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55 Cards in this Set
- Front
- Back
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Tumor‐specific antigens
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Molecules that are unique to cancer cells
eg. BCR-ABL Path-Neo4-ppt-6 |
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Tumor‐associated antigens
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Molecules shared by normal cells and cancers of the same type, but which are expressed differently on tumor cells.
Prostatic Acid Phosphatase Path-Neo4-ppt-6 |
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Prostatic Acid Phosphatase
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a Tumor‐associated antigen: shared by normal cells and cancers of the same type, but which are expressed differently on tumor cells.
Path-Neo4-ppt-6 |
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BCR-ABL
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a Tumor‐specific antigen (unique to cancer cells)
Path-Neo4-ppt-6 |
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α‐fetoprotein
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Onco-fetal type Tumor Associated Antigen
Path-Neo4-ppt-6 |
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CEA
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Onco-fetal type Tumor Associated Antigen
Path-Neo4-ppt-6 |
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MAGE family
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Cancer Testis Antigens
Tumor Assicated Antigen Path-Neo4-ppt-6 |
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CD20 & Cancer
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Differentiation type Tumor Associated Antigen in in B cell lymphoma
Path-Neo4-ppt-6 |
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Her2/neu
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Overexpression type Tumor Associated Antigen
Path-Neo4-ppt-6 |
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MUC
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Altered cell surface glycolipid type Tumor Associated Antigen in Breast Cancer
Path-Neo4-ppt-6 |
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What are the antitumor effector mechanisms that may be involved in tumor immunity.
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CD8+T Lymphocytes (Most Important)
NK Macrophage (ROS's) Antitumor Antibodies not useful Path-Neo4-ppt-11 |
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Principal mechanism of antitumor immune activity
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CTLs (CD8+)
Path-Neo4-ppt-11 |
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Antitumor Antibodies
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No effective humoral immunity
Antibodies are commonly formed: ‐ may cause paraneoplastic syndromes ‐ may be detected by blood tests (early dx in future) Theraputic Ab's have been developed --anti‐Her2 / neu --anti‐EGF --many more Path-Neo4-ppt-13 |
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What is the status of the immune system by the time cancer is diagnosed?
What are the mediators of this? |
immunosuppression
‐ switch from TH1 to TH2 response ‐ immunosuppressive cytokines: TGF‐Beta, IL10 ‐ immunosuppressive immune cells: Tregs, macrophages and PMNs ‐ disrupted cell signaling, eg loss of class I MHC Path-Neo4-ppt-16 |
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What are the functions of TGF‐Beta in cancer?
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• Tumor suppressor gene
• Produced by Tregs and fibroblasts in tumor stroma • In cancer: ‐ increased angiogenesis ‐ increased deposit of ECM ‐ immunosuppression Path-Neo4-ppt-20 |
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Sipuleucel‐T
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First cancer vaccine for castration‐resistant prostate cancer
• Peripheral blood mononuclear cells harvested, stimulated to replicate ‐ GM‐CSF with prostatic acid phosphatase (a tumor associated antigen) • APCs reinfusion back into patient Path-Neo4-ppt-21 |
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Myxoma
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Primary neoplasms of the heart
• Benign; uncommon • Clinical presentation ---Ball valve obstruction‐heart failure ---Fragmentation with systemic embolization ---Systemic inflammatory reaction‐fever due to IL 6 from tumor • 90% in atria; L>R by 4:1 • Sessile or Pedunculated • Myxoid (gelatinous); mesenchymal cells Path-Neo4-ppt-25 |
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hemiparesis
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Weakness on one side of the body
Path-Neo4-ppt-30 |
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What is the most common neoplasm of the heart of infants?
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Rhabdomyoma
• Rare, benign tumor or hamartoma • Occurs in infants/children‐ first year of life • May produce obstruction Path-Neo4-ppt-36 |
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Rhabdomyoma
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• Rare, benign tumor or hamartoma
• Occurs in infants/children‐ first year of life • May produce obstruction Path-Neo4-ppt-36 |
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What aggressive primary malignancy occurs in the heart?
