HEMATOLOGY- ONCOLOGY

HEMATOLOGY-ONCOLOGY Overview

The Brown University/Lifespan Hematology/ Oncology group was formed when The Miriam Hospital Hematology/Oncology Division, the Rhode Island Hospital Division of Hematology and the Rhode Island Hospital Department of Medical Oncology merged in 1999. Our mission is to achieve academic excellence in basic research, clinical research and education, and to provide the highest quality of care to our patients. The creation of a Comprehensive Cancer Center, which is a collaborative effort to provide coordi- nated and comprehensive care for cancer patients at three Lifespan hospitals (The Miriam Hospital, Rhode Island Hospital and Newport Hospital), has now become a reality. Both the patients and the staff appreciate the many benefits afforded by the new Comprehensive Cancer Center at The Miriam Hospital which opened in May 2002. Extensive renovations to the George Clinic at Rhode Island Hospital were completed as a temporary measure. The groundbreaking ceremony for the Comprehen- sive Cancer Center at Rhode Island Hospital was held on April 28, 2003 with an anticipated opening in February 2004. A recent goal has been the establishment of multi- disciplinary clinics for all the major malignancies. This conveniently allows the patient to receive the Edward Wittels, M.D., Associate Professor of expertise of the surgeon, radiation oncologist and Medicine; Interim Director of Hematology- medical oncologist at the time of their first visit. Oncology and Interim Director of medical Presently, upper GI and melanoma multidisciplinary Oncology Division at Brown Medical School clinics are up and running at Rhode Island Hospital. A thoracic multidisciplinary tumor board has been implemented at each hospital. Future multi-discipli- Our laboratory and clinical researchers distin- nary clinics are being planned for head and neck guished themselves through national appointments cancer as well as breast cancer. as well as being awarded significant research grants. In the clinical arena, three of our physicians, Drs. A Center of Biomedical Research Excellence Fred Schiffman, Anthony Mega, and Sundaresan (COBRE) award of $8.2 million has established the Sambandam were included in the “Rhode Island Center for Cancer Research Development under the Monthly” magazine’s list of “Top Docs.” Dr. Mega leadership of Dr. Douglas Hixson as Principal was also honored with the “Teacher of the Year Investigator and Dr. Nancy Thompson as Deputy 2001-2002” award by the Hematology/Oncology Director. The mission of the Center is to foster  fellows. outstanding interactive, laboratory-based cancer BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

research focused on the Molecular and Cellular National Cancer Institute Subcommittee C Pathogenesis of Cancer by mentoring promising (Program Projects). junior investigators and establishing state of the art Dr. Deborah Britt is the Principal Investigator for core facilities. two grants that were awarded – a Lifespan Dr. Douglas Hixson served as a member of the Developmental Grant entitled “Examination of National Institute of Environmental Health Services Differential Expression of a Novel Protein, LYRIC, in (NIEHS) Study Section, Review of ToxicoGenomics Normal Rat Liver and Hepatocellular Carcinoma” Consortium Member Applications, 2001 and was ”and a grant from the U.S. Army Prostate Cancer the Chair and organizer of the 12th International Research Program entitled “Examination of a Novel CEA Symposium in Providence, RI. Dr. Hixson is Protein, LYRIC, and Its Involvement in Prostate on the Editorial Board for “Hepatology,” a member Tumor Suppression Mediated by the Cell Adhesion of the Program Committee for the American Molecule CEACAM1-L.” Society for Investigational Pathology and is Vice Dr. Yow-Pin Lim was awarded a Lifespan President and co-founder of ProThera Biologics in Developmental Grant for a project entitled East Providence, RI. He received an RO1 grant “Granzyme in Sepsis,” which will examine the role of funded by the National Institutes of Health for a lymphocyte serine proteases (granzymes) in project entitled “Genesis of Liver Carcinomas with inflammation and sepsis. He also received grants Oval Cell Traits.” from The Slater Center for Biological Research and Dr. Nancy Thompson is the Principal Investigator NIH/NIGMS (SBIR Phase I). Dr. Lim is the for a National Institutes of Health (NIH) RO1 President and co-founder of ProThera Biologics, a Grant entitled “Expression and Role of TA1 start-up biotechnology company, in East Providence, Oncofetal Gene in Liver Cancer” and an American Rhode Island. Dr. Loren Fast was awarded a Rhode Institute for Cancer Research (AICR) Grant entitled Island Cancer Council Grant. “Amino Acid Regulated Gene Expression in Dr. Howard Safran is the Principal Investigator for Tumorigenesis.” an RTOG-sponsored adjuvant pancreatic cancer Dr. Alan Rosmarin chairs the American Cancer trial, which is the largest adjuvant pancreatic trial Society’s Leukemia, Immunology and Blood Cell ever performed in the United States. He also directs Development Study Section and is a member of the a Radiation Therapy Oncology Group (RTOG) trial

Alan Rosmarin, Associate Professor of Hematology- Oncology; Interim Director of Hematology Division at Brown Medical School and Director of Brown University Oncology Group (BrUOG)

