Chapter 11: Cancer Biology Flashcards
Final Exam (129 cards)
1
Q
Cancer
A
“diseases in which abnormal cells divide without control and are able to invade other tissues.”
2
Q
tumor
A
Generally reserved for describing a new growth, or neoplasm
3
Q
Two ways to describe tumors
A
- Benign
- Malignant
4
Q
Benign tumors are usually encapsulated with what?
A
Benign tumors are usually encapsulated with connective tissue
5
Q
Benign tumors contain what kind of cells?
A
contain fairly well-differentiated cells and well-organized stroma
6
Q
What kind of tissue do benign tumors usually contain? How do they interact with other structures?
A
They retain recognizable normal tissue structure and do not invade beyond their capsule, nor do they spread to regional lymph nodes or distant locations.
7
Q
How do benign tumors spread?
A
they do not spread to regional lymph nodes or distant locations.
8
Q
What kinds of cells are rarely present in benign tumors?
A
Mitotic cells are very rarely present during microscopic analysis
9
Q
How are benign tumors named?
A
Benign tumors are generally named according to the tissues from which they arise with the suffix “-oma,”
10
Q
Suffix of “oma” indicates what?
A
Indicates a tumor or mass
11
Q
Leiomyoma
A
Benign tumor of smooth muscle of the uterus
12
Q
Lipoma
A
A benign tumor of fat cells
13
Q
Some tumors initially described as benign can become what?
A
Can progress to cancer and then are referred to as malignant tumors
14
Q
How are malignant tumors distinguished from benign tumors?
A
malignant tumors , which are distinguished from benign tumors by more rapid growth rates and specific microscopic alterations, including loss of differentiation and absence of normal tissue organization
15
Q
What is one of the microscopic hallmarks of cancer cells?
A
Anaplasia
16
Q
Anaplasia
A
The loss of cellular differentiation
17
Q
Pleomorphic
A
marked variability of size and shape
18
Q
How are the size and shape of malignant cells described?
A
Pleomorphic
19
Q
How are the nuclei of malignant tumors described?
A
They often have large darkly stained nuclei
20
Q
What type of cells are common in malignant tumors?
A
Mitotic cells are common
21
Q
Stroma of Malignant tumors
A
Malignant tumors may have a substantial amount of stroma, but it is disorganized, with loss of normal tissue structure.
22
Q
How do malignant tumors grow? What do they lack?
A
Malignant tumors lack a capsule and grow to invade nearby blood vessels, lymphatics, and surrounding structures.
23
Q
Most important and deadly characteristic of malignant tumors
A
their ability to spread far beyond the tissue of origin, a process known as metastasis.
24
Q
Metastasis
A
Process in which tumors spread far beyond the tissue of origin
25
How are cancers named?
cancers generally are named according to the cell type from which they originate.
26
Carcinomas
Cancers arising in epithelial tissue
27
Adenocarcinomas
Cancers arising from or form a ductal or glandular structures.
28
Mammary adenocarcinoma
A malignant tumor arising from breast glandular tissue
29
Fibroadenoma
a benign breast tumor
30
Sarcoma suffix
Cancers arising from mesenchymal tissue (including connective tissue, muscle, bone)
31
Leukemias
Cancers of blood forming cells
32
Lymphomas
Cancers of lymphatic tissue
33
Carcinoma in situ (CIS)
refers to preinvasive epithelial tumors of glandular or squamous cell origin.
a group of abnormal cells that are found only in the place where they first formed in the body
34
Where are early stage cancers localized?
These early-stage cancers are localized to the epithelium and have not penetrated the local basement membrane or invaded the surrounding stroma.
Based on these characteristics, they are not malignant.
35
CIS lesions can have one of the following three fates:
1. they can remain stable for a long time,
2. they can progress to invasive and metastatic cancers
3. they can regress and disappear.
36
How does CIS vary?
CIS can vary from low-grade to high-grade dysplasia
37
High grade CIS lesions
high-grade lesions having the highest likelihood of becoming invasive cancers.
38
Tumor initiation
the process that produces the initial cancer cells
39
Tumor initiation is dependent on what?
dependent on mutational and epigenetic changes and characteristics of the microenvironment.
