Medulloblastoma- A primitive neuroectodermal tumors (PNETs) is the most common malignant brain tumor of childhood (WHO IV)
arising from the vermis in the inferior medullary velum.
It comprises up to 18% of all pediatric brain tumors.
WNT and Shh pathway plays major role in its pathogenesis.
c-erbB-2 (HER2/neu) oncogene expression has prognostic value. Norcantharidin, Vismodegib, Sonidegib are the future in medulloblastoma.
Opportunities for Immune Therapy and Preventionbkling
Dr. Margaret Gatti-Mays of the National Cancer Institute, a Staff Clinician of Laboratory of Tumor Immunology and Biology and the Co-Director of the Clinical Trial Group, explores the future of immunotherapy in breast cancer treatment.
Last update of thyroid cancer management from diagnosis till follow up
You can request other lectures by emailing me at salahmab76@yahoo.com or calling me 0020 100 408 1234
Dr Salah Mabrouk Khallaf
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Medulloblastoma- A primitive neuroectodermal tumors (PNETs) is the most common malignant brain tumor of childhood (WHO IV)
arising from the vermis in the inferior medullary velum.
It comprises up to 18% of all pediatric brain tumors.
WNT and Shh pathway plays major role in its pathogenesis.
c-erbB-2 (HER2/neu) oncogene expression has prognostic value. Norcantharidin, Vismodegib, Sonidegib are the future in medulloblastoma.
Opportunities for Immune Therapy and Preventionbkling
Dr. Margaret Gatti-Mays of the National Cancer Institute, a Staff Clinician of Laboratory of Tumor Immunology and Biology and the Co-Director of the Clinical Trial Group, explores the future of immunotherapy in breast cancer treatment.
Last update of thyroid cancer management from diagnosis till follow up
You can request other lectures by emailing me at salahmab76@yahoo.com or calling me 0020 100 408 1234
Dr Salah Mabrouk Khallaf
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
This presentation demonstrates the current paradigm in the treatment of desmoid tumors. As the management is shifting from surgical approach to medical management.
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
nside Myriad. At Myriad, our goal is to make a difference in patients' lives and our work has been guided by this mission throughout the Company's history. ... Since 1991, Myriad has invested heavily in educating patients and healthcare professionals about the role genes and proteins play in disease.
Presentazione a cura del Dottor Gabriele Capurso - "HOT TOPICS IN GASTROENTEROLOGIA - I TUMORI DELL'APPARATO DIGERENTE: cosa è cambiato e cosa bisogna sapere" - Roma 10/11/2018
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Couples presenting to the infertility clinic- Do they really have infertility...
Mesothelioma - Multidisciplinary Treatment Update
1. Speaker:
Michele Carbone, MD, PhD
Director, Thoracic Oncology
University of Hawaii Cancer Center
Professor, Department of Pathology
John A. Burns School of Medicine
Speaker:
Harvey I. Pass MD
Stephen E. Banner Professor of Thoracic Oncology
Vice-Chairman, Research
Department of Cardiothoracic Surgery
Director, General Thoracic Surgery
Mesothelioma - Multidisciplinary Treatment Update
2. Mesothelioma, Causes and Prevention
Michele Carbone, MD, PhD
Director, Thoracic Oncology
University of Hawaii Cancer Center
Professor, Department of Pathology
John A. Burns School of Medicine
3. Disclosures
• FUNDING:
– University of Hawai‘i Cancer Center
– P30 CA071789 to MC
– V-Foundation 203-16 to MC & HY
– 1R01CA198138-01 2015-20 to MC
– DoD Team Translational grant 2016-2019 to HY and MC
– DoD Idea grant 2016-19 To MC and HY
– UH Foundation through donations from Honeywell Int. Inc. and from UNITED-
FOR-A-CURE to MC Open
• PATENTS:
– Awarded and/or pending patent applications on HMGB1 and BAP1.
• CONSULTING:
– Provides expertise and diagnosis at no cost to patients and colleagues and for a
fee to lawyers.
4. Malignant Mesothelioma (MM)
• The latency between initial asbestos exposure
and the development of MM is ~30-60 years.
• About 4.6% of miners who worked in crocidolite
asbestos mines for 10+ years developed MM.
• NGS 2-51 mutations/MM; average 23 (Guo et al.,
Cancer Res 2015)
• MM causes ~3,200 deaths per year in the US,
and > 100,00 deaths/year worldwide.
