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Publications
Research Projects
A variety of funded research protocols have used the ACSR's HIV and non-HIV infected tissues. More than 1400 specimens have been awarded to 50 approved researchers worldwide since the beginning of 1996. These specimens were from patients with AIDS-related lymphoma, KS, anogenital disease and lung cancer. The broad type of studies performed using ACSR specimen include the following:
  • Search for specific or novel viruses in cancer tissue
  • Examine the role of chemokines, cytokines and growth factors in cancer
  • Study the contribution of chronic B-cell stimulation to B-cell lymphomas
  • Search for genomic/chromosomal changes (some virally mediated) or changes in gene expression profiles
  • Diagnostic assay development and validation
  • Search for markers of oncogene activation
  • Effect of HIV integration site on cancer development
  • Mechanisms of resistance and susceptibility to antiviral agents
  • Identification of viral CTL epitopes

Results of selected studies:

First description of angiogenic responses associated with in vivo growth of HHV-8+ PEL cells transplanted into SCID mice. Subsequent studies by other investigators indicated that PEL cells secrete VEGF and that HHV-8 vIL-6 may contribute to the pathogenesis of these infusion lymphomas via VEGF stimulation and subsequent increases in vascular permeability.

Molecular evidence of the polyclonality in HIV associated polyclonal lymphoma, qualitative differences in somatic hypermutations of Ig V(H) genes associated with malignant versus B-cell lymphompropliferations. Subsequent work using SCID mice injected with BCBL-1 cells revealed an association of large cell lymphomas with human macrophages supporting the macrophage initiated sequential pathogenesis model of lymphomagenesis.

HIV+ individuals have aberrant and unstable expression of Ig genes suggestive of a high degree of humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens. Results were consistent with the hypothesis that rapid B-cell turnover due to antigenic stimulation may result in somatic mutations leading to malignant transformation.

Widespread genomic instability, manifested by increase frequency of micro satellite alterations, was greatly increased in HIV+ patients with lung cancer.

Impaired cellular capacity of KS cells to degrade oxidants resulting in intracellular retention of reactive oxygen intermediates and subsequent oxidant stress. This perturbation results in increased responsiveness to TNF-a which may cause a feedback growth signaling loop in KS cells.

Using a variety of in situ techniques, HHV-8 gene expression and virion localization was demonstrated within endothelial cells of KS lesions.

Several genes of HHV-8 were indentified including the immunodominant K8.1 viral glycoprotein subsequently employed in development of sensitive and specific serologic assays. Latent messages encoded with the ORF K15 were identified; one is related to the EBV LMP2 gene, a target for immunotherapy.

Development, calibration and validation of HHV-8 immunoassays.

