Mesothelioma/Mount Sinai School
of Medicine
• 1960s: Irving Selikoff and colleagues at
Mount Sinai: co-discovered and publicized
link between asbestos exposure and
mesothelioma
• Early 21st century: Dr. Raja Flores, Dr.
Cordon-Cardo providing dynamic
leadership in thoracic surgery and
molecular pathobiology/specimen banking
Selikoff
Occupational Safety and Health
WIKIPEDIA: In the 1960s Selikoff documented
asbestos-related diseases among industrial
workers. He found that workers exposed to
asbestos often had scarred lung tissue 30 years
after exposure. His research is credited with
having pressured the Occupational Safety and
Health Administration (OSHA) to limit workplace
exposure to asbestos.[2]
Selikoff
In the 1950s, Selikoff had opened a general-medicine
practice called the Paterson Clinic in Paterson, NJ. A few
years later, the Asbestos Workers Union asked him to
add their membership to his practice. He agreed, and
business picked up noticeably. In a few years, however,
Selikoff noticed surprising events; several new cases of
mesothelioma were diagnosed in a year—the expected
incidence was about 5/100,000. (The new cohort
(asbestos workers) were still a small fraction of the
clinic's patient list, but this small group faced grave and
novel risks.)
Selikoff
This anomaly led Selikoff into an examination of the
relation between asbestos exposure and mesothelioma.
He became aware of hundreds of articles previously
published on this issue. He engaged in additional studies
of groups of asbestos workers, in particular shipyard
workers including those at the Long Beach Naval
Shipyard. By 1965, he had conducted various studies,
published several articles, conducted special scientific
symposia, and been interviewed by the New York Times.
Each of these raised public awareness of the issue,
which had been known to the occupational health
community but which had not yet reached widespread
public awareness
Mt Sinai
• Twenty top funded medical institutions, most
rapidly growing in research funding in NY Area.
• Renowned in environmental medicine
• Dynamic thoracic surgery division
• Drs. S. Levin and A. Todd: close relationship
with International Association of Heat and Frost
Insulators and Allied Workers (IAHFIAW):
asbestos exposure
• World-class team of interventional thoracic
radiologists
• Active and expanding specimen biorepository
Commitment to NMVB
• Mesothelioma resections/year at Mount
Sinai: 30
• Commitment includes contributing
specimens for any Letter of Intent
approved by NMVB’s Research Evaluation
Panel
Commitment to NMVB
• Within 2 months of notification of funded
participation in NMVB, we received
approval from Mt. Sinai’s IRB
• First patient identified this week who will
participate in the program.
• NMVB protocols are in alignment with Mt.
Sinai’s biorepository protocols for tumor
tissue banking.
Mission
The Cancer Institute Biorepository is a shared
resource administered directly by the Tisch Cancer
Institute which provides an extensive biospecimen
resource with associated clinical data in order to
facilitate translational research for Mount Sinai
investigators and collaborators. The highest quality
annotated collections provide a platform for
translational research that can lead to improved
diagnosis and care of cancer patients.
Services/ Process Flow
•
•
•
•
•
•
•
•
Coordinate patient consent for donation of specimens
Coordinate timely processing, annotation and storage of specimens
Collect pre-and post-surgical blood samples and process into
serum, plasma and peripheral blood leukocyte fractions
Collect urine samples for specific projects
Perform histologic staining and pathology review of tissue
specimens, using mirror image samples adjacent to frozen samples.
Oversee regulatory compliance: IRB, HIPAA, NY State Dept. of
Health; best practice methods for safe processing and usage of
specimens
Oversee quality assurance, both for integrity of specimens and
reliability of clinical data
Maintain utilization committee to perform regulatory and scientific
review of, and prioritize requests for, specimen-related projects
Radiology
( GE IDXRAD
Laboratory
)
( SCC
Pathology
)
( TAMTRON
External
)
Lab
( QUEST
Caregiver
)
External Master
Credential
Code Sets
( ICD 9 , CPT
Access Management
( CERNER
4 etc .)
