• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/441

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

441 Cards in this Set

  • Front
  • Back
What is neoplasia?
A term for cancer that means "new growth"
What are the most common types of cancer in childreN?
Leukemia and brain/CNS tumors
What is different about the mortality fraction and the number of people with cancer?
While the number of people with cancer is increasing (because there are MORE people!) the fraction of mortality is DECREASING
What is the most common cancer for females?
Breast cancer
What is the most common cancer for males?
Prostate cancer
What is the highest KILLER cancer?
Lung (prostate and breast have higher survival though they have a higher incidence!)
What percentage of breast cancer patients have hertiable genetic traits linked to breast cancer?
5%
What are the two types of tumors?
Malignant and benign
What is the difference in the cancerous abilities of benign tumors and malignant tumors?
Benign tumors are NOT CANCEROUS
Malignant tumors are CANCEROUS
Out of the two types of tumors, which is life threatening?
Malignant
How fast do benign tumors grow?
Slowly
How fast do malignant tumors grow?
Fast
How do benign tumors affect other tissues?
Benign tumors do NOT dessimate or invade other tissues
How do malignant tumors affect other tissues?
They will invade and destroy other tissues through metastasis
What is metastasis?
The spread of the disease from an organ to another that is non-adjacent
What are the morphological properties of benign tumors?
They have a distinct round shape with a capsule
What are the morphological properties of malignant tumors?
They are crab shaped, with arms spreading to other tissues, and do not have a capsule but rather blood vessels growing into the tumor
In what direction is the growth of a benign tumor?
Outwards (into the lumen of the tissue)
In what direction is the growth of a malignant tumor?
Inwards (down into the tissue)
What does the benign tumor look like when you open it up?
Homogenous
What does the malignant tumor like when you cut it up?
It is heterogenous
Why is a malignant tumor heterogenous?
Cell necrosis in the center
What do the individual cells of the benign tumor look like?
Normal looking like their cell of origin
What do the individual cells of the malignant tumor look like?
Haphazard rearrangement (poor geometry)
Pleomorphic (many sizes and shape)
What type of mitosis do benign tumor cells undergo?
Low rates, and get normal appearance in cells that do divide
What type of mitosis do malignant tumor cells undergo?
Rapid mitosis with irregular results
Do benign tumor cells retain parental cell function?
They may retain some of the function
Do malignant tumor cells retain parental cell function?
No- there is little evidence of normal or specialized cell function at all
How is the prefix of a tumor name done?
The prefix is the type of tissue the tumor originated in
How is the suffix of a tumor name done?
Whether it is benign or malignant
What does adeno mean?
Gland
What does angio mean?
Vessels
What does chondro mean?
Cartilage
What does fibro mean?
Fibrous tissue
What does hemangio mean?
Blood vessels
What does lymphangio mean?
Lymph vessels
What dose lipo mean?
Fat
What does myo mean?
Muscle
What does neuro mean?
Nerve
What does osteo mean?
Bone
How is the suffix named for benign tumors in the epithelial tissue?
"oma"
What is the suffix for malignant tumors in the epithelial tissue?
"carcinoma"
What is the suffix for benign tumors in the connective tissue?
"oma"
What is the suffix for malignant tumors in the connective tissue?
"sarcoma"
What is the "connective tissue" that would have a sarcoma name?
Fibroblasts, fat, bone, cartilage, or endothelium
What is a teratoma?
A tumor that contains multiple cell types
Out of all the cell adaptions, which is considered a risk for cancer?
Dysplasia
How can dysplasia lead to cancer?
If the stimulus is not removed, it can progress to anaplasia, then to invasion
What happens after the development of a malignant tumor?
The cells become more disorganized, fragmented
What is the stage after malignant tumor?
Carcinoma simplex
What is the stage after carcinoma simplex?
Anaplastic carcinoma
What is characteristic about anaplastic carcinoma?
It is almost impossible to distinguish where the cells came from
How can one determine how organized the tissue cells are to make an accurate prognosis?
Culture cells in vitro and expose them to carcinogens, enabling us to see cancer progress
What is the main problem with benign tumors?
They can cause pain by COMPRESSION of nearby tissues
Where would this compression by benign tumors be problematic?
-Tumors in the brain
-TUmors in the esophagus buldge into lumen causing dysphagia
What is dysphagia?
Difficulty swallowing
How can benign tumors lead to infection?
By obstructing openings or ducts in tissues
What is an example of a tumor that imitates parent cell function?
Neuroendocrine tumors can SECRETE SUBSTANCES (adrenaline)
What types of effects do both benign and malignant tumors have?
-Obstruction of ducts/important tissues
-Infection
-Cachexia (though to a lesser extent in benign)
-Paraneoplastic syndromes
-Immunosuppression
What occurs during cachexia?
Person loses appetite, metabolic rate increases, and they waste away to skin and bones
What are paraneoplastic syndromes?
The tumor secretes abnormal compounds into the system
What type of additional effects do malignant tumors have?
-Destruction of tissue
-Haemorrhage (eroding blood vessels or continual bleeding)
-Metastasis to vital organs
What are "systemic effects of malignant tumors"?
These effects are in addition to the effects of the original tumour itself at any metastatic sites
What is a papilloma?
Simple, benign EPITHELIAL tumour
What is a papilloma caused by?
It is a wart: caused by a viral infection
What does a papilloma consist of?