Four distinct subtypes of HHV-8 were identified that clustered by geographic location implicating that HHV-8 is an ancient human virus preferentially transmitted vertically in a familial fashion and is difficult to transmit horizontally in the absence of immune supporesion. Subsequent virus transmission by others have supported these results.
Publications
Abstracts
  1. Mack K, Wei R, Shiramizu B, Herndier B, Elbaggari A, Gascon R, Hurt M, McGrath MS. “Sequential Pathogenesis” of AIDS malignancies: Clonal insertion of HIV into macrophages may serve as an early neoplastic event. Keystone Symposia on Molecular and Cellular Biology Park City, UT, March 13-19, 1998
  2. Flickinger M, McGrath M, Silver S, Orenstein J, Miles S, Ayers LW. AIDS Malignancy Bank: a source for tissue and biological fluids of HIV-related malignancies. In Proceedings of the Second National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8, 1998. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S1-86.
  3. Herndier B, Wei R, Abbey N, Weinstein M, Mack K, Shiramizu B, McGrath MS. Kaposi’s sarcoma: a multicellular, mulitviral process initiated by retroviral insertional mutagenesis?. In Proceedings of the Second National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8, 1998. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S1-86.
  4. Mack K, Wei R, Shiramizu B, Herndier B, Elbaggari A, Gascon R, Hurt M, McGrath MS. Evidence for HIV mediated cis-activation of the c-fes protooncogene in a subset of AIDS associated lymphomas. In Proceedings of the Second National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8, 1998. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S1-86.
  5. Mallery SR, Clark YM, Ness GM, Ayers LW and CM Hohl. AIDS-Kaposi's Sarcoma Demonstrate Increased Susceptibility to a Redox Cycling Drug. In Proceedings of the Second National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8, 1998. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S1-86.
  6. Flickinger M, McGrath M, Silver S, Orenstein J, Miles S, Ayers LW. AIDs malignancy bank: a source for tissue and biological fluids of HIV-related malignancies. 12th World AIDS Conference Geneva, Switzerland, June 28 - July 3, 1998 [Conference WebSite]
  7. McGrath MS, Shiramizu B, McGuire D, Pulliam L, Herndier B. HIV-associated neoplastic dementia: A model implicating a role for clonal macrophages. In  Proceedings of the Second National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8, 1998. J Acquir Immune Defic Syndr. 1999 Aug 1;21 Suppl 1:S1-86.
  8. Ayers LW, McGrath MS, Silver S, Miles S, Axiotis C. The AIDS and Cancer Specimen Bank (ACSB), A NCI Tissue and Biological Fluids Bank of HIV Infected Tissues. In The 3rd National AIDS Malignancy Conference. Bethesda, Maryland, USA. May 26-27, 1999. Abstracts. J Acquir Immune Defic Syndr. 1999 May 1;21(1):A1-41.
  9. Flickinger M, McGrath M, Silver S, Orenstein J, Miles S, Ayers LW, Axiotis C. Tissue and biological fluids banks of HIV-related malignancies. In The 3rd National AIDS Malignancy Conference. Bethesda, Maryland, USA. May 26-27, 1999. Abstracts. J Acquir Immune Defic Syndr. 1999 May 1;21(1):A1-41.
  10. Parris L, Ayers LW. Iron Loading of Alveolar Macrophages in HIV Positive Patients. The MRI Science Symposium, Medical/Science Research Initiative, (MRI), Office of Minority Affairs Columbus, OH, August 1999
  11. Abbey NW, McGrath MS, Herndier BG. C-fes proto-oncogene expression in HIV and non-HIV lymphoid tissues. Seventh Conference on Retroviruses and Opportunistic Infections San Francisco, CA, January 30 – February 2, 2000
  12. Mack KD, Wei R, Herndier B, Shiramizu B, Abbey N, Gascon R, Elbaggari A, Hurt M, Earnst T, McGrath MS. HIV implicated in the cis-activation of c-fes in a subset of HIV associated lymphomas. Seventh Conference on Retroviruses and Opportunistic Infections San Francisco, CA, January 30 – February 2, 2000
  13. Davis, AT, Mosunjac MB. Cervical dysplasia in women infected with human immunodeficiency virus {HIV): a correlation with HIV viral load. United States and Canadian Association of Pathology meeting New Orleans, LA, March 2000
