Preliminary Program (PDF)

(information subject to change)

| Saturday | Sunday | Monday | Tuesday | Wednesday | Thursday |

This interactive symposium is organized by Susan Elmore, MS, DVM, DACVP of NIEHS. The object of this symposium hasn’t changed from the last couple of years—it is to provide continuing education on interpreting pathology slides, to generate lively and productive conversation, and to have a good time. This is a free session, for meeting attendees, but due to space limitations, registration is required.

A select group of images from each speaker on the Website listed below. This is something new that we are trying this year and we hope that attendees will have a chance to view some or all of these images before the symposium. Follow the directions below to view the images at a variety of magnifications.

1. Go to http://sci-images.niehs.nih.gov/pwg/STP_07

2. Open the folder that corresponds with the image that you are looking
for.

3. Scroll to the bottom of that folder.

4. Click on the file named "Zoomify_AutoResize.htm"

5. Use the characters at the bottom to manipulate the image (move image,
increase or decrease the magnification).

CE Courses
Continuing Education Course Chair: Eugenia Floyd, DVM, DACVP, Pfizer, Inc.

Continuing Education Course #1:
Toxicologic Pathology of Natural Products

Co-sponsored with the C. L. Davis Foundation

Chair: Zadok Ruben, DVM, PhD, Patoximed Consultants, Westfield, NJ

The general orientation of this course is toward natural products that are related to pharmaceuticals. The history of natural products as medicines, issues in toxicologic pathology, and in regulatory-product development-cultural considerations will be addressed.

Introduction

Toxins in Nature—Mother Nature’s Little Surprises

Mother Nature is fickle and her character is often unique and surprising. Through selected case studies of toxicoses in animals, the interesting presentations, observed pathological lesions and necessary management will be reviewed. Clinical cases of blue-green algae, marine toads, venomous snakes, and mycotoxins in food supplies illustrate the special features of these naturally occurring hazards.

Fred Oehme, DVM, PhD
Kansas State University, College of Veterinary Medicine, Manhattan, KS

Potential and Approved Anti-neoplastic Drugs

A Historical perspective of Regulation of Natural Products in the USA

A historical perspective of regulation of natural products in the USA, as well as an overview of the Regulatory issues as they would impact Research and Development.

Regulatory Aspects of Natural Products Development

Continuing Education Course #2:
Carcinogenomics: An evolution of oncogenicity assessment for chemicals and pharmaceuticals

Chair: Jack A. Reynolds, DVM, DACLAM, DACVP, FIATP,
JA Reynolds & Associates, Madison, CT

Introduction

Carcinogenomics Assessment of Chemicals and Pharmaceuticals: An alternative strategy to the rat carcinogenesis bioassay

Rodent cancer bioassays are part of a legacy of safety testing that has not changed significantly over the past 30 years. The bioassays are expensive, time-consuming, and use hundreds of animals. In this session, the application of short-term genomic signatures for predicting rodent cancer bioassays will be demonstrated and the pros and cons of using the genomics signatures will be discussed.

The transformation of biological methods driven by rapidly emerging enabling technologies has resulted in our ability to readily generate millions of data points around biological processes. The ability to integrate, manage and query this plethora of data is essential to knowledge creation. This session will review the challenges and available solutions to interpretation and decision making using “omics” data.

Emerging Statistical Methods for Decision Making Utilizing Polyomics and Carcinogenomics Datasets

Analysis of microarray data presents unique challenges there are up to 500,000 data points distributed among a large number of subjects. Reliably determining significant genes requires sophisticated experimental design and analysis methods. In this seminar, we will discuss how to design, assess and analyze microarray experiments, thus providing high quality, significant gene lists for further research.

Continuing Education Course #3:
Toxicogenomics for Pathologists: Transcriptome Data Bring H&E Slides to Life (limited to 30 people)

Co-chairs: Gary A. Boorman, DVM, PhD, DACVP, NIEHS, Research Triangle Park, NC and Kevin Morgan, PhD, DACVP, sanofi-aventis, Bridgewater, NJ

This course offers a "hands-on" review of pathology lesions with associated gene lists which is where the pathologists can play an important role in relating gene transcript information to changes seen on H&E slides. The class will be limited to 30 participants.

The morning session will be informational lectures and the afternoon will be "hands on" evaluation of gene expression data with groups assigned to different data sets. Each data set will have a microscopic slide of the tissue from which the gene list was extracted with computers containing the expression data. Each group will be supervised by a pathologist in reviewing the gene lists to help understand the changes leading to the histological alterations.