40
Tumor promotion
the process during which the population of cancer cells expands with diversity of cancer cell phenotypes
41
What is tumor promotion dependent on?
is dependent on additional genetic mutations and epigenetic changes and a changing tumor microenvironment.
42
Tumor progression
the process leading to spread of the tumor to adjacent and distal sites (metastasis),
43
What is tumor progression governed by?
is governed by further genetic mutations, epigenetic aberrations, and changing microenvironments at the primary tumor and at sites of metastasis.
44
driver mutations
Some mutations, referred to as driver mutations , “drive” the progression of cancer.
45
How does a cell become cancerous?
After a critical number of driver mutations have occurred, the cell becomes cancerous.
46
What selective advantage does cancer cells have over others? What is it called?
its progeny can accumulate faster than its nonmutant neighbors.
This is referred to as clonal proliferation or clonal expansion
47
Malignant transformation
the process by which a normal cell becomes a cancer cell,
48
What is malignant transformation directed by?
is directed by progressive accumulation of genetic and epigenetic changes that alter the basic nature of the cell and drive it to malignancy.
49
Stroma
tumor microenvironment
50
Hallmarks of Cancer (1-5)
1. Evading growth suppressors
2. Enabling replicative immortality
3. Tumor promoting inflammation
4. Activating invasion and metastasis
5. Genomic instability (mutator instability)
51
Hallmarks of Cancer (6-9)
6. Inducing angiogenesis
7. Resisting cell death
8. Deregulating cellular energetics
9. Sustaining proliferative signaling
10. Avoiding immune destruction
52
Genomic alterations of cancer that initiate and maintain development of cancer?
1. sustained proliferative signaling,
2. evading growth suppression,
3. genomic instability,
4. replicative immortality
53
Hallmarks/enablers that are secondary to genomic change:
angiogenesis and reprogramming energy metabolism.
54
Hallmarks of cancer that include tumor resistance to destruction by the host's protective mechanisms:
resistance to apoptotic cell death, tumor-promoting inflammation, and avoiding immune destruction.
55
First and foremost hallmark of cancer:
uncontrolled cellular proliferation
56
How do normal cells enter proliferative phases?
Normal cells generally only enter proliferative phases in response to growth factors that bind to specific receptors on the cell surface.
57
Proto-oncogenes
The genes that encode components of receptor-mediated pathways designed to regulate normal cellular proliferation.
58
Oncogenes
mutated or overexpressed proto-oncogenes.
Are cancerous cells
59
Why are oncogenes driven into a state of unregulated expression of proliferation signals and uncontrolled cell growth?
Oncogenes are independent of normal regulatory mechanisms;
thus the cell is driven into a state of unregulated expression of proliferation signals and uncontrolled cell growth.
60
Autocrine stimulation
some cancers acquire the ability to secrete growth factors that stimulate their own growth, a process known as autocrine stimulation
61
Uncontrolled cancer cell proliferation is also related to?
Uncontrolled cancer cell proliferation also is related to inactivation of tumor-suppressor genes.
62
Tumor suppressor genes- what do they do?
1. normally regulate the cell cycle,
2. inhibit proliferation resulting from growth signals,
3. stop cell division when cells are damaged,
4. and prevent mutations.
63
What are tumor suppressor genes also referred to as?
Anti-oncogenes
64
How do oncogenes and tumor suppressors differ?
Whereas oncogenes are ACTIVATED in cancers, tumor suppressors must be INACTIVATED to allow cancer to occur
65
Prototypical tumor suppressor gene
A prototypical tumor-suppressor gene is the retinoblastoma (RB) gene
66
How do tumor suppressor genes like RB work?
Tumor-suppressor genes, such as RB, monitor antigrowth cellular signals and block activation of the growth/division phase in the cell cycle;
67
Anti-proliferative activity of RB depends on what?
Anti-proliferative activity of RB depends on the degree of protein phosphorylation.
Low levels of phosphorylation result in RB binding to and inhibiting transcription factors.
68
Mutations in RB lead to:
mutations in RB lead to persistent cell growth.
69
Another tumor suppressor gene, not RB gene?
tumor protein p53 (TP53) .