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Cardiac angiosarcoma: aggressive; metastasizing; usually fatal
Path-Neo4-ppt-38 |
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Primary Neoplasms of Heart
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• Lipomas, anywhere w/in heart
• Papillary fibroelastoma: occur on valves, incidental at autopsy • Cardiac angiosarcoma: aggressive; metastasizing; usually fatalc Path-Neo4-ppt-38 |
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Oncomirs
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oncogenic miRNA
• Noncoding ssRNAs 22 nucleotides long • Repress gene translation or cleave mRNA • MiRNA profiling may yield diagnostic and therapeutic data about tumors • MiRNA may be used therapeutically to treat cancers Path-Neo4-ppt-42 |
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Alpha particles
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2 protons, 2 neutrons
released from radon stronly ionizing low penetration Path-Neo4-ppt-44 |
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beta particles
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electrons, eg radioactive iodine
--weaker ionization potential --deeper penetration Path-Neo4-ppt-45 |
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positron emissions
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short‐lived emissions
used for evaluating mass lesions for malignancy (PET scan) Path-Neo4-ppt-45 |
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Particle decay
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disentegrations:
--expressed in curies (Ci) or becquerel (Bq) --radiation hazard related to half life of radionuclide Path-Neo4-ppt-45 |
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rad
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dose of radiation expressed in as
energy/gram of tissue exposed Path-Neo4-ppt-46 |
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gray
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(Gy) 100 rads
Path-Neo4-ppt-46 |
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sivert
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measure of the relative biologic effectiveness x grays
Path-Neo4-ppt-46 |
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Annual permissible radiaton exposure of industry workers
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50 mSv
Chest x‐ray: 0.01 mSv Chest CT: 6‐8 mSv Path-Neo4-ppt-46 |
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Biologic factors involved in
radiation injury |
• Dose rate: divided tolerated better
• Field size: Single dose to whole body more lethal than regional doses with shielding • Cell types vary in vulnerability to radiation • Injury enhanced by hyperbaric 02; reduced by hypoxia Path-Neo4-ppt-48 |
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LD50 of Radiation
& Cancer Therapy Levels |
2.5-4 Gy
radiation cancer therapy is 40-70 Gy fractionated over weeks with shielding of non-tumor bearing tissue. Path-Neo4-ppt-48 |
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What cells are most radiosensitive?
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cells in G2, M are most sensitive to radiation injury
--Hematopoietic cells, especially lymphocytes --Germ cells: ova and spermatogonia --GI epithelium, salivary glands, skin and endothelium Path-Neo4-ppt-50 |
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Radioresistant tissues
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G0
--Bone and cartilage in adults --Muscle and peripheral nerves Path-Neo4-ppt-50 |
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Cellular Mechanisms of Radiation Injury
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• High dose of radiation: Direct DNA damage, tissue necrosis
• Intermediate dose: Direct DNA damage, kills proliferating cells • Lower dose radiation, indirect: O2‐derived free radicals cleaved from water ---may exhibit no histologic defect ---DNA damage may produce delayed effect of organ dysfunction or cancer Path-Neo4-ppt-51 |
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Types of Direct DNA damage produced by Radiation
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All kinds of types
Most Serious Damage: Double Stranded Breaks: repair via homologous recombination, or more frequently non-homologous end joining which produces chromosomal aberrations Path-Neo4-ppt-54 |
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Acute Effects of radiation injury
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Cell death in radiosensitive (G2, M phase) Hematopoietic, Germ, Epithelial
Endothelium apoptosis and cytokine release cause “burns” Damage to intestinal crypt stem cells causes GI syndrome Path-Neo4-ppt-56 |
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Chronic/Delayed Effects of Radiation
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• Vascular injury
--Fibrosis of wall with obliteration --Thrombosis --Ectatic (dilated) vessels (telangiectasia) • Ischemia of organs supplied by scarred vessels • Fibrosis: due to ischemia; loss of stem cells Path-Neo4-ppt-58 |
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Carcinogenesis from Radiation
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• Latent period of 10‐20 years
• Accident/occupational exposures • Thyroid cancer in particle emissions: atomic bomb; nuclear energy plant accident • Hiroshima/Nagasaki survivors --Adults : acute leukemias 20x more common --Children: thyroid; breast; GU and GI cancers Path-Neo4-ppt-60 |
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strontium 90
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Risk for Osteogenic Sarcoma cancer
Path-Neo4-ppt-60 |
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figure 9‐19
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Path-Neo4-ppt-64
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In utero radiation exposure
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• In utero exposure:
--Preimplantation: radiation may be lethal --Organogenesis‐ implantation to 9 weeks: malformations likely --Fetal period: 9 weeks to birth -----CNS dysfunction; underdeveloped reproductive organs; increased risk of leukemia; brain tumors Path-Neo4-ppt-65 |
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Radiation Exposure in Infants
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retarded bone growth and maturation.