Participants will receive a handout at the meeting and a CD that contains all of the data for the participants to take with them. The CD will also include the PowerPoint presentations presented in the morning session. The goal of the workshop is to familiarize pathologists with using gene expression data sets just as they would special stains to enhance the interpretation of the pathology alterations that they encounter in a toxicology study.

Scientific Sessions

Symposium Co-Chairs: Lynda Lanning, DVM, DABT, Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD; Kathleen A. Funk, DVM, PhD, DACVP, Experimental Pathology Laboratories, Inc., Herndon, VA

Welcome
Gerald G. Long, DVM, PhD, DACVP
STP President, Eli Lilly & Company
Greenfield, IN

Keynote Address

STP is very fortunate to have Dr. Edith Mathiowitz, Professor of Medical Science and Engineering and Director of the Graduate Program in Artificial Organs, Biomaterials, and Cellular Technology in the Department of Molecular Pharmacology and Biotechnology of Brown University as the keynote speaker. Dr. Mathiowitz received her Ph.D. in the Department of Structural Chemistry at the Weizmann Institute. At MIT, she continued her research as a postdoctoral student under Dr. Robert Langer. Since then, Dr. Mathiowitz has been involved in research, developing oral bioadhesive delivery systems for proteins and genes, microencapsulation of proteins and genes, and tissue engineering of vascular grafts. She has published 90 papers, has 30 patents, and is a consultant to many biotech companies. She is also the founder of Spherics. A Rhode Island biotech company.

Session A–Part1: Excipients, Vehicles and Drug Delivery Technologies
Chair: Julian L. Oliver III, DVM, PhD, DACVP
sanofi aventis, Bridgewater, NJ

This session will kick off the 2007 STP Symposium on Novel Technologies and will cover the use of, and issues associated with modern day vehicles and excipients as well as current and potential future methods of drug delivery / administration. Currently many new methods of administering medications are being developed that are more "user-friendly" to the patient, provide better bioavailability of the active compounds and /or enhance the desirable action of the products being administered. With these rapidly developing technological breakthroughs comes a new spectrum of toxicological and pathological issues. This session will cover some of these issues and some of the success stories of modern-day pharmaceutical delivery science.

Liposomes

Cyclodextrins

Anticipating, preparing for, and actually making a change can be daunting tasks. At the same time, the process can provide opportunity, challenge, clarity and growth, whether an actual job change is made or not. We all need to be curious about what lies beyond our field of vision (experience) and willing to embrace the discovery process lest we be left behind. Using real life stories of transition, Mary Lou Drake will be our guide as we focus on the future and on moving from where we are to where we want to be. Ms. Drake is President of Drake & Associates, a North Carolina - based Human Capital Management consulting company with over 30 Associates.

Session A–Part2: Excipients, Vehicles and Drug Delivery Technologies

Chair: Karyn Colman, BVetMed, MRCVS,
Bristol-Myers Squibb, New Brunswick, NJ

Session Introduction

Biolistics - Using Nanotechnology to Inject Pharmaceuticals Via Skin Patches

Novel Long-Acting Parenterals-Microparticles and Injectable Solid Implants

Break

Members of the STP Scientific and Regulatory Policy Committee will lead a discussion on Image Handling in Pathology.

Session B: Medical Devices: Current Materials, Methods And Development
Chair: JoAnn C. L. Schuh, DVM, PhD, DACVP, DABT
Applied Veterinary Pathobiology, PLLC,
Bainbridge Island, WA

Traditionally, toxicologic pathologists have had limited involvement with safety or efficacy evaluation of medical devices. However, advancements in biomaterials, increasing complexity of devices and advent of tissue engineering suggest future opportunities for more extensive involvement of toxicologic pathologists in the field of bioengineering. This session introduces toxicologic pathologists to ISO 10993 and other regulatory requirements, and provides a review of natural and synthetic biomaterials used to manufacture medical devices. Histologic techniques, animal models and the histopathology of biocompatibility at device-tissue interfaces and pathobiological responses during device failure will be discussed for a variety of products and in multiple tissue settings.

Slicing Devices

Break

Surface, External Communicating, and Implanted Devices

Medical Devices in Orthopedic Applications

Phil Long, DVM, PhD, DACVP
Vet Path Services, Inc
Mason, OH

Tissue Engineering and Regenerative Medicine

Free Time—Optional tours available

Session C: Genetically Based Therapies
Chair: Susan A. Elmore, MS, DVM, DACVP
NIEHS, Research Triangle Park, NC

Gene therapy represents one of the fastest growing areas in biotherapeutic research and the toxicologic pathologist has a central role in the integration of new technologies and more traditional assays in the safety assessment of gene-based medicines. This session will begin with an overview of gene therapy including history, various modalities of gene transfer and current applications of genetically based therapies in the treatment of a variety of disorders and diseases. A number of safety concerns surrounding the use of gene-based therapies will be discussed, particularly the inappropriate distribution or expression of vectors, transfection of germ cells and undesirable genomic integration. Speakers will also provide examples of current research investigating novel applications and modalities of gene therapy with a focus on the efficacy and safety of these applications.