• In the US incidence stable since 2004, in the
rest of the world is increasing
• Median survival is ~12 months.
• About 5% diagnosed in Stage I.
• Asbestos and erionite exposure cause most
cases of MM.
• >20M people exposed to asbestos in the US
5. MM cases diagnosed in the US by sex
and year, 2003–2008
MM Incidence >75
1999: 42%
2010: 52%
Henley SJ et al 2013
9. Mechanisms of Asbestos Carcinogenesis
Yang H et al PNAS 2006, PNAS 2010, Cancer res 2012, CDD 2015
10. Animal model- mouse injected with asbestos
Strong HMGB1 and TNF- staining around areas of asbestos deposits
Yang H et al, PNAS 2010
11.
12. Animal model- mouse injected with asbestos
HMGB1 levels in the serum of mice injected with with a total of 5 mg of crocidolite
or chrysotile in a high-dose, short-term protocol with two weekly injections of 2.5
mg each. Qi et al Am j Pathol 2013.
HMGB1 serum levels are long-term persistent after exposure to
crocidolite but not to chrysotile
13.
14. Mesothelioma and Genetics:
The hunt for the meso gene
Roushdy-Hammady, ..., & Carbone. Lancet 2001.
Dogan, ..., & Carbone. Cancer Res 2005.
NCI P01 2007-13: M. Carbone PI , Testa, Pass, Cox, co-Pis
27. BAP1 mutations in the centuries
PLOS Genetics Dec 8, 2015 Advanced on line publication
• BAP1 mutations are transmitted through multiple generations over
the centuries
• These individual are very susceptible to environmental carcinogens,
such as UV light and asbestos
• Building large family trees allows to identify additional branches of
the family that inherited the mutation and have high incidence of
cancers and implement genetic counseling and preventive
measures
• The families we study undergo yearly ophtalmological and
dermatological examination past age 20 and every 6 months past
age 30.
• In addition we are enrolling them in a prospective biomarker clinical
trial study for HMGB1 and fibulin.
28. Mesothelioma Patients with Germline BAP1 Mutations
Have 7-Fold Improved Long-term Survival
Francine Baumann, Erin Flores, Andrea Napolitano, Shreya Kanodia,
Emanuela Taioli, Harvey Pass, Haining Yang, and Michele Carbone
2015
30. Kaplan-Meier survival curves of the BAP1 MM cohort
according to sex, age, MM site, and presence of other cancers
31. DoD IDEA 2016: New meso-genes.
M. Carbone & H. Yang
• This project will focus on the identification of those genetic
predisposing factors that increase susceptibility to asbestos
carcinogenicity and contribute to MM pathogenesis.
32.
33.
34. Positive nuclear BAP1 immunostaining helps
differentiate non-small cell lung carcinomas from
malignant mesothelioma.
• Michele Carbone, David Shimizu, Andrea
Napolitano, Mika Tanji, Harvey I. Pass, Haining
Yang, Sandra Pastorino
36. Yoshikawa Y et al., doi: 10.1073/pnas.1612074113
PNAS November 9, 2016
• We found that gene mutations/deletions are frequent in
mesothelioma and occur through a variety of DNA
alterations.
• We identified new genes implicated in malignant
mesothelioma: SETD2, SMARCC1, PBRM1.
• Previous next-generation studies (NGS) underestimated
the frequency of genetic alterations in malignant
mesothelioma because NGS mainly identifies nucleotide
level mutations
37. Conclusion
• In the US the incidence of mesothelioma has peaked to about 3200
and has remained stable for the past decade.
• Asbestos deposition induces chronic inflammation driven by HMGB1
and TNF-alpha that over time leads to MM.
• Inherited heterozygous BAP1 mutation cause MM and other
cancers. In germline BAP1 mutation carriers cancers are less
aggressive than their sporadic counterparts.
• Families with BAP1 mutations should be closely monitored for early
cancer detection.
• BAP1 is the most commonly mutated gene in sporadic MM.