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for advanced pancreatic cancer. Dr. William Sikov the local Chair for the National Cancer Survivors served as a Principal Investigator for a national study Day planning group. Ms. Grossi is an Oncology in advanced breast cancer, which he presented at the Nurse Clinician at The Miriam Hospital and serves American Society of Clinical Oncology (ASCO) on the Board of Directors of The Leukemia and meeting in May 2002. He also serves as a member of Lymphoma Society. Ms. Higginbotham, who is an the Board of Directors of Cancer and Leukemia Oncology Clinical Social Worker at The Miriam Group B (CALGB) and as the Principal Investigator Hospital, also volunteers for The Leukemia and representing Rhode Island. Dr. Anita Kestin is the Lymphoma Society. Both Ms. Grossi and Ms. Principal Investigator for the Prevention of Higginbotham coordinate and participate in Recurrent Venous Thromboembolism (PREVENT) numerous activities such as National Cancer study. The PREVENT trial evaluates the efficacy of Survivors Day as well as various support and prolonged treatment with low-dose warfarin in the educational programs, some of which are held in secondary prevention of venous thromboembolism. conjunction with the American Cancer Society. They Dr. Gary Strauss was recently recruited to fill a also have been invited to address PTA meetings fulltime faculty position in Hematology/Oncology at about speaking to children about cancer and they Rhode Island Hospital. Dr. Strauss received his M.D. have conducted tours of the treatment area for young from Yale University and M.P.H. from Harvard children of cancer patients. Recently Pat Grossi has School of Public Health. While he is an experienced taken a job at another institution and we are in the clinician in all aspects of Medical Oncology, he is process of hiring an equally accomplished and particularly interested in breast and lung cancers. He experienced oncology nurse to fill her position. is a nationally recognized researcher in lung cancer and has been in the forefront of the controversy regarding the efficacy of lung cancer screening. Dr. Strauss’s clinical expertise and research accomplish- Faculty Members ments make him an invaluable addition to the Division of Hematology/Oncology. FULL-TIME FACULTY (Hospital and Foundation Based) We are proud to report that five of our fellows were Edward Wittels, M.D., Director, Hematology/ authors of abstracts at the American Society of Oncology, Associate Professor, Miriam Hospital, Clinical Oncology (ASCO) meeting in May 2002. University Medicine Foundation One of the fellows, Dr. Vanessa Johnson, received Deborah Britt, Ph.D., Assistant Professor, Oncology, both a Merit Award and the Pain Merit Award, which Rhode Island Hospital was presented to the author who submitted the best James Butera, M.D., Clinical Assistant Professor, abstract paper on the subject of pain management. Hematology, Rhode Island Hospital, University Dr. Johnson was honored during the Opening Medicine Foundation Ceremony and was also featured in the ASCO daily James Crowley, M.D., Professor, Hematology, newsletter. Memorial Hospital The Cancer Program at Rhode Island Hospital as Loren Fast, Ph.D., Associate Professor, Hematology, well as the Cancer Program at The Miriam Hospital Rhode Island Hospital were surveyed by the Commission on Cancer of the Mary Anne Fenton, M.D., Clinical Instructor, American College of Surgeons and both were Hematology, Rhode Island Hospital, University awarded the maximum accreditation of three years. Medicine Foundation Michelle Haskell, Ph.D., Assistant Professor (Res.) Three members of The Miriam Hospital Cancer Rhode Island Hospital Control Committee who are actively involved in Douglas Hixson, Ph.D., Professor, Oncology, Rhode community activities are Marsha Weiss, RN, MS, Island Hospital Patricia Grossi, RN, BSN, OCN, and Kathleen Vanessa Johnson, M.D., Instructor (Research) Miriam Higginbotham, LICSW. Ms. Weiss is the Director of Hospital Lifespan Community Health Services, which Anita Kestin, M.D., Clinical Assistant Professor, coordinates community health education, screen- Hematology, Rhode Island Hospital, University ings, outreach programs and follow-up for the Medicine Foundation  Lifespan affiliates in Rhode Island. She also serves as BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

Yow Pin Lim, M.D., Ph.D., Assistant Professor, Nancy Freeman, M.D., Clinical Associate Professor, Oncology, Rhode Island Hospital Hematology, VA Medical Center Leslie Lockridge, M.D., Assistant Professor, Memorial Linda Hassan, M.D., Clinical Assistant Professor, Hospital Memorial Hospital Anthony Mega, M.D., Assistant Professor, Peter Hoffmann, M.D., Clinical Assistant Professor, Hematology, Miriam Hospital, University Medicine Hematology, Miriam Hospital Foundation Plakyil Joseph, M.D., Clinical Assistant Professor, Ahmed Nadeem, M.D., Assistant Professor, Memorial Oncology, Roger Williams Medical Center Hospital A. Sattar Memon, M.D., Clinical Associate Professor, Neal Ready, M.D., Assistant Professor, Oncology, Oncology, Memorial Hospital Rhode Island Hospital, University Medicine Vishram Rege, M.D., Clinical Associate Professor, Foundation Oncology, Rhode Island Hospital Alan Rosmarin, M.D., Associate Professor, Hematol- Peter Rintels, M.D., Clinical Assistant Professor, ogy/Oncology, Miriam Hospital , University Hematology, Rhode Island Hospital Medicine Foundation Sundaresan Sambandam, M.D., Clinical Assistant Howard Safran, M.D., Assistant Professor, Oncology, Professor, Oncology, Rhode Island Hospital Miriam Hospital, University Medicine Foundation Anthony Testa, M.D., Clinical Instructor, Oncology, St. Fred Schiffman, M.D., Professor, Hematology, Miriam Joseph’s Hospital Hospital, University Medicine Foundation Kathy Theall, M.D., Clinical Instructor, Hematology/ William Sikov, M.D., Clinical Assistant Professor, Oncology, Memorial Hospital Oncology, Miriam Hospital, University Medicine Anthony Thomas, D.O., Clinical Assistant Professor, Foundation Hematology, Rhode Island Hospital Gary Strauss, M.D., M.P.H., Brown faculty appoint- Fred Vohr, M.D., Clinical Assistant Professor, ment pending, Rhode Island Hospital, University Hematology/Oncology, Rhode Island Hospital Medicine Foundation Francis Cummings, M.D., Adjunct Associate Professor, Rochelle Strenger, M.D., Clinical Assistant Professor, Oncology, Roger Williams Medical Center Hematology, Miriam Hospital , University Medicine A. Raymond Frackelton, Ph.D., Adjunct Associate Foundation Professor, Oncology, Roger Williams Medical Center Nancy Thompson, Ph.D., Professor, Oncology, Rhode Seth Rudnick, M.D., Adjunct Associate Professor, Island Hospital Oncology, Rhode Island Hospital

VOLUNTEER FACULTY Philip Schein, M.D., Adjunct Professor, Oncology, Rhode Island Hospital Kwang Ahn, M.D., Clinical Assistant Professor, Alan Weitberg, M.D., Adjunct Professor, Oncology, Oncology, Roger Williams Medical Center Roger Williams Medical Center Joseph DiBenedetto, Jr., M.D., Clinical Assistant Profes- sor, Hematology/Oncology, Rhode Island Hospital