Fibrous tissue core surrounded by hyperplastic squamous epithelium
What is a squamous cell carcinoma?
A malignant tumor of epithelial origin
How do squamous cell carcinomas begin?
It starts as a small papular mass that invades the epithelium below it
What is characteristic of squamous cell carcinoma after it breaks thorugh the epithelium?
A charcteristic fibrous ulcer is produced on the surface
What is a "polyp"?
A benign tumor in a gland (Adenoma)->they project out into the lumen on stalks
What are characteristic of adenocarcinomas?
Irregular craters on the surface with characteristic, undifferentiated cells
What is a lipoma?
A connective tissue tumor that is benign, fat
What is the appearance of a lipoma like?
Lobular, yellow in colour, encapsulated and contains normal-looking adipocytes
What is a liposarcoma?
A malignant connective tissue tumor that begins in fat cells
What is characteritic of liposarcomas?
Coarse emulsion of lipids, pleomorphism, and invasion of surrounding tissues
What are myomas and osteomas?
Examples of connective tissue tumors (benign)
What is an osteogenic sarcoma?
A malignant tissue tumour, metasticizes quickly, and causes alot of damage to the bone of origin
What is a local invasion?
After a primary cancer starts, will invade the tissue beneath it
What is a carcinoma in situ?
When a cancer has not yet gone through the basement membrane - can cure cancer at this stage
How can a cancer spread away from its site of origin?
It gets into the lymphatics or blood after invading the local tissue
What is a regional tumour?
When the tumor invades through the basement membrane - if caught early can still correct but possibility that it went to other organs
How do we get cells that are metastatic?
-Cancerous cells are genetically unstable, eventually get a heterogenetity between cells in the tumor and eventually get a sublcone that is metastatic
Why are these metastatic subclones able to get into the circulation?
They are motile, can eat through connective tissue and basement membrane, into a blood or lymphatic vessel
How do cancer cells attach to its surroundings?
They have receptors for laminin
What does laminin provide for the cell?
The laminin is bound to type IV collagen (cancer cell also makes laminin so it can bind!!)
What happens once cancer cells are bound?
THey release type IV collagenases which will DISSOLVE the type IV collagen found in the basment membrane
What happens once the cancer cell releases these collagenases?
It passes through (invades) the hole it has created into the tissue
What happens once the cancerous tissue gets into the stroma?
It has receptors for and binds to FIBRONECTIN in the stroma
What happens once the cancer cells bind the fibronectin on the stromal cells?
It can release enzymes and dissolve the connective tissue stroma
How do tumour cells have motility?
They release autocrine motlilty factors which will act back on the cells in an autocrine manner
Why do some malignant tumors get areas of necrosis at the center?
The tumor is growing so rapidly that the cells on the edge take up the resources and the ones at the center do not get any
What are other ways cancer cells can spread?
-Via perineural spaces (along nerves)
-Laterally along the basal layers of the skin epithelium
What happens when cancer cells get into the lymphatics?
They spread to lymph nodes and can completely occlude them, reversing the flow of lymph and directing the malignant cells elsewhere
How can the lymph nodes help you see how far along the cancer is?
-The lymph nodes closes to their tissue origin will be first affected
Why are tumor cells able to penetrate veins more easily?
They have thinner walls
What are common sites that the cancer will metastacize to?
Bones, liver, cerebrospinal fluid and the adrenals
Where do sarcomas tend to spread?
To the venous system
Why do sarcomas tend to spread to the venous system?
The tissues in which they originate (connective tissue) are well upplied with vasculature
Where do carcinomas tend to spread?
To the lymphatic system
What happens if a tumor embolus gets into the portal circulation?
It will pass into the liver quite quickly
What happens if the tumour embolus gets into the systemic venous system?
Metastasize to the heart and lungs
What happens if the tumour cell gets into the pulmonary circulation (from lung tissue)?
Mestastasizes to the heart and then to the general circulation
Where will cancer in the small intestine tend to metastasize?
To the liver
Why can tumor cells easily invade areas such as the spinal veins?
The spinal veins are rich in venous plexusses, and there are no valves or ducts controlling the direction so the blood flow is slower, allowing them to invade really easily
Where does prostate cancer tend to metastasize to? (characteristic pattern)
Bone
What is the characteristic pattern of metastasis of colon cancer?
To the stomach
What is the characteristic pattern of metastasis of breast cancer?
To the lung
How does hterogeneity cause problems for cancer treatment?
Cancer cells that metastasis are prne to getnetic mutations and are thus harder to get rid of
What is tumor angiogenesis factor?
It is a factor that malignant tumor cells posses that cause vessels to grow into the tumor to supply it with increased nutrients so it can grow larger
What is the TNM system?
A way to evaluate the extent of the tumor
What does T stand for?
Tumour
What does N stand for?
Lymph nodes
What does M stand for?
Metastasis
What does the TNM system evaluate?
The state of the original tumour, whether lymph nodes are involved, and whether or not there is metastasis
What is survival rate related to?
Lymph node involvement
What is the score of the primary tumour (T) based on?
How large it is and to what extent it has invaded into the other tissues
What would the T be for in situ carcinoma?
Tis
What is the highest level of N?
3
At what stage is cancer typically diagonosed?
Rarely at the in situ stage, typically when the cancer is localized but a fraction has begun to metastasize
How are tumor grades based?
On the level of differentiation
What does a high tumor grade mean?