• Many mutations are identified in sporadic MM using a combined
high density array CGH and target NGS sequencing. Previous
studies based only on NGS had underestimated mutation frequency
in MM
38. Biomarkers for Pleural Mesothelioma
Harvey I. Pass MD
Stephen E. Banner Professor of Thoracic Oncology
Vice-Chairman, Research
Department of Cardiothoracic Surgery
Director, General Thoracic Surgery
39. Disclosures
• Grants: NCI EDRN,TCGA, DOD, Technion, CDC,
• Philanthropy: Rosenwald Foundation, Stephen A. Banner Lung
Cancer Foundation, Belluck and Fox, Levi, Phillips and Konigsberg,
Simmons Foundation, Baron and Budd, multiple patients who shall
remain anonymous
• Industry: Fujirebio, 20/20 Gene, MesoScale Diagnostics,
Cynvezio, Source MDX, Celera, OPKO, SomaLogic, Genentech,
Integrated Diagnostics, Transgenomics, Rosetta Genomics,
Calithera, Pinpoint Genomics, Cizzle, emeraldLogic, HTG,
• Patents (no money): osteopontin for diagnosis and prognosis of
MPM; fibulin 3 for diagnosis and prognosis of MPM; mir-29c* for
prognosis of MPM; mir-31 for diagnosis of MPM, HMGB1 for
diagnosis of MPM
40. 0
20
40
60
80
100
Survival of 350 MPMs
14 deaths (4%) < 60 days
0 12 24 36 48 60 72 84 96 108 120 132 144 156
Time
(months)
Survival probability (%)
Number at risk
336 177 80 44 33 24 19 15 10 8 5 3 1 0
0
20
40
60
80
100
Survival of 350 MPMs
14 deaths (4%) < 60 days
0 12 24 36 48 60 72 84 96 108 120 132 144 156
Time
(months)
Survival probability (%)
Number at risk
336 177 80 44 33 24 19 15 10 8 5 3 1 0
13
0
20
40
60
80
100
Survival by HIP Site
1990‐2016
0 24 48 72 96 120 144
Time
Survival probability (%)
Number at risk
Group: Detroit MS 12 m
144 72 34 22 15 12 10 9 5 4 2 1 0 0
Group: New York MS 16 m
80 49 22 11 9 6 3 0 0 0 0 0 0 0
Group: Bethesda MS 12m
112 56 24 11 9 6 6 6 5 4 3 2 1 0
Site
Detroit MS 12 m
New York MS 16 m
Bethesda MS 12m
0
20
40
60
80
100
Survival by HIP Site
1990‐2016
0 24 48 72 96 120 144
Time
Survival probability (%)
Number at risk
Group: Detroit MS 12 m
144 72 34 22 15 12 10 9 5 4 2 1 0 0
Group: New York MS 16 m
80 49 22 11 9 6 3 0 0 0 0 0 0 0
Group: Bethesda MS 12m
112 56 24 11 9 6 6 6 5 4 3 2 1 0
Site
Detroit MS 12 m
New York MS 16 m
Bethesda MS 12m
0
20
40
60
80
100
Survival of 336 Pleural Mesotheliomas
1990-2016
0 12 24 36 48 60 72 84 96 108 120 132 144 156
Time
(months)
Survivalprobability(%)
Number at risk
Group: I
34 32 23 18 16 14 12 9 7 7 5 3 1 0
Group: II
61 41 26 15 12 7 5 4 2 0 0 0 0 0
Group: III/IV
166 86 27 10 4 3 2 2 1 1 0 0 0 0
Group: No MCR
75 18 4 1 1 0 0 0 0 0 0 0 0 0
Stage
I
II
III/IV
No MCR
58
18
12
6
41. “SCREENING” for Mesothelioma
• How do patients present in the US?
– 91% have an exposure to asbestos
– 90% of pleural patients present with an effusion
– 77% of abdominal patients present with ascites
• Effusions do NOT OCCUR OVERNIGHT
• Screening is done in asymptomatic patients with a
history of exposure to asbestos
– Therefore, you are attempting to define plasma biomarker changes
which could reflect the development of an asymptomatic effusion or
some “perturbation of mesothelial physiology” over time.
• A change in marker indices could lead to a CT of the
chest/abdomen
42. Biomarker Discovery
• Markers of Exposure (HMGB1 and isoforms)
– Non-exposed vs Exposed
– Matched for age, sex, smoking history
• Markers of Mesothelioma (Osteopontin, Fibulin 3, Soma 13)
– Asymptomatic, asbestos exposed vs MPM
– Refinement of Specificity
• Asymptomatic, asbestos exposed vs benign respiratory
disease vs other malignancies (preferably presenting as
effusions) vs MPM
• Prognostic Markers (Osteopontin, SMRP, Soma 13)
– Who needs further therapy?
