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VASUpharm14
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context: cell life
Proliferation
- day 1 = 1 cell zygote
- day 4 = 8 cells morula
- day 270 (birth) = ~10 trillion cells baby
- day 5000 = ~75 trillion cells fully grown
- day 15,000 = ~85 trillion cells older adult
- NOTE: Starting life with one cell then multiply rapidly
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context: cell life
differentiation
- day 1 = 1 cell type zygote
- day 4 = 1 cell type morula
- day 270 (birth) = ~300 cell types baby
- day 5000 = ~300 cell types fully grown
- day 15,000 = ~301 cell types older adult
- NOTE: someone becoming someone else. extra one can be CANCER
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context: cell life (TIME)
oocytes (eggs)
lifetime
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context: cell life (TIME)
neurons
- lifetime? (more connections)
- You don't make new ones, you make new connections.
- (more connections)
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context: cell life (TIME)
muscle cells
- lifetime? (more volume)
- You don't make new ones, you stretch and bulk.
- (more volume)
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context: cell life (TIME)
bone cells
~25 years
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context: cell life (TIME)
lymphocytes (WBC)
~1 year
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context: cell life (TIME)
red blood cells (RBC)
~4 months
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context: cell life (TIME)
skin cells
~1 month
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context: cell life (TIME)
platelets
~10 days
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context: cell life (TIME)
colon cells
~3 days
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context: cell life (TIME)
stomach cells
~2 days
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context: cell life (TIME)
spermatozoa
~2 days
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T/F
cell death is not important to organism life
False!
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context: methods of cell death
Necrosis or Apoptosis (programmed cell death)?
homocide
necrosis
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context: methods of cell death
Necrosis or Apoptosis (programmed cell death)?
traumatic accident
necrosis
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context: methods of cell death
Necrosis or Apoptosis (programmed cell death)?
old age or "seppuku"
apoptosis
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context: methods of cell death
Necrosis or Apoptosis (programmed cell death)?
natural or purposeful
apoptosis
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context: why die?
Necrosis or apoptosis?
physical/mechanical
necrosis
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context: why die?
Necrosis or apoptosis?
lots of chemicals
necrosis
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context: why die?
Necrosis or apoptosis?
lots of microbes invade
necrosis
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context: why die?
Necrosis or apoptosis?
old age, mutations
apoptosis
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context: why die?
Necrosis or apoptosis?
some chemicals
apoptosis
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context: why die?
Necrosis or apoptosis?
some microbes invade
apoptosis
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context: how die?
Necrosis or apoptosis?
fast death
necrosis
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context: how die?
Necrosis or apoptosis?
kill and spill
necrosis
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context: how die?
Necrosis or apoptosis?
slow death
apoptosis
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context: how die?
Necrosis or apoptosis?
tag and bag
apoptosis
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context: response
Necrosis or apoptosis?
inflammation
necrosis
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context: response
Necrosis or apoptosis?
minimal
apoptosis
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context: cell death process
necrosis or apoptosis?
small blebs form; the structure of the nucleus changes
necrosis
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context: cell death process
necrosis or apoptosis?
the blebs fuse and become larger;
no organelles are located in the blebs
necrosis
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context: cell death process
necrosis or apoptosis?
the cell ruptures and releases the cell's contents;
the organelles are not functional
necrosis
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context: cell death process
necrosis or apoptosis?
small blebs form; no nucleus change
apoptosis
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context: cell death process
necrosis or apoptosis?
the nucleus begins to break apart, and the DNA breaks into small pieces.
organelles located in blebs
apoptosis
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context: cell death process
necrosis or apoptosis?
the cell breaks into several apoptotic bodies;
the organelles are still functional.
- duh!
- apoptosis (cause it says so lol)
- remember things are still functional!!
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where do new cells come from?
- STEM CELLS! (booya)
- with high replication rates too :D
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2 major types of stem cells
- 1) totipotent (pre-blastocyst stem cells)
- 2) pluripotent (embryonic --> adult stem cells)
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context: stem cells
totipotent
- Each cell can develop into ANY cell type.
- "Totally powerful"
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context: stem cells
pluripotent
Each cell can develop into a LIMITED selection of cell types
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what type of stem cell inside bone marrow?
what cell type does it make?
hemopoietic stem cells; blood cells
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context: contemporary stem cell therapies
problems
- damage stem cells.