Introduction

Gene Therapy: Some History, Applications, Problems and Prospects

Safety Assessment of Genetically Based Therapies

Break

Safety Assessment of an Adenoviral Vector

Safety Evaluation of Small Interfering RNA Therapy for
Age-Related Macular Degeneration

Gene Therapy Targeting Skin and Keratinocyte Stem Cells

Lunch (In Exhibit Hall)

Significance of Parameters from Hematology,
Biochemistry and Clinical Lesions for Pathology
Evaluation. Example: Lipopolysaccharide
(Significado de Parámetros Hematológicos, Bioquímicos y Síntomas Clínicos para la Evaluación de Estudios de Toxicología. Derivado de Lipopolisacáridos (LPS) – Un Ejemplo)

This session will be presented in Spanish and is open to all registrants. Please see page 10 for session details. La presentación será en español. Numerous detailed parameters of haematology, biochemistry and clinical symptoms are recorded during a toxicity study. These parameters may be helpful in the interpretation of results obtained by pathology evaluation. However, as standalone results, and without taking into consideration pathology parameters, they often are equivocal. Usefulness and possible misinterpretation of the aforementioned parameters will be discussed using the results of a 13-week toxicity study with a Lipopolysaccharide derivate (LPS, endotoxin). Released LPS causes pathological reactions including fever, leucopoenia, tachycardia, tachypnea, hypotension, disseminated intravascular coagulation and multiorgan failure. Endotoxinrelated pathology consists mainly of micro- and macrocirculatory changes (hyperdynamic shock form). Other than the septic shock related pathology, the stimulation of immuno-competent cells, hemorrhagic inflammation, and probably osteolysis, little is published on endotoxin-related organ changes. It is unknown to the authors, if other organ changes similar to those described in this presentation (organs involved are heart, lung, liver, kidneys, bone marrow, bone etc.) are present in human beings.

Promise and Challenges of Novel Therapeutic Modalities

Chair: Daniel Tumas, DVM, PhD, DACVP
Gilead Sciences, Inc., Foster City, CA

The pharmaceutical/ biotechnology industry continues to innovatively push the envelope in the treatment of complex chronic diseases and in so doing often has been the leader in validating targets and targeted approaches to the treatment of complex diseases in patients. This session will review some of these successes and failures and will focus on potential and real issues associated with specific targets and therapeutic approaches to these targets in oncology, immunology and virology. The intent is to demonstrate by example the progression of specific approaches and highlight some of the known or potential toxicological issues of these approaches. Topics will include: a broad overview of kinase inhibitors and the potential pitfalls and benefits of the “polypharmacy” of inhibitors that target more than one kinase, a review of antibody targeted therapeutics and the resurgence of toxin-conjugated antibodies, an approach touted a few decades ago as the “magic bullets” of oncology, a review of a new class of the therapeutics with potential broad application, aptamers, and lastly a brief review of the TLR system and efforts with agonists of these innate immune system “danger” receptors in viral and immune-mediated disease therapy.

Session D: Emerging Tools in Toxicologic Pathology
Chair: Mark F. Cesta, DVM, DACVP
NIEHS, Research Triangle Park, NC

Recent advances in materials science, digital technology and molecular biology have engendered a host of exciting and provocative research tools. Quantum dots, one of several new classes of fluorescent probes, are suited to a number of fluorescent imaging modalities. Digital breakthroughs have ushered methods in morphometric and cytometric analyses and heralded the debut of “digital pathology.” These emerging tools can increase productivity and facilitate scientific discovery. They allow us to efficiently gather, quantify, and process large amounts of data and more easily preserve and share our data with the scientific community. In the final session of the symposium, we will explore some of these powerful and sophisticated new tools and discuss their utility in toxicologic pathology.

The Application of Fluorescent Quantum Dots to Confocal, Multi-Photon, and Electron Microscopic Imaging

Applications of Laser Scanning Cytometry in Immunohistochemistry and Routine Histopathology

Monitoring Signal Transduction Inhibitors in Leukemia Patients by Flow Cytometry During Early Phase Clinical Trials

Break

Metabolic Profiling as a Tool for Understanding Mechanisms of Toxicity

The Evolution of Digital Pathology—What to Expect in the Near Future