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56 Cards in this Set
- Front
- Back
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What is Cancer
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A diseased state that arises due to violations of the social rules for cells
A large group of heterogeneous diseases |
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Cancer Cells Characterized By
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Cells that DO NOT respond to environmental signals for division and death
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Initial Cancer
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Tumors canot grow beyond a few millimeteres in volume without blood supply
The body is capable of destroying cancer cells |
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How does cancer become a "Disease"
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Angiogenesis - development of blood supply for tumor growth
Metastasis - migration throughout the body By outgrowing neighboring cells and destroy tissues |
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Classes of Cancer
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Benign
Malignant Metastatic |
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Benign Cancer
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Tumor that does NOT spread into surrounding tissue
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Malignant
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Tumor that spreads into other tissues
INVASIVE - primary tumor |
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Metastatic
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Movement of cancer cells from the PRIMARY tumor
Also the name for the tumor that forms from this process |
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All Cancers are a result of
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DNA Mutations
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All cancers lose
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Normal regulation of division and Death
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Cancer results of mutation from _________ and ________
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Environmental factors and Inherited genes
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Cancer cases in the world and USA`
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3 million and 1.5 million in USA
500,000 deaths per year |
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Cancer genes normally participate in
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Every system that promotes survival, propagation, death, and vascularization
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Some Cancer gene specifics include
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Cell cycle regulation
Mitosis Apoptosis DNA repair Telomerase activity DNA methylation Vascularization |
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Chromosomal abnormalities and Cancer
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Cancer cells usually have multiple chromosome abnormalities
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Angiogenesis
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The creation of blood vessels
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_________ limits the ability of oxygen and nutrients to reach the center of a tumor mass
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Diffusion
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Metabolic Changes in cancer cells
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Warburg Effect
Discovered in 1924 |
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Warburg Effect
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Cancer cells are addicted to glucose
Run high amounts of ANAEROBIC glycolysis pathway in AEROBIC conditions! |
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Cancer Metabolism in absence of glucose
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USE galactose and Fructose
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Cancer Glycolysis and Metabolism is not performed to produce _______ but instead create intermediates for _________
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ATP, cell division
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Common Anticancer Drugs
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DNA Replication Inhibitors
DNA Synthesis Inhibitors Mitosis Inhibitors |
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Doxorubicin
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DNA Replication inhibitor
Inhibits Topoisomerase |
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Cyclophosphamide
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DNA Replication Inhibitor
Cross links DNA so it cannot unwind |
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5-Fluorouricil
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DNA Synthesis Inhibitor
Inhibits dNTP synthesis |
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Methotrexate
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DNA Synthesis Inhibitor
Inhibits dNTP synthesis |
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Taxol
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Mitosis Inhibitor
Interfere with mitotic spindle fibers |
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Vincristine
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Interfere with Mitotic spindle fibers
Mitosis Inhibitor |
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Copper
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Found throughout the diet
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Sources of Copper
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Seeds, grains, nuts, beans, shellfish, and liver
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Toxicity from Copper Overload
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Redox activity
Reactive Oxygen Species Displaces other metal ions Peroxidize lipids Cleave DNA / RNA |
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Copper Absorption
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Absorbed in small intestine by HCTR I
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Copper Transportation
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ATOX-I (Metallochaperone)
Addition carriers and chaperones for specific enzymes |
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Copper Proteins and Enzymes
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Ceruloplasmin
Cytochrome C Oxidase Cu/Zn Superoxide Dismutase Metallothionin Lysyl Oxidase Matrixmetalloproteinase |
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Ceruloplasmin
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Seen also in iron metabolism
Primary copper transporter in the blood |
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Copper Deficiency
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Iron remains in the liver
Addition of copper bearing ceruloplasmin releases iron from the liver into the blood |
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Cytochrome C Oxidase
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Electron transport chain
Converts oxygen to water |
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Cu/Zn Superoxide Dismutase
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Converts Superoxide to peroxide
First enzyme to lose activity in copper deficient state |
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Metallothionin
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Metal Storage
Binds: Cu, Zn, Cd, Hg, Ag, Ni Cu Has highest affinity and displaces others |
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Lysyl Oxidase
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Cu is structural
Failure is found in MENKES disease Important for connective tissue architecture |
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Matrixmetalloproteinase
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Important enzyme in ANGIOGENESIS
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Menkes Disease
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Systemic copper deficiency
Fatal disorder: 3-4 years |
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Menkes Disease Pathology
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ATPase failure that prevents copper being moved out of cells
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Menkes Disease Symptoms
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Connective tissue abnormalities
Neuronal Degeneration Kinky hair Cells from patient accumulate copper |
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Menkes disease therapy
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Detection (MUSt BE AFTER BIRTH)
Administer Copper-Histidine -Main copper/amino acid complex found in serum Stabilize and improve disease -Experimental -Old survivor at time of report: 20 years |
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Wilsons Disease
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Liver Copper Overload
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Wilsons Disease Pathophysiology
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Copper elimination into the bile is impaired
Liver copper levels increase (copper deposition in other tissues) Ceruloplasmin levels decrease (can affect iron) |
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Wilsons disease symptom
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Hepatic symptoms
Neurological Symptoms Kayaer-Fleischer rings |
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Wilsons disease therapy
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Copper Elimination
Zinc maintenance Elimination via chelation and excretion in the urine |
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Zinc Maintenance in Wilsons disease
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DANGEROUS and CANNOT be used initially
Severe neurological damage is used during overload stage of disease Completely benign once acute copper storage phase passes |
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Proteasome
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Huge complex
Principle degradation machinery REPRESSES APOPTOSIS PROMOTES proliferation PROMOTES drug resistance |
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Inhibition of Proteasome promotes ___________
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APOPTOSIS
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Copper and Cancer
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Cancer tissues accumulate high levels of copper
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Copper and Proteasome
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Copper can DIRECTLY inhibit purified proteasome in vitro
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Potency of copper inhibition
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Organic Ligands alter potency of copper
Cells with high levels of copper are sensitive to ligand treatment |
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Cure
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Treatment with copper binding compounds to "detect" copper and form a proteasome inhibitor within tumor cells could prove an effective strategy for non-toxic chemotherapy.
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