70
TP53 gene- what does it do?
P53 monitors intracellular signals related to stress and activates caretaker genes
71
Caretaker genes
genes that are responsible for the maintenance of genomic integrity
72
Caretaker genes encode proteins involved in what?
Caretaker genes encode proteins involved in repairing damaged DNA, such as occurs with errors in DNA replication, mutations caused by ultraviolet or ionizing radiation, and mutations caused by chemicals and drugs.
73
P53 protein controls initiation of what?
The p53 protein also controls initiation of cellular senescence (cease dividing) or apoptosis, and suppresses cell division until DNA repair is complete or other effects of stress are corrected.
74
If repair of a cell is not completed, what happens to the cell? (having to do with p53)
If not corrected, the cell enters senescence or apoptosis, thus preventing further DNA damage and mutations.
75
Loss of function of TP 53 or caretaker genes leads to what?
Loss of function of TP53 or caretaker genes leads to increased mutation rates and cancer.
76
Genomic instability
Genomic instability refers to an increased tendency of alterations—mutability—in the genome during the life cycle of cells.
77
A hallmark of cancer cells is their immortality, what does that mean?
they seem to have an unlimited life span and will continue to divide for years under appropriate laboratory conditions.
78
Hayflick limit
Most normal cells are not immortal and can divide only a limited number of times (known as the Hayflick limit) before they either enter senescence (cease dividing) or enter crisis (apoptosis) and die.
79
What is one major block to unlimited cell division
One major block to unlimited cell division (i.e., immortality) is the size of a specialized structure called the telomere.
80
Telomeres
are protective ends, or caps, of repeating hexanucleotides (six nucleotide units) on each chromosome
81
Telomerase
Enzymes that place and maintain Telomeres
82
Where are telomerase usually active?
Telomerase is usually active only in germ cells (in ovaries and testes) and in stem cells.
83
What happens when non germ cells begin to proliferate abnormally?
when non–germ cells begin to proliferate abnormally their telomere caps shorten with each cell division.
84
What do short telomeres normally signal the cell to do?
Short telomeres normally signal the cell to cease cell division.
85
If telomeres become critically small, what happens to the chromosome?
If the telomeres become critically small, the chromosomes become unstable and fragment, and the cells die.
86
When most cancer cells reach a critical age, what do they do?
When they reach a critical age, most cancer cells activate telomerase to restore and maintain their telomeres, thereby allowing continuous division.
87
Telomerase activity is restored in what percent of cancers?
90%
88
Neovascularization or angiogenesis
the process of establishing new blood vessels within the tissue undergoing repair
Major component of wound healing
89
What is obligatory for the growth and spread of cancer?
Access to a blood supply
90
Angiogenic factors and angiogenic inhibitors-what do they do?
Normally control development of new vessels
91
Hypoxia-inducible factor-1α (HIF-1α)
an oxygen-sensitive transcription factor, is a major regulator of angiogenesis in normal tissue;
92
What does HIF-1a do?
HIF-1α is stabilized under hypoxic conditions and induces expression of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
93
What leads to increased expression of HIF-1a. (CONFUSING SLIDE)
Inactivation of tumor-suppressor genes (e.g., p53) or increased expression of oncogenes (e.g., HER2) leads to increased expression of HIF-1α–regulated angiogenic factors and increased vascularization.
94
How do vessels formed within tumors differ from those in healthy tissue?
They originate from endothelial sprouting from existing capillaries and irregular branching, rather than regular branching seen in healthy tissue.
The interendothelial cell contact is less tight so the vessels are more porous and prone to hemorrhage, as well as allowing passage of tumor cells into the vascular system.
95
Programmed Cell Death (Apoptosis)
Programmed cell death ( apoptosis ) is a mechanism by which individual cells can self-destruct under conditions of tissue remodeling or as a protection against aberrant cell growth that may lead to malignancy.
96
The ______may contribute to the onset of cancer and can be manipulated throughout the process to benefit tumor progression and spead
inflammatory response
97
Example of inflammation associated with cancer
Gastric inflammation induced by infection with the bacterium Helicobacter pylori (H. pylori) and the risk for gastric cancer.
