santosh patnaik, md, phd assistant professor … patnaik, md, phd assistant professor department of...
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Santosh Patnaik, MD, PhDAssistant Professor
Department of Thoracic SurgeryRoswell Park Cancer Institute
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First case of lung cancer 1751
World-wide lung cancer cases up to 1898 140World-wide lung cancer cases up to 1912 374
World-wide lung cancer cases in 2012 1800000
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Mayan god smoking (ca. 1c BC)
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1612 China1723 Berlin–1920s 14 US states
Bonsack cigarette roller, 1880 invention
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in 2012
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Ephemeral value of research
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Epidemiology Diagnosis
Treatment Biology
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British Doctors' Study 1951–200180% UK doctors smoked in 50s
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80% of mesothelioma (pleural cancer) by asbestos
2013: 50,000 mesothelioma cases world-wide
2002: US asbestos production ends
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Not because of UV, radon, etc.
Not seen for breast cancer
Oxygen-driven tumorigenesis?
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CDC MMWR, 2015, 64(14)
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Am J Physiol, 309(12), 2015
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Lung adenocarcinomaCancer Genome Atlas; Nature 511:543, 2014
aaa
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Lung squamous cell carcinomaCancer Genome Atlas; Nature 598:520, 2012
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Major lung cancer-associated signaling pathways
Eur Resp J, 35(2), 2009
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Spontaneous/treatment-inducedmouse models of lung cancer
Spontaneous
~3% of wild mice100% of A/J strain mice (KRAS polymorphism)
Treatment-induced
Cigarette smoke: very weakCigarette smoke constituents: stronger
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i.p.=intraperitoneal,i.g.=intragastric,i.t.=intratracheal,AD=adenoma,ADC=adenocarcinomaBenzo(a)pyrene=B(a)P4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone=NNKN-nitroso-tris-chloroethylurea=NTCU
FrontiersinBioscienceE5,939-946,June1,2013
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Systems for genetically engineering mouse models
Eur Resp J, 35(2), 2009
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Eur Resp J, 35(2), 2009
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Human lines >> mouse
Examples; ATCC®
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Human Mut, 30(8), 2009
Genetic alterations in lung cancer cell lines
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Tumoral mechanisms of immune escape•Reduced antigen presentation•Antigenic loss•Immune checkpoints
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Tumoral mechanisms of immune escapeReduced antigen presentationAntigenic lossImmune checkpoints
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(MUC-1 epitope)
(4 irradiated cell-lines with TGF-b2 antisense)
(MAGE-A3 protein)
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CIMAvax-EGF
•First therapeutic cancer vaccine for non-small cell lung cancer•Immunization with EGF–Neisseria P24 protein (+adjuvant)•Center of Molecular Immunology, Cuba (25 y to develop)•Preventive?•Available in Cuba•Testing to begin in US, Japan, etc. Vaccinated Control
stage IIIB/IV NSCLCJCO 26(9), 2008
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Time (months)Clin Cancer Res, 2016 Feb 29
Phase III, randomized trialStage IIIB/IV NSCLC
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Adoptive cell therapyIsolate immune cells > engineer in vitro > inject
1. Introduce chimeric antigen T cell receptor (CAR) against cancer antigens
2. Expand killer or infiltrating cell populations
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Cancers 2015, 7(3)
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F1000 Med Rep 2011, 3:21
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MetforminBiguanide
French lilac used against diabetes for centuries
Synthesized in 1920sHypoglycemic effect noticed in 1920sAnti-diabetic trial 1957US use 1995
Now most widely used anti-diabetic
Metformin may reduceoccurrence of cancercancer mortality, recurrence, metastases...variety of cancers
Vitamins, anti-oxidant, anti-inflammatory, anti-lipid...
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J Med Endocrin 48, 2012
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Metformin and survival after early-stage NSCLC
Ovarian cancer. Cancer. 2013 Feb 1;119(3):555-62
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Metformin
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