The less differentiated the tissues are, lower survival rate
How can we gauge how far along a cancer or tumor is?
By the degree of disorganization
Where do cancer cells originate from?
Not completely differentiated cells
-Froms omewhere along the pathway from stem cell to specialized cell
What happens if the mutation occurs to a cell that is early in the pathway of a stem cell to special cell?
It is poorly differentiated -> more malignant and metastasize rapidly
How can you identify what type of cancer you have once the cells are so undifferentited?
Use immunohistochemistry with specific marker anti-Abs
How can you check for abnormalities in the DNA?
Comparing DNA with cancer cells to normal cells using flow cytometry to look for abnormal peaks
What is cytology a basis for?
The pap smear to test for cervical cancer -> it is looking at individual cells for abnormalities
Why can the blood be analyzed to diagnose a tumor?
Tumors secrete different factors into the blood
What are some other methods used to diagnose tumors?
X-rays and imaging
How does smoking cause cancer?
Cigarettes have thousands of chemicals that over time, develop enough mutations to turn into malignant cells
At what point could you cure someone with lung cancer?
At the point where the cancer cells havent mutated enough to metastasize
What are the five stages of cancer?
-Metaplasia
-Dysplasia
-Anaplasia
-Invasion
-Metastasis
What happens during metaplasia in lung cancer?
Ciliated columnar cells are replaced by a thick layer of squamous cells
What happens during dysplasia in lung cancer?
There are an accumulation of mutations that lead to abnormal cells
What happens during anaplasia in lung tissue?
Carcinoma in situ
What happens during invasion in lung cancer?
There is erosion through the BM and surrounding tissue
What is large cell carcinoma?
Undifferentiated type of tumor
What is small cell carcinoma?
A neuroendocrine type of tumor
What is an adenocarcinoma?
It is a tumor originating in the glandular tissue
What is squamous carcinoma?
It is a tumor where you often see necrosis at the center because the blood supply can't keep up with the rapidly growing tumor
Where are small cell and squamous cell carcinomas located?
Centrally located near the main bronchi
Where are large cell and adenocarcinomas located?
They are peripherally located
What is bronchoscopy?
A procedure used to look for abnormalities in the airways
How could you diagnose a tumor based on the examination of sputum?
Centrally located tumors often shed their cells and are then found in the sputum
What percentage of lung cancers can be attributed to large cell carcinoma?
15%
How does large cell carcinoma tend to spread?
Through the lymph nodes and distant organs by the time it is detected
Which type of lung cancer has the worst prognosis?
Small cell lung cancer
Which types of lung cancer have the better prognoses?
Squamous cell and adenocarcinoma
Which lung cancer has the best prognosis?
Squamous cell carcinoma
What does a biopsy of the tumor determine?
The origin and extent of invasion
What does N1 mean?
Nodes are affected just in the region of the cancer
What does N2 mean?
Nodes are affected on the other side of the region of the cancer (greater involvement)
What does "regional" lung cancer mean?
Lung and lymph nodes, but no metastasis
What does "distant" lung cancer mean?
Lung, lymp nodes, and metastasis
What is a wedge resection?
Removing a small mass via segment resection
What is a lobectomy?
Removal of an entire lobe of the lung
What is a pneumonectomy?
Entire lung removal
What percentage of lung cancer patients survive?
10%
What are some local effects of lung cancer?
-Obstruction
-Dilation of bronchus
-Pleural effusion
-Hameoptysis
-Metastasis to lymph nodes
What does obstruction lead to?
Vulnerability to distal infection due to inefficient clearance
What is pleural effusion?
Fluid in the pleural space
What is haemoptysis?
Coughing up blood
What can cause haemoptysis?
Damage and surrounding tissues
What are the distal effects of lung cancer?
Cerebral metastases
Bone metastases
Liver metastases
Finger clubbing
Inncreased ACTH release
Increased ADH release
Cachexia
What does increased ACTH release during cancer result in?
Increased endocrine effect
What does increased ADH release during cancer result in?
Increased sodium retention
What is cachexia?
Loss of appetite and weight loss, patient wastes away
What are the classic symptoms of lung cancer?
Cough, chest pain, coughing blood, chest infection, malaise, weight loss, shortness of breath, hoarseness (if larynx affected), distant spread
What happens if the tumor grows into the thoracic cavity (outside the lung)?
-Tracheal obstruction
-Esophageal compression
-Hoarseness
-Lymphatic obstruction
-Obstruction of vena cava
Why does hoarseness result?
The tumor affects the larynx
What does lymphatic obstruction result in?
PLeural effusion
What does obstruction of the vena cava result in?
Impaired venous return to the heart
What is the route of tumor spread from the lung?
-Local invasion
-Transcoelom spread
-Blood-borne spread
-Lymphatic spread
What happens during local invasion of the tumor from the lung?
The tumor extends into lung tissue
What happens during transcoelom spread?
The tumor migrates along the pleural space
What happens during blood-borne spread?
Tumor enters draining veins and cells enter the systemic circulation
WHat happens during lymphatic spread?
TUmor extends along the pulmonary lymphatic vessels
What are three common sites of metastasis of lung cancer?
Brain
Bone
Liver
What is a gland that lung cancer tends to spread to alot?
The adrenal glands
Why do lung tumors tend to spread to the adrenal glands?
There is high blood flow in the area
Which cancers tend to metastasize to the bone?
