Neoplasia Flashcards
What are the three types of cells? What are their functions and give examples
Permanent cells: unable to divide or reproduce; neurons and cardiac cells
Labile: constant state of renewal (can go into G0 if needed); GI or hematopoietic system
Stable cells: can grow but do it more slowly & mostly when tissue is injured or lost
What is cell differentiation?
proliferating cells are transformed into different and more specialized cell types; each specialization step the cell takes, the less ability it has to develop different cell characteristics and cell lines
What are progenitor cells?
parent cells; cells of the same lineage that are able to differentiate providing large numbers of replacement cells
What is a stem cell? What are the two types?
remain incompletely differentiated throughout life
1) . Pluripotent: embryos contains these; able to give rise to every tissue in the body
2) . Adult: reservoirs of stem cells in fully grown tissue; lineage specific
What does it mean if a cell is poorly differentiated?
cells look like something else than what the cell was supposed to differentiate into
Where are the two checkpoints controlling cell division located in the cell cycle?
G1- post-mitotic phase (DNA at rest)
G2- pre-mitotic phase (volume of cell has doubled)
What do growth factors in cancer cells destroy (in terms of the cell cycle)?
They destroy the gap phases so cell keeps proliferating without checkpoints
What are 4 functions of cell proliferation?
Replace skin cells, replace blood cells, increasing cells during periods of growth, and tissue repair/wound healing
What three proteins control the cell cycle?
Cyclin, cyclin dependent kinases (CDKs), and their inhibitors (cyclins and CDKs are found in every stage of the cell cycle)
What is the function of CDKs in the cell cycle?
they are enzymes that phosphorylate target proteins (on/off switch)
What is the function of inhibitors of the cyclin-CDK complexes (in terms of the cell cycle)?
They function as tumor suppressors; checks and balances system for cancer
What is cell proliferation?
the process of cell growth and differentiation (bad when it is uncontrolled)
What are characteristics of a benign neoplasm? Are the cells poorly or well differentiated? What tissue do their cells resemble? How fast/slow do they grow? Are they encapsulated?
well-differentiated cells; cells resemble tissue of origin; slow, progressive growth; may stop or regress; Usually does not cause death unless the location or size interferes with vital functions; not invasive; usually encapsulated (don’t extend past basement membrane); lost ability to suppress proliferation but not differentiation
What characteristics of a malignant neoplasm? Are the cells poorly or well differentiated? What tissue do their cells resemble? How fast/slow do they grow? Are they encapsulated?
Have lost the ability to control cell proliferation and differentiation; invade and destroy surrounding tissue; metastasize; poorly differentiated (mildly PD is better than severely PD); the more rapid the growth the more differentiated ; can compress BVs and outgrow their own blood supply; can be solid tumor or hematologic (arise from bone marrow/lymph)
What is anaplastic cancer?
cancer cells that look nothing like cells of origin; new cells look like cancer cells
What are the two tissue types that make up benign and malignant tumors? Define them both
1) . Parenchymal: cells that represent functional components of an organ (determine behavior of the tumor)
2) . Supporting tissue: connective tissue; blood vessels and lymph structure
What is a carcinoma vs sarcoma vs cancer in situ?
carcinoma- malignant tumors of epithelial cell origin
sarcoma- malignant tumor of mesenchymal (bone marrow) cell origin
cancer in situ- localized pre-invasive tumor
What three things does the rate of growth of a neoplasm (normal or malignant tissue) depend on?
1) . number of cells actively dividing and moving through cell cycle (cancer has more cells doong this)
2) . duration of the cell cycle (faster the cycle, faster the cells will grow; cancer & normal cells don’t have much of a difference here)
3) . Number of cells lost vs the number of cells produced (NOT a lot of cancer cells are lost, which makes the difference in malignancy)
What is growth fraction in terms of a malignant neoplasm?
it is the ratio of dividing cells to resting cells
Explain a cancer’s growth fraction. Explain lymphoma/leukemia vs colon/lung cancer growth fractions
when someone has cancer, there are more cells in the active cycling phase so cells are dividing/gorwing faster
colon/lung- have low growth fraction, resemble more like normal cell growth; respond to chemo less
Lymphoma/leukemia- respond to chemo better
What is doubling time in terms of a malignant neoplasm?