- Disease or chemotherapy can kill off hematopoietic stem cells in bone marrow
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context: SOLUTIONS in contemporary stem cell therapies
bone marrow
- good: Concentrated source of hematopoietic stem cells
- bad: Needs to be close genetic match AND Painful
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context: SOLUTIONS in contemporary stem cell therapies
blood transplant
- good: less painful
- bad: Needs to be close genetic match AND dilute source
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context: SOLUTIONS in contemporary stem cell therapies
cord blood
- good: Concentrated source of hematopoietic stem cells
- bad: Does not need to be close genetic match
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context: POTENTIAL stem cell therapy sources
Embryonic stem cells
- pros: controversy of sources. (in vitro fertilization extra blastocysts. aborted/miscarried fetuses/embryos)
- cons: easy to isolate, easy to coax to another cell type
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context: POTENTIAL stem cell therapy sources
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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context: stem cell updates
Year?
isolated adult stem cells from liposuctioned fat
2001
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context: stem cell updates
Year?
isolate single stem cell from embryo without harming it
2006 (Nature)
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context: stem cell updates
Year?
isolate embryonic stem cells from human amniotic fluid
2007 (Nature Biotech.)
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context: stem cell updates
Year?
isolated stem cell from newborn foreskin cells (ouch)
2007 (Science)
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context: stem cell updates
Year?
isolated adult stem cell from menstruated endometrium
2007 (J of Translat. Med.)
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context: stem cell updates
Year?
coaxed adult cheek cell into 200 cell types
2007 (Cell)
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Good news about Stem Cells
- useful for therapies
- potential: Human neuronal cells for: Parkinsons, Spinal Cord injury, Alzheimers
- achieved: Success in mice for: Parkinson’s, Diabetes Mellitus
- Success in humans for: Incontinence (bladder problems), Multiple Sclerosis
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Bad news about Stem Cells
- cancer causing (lose regulation)
- Stem cells discovered as source for several cancers: Leukemia (WBCs), breast, brain, prostate, ovarian, colon, pancreatic
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context: stem cells vs tumor cells
3 similarities
- 1) high rate of proliferation
- 2) may remain quiescent for a long time (only replicate when triggered)
- 3) resistent to apoptosis = immortal = increased longevity (enhanced telomerase activity, DNA repair activities,
- Membrane bound transporters that exclude foreign agents
- Good: keep your wanted stem cells
- Bad: difficult to kill unwanted cancer cells resistant to chemotherapeutic agents
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context: tumor cells
tumor
- aka neoplasm
- “A mass or swelling produced by abnormal cell growth and division”
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context: tumor cells
benign
- "good" compared to malignant
- 1) remains within connective tissue area
- 2) Less threatening, remove via surgery
- 3)Technically not “Cancer”
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context: tumor cells
malignant
- "bad"
- 1) spread to other tissues
- 2) More threatening, difficult to remove
- 3) Technically called “Cancer”
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How many tumor types?
- 300 = 300 cell types in body
- THIS. IS. SPARTA!!!!!
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context: tumor types
Epithelial tissue (skin, orifices, G.I. tract)
- carcinoma
- adenocarcinoma - glandular epithelia
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context: tumor types
connective tissue
- 1. Leukemia- WBCs and precursors
- 2. Osteoma- bone
- 3. Chondroma - cartilage
- Remember: LOC ... as in Pop it and LOC it. (sadly this is how lame I can get)
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context: tumor types
muscle tissue
- myoma
- leiomyoma - smooth muscle
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context: tumor types
neural tissue
- glioma - neuroglia
- neuroma- neurons
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context: tumor types
Suffix?
Benign
- -OMA
- ex: lipoma = benign tumor of fat cells
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context: tumor types
Suffix?
