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UTS Biokank, Soal UTS
Yang membedakan kanker sama sel normal (Hallmark…
UTS Biokank
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Tumor Micro Environtment
Mekanisme
- Pre invasive tumor (kerusakan DNA, proliferasi, menghambat kerja Sel imun T)
- Tahap invasive (Menhancurkan ECM, angiogenesis, hijacke imun sel)
- Tahap Intravasi ( Masuk ke pembuluh darah, beredar, hijacke imun dan trombosit to survive)
- Pre-Metastatis nische ( Mengirim sinyal in besikel or sitokin to preparing place in other organ, hijacked imun, fibroblast growth factor)
- Metastatsis (ekstravasi, menempel jaringan baru, develop new tumor n angiogenesis)
- Complex ecosystem surrounding cancer Cell
- Active promoter of cancer progression
Components
Imune Cell
- Adaptive ( CD8+/CD4+, T cell, B cell)
- Myeloid (TAMs, Neutrofil, MDSCs, DCs)
- Innate (NK cell)
- Reprogramming to immunosupressive state common
Stromal Cell and matrix)
- Cancer asosiated fibroblast (CAFs)
- Synthesize/ remodel ECM
- Promotes tumor proliferation/metastasis/immunosupression
- Endothelial Cell (EC) = blood vessel n intravasion
- Extracelular matrix ( sacffold, cell influence, promotes spread)
- Adipocytes ( obesity link, release growth factor)
Exosomes ( Microvesicle, critical for crosstalk and progression, making CAFs, worsen prognosisi)
Immune Evasion Mechanism
- Downregulating MHC class1
- Expressing inhibitory receptor
- secreting immunorsupression cytokines
- Exploiting immune checkpoints
- Recruiting Tregs and MDSC
Immunoediting Phase
- Elimination (immune system clears tumor cells)
- Equilibrium (Balance between tumor and immune system)
- Escape ( Tumor growth unrestricted)
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Hallmark of Cancer
Core Hallmark of Cancer
- Sustaining proliferation signaling (oncogene)
- Evading Growth Suppressor (TGS)
- Resiting cell death (P53)
- Activating invasion and metastasis
- Enabling replicative immortality (telomerase enzim)
- Inducing Angiogenesis (nutrient, O2 and waste)
Emerging Hallmark
- Deregulating cellular energetic = Phosporylation oxidative -> Aerobic glycolysis for rapid growth
- Enabling replicative immortality = avoiding immune destruction
Enabling Characteristic
- Genome instability and mutation = akumulusi mutasi dan kerusakan DNA mendukung resistensi kematian sel
- Tummor-promoting inflammatin = Peradangan kronis dapat menyebabkan lingkungan yang mendukung pertumbuhan kanker. Sel imun SWITCH TEAM
Cell Cycle, Apoptosis, dan Immortality
Cell cycle
- Phase:
- G1 (First Gap)
- S (DNA Synthesis)
- G2 ( preparation for Mitosis)
- M (Mitosisi: Profase, Metafase, Anafase, Telofase)
- Control:
- Checkpoints (Surveillance mechanism often inactive in cancer)
- Restriction Point ( R point= G1 decision point)
- CDKs and Cyclins (Kinase regulated by Cyclins)
- pRb Proteins (Gyard R-point, inactivation leads to proliferation)
Apoptosis
- P53 role ( Arrest cell or trigger apoptosis)
- Cancer Evasion Strategies:
- Innactivation of P53 pathway
- Deregulated BCL2 (Anti-apoptotic agent)
- Hyperactivation of PI3k -> Akt/PKB pathway)
- Celular sel-destruction (via capcase activation)
- Pathway:
- Intrinsik (Mitokondria mediated)
- Extrinsik (Receptor activated = Death receptor, DISC)
Cell Immortalization
- Prerequisite for all human cancer
- Normal cell limited by senecense and Crisis
- Telomere Maintenance (Avoid shortening and crisis):
- Telomerase (Protect chromosome ends)
- Crisis ( Telomere erosion, chromosomal fusion, apoptosisi)
- hTERT (Telomerase enzyme, regenrates telomeres, active in 85-90% tumor)
- ALT mechanism ( Alternative Lengthning of Telomeres, telomerase-independent)
- BFB Cycle (Breakage-Fussion-Bridge, promotes karyotypic chaos)
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Cancer Risk Factor
Classification
- Unmodifable intrinsic (Random DNA replication errors)
- Modifable Exogenous ( Lifestyle, Environtment)
- Partially Modifable Endogenous ( Immune, DNA repair response)
Key Factors
Tobaco use
- Leading preventable cause
- Carcinogens cause DNA damage (benzo[a]phyrene)
- Seconhand smoke increase risk 30%
- Alcohol consumption ( Synergistic with tobaco, liver/ephitelial cancers)
- Aging (Most significant risk factor, reflects accumulated damage)
- Heritable factors (Inherited mutation, ussualy TSGs or DNA repair genes
Diet/Bodyweight/activity
- High fruit, veg intake decrease risk (antioxidant)
- Red meat consumption link ( fat, cooking carcinogens0
- Excess bodyweight/ inactivity increase risk (13 types)
Radiation
- UV Radiation ( Skin cancer, melanoma)
- Ionizing radiation ( Xrays, nuclear, penetrates internal organs)
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Hormonal Factor
- Lifetime menstrual cycles (higher risk breast/ovarian cancer)
- Obesity (Increase estrogen synthesis)
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Soal UTS
- Yang membedakan kanker sama sel normal (Hallmark of cancer)
- Tiga mekanisme aktivasi Onkogen Myc
- Peran P53 dalam meregulasi Kanker
- Jelaskan 2 mekanisme regulasi yang mengatur kapasitas replikasi sel secara in vitro
- Jelaskan gambar tahapan metastasis kanker ke organ organ
- Faktor intrinsik yang meregulasi kanker