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441 Cards in this Set
- Front
- Back
What is neoplasia?
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A term for cancer that means "new growth"
|
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What are the most common types of cancer in childreN?
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Leukemia and brain/CNS tumors
|
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What is different about the mortality fraction and the number of people with cancer?
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While the number of people with cancer is increasing (because there are MORE people!) the fraction of mortality is DECREASING
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What is the most common cancer for females?
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Breast cancer
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What is the most common cancer for males?
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Prostate cancer
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What is the highest KILLER cancer?
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Lung (prostate and breast have higher survival though they have a higher incidence!)
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What percentage of breast cancer patients have hertiable genetic traits linked to breast cancer?
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5%
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What are the two types of tumors?
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Malignant and benign
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What is the difference in the cancerous abilities of benign tumors and malignant tumors?
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Benign tumors are NOT CANCEROUS
Malignant tumors are CANCEROUS |
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Out of the two types of tumors, which is life threatening?
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Malignant
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How fast do benign tumors grow?
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Slowly
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How fast do malignant tumors grow?
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Fast
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How do benign tumors affect other tissues?
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Benign tumors do NOT dessimate or invade other tissues
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How do malignant tumors affect other tissues?
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They will invade and destroy other tissues through metastasis
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What is metastasis?
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The spread of the disease from an organ to another that is non-adjacent
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What are the morphological properties of benign tumors?
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They have a distinct round shape with a capsule
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What are the morphological properties of malignant tumors?
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They are crab shaped, with arms spreading to other tissues, and do not have a capsule but rather blood vessels growing into the tumor
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In what direction is the growth of a benign tumor?
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Outwards (into the lumen of the tissue)
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In what direction is the growth of a malignant tumor?
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Inwards (down into the tissue)
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What does the benign tumor look like when you open it up?
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Homogenous
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What does the malignant tumor like when you cut it up?
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It is heterogenous
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Why is a malignant tumor heterogenous?
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Cell necrosis in the center
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What do the individual cells of the benign tumor look like?
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Normal looking like their cell of origin
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What do the individual cells of the malignant tumor look like?
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Haphazard rearrangement (poor geometry)
Pleomorphic (many sizes and shape) |
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What type of mitosis do benign tumor cells undergo?
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Low rates, and get normal appearance in cells that do divide
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What type of mitosis do malignant tumor cells undergo?
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Rapid mitosis with irregular results
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Do benign tumor cells retain parental cell function?
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They may retain some of the function
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Do malignant tumor cells retain parental cell function?
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No- there is little evidence of normal or specialized cell function at all
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How is the prefix of a tumor name done?
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The prefix is the type of tissue the tumor originated in
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How is the suffix of a tumor name done?
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Whether it is benign or malignant
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What does adeno mean?
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Gland
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What does angio mean?
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Vessels
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What does chondro mean?
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Cartilage
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What does fibro mean?
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Fibrous tissue
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What does hemangio mean?
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Blood vessels
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What does lymphangio mean?
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Lymph vessels
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What dose lipo mean?
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Fat
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What does myo mean?
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Muscle
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What does neuro mean?
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Nerve
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What does osteo mean?
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Bone
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How is the suffix named for benign tumors in the epithelial tissue?
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"oma"
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What is the suffix for malignant tumors in the epithelial tissue?
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"carcinoma"
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What is the suffix for benign tumors in the connective tissue?
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"oma"
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What is the suffix for malignant tumors in the connective tissue?
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"sarcoma"
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What is the "connective tissue" that would have a sarcoma name?
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Fibroblasts, fat, bone, cartilage, or endothelium
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What is a teratoma?
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A tumor that contains multiple cell types
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Out of all the cell adaptions, which is considered a risk for cancer?
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Dysplasia
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How can dysplasia lead to cancer?
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If the stimulus is not removed, it can progress to anaplasia, then to invasion
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What happens after the development of a malignant tumor?
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The cells become more disorganized, fragmented
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What is the stage after malignant tumor?
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Carcinoma simplex
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What is the stage after carcinoma simplex?
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Anaplastic carcinoma
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What is characteristic about anaplastic carcinoma?
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It is almost impossible to distinguish where the cells came from
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How can one determine how organized the tissue cells are to make an accurate prognosis?
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Culture cells in vitro and expose them to carcinogens, enabling us to see cancer progress
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What is the main problem with benign tumors?
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They can cause pain by COMPRESSION of nearby tissues
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Where would this compression by benign tumors be problematic?