CNS, teeth and eye development perturbed Path-Neo4-ppt-65 |
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Radiation Injury: Skin changes
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• Erythema day 2‐3 followed by edema, blistering; hair loss‐ early
• Late or delayed: Radiation dermatitis ---Telangiectasia from weakened vessels ---Dermal atrophy with fibrosis; hair follicles lost ---Hyper‐ or hypopigmentation ---Impaired healing; increased infections • Skin cancer up to 20 yrs. after exposure -----Basal cell carcinoma; Squamous cell ca. Path-Neo4-ppt-67 |
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Radiation Injury: Bone Marrow;
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• Acute: atrophy of bone marrow precursors
---Lymphocytopenia within hours ---Granulocytes fall at end 1st week ---Platelets lag behind granulocytes ---Anemia with heavy exposure after 2 wks. • Late or delayed ---Hypoplasia – aplasia/aplastic anemia ---Precancer ‐ Myelodysplasia ---Leukemia/lymphoma Path-Neo4-ppt-73 |
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Radiation Injury: Gonads/Reproductive
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• Permanent sterility may occur even with low dose
• Necrosis and atresia of germ cells result in testicular atrophy : permanent sterility • Fertility rates are decreased but offspring born years later are normal Path-Neo4-ppt-74 |
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Radiation Injury: Lungs
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• Early:
--Pulmonary congestion / edema from endothelial damage --ARDS • Late, months to years --“Radiation pneumonitis”: interstitial fibrosis --Primary lung cancer Path-Neo4-ppt-75 |
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Radiation Injury:
Gastrointestinal tract |
• Acute injury: Villar atrophy leads to malabsorption / diarrhea
--Mucosal ulcers may occur: nausea, vomiting, diarrhea --Susceptible to infection --Fluid and electrolyte loss • Late effects from vascular injury --Fibrosis with strictures, obstructions --Ulceration Path-Neo4-ppt-76 |
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Radiation Injury: Heart
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--Myocardial fibrosis with restrictive cardiomyopathy
--Fibrosis of pericardium with constrictive pericarditis --Accelerated atherosclerosis --Myocardial ischemia from vascular injury Path-Neo4-ppt-77 |
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Acute Radiation Syndrome
with Subclinical Exposure |
• Consequence of total body radiation
--No Sx --possible chromosomal damage may occur --Lymphocytes normal Path-Neo4-ppt-80 |
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Acute Radiation Syndrome
with mild Hematapoietic Changes |
• Hematopoietic‐ moderate decrease in lymphocytes (immediate)
--Decreased neutrophils develops in 1 day to 1 week --nonlethal Path-Neo4-ppt-80 |
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Acute Radiation Syndrome
with Severe Hematopoietic Changes |
--immediate lymphocytopenia plus
--leukopenia, thrombocytopenia with hemorrhage; epilation; vomiting --onset in 2‐6 weeks; lethal in up to 80% Path-Neo4-ppt-81 |
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Acute Radiation Syndrome
with GI involvement |
Hematopoietic findings plus:
GI symptoms in 5‐14 days: diarrhea, vomiting; fluid and electrolyte loss always lethal Path-Neo4-ppt-81 |
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Acute Radiation Syndrome
with CNS invovment |
immediate onset of symptoms (1‐4 hrs.):
vomiting, coma convulsions death w/in hours no lymphocytes Path-Neo4-ppt-82 |
