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Steam Punk
blending of the old and the new
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different categories of stem cells
- Pre-Blastocyst Stem Cells
- Embryonic->Adult stem cells
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each cell can develop into ANY cell type
Totipotent
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each cell can develop into a LIMITED selection of cell types
Pluripotent (slightly differentiated)
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where do new cells come from?
Stem Cells
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pre-blastocyst Stem Cells
Totipotent
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embryonic->Adult Stem Cells
Pluripotent
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stem cells inside bone marrow
Hematopoetic stem cells
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what cells can come from hematopoetic stem cell?
- Macrophages
- Neutrophils
- Basophils
- Eosinophils
- Platelets
- RBCs
- Plasma Cells
- T Cells
- NK cells
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IMMORTAL cells
Stem Cells
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different sources used for stem cells
Bone Marrow
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Contemporary Stem Cell Therapies
Bone Marrow Transplantation
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what is chemotherapy?
- Systemic toxin that inhibits cells that divide rapidly?
- will inhibit many stem cell types
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Anemia
- lack of Fe in blood
- means they need more RBCs
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good/bad about
Bone Marrow Transplant
- Good: Concentrated source of hematopoietic stem cells
- Bad: Needs to be close genetic match AND Painfull
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good/bad about
Blood Transplant
- Good: less painful than Bone Marrow transplant
- Bad: Needs to be close genetic match AND dilute source
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good/bad about
Cord Blood
- (from newborn baby)
- Good: Concentrated source of hematopoietic stem cells
- Real Good: Does not need to be as close of a genetic match!
- why? B/c not as differentiated as an adult.
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pros/cons about
Embryonic Stem Cells
- Pros: easy to isolate
- easy to coax to another cell type
- Cons: Controversy of sourced
- Surplus blastocysts from IVF treatments
- Aborted or miscarried embryos/fetuses
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pros/cons about
Adult stem cells
- Pros: Less controversy about sources (found in most tissues)
- Cons: Hard to isolate,
- Less easy to coax to another cell type
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general controversies about stem cells
- very political-abortion
- whether scientists can use stem cells from
- aborted or miscarried embryos/fetuses
- surplus blastocysts from IVF treatments.
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2001
isolated adult stem cells from Liposuctioned fat
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2006
(nature) isolated single stem cell from embryo without harming it
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2007
- (Nature Biotech) isolated embryonic stem cells from HUMAN AMNIOTIC FLUID
- (Science) Isolated stem cells from newborn foreskin cells
- (J of Translat. Med) Isolated adult stem cells from menstruated endometrium
- (Cell) Coaxed Adult Cheek Cell into 200 different cell types
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where are stem cells in your body?
EVERYWHERE
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potential Stem cell therapies
- Human Neuronal Cells for:
- Parkinsons
- Spinal Cord injury
- Alzheimers
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theory of stem cells as origins of cancer
- when they loose regulation can become cancer
- confirmed: they are the source of many cancers.
- Leukemia (way too many WBCs)(hematopoietic stem cells)
- Breast Cancer
- Brain Cancer
- Prostate Cancer
- Ovarian Cancer
- Colon Cancer
- Pancreatic cancer
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difference between proliferation and differentiation
- Proliferation is multiplying rapidly vs.
- Differentiation is cells becoming specialized to perform specific jobs.
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proliferation
multiplying rapidly
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differentiation
- Differentiation is cells becoming specialized to perform specific jobs.
- different from cell before
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something external comes along and kills cells
NECROSIS
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apoptosis
normal cellular death
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Which cells live the entire lifetime of the organism?
- Oocytes (eggs)
- Neurons
- Muscle cells
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how long do bone cells live?
~25 years
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how long do lymphocytes live (WBCs)?
~1 year
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How long do RBCs live?
~120 days=4months (then liver breaks down)
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How long do skin cells live?
~1 month
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How long do platelets live?
~10 days
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How long do colon cells live?
~3 days
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How long do stomach cells live?
~2 days
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How long do spermatozoa live?
~2 days
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Cellular Life and Death:
Longest to
Shortest (cell life)
- Oocytes, Neurons, Muscle Cells
- Bone Cells
- Lymphocytes
- RBCs
- Skin Cells
- Plateletts
- Colon Cells
- Stomach Cells
- Spermatozoa
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Important to life of an organism
Cell Death
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Why do colon cells only live a few days?
