A formal Neuro- oncology research group including our medical oncologist, Dr. Margie Lewis, was formed; the group is bringing several clinical protocols together. Recently an algorithm for management of patients with brain tumors on several clinical trials was presented. The neuro-oncology group will have several clinical trials to treat patients with brain tumors at different stages.

Head and Neck Cancer Program:

We have several RTOG studies open. In addition this year, we had two pharmaceutical initiated studies opened with Dr. Pancoast and Dr. Safa.

Lung Cancer program:

The lung cancer program has several SWOG, RTOG and pharmaceutical studies.

Manuscripts:

Jazieh AR, Younas A, Safa M, Redmond K, Buncher R, Howington J. Phase I clinical trial of concurrent paclitaxel, carboplatin, and external beam chest irradiation with glutamine in patients with locally advanced non-small cell lung cancer. Cancer Invest. 2007 Aug;25(5):294-8.

Lowy AM, Firdaus I, Roychowdhury D, Redmond K, Howington JA, Sussman JJ, Safa M, Ahmad SA, Reed MF, Rose P, James L, Jazieh AR. A phase II study of sequential neoadjuvant gemcitabine and paclitaxel, radiation therapy with cisplatin and 5-fluorouracil and surgery in locally advanced esophageal carcinoma. Am J Clin Oncol. 2006 Dec;29(6):555-61.

Breast Cancer Program:

The program has several NSABP, SWOG, and pharmaceutical sponsored studies. Also we have an investigator initiated study for first line metastatic breast cancer.

In collaboration with Clinical Effectiveness Center, Rami Komrokji, and Kathleen Havlin are co-investigators on R01 NIH grant that was submitted for 1 million dollars towards developing a markovian model to address use of herceptin in adjuvant breast cancer. This project will have international collaboration with the Canadian and European breast cancer groups.

Manuscripts:

Nahleh ZA, Srikantiah R, Safa M, Jazieh AR, Muhleman A, Komrokji R. Male breast cancer in the veterans affairs population: a comparative analysis. Cancer. 2007 Apr 15;109(8):1471-7.

Nahleh Z, Girnius S. Male breast cancer: a gender issue. Nat Clin Pract Oncol. 2006 Aug;3(8):428-37. Review

Abstracts:

R. Bakkar, Z. Nahleh, H. Bui, S. Samaan, J. Sanders, A. Namakydoust, R. Komrokji: A comparative analysis of angiogenesis between male and female breast cancers. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 21101 R. S. Komrokji, Z. Nahleh, S. Dhaliwal, D. Sivasubramaniam: Outcome of patients with locally advanced breast cancer (LABC) followed at the University of Cincinnati (UC). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 21160 D. Sivasubramaniam, R. Komrokji, S. Dhaliwal, V. Sundarajan, Z. Nahleh: Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 21103

GI oncology Program:

The program has several SWOG, pharmaceutical studies; Dr. Safa has an investigator initiated study addressing the role of amifostine in preventing oxaliplatin neuropathy. The University of Cincinnati was one of the top accruing institutions to SWOG pancreatic cancer protocol. The program is also working with the surgical oncology and liver transplant group to form a liver cancer research group.

Manuscripts:

Schmulewitz N, Singh P, Safa M, Robinson-Smith T. Diagnosis of peritoneal carcinomatosis by EUS-guided FNA.Gastrointest Endosc. 2007 Aug 23.

Atiq M, Safa M. Recurrent hypoglycemia associated with poorly differentiated carcinoma of the liver. Am J Clin Oncol. 2007 Apr;30(2):213-4

Abstracts:

S. F. Mekan, R. S. Komrokji, M. S. Beg, M. Atiq, M Safa.: Does adjuvant therapy improve survival in pancreatic cancer in the VA population? Abstract - No. 133 2007 Gastrointestinal Cancers Symposium

M. S. Beg, R. S. Komrokji, M. Atiq, S. Ali, S. F. Mekan, A. Gupta, P. John, M. M. Safa: Esophageal cancer at the VA: Does histology matter? Abstract - No. 61 2007 Gastrointestinal Cancers Symposium

M. S. Beg, R. S. Komrokji, M. Atiq, S. F. Mekan, S. Ali, A. Gupta, J. Pancoast, M. M. Safa: Esophageal squamous cell carcinoma in the VA population: What is the optimal treatment modality? Abstract - No. 33 2007 Gastrointestinal Cancers Symposium

S. F. Mekan, R. S. Komrokji, M. S. Beg, M. Atiq, Z. A. Nahleh, M. M. Safa Treatment of unresectable or metastatic pancreatic cancer in the VA population: Does it improve survival? Abstract - No. 134, 2007 GI Cancers Symposium

