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Cancer (HALLMARKS OF CANCER :warning: (Evade apoptosis, Self-sufficient…
Cancer
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Types of cancer drugs
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Imatinib :fire:
Specific for Chronic myeloid leukemias (CML) :pen: Translocation of gene from 9 to 22 ABL-BCR hybrid gene :warning: PHILADEPHIA CHROMOSOME
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Cancer Biology
Cell signalling pathway
Cellular function is controlled by a highly complex and interconnected network of intracellular signalling pathway
For functional regulation: Embryonic development, tissue differentiation and systemic responses
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Treatment for cancer
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Treatment response
Complete response, Partial response, Minor response, Stable disease, No response
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Drug types
Cytotoxic
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Nucleotide ends with "uracil, guanine" :fire:
Microtubule "vin, taxel :fire:
Antibiotics "mycin, rubicin" :fire:
Topoisomerase "tecan, toposide :fire:
Alkylating "Cyclophosphomide, chlorambucil, dacarbazine :fire:
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Endocrine based
Estrogen
Tamoxifen, Fulvestrant, Letrozole, Anastrazole
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Causes of cancer
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Environmental factor
Radiation
Remove electrons from atom, changes DNA
Bone marrow, breast, thyroid
Solar radiation
Squamous cell cancer, basal cell cancer, melanoma
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Virus
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HIV causes non-hodkin lymphoma, Kaposi's sarcoma and Cervical cancer
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Diet
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Alcohol
Liver, breast, oropharyngeal, oesophageal, stomach
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Cancer screening
Colon cancer
People with average risk, FOBT (yearly) or Colonoscopy (10 yearly) for people above 50
Breast cancer
Mammogram, once every 2 years, 50-69 years, 40-49 should have annual screening
Cervical cancer
Pap smear 25-69, once every 3 years
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Grading and Staging
Grading: Degree of differentiation, determined histologically
3 grade system: Well, moderate, poor
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Screening of cancers:
- Breast
- Cervix
- Stomach
- Colon
Effects of tumour:
- Mass
- Ulcer
- Hemorrhage
- Pain
- Seizure, cerebral dyfunction
- Obstruction
- Perforation
- Inflammation
- Edema
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Example: breast cancer
Benign tumour normally are well encapsulated, they will be freely movable unlike malignant
Tumour desmoplasia :warning:
When cells secrete cytokines to stimulate growth of fibrins, feel firm
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Example: Lung, Breast, Renal cancer produces parathyroid hormone leading to hypercalcemia
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All these are still "Carcinoma-in-situ" :warning:because they have not developed the ability to penetrate through the basement membrane
:tornado: Is there such thing as sarcoma-in-situ :tornado:
No, Mesenchymal cells are not bound by basement membrane, they do not need to penetrate basement membrane
:tornado: Why some tumours give rise to pain :tornado:
Perineural infiltration invading the nerves and causing pain
Pagetoid spread :warning:
Malignant epithelial cells spread along the epidermis etc Paget disease at the nipple pus and enter breast ducts without passing basement membrane
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Sentinel node :warning: Identification of sentinel node to prevent removal of all to prevent lymphedema
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:tornado: Is there such thing as arterial spread? :tornado:
Most of the time it goes via venous, pass microcirculation of pulmonary vessels then travel to brain OR AV shunts, definitely not arterial because walls too thick
- Oncogenes
- Tumour suppressor gene
- Gene that regulate apoptosis
- DNA repair gene
LIST OF CANCER GENE THAT MUST KNOW
- RTK
- MAPK pathway with RAS BRAF
- p53 gene
- Bcl-2 molecule
- Cyclin/CDK
Rb protein
Proto-oncogene codes for:
- Growth factors
- Receptors
- Cell signalling molecules
- Transcription factor
- Cell cycle component
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:warning: EGFR point mutation will lead to lung adenocarcinoma in non-smokers, this is diff from colorectal as this is a hyperactive one
:warning: KIT (80%) most commonly in Exon 11 and PDGFR (10%) most commonly in Exon 18 point mutation will lead to Gastrointestinal stromal tumour
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:warning: Ras protein Point mutation will lead to pancreatic adenocarcinoma (80%) and 50% of colon/thyroid and 30% of lung adenocarcinoma and leukemias
Example: Ras protein and BRAF family and PI3K
BRAF is a member of RAF family and triggers MAPK pathway a serine/threonine protein
PI3K family = PI3K, akt, mTOR
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Example: Myc transcription factor Translocation chromosome 8 to 14 will lead to Burkitt's lymphoma :warning: translocated downstream of IgG promoter, amplification can also be seen in neuroblastoma :warning:
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CD1 gives mantle cell lymphoma, myeloma and breast cancer :warning:
CDK4 gives glioblastoma, melanoma :warning:
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MDM2 binds to p53 and inhibits it, once damage is detected ATM/ATR will stop MDM2
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Follicular B cell lymphoma :warning: (85%) anti-apoptotic gene BCL2 is activated by translocation T14:T18
Mutated APC :warning: will lead to accumulation of undifferentiated cells will lead to adenomatous polyp formation
Changes that build up to colorectal cancer: :warning:
- APC
- K-ras
- DCC
- p53
Undergoes the Vogelstein's model
In 15% of sporadic HNPCC, it is not via MMR but via hypermethylation of MLH promoter :pen: resulting in no expression of MLH and deficiency
:tornado: Ways tumour avoid immune system :tornado:
- Loss of tumour specific antigen
- Loss of MHC
- Expression of PD1 inhibitory