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-Tumors in the brain
-TUmors in the esophagus buldge into lumen causing dysphagia |
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What is dysphagia?
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Difficulty swallowing
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How can benign tumors lead to infection?
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By obstructing openings or ducts in tissues
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What is an example of a tumor that imitates parent cell function?
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Neuroendocrine tumors can SECRETE SUBSTANCES (adrenaline)
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What types of effects do both benign and malignant tumors have?
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-Obstruction of ducts/important tissues
-Infection -Cachexia (though to a lesser extent in benign) -Paraneoplastic syndromes -Immunosuppression |
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What occurs during cachexia?
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Person loses appetite, metabolic rate increases, and they waste away to skin and bones
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What are paraneoplastic syndromes?
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The tumor secretes abnormal compounds into the system
|
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What type of additional effects do malignant tumors have?
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-Destruction of tissue
-Haemorrhage (eroding blood vessels or continual bleeding) -Metastasis to vital organs |
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What are "systemic effects of malignant tumors"?
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These effects are in addition to the effects of the original tumour itself at any metastatic sites
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What is a papilloma?
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Simple, benign EPITHELIAL tumour
|
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What is a papilloma caused by?
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It is a wart: caused by a viral infection
|
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What does a papilloma consist of?
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Fibrous tissue core surrounded by hyperplastic squamous epithelium
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What is a squamous cell carcinoma?
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A malignant tumor of epithelial origin
|
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How do squamous cell carcinomas begin?
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It starts as a small papular mass that invades the epithelium below it
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What is characteristic of squamous cell carcinoma after it breaks thorugh the epithelium?
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A charcteristic fibrous ulcer is produced on the surface
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What is a "polyp"?
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A benign tumor in a gland (Adenoma)->they project out into the lumen on stalks
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What are characteristic of adenocarcinomas?
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Irregular craters on the surface with characteristic, undifferentiated cells
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What is a lipoma?
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A connective tissue tumor that is benign, fat
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What is the appearance of a lipoma like?
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Lobular, yellow in colour, encapsulated and contains normal-looking adipocytes
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What is a liposarcoma?
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A malignant connective tissue tumor that begins in fat cells
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What is characteritic of liposarcomas?
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Coarse emulsion of lipids, pleomorphism, and invasion of surrounding tissues
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What are myomas and osteomas?
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Examples of connective tissue tumors (benign)
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What is an osteogenic sarcoma?
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A malignant tissue tumour, metasticizes quickly, and causes alot of damage to the bone of origin
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What is a local invasion?
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After a primary cancer starts, will invade the tissue beneath it
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What is a carcinoma in situ?
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When a cancer has not yet gone through the basement membrane - can cure cancer at this stage
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How can a cancer spread away from its site of origin?
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It gets into the lymphatics or blood after invading the local tissue
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What is a regional tumour?
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When the tumor invades through the basement membrane - if caught early can still correct but possibility that it went to other organs
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How do we get cells that are metastatic?
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-Cancerous cells are genetically unstable, eventually get a heterogenetity between cells in the tumor and eventually get a sublcone that is metastatic
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Why are these metastatic subclones able to get into the circulation?
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They are motile, can eat through connective tissue and basement membrane, into a blood or lymphatic vessel
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How do cancer cells attach to its surroundings?
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They have receptors for laminin
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What does laminin provide for the cell?
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The laminin is bound to type IV collagen (cancer cell also makes laminin so it can bind!!)
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What happens once cancer cells are bound?
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THey release type IV collagenases which will DISSOLVE the type IV collagen found in the basment membrane
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What happens once the cancer cell releases these collagenases?
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It passes through (invades) the hole it has created into the tissue
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What happens once the cancerous tissue gets into the stroma?
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It has receptors for and binds to FIBRONECTIN in the stroma
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What happens once the cancer cells bind the fibronectin on the stromal cells?
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It can release enzymes and dissolve the connective tissue stroma
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How do tumour cells have motility?
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They release autocrine motlilty factors which will act back on the cells in an autocrine manner
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Why do some malignant tumors get areas of necrosis at the center?
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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
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What are other ways cancer cells can spread?
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-Via perineural spaces (along nerves)
-Laterally along the basal layers of the skin epithelium |
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What happens when cancer cells get into the lymphatics?
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They spread to lymph nodes and can completely occlude them, reversing the flow of lymph and directing the malignant cells elsewhere
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How can the lymph nodes help you see how far along the cancer is?