FACULTY TRANSITIONS Departing Faculty Thomas Myers, Clinical Associate Professor, Memorial Hospital Peter Hoffmann, Clinical Assistant Professor, Miriam Hospital New Faculty Name Former Position Faculty Rank James Butera, M.D., Clinical Assistant Professor, Rhode Island Hospital Gary Strauss, M.D., MPH, Appointment pending,Rhode Island Hospital Leslie Lockridge, M.D., Assistant Professor, Memorial Hospital Ahmed Nadeem, M.D., Assistant Professor, Memorial Hospital Vanessa Johnson, M.D., Instructor (Research) Miriam Hospital Michelle Haskell, Ph.D., Assistant Professor (Res.) Rhode Island Hospital  HEMATOLOGY- ONCOLOGY

Hospital, Zagreb, Croatia National and • “Role of Protease Inhibitors in Neonatal Sepsis” at 28th Annual New England Conference on Perinatal International Honors Research, Chatham, MA Anthony, Mega, M.D. and Recognition of • “TopDoc” – Rhode Island Monthly Magazine Invited presentations: Faculty • “Communicating Options in Prostate Cancer” at Schwartz Center Rounds, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island Loren Fast, PhD Invited presentations: • “High Risk Local Prostate Cancer – Can We Improve Outcome?” at Brown University Oncology • Two seminars at the Blood Center of the Pacific, Group Education Advisory Board, Edgartown, MA SanFrancisco, CA • “From Herbs to Chemotherapy, Choices in the Mary Anne Fenton, M.D. Management of the Patient with Androgen- Invited presentation: Independent Prostate Cancer” at Caritas Good • “Pathophysiology of Breast, Cervical and Samaritan Medical Center, Brockton, MA Endometrial Cancers” at University of Rhode Island, • “Update on Prostate Cancer” at CRI Communica- Kingston, RI tions on The Rhode Island Health Update program, Douglas Hixson, PhD Providence, RI • Chair and organizer, 12th International CEA/PSG Neal Ready, M.D., PhD Symposium, Providence, RI; Consultant, Invited presentation: Octapharma Therapeutics, Vienna, Austria • Abstract/poster “Induction Weekly Paclitaxel and • Member, Editorial Board of “Hepatology” Carboplatin (IT) followed by concurrent Paclitaxel, • Member, Program Committee for American Society Carboplatin and Radiotherapy (CRT) in Advanced for Investigational Pathology Head and Neck Squamous Cell Cancers (HN-SCC)” • Vice President, co-founder of Prothera Biologics, at American Society of Clinical Oncology Meeting, East Providence, RI Orlando Florida Invited presentations: Committee: • “Hepatic Stem Cells, An Older and Wiser Alternative • Chairman, Thoracic Committee, Brown University to Embryonic Stem Cells” at UTMDAH Cancer Cen- Oncology Group ter, Science Park Research Division, Smithville, TX • Society: Member, Executive Committee, New • “Stages in Hepatic Ductal Cell Development England Cancer Society Defined by Surface Reactive Monoclonal Alan Rosmarin, M.D. Antibodies” at Albert Einstein College of Medicine, Invited presentations: Bronx, NY “Hepatic Stem Cells of Ductal Origin” at • “Myelodysplastic Syndromes: Contemporary Loyola University, New Orleans, LA Management and Novel Approaches” at Beth Israel Anita Kestin, M.D. Deaconess Medical Center, Boston, MA Invited presentations: • “CML: A Model Disease for Targeted Therapy” at • “Coagulation Disorders” at University of Rhode Rhode Island Hospital Grand Rounds, Providence, Island, Kingston, RI RI • “Hematology Update: Hypercoagulable States” at • “Current Approaches and Future Trends in Cancer Newport Hospital’s Grand Rounds, Newport, RI Therapy” at Brown University Oncology Group Yow Pin Lim, M.D., PhD (BrUOG) Seminar, Edgartown, MA Invited presentations: ·• “Myelodysplastic Syndromes: Contemporary • “Development of Monoclonal Antibody for Early Management and Novel Approaches” at Boston Detection of Colon Cancer” at Biochemistry University Medical Center, Boston, MA Seminar at the Free University, Berlin, Germany • “Workshop on Myeloid Development” at Annual • “Inter-alpha inhibitors in Sepsis and Cancer” at Myeloid and Stem Cell Workshop, Philadelphia, PA Institute for Immunology Zagreb and Dr. Josip • “GABP (GA Binding Protein), Sp1 and p300 Physically and Functionally Interact to Regulate  Myeloid Transcription of CD18 in Response to BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

Retinoic Acid” at Fifth International Meeting on Gary Strauss, M.D., MPH Myeloid Stem Cell Development and Leukemia, Invited presentations: Annapolis, Maryland. • “Island-Lake Model and Cancer: Implications for ·• “GA Binding Protein (GABP) in the Regulation of Randomization Failure in Randomized Population Myeloid Gene Expression and Differentiation” at Trials” at Working Group in Quantitative Methods Chicago Department of Biochemistry and in Cancer: Harvard School of Public Health, Boston, Molecular Biology at University of Illinois, MA Chicago, IL • “Should We Be Screening for Cancer?” at National Howard Safran, M.D. Council of Jewish Women, Providence, RI Invited presentations: • “Cancer Screening is Effective and Cost-Effective: • “Neoadjuvant Herceptin, Paclitaxel and Cisplatin Pro” at American Association of Thoracic Surgery, and Radiation for Adenocarcinoma of the Boston, MA Esophagus” at the Eighth International Conference • “Smoking-related Adenocarcinoma of the Lung: on Gastrointestinal Malignancies, Washington, Now the Most Common Cause of Cancer Death in D.C. the United States” at American Society of Clinical • “A phase II trial of Herceptin and Gemcitabine for Oncology Annual Meeting, Chicago, IL Metastatic Pancreatic Cancers that Overexpress Rochelle Strenger , M.D. HER-2/neu” at ECCO in Lisbon, Portugal • Co-recipient of the Rhode Island Medical Women’s Fred Schiffman, M.D. Association’s “Woman Physician of the Year Award • “Top Doc” – Rhode Island Monthly Magazine for 2001” William Sikov, M.D. Nancy Thompson, PhD Invited presentations: Invited presentations: • “Multicenter, 3-arm randomized study of high- • “Oncofetal and Amino Acid-Responsive hepatic dose weekly paclitaxel versus standar-dose weekly LAT1/CD98 Expression” at International Society of paclitaxel for metastatic breast cancer” at Amrican Differentiation Meeting, Lyon, France Society of Clinical Oncology (ASCO) annual • “Mentoring and Minority Recruiting in meeting, Orlando, FL Pathobiology” at American Society for Investigative • “Metastatic Breast Cancer: Beyond Taxanes and Pathology Graduate Program Director’s Workshop, Anthracyclines” at Breast Cancer Forum, San Diego, CA Presbyterian Healthcare, Charlotte, NC “Metastatic Edward Wittels, M.D. Breast Cancer: Beyond Taxances and • Elected to faculty of the Alpha Omega Alpha Honor Anthracyclines” at Harvard Vanguard Medical Medical Society, Brown Medical School Associates, Boston, MA • “Cancer Clinical Trials and Older Patients” at Combined Onoclogy/Geriatrics Symposium, Providence, RI • “The Changing Face of Hormonal Therapy” at Oncology Grand Rounds, Dartmouth Hitchcock Medical Center, Hanover, NH