M. S. Beg, A. Gupta, R. Komrokji, M. Atiq, S. Ali, M. Safa: Impact of screening on presentation and survival of colorectal cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1535

A. K. Gupta, M. S. Beg, R. Komrokji, M. Atiq, S. Mekan, M. Safa: Esophageal cancer at the VA: Does histology matter? Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15069

M. M. Safa, M. S. Beg, M. Atiq, S. Ali, R. Komrokji: Esophageal squamous cell carcinoma in the VA population: What is the optimal treatment modality? Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15042

S. F. Mekan, R. S. Komrokji, M. S. Beg, Z. A. Nahleh, M. M. Safa: Treatment of unresectable or metastatic pancreatic cancer in the VA population: Does it improve survival? Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15121

GU oncology Program:

We have several SWOG, RTOG, and pharmaceutical studies.

Manuscripts:

Kham I, Atiq M, Partridge S, Budhani I, Riss D, Adeniran D, Oleksowicz, L: Mature mediastinal teratoma with elevated a-fetoprotein in a patient with klinefelter's syndrome. 7/06. Submitted for publication.

Hematological Malignancies Program (Leukemia & Lymphoma):

We have several SWOG, pharmaceutical studies. Dr. Rami Komrokji is PI for several investigator-initiated studies including cetuximab for multiple myeloma, CLAG Gleevec for relapsed or refractory AML, erlotinib for Myelodysplastic syndrome and alimta for cutaneous T cell lymphoma.

Dr. Komrokji is working in collaboration with Dr. Eckman to develop a markovian model to address the best treatment strategy for post remission in AML.

Dr. Rami Komrokji is the co-investigator on a National multi-institution NCI study for risk Acute promyelocytic Leukemia.

Manuscripts:

Rami S Komrokji, John M Bennett: Who is WHO in Myelodysplastic Syndromes? Clinical Implications of the WHO Classification. Current Hematologic Malignancy Reports 2006, 1:9-15

Rami S. Komrokji, Nikhil P. Uppal, Alok A. Khorana, Karen L. Kaplan, Gary H. Lyman, Richard I. Fisher, Charles W. Francis. Venous Thromboembolic Events in Patients with Diffuse Large B cell Non- Hodgkin Lymphoma. Leukemia Lymphoma Journal, June 2006; 47(6): 1029-1033

Rami S Komrokji: Myelodysplastic syndromes: A View from Where the Sun Rises and Where the Sun Sets. Leukemia Research Journal; epub 2006 May 22

Rami S Komrokji, john M Bennett: Evolving Classifications of Myelodysplastic syndromes, Current Opinion in Hematology 2007 Mar;14(2):98-105. Review

Abstracts:

Sanjay Maraboyina, Rami S Komrokji, Rami Y Haddad, Zeina A Nahleh and Malek M Safa: Racial Disparities in Diffuse Large B Cell Lymphoma: A VA population study. Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 4614.

Rami S Komrokji, Sanjay Maraboyina, Malek M Safa, Zeina A Nahleh, and Rami Y Haddad: Outcome of Diffuse Large B Cell Lymphoma in the VA Health System: Do We Need to Do Better? Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 4657.

Rami S Komrokji, Sanjay Maraboyina, Rami Y Haddad, Zeina A Nahleh, and Malek M Safa: Outcome of Diffuse Large B cell Lymphoma in the VA system: The Rituximab Era. Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 4729.

Rami Y. Haddad and Rami S. Komrokji: Infectious Mononucleosis Presenting with Severe Thrombocytopenia, Positive Anti-Platelets Antibodies, and Peripheral Blood Blasts. Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 3976.

Camille N Abboud, Alison Walker, Rami S Komrokji, et al: Phase I Study of Cladribine, Cytarabine (Ara?C), Granulocyte Colony Stimulating Factor (G?CSF) (CLAG Regimen) and Simultaneous Escalating Doses of Imatinib Mesylate (Gleevec) in Relapsed/Refractory AML. Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 1958.

G. Murphy, N. Al Ali, S. Beg, J Schrager, M Safa, R. S. Komrokji: Myelodysplastic Syndromes: VA population Study ( submitted to ASH 2007)

S Desai, M Safa, R. S. Komrokji: Out come of Follicular NHL has improved among VA patients. (submitted to ASH 2007) R.S. Komrokji, N Al Ali, S Beg, J Schrager, M safa: Outcome of Diffuse large B cell Lymphoma in the United States: SEER review (submitted to ASH 2007) Francine Foss, Nelida Sjak-Shie, Andre Goy, Eric Jacobsen, Ranjana Advani, Mitchell Smith, Rami Komrokji, Kelly Pendergrass, Vanessa Bolejack, Karen Watts, and Mark Acosta: Denileukin Diftitox (ONTAK) plus CHOP Chemotherapy in Patients with Peripheral T-cell Lymphomas, the CONCEPT Trial. (submitted to ASH 2007)

Sickle Cell Program and Benign Hematology Program:

The laboratory of Robert S. Franco, PhD, is the recipient of a major research grant from the NIH to study the red blood cell in sickle cell anemia. The physiological and molecular determinants of aberrant sickle red blood cell aging and density are characterized using a novel, in vivo method developed by Dr. Franco's laboratory. Dr. Franco also applies this new technology to studies in transfusion medicine.