Breast, prostate, kidney, bronchus, thyroid gland, GI and reproductive cancers
Which sites are particularly sensitive to bone metastasis?
Proximal portion of long bones
Ribs, skull, and vertebrae
Besides smoking, what are two other main causes of lung cancer?
-Carcinogens
-Radon
What are some carcinogens that cause lung cancer?
Fossil fuels, asbestos, arsenic, chromium, soot, tars, oils
What is radon?
Decay product of uranium that is a volatile gas
What is radon?
Decay product of uranium that is a volatile gas
What is colorectal cancer?
Cancer of the large intestine or the rectum
What is colorectal cancer?
Cancer of the large intestine or the rectum
Which cells become mutated in colorectal cancer?
Cells in the base of the crypts
What is the benign growth that is part of colorectal cancer?
An epithelial origin benign growth that projects into the lumen of the colon, refered to as a polyp
What is special about this polyp formed in colorectal cancer?
It can put you at risk for malignant tumor and cancer
What is the pathway from normal epithelia in the large intestine to colorectal cancer?
-Normal epithelia
-Small adenoma
-Large adenoma
-Pre-malignant changes
-Colorectal carcinoma
What is the different between adenocarcinoma and adenomatous polyp?
Adenocarcinoma is malignant and no longer projects into thelumen and instead grows down through the intestine
What does the adenocarcinoma in colorectal cancer cause?
Ulcers and bleeding on the surface and constriction of the colon
What is stage 0 of colorectal cancer?
Carcinoma in situ that can be detected (in some cases)
What is stage 1 of colorectal cancer?
Cancer is confined to the site of origin
What is stage 4 of colorectal cancer?
There is growth into the wall, lumen, and there is involvement of distant organs
Why is colorectal cancer more promising at diagnosis than lung cancer?
There is less metastasis at diagnosis in colorectal cancer than lung cancer
How does the colorectal tumor get to the liver?
It goes through the walls of the intestine, through the lymph nodes, and then through the portal vein to the liver
What are tumor markers in colorectal cancer?
Expression of embryonic antigens not normally seen in adult tissue
What is this embryonic antigen?
CEA (Carcinoembryonic antigen)
What are the locations of colorectal cancer?
Appendix, ascending colon, transverse colon, descending colon, sigmoid colon or rectum
What is another term for the sigmoid colon?
Pelvic colon
Which colorectal cancers are more easily detected and why?
Recto-sigmoid area because bleeding is more obvious in this region
Which area of the colon has the least detectable colorectal cancer?
Tumors in the cecum area are less detectable
Why are tumors in the cecum area less detectable?
Because of occult blood loss
What is occult blood loss?
Blood gets mixed with fecal material as it passes through the intestine, making it less obvious and less detectable
What does chronic occult blood loss lead to?
Fatigue and anemia
Where is pain from colorectal tumors on the RIGHT side felt?
At the midline above the umbilicus
Where is pain from colorectal tumors on the LEFT side felt?
At the midline below the umbilicus
Where is pain from tumors in the rectum located?
Localized distally
What is tenesmus?
Difficulty with defecation
What is the main cause of colorectal cancer?
Environmental
What are some other risks for colorectal cancer?
-Abnormal diet
-Cigarette smoking
-Inflammatory bowel disease
-Familal adenomatous polypopsis
How do HIGH fat and LOW fiber diets promote tumor growht?
They promote high bile acid production
How does inflammatory bowel disease result in colorectal cancer?
Chronic inflammation increases risk
What is familial adenomatous polyposis?
A rare genetic disorder in which there are 100's of glandular polyps in the intestine which puts you at risk for the development of malignancy
What are three tests to perform to get an early diagnosis of colorectal cancer?
-Fetal occult blood test
-Sigmoidscopy
-Colonoscopy
What is the difference between sigmoidoscopy and colonoscopy?
Sigmoidoscopy looks at a small portion of the intestine (rectum and sigmoid region), while colonoscopy looks at the entire colon for polyps
How is chemoprevention applied to prevent development of colorectal cancer?
Chronic used of NSAIDS such as aspirin
What is the incidence and death rate like of other GI cancers?
Less frequent, very high death rates
What are the GI cancers in order of survival rate?
Pancreatic, Liver, Esophagus, Stomach
What are paraneoplastic syndromes?
Distal effects of the tumor not due to the direct effect of the metastatic lesion
What are paraneoplastic syndromes typically caused by?
Mediators released from tumor cells
What are two cases that something the tumor is releasing causes issues?
Abnormal synthesis
Abnormal access
What is "abnormal synthesis"?
The tumor is making something it shouldnt be making
What is "abnormal access"?
The tumor is releasing something in high amounts it shouldn't be releasing
What does the release of these mediators cause?
Inappropriate physiological or immune responses
What are some symptoms of these paraneoplastic syndromes?
Fever, cachexia, endocrine syndromes, neurological impairment, hematological syndromes,changes in the intestine, kidneys and skin
What are some examples of mediators these malignant cells can be releasing?
ACTH, ADH, calcitonin, HGH, cytokines and growth factors
Which type of cancer can cause distal effets on nerves and muscle?
Small cell lung cancer
What is the paraneoplastic neurological syndrome?
-An immune reaction against a tumor cell, which may help destroy it. Cytotoxic T cells are being produced and these can pass through the BBB and react against some of the neurons leading to damage and malfunction
What does cachexia lead to?
Dying of malnutrition
When is cachexia most common?