)
Inpatient
CPOE
( Eclipsys
Discharge
Team
)
Assignment
Discharge
Planning
&
Summary
Operative
Report
Mount Sinai Data Warehouse
Outpatient
CIS
( EPIC
)
Surgery
Chemotherapy
ED CIS
( IBEX
)
(EAGLE
Clinical and
Case
Billing
)
Financial
Management
( CANOPY
)
Decision Support
System
Heme/Onc
Radiation Oncology
&
Staffing
William K. Oh, MD, Medical Director
David E. Burstein MD, Pathology Co-Director
Carlos Cordon-Cardo, MD, PhD, Pathology Co-Director
Administrative Director: TBN
Maria Saravia: Tissue procurement and consenting
Tricia Ali-Shaw: Tissue procurement and consenting
Camelia Iancu-Rubin, Program Coordination, Heme
Boris Rudoy, IT programmer
Equipment
• Three -80 degree Revco freezers with emergency power
backup
• Five 50 gallon liquid nitrogen tanks
• Freezers located in the basements of Atran and
Guggenheim Pavilions
• Sample processing located on Annenberg 15 and 24
Representative Projects
Specimen
Type
Lung cancer,
frozen
N
PI
Primary and
metastatic
carcinoid,
frozen
Melanoma,
frozen
19
D Zhang HCC
15
E Bernstein CMT
Soft tissue
sarcomas,
frozen
18
S Aaronson CMT
MPN, blood,
aspirates
89
R Hoffman MMP
MPN, blood,
aspirates
34
M Xu MMP
132 S Aaronson CMT
Findings and outcome
“Wnt activation predicts worse prognosis in Stage 1 lung cancer” led
to platform presentation, 2010 American Assoc. of Thoracic Surgery
by collaborator, C Chin
“Differential protein expression in small intestinal carcinoids and
liver metastases” led to presentation, 2010 North American
Neuroendocrine Tumor Society
Resulted in K12 award to collaborator, M Kim.
Publication: Kapoor A et al. “The histone variant macroH2A
suppresses melanoma progression through regulation of CDK8,
Nature 2010, 468:1105-9.”
Contributed to RO1 renewal
Publication: Vijayakumar S et al. “High-frequency canonical Wnt
activation in multiple sarcoma subtypes drives proliferation through
a TCF/β-catenin target gene, CDC25a.” Cancer Cell 2011, 19:60112.
“Use of stem cells derived from the chromosome-negative
myeloproliferative disorders as a chemotherapeutic target”
Funded by MPD Foundation
Multiple publications
Contributed to NY State Stem Cell grant, awarded
“Rational use of combinations of chemotherapeutic agents for the
treatment of myeloproliferative disorders”
Funding: Leukemia and Lymphoma Society
Contributed to RO1 grant, awarded
Recent research
• Mutat Res. 2011 Aug 16;723(2):171-6.
Epub 2011 May 6.
• Crocidolite asbestos-induced signal
pathway dysregulation in mesothelial
cells.
• Wang H, Gillis A, Zhao C, Lee E, Wu J,
Zhang F, Ye F, Zhang DY.
Recent research
• Cancer Res. 2005 Apr 1;65(7):2602-9.
• Evidence against a role for SV40 in human
mesothelioma.
• Manfredi JJ, Dong J, Liu WJ, Resnick-Silverman
L, Qiao R, Chahinian P, Saric M, Gibbs AR,
Phillips JI, Murray J, Axten CW, Nolan RP,
Aaronson SA.
• Source
• Department of Oncological Sciences, Mount
Sinai School of Medicine, New York, New York,
USA.
Recent research
• Am J Ind Med. 2008 Nov;51(11):877-80.
• Environmental exposure to Libby
Asbestos and mesotheliomas.
• Whitehouse AC, Black CB, Heppe MS,
Ruckdeschel J, Levin SM.
Publications
• Surgical treatment of malignant pleural
mesothelioma.
• Kaufman AJ, Flores RM.
• Curr Treat Options Oncol. 2011
Jun;12(2):201-16.
Publications
• Clin Chem Lab Med. 2010 Feb;48(2):271-8.
• Soluble mesothelin related peptides (SMRP)
and osteopontin as protein biomarkers for
malignant mesothelioma: analytical
validation of ELISA based assays and
characterization at mRNA and protein levels.
• Rai AJ, Flores RM, Mathew A, GonzalezEspinoza R, Bott M, Ladanyi M, Rusch V,
Fleisher M.