Organization Chart Title

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Mission Statement

• M. D. Anderson Cancer Center Orlando will use
  every available
• resource to defeat cancer

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Medical Staff

• Employed full time (37)
• Medical oncology (9)
• Medical neuro-oncology (2)
• Radiation oncology (5)
• Pediatric hematology/oncology (5)
• Gynecologic oncology (3)
• Thoracic surgical oncology (2)
• Head/neck surgical oncology (1)
• Plastic/reconstructive surgery (2)
• Internal medicine/Palliative care (3)
• Nuclear medicine (4)
• Dental oncology (1)

• Contracted Community based (20)
• Surgical oncologists (5)
• Urology (3)
• Colo-rectal surgery (5)
• Neuro-surgery (2)
• Medical pulmonology (1)
• Dental surgery (4)
• 2009 Total - 57

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Medical Staff Model

• 14 Medical/Surgical Specialty Sections
• Breast
• Cancer medicine/palliative care
• Gastrointestinal
• Genitourinary
• Gynecologic
• Hematology (benign)
• Leukemia
• Lymphoma/myeloma
• Melanoma/sarcoma
• Neuro-oncology
• Nuclear medicine
• Pediatric hematology/oncology
• Plastic/reconstructive surgery
• Thoracic/Head Neck

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Fellowship programs

• Hematology/Medical Oncology Fellowship (3 yr)
• 2 finishing 2nd year
• 2 finishing 1st year
• 2 starting July 1 (26 candidates interviewed)
• Colorectal Surgery Fellowship (2 yr)
• 2 finishing 2nd year
• 2 finishing 1st year
• 2 starting July 1
• Infectious Disease Fellowship (2 yr)
• 2 finishing 1st year
• 2 starting July 1

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THE MAJOR CAUSE OF DEATH FROM CANCER IS DUE TO
METASTASES THAT ARE RESISTANT TO CONVENTIONAL
THERAPIES
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METASTATIC CASCADE
TRANSFORMATION
ANGIOGENESIS
MOTILITY INVASION
Capillaries,Venules, Lymnphatics
ARREST INCAPILLARY BEDS
EMBOLISM CIRCULATION
TRANSPORT
ADHERENCE
MULTICELL AGGREGATES (LYMPHOCYTES, PLATELETS)
EXTRAVASATIONINTO ORGANPARENCHYMA
RESPONSE TOMICROENVIRONMENT
METASTASIS OFMETASTASES
TUMOR CELLPROLIFERATION ANGIOGENESIS
METASTASES
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CANCER METASTASIS

• PRIMARY NEOPLASMS ARE BIOLOGICALLY HETEROGENEOUS.
• THE PROCESS IS HIGHLY SELECTIVE FOR
• PRE-EXISTING METASTATIC CELLS.
• THE PROCESS DEPENDS ON THE INTERACTION OF TUMOR
  CELLS WITH HOMEOSTATIC FACTORS.

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Tissue Bank Collect human tissue-
normal/diseased, blood, urine Generate human
cancer cell lines from patients Murine models
primary and metastatic models Orthotopic (brain,
breast, colon, esophageal, head and neck, kidney,
lung, pancreas, prostate) In vivo Imaging
Assessing Tumor Growth and Metastasis Fluorescenc
e, bioluminescence, X-ray Evaluate the
therapeutic efficacy of nanoparticles, targeted
agents, chemotherapy, radiation Administer
therapy by oral gavage, intravenous,
intraperitoneal, subcutanous methods On-site
irradiator for whole body and site-specific
radiation Harvest and necropsy tumors
Pathology/Histology/Immunohistochemistry Process
tissue (snap-freeze, paraffin and
frozen) Chromogen staining (bright
field) Fluorescent staining (fluorescence
microscope)
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MODELS FOR CANCER METASTASIS MUST EMPLOY

• Relevant cell populations
• Relevant organ environment

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Orthotopic murine model of human pancreatic cancer
Human pancreatic cancer L3.6pl cells were
injected into the pancreas of nude mice and a
primary tumor was formed at 1 week. The tumor
continued to grow for 4 weeks before the mice
became moribund
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Orthotopic lung tumor growth in mice
4 weeks
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Orthotopic murine model of human lung cancer
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GN963ECPT-11 Treatment
Normal Cecum Control
Treatment
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ORTHOTOPIC PROSTATE MODEL Group Daxx KD
M-04 Date of injection 3-11-09 Injection 1
Million cells / 5µL Right lobe of Prostate Date
of Termination 4-13-09 (4 Weeks post injection)
SEMINAL VESICLES
TUMOR
BLADDER
TESTES
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ORTHOTOPIC PROSTATE MODEL Group rhRNA Control
M-08 Date of injection 3-11-09 Injection 1
Million cells / 5µL Right lobe of Prostate Date
of Termination 4-13-09 (4 Weeks post injection)
SEMINAL VESICLES
TUMOR
BLADDER
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Prostate cancer cells labeled with luciferase
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Cutaneous injury caused by therapeutic radiation
to the chest wall
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Challenge

