kandakumar s (kk) molecular oncology lab (mol) seminar
TRANSCRIPT
MULTISTEP CARCINOGENESIS
KANDAKUMAR S Ph.D RESEARCH SCHOLAR PERIYAR UNIVERSITY
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Mol
ecul
ar O
nco
logy
Lab
(M
OL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular O
ncology Lab (MO
L)
Molecular Oncology Lab (MOL)
16.09.2014
Hallmarks of CancerSix fundamental changes
1. Self sufficiency in growth factors2. Insensitivity to growth-inhibitory signals3. Evasion of apoptosis4. Limitless replicative potential5. Sustained angiogenesis6. Ability to invade and metastasize
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
16.09.2014
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)Molecular Oncology Lab (MOL)
16.09.2014
Molecular Basis of multistep carcinogenesis
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
16.09.2014
CARCINOGENESISCarcinogenesis is a multistep process at both the phenotypic
and the genetic levels. CARCINOGENSIt starts with a (genetic damage):
EnvironmentalChemicalRadiationViral
Inhereted
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
16.09.2014
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Mole
cula
r Onco
logy
Lab (M
OL)
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Multistep CarcinogenesisColon Cancer:
APC – RAS – P53Hyperplasia – Adenoma – Carcinoma
Tumor progression and heterogeneity
Molecular Oncology Lab (MOL)M
olecu
lar O
ncolo
gy Lab
(MOL)
Molecular Oncology Lab (MOL)
16.09.2014
Molecular Basis of multistep carcinogenesis
Neoplastic transformation is a progressive process involving multiple “hits” or genetic changes.
Accumulation of multiple mutations since we need six fundamental changes
Evidence is both Epidemiologic: cancer increase with age Molecular : cancers analyzed show multiple genetic mutations
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Molecular Basis of multistep carcinogenesisAlterations in DNA cause changes in one or both of
the following types of genes:Proto-oncogenesTumor suppressor genes Best example is colonic cancerAPCRAS18qp53
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Molecular Basis of Multistep Carcinogenesis
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Molecular Basis of multistep Carcinogenesis
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Development of Sustained Angiogenesis
Tumors cannot enlarge beyond 1-2 mm thickness unless they are vascularized, hypoxia will induce apoptosis by activation of TP53 .
Angiogenesis is required for tumor growth & metastasis.Tumor-associated angiogenic factors may be produced
by the tumor or by inflammatory cellsTP53 inhibit angiogenesis by stimulation of anti-angiogenesis moleculesVEGF is under the control of RAS oncogene .Proteases are involved in regulating angiogenic &
antiangiogenic factors .
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Ability to Invade & Metastasize
1)Invasion of extracellular matrix
2)Vascular dissemination & homing of tumor cells
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Vascular dissemination & homing of tumor cells
Tumor cells binds to leukocytes, this protect them from host defense mechanisms
Tumor cells adhere to vascular endothelium & pass through BM
Site of extravasations & Meyts depends on: -Blood & Lymphatic supply -Organ tropism/adhesion molecules
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THANK YOU
Mol
ecul
ar O
ncol
ogy
Lab
(MO
L) Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
Molecular Oncology Lab (MOL)
16.09.2014