  14. Davis, AT, Walliang R, Mosunjac MI, Mosunjac MB. Human immunodeficiency virus (HIV)-associated premalignant and malignant lesions by gender in a large inner-city hospital: a retrospective study. United States and Canadian Academy of Pathology Annual Meeting New Orleans, LA, March 25-31, 2000
  15. Abbey NW, Silver S, Orenstein JM, Miles S, Ayers L, Axiotis C, McGrath MS. The AIDS and Cancer Specimen Bank. In The 4th International AIDS Malignancy Conference. Bethesda, Maryland, USA. May 16-18, 2000. Abstracts. J Acquir Immune Defic Syndr. 2000 Mar 1;23(3):A1-37.
  16. Ayers LW, and The Midregion ACSB Consortium. The Ohio State University, Emory University, Rush University, University of Texas, Southwestern and Vanderbilt University: Application of the Tissue Microarray (TMA) method by the Midregion AIDS and Cancer Specimen Bank (ACSB) to prepare study sets from HIV infected and control tissues. In The 4th International AIDS Malignancy Conference. Bethesda, Maryland, USA. May 16-18, 2000. Abstracts. J Acquir Immune Defic Syndr. 2000 Mar 1;23(3):A1-37.
  17. McGrath MS, Elbaggari A, Gascon R, Herndier B, Meuer S, Giese T, Zenger E. Quantitation of AIDS lymphoma associated macrophage RNA. implications for “sequential pathogenesis” of extranodal lymphoma. In The 4th International AIDS Malignancy Conference. Bethesda, Maryland, USA. May 16-18, 2000. Abstracts. J Acquir Immune Defic Syndr. 2000 Mar 1;23(3):A1-37.
  18. Ayers LW, Romer D, Yi H, The Midregion AIDS and Cancer Specimen Bank (ACSB). Cancer Research Data from Tissue Microarrays (TMA) and the Associated Patient Demographic and Clinical Information Facilitated by a Graphical Microsoft Access Database. Cancer research data from tissue microarrays (TMA) and the associated patient demographic and clinical information facilitated by a graphical Microsoft Access database. Third Annual Comprehensive Cancer Center Scientific Meeting Dublin, OH, January 24, 2001
  19. Ayers LW, Romer D, Yi H, and The Midregion AIDS and Cancer Specimen Bank (ACSB), and Division of Informatics, Department of Pathology, The Ohio State University, Columbus, OH 43210. AIDS-Associated Malignant Tissue Research using Tissue Micro-Arrays (TMAs) Facilitated by a Graphical Microsoft Access Database. Fifth International AIDS Malignancy Conference Bethesda, MD, April 23-26, 2001 [program only]
  20. Garcia D, McGrath MS, Silver S, Miles S, Ayers L, Axiotis C. AIDS and Cancer Specimen Bank. Fifth International AIDS Malignancy Conference Bethesda, Maryland, 26, April 23-25, 2001 [program only]
  21. Ayers L, Romer D. Development of a Tissue Array Data System (TADS) for AIDS and Cancer Specimen Bank (ACSB). In Advancing Pathology Informatics, Imaging, and the Internet (APIII 2001). Arch Pathol Lab Med. 2002 Jul;126(7):791–792.
  22. Romer D, Ayers L. Adding a Robotic Stage to the Desktop Microscope and Creating Virtual Slides with Image Pro Plus. In Advancing Pathology Informatics, Imaging, and the Internet (APIII 2001). Arch Pathol Lab Med. 2002 Jul;126(7):792.
  23. Garcia DL, McGrath MS, Silver S, Orenstein J, Ayers L. AIDS and Cancer Specimen Bank. The XIV International AIDS Conference, 2002 Abstract no. C11034.
  24. Ayers LW, Romer D, Yi H. The Midregion AIDS and Cancer Specimen Bank (ACSB). A Tissue Array Database System (TADS) for the AIDS Cancer and Specimen Bank (ACSB) Developed to Manage Numerical and Digital Image Cancer Research Data From Tissue Microarrays (TMAs). The Fourth Annual Comprehensive Cancer Center Scientific Meeting Dublin, OH, January 11, 2002
  25. Mihm M, Schanbacher BL, Basuray A, Lui C, Amann DM, Ayers LW, John Anthony Bauer, JA. Protein Oxidation and Immune Cell Trafficking in Human AIDS-Related Cardiomyopathy. The Ohio State University Medical Center Graduate and Postgraduate Research Day April 4, 2002
  26. Ayers LW, D. Romer, H Yi. The Midregion AIDS and Cancer Specimen Bank (ACSB). A Tissue Array Management System (TAMS) for the AIDS Cancer and Specimen Bank (BANK) Developed to Manage Numerical and Digital Image Cancer Research Data From Tissue Microarrays (TMAs). Sixth International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research Bethesda, MD, April 22-24, 2002 [program only]
  27. Garcia DL, Ayers LW, Axiotis C, Orenstein J, Miles S, Silver S, McGrath MS. ACSB CODCC, AIDS and Cancer Specimen Bank: A Resource for Your Research. Sixth International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research Bethesda, MD, April 22-24, 2002 [program only]