– Who should receive aggressive, potentially toxic therapy?
43. 2004: use U133A arrays to compare 7
MPMs to 3 normal peritoneum
(mesothelium)…14,500 genes
N Engl J Med. 2005 Oct 13;353(15):1564-73.
45. • Resulted in a whirlwind of
controversy
– Failure to validate in
Australian Cohort or CARET
• Problems
– Thrombin Cleavage Site
– The ELISA being used
– Different populations for
controls not reflecting a high
risk screening population
Publication #MPM Notes
Cristaudo A,. J Thorac Oncol. 2011
Sep;6(9):1587‐93
31 Plasma AUC=0.8
Creaney J, Lung Cancer. 2011
Mar 11
66 Plasma AUC=0.76
Cristaudo A, Int J Biol Markers. 2010
Jul‐Sep;25(3):164‐7
32 Plasma AUC=0.78
Rai AJ. Clin Chem Lab Med. 2010
Feb;48(2):271‐8
205 Serum AUC=0.68
Paleari L. Int J Biol Markers. 2009
Apr‐Jun;24(2):112‐7
24 Plasma AUC=0.6
Grigoriu BD, Clin Cancer Res. 2007
May 15;13(10):2928‐35
94 Serum AUC=0.724
Pass HI, N Engl J Med. 2005
Oct 13;353(15):1564‐73
76 Serum AUC=0.88
Issues:
1. Was the ELISA for OPN satisfactory
2. Is plasma important?
48. Can Plasma Biomarkers “add value” to already
established Clinical Prognostic Indices?
• EORTC and CALGB Prognostic Indices are already an established clinical Prognostic
Index for MPM
• Can any of the Biomarkers we have talked about add value to the EORTC
Prognostic Index?
– Take the most relevant biomarkers in the literature and investigate that…..
• SMRP, Fibulin-3, Osteopontin
– Discovery Set: 83 MPMs from NYU and Wayne State University
– Blinded Validation Set: 111 MPMs from Princess Margaret Hospital
51. 37matched Peritonea and MPMs
RNA extraction
HG 1.0 ST Arrays
28,869 genes
• Candidate Genes for Secreted Proteins
Inquire GEO profiles
ELISA determination in Plasma
58 NYU MPM
96 NY Asbestos Exposed
30 “other” NYU Effusions
DISCOVERY
IN SILICO VALIDATION
FIRST ORDER VALIDATION
52. #/32,321 probe_id symbols annotation ttest.paired.fdr fold.change.paired
1 8178193 HLA‐DRA
major histocompatibility complex, class II, DR
alpha 4.49E‐07 11.7560741
2 7896308 NA NA 6.65E‐08 11.58329688
3 7899480 SNORA73A small nucleolar RNA, H/ACA box 73A 1.42E‐09 10.8688601
4 7896561 NA NA 4.88E‐14 10.81826501
5 7895001 NA NA 3.37E‐13 10.33878988
6 7896258 NA NA 2.55E‐11 10.27347585
7 7894315 NA NA 2.57E‐09 10.22125339
8 7895101 NA NA 6.47E‐11 9.946499931
9 7892514 NA NA 1.75E‐11 9.499949191
10 7893543 NA NA 9.36E‐07 9.285996806
11 8096301 SPP1 secreted phosphoprotein 1 1.92E‐13 9.191609924
12 7893424 NA NA 2.98E‐07 9.024945572
13 7892639 NA NA 5.63E‐10 8.992779777
14 7894264 NA NA 1.86E‐09 8.653358226
15 7895873 NA NA 4.83E‐11 8.482593475
16 8058765 FN1 fibronectin 1 9.94E‐14 8.452420124
17 7892599 NA NA 3.55E‐10 8.332134431
18 7893103 NA NA 2.65E‐07 8.318946229
19 7895299 NA NA 5.40E‐10 8.227536834
20 7893173 NA NA 2.43E‐09 8.175192493
21 7896542 NA NA 1.98E‐12 8.148581397
22 7894516 NA NA 2.07E‐10 8.126757075
23 7894074 NA NA 7.44E‐10 8.096863972
24 7892972 NA NA 1.02E‐06 8.047826351
25 7895334 NA NA 3.88E‐10 7.989057851
26 7895012 NA NA 9.76E‐07 7.864289572
27 7895907 NA NA 2.67E‐10 7.846854849
28 7893782 NA NA 4.29E‐11 7.806424167