The time it takes for the total mass of cells in a tumor to double (higher the growth fraction in cancer cells, the less the doubling time bc limited by resources)
Describe a malignant tumor’s growth curve? Explain how a malignant tumor’s doubling time affects detection
It has a steep growth curve but then flattens out when supply is outstripped by growth
Tumor is undetectable until it has doubled 30 times and contains about 1 billion cells (after 35 doublings, it has about 1 trillion cells and death can occur)
Why is cancer considered “crab-like”? What three cavities can it invade?
its difficult to remove bc of its tendrils invading tissue (benign is well circumscribed and surrounded by a capsule); can invade peritoneal, pleural, & pericardial spaces; metastatic tumor retains some characteristics of tissue from which it was derived
What two forms of spreading can occurring in a malignant neoplasm?
Lymphatic system (lymphatic spread) OR Blood (hematologic spread)
Which form of malignancy spreading do carcinomas follow? How about sarcoma? Osteosarcoma?
Carcinoma- lymphatic system
Sarcoma- blood, capillaries, and venules
Osteosarcoma- malignancy of bone
Define metastasis
development of a secondary tumor in a location distant from the primary tumor
What 7 things must a neoplasm do to successfully metastasize?
1) . break loose from primary tumor
2) . invade surrounding ECM
3) . gain access to a BV
4) . survive its passage in the bloodstream
5) . emerge in a favorable location
6) . invade the surrounding tissue
7) . Begin to grow- creating a blood supply (angiogenesis)
Describe how lymphatic spread of metastasis works? What is a sentinel lymph node?
Spreading in this manner means the tumor cells lodge first in the initial lymph node that receives drainage from that site
Sentinel lymph node is the 1st lymph node to which a primary tumor drains
Explain how a sentinel node biopsy works
Inject a radioactive tracer and blue dye into the tumor to determine which is the sentinel node; looking at the sentinel node, you determine if cancer cells are present or absent. If blue dye travels to lymphatic system, then tumor has traveled (Breast cancer/melanoma)
Describe how hematologic spread of metastasis works?
It enters into venous system via capillaries and venues (GI, pancreas, spleen, drain venous blow to liver first SO LIVER COMMON SITE FOR METASTASIS); liver is optimal because it is very fertile and vascular organ which supplies the tumor with the right growth factors
What do cancer cells HAVE to do once reaching a new site in order to keep growing?
Establish a blood supply (angiogenesis)
What is oncogenesis?
The genetic mechanism whereby the normal cell is transformed into a cancerous one
What are oncogenes?
genes that encode proteins that promote the loss of growth control & conversion of cell to malignant state
What are four types of genes that control growth and replication?
- *1). Proto-oncogenes: genes that become oncogenes (VARY person to person)
- *2). Tumor suppressor genes- genes that protect normal cells from activated oncogenes
3) . Genes that program apoptosis
4) . Genes that regulate repair of damages DNA - cancer requires activation of MANY mutated genes
What are 6 types of proteins encoded by proto-oncogenes?
1) . Growth factors
2) . Growth factors receptors
3) . Protein kinases & proteins that activate them
4) . Proteins that regulate cell cycle
5) . Proteins that activate or inhibit apoptosis
6) . DNA binding proteins
* *become oncogenes if mutated
What are three ways proto-oncogenes can become oncogenes?