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cellular Homicide or
traumatic accident
Necrosis
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fast death
kill and spill
Necrosis
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response from Necrosis
Inflammation
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what causes inflammation
- WBCs rush over to clean up cell death
- water comes in
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response from Apoptosis
- minimal
- macrophages come along
- envelop it.
- break up more
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death due to Old age or "seppuku"
natural and purposeful
apoptosis
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programmed cell death
apoptosis
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Why would cells want to die?
- Apoptosis:
- Old age
- senses Mutations
- senses chemicals
- senses microbes invade
- KNOWS it needs to DIE to protect body.
- Necrosis:
- Physical/Mechanical
- Chemicals
- Microbes invade
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Seppuku
- Hari Kari
- Japanese warriors killing themselves for the greater good.
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Stem Cells vs.
Tumor Cells
- SIMILAR:
- High Rate of Proliferation
- May remain Quiescent for long time
- Resistant to Apoptosis
- 1)enhanced Telomerase activity
- 2)Enhanced DNA repair activities
- 3)membrane bound transporters that exclude foreign antigens better and more so than other cell types
DIFFERENT:
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May not replicate for a long time until triggered
Quiescent
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Why is it so bad that stem cells may be the cause of all tumor cells?
- their high rate of proliferation
- may remain quiescent for long time
- Resistance to Apoptosis makes them extremely difficult to kill!
- -resistant to chemotherapeutic agents
- -you must come close to killing the patient to kill the cancer
- only difference between stem cells and tumor cells is
- ABNORMAL
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benign
- Good
- REMAINS WITHIN CONNECTIVE TISSUE AREA
- less threatening, can be removed via surgery
- technically NOT Cancer
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malignant
- spreads to other tissuesMore threatening than benign. difficult to remove
- technically CANCER
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TUMOR
- (NEOPLASM)
- -a mass or swelling produced by abnormal cell growth and division
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how many tumor types?
100+ known. (about 100 types of stem cells)
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***tumor of any epithelial cells
***Carcinoma
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tumor of glandular epithelia
ADENOCARCINOMA
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Tumor of Connective Tissue
- Leukemia-WBCs and precursors
- Chondroma-cartilage
- Osteoma-bone
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how do you say malignant?
--SARCOMA
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how does a malignant tumor spread to other sites?
gets into the circulation.
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difference between cancer incidence and mortality with high/low examples of each
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carcinogens and affected tissue types
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difference between benign and malignant neoplasms
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pathophisiology of cancer
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how do oncogenes create cancer cells?
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explain and give examples of different cancer types
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general methods of cancer identification and treatment
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Cancer
- rapidly growing mass of tissue that
- invades surrounding tissues
- escapes immune surveillance
- connects itself to the blood supply of the host
- steals glucose and oxygen
- interferes with adjacent organs
- makes the host sick
- possibly leads to death of host
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how many different cell types are in a normal healthy adult/baby at birth?
300 cell types
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anti-cancer drugsand how they interfere with DNA or cell replication
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Pro-hormone drug
Prednisone
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corticosteroid that inhibits cytokine production
Prednisone
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estrogen receptor antagonist for some tissues
Tamoxifen
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Anti-tumor cell surface
Trastuzumab
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Trastuzumab
Antibody that binds to HER2 on breast cancer cells
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Anti-tumor cell signaling
Imatinib
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Imatinib
Inhibits a tyrosine kinase
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Paclitaxel
Inhibits tubulin from depolymerizing
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Anti-metabolites
- Methotrexate
- 6-Mercaptopurine
- 5-Fluorouracil
- Irinotecan
- Etoposide
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Inhibits formulation of precursors of nucleotides
Methotrexate
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Inhibits purine synthesis
6-mercaptopurine
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Inhibits DNA/RNA synthesis
5-fluorouracil
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Inhibits Toposiomerase I
Irinotecan
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Inhibits Topoisomerase II
Etoposide
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Anti-DNA
- Cyclophosphamide
- Cisplatin
- Doxyrubicin
- Bleomycin
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Cross-links DNA
Cyclophosphamide
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Cross-links DNA (RNA and protein also)
Cisplatin
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Intercalates into DNA, inhibits Topoisomerase II
Doxorubicin
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formulation of free radicals-> damages DNA
Bleomycin
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