29 7894798 NA NA 5.64E‐09 7.805304933
30 7895985 NA NA 6.39E‐09 7.782686318
31 8091283 PLOD2
procollagen‐lysine, 2‐oxoglutarate 5‐
dioxygenase 2 1.12E‐14 7.760882762
32 7894044 NA NA 3.08E‐09 7.5976604
33 7943160 SCARNA9 small Cajal body‐specific RNA 9 8.75E‐11 7.557312113
34 8130867 THBS2 thrombospondin 2 7.47E‐12 7.557021973
35 7894512 NA NA 2.46E‐08 7.512051025
36 8019762 NA NA 9.75E‐15 7.505448533
37 8052355 EFEMP1
EGF‐containing fibulin‐like extracellular
matrix protein 1 1.32E‐09 7.357396759
53. Fibulin-3 (EFEMP1)
• One of the “short” fibulin members
• 2p16
• Extracellular glycoprotein
• Knockouts associated with early aging
• Missense mutation is the cause of autosomal
dominant macular degeneration.
• Functional ligand of EGFR activating Akt- and
mitogen-activated protein kinase (MAPK)-
signal transduction.
54. Fibulin-3 Is Uniquely Upregulated in Malignant Gliomas
and Promotes Tumor Cell Motility and Invasion
• Promotes invasion,
adhesion, and
migration
• Has a predominant
isoform
56. Plasma FBLN3 Can Discriminate MPM From Other
Conditions And Is Elevated In Early Stage MPM
Mesothelioma
**
N Engl J Med 2012 Oct 11;367(15):1417-27.
57. Plasma FBLN3 Blinded Validation:
The Princess Margaret Cohort
AUC=0.87
N Engl J Med 2012 Oct 11;367(15):1417-27.
58. Plasma FBLN3 Falls After MPM
Cytoreduction and Rises at Recurrence
N Engl J Med 2012 Oct 11;367(15):1417-27.
59. What about Effusion Fibulin-3 Levels?
N Engl J Med 2012 Oct 11;367(15):1417-27.
60. EFEMP1 Message/Media Protein is present in all MPM
cell lines and not in Tag/Tert Transformed mesothelial
cell lines or lung cancer cell lines
British Journal of Cancer (2015), 1–7 | doi: 10.1038/bjc.2015.286
62. Biomarker Discovery with SomaLogic Slow Off
Rate Modified Aptamers Platform
N
N**
N*
Pi
A
Pi
P
Pi
A
A
A
hv
A PC
A PC
Pii
Piii
63.
64. Future Plans: SomaLogic
• EDRN Competetive Renewal
• Develop a luminex based SomaMer 13 assay in the NYU Laboratory
for further validation
• Combine the SomaMer 13 with a novel Fibulin 3 SomaMer to create
a more specific SomaMer 14 assay
• Validate the SomaMer 13 assay for prognostic potential
69. Conclusions
• Exploration of blood based biomarkers may lead
to novel biomarkers of asbestos exposure as
well as the development of mesothelioma.
• Blood based biomarkers may also help in
determining which pleural mesotheliomas are
most aggressive, altering therapeutic decisions.
• Validation of these markers is necessary before
their use in the clinic.
70. Thanks to…
• NYU Thoracic Lab
– Chandra Goparaju PhD
– Jessica Donington MD
– Ryan Harrington BS
– Amanda Beck BS
– Joe Levin BS
– Nathalie Hirsch BA
• Mt. Sinai Selikoff Foundation
– Stephen Levin MD
• DMCC
– Mark Thornquist PhD
• Carbone Laboratory, University of Hawaii
– Michele Carbone MD, PhD
– Haining Yang, PhD
• Antoine Laboratory, University of Liverpool
• University of Toronto
– Ming-Sound Tsao MD
– Geoffrey Liu MD
• NCI Early Detection Research Network
• CDC National Mesothelioma Virtual Bank
• NCI TCGA Mesothelioma
• Department of Defense CDMRP
• SomaLogic
– Rachel Ostroff PhD