Uncontrolled growth, increased cell division, or decreased cellular death
Cancer breaks many of the rules of basic cellular behavior as they exhibit what?
DNA repair, cell signaling, cell cycle, apoptosis and tissue architecture
Defects in numerous pathways can lead to cancer including proteins involved in what?
1) Cells that reproduce in defiance of normal restraints
2) Cells that invade areas normally reserved for other cells
What are two heritable properties of cancer?
What is a cell that grows and divides out of control; a tumor?
What is a noninvasive tumor whose removal achieves a 'cure'?
What is an invasive tumor; cancer?
What are cancer cells that have broken from the original mass to form secondary tumors at other sites?
What are two types of benign Cancers?
What is a benign cancer of the epithelial cell with a glandular organization?
What is a benign cancer that is cartilage derived?
What are three examples of malignant Cancers?
What is a malignant cancer arising from epithelial cells?
What is a malignant cancer arising from connective tissues or muscle cells?
What is a malignant cancer derived from white blood cells or their precursors?
It begins as an individual mutant cell that prospers at the expense of its neighbors
How does cancer begin?
Cells rest, grow, divide, differentiate and die as needed for the good of the organism
What do healthy cells do for the good of the organism?
It enters a diseased state that can destroy the organism
What can happen when a cell "escapes" the normal functions of cells?
Cancer is roughly defined as cells that reproduce in defiance of the normal restraints placed on cell growth and division and invade areas normally reserved for other cells
What is the definition of cancer?
Are benign tumors considered cancerous?
What kind of tumors give rise to metastases making the cancer difficult to eliminate?
Epithelial based cancers (carcinomas)
What are the most prevalent cancers?
1. Epithelial cells are continue to proliferate in adults
2. Epithelial cells are exposed most often to physical and chemical damaging agents
3. A combination of 1 and 2
The high cancer rate in epithelial cells is likely due to what?
A single abnormal cell from a specific tissue
Most cancers can be traced back to what?
Additional changes in one of its descendents
The single cell that causes cancer experienced a heritable change that was followed by what?
The cells to out-compete and out-live their neighbors
The single cell that causes cancer experienced a heritable change that was followed by additional changes in one of its descendents. These changes allowed the cells to do what?
A malignant tumor
What is formed by a cell mass that was able to escape its original location and enter the blood or lymphatic vessels to form secondary tumors?
At the time of detection, how long have cancer cells been growing?
What test identifies translocation events?
Chronic myelogneous leukemia
What disease has the long arm of chromosome 22 transferred to the long arm of chromosome 9?
An identical break and refusion pattern
All leukemic cells from a single patient have what?
The mosaic nature of tissue due to the randomness of what?
They vary in which of the two X chromosomes have been inactivated
Tissue in women are made up of a mixture of cells which varies in what way?
In their pattern of X-linked inactivation
When analyzed for their expression of an X-linked gene, how were cancerous cells found to be identical?
What is a heritable trait that involves changes in genetic material?
What is the generation of cancer?
What are changes in DNA sequence information?
Chemical carcinogens and radiation
Agents identified as cancer causing agents include what?
Cancer is clonal in nature but cancer does not arise from what?
The probablity of cancer increases with what?
A young individual would be just as likely to get cancer as an older one (onset independent of age)
If a single mutation event triggered the formation of a cancerous cell, what would happen?
Specific combinations of mutations that over time produces a cancerous cell
The incidence of cancer rises with age therefore it is the progressive accumulation of what?
Delayed from the time of initial exposure
Even for cancers associated with a known external agent, the time of onset is what?
Initial genetic mutation(s) introduced by chemical exposure
It is the accumulation of mutations over time, in addition to what, are necessary to induce cancerous cells?
At late stages of tumor progression
Most cancers are identified when?
What can identify uterine cancer at early steps in its development?
The epidermis of the skin
The epithelium covering the cervix is similar in its organization to what?
Flat and differentiated keratin rich cells which are lost when they reach the surface
The outer layer of the epithelium in the cervix is composed of what?
The basal layer and stain dark purple
Actively dividing epithelial cells in the cervix are confined to what layer? They stain what color?
The connective tissue layer
The layer underneath the basal layer of the cervix is what?
Which picture shows normal epithelium (of the cervix)?
1. Undifferentiated and actively dividing cells are found throughout the lower 1/3 of the epithelium
2. Upper layer still contains flattened and differentiated cells
3. Upper layer somewhat unorganized
Why is panel B considered a low grade lesion?
The undifferentiated and actively dividing cells occupy the entire epithelium
Why is panel C considered a high-grade neoplasia?
Physically removing them (surgery)
As long as the undifferentiated and actively dividing cells are confined to the epithelial side of the basal lamina, how can this condition be cured?