• Create a drug that protects normal tissue from RT
• Radioprotective Pharmaceuticals
• Decades of development 1 FDA approved drug
• Amifostine (only approved for limited
  applications)
• Why?
• Difficult to create a drug that protects normal
  tissue
• without protecting cancerous tissue
• Many tested radioprotective drugs have
  significant side effects
• These side effects negate the potential benefits
  of use

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Potential Solution

• Nanoceria
• Antioxidant Properties
• Numerous studies indicate nanoceria scavenges
  free radicals
• Toxicity
• Molecular cerium oxide toxicity is relatively low
• LD50 465 mg/kg (mouse)

Silva, G. Nature Nanotechnology. Vol.1. Nov.
2006. Pg. 92
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Administration of radiation to small animals
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In Vivo Validation
Survival Curve
Nanoceria increased median radiation survival
from 132 to 225 days
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Development of Radiation-Induced Pneumonitis in a
Murine Model
Lungs from mice treated with 18 Gy radiaton in
combination with NPs
Lung from mice treated with 18 Gy radiation only
Lungs were removed 9 weeks
post radiation Note Protection of
radiation-induced pneumonitis in the presence of
NPs
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In Vivo Validation
Histology of Lung Tissue H E Stain
Nanoceria decreases radiation induced pneumonitis
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In Vivo Validation
NPs protect normal tissue from radiation-induced
damage, while sensitizing tumor cells to
radiation treatment
N
A (Radiation alone)

• Slide A (radiation alone) shows a radiated
  pancreatic tumor surrounded by non-functional
  pancreas tissue
• Slide B (NPs radiation) shows a radiated tumor
  surrounded by functional normal pancreas tissue

T
N
B (Radiation NPs)
T
T Tumor N Normal
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XEROSTOMIA EXPERIMENT
5 Gy x 6 Doses
5Gy x 6 doses 15nM Nano Particles
5 Gy x 6 doses 15uM Nano Particles
Control No Rad.
1 Week Post Rad.
4 Week Post Rad.
12 Week Post Rad.
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PROTEASE INHIBITION OF INVASION IN HEAD AND NECK
CANCER

• LEKTI (Lympho-Epithelial-Kazal-Type-related-Inhi
  bitor), an inhibitor of multiple serine
  proteinases that regulate degradative enzymes,
  contributes to the invasive and aggressive
  behavior of head and neck cancer, characterized
  by perineural and lymphovascular invasion.

• LEKTI has an abundant expression in normal
  mucosa and conspicuous absence from HNSCC biopsy
  specimens.

• Forced expression of LEKTI in an established
  HNSCC line inhibits perineural and lymphovascular
  invasion in an animal model. We hypothesize that
  HNSCCs that fail to express LEKTI exhibit a
  critical set of active proteinases and pathways
  that establish invasive and aggressive
  phenotypes.

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PROTEASE INHIBITION OF INVASION IN HEAD AND
NECK CANCER
Previous experiments on tissue samples obtain
from patients that presented with squamous cell
carcinoma of the tongue, demonstrated the
expression pattern of LEKTI. It was determine
that patients that had a strong expression of
LEKTI had better treatment outcome, including a
less aggressive nature of their disease and less
recurrence during the follow up period.
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Sp PROTEINS EXPRESSION IN TUMORS
Colon cancer
Colon cancer
Normal Colon
Sp1

/-
Ku70/Ku80 (DD protein kinase)

/-
Hosoi Y, Watanabe T et al. Int J Oncol 2004, 25,
461-468.
Pancreatic cancer
Pancreatic cancer
Normal pancreas
Sp1

/-
VEGF

/-
Shi Q, Le X et al.. Cancer Res 2001, 61,
4143-4154.
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Tolfenamic Acid
Tolfenamic acid and derivatives
Sp proteins
Genes critical for cancer cells/tumor growth and
radiosensitization
Increase tumor response to therapy
Suppress tumor growth
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Cytokeratin 8 (CK8)

• Cytokeratin 8 (CK8) is an intracellular,
  structural protein found in normal epithelial
  cells
• Cancer cells (epithelial) display CK8 on the
  cellular surface (sCK8)

Normal Prostate
Prostate- cancer
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Cancer Recognition (CARE) Test

• Serological, ELISA-based assay to distinguish
  cancer
• Detects anti-cytokeratin 8 (CK8) IgM produced in
  response to surface CK8

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Construction of a cancer vaccine

• Vaccine antigens
• Oral
• Intranasal

• Cellular activation
• Antigen presenting cells
• Helper T cells
• Cytotoxic T cells
• B cells