In GI cancers
What does cachexia cause?
Progressive weakness, anorexia and weight loss
When is cachexia relieved?
After eradication of the tumor
Why is cachexia releived after eradication of the tumor?
The cachexia was due to abnormal compounds released by the tumor
How is cachexia caused in cancer?
Cytokines released from tumors (TNFalpha, IL-6, IFN gamma) act on the hypothalamus and appetite centers
What can release of these cytokines lead to?
Anoreia, Skeletal muscle catabolism, release of inflammatory proteins by the liver
Why does cachexia pose a risk of death?
Increased vulnerability to infection
Cardiovascular collapse
What is the difference between cachexia and starvation?
The resting energy expenditure can INCREASE and there is a degradation of protein at a higher rate than normal
How does the tumor affect metabolism?
-sends signals to adipose tissue to mobilize lipids
-moblizes aa from skeletal muscle
-converts everything to glucose to feed the tumor
Which treatments are used in treating breast and prostate cancer?
Hormone therapy
Radiation
Chemotherapy
Why do you need to look at the 10 year survival rate rather than 5 years when considering carcinoma of the breast and prostate?
These cancers undergo late metastasis. They undergo micro-metastasis in which the tumor migrates to other organs but remains dormant
How is breast cancer detected?
When the breast cancer invades the surrounding adipose tissue and you can detect a lump/change in surface of the features of breast
What is the most common type of breast cancer?
Ducts
What are the other types of breast cancer in decreasing incidene?
Mucoid, medullary, lobular, ductal mixed, etc..
At what point is ductal carcinoma detected?
When it is carcinoma in situ (curable at this point) but there has been some invasion into surrounding tissue
How can estrogen receptors be used to treat breast cancer?
If you use a drug that blocks estrogen receptors, you can decrease the growth rate (hormone therapy)
What is HER2 and how does it contribute to the prognosis of breast cancer?
It is a growth factor receptor not normally present on cells but in breast cancer can be expresed, leading to increased dysplasia
How is the tumor studied?
By looking at the TNM, angiogenesis, receptors, and genetic mutations
What is the level of estrogen receptors like in progressed breast cancer?
Lower (become more undifferentiated)
Where is the greatest frequency of location of malignant breast cancer tumors?
Upper outer quadrant of breast
What is a mammography for?
To detect small tumors
What is done once a mammography detects small tumors?
Fine needle aspiration cytology (removal of a small number of cells from the lump) is done to get more information
What is usually done to remove the breast cancer?
A lumpectomy
What is a sentinel lymph node?
The lymph node that drains the particular tissue
How is the sentinel lymph node detected for removal in order to minimize invasiveness of the surgery?
A tracer is injected into the tumor and the node it travels to is detected and removed
What is tomoxifen?
A drug that blocks the estrogen reeceptor (preventing the synthesis of particular proteins)
What is herceptin?
A monoclonal antibody that can block the HER2 GFR that is overexpressed in breast cancer
What does herceptin allow?
Growth of the tumor to slow allowing the use of other treatments to be more effective in order to possible cure the cancer
What is a possible reason why rates of breast cancer and prostate go together?
There is possible a correlation with dietary fat and the development of breast cancer/prostate cancer
Why is hormone replacement therapy (used to treat osteoporosis and cardiovascular disease) a problem?
People have an increased risk of breast cancer
What are other risks for breast cancer development?
Obesity, alcohol consumption, lack of exercise, weight gain (post menopausal)
What shape of abdominal adipocytes is indicative of a higher risk of breast cancer?
Apple shape
How does age of getting BC correlate with progrnosis?
The younger, the worse the prognosis
Which genes, if defective, involve an increased risk of breast and ovarian cancer?
BRCA1 and 2
What is the role of BRCA1 and 2?
DNA repair
What are some symptoms of male breast cancer?
Lump and nipple discharge
Where is the prostate located?
Base of bladder and surrounds the urethra
What type of symptoms involve with prostate problems?
Symptoms involving the urinary tract
What change in the cells is normal in males within the prostate?
Hyperplasia (the number of cells increases)
Why does BLADDER hypertrophy occur in prostate cancer?
Nodules form in the prostate, causing the prostate to be enlarged, which compresses the urethra and causes difficulty urinating, and the bladder has to work harder to compensate
When would a diverticulum form?
A diverticulum (buldge) would form in the bladder if the compression onn the urethra is severe
What does it mean if androgen receptors are still present in the prostate when diagnosing?
There is a better prognosis
What is a transurethral prostatectomy? (TURP)
Go in through the urethra and remove excess tissue and study to make sure its not malignant (benign)
What can prostate cancer occur simultaneously with?
Benign prostatic hyperplasia
Which bones are the main targets of prostate cancer metastasis?
Bones in pelvis and vertebrae
Why does metastasis to the pelvic plexu so easily cause metastasis to the vertebral system?
In the pelvic plexus region there is an absence of valves
How is stage A prostate cancer treated?
Through transurethral recection
What are common therapies for stage B cancer (when a lump is detected)?
-Hormonal therapy
-Anti-androgen therapy
-Chemotherapy
-Brachytherapy
How does anti-hormonal therapy target the increased testosterone production in prostate cancer?
The pituitary/testicular axis may be interupted
Why is decreased testosterone production helpful following anti-hormonal therapy?
Interupts action of testerone on androgen receptors in the prostate, decreasing tumor growth
How does blocking 5-alpha reductase ameliorate the situation of increased testosterone?
