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Neoplasia-II

8 Hallmarks of cancer
1. Insensitivity to anti-growth signals
  1. Tumor suppressor genes
    1. Loss of function mutations
    2. APC(Ch.5)
      1. Familial adenomatous polyposis
      2. Normal function: Binds to beta-catenin and degrades
    3. NF-1
      1. Neurofibromatosis
        Multiple cutaneous tumors
      2. Normal: Neurofibromin GTPase activity
    4. NF-2
      1. b/L Acoustic neuroma+schwannoma
      2. Normal: cytoskeletal protein merlin
    5. BRCA-1&2
      1. Familial breast cancer
      2. Normal: DNA Repair
    6. Rb
      1. Knudson 2 hit
      2. Retinoblastoma
        Familail
        Bilateral
        Osteosarcoma
        Sporadic
        Unilateral
        No osteosarcoma
    7. DCC
      1. Colon cancer
    8. p53
      1. Lifraumeni syndrome
    9. VHL(CH3)
      1. RCC+ Cerebellar hemagiblastoma
    10. WT-1
      1. Nephroblastoma
      2. Normal : Helps in differentiation of fetal kidney
2. Limitless replicative potential
3. Altered metabolism
  1. Aerobic glycolysis
  2. Principle of PET scan
4. Evasion of apoptosis
  1. bcl-2
    1. Follicular lymphoma
5. Sustained angiogenesis
  1. Notch pathway
    1. Angiostatin inhibits
    2. FGF PDGF Promotes
6. Ability to invade and metastasis
  1. steps
    1. 1. Loosening by loss of E-cadherin
    2. 2. Degradation of BM by MMPs
    3. 3. Integrin binding
    4. 4. Locomotion of tumor cells form emboli
7. Self sufficient growth signals
  1. Oncogenes
    1. Growth factors
      1. PDGF
        Astrocytoma
    2. Growth factor receptor
      1. Her-2-neu
        Breast ca
      2. ret
        MEN medullary carcinoma thyroid
      3. kit
        GIST
    3. Signal transduction pathway
      1. abl
        CML
      2. braf
        Melanoma
        Hairy cell leukemia
      3. K-RAS
        Colon carcinoma
      4. H-RAS
        Kidney cancer
        Bladder cancer
    4. Nuclear regulators
      1. N-myc
        Neuroblastoma
      2. c-myc
        Burkitt lymphoma
      3. Cyclin D
        Mantle cell lymphoma
    5. Oncogene addiction
      1. E.g. CML, Breast cancer, Burkitt lymphoma
    6. Gain of function mutation
8. Ability to invade host immunity
  1. 1. Reduced HLA-1
  2. Increased TREGs
Nonlethal genetic damage
Oncogeneic viruses
1. HBV/HCV
  1. HBx gene
2. EBV
  1. Burkitt lymphoma
  2. LMP gene
3. HHV-8
  1. Kaposi sarcoma
4. HPV
  1. E7, E6
    1. Cervical cancer
5. HTLV
  1. Adult Tcell leukemia
  2. Tax gene
Clinical aspects of neoplasia
1. Cancer cachexia
  1. TNF-A
2. Grading and staging
  1. Grading by Pathologists
  2. TNM Staging by oncologists
    1. Metastasis(M) CARRIES A BAD
3. Paraneoplastic syndromsa
  1. Cushings syndrome
    1. Small cell carcinoma
    2. ACTH
  2. SIADH
    1. Small cell carcinoma
    2. ADH
  3. Hypercalcemia
    1. SCC lung
    2. PTH
  4. Myasthenia
    1. Thymoma
    2. Ab to postsynaptic ACH receptors
  5. Lambert-Eaton
    1. small cell lung cancer
    2. Ab to presynaptic Ca channels
4. Dancing eye
  1. Neuroblastoma
5. Migratory thrombophlebitis
  1. Pancreatic cancer
Tumor markers
1. CEA
  1. Colon cancer
2. HCG
  1. Choriocarcinoma
3. PSA
  1. Prostate cancer
4. AFP
  1. HCC , non seminomas
5. CA-125
  1. Ovarian ca
Lab diagnosis of cancer
1. H&E
2. FNAC
3. IHC
  1. Role of intermediate filaments
    1. Cytokeratin
      1. Carcinoma
    2. Vimentin
      1. Sarcoma
    3. Desmin
      1. Rhabdomyosarcoma
    4. S-100
      1. Melanoma
    5. GFAP
      1. Astrocytoma
4. FISH
5. Flowcytometry
6. Frozen section

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Neoplasia-II

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	Created by Pooja Acharya over 4 years ago