Please enable JavaScript.

Coggle requires JavaScript to display documents.

Cancer - Coggle Diagram

- - - - No 3' hydroxyl group to prime DNA synthesis
  - - - Cancer pass mortality
    - - Anti telomerase activity
        
        Selective destruction of cancer cell
        
        Minimizing effect on normal cell
        
        immunotherapies
        
        peptide, DNA vaccines (GV100)
        
        Stimulates immune response against telomerase expressing cancer cell
        
        Target, recognise telomerase expressing cell
        
        Direct telomerase inhibitor
        
        Small molecules binds and inhibits the catalytic activity of telomerase resulting shortening of telomere
        
        imetelstats
        
        replicative senescence
        
        Advanced to early stage of clincal trails, but no clincal efficacy
        
        Correlation of baseline telomere length shortening and patient benefit has not yet establish on solid tumors
        
        Through tissue studies and xenograft studies
        
        Nucleotides analogues
        
        Destablished the binding of protein that aid tolmerase assembly at tolmerase
        
        Alternatives
        
        Traget expression of telomerase in cancer cell and location of telomerase so it don't bind
    - - Recoginsied the G repeating using RNA template within the enzyme
      - Elongates the parental strand
      - Daughter strand complete by DNA polymerase α
        
        Carries DNA primerase as subunit
    - - Most normal somatic cell does not contain
      - 85% of cancer cells have stable tolmerase
      - Extend lifespan- normal somatic cell + engineered tolmerase
  - - - Healthy aging, longevity, no or mid diabites complications and slow progression of complications
    - - Biologically aged, premature death, higher risk of complication, advanced diabites complications
- - - - invade healthy tissue
    - - Migrate to other part of body
        
        Accquire different propertities in order to adapt the tissue
  - - - in single cell
      - can not be inherited
    - - Present in every cell of body
      - Can be inherited
  - - - Hypertrophy
      - Hyperplasia
        
        thyroid
        
        Reversible scenario
      - Metaplasia
        
        reversible
      - Dysplasia
    - - Accompany by a typical or bizzare mitotic feature
      - not able to divide into 2 daughter cell
      - Overabundance DNA
      - Ratio between nucleus, cytoplasm is off
      - Nucleus shape variable
      - Chromatin clump around nucleur membrance
      - Not properly aligin at metaphase
      - Thripolar, quadrupolar mitotic spindle, abnormal sidtrubtion of chormatin
  - - - More mutations
    - - Occur in the mucosa of colon
      - APC loss
        
        80% sporadic
        
        Germiline due to Familial Adenomatous Polyposis
        
        autosomal dominant
      - STEPS
        
        Loss of APC tumor suppressor gene, chromosome 5
        
        Small polyp -> no cancerous growth
        
        Activation of ras oncogene, chromosome 12
        
        loss of DCC tumor supressor geme, chromosome 18
        
        Loss of p53 tumor supressor gene, chromosome 17
        
        Metastasis
- - - - Cancer phenotype
  - - - Promotes cancer
      - First gene cause cancer
      - Promote cell proliferaction
      - oncogene
  - - - More than 200 HPV subtype
      - More than 40 transmitted sexcually
      - High risk- 12 subtypes (HPV16)
    - - L1
        
        Binds other cellular protein
        
        to disrupt homostasis
        
        Take over function
        
        to replicate L1 and several protein
        
        E6, E7
        
        Fundamental improtant for cancer phenotype arising from HPV infection
        
        bind and inactivate p53 and RB1, respectively, disrupting cell cycle checkpoints and promoting uncontrolled cell division
        
        HPV E6 protein binds and inactivates p53, and E7 binds RB1, disabling tumor suppressor functions.
      - L2
        
        Establish interaction, promote entry of virus at cytoplasmic side
    - - Stay 24 hr in nucleus
      - viral genome does not integrate within the host
      - stay in circular DNA form for many cell cycle
      - become indisgues
      - Not target by therapy
    - - take place in human chromosome, transcription of active region
    - - Translocation between chromosome 8 and 15
  - - - Causes chronic inflammation
        
        Maligant to develope cancer
      - Increases risk of developing duodenal and gastric ulcer disease and cancer
      - Maligant transformation of tissue
      - Cancer - 2-3% develope
      - Grow in lining of stomach
- - - - Point mutation
        