5-alpha reductase is responsible for converting testosterone to DHT (active form). Therefore testosterone cannot exert its function (unable to act on receptor)
Why is chemotherapy used in prostate cancer?
Chemotherapy kills tumors directly
What is brachytherapy?
Inserting radioactive pellets at the site of the tumor, targets just the tumor and doesn thave any systemic effects
What is characteristic of the undifferentiating pattern in prostate tumors?
Carcinoma grows so slowly and it appears highly differentiated for a long period of time
What is prostate specific antigen and what is it used for?
It is regulated by androgens and secreted into the circulation. Since there is a higher level of testosterone secreted by the testes in prostate cancer (androgen) there will be higher levels of PSA in circulation and this is predictive of prostate cancer
Which molecules are thought to be protective against prostate cancer?
Selenium and Vitamin E
At what point (how many divisions) can the tumor be detected?
30 doublings of the cell
What is the weight of this tumor?
1 g
What is the problem that you can only detect the tumor at 1 g?
Microscopic metastasis may have already occured
Which normal cellular phenomena have tumor cells lost?
Contact inhibition
How are cancer cells able to avoid this contact inhibition?
They have abnormalities in cell contact sites and surface antigens
What is a correction of a misconception about tumor cells?
They do not have an appreciably shorter cell cycle time
What proportion of tumor cells are actively dividing?
Less than 1/2
What is the difference between malignant and benign tissue considering apoptosis of progeny cells?
In malignant tissue, MOST progeny cells die but not ALL of them. Only a fraction needs to survive for the tumor to grow continuously
How does angiogenesis affect tumor size?
Once the tumor starts to make angiogenesis factor, the growth rate increases dramatically
To what point can a tumor grow before it induces angiogenesis?
2 mm
How does GF increase tumor growth?
Tumors can upregulate GFR as well as produce GF to stimulate itself and neighbours
What does the immune system recognize when it targets tumor cells?
Abnormal antigens produced by tumor cells
What are some of these altered antigens?
Compounds that aren't found normally like altered carbohydrates, mutated proteins. oncofetal antigens
What are oncofetal antigens?
Antigens that are NORMALLY only present in fetal cells
What are three reasons why the immune system doesn't work properly to get rid of cancerous cells?
-Low antigenecity
-Antigenic modulation
-Tumor-induced immune suppression
How does the tumor cell manifest low antigenicity?
Some cancers express anigens that are NOT perceived as abnormal by the immune system
What is an example of antigenic modulation?
The tumor cell can control the immune response, for instance by internalizing antibodies, preventing T cell activation and cytotoxicity
What is an example of a mechanism of tumor-induced immune suppression?
Tumor cells can produce cytokines such as TGF-beta that will inhibit cytotoxic T cells or activate suppressor T cells
What is immune therapy?
Use of our immune system in a strategic way to treat tumors
What are some examples of immunotherapy?
-Chimeric monoclonal antiody to attract macrophages
-Monoclonal antibody with a toxin conjugate
-Radiolabelled monoclonal antibody
-Enzyme coupled Ab that converts prodrug to drug
What is carcinogenesis related to?
How certain genes control cell proliferation and cell death
What are the three steps of cellular carcinogenesis?
1-Initiation
2-Promotion
3-Progression
What is the initiation stage of carcinogenesis?
Cellular DNA is damaged irreversibly and this results in a mutation in the genome
What does the mutation in the DNA genome give to the tumor cell?
A growth advantage over other cells
What is the promotion stage of carcinogenesis?
There is selective expansion of the initiated cells which means that the mutations in the initiated cells allow them to grow faster
What is the progression stage in carcinogenesis?
Preneoplastic cells develop into tumors
What mechanism is evaded when these pre-cancerous cells progress to cancer?
Induction of apoptosis due to protective mechanisms
What are oncogenes?
Mutations in genes that normally regulate cell growth
How do oncogenes change the cell?
They make the cell hyperactive and it is able to divide continuously
What is a proto-oncogene?
A normal gene that CAN become an oncogene through a mutation
What are some ways that a proto-oncogene is activated and classified as an oncogene?
-Person is born with mutation
-Point mutation/deletion/insertion
-Gene amplification
-Chromosome rearrangement/translocation
How can chromosome rearrangement result in an oncogene production?
Gene fusion can cause the formation of an abnormal protein that the body doesn't normally make
How can gene translocation result in an oncogene?
If the gene moves to a chromosome in an environment that promotes its hyperactivation
What is an example of a cancer that results from the formation of an oncogene because of gene translocation/fusion?
Chronic myelogenous Leukemia
What happens in chronic myelogenous leukemia?
Part of chromosome 22 is replaced with part of chromosome 9
What is this chromosomal abnormality refered to in CML (Chronic Myelogenous Leukemia)?
Philadelphia chromosome
What is the name of the oncogene in CML (chronic myelogenous leukemia)?
abl oncogene
What is the name of the abnormal protein formed in CML (Chronic myelogenous leukemia)?
Abnormal protein (BCR-ABL)
What leads to Burkitt's lymphoma?
The fusion of c-myc with genes
What does c-myc gene fusion lead to that results in Burkitt's lymphoma?
Increased transcription
What is the process of cell proliferation?
-Growth factors act on receptors on PM
-Growth factor receptors induce a signalling cascade
-The signal transduciton leads to increased transciption
-This leads to protein production and progression of the cell cycle
What can oncogenes encode for that stimulate cell growth?