Malignant
- -SARCOMA
- ex: liposarcoma = malignant tumor (cancer) of fat cells
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context: malignancy
primary site/primary tumor
origin of tumor
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context: malignancy
spreads to other sites
Into circulation --> another tissue
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context: malignancy
Metastasis (verb)
action of leaving site
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context: malignancy
Malignant (adjective)
some cells have left primary site
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context: malignancy
Cancerous (adjective)
some cells have left primary site
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context: malignancy
Secondary sites/Secondary tumors
- Metastasis (noun): secondary site/tumor
- Malignancy (noun): secondary site/tumor
- Cancer (noun) = tumor cells at primary AND secondary sites
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context: cancer identification
Oncology
detection, identification, and treatment of cancers
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context: cancer identification
Biopsy
- identification
- 1) examine primary or secondary tissue site
- 2) examine routes between tissues. (ex: lymph node biopsy = common route for cancer cells to spread)
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needs to appear big in x-ray to detect!
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2 causes of cancer and percentages
- 1) 25% -inherited (genetic) - bad gene
- 2) 75% - environment: a) radiation (UV, X-ray), b) carcinogens (smoking, asbestos), c) viruses (Human papilloma, hepatitis B - insert viral DNA)
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context: causes of cancer
cells affected by environmental factors
- 1) interaction - UV = skin cancer, Smoking = lung cancer
- 2) sensitivity - replicating cells are more sensitive
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Oncogenes
- A normal cell is converted to a cancer cell via one of the following:
- A mutated gene (via mutagen or carcinogen)
- An inserted gene (via virus)
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How many Oncogenes are there?
50 different human genes have potential to mutate to oncogenes
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context: oncogenes
mutations that turn ON proteins
- Stimulating cell replication
- ex: RAS gene/protein (mutated ON in 25-30% of all cancers)
- kinase normally stimulates growth/ cell replication
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context: oncogenes
mutations that turn OFF proteins
- Inhibiting cell replication, metabolizing toxins, repairing DNA damage
- Identification or destruction of abnormal cells
- ex: P16 gene/protein: (mutated OFF in 50% of all cancers) = normally inhibits cell cycle
- ex: p53 gene/protein: (mutated OFF in 50% of all cancers) = normally inhibits cell cycle, monitors damage to DNA, stimulates apoptosis
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T/F
Cancer is just marked by proliferation
- FALSE
- Cancer is not just about “proliferation”
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context: cancer pathophysiology
6 pathophysiologies that WILL happen
- 1) loss of contact inhibition - Density inhibition usually via Cadherins
- 2) unregulated proliferation - Abnormal replication
- 3) evasive - Escape detection by Natural Killer Cells (WBCs)
- 4) invasive - Have capacity to invade other tissues
- 5) angiogenesis- Tumors stimulate blood vessels to grow toward them. Need lots of nutrients
- 6) loss of apoptotic termination - Normal cells have programmed self-termination
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context: cancer pathophysiology
3 pathophysiologies that MAY happen
- 1) May interfere at primary and secondary sites - Organ disabled
- 2) May interfere with nearby structures - Pressure on nerves, blood vessels, organs
- 3) May alter control and coordination - Endocrine tissue tumors release excess hormones
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? % will develop cancer
25%
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?% will die from cancer
13%
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context: cancer treatment
remission
cessation or decrease of size of tumor(s)
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context: cancer treatment
2 ways to obtain remission
- 1) Targeted removal or destruction - with: Surgery, radiation, heat, freezing, immunotherapy
- 2) Non-targeted destruction - with: Systemic chemotherapy (cytotoxic chemicals)
- --Most work by inhibiting cell replication
- --hair loss and vomiting (Epithelial cells largely effected)
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context: anti-cancer drugs
General goal
inhibit cell replication (directly or indirectly)
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context: anti-cancer drugs
General tactics
Pro-hormone
inhibit replication by adding hormones
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context: anti-cancer drugs
General tactics
anti-hormone
inhibit replication by inhibiting hormones
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context: anti-cancer drugs
General tactics
anti-tumor cell surface
target specific surface proteins
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context: anti-cancer drugs
General tactics
anti-tumor cell signaling
inhibit specific signaling proteins
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context: anti-cancer drugs
General tactics
anti-mitosis
Inhibit mitotic-specific activity (eg tubulin)
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context: anti-cancer drugs
General tactics
anti-metabolites
- Alter precursors/enzymes needed for
- a) DNA replication
- b) DNA transcription
- c) RNA translation to protein.
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context: anti-cancer drugs
General tactics
anti-DNA
Inhibit DNA from replicating /transcribing
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