• Adjuvants
• Cytokines
• Bacterial toxins

• Candidate tumor sites
• Lung
• Intestine
• Colon
• Rectum

Antitumor immune response
Lefrancois and Puddington, Ann Rev Immunol (2007)
24 681
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MDACCO Office of Clinical Trials

• Director Gregory Pennock, M.D.
• CRC (Nursing) Lead Trudy Graves, RN
• Regulatory Lead Allisun Feazell
• 7 full-time CRCs
• 7 full-time data managers/regulatory personnel

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2009 Highlights of Clinical Research

• Completed first phase I study (ALT-801)
• Received FDA approval to proceed with first
  in-house phase I study (tolfenamic acid)
• Started several investigator-initiated trials
• Lung cancer breath test
• CARE protocol
• FDG-PET study for oral cavity cancers

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2009 Goals for Clinical Research

• Branch out to different disease sites
• Pediatric
• Symptom management (CCOP)
• Introduce more investigator-initiated trials
• CARE protocol
• Additional phase I studies (tolfenamic acid)
• Maintain adequate enrollment in cooperative group
  trials

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Grant Funders to Date

• 2006
• FOE National Art Ehrmann Cancer Fund 30,000
• ASTRO Therapeutic Radiology and Oncology 12,000
• FOE Local Art Ehrmann Cancer Fund 5,000
• Publix Super Market Charities, Inc. 5,000
• Phi Beta Psi Sorority Foundation Veerman Family
  2,000
• FL DOH Office of Public Health Research
  437,000
• 2007
• RSNA Research Education Foundation 29,900
• FL DOH Bankhead-Coley 209,520
• FOE National Art Ehrmann Cancer Fund 30,000
• 2008
• FL DOH Bankhead-Coley 346,298
• FL DOH Bankhead-Coley 372,600
• FL DOH Bankhead-Coley 359,286
• FL DOH James Esther King 949,717

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Research Symposium - Personalized Cancer Therapy
in Basic, Translational and Clinical Research

• Focus New research applications to personalized
  cancer therapy in basic, translational and
  clinical arenas
• Audience Oncology scientists, physicians and
  nursing staff
• M. D. Anderson - Orlando
• M. D. Anderson Houston
• Orlando Health Medical Education Faculty and
  Residents
• University of Central Florida
• The Burnham Institute for Medical Research

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Additional Information
The Burnham Institute Orlando
Educational Objectives Identify various
therapeutic strategies being tested to treat
cancer with an emphasis on nanotechnology,
radiation and chemotherapy

• ? Continuing Education Credits Available
• Poster Session Wed, October 28th

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Working Relationships Orlando Health Developed
an agreement with Department of Medical Education
surgical labs Developed an agreement with APH
Cardiovascular Group UCF - Burnett School of
Biomedical Sciences/College of Medicine Developed
a research/university affiliation agreement
between MDACCO and UCF Developed a Cancer
Center/NCI Committee between UCF and
MDACCO Established research collaborations UTMD
ACC Houston Established a Scientific Advisory
Council Establishing adjunct appointments Contin
uing research collaborations Burnham Medical
Research Institute Developed a research
agreement and strategic plan Established
research collaborations
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Cancer Research Institute where are we going?

• Lake Nona
• Provide synergy with UCF (Medical School and
  Burnett School), Burnham, etc.
• Recruit highly qualified research scientists
• (22 Principal Investigators research support
  staff) totally up 200 FTEs by year 2012
• Three Centers of Excellence within the cancer
  research program
• Nanobiology/Radiation Biology
• Cancer Biology
• Immunology

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5th floor M. D. Anderson-Orlando
CRI
UCF Burnett School
UCF College of Medicine
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where are we going?

• Continue to develop strong basic and
  translational research relationships with
  UTMDACC, UCF, Burnham, Industry with formal
  agreements and affiliations
• Preclinical Clinical testing leading to
  more clinical trials, INDs, patents
• Availability for large grants (SPORES, Project
  Program grants, U54) totally up to 5 million -
  20 million/year
• Competitively compete and receive peer-reviewed
  funding from NCI/NIH
• Establishing a critical mass of world class
  scientists (junior and senior)
• Create an institution that attracts philanthropy
• Endowed Chairs, Labs, Technology, Scholarship
  Programs

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How are we going to get there?

• EXPANSION (land, research building, core
  facilities) campaign
• RECRUITMENT must provide synergy between
  clinical practice and research agenda
• Research Package must be competitive! grant
  and seed
• Start-up monies
• (research funds available on day 1 year 3)
• clear outline of how long an investigator has
  before obtaining external funding (i.e., NIH,
  ACS, Industry, state funds)

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how are we going to get there?

• Funding will come as a result of recruited
  scientists, physicians
• Promote synergy between the radiation department,
  nuclear medicine, surgeons, pathology, medical
  oncology, clinical research department
• NCI Designation in 2012
• All the above

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