11

• small and large DNA mutations that alter genes, chromosomes, and non-coding RNAs
• epigenetic changes

Question 12

cancer occurs…

Answer 12

• it is predominantlyl a disease of aging
• each individual acquires a number of genetic “hits” or mutations over time
• the accumulation of four to seven specific hits over time is required to cause a full-blown cancer

Question 13

clonal proliferations or clonal expansion

Answer 13

• mutant cancer cell has a selective advantage over its neighbors because of anchorage-independent growth, lack of contact inhibition, and immortality
• its progeny (descendants) can accumulate faster than its nonmutant neighbors

Question 14

what are oncogenes?

Answer 14

• mutant genes that in their normal nonmutant state direct synthesis of proteins that positively regulate proliferation
• aka, they encode proteins that promote growth

Question 15

what are tumor-suppressor genes?

Answer 15

• they encode proteins that in their normal state negatively regulate proliferation (anti-oncogenes)
• aka, they encode proteins that inhibit proliferation and prevent or repair mutations

Question 16

what is a proto-oncogene?

Answer 16

• it is an oncogene in its normal, nonmutant state

- ex. is growth factor or a growth factor receptor

Question 17

what are point mutations?

Answer 17

• type of genetic event that can activate oncogenes
• small scale changes in DNA
• effects the activity of proteins
• activating point mutations in RAS are found in many cancers, especially PANCREATIC and COLORECTAL cancer

Question 18

what are chromosome translocations?

Answer 18

-large changes in chromosome structure in which piece of one chromosome is translocated to another chromosome

-these translocations can activate oncogenes
1. they can cause excess and inappropriate production of a proliferation factor
2. they can lead to production of novel proteins with growth-
promoting properties

Question 19

what is copy number variation?

Answer 19

• when larger regions of DNA encompassing entire genes are gained or lost
• can be inherited

Question 20

gene amplication

Answer 20

• type of chromosome structural abnormality that can activate oncogenes
• these amplifications are the result of duplication of a chromosome over and over again

Question 21

tumor-suppressor genes

Answer 21

• major function is to negatively regulate cell growth and prevent mutations
• RB1, TP53, CDKN2A, NF1, APC, BRCA1
• tumor suppressors must be INACTIVATED to allow cancer to occur

Question 22

how many “hits” does it take to inactivate the two alleles of a tumor-suppressor gene?

Answer 22

TWO HITS

-because we have two copies or alleles of each gene (one from each parent)

Question 23

loss of heterozygosity (LOH)..?

Answer 23

-occurs when a one copy (allele) of a specific chromosome region is lost

Question 24

When does epigenetic silencing occur?

Answer 24

-it is caused by reversible chemical modification or acetylation of histones and related chromatin components, as well as methylation of cytosine residues in DNA

• whole regions of chromosomes are shut off by silencing
• this causes the pattern of gene expression to be different in one cell than another cell with the same genes

Question 25

affects of silencing…

Answer 25

• silencing can shut off critical tumor-suppressor genes in the absence of mutations in the gene
• this can lead to selective advantage for affected cells, perhaps leading to their immortalization and clonal expansion
• silencing of tumor suppressors may be a faster way to create cancer cells than mutational or genetic loss of tumor suppressors

Question 26

oncomirs

Answer 26

• miRs (microRNAs, non-coding RNAs) that stimulate cancer development and progression
• decrease the stability and expression of other genes by pairing with mRNA in a process that involves RNA-induced silencing complex

Question 27

caretaker genes

Answer 27

• genes that are responsible for the maintenance of genomic integrity
• they encode proteins that are involved in repairing damaged DNA

Question 28

which genetic mutations are inherited…somatic cells or germ cells?

Answer 28

GERM CELLS

• individuals who inherit one mutant allele, are predisposed to a specific form of cancer
• those who inherit this one germline mutant will inevitably suffer loss of the normal allele by loss of heterozygosity (LOH) or epigenetic silencing

Question 29

examples of human cancers that can be inherited

Answer 29

1. retinoblastoma
2. Wilms tumor (cancer of the kidney)
3. neurofibromatosis
4. inherited breast cancer
5. familiar polyposis coli or adenomas of the colon

Question 30

what is autocrine stimulation?

Answer 30

it is the ability of a cancer cell to secrete their own growth factor in order to proliferate and stimulate their own growth

Question 31

receptor tyrosine kinases are present in…

Answer 31

cancer cells that have increase in growth factor receptors which cause them to proliferate

Question 32

What is neovascularization or angiogenesis?

Answer 32

it is the ability of advanced cancers to secrete multiple factors that stimulate new blood vessel growth

examples include…vascular endothelial growth factor; platelet-derived growth factor; and basic fibroblast growth factor

these examples recruit new vascular endothelial cells and initiate the proliferation of existing blood vessel cells, allowing small cancers to become large cancers

Question 33

What are telomeres?

Answer 33

telomeres are protective ends, or caps, on each chromosome and are placed and maintained by a specialized enzyme called telomerase

• only active in germ cells (ovaries and testes)
• cancer cells activate telomerase to restore and maintain their telomeres, thereby allowing them to continue dividing (this makes telomerase an attractive therapeutic target)

Question 34

What kind of environment must cancer cells grow in?

Answer 34

a hypoxic and acidic environment

-they are also parasites, able to selectively extract nutrients from the bloodstream without any evolutionary pressure for balanced metabolism

Question 35

cancer cells and glucose

Answer 35

• they are able to perform glycolysis even with sufficient oxygen present
• this may be detected by use of FDG (this is like glucose but is not able to be broken down by glycolysis and therefore accumulates in cells)
• FDG can also be imaged and detected
• small metastatic tumor masses that are consuming huge amounts of glucose can readily be detected

Question 36

What is the concept of oncogene addiction?

Answer 36

oncogene addiction is the term used to describe the cancer cells “addiction” to the mutant genes and their use of these mutations to continue to grow and survive
-when these mutations are returned to their normal states, the cancers often stop growing and even regress

*treating the addiction, treats the cancer

Question 37

What are the two essential characteristics of adult stem cells?

Answer 37

1. they self-renew

2. they are multipotent- they have the ability to differentiate into multiple different cell types

Question 38

how are inflammation and cancer related?

Answer 38

• during both cancer and inflammation, inflammatory cells migrate to the site of injury and release cytokines and growth and survival factors that stimulate local cell proliferation and new blood vessel growth to promote wound healing by tissue remodeling
• inflammatory cells release compounds such as reactive oxygen species and other reactive molecules that can promote mutations and block the cellular response to DNA damage