        Translate into any amino acid of certain property that leads to mutated protein to be always at ON state
      - Translcoation
        
        Leading to new fusion of protein
        
        New fusion can be harmful
      - Ampllifcation
        
        Multiple copies of protein of mRNA translate into protein in a cell
        
        Amplifed expression
  - - - Seen as oncogene
  - - - C-myc
        
        Potent oncogene, promote tumorigensis in wide range of tissue being amplified
        
        Elvated level of c-myc molecules
        
        ovarian- 64%
        
        Esophageal- 45.3%
        
        Squamous lung- 37.2%
        
        Breast- 30%
        
        Associated with poor prognosis and early relapse
        
        Stimulates gene in protein biosyntheis, cancer metabolism, transcription factor, cell cycle genes
        
        Cellular proloferation no lnoger depends on growth factor
        
        uncontrol proliferation
        
        Enchanced occupancy of contol regions and increases Pol ll pause release at actively transcribe gene
        
        Reduction of rate limiting constraints for tumor cell growth and proliferation
        
        Transcriptional amplifcation for genes withinin the cell's existing gene expression program
        
        Regulatory control
        
        cmyc regulation by signaling pathway
        
        cmyc contol expression of many genes
        
        In tissue
      - n-myc
        
        Amplifaction in neuroblastoma patient is 20-30%
        
        Survival less than 50%
        
        Type of paediatric cancer develope in nervous system of babies, young children, growing immature tissue (neuroblast)
        
        Important in neurons, stroongest predictor of prognosis
  - - - By reciporcal translocation of chromosome 9, 22
        
        Activates proto oncogene
        
        Involves breakpoints with ABL, BCR genes
        
        Fuses, gernerating functional kinases
        
        Abnormal function protein
        
        ABL is controlled by BCR promoter
        
        ABL always ON, premanently active in white blood cell
        
        Causes leukaemia
        
        proliferation of white blood cell
        
        more than 95% chronic myeloid leukaemia
        
        20% acute lymphoblastic leukaemia
      - Tryosine kniase enzyme
        
        Use ATP to attach phosphate group onto target protein
        
        Activates certain protein involves in cell division
        
        Fully regulated to control cell cycle
        
        At chromosome 9
        
        Phosphorylated over 20 protein
        
        Activating signal transduction pathway, proliferation, survival, migration pathway to induce growth, prevent apoptosis
      - Treatment
        
        Destory patient bone marrow, restore blood cells by infusing stem cell from bone marrow of a healthy donor
        
        Imatinib
        
        Fit into active site, preventing ATP from binding
        
        Substrate cannot enter kinase site and not activated
        
        Tumor cell con not proliferate
        
        Target abnormal kinases activity
        
        90% patient show no further progression
- - - - RB1
        
        First tumor supressor gene
        
        Retinoblastoma
        
        Occur in retina of eye
        
        Stops the expression of gene that required for cell to progress
        
        uncontrolled cell division
        
        Types
        
        inherited, occurs in the first few year of life
        
        One mutation from parent
        
        Not unlikely second mutation occurs in the retinal cell at early age, leading to disease
        
        Noninherited, occur later in life
        
        Two mutation in the same retinal cell
        
        Much later in life, rarely
        
        Loss of RB
        
        induce cell re-entry
        
        Cancer progression
        
        increase proliferation
        
        increases metastatic potential
        
        Prevent induction of cellular senscence
        
        increase chromosome instability
        
        Promote angiogensis
        
        inhibits transcription by E2F transcription factor to prevent cell advancement
        
        Checkpoints pass when cyclin and CDK work to free E2F from RB
        
        At G1 checkpoint
        
        RB degraded, allow RB phosphorylation to there after decline, re-instate the regulation of E2F
        
        E2F activates gene that start the path of cell cycle
        
        Mutated RB does not bind E2F
        
        Act without control to promote cell division
        
        Missense / frameshift
    - - P53
        
        Second
        
        50% cancer are associated
        
        Preventing cell division when cell damage
        
        Double strand break
        
        DNA damage sensor duriing DNA application signaling several DNA damage pathway for repair, cell cycle arrest
        