 HEMATOLOGY- ONCOLOGY

HEMATOLOGY/ONCOLOGY FELLOWSHIP PROGRAM

GRADUATES 2002

Fellow Medical School Residency Program Post-fellowship Position

Vanessa Johnson, M.D. Cornell University Brown General Internal National Cancer Institute Medical College, New Medicine, Rhode Island Post-doctoral R25 Training York, NY Hospital, Providence, RI Grant, Providence, RI

Full-time Staff, Memorial Ahmed Nadeem, M.D. King Edward Medical Yale University, Bridgeport Hospital of Rhode Island, CollegeLahore, Pakistan Hospital, Bridgeport, CT Pawtucket, RI

Private practice of Nadia Ramdin, M.D. UMDNJ – Robert Wood Boston University, Roger Hematology/Oncology, Ft. Johnson School of Williams Medical Center, Lauderdale, FL Medicine, NJ Providence, RI

GRADUATES 2003 Private practice with Maria Constantinou, M.D.Ross University Yale University, Norwalk Vincent Armenio, M.D., Portsmouth, Dominica Hospital, Norwalk, CT East Providence, RI

Wojciech Dolata, M.D. Academy of Medicine, Michigan State University, Practice in Canada Poznan, Poland McLaren Regional Medical Center, Flint, MI

Humera Khurshid, M.D. Aga Khan University University of Connecticut, Private practice, University Medical College, Karachi, John Dempsey Hospital, Medical Group, Warwick, Pakistan Farmington, CT RI

2001-2003

Fellow Medical School Residency Program

Debra Holik, M.D. New York Medical College, Brown University – The Miriam & Valhalla, NY Rhode Island Hospitals, Providence, RI

Katrina Rolen, M.D. St. Louis University School of St. Louis University Health Medicine, St. Louis, MO Sciences Center, St. Louis, MO

Amanda Sun, M.D., Ph.D. Sun Yat-sen University of Medical Yale University, Norwalk Hospital, Sciences, Guangzhou, P.R.China Norwalk, CT

James Tsai, M.D. St. George’s University, St. George’s, UMDNY – New Jersey Medical School, Granada Newark, NJ

George Zahrah, M.D. University of Ancona, Ancona, Italy Yale University, Danbury Hospital, Danbury, CT

2002-2003

Douglas Brandoff, M.D. Mt. Sinai School of Lahey Clinic, Burlington, VT Medicine, New York, NY

Bharti Chauhan, M.D. Pandit JJM Medical College, Raipur, Brown University, Memorial Hospital of India RI, Pawtucket, RI

Samir Desai, M.D. Northeastern Ohio Universities of Summa Health System, Akron, OH Medicine, Rootstown, OH

Ronald Harris, M.D. Lake Erie College of Osteopathic Temple University, Conemaugh Valley Medicine, Erie, PA Memorial Hospital, Johnstown, PA

Linda McMorrow-Ries, University of Vermont, Burlington, Brown University, Rhode Island Hospital, M.D. VT Providence, RI  BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

Anthony Mega, M.D. Research and Other • Chairman, Genitourinary Subcommittee, Brown University Oncology Group; Scholarly Activities • Member, Scientific Review Board, Brown University Oncology Group FACULTY MEMBERS OF STUDY Fred Schiffman, M.D. SECTIONS AND ADVISORY COMMITTEES • Co-Chairperson, Committee on Clinical Appoint- ments and Promotions, Brown University Loren Fast, PhD Department of Medicine • Member, ZRG H10 study section at NIH • Chairperson, Chiefs of Medicine of Federation of Douglas Hixson, PhD Jewish Philanthropies Hospitals • Member, NIEHS study section, Review of Toxico- • Governor, American College of Physicians/ Genomics Consortium Member Applications American Society of Internal Medicine Neal Ready, M.D., PhD Nancy Thompson, PhD • Study section: Chair, Cancer and Leukemia Group B • Chair, American Society of Investigative Pathology Protocol #30106: “ZD-1839 (NSC# 715055) with (ASIP) Committee on Career Development, Induction Paclitaxel and Carboplatin followed by Women and Minorities; Member, ASIP Council either Radiation or Concomitant Radiation with • Chair, Federation of American Societies of Experi- Weekly Paclitaxel and Carboplatin in Stage III Non- mental Biology (FASEB) Excellence in Science small Cell Lung Cancer, a Phase II Study” Award Committee Alan Rosmarin, M.D. • ASIP Delegate to AXXS 2002 Meeting in • Chairman, American Society of Hematology Washington, D.C., sponsored by Office of Research Simultaneous Session “Regulation of Transcription in Women’s Health in Hematopoiesis” at annual meeting, Orlando, FL • Co-chair and organizer, American Society for • Member, Myeloid Subcommittee, American Society Investigative Pathology Career Development of Hematology Workshop: “Playing to Win: Elements of Success” • Chairman, American Cancer Society Leukemia, in San Diego, CA Immunology, and Blood Cell Development • Member, National Cancer institute Subcommittee C TEACHING ACTIVITIES Howard Safran, M.D. • Member, Gastrointestinal Oncology Committee, EDUCATION HONORS Radiation Therapy Oncology Group (RTOG) • Ad Hoc Member, Study Section, “Rapid Access to Anthony, Mega, M.D. Intervention Development;” Medical Oncology • Dean’s Teaching Excellence Award, BioMed 281: Chairman, RTOG national protocol, “A Phase II Trial Pathophysiology – Hematology, Brown Medical of External Irradiation and Weekly Paclitaxel for School Non-Metastatic Unresectable Pancreatic Cancer” • Preceptorship Award – Brown Medical School, • Medical Oncology Chairman, RTOG/Intergroup Rhode Island Hospital, The Miriam Hospital national protocol, “A Phase III Study of Pre and Post • “Teacher of the Year 2001-2002” – Brown Medical Chemoradiation 5-FU vs. Gemcitabine for School, Hematology/Oncology Fellowship Program Postoperative Adjuvant Treatment of Resected Fred Schiffman, M.D. Pancreatic Adenocarcinoma” • Senior Class Award from Brown University Medical • Medical Oncology Chairman, RTOG national proto- School Class of 2001 in recognition of support and col, “Phase II Study of Paclitaxel, Gemcitabine and dedication to teaching Radiation Followed by the Farnesl Transferase • Brown University Dean’s Teaching Excellence Inhibitor R115777 for Locally Advanced Pancreatic Award-2002 Cancer” • Medical Oncology Liaison to Translation Research Edward Wittels, M.D. Program, RTOG • Dean’s Teaching Excellence Award, BioMed 281: • Medical Oncology Chairman for upcoming RTOG Pathophysiology – Hematology, Brown Medical protocol testing a ras peptide vaccine with chemo- School radiation as adjuvant therapy for pancreatic cancer