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-The lymph nodes closes to their tissue origin will be first affected
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Why are tumor cells able to penetrate veins more easily?
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They have thinner walls
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What are common sites that the cancer will metastacize to?
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Bones, liver, cerebrospinal fluid and the adrenals
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Where do sarcomas tend to spread?
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To the venous system
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Why do sarcomas tend to spread to the venous system?
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The tissues in which they originate (connective tissue) are well upplied with vasculature
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Where do carcinomas tend to spread?
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To the lymphatic system
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What happens if a tumor embolus gets into the portal circulation?
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It will pass into the liver quite quickly
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What happens if the tumour embolus gets into the systemic venous system?
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Metastasize to the heart and lungs
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What happens if the tumour cell gets into the pulmonary circulation (from lung tissue)?
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Mestastasizes to the heart and then to the general circulation
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Where will cancer in the small intestine tend to metastasize?
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To the liver
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Why can tumor cells easily invade areas such as the spinal veins?
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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
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Where does prostate cancer tend to metastasize to? (characteristic pattern)
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Bone
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What is the characteristic pattern of metastasis of colon cancer?
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To the stomach
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What is the characteristic pattern of metastasis of breast cancer?
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To the lung
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How does hterogeneity cause problems for cancer treatment?
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Cancer cells that metastasis are prne to getnetic mutations and are thus harder to get rid of
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What is tumor angiogenesis factor?
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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
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What is the TNM system?
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A way to evaluate the extent of the tumor
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What does T stand for?
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Tumour
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What does N stand for?
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Lymph nodes
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What does M stand for?
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Metastasis
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What does the TNM system evaluate?
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The state of the original tumour, whether lymph nodes are involved, and whether or not there is metastasis
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What is survival rate related to?
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Lymph node involvement
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What is the score of the primary tumour (T) based on?
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How large it is and to what extent it has invaded into the other tissues
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What would the T be for in situ carcinoma?
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Tis
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What is the highest level of N?
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3
|
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At what stage is cancer typically diagonosed?
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Rarely at the in situ stage, typically when the cancer is localized but a fraction has begun to metastasize
|
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How are tumor grades based?
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On the level of differentiation
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What does a high tumor grade mean?
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The less differentiated the tissues are, lower survival rate
|
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How can we gauge how far along a cancer or tumor is?
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By the degree of disorganization
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Where do cancer cells originate from?
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Not completely differentiated cells
-Froms omewhere along the pathway from stem cell to specialized cell |
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What happens if the mutation occurs to a cell that is early in the pathway of a stem cell to special cell?
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It is poorly differentiated -> more malignant and metastasize rapidly
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How can you identify what type of cancer you have once the cells are so undifferentited?
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Use immunohistochemistry with specific marker anti-Abs
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How can you check for abnormalities in the DNA?
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Comparing DNA with cancer cells to normal cells using flow cytometry to look for abnormal peaks
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What is cytology a basis for?
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The pap smear to test for cervical cancer -> it is looking at individual cells for abnormalities
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Why can the blood be analyzed to diagnose a tumor?
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Tumors secrete different factors into the blood
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What are some other methods used to diagnose tumors?
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X-rays and imaging
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How does smoking cause cancer?
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Cigarettes have thousands of chemicals that over time, develop enough mutations to turn into malignant cells
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At what point could you cure someone with lung cancer?
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At the point where the cancer cells havent mutated enough to metastasize
|
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What are the five stages of cancer?
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-Metaplasia
-Dysplasia -Anaplasia -Invasion -Metastasis |
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What happens during metaplasia in lung cancer?
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Ciliated columnar cells are replaced by a thick layer of squamous cells
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What happens during dysplasia in lung cancer?
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There are an accumulation of mutations that lead to abnormal cells
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What happens during anaplasia in lung tissue?
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Carcinoma in situ
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What happens during invasion in lung cancer?
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There is erosion through the BM and surrounding tissue
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What is large cell carcinoma?
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Undifferentiated type of tumor
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What is small cell carcinoma?
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A neuroendocrine type of tumor
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What is an adenocarcinoma?
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It is a tumor originating in the glandular tissue
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What is squamous carcinoma?
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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
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Where are small cell and squamous cell carcinomas located?
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Centrally located near the main bronchi
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Where are large cell and adenocarcinomas located?
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They are peripherally located
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What is bronchoscopy?
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A procedure used to look for abnormalities in the airways
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How could you diagnose a tumor based on the examination of sputum?