Manuscripts:

Franco RS, Yasin Z, Palascak MB, Ciraolo P, Joiner CH, Rucknagel DL.
The effect of fetal hemoglobin on the survival characteristics of sickle cells.
Blood. 2006 Aug 1;108(3):1073-6.

Supportive Care:

We had one investigator initiated study: Melatonin for prevention of Taxane related neuropathy. We have several pharmaceutical studies being opened for growth factor support, anti-emetics and pain management.

Manuscripts:

Jazieh AR, Foraida M, Ghouse M, Khalil MM, Kopp M, Savidge M. The impact of cancer diagnosis on the lifestyle and habits of patients served at a Veterans Administration Hospital. J Cancer Educ. 2006 Fall; 21(3):147-50.

Swarup AB, Barrett W, Jazieh AR. The use of complementary and alternative medicine by cancer patients undergoing radiation therapy. Am J Clin Oncol. 2006 Oct. 29(5):468-73.

Whitmer KM, Pruemer JM, Nahleh ZA, Jazieh AR. Symptom management needs of oncology outpatients. J Palliat Med. 2006 Jun; 9(3):628-30.

Lee AH, Ingraham SE, Kopp M, Foraida MI, Jazieh AR.The incidence of potential interactions between dietary supplements and prescription medications in cancer patients at a Veterans Administration Hospital. Am J Clin Oncol. 2006 Apr;29(2):178-82.

Basic Science Research:

Drs. Malaya and Sunil Chatterjee are nationally recognized authorities in cancer vaccine research. They have developed several novel tumor vaccines that are currently in national and international clinical trials. Their basic and clinical research is supported by grants from the NIH.

Some recent publications from their lab include:

1. Saha A, Baral RN, Chatterjee SK, Mohanty K, Pal S, Foon KA, Primus FJ, Krieg AM, Weiner GJ, Bhattacharya-Chatterjee M. CpG oligonucleotides enhance the tumor antigen-specific immune response of an anti-idiotype antibody-based vaccine strategy in CEA transgenic mice. Cancer Immunology Immunotherapy 55(5): 515?527, 2006.

2. Saha A, Chatterjee SK, Foon KA, Bhattacharya-Chatterjee M. Anti-idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen. Immunology 118(4): 483?496, 2006. Erratum in: Immunology 119(1): 143, 2006.

3. Saha A, Chatterjee SK, Foon KA, Celis E, Bhattacharya-Chatterjee M. Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Research 67(6): 2881?2892, 2007.

4. Mohanty K, Saha A, Pal S, Mallick P, Chatterjee SK, Foon KA, Bhattacharya-Chatterjee M. Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu. Breast Cancer Research and Treatment, in press, 2007.

5. Dasgupta, S., Tripathi, P.K., Hongxing Qin, Bhattacharya-Chatterjee, M., Valentino, J., Chatterjee, S.K. Identification of molecular targets for immunotherapy of patients with head and neck squamous cell carcinoma. Oral Oncol., 42: 306-316, 2006.

6. Dasgupta S, Bhattacharya-Chatterjee, M., O'Malley, B.W., Jr., and Chatterjee, S.K. Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF-beta 1 secreted by the tumor cells. J. Cellular Biochem. 97: 1036-1054, 2006.

7. Dasgupta S, Bhattacharya-Chatterjee, M., O'Malley, B.W., Jr., and Chatterjee, S.K. Recombinant vaccinia virus expressing interleukin-2 invokes anti-tumor cellular immunity in an orthotopic murine model of head and neck squamous cell carcinoma. Mol. Ther. 13: 183-193, 2006.

Dr Dong has an active lab focusing on prostate cancer research. Some of his recent publications include:

1. Yun, Y., Shanov, V., Schulz, M. J., Dong, Z., Jazieh, A., Heinemand, W., Halsall, H. B., Wong, D., Bange, A., Tu, Y., and Subramaniam, S. High sensitivity carbon nanotube tower electrodes. Sensors and Actuators B, 120: 298-304, 2006.

2. Zhang, F., Lee, J., Wang, D., Dong, Z. Differential growth of interferon-b-engineered tumor cells in nude and interferon receptor-null mice. J. Interferon & Cytokine Res., 26: 108-118, 2006.