 HEMATOLOGY- ONCOLOGY

PUBLICATIONS • Hixson DC. Animal models for assessing the contribution of stem cells to liver development. In: James Butera, M.D. Sell S; Stem Cell Handbook.Towanda, NJ. Humana • Yango A, Morrissey P, Monaco A, Butera J, et al. Press 2003:353-66. Successful treatment of tacrolimus-associated Anthony Mega, M.D. thrombotic microangiopathy with sirolimus • Lopez F, Mega A. Aortitis as a manifestation of conversion and plasma exchange. Clin Nephrol myelodysplastic syndrome. Postgrad Med J 2001 2002 Jul; 58(1):77-8. Feb; 77:116-8. Loren Fast, Ph.D. Alan Rosmarin, M.D. • Fast L, DiLeone G, Edson C, Purmal A. INACTINE • Sedivy JM, Vogelstein B, Liber HL, Hendrickson E, PEN110 treatment functionally inactivates the PBMNC present in RBC units: Comparison to the Rosmarin AG. Gene targeting in human cells effects of exposure to g-irradiation. Transfusion without isogenic DNA. Science 1999; 283(1):5. 2002; 42:1318 - 25. • Khurana TS, Rosmarin AG, Shang J, Krag TOB, Das • Fast LD, DiLeone G, Edson C, Purmal A. Inhibition S, Gameltoft S. Activation of utrophin promoter by of murine GVHD by INACTINE PEN110 heregulin via the ets-related transcription factor treatment. Transfusion 2002; 42:1326-32. complex GABP/. Mol Biol Cell 1999; 10(6):2075-86. • Fast L. The effect of exposing murine splenocytes • Gupta AK, Zibello T, Simkevich CP, Rosmarin AG, to UVB light, psoralen plus UVA light or g- Berliner N. Sp1 and C/EBP are necessary to activate irradiation on in vitro and in vivo immune the lactoferrin gene promoter during myeloid responses. Transfusion 2003; 43:576-83. differentiation. Blood 2000; 95:3734-41. • Fast L. Genotypic regulation of alloantibody ·• Bush TS, St. Coeur M, Resendes KK, Rosmarin AG. production in response to ultraviolet B irradiated GA binding protein (GABP) and Sp1 are required, allogeneic donor cells. Transfusion 2003; in press. along with retinoid receptors to mediate retinoic Mary Anne Fenton, M.D. acid responsiveness of CD18 (2 Leukocyte • Fenton, MA. Breast cancer update. Med Health RI Integrin): a novel mechanism of transcriptional 2002 Jan; 85(1):10-4. Review. regulation in myeloid cells. Blood 2003; 101:311-7. • Dupuy D, Chauhan B, Ready N, DiPetrillo T, • Rosmarin AG, Resendes KK, Yang Z, McMIllan J, Gaissert H, Fenton MA. Radiofrequency ablation Fleming SL. GA binding protein (GABP) (RFA) followed by conventional radiotherapy (RT) transcription factor: a review – GABP as an for inoperable non-small cell lung cancer integrator of intracellular signaling and protein- (NSCLC). ASCO Proceedings 2003 June; protein interactions. Blood Cells, Molecules, and 22:654,abstr. #2632. Diseases 2003, in press. Douglas Hixson, Ph.D. Howard Safran, M.D. • Gordon GJ, Coleman WB, Hixson DC, Grisham • Safran H, Gaissert H, Akerman P, Hesketh P, Chen JW. Liver regeneration in rats with retrorsine- MH, Moore T, Koness J, Graziano S, Wanebo H. induced hepatocellular injury reveals the existence Paclitaxel , cisplatin and concurrent radiation for of a novel liver progenitor cell population. Am J esophageal cancer. Cancer Invest 2001; 1:1-7. Pathol 2000; 156:607-19. • Safran H, Moore T, Iannitti D, DiPetrillo T, • Hixson DC, Brown J, McBride A, Affigne SA. Akerman P, Cioffi W, Harrington D, Quirk D, Differentiation status of rat ductal cells and Ratesh R, Cruff D, Vakharia J, Vora S, Savarese D, ethionine-induced hepatic carcinomas defined Wanebo H. Paclitaxel and concurrent radiation for with surface-reactive monoclonal antibodies. Exper locally advanced pancreatic cancer. Int J Radiat and Mole Pathol 2000; 68:152-69. Oncol Biol Phys 2001; 49:1275-9. • Estrera VT, Chen DT, Luo W, Hixson DC, Lin SH. • Safran H, Rathore R. Paclitaxel as a radiation Signal transduction by the CEACAM1 tumor sensitizer for locally advanced pancreatic cancer. Crit Rev Oncol Hematol 2002 Jul; 43(1):57-62. suppressor. J Biol Chem 2001; 276:15547-53. • Safran H, King TC, Steinhoff MM, Rathore R, • Makarovskiy AN, Siryaporn E, Hixson DC, Akerley Mangray S, Chai L, Berezein K, Moore T, Iannitti D, W. Survival of docetaxel-resistant prostate cancer Pasquariello T, Akerman P, Quirk D, Goldstein L, cells invitro depends on phenotype alterations and Reiss P, Mass R and Tantravahi U. Overexpression continuity of drug exposure. Cell Mole Life Sci of the HER-2/neu oncogene in pancreatic 2002; 59:1198-211. adenocarcinoma. Am J Clin Oncol 2001; 24:496-9.

 BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

Fred Schiffman, M.D. Rochelle Strenger, M.D. • Akhtar M, Hussain SI, Lamberton P. Schiffman FJ. • Legare RD, Strenger R. Adjuvant therapy in breast Resolution of methimazole-induced agranulocyto- cancer. Obstet Gynecol Clin North Am 2002 Mar; sis with the use of human granulocyte colony 29(1):201-8, ix. Review. stimulating factor (G-CSF). Geriatrics 2000; Nancy Thompson, Ph.D. 55(2):89-91. • Diah SK, Padbury JF, Campbell WA, Britt D, • Sikov W, Schiffman FJ, Weaver M. Schulman R, Thompson NL. Molecular cloning of the rat TA1/ Dyckman J. Griffith R, Torgan P. Splenosis LAT-1/CD98 light chain gene promoter. Biochimica presenting as occult gastrointestinal bleeding. AM et Biophysica Acta 2001; 1518:267-70. J. Hematol 2000; 65(1):56-61. • Campbell WA, Thompson NL. Overexpression of • Lopez F, Mega A, Schiffman FJ, Vaidyan P. Aortitis LAT-1/CD98 light chain is sufficient to increase as a manifestation of myelodysplastic syndrome. system L amino acid transport activity in mouse Postgraduate Med J 2001; 77:116-8. hepatocytes but not fibroblasts. J Biol Chem 2001; • Tuohy K, Nicholson W, Schiffman FJ. Agitation by 276:16877-84. sedation. Lancet 2003; 361:308. Edward Wittels, M.D. • Lee SI, Honiden S, Fain EB, Schiffman FJ, Tammaro • Wittels EG, Siegel RD, Mazur EM. Thrombocy- D. Severe hyponatremia caused by an intrasella topenia in the intensive care unit setting. J Intensive carotid artery aneurysm. Med and Health Rhode Care Med 1990; 5:224-40. Island 2003 Feb; 86(2): 52-5. • Akerley W, Choy H, Safran H, Sikov W, Rege V, William Sikov, M.D. Sambandam S, Wittels E. Weekly paclitaxel in • Akerley W, Rathore R, Ready N, Leone L, Sikov W, patients with advanced lung cancer: preliminary Safran H, Kennedy T. A phase I study of a weekly data from a phase II trial. Semin Oncol 1997; 24(4 schedule of paclitaxel and carboplatin in patients suppl 12):S12-10-S12-13. with advanced carcinoma. Cancer. 2002; 95(9):2000-5 • Sikov WM. Locally advanced breast cancer. Current Treatment Options in Oncology 2000; 1:228-38.

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Direct Indirect Total

Total Basic Research Expenses Academic Year 2002 $1,030,201 $454,219 $1,484,420 Academic Year 2003 $1,514,861 $430,300 $1,945,161

Total Clinical Research Expenses Academic Year 2002 $417,141 $123,708 $540,849 Academic Year 2003 $371,289 $89,624 $460,913

BASIC RESEARCH • Immunoregulajtory Role of Granzyme in Sepsis, Lifespan

Deborah Britt, Ph.D. Andrew Makarovski, Ph.D. • Examination of a Novel Protein, LYRIC, and Its • Effect of Taxotere/Estramustine on the Phenotype Involvement in Prostate Tumor Suppression of Aggressive Prostate Cancer Cell, Aventis Mediated by the Cell Adhesion Molecule Pharmaceuticals Products, Incorporated (CEACAM1-L), Department of Defense Alan Rosmarin, M.D. • The Role of a Novel Protein, LYRIC in • Center for Genetics and Genomics, NIH/National Development of Hepatocellular Carcinoma, Institutes of Health/Brown Lifespan (COBRE Pilot Project) Nancy Thompson, Ph.D. Loren Fast, Ph.D. • Director, Pathobiology Graduate Program, Brown • The Effect of INACTINE on Lymphocyte University Response, V. I. Technologies, Incorporated (VITEX) • Amino Acid Regulated Gene Expression in Tumorigenesis, American Institute for Cancer • Immunological Consequences of Transfusion, Research NIH/National Heart Lung & Blood Institute • Expression & Role of TA1, Oncofetal Gene in Liver • Induction of Anti-Tumor Immunity Using CD4+ T Cancer, NIH/National Cancer Institute Cells as Antigen-Presenting Cells, Rhode Island Cancer Council, Incorporated CLINICAL RESEARCH Douglas Hixson, Ph.D. • COBRE-The Role of Mitochondrial Uncoupling Protein-2 (UCP2) in Colon Carcinogenesis, NIH/ James Butera, M.D. National Center for Research Resources • Phase III Study of ST1571 vs Interferon-a • Center for Cancer Research Development Combined with Cytarabine in Patients with Newly (COBRE) Proteomics, NIH/National Center for Diagnosed Cancer, Novartis Pharmaceuticals Research Resources Corporation • Center for Cancer Research Development Anita Kestin, M.D. (COBRE) Administrative, NIH/National Center for • Prevent Study, Brigham & Women’s Hospital Research Resources • Molecular Determinants of Multicellular Louis Leone, M.D. Organization, NIH/National Cancer Institute • Cancer and Leukemia Group B Foundation, Cancer • Cellular Origins of Liver CancerGenesis of Liver and Leukemia Group B Foundation Carcinomas With Oval Cell Traits, NIH/National Anthony Mega, M.D. Cancer Institute • BrUOG NHL-83(Amgen) A Phase I Study of • FACTOR VIII12th International CEA Symposium, Escalating Doses of Gemcitabine Combined with Octapharma Pharmaceutical , NIH/National Standard CHOP Chemotherapy with G-CSF Cancer Institutue Support (G-CHOP-G) in Patients with Yow-Pin Lim, M.D., Ph.D. Intermediate/high Grade or Mantle Cell NHL, • Therapeutic and Prognastic Application of Human Amgen Plasma Inter/alpha Inhibitor in the Management of • LS-P-RE-107 Interleukin-2 in an Alternative Dose Sepsis, The Slater Center for Biomedical (The ILIAD Trial) Treatment of Patients with Technology Metastatic Renal Cell Carcinoma with Low-Dose  Proleukin, Chirion BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