98
Chronic infection of H.pylori is an important cause of what diseases?
1. peptic ulcer disease and
2. is strongly associated with gastric carcinoma
3. Gastric mucosa–associated lymphoid tissue (MALT) lymphomas.
99
What can be done to cancers that have not metastasized?
Cancer that has not metastasized can often be cured by a combination of surgery, chemotherapy, and radiation.
100
How are cancers involved with inflammation?
Cancers disrupt the environment, initiate or enhance inflammation, and in turn recruit local and distant cells (macrophages, lymphocytes, and other cellular components of inflammation).
101
How is inflammation in successful tumors?
Successful tumors appear capable of manipulating cells of the inflammatory response
102
Metastasis
Metastasis is the spread of cancer cells from the site of the original tumor to distant tissues and organs through the body.
103
What initiates tumor metastasis?
Changes in the tumor microenvironment initiate the metastatic process and may include stromal cell adaptation to increase tumor mass and intratumor hypoxia.
104
The model for transition to metastatic cancer cell is called?
The model for transition to metastatic cancer cells is called epithelial-mesenchymal transition.
105
What is a prerequisite for metastasis?
Invasion, or local spread, is a prerequisite for metastasis.
106
In earliest stages, local invasion occurs how?
In its earliest stages, local invasion may occur by direct tumor extension.
107
To transition from local to distant metastasis, what must occur?
To transition from local to distant metastasis, the cancer cells must also be able to invade local blood and lymphatic vessels
108
Paraneoplastic syndromes
are symptom complexes that are triggered by a cancer but are not caused by direct local effects of the tumor mass.
109
Pareneoplastic syndromes are most commonly caused by what?
They are most commonly caused by biologic substances released from the tumor (e.g., hormones, cytokines) or by an immune response triggered by the tumor.
110
Example of paraneoplastic syndrome?
a small fraction of carcinoid tumors release substances, including serotonin, into the bloodstream that cause flushing, diarrhea, wheezing, and rapid heartbeat.
111
Most severe form of malnutrition associated with cancer?
Cachexia
112
Cachexia
Cachexia is a multiorgan, energy wasting syndrome or type of energy balance disorder where energy intake is decreased and energy expenditure 248is increased
113
Cachexia involves?
(1) weight loss mainly from loss of skeletal muscle
(2) body fat and inflammation.
114
Cachexia results in:
Results in wasting, emaciation, and diminished quality of life.
115
Symptoms of Cachexia
A syndrome that has many symptoms, including:
anorexia,
early satiety (filling),
weight loss,
anemia,
asthenia (marked weakness),
taste alterations, and
altered protein, lipid, and
carbohydrate metabolism.
116
What may contribute to cachexia?
Cytokines and metabolites from the tumor may contribute to cachexia.
117
Cancer staging initially involves what?
Cancer staging initially involves:
1. determining the size of the tumor,
2. the degree to which it has invaded locally, and
3. the extent to which it has spread (metastasized)
118
In general, what is the staging system used?
In general, a four-stage system is used, with carcinoma in situ regarded as a special case.
119
Stage 1 cancer
Cancer confined to the organ of origin is stage 1
120
Stage 2
cancer that is invasive locally is stage 2
121
Stage 3
cancer that has spread to regional structures, such as lymph nodes, is stage 3
122
Stage 4
cancer that has spread to distant sites (e.g., a liver cancer that has spread to a lung or a prostate cancer that has spread to bone) is stage 4.
123
A common scheme for standardizing staging?
One common scheme for standardizing staging is the World Health Organization's TNM system
124
T in TNM system
T indicates tumor spread,
125
N in TNM system
N indicates node involvement
126
M in TNM system
M indicates the presence of distant metastasis
127
How is the prognosis with increasing tumor size, lymph node involvement, and metastasis.
The prognosis generally worsens with increasing tumor size, lymph node involvement, and metastasis.
128
Tumor markers
substances produced by both benign and malignant cells that are either present in or on tumor cells or found in blood, spinal fluid, or urine.
129
Tumor markers include:
Tumor markers include hormones, enzymes, genes, antigens, and antibodies