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Centrally located tumors often shed their cells and are then found in the sputum
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What percentage of lung cancers can be attributed to large cell carcinoma?
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15%
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How does large cell carcinoma tend to spread?
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Through the lymph nodes and distant organs by the time it is detected
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Which type of lung cancer has the worst prognosis?
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Small cell lung cancer
|
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Which types of lung cancer have the better prognoses?
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Squamous cell and adenocarcinoma
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Which lung cancer has the best prognosis?
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Squamous cell carcinoma
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What does a biopsy of the tumor determine?
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The origin and extent of invasion
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What does N1 mean?
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Nodes are affected just in the region of the cancer
|
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What does N2 mean?
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Nodes are affected on the other side of the region of the cancer (greater involvement)
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What does "regional" lung cancer mean?
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Lung and lymph nodes, but no metastasis
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What does "distant" lung cancer mean?
|
Lung, lymp nodes, and metastasis
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What is a wedge resection?
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Removing a small mass via segment resection
|
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What is a lobectomy?
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Removal of an entire lobe of the lung
|
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What is a pneumonectomy?
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Entire lung removal
|
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What percentage of lung cancer patients survive?
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10%
|
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What are some local effects of lung cancer?
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-Obstruction
-Dilation of bronchus -Pleural effusion -Hameoptysis -Metastasis to lymph nodes |
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What does obstruction lead to?
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Vulnerability to distal infection due to inefficient clearance
|
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What is pleural effusion?
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Fluid in the pleural space
|
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What is haemoptysis?
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Coughing up blood
|
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What can cause haemoptysis?
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Damage and surrounding tissues
|
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What are the distal effects of lung cancer?
|
Cerebral metastases
Bone metastases Liver metastases Finger clubbing Inncreased ACTH release Increased ADH release Cachexia |
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What does increased ACTH release during cancer result in?
|
Increased endocrine effect
|
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What does increased ADH release during cancer result in?
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Increased sodium retention
|
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What is cachexia?
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Loss of appetite and weight loss, patient wastes away
|
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What are the classic symptoms of lung cancer?
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Cough, chest pain, coughing blood, chest infection, malaise, weight loss, shortness of breath, hoarseness (if larynx affected), distant spread
|
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What happens if the tumor grows into the thoracic cavity (outside the lung)?
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-Tracheal obstruction
-Esophageal compression -Hoarseness -Lymphatic obstruction -Obstruction of vena cava |
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Why does hoarseness result?
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The tumor affects the larynx
|
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What does lymphatic obstruction result in?
|
PLeural effusion
|
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What does obstruction of the vena cava result in?
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Impaired venous return to the heart
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What is the route of tumor spread from the lung?
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-Local invasion
-Transcoelom spread -Blood-borne spread -Lymphatic spread |
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What happens during local invasion of the tumor from the lung?
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The tumor extends into lung tissue
|
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What happens during transcoelom spread?
|
The tumor migrates along the pleural space
|
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What happens during blood-borne spread?
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Tumor enters draining veins and cells enter the systemic circulation
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WHat happens during lymphatic spread?
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TUmor extends along the pulmonary lymphatic vessels
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What are three common sites of metastasis of lung cancer?
|
Brain
Bone Liver |
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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
|
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Which cancers tend to metastasize to the bone?
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Breast, prostate, kidney, bronchus, thyroid gland, GI and reproductive cancers
|
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Which sites are particularly sensitive to bone metastasis?
|
Proximal portion of long bones
Ribs, skull, and vertebrae |
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Besides smoking, what are two other main causes of lung cancer?
|
-Carcinogens
-Radon |
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What are some carcinogens that cause lung cancer?
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Fossil fuels, asbestos, arsenic, chromium, soot, tars, oils
|
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What is radon?
|
Decay product of uranium that is a volatile gas
|
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What is radon?
|
Decay product of uranium that is a volatile gas
|
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What is colorectal cancer?
|
Cancer of the large intestine or the rectum
|
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What is colorectal cancer?
|
Cancer of the large intestine or the rectum
|
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Which cells become mutated in colorectal cancer?
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Cells in the base of the crypts
|
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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
|
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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 |
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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
|
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What does the adenocarcinoma in colorectal cancer cause?
|
Ulcers and bleeding on the surface and constriction of the colon
|
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What is stage 0 of colorectal cancer?
|
Carcinoma in situ that can be detected (in some cases)
|
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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
|
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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
|