• BrUOG Pros-90 A Phase I/II Study of Taxol, • A Phase I/II Study of Estramustine, Docetaxel and Carboplatin and Colchicine (TCC) in Androgen Ifosfamide with Carboplatin in recurrent or Meta- Independent Prostate Cancer, Bristol Myers Squibb static Head and Neck Squamous Cell Cancers • BrUOG NHL-83(Eli Lilly) A Phase IStudy of (HN-SCC), Aventis Pharmaceuticals Products, Escalating Doses of Gemcitabine Combined with Incorporated Standard CHOP Chemotherapy with G-CSF • A Phase 3 Randomized Study of Lonafarbin in Support (G-CHOP-G) in Patients with Combination with Paclitaxel and Carboplatin vs. Intermediate/high Grade or Mantle Cell NHL Placebo in Combination with Paclitaxel and • A Randomized, Multicenter, Phase II Evaluation of Carboplatin in Patients with Non-Small Cell Lung Ontak in Patients with Previously Treated, Cancer, Schering-Plough Corporation Indolent, B-Cell, Non-Hodgkin’s Lymphoma, • Sigma-Tau-ST 01-401 Phase I Study of Oral St Ligand 1481 Administered Once Weekly Every 3 Out of 4 Weeks in Patients With Advanced Solid Neal Ready, M.D. Malignancies, Sigma-Tau Pharmaceuticals • Comparison of Strontium and Samarium Uptake Incorporated and Retention in a Murine Model for Bone • BrUOG H & N 86 Induction Chemotherapy with Metastasis, Amersham Corporation Weekly Taxol, Ifosfamide, and Carboplatin • A Phase I Multicenter Study of Continuous Oral Followed by Concurrent Weekly Taxol and Administration of SCH 66336 and IV Paclitaxel in Carboplatin and Radiotherapy in Locally Advanced Pati, Schering-Plough Research Institute Head and Neck Cancers, Bristol-Myers Squibb, • A Phase III Randomized Trial of Active Immuno- Incorporated therapy with a Polyvalent Melanoma Vaccine (C- • A Phase III Randomized Trial of Active Immuno- VAX) Versus Biotherapy with Interferon x-2b as a therapy with a Polyvalent Melanoma Vaccine (C- Post-Surgical Treatment for Stage III Melanoma, VAX) Versus Biotherapy with Interferon x-2b as a Brown University Post-Surgical Treatment for Stage III Melanoma, • A Phase III Randomized Double Blind Trial of Brown University/NCI/John Wayne Cancer Immunotherapy with Polyvalent Melanoma Institute Vaccine (C-VAX) Plus BCG vs Placebo Plus BCG as • Phase II Study of Weekly Gemcitabine and a Post Surgical Treatment for Stage IV Melanoma, Paclitaxel for Advanced Non-Small Cell Carcinoma Brown University of the Lung (Eli Lilly & Co), Eli Lilly and Company • BRUOG PA-77 Herceptin and Gemcitabine for • Outpatient Concurrent Chemo-Biotherapy for Metastatic Pancreatic Cancer That Overexpresses Metastic Malignant Melanoma Phase II, Chiron HER-2NEU, Brown University Corporation • BrUOG PA-A-128 A Phase III Double Blind • Outpatient Concurrent Chemo-Biotherapy for Placebo Controlled Trial of Gemcitabine Plus Metastatic Malignant Melanoma, Phase II, Placebo Versus Gemcitabine Plus R115777 in Schering Corporation Patients With Advanced Pancreatic Cancer, Brown • The SILVA Study: Survival in International Phase University III Prospective Randomized LD Small Cell Lung • BRUOG ESO-78 A Phase I/II Trial of Herceptin, Cancer Vaccination Study with Adjuvant BEC2 and Paclitaxel, Cisplatin and Radiation Followed by BCG , Imclone Systems Incorporated Maintenance Herceptin for Adenocarcinomas of • A Multicenter, Open Label Randomized Study of the Esophagus, Brown University Three Schedules of Weekly Taxol Induction • A Randomized Double Blind Phase III Therapy Followed by Weekly Taxol Maintenance Comparative Trial of 2 Doses of ZD1839 (IRESSA) Therapy in Metastatic Breast Cancer Patients, In Combination W, Covance, Incorporated Theradex • Sunbelt Melanoma Trial: A Multicenter Trial of Adjuvant Interferon Alfa-2B for Melanoma Alan Rosmarin, M.D. Patients with Early Lymph Node Metastasis • BrUOG MDS-85 Phase I/II Study of ONTAK in the Detected by Lymphacic Mapping and Sentinel Treatment of Myelodysplastic Syndromes, Brown Lymph Node Biopsy, Schering-Plough Corporation University • A Two Part Multiple Dose Clinical Trial of Safety • An Open-label, Randomized Study to Develop a and Efficacy of ABX-EGF in Combination with Screening Tool for Functional Capacity in Anemic Paclitaxel and Carboplatin in Patients with Subjects with Nonmyeloid Malignancies Receiving Advanced Non-Small Cell Lung Cancer (LS-P-LU- Chemotherapy with Darbepoetin also (NESP), 303), Amgen, Incorporated Amgen