-Growth factors
-Growth factor receptors
-Proteins that alter signal transduction
-Proteins in the nucleus that alter DNA
How does oncogene encoding for GF lead to increased proliferation?
This leads to a constant stimulus for cell division
How does oncogene encoding for growth factor receptors result in increased proliferation?
This increases the chance that the cell will be activated
How does oncogenes encoding for proteins that alter signal transduction lead to increased cell proliferation?
If they encode a protein in the signalling pathway this leads to a constant activation of signal transduction even in the case of a lack of growth factor signal
How can we determine the exact mutation that resulted in the formation of the tumor?
-Biopsy the tumor and check for the exact mutation that caused the cancer using DNA microarrays
What happens when Ras is transformed into an oncogene?
The GTP on Ras cannot be hydrolyzed to GDP and thus you have constitutive activatin and the signal transduction pathway is always on
What can the overexpression of cyclins/CDKs result in?
Continual cycling of the cell
What is Bcl-2?
An anti-apoptosis gene that is commonly found in cancer cells
Which type of cancer commonly has a mutated version of Ras?
Pancreatic cancers
What happens when one of the two alleles encoding pro-oncogenes is mutated?
You get formation of the tumor because you have an abnormal protein
What happens when you lose one of the two alleles encoding tumor suppressor genes?
You can still get tumor suppression since the remaining allele is still encoding function tumor suppressor protein
How must tumor suppressor genes be affected to lead to cancer?
You must have a knock out of BOTH alleles
What can tumor suppressor genes act on?
Growth factors, growth factor receptors, signal transduction, or in the nucleus
What happens to tumor suppressor genes when someone is exposed continually to a carcinogen such as in cancer?
-The 1st allele of the tumor suppressor gene can get knocked out, and after some time so can the second allele
What is retinoblastoma (Rb) gene?
A tumor supressor gene
What happens when Rb is non functional?
You get destruction of the eye
What is hereditary Rb?
A person is born with one mutated Rb allele and are thus at a greater risk for developing cancer
What is sporadic Rb?
A child is born healthy and gets both Rb alleles mutated
-There is a smaller chance of getting both alleles mutated
How does Rb work?
It attaches to a TF and binds to DNA to block transcription
How can this repression by Rb be relieved?
THrough phosphorylation, allowing cells to go from G1 to S
What is Rb phosphorylated by?
cyclins/CDKs
What is p16?
A tumor suppressor gene that inhibits CDK (CDKs permit the continuation of the cell cycle)
Which tumor suppressor gene is on chromosome 11?
Nephroblastoma
Which tumor suppressor gene is on chromosome 5?
APC
Which cancer is APC involved in?
Colon cancer
What does loss of APC result in?
Elevated transcription
What is the normal function of APC?
Regulates beta-catenin
What is beta-catenin?
A transcription factor
How does APC regulated beta-catenin?
It binds to beta-catenin, lowering cell proliferation
How is beta-catenin normally released?
When GF binds its receptor, this promotes beta-catenin release from APC
How is beta-catenin released when there is a mutation in APC?
There is the spontaneous release of beta catenin, allowing the cell to proliferate without growth factor
What does APC stand for?
Adenoma polyposis coli
What is p53?
A tumor suppressor gene whose mutation is characteristic of many cancers
What is the role of p53?
Cell reproduction
What is p53 activated by?
Stress
What are some examples of stressors that activate p53?
Carcinogens, UV, cytotoxic poisons, changes in the environment, extremes of temperature, lack of O2, nutritional deficiencies
What are the two things that p53 can do upon activation during stressful conditions?
-It can stop cell division allowing time for repair
-It can trigger apoptosis
How does p53 ensure that cells do not have DNA mutations?
It either induces apoptosis under the case of high DNA damage, or gives time for small DNA damage to repair
What happens when p53 is mutated?
The cell divides even when there is DNA damage
What is p21?
The target gene of p53 that induces cell arrest to allow for DNA repair
What is the DNA repair that is activated by p53?
GADD45
In what form does p53 act?
As a tetramer
In what codons of p53 do most mutations occur?
175, 248, 273
What component of cigarettes causes alot of the mutagenesis?
Benzo-a-pyrene
What does mutation of p53 result in in cancer cells?
Clonal expansion
What is Li-Fraumeni?
A medical condition where a person has multiple tumors in the body due to p53 mutation
What is the difference between mutations of p53 in glioblastoma and low-grade astrocytoma?
There are more p53 mutations in higher grade brain cancers like glioblastoma compared to lower grade cancers like low-grade astrocytoma
What is BRCA?
Defective DNA repair gene
How is DNA damage eliminated?
Mismatch repair
What percentage of peope with breast cancer have the BRCA mutation?
5%
What controls the variation of protein expression?
Epigenetic changes
What are "epigenetic changes"?
The gene sequence is unchanges but that proteins that bind and control DNA expression are controlled
What are epigenetic targets used for in cancer?
To understand cancer, to look for early detection methods, to consider targets of therapy
What do epigenetics control?
Apoptosis, tumor cell properties, growth and metastasis of cancer
What is the major epigenetic change that can silence gene expression?
Methylation
Where does methylation typically occur?
On cytosines in C-G base pairs
What does methylation of DNA do?
Silences gene expression
How can hypomethylation lead to cancer?