1) . Mutation of gene itself
2) . Mutation in nearby regulatory sequence which alters gene expression
3) . Chromosome rearrangement which alters gene expression (dominant trait; only need one copy for damage to be done)
What are tumor suppressor genes? Are they dominant or recessive genes?
act as cell brakes; they encode proteins that restrain cell growth & prevent cells from becoming malignant
– becomes problems when these genes are INACTIVATED
They are typically recessive, which means cells are normal until both genes are deleted/mutated
Why is p53 significant?
it is one of the genes that is a tumor suppressor and also sends damaged cells on to apoptosis
What are the three stages of how a carcinogenic agent causes normal cells to turn cancerous?
1) . Initiation: exposure of cells to a carcinogenic substance that makes them more susceptible (ex: smoking, drugs)
2) . Promotion: induction of unregulated growth in an initiated cell (can be long latency period, years)
* *CAN REVERSE IF STIMULUS IS REMOVED
3) . Progression: when tumor cells acquire malignant properties
What are 4 host factors linked to cancer?
Hereditary, hormones (estrogen), obesity (insulin), immunologic mechanisms
What are 3 environmental factors linked to cancer?
Chemical carcinogens, radiation(ionizing), and oncogenic viruses
Explain mendelian inheritance patterns for breast cancer
10% risk with 1 first degree relative
15% risk with 2 affected family members
30% risk with 3 affected family members
50% risk in women >65 yrs with multiple family members with BC BRCA-1 and BRCA-2
Explain autosomal dominant inheritance pattern in retinoblastoma
People are born with ONE mutant allele of tumor suppressor gene; for disease to occur, normal allele must also mutate
40% of retinoblastomas are inherited; carriers of this gene have 10,000 fold risk in developing it, usually bilaterally (sign of white eye during exam)
Explain how endometriosis could occur through excess estrogen exposure
Constant estrogen influx can actively drive a cancer cell to divide (why we alternate estrogen & progesterone)
What are direct vs indirect carcinogens?
Direct- reacting agents that require activation in body to become carcinogenic (ex: smoking)
Indirect- reacting agents, procarcinogens, which become active ONLY after metabolic conversion (ex: hydrocarbons/aromatic rings)
How do carcinogens cause cancer?
They form highly reactive species that bind with DNA< RNA, and cellular proteins
When someone is exposed to radiation, what factors have influence on the type of cancer that person might develop?
Type of radiation, age of person, sex of person, dose dependent, latency period changes
What are 4 examples of cancerous viruses
HPV, EBV, Hep B virus, Human T cell leukemia virus (HTLV-1)
What are 5 generalized symptoms of cancer? What happens to tissue integrity when someone has cancer?
Malaise, fatigue, anorexia, weight loss, anemia
Tumors invade so tissue compresses and erodes BVs causing necrosis/bleeding
What is cancer anorexia?
“cachexia syndrome”
weight loss and wasting of body fat/muscle tissue; profound weakness anorexia & anemia
What is paraneoplastic syndrome? What are three main groupings for this syndrome?
Cancer can produce manifestations in sites that are not directly affected by the disease
1) . Hormones- cause endocrine disturbances (ADH, ACTH, PTH)
2) . Hematopoietic: increase in clotting, thrombolytic endocarditis (usually first indicator)
3) . Neurologic: myasthenic syndrome caused by small cell lung cancer
How often should a woman get a pap smear?
start at age 21 and every 3 years if normal
What age should people start having screening rectal, prostate exams, and colonoscopies? How about mammograms
50 yrs old
40 for mammogram
What type of cancer should you do a bone marrow aspiration to diagnose?
Leukemia
What is grading of a cancer?
histologic or cellular characteristics of a tumor (level of differentiation and number of mitoses)
**Obtained by biopsy & observed under microscope
What is staging of a cancer?
method to determine extent and spread of a disease (TNM system)
0- no evidence
x- not assessed
1-4 varying degree of severity (4 is more severe)
What are some treatment options for cancer?
Surgery, radiation, chemo, hormone & antihormone therapy, immunotherapy, biologic response modifiers (interferons, interleukins), targeted therapy (bevacizumab injection)
**could be combo