 HEMATOLOGY- ONCOLOGY

Howard Safran, M.D. • Radiation Therapy Oncology Group (RTOG), • BrUOG ESO-78 A Phase I/II Trial of Herceptin, NIH/Brown University Paclitaxel, Cisplatin and Radiation Followed by • A Phase II Study to Determine the Antitumor Maintenance Herceptin for Adenocarcinomas of Activity of Farnesyltransferase Inhibitor R115777 the Esophagus, Genentech Inc./Brown University in Subjects with Relapse Small Cell Lung Cancer, • Ls-P-PA103 Randomized Phase II Trial to Evaluate Jannsen Pharmaceuticals/Brown University the Effect of Gemcitabine Plus R115777 Versus • A Double-blind, Placebo Controlled, Minimized Gemcitabine Plus Placebo on Time to Phase III Study Comparing Marimastat to Placebo Deterioration in Patients with Advanced Pancreatic as Adjuvant Therpay in Patients with Respectable Cancer (R115777-INT-16), PRA/Janssen Pancreatic Cancer, Brown University • BrUOG PA-77 Herceptin and Gemicitabine for • Phase II Study of TLC D-99 for Hepatobiliary Metastic Pancreatic Cancers that Overexpress HER- Carcinomas, Liposome/Brown University 2/neu, Brown University • A Compassionate Use Study of Oxaliplatin for • BrUOG LU-A-117 The Silva Study-Survival in an Previously Treated Colorectal Cancer Patients, International Phase III Prospective Randomized Jansenn Pharmaceuticals/Brown University LD Small Cell Lung Cancer Vaccination Study with • A Phase I Trial of Tarceva, Gemcitabine, Paclitaxel, Adjuvant BEC2 and BCG (EORTC Protocol and Radiation for Locally Advanced Pancreatic 08971), Brown University Cancer, Genentech, Incorporated • BrUOG LU-A-109 A Phase III, Multi-Center, • An Open-Label, Phase I Study to Evaluate the Randomized, Double-Blind, Placebo-Controlled Safery and Tolerability of rV-CEA(6d)Tricom Study Marimastat in Patients with Minimal Disease Admixed With rV-MUC-1 followed by rV- Stage III Non-Small Cell Lung Cancer (CO3/IVB/ CEA(6D)/Tricom in Combination With GM-CSF 173), Brown University in Subjects with Unresectable Adenocarcinoma of • BrUOG PA-77 Phase II Study of Herceptin and the Pancreas, Therion Pharmaceuticals Gemcitabine For Metastatic Pancreatic Cancers • Safety and Efficacy of Oral Gimatecan (ST 1481) That Overexpress HER-2/Neu, Lilly Research/ Administered on a dx5 Schedule Every 28 Days as Brown University Second Line Therapy for Metastatic Colorectal • BrUOG PA-A-128 Phase III, Couble-Blind, Placebo Cancer in Patients without Previous Exposure to Controlled Trial of Gemcitabine vs. R115777 Plus Camptothecins (A Phase II Trial), Sigma-Tau Gemcitabine in Patients With Advanced Pancreatic Pharmaceuticals Incorporated Cancer, Janssen Pharm./Brown University William Sikov, M.D. • Herceptin and Gemcitabine for Metastatic Pancreatic Cancers That Overexpress Her2/NEU • Cancer and Leukemia Group B, NIH/National (Genentech), Genentech, Incorporated Cancer Institute, , • R115777-INT-11, A Phase III, Double-blind, • CALGB Foundation Grant, NIH/National Placebo-Controlled Trial of Gemcitabine Plus Institutes of Health/University of Chicago Placebo Versus Gemcitabine Plus Placebo versus • BrUOG LU-76 Phase II Study of Weekly Gemcitabine plus R115777 in Subjects with Gemcitabine and Paclitaxel for Advanced NSCL, Advanced Pancreatic Cancer, Janssen Brown University • LS-P-GA101 “A Phase II Study of Epothilone • A Phase II Study of Glutamine Supplementation in Analog BMS-247550 in patients with Metastatic Patients Receiving Weekly Taxol for Metastic Breast Gastric Adenocarcinoma Previously Treated with a on Non-Small Cell Lung Cancers, Bristol-Myers Taxane, Bristol Myers Squibb Squibb/BU • LS-P-PA-109 A Randomized, Open-Label, Multi- • A Randomized Multicenter, Phase II Study of center Phase III Study Comparing the Efficacy and Bolus/Infusion 5FU/LV vs Oxaliplatin and Bolus Safety of a Combination of Intravenous DX-8951F Infusion 5-FU/LV as Third-Line Treatment of (exatecan mesylate) plus Gemcitabine to Gemcita- Patients with Metastatic Colorectal Carcinoma EFC bine Alone in Patients with Locally Advanced or 4760, Prologue Research Metastatic Cancer, Daiidhi Pharmaceutical • BMS CA 163-012-010 A Phase II Study of • Phase I/II Study of Capecitabine/Taxotere and Epothelone analog BMS-247550 in Patients with Carboplatin in Metastatic Adenocarcinoma of the Metastatic Colorectal Cancer Previously Treated Esophagus and Stomach, Aventis Pharmaceuticals with a Fluorphyrimidie and Irinotecan, Bristol Products, Incorporated Myers Squibb • Percutaneous Radiofrequency Ablation of Bone Metastasis Using CT Guidance, Radionics Instruments/Brown University  BROWN MEDICAL SCHOOL DEPARTMENT OF MEDICINE

• A Multicenter, Open-label, Randomized, Two-arm Study of Irinotecan (CPT-11) versus the combination of Oxaliplatin and Irinotecan (CPT- 11) as Second Line Treatment of Metastatic Colorectal Carcinoma, Sanofi-Synthelabo • Gemcitabine and Capectibine in Advanced Breast Cancer: A BrUOG Phase II Study, Roche Laboratories • A Randomized, Open Label, Multicenter Study of Primary Prophylaxis with Neulasta Versus Secondary Prophylaxis as and Adjunct to Chemotherapy in Elderly Subjects with Cancer, Amgen, Incorporated • A Multicenter, Open-label, Randomized Study of Three Schedules of Weekly Taxol Induction Therapy Followed by Weekly Taxol Maintenance Therapy In Metastatic Breast Cancer Patients, Brown University • Phase I Study of Weekly Docetaxel and Doxorubicin in Advance Cancers, Brown University • Phase I Study of Weekly Docetaxel and Lipsomal Doxorubicin HCI (Doxil) in Advanced Cancers, Brown University • An Open-Label, Multicenter, Randomized, Phase III comparator Study of Oral Topotecan Versus Intravenous Topotecan for Second-Line Therapy in Patients with SCLC Who Have Relapsed Greater than or equal to 90 Days After Completion of First Line Therapy, SmithKline Beecham/Brown University • Multicenter Phase II Study of Herceptin and Navelbine as First-Line Therapy for HER2-positive. Metastatic Breast Cancer, Dana Farber/GLAXO • Gemcitabine and Capectibine in Advanced Breast Cancer: A BrUOG Phase II Study, Lilly Research/ Brown University Rochelle Strenger, M.D. • NSABP Breast Cancer Prevention Trial, NIH/ National Institutes of Health/Dana Farber Cancer Inst.

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