When these cells break through the basal lamina to invade the underlying connective tissue
Why is panel D considered malignant?
The accumulation of mutations
What gives rise to malignant cancer?
Its own proliferation or decrease its death
In each step, a cell accumulates a mutation that acts to enhance what?
Generations and involve a large element of chance
A cell accumulates a mutation that acts to enhance its own proliferation or decrease its death. These changes occur over what?
Many, many years
Development of cancerous cells can take how long?
Genetic and epigenetic changes
Development of cancerous cells can take many, many years and is a process driven by what kind of changes?
1. An accidental change in the genomic DNA leads to tumor formation
2. This type of mutation is heritable (i.e. can be passed from generation to generation)
What are two paths to genetic based mutagenesis?
1. Changes in heterochromatin packaging leads to gene inactivation, which in turn leads to tumor formation
2. Changes in methylation patterns trigger changes in gene activity leading to tumor cell progression
What are two scenarios of epigenetic changes leading to tumor formation?
The inactivated gene products normally protect against tumor progression, therefore their loss promotes what?
the inactivation of proteins involved in determining chromatin structure (e.g. enzymes involved in histone modification or involved in 'reading' the histone code)
The formation and maintenance of inappropriate heterochromatin may result from what?
The inherited pattern of DNA methylation reinforces gene silencing events established by the packaging of DNA into what?
Methylation mediated gene silencing
What may occur independent of heterochromatin packaging leading to tumor formation?
Large amounts of what typically occurs on selected genes during tumor progression?
Cancer cells have a high rate of genetic changes and are therefore what?
1. Decreased rate of DNA repair
2. Failure to maintain chromosomal copy number during division
The high rate of mutagenesis may be due to what?
Mutations that inactivate cell cycle checkpoints
Continued cell division with unrepaired and/or missegregated DNA is due to the acquisition of what? That inactivate what?
Damage which accelerates the accumulation of DNA damage
In cancer cells, ignoring checkpoints provides a cell with the selective advantage of continued cell division in the presence of what?
The rate of mutation is balanced against what?
The rate of mutation is balanced against death, since an excessive mutation rate would lead to what?
Is it only the accumulation of a large number of mutations that gives rise to a tumor?
Cells isolated from breast and colon cancer have accumulated ~1 amino acid change in 100 different proteins, but alterations in only 20 of these genes are likely needed for tumor progression
What evidence supports the fact that it is not simply the accumulation of large number of mutations that gives rise to a tumor?
The rate of cell division or apoptosis
Alterations in what can result in tumor formation?
In normal tissue, the rate of cell division is balanced by what to keep the number of cells constant?
An increase in cell division gives rise to an increased chance that one of these cells will undergo an additional mutagenic or epigenetic change further promoting the progression towards what?
2 and 3
Which ones will lead to tumor formation (1,2 or 3)?
Which one will lead to homeostasis?
Replicative cell senescence
What is the number of times a single cell can double before halting proliferation?
Replicative cell senescence is controlled by what, an enzyme required for the maintenance of the repeative ends of
Permanent cell-cycle arrest
Shortening of telemeres ends with each cell division ultimately leads to what?
Do normal cells have a llimited number of times they can divide?
What kind of cells are able to escape the limitations placed on cell proliferation?
The length of the DNA at telomere ends
The ability to 'count' the number of times an individual cell has divided is linked to what?
What enzyme complex is responsible for maintaining the ends of chromosomes?
Most proliferating cells are deficient in what activity?
They become progressively shorter with each DNA replication cycle
Most proliferating cells are deficient in telomerase activity. What happens to the telomere ends with each DNA replication cycle?
In fibroblast cells, cellular division stops after how many divisions?
1. Accumulating mutations that disable the checkpoint system that monitors the length of
2. Acquiring mutations that maintain or activate telomerase activity
3. Acquiring an alternate mechanism to maintain chromosome ends even in the absence
of telomerase activity
Cancer cells avoid replicative cell senscence by what three methods?
What process makes a 'tumor' a 'cancer'?
The invasion of tumor cells into other tissue
What is the defining property of metastasis?
Disruption of the adhesion mechanism the normally keeps cells tethered to their neighbor and the extracellular matrix
The invasiveness expressed in metastasis requires what?
The blood or lymphatic vessel
After tumor cells invade tissues, the tumorous cells enter what for transport to a different location?
The basal lamina and endothelial lining of the vessel
The transport of tumor cells through the tissues and into the circulatory system is a difficult step as the cell must cross what two layers?
It exits the blood/lymphatic vessel and establishes growth at this new location
At its destination, what does the tumor cell do?
What are cells that are able to escape the vessel and grow to form a small clump of cells?
Extracellular survival signals
A small number of micrometastases are able to grow in the new environment, with its absence of what?