        Halts cell cycle until damage repaired
        
        turning on p21
        
        Keep cyclin and CDK from interacting
        
        not form complex, can not pass through check points
        
        Fail- dies not halt the cycle
        
        Fuctions
        
        Activates gene that promote DNA repair, to prevent accumulation of mutation
        
        Activate gene that arrest cell division
        
        repress other gene that are require for cell division
        
        Stimulate expression of p21
        
        inhibits formation of cyclin CDK complex that is needed to advanced cell cycle
        
        Activates gene promote apoptosis
        
        Involves cell shrinkage, chromatin condensationm DNA degradtion
        
        Facilitated by proteases "capases"
        
        Digest selected cellular protein
        
        For G1, G2
        
        Li-Fraumeni Syndrome
        
        inherited autosomal dominant
        
        abnormalities in the tumor suppressor protein P53 gene (TP53) located on chromosome 17p13
        
        Repair pathway
        
        ATM
        
        Serine threonine protien kinase
        
        recruited and activate DNA damage site by myriad of protein that recognised the damage
        
        Medicate the homology directed repair
        
        ATR
      - BRCA
        
        Women
        
        Ovarian
        
        No effective way for screening
        
        Ovaries removed
        
        Before menopause - reduce risk of breast cancer
        
        Breast
        
        Mammography- 40
        
        Breast screening avaiable at 47
        
        With mutation start eailer
        
        MRI scanning- 30
        
        Sugery remove breast
        
        Medication regulate horomones
        
        Significant side efffect
        
        Men
        
        BRCA 2 mutation
        
        15% develope prostate cancer by 65
        
        7% breast cancer over lifetime
        
        Have annual blood test PSA
        
        Increase PSA level -> postate cancer
        
        BRCA 1 mutation
        
        chance for prostate cancer minimally increased
        
        not increase risk of developing breast cancer
        
        Guradians of the genome
        
        Work in DNA repair machanism
        
        Repair double strand break
        
        via Homologous recombination pathway
        
        Transition between S, G2 cell cycle
        
        Genetic testing
        
        For someone who had has cancer
        
        Blood taker send to lab
        
        Possible outcome
        
        Know mutation in BRCA1/2
        
        Option to manage cancer
        
        No mutation
        
        Extra screening depend on family history
        
        Variant in genetic code that isn't known cause of cancer
        
        Extra screening depend on family history
        
        Major- harmless, no side effect
        
        Minior- may disrupt, stop genetic code
        
        Mutation
        
        50-80% delevope breast cancer
        
        BRCA1- 20-50%
        
        BRCA2- 10-20%
        
        General population- 1-2%
        
        Slightly higher chance for pancrease cancer
        
        autosomal dominant
        
        BRCA1
        
        germline mutation in breast cancer associated with brain metastases -> hard to treat
        
        Age 70, increase breast cancer risk to 47-66% ovarian 37-46%
        
        Give rise to agressive higher grade triple negative breast cancer subtype
- - - - Enhance the expression of oncogene
    - - RASSF1A
        
        inactivates Tumor supressor
      - Lead to lung, breast, prostate, kidney, neuroblastoma cancer
    - - Noncoding RNA -> interfere with gene expression
    - - inactive tumor supressor, DNA repair
        
        gobal chormatin instability
  - - - Differentiate into different cell
  - - - Revert expression of oncogene
    - - DNMTi
        
        DNA methyltransferase inhibitors
        
        promotes loss of methylation and activation of aberrantly silenced gene
        
        Vidaza, Dacogen
      - HADCi
        
        induce actetylation
        
        promoting transcriptional activation
        
        Keep activation of tumor supressor
        
        HADC- remover acetyl group
      - Epidrugs- TETi, IDHi, PRMTi, BETi
        
        EZH2- activation of k27 on h3 of histone
- - - - 1% of protein coding gene in human genome
- - - - Food- asbestos - component of tabacco smoke, alchol, atcatoxin
        
        Lung cancer
      - Drink - arsenic - drinking water containment
    - - Initiation
      - Promotion
      - Progression to cancer
- - - - Confers a cancer cell a growth advantages
      - Induce cell proliferation, hit tumor supress gene, oncogene
      - P53
    - - not necessarily determine cancer development
      - Hijacking mutation
      - Can be netural
      - Important for cancer to survive in new environment