Overexpression of growth factors or oncogenes, alterations in DNA repair enzymes
How can hypermethylation lead to cancer?
Silencing of tumor suppression genes
What are miRNAs?
Small, noncoding RNAs that can bind and alter protein production
How long are miRNAs?
Typically 20 bp long
How are miRNAs synthesized?
As pre-miRNA
How is miRNA activated and what happens to it once it is activated?
The active part is cleaved and this allows it to travel to the cytoplasm
What type of effects can miRNA have in the cytoplasm?
It can bind mRNA leading to either silencing of protein expression (translation) or destruction of mRNA
How is miRNA activated and what happens to it once it is activated?
The active part is cleaved and this allows it to travel the cytoplasm
What type of effects can miRNA have in the cytoplasm?
It can bind mRNA leading to either silencing of protein expression (translation) or destruction of mRNA
What does this targeting of mRNA by miRNA result in?
Interuption of tumor suppressor genes resulting in abnormal oncogene production
What is a possible therapy to consider when looking at miRNA influence on development of cancer?
Can make a counterproduct that will bind and destroy miRNA that prevents its inhibitory effect on the mRNA of tumor suppresor genes
What are some properties that tumor cells have that quiescent cells in the region do not?
Promotion of angiogenesis, synthesis of enzymes that destroy the ECM, ability to recruit immune cells to the region of tumor
What type of effect do tumor cells have on actin bundles and what does this result in?
A tumor cell can use proteases to disrupt adhesion caused by certain proteins that anchor actin bundles. This allows the cells to move
What are some general ways that tumor cells increase cell motility?
Increasing the production of cytoskeletal proteins
How does tyrosine kinase activity in some oncogenes allow cell motiltiy?
They can phophorylate proteins holding the cell in place, which allow it to move away
How does a tumor progress from carcinoma in situ to stage 1 of invasion?
There are proteases secreted by the tumor cell that dissolve the basement membrane so the tumor can move and metastasize
How does chemical exposure lead to cancer?
Chemicals promote the formation of DNA adducts (DNA bound to cancer causing chemical)
How does radiation result in cancer?
Radiation results in the production of free radicals that damage DNA
What is an example of a virus that results in cancer production?
HPV (Human papilloma virus)
What is an example of a virus that results in cancer production?
HPV (Human papilloma virus)
What is an important example of a virus that causes cancer?
HPV (Human papilloma virus)
What are high antibodies against HPV correlate with?
A higher rate of cervical cancer
How does cancer result upon HPV infection?
An HPV protein inactivates tumor suppressors Rb and p53
What does HBV cause?
Hepatocellular carcinoma
What does EBV cause?
Burkitt's lymphoma
What is required for EBV causing Burkitt's lymphoma?
Coinfection with malaria
How does the mechanism of cancer development by EBV/malaria coinfection?
EBV initiates the B cell and the malaria triggers the continual turnover of B cells
How does the EBV virus promote cancer development?
A viral promoter inserts itself next to a host proto-oncogene and tursn it into an oncogene
What does CMV result in?
Kaposi's sarcoma
What does HTLV-1 cause?
T cell leukemia
What type of damage can free radicals (induced by radiation) have on the DNA?
Translocations, deletions, mutations, etc
Why is chronic inflammation considered a high risk for cancer?
Phagocytic cells release free radicals
How does radiation selectively kill tumor cells?
Normal cells can recover better because they have DNA repair enzymes
What is cryotherapy?
Freezing the tumor
What type of cancer is cryotherapy affective against?
It is performed in the liver if the tumor is small and accessible
How does immunotherapy work to eliminate the tumor?
Use a drug linked to an antibody that specifically targets tumor antigens (can use multiple Abs for multiple Ags)
Why is Burkitt's lymphoma sensitive to chemo?
Chemo targets cells that are rapidly dividing, and in Burkitt's lymphoma the tumor is growing rapidly
What types of cells is a tumor composed of?
Dividing cells, non-dividing and some dead cells
Why are body parts like the skin, intestine and hair affected by side affects of cancer treatment?
Therapy targets cells that are rapidly dividing and causes apoptosis, and these cells have a high turnover rate
Why do people being subjected to cancer therapy typically get GI problems?
From each villus, we shed over 1000 cells per day (high turnover)
What is another name for Gleevec?
STI571
What does Gleevec treat?
Chronic Myelogenous Leukemia
How does Gleevec treatment of chronic myelogenous leukemia work?
It blocks the ATP supply of the abnormal protein BCR-ABL so it cant function
What can monoclonal Ab be linked to in treating cancer?
Cytokines, radiactive compounds, toxins, etc
What does inhibition of angiogenesis do?
It helps diminish the tumor but might not completely cure the cancer
What is an important enzyme in inflammation that can be targeted for anticancer therapy?
Cyclooxygenase
Where is Burkitt's lymphoma present?
In areas where malaria is endemic (EBV + malaria=BL)
Where is stomach cancer prevalent?
Japan
Where is colon cancer prevalent?
North America
What are some causes of stomach cancer?
Infection, Diet
How can one determine the carcinogenicity of a compound?
Through the Ame's test
What is important to consider when looking at carcinogen potential of a compond?
At what concentration it is carcinogenic
What are the three main causes of Cancer in canada?
Tobacco, high fat diet and alchohol
Why have stomach cancer rates decreased?
Because of increased use of preservatives, which decrease toxins in foods