An adequate blood supply for the delivery of nutrients and oxygen
For continued cell proliferation, a tumor must also receive what?
What is the process of forming new blood vessels?
Oxygen becomes limiting and hypoxia kicks in
When a tumor reaches a certain size, what becomes limited? What kicks in?
Hypoxia inducing factor, or HIF-1α,
Hypoxia triggers expression of what?
HIF-1α activates the transcription of genes encoding what?
Pro-angiogenic factors act to attract what to the area?
1. Cells that make up the supporting connective tissue (fibroblast cells)
2. Inflammatory white blood cells, and
3. Vascular epithelial cells
Tumorigenesis requires the assistance of other cell types. What are they?
1. They provide the framework for tumor growth
2. They provide signal proteins that stimulate cell growth and division,
3. They secrete proteases that further remodel the extracellular matrix
Tumorigenesis requires the assistance of other cell types. What are the functions of these cells?
1. Self-sufficient for growth and proliferation
2. Insensitive to anti-proliferative extracellular signals
3. Less prone to undergo apoptosis
4. Defective in control mechanisms to stop cell division
5. They induce help from the surrounding stromal cells
6. They induce angiogenesis
7. They can escape from their home tissue and can
proliferate in an alternate site
8. They are genetically unstable
9. They produce telomerase, or acquire other ways to stabilize their telomeres
What are properties that contribute to cancerous growth?
An individuals genetic makeup, environment and lifestyle
What are some factors that govern the development of cancer?
An irreducible background incidence of cancer
The inherent limitations on the accuracy of DNA replication and repair will generate what?
If humans lived long enough, would mutations accumulate to the extent that all individuals will acquire cancerous cells?
Environmental and lifestyle choices
What plays a role in the incidence of cancer that has evidence that supports it?
Except for tobacco use, has a clear link between an environmental factor and the establishment of cancer been fully established?
What are agents known to cause cancer?
1. UV light from the sun,
2. Ionizing radiation from radioactive decay,
3. Chemical compounds
What are the best studied group of carcinogens that induce DNA damage?
DNA (UV and ionizing radiation)
Some carcinogens act directly on what?
They become damaging only after they have been modified by cytochrome P-450 enzyme found in the liver
Some carcinogens act directly on DNA (UV and ionizing radiation); when do many of them become damaging?
Harmless and easily secreted compounds
Cytochrome P450 converts toxins into what?
Cytochrome P450 converts toxins into harmless and easily secreted compounds. However, modification by P450 may generate a product that is extremely what?
It binds guanine residues in DNA. It generates DNA adducts
P450 mediated aflatoxin modification generates a compound that binds what? Generating what?
DNA strand breaks and block RNA polymerase progression
Adducts formed by P450 mediated aflatoxin induce what? Block what?
Adducts formed by P450 mediated aflatoxin induce DNA strand breaks and block RNA polymerase progression thereby reducing what?
What a carcinogen that causes latent genetic damage, damage that sets the stage for an increased incidence of cancer if exposed to additional cancer inducing agents at a later time?
What are chemicals that are not themselves
mutagenic, but can cause cancer in cells previously
exposed to a tumor initiator.
Increased cell proliferation increasing the probability of tumor progression.
Tumor promoters induce a inflammatory response which results in what? Increasing the probability of what?
Not all agents that cause cancer are what?
Cancerous cells by activating cell proliferation through the use of a "tumor promoter"
Cells that have been primed by treatment with a known chemical carcinogen (i.e. a tumor initiator) can be induced to form what? By activating cell proliferation through the use of what?
An inflammatory response
Tumor promoters are chemical agents which by themselves are not mutagenic but have been shown to induce cancer by activating what?
Cell proliferation which leads to an increased probability of tumor progression by increasing the number of cells containing the initial mutagenic event
Tumor promoters are chemical agents which by themselves are not mutagenic but have been shown to induce cancer by activating an inflammatory response. This inflammatory response triggers an increase in what?
Viruses, bacteria or parasites
15% of cancers have been linked to what?
1. Subverting cell division control of the host cell,
2. Inducing chronic inflammation which triggers continual cell division,
3. Destruction of the immune system which promotes secondary infections that have a direct carcinogenic effect,
4. Triggering chronic infections which have been linked to specific cancers
The role of viruses, bacteria and parasites in cancer induction include what?
What is the most important environmental cause of cancer and it is one of the few cancer causing agents for which there is epidemiological support for a link between exposure and cancer development?
Excess food consumption, which leads to obesity
Besides tobacco use, what else increases the risk of cancer?
Lung and broncheal cancers
What two cancers have been linked to increased tobacco use?
Decreased rates of H. pylori infection or changes in diet
Decreased stomach cancer is likely due to what?