3. Shi, D., Lian, J., Wang, W., Liu, G., He, P., Dong, Z., Wnag, L., Ewing, R.C., Lucinescent carbon nanotubes by surface functionalization. Adv. Materials, 18:189-193, 2006.

4. Yun, Y., Gollapudi, R., Shanov, V., Schulz, M., Dong, Z., Jazieh, A., Heineman, W., Halsall, B., Wong, D., Tu, Y., Subramaniam, S. Carbon Nanotubes Grown on Stainless Steel to form Plate and Probe Electrodes for Chemical/Biological Sensing. J. Nanoscience & Nanotechnol. In press.

5. Olson, M.V., Lee, J., Zhang, F., Wang, A., and Dong, Z. Inducible nitric oxide synthase activity is essential for inhibition of prostatic tumor growth by interferon- gene therapy. Cancer Gene Ther. 13: 676-685, 2006.

6. Lu, S. and Dong, Z. Characterization of TGF-b-regulated interleukin-8 expression in human prostate cancer cells. Prostate, 66: 996-1004, 2006.

7. Dong, Z., Liu, Y., Lu, S., Wang, A., Lee, K., Wang, L. H., Revelo, M., and Lu, S. Vav3 oncogene is overexpressed and regulates cell growth and androgen receptor activity in human prostate cancer. Mol Endocrinol, 20: 2315-2325, 2006.

8. Yun, Y., Bange, A., Shanov, V., Heinemand, W., Halsall, H. B., Wong, D. K. Y., Behbehani, M., Pixley, S., Bhattacharya, A., Dong, Z., and Schulz, M. J. A nanotube composite microelectrode for monitoring dopamine levels using cyclic voltammetry and differential pulse voltammetry. J Nanoegineering and Nanosystems, 220: in press.

9. Lee, J., Wang, A., Hu, Q., Lu, S., and Dong, Z. Adenovirus-mediated interferon-beta gene transfer inhibits angiogenesis in and progression of orthotopic tumors of human prostate cancer cells in nude mice. Int J Oncol, 29: 1405-1412, 2006.

10. Yun, Y., Dong, Z., Shanov, V., Schulz, M., et al, A Nanotube Array Immunosensor for Direct Electrochemical Detection of Antigen-antibody Binding, Sensors and Actuators B, 123:177-182, 2007.

11. Yun, Y. H., Bange, A., Shanov, V. N., Heineman, W. R., Halsall,H.B., Dong,Z.Y., Jazieh,A., Tu,Y.,Wong,D.K.Y., Pixley, S., Behbehani, M., and Schulz, M. J. Highly sensitive carbon nanotube needle biosensors. J. Nanoscience and Nanotechnology, 7, 2293-2300, 2007.

12. Lu, S., Wang, A., Lu, S., and Dong, Z. A novel synthetic compound that interrups androgen receptor signaling in human prostate cancer cells. Molecular Cancer Therapeutics. In press.

Education:/

Manuscripts:

Nahleh Z, Komrokji R, Jazieh AR, Benedetti J, Sparks D: Cancer Research Training:The Southwest Oncology Group Young Investigator Training Program (YITP). J Cancer Educ. 2006 Summer; 21(2):77-9. Safa M, Jazieh AR. Lack of a uniform approach to clinical research training for hematology oncology fellows. J Cancer Educ. 2006 Fall; 21(3):166-8. Byrnes AB, McCormack FX, Diers T, Jazieh AR. The resident scholar program: a research training opportunity for internal medicine house staff. J Cancer Educ. 2007 Spring; 22(1):47-9.

The following projects are underway:

New approaches to breast cancer therapy using anti-idiotype antibody as a surrogate antigen for human HER2/Neu. Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the immunotherapy of cancer. We have developed and characterized a murine monoclonal anti-Id antibody that mimics a specific epitope of human HER2/Neu protooncogene and can be used as a surrogate antigen for HER2/Neu. The efficacy of this anti-Id as a tumor vaccine is being evaluated in a murine tumor model transgenic for HER2/Neu (supported in part by NIH grant RO1 CA 91878).

Rational design of therapeutic vaccines for CEA-positive tumors. We are also involved in the further characterization of an anti-Id vaccine 3H1 which mimics Carcino Embryonic Antigen (CEA) and has shown clinical efficacy in Phase I/II clinical trials of gastrointestinal cancer patients. In a murine tumor model double transgenic for CEA and human HLA-A2, we are exploring the combined use of 3H1 plus agonistic peptides of CEA to see if the combined regimen has better therapeutic benefits than the anti-Id or peptides used alone (supported by the NIH grant RO1 CA104804).