  28. McGrath MS, Jin X, Yu S, Wei R, Kapp L, Green C, Abbey NW, Elbaggari A, Liu Y, Herndier B, Mack KD. HIV insertions within and proximal to host cell genes are a common finding in tissues containing high levels of HIV DNA and macrophage associated P24 antigen expression. Fifth International Workshop on HIV, Cells of Macrophage/Dendritic Lineage and Other Reservoirs Rome, Italy, 15, October 13-15, 2002.
  29. Hadlock KG, Miller RG, Gelinas D, Jin X, Reis J, Mass J, McGrath MS. Elevated reactivity to HML-2 /HERV-K but not other endogenous retroviruses in ALS. 55th Annual Meeting of the American Academy of Neurology Honolulu, HI, March 29-April 5, 2003
  30. McGrath MS, Gascon RL, Miller RG, Gelinas D, Yu S, Zhang RZ, Frydman B, Marton L. Pathogenesis of ALS: Removal of abnormal macrophages (MO) and source of pathogenic factor production from ALS blood in vitro with a novel polyamine analogue, SL-11047. 55th Annual Meeting of the American Academy of Neurology Honolulu, HI, March 29-April 5, 2003
  31. Ayers LW, Mihm MJ, Hackman B, Bauer JA, Midregion AIDS and Cancer Specimen Resource (ACSR). AIDS Patients have High Levels of Protein Nitration within Actively HIV Infected Cells. Does this Cause Organ Malfunction and Cancer? Abstracts from the Seventh International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Natcher Conference Center Bethesda, MD, April 28-29, 2003. [http://www.cancer.gov/dctd/aids/conference] 2003:86.
  32. Silver S, Ayers L, Orenstein J, McGrath M. Aids and Cancer Specimen Resource: a Resource for Your Research. In Abstracts of the ISBER Annual Meeting: Biodiversity and International Regulations. May 4-7, 2003, Philadelphia, Pennsylvania, USA. Biotech Histochem. 2003 Jun-Aug;78(3-4):207-28.
  33. Nohle DG, Hackman BA, Ayers LW. Web-based Virtual Tissue Micro-array Slides with clinical Data F or Researchers in HTML, Excel and API Standard XML Data Exchange Specification Formats Produced with Microsoft Office® Applications. In Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2003): Scientific Session and E-Poster Abstracts. Arch Pathol Lab Med. 2004 Oct;128(10):1089–1123.
  34. Bachowski GJ, Birdsong GG, Lau SK, Tadros TS, Oprea GM. Evolution of High Grade Squamous Intraepithelial Lesion (HSIL) in HIV-Positive Women compared to the General Population: 5 year Follow-Up. United States and Canadian Academy of Pathology Meeting Vancouver, Canada. March 17–19, 2004
  35. Yu S, Lamers S, Jin X, Reis J, McGrath MS. Restricted HIV genomic variability in AIDS dementia and lymphoma. Keystone Symposia, Molecular mechanisms of HIV Pathogenesis Whistler, British Columbia, April 12-18, 2004 [program only]
  36. Ayers LW, Jin X, Bauer JA, McGrath M. HIV Integration Sites Found in Cardiac Myocyte Nuclei and Adjacent PCNA Positive Macrophage Nuclei from AIDS Cardiomopathy Heart Tissue. Abstracts from the 8th International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research Bethesda, MD, April 29-30, 2004. [http://www.cancer.gov/dctd/aids/conference] 2004:74.
  37. Lamers S, Yu S, McGrath MS. Genetic analysis of HIV-1 from site-specific brain tissue: Does compartmentalization occur within the brain? 11th International Workshop, HIV Dynamics and Evolution Stockholm, Sweden, April 29-May 4, 2004
  38. Nohle DG, Hackman B, Ayers L. Tissue Micro-Array Data Using TMA Standard and Public Tool Linked Legend and Clinical Details at ACSR.Mid-Region.org. Tissue Micro-Array Data Using TMA Standard and Public Tool Linked Legend and Clinical Details at acsr.mid-region.org. Abstracts from the 8th International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Natcher Conference Center Bethesda, MD, April 29-30, 2004. [http://www.cancer.gov/dctd/aids/conference] 2004:75.
  39. McGrath MS, Garcia D, Ayers L, Silver S, Orenstein J, Lamers S. AIDS and cancer specimen resource: A resource for HIV reservoir research. The XV International AIDS Conference, 2004 Abstract no. A10525.
  40. McGrath MS, Yu S, Jin X, Reis J, Lamers S. Restricted HIV genomic variability in AIDS dementia and lymphoma. The XV International AIDS Conference, 2004 Abstract no. ThOrA1399.
  41. Nohle DG, Hackman BA, Ayers LW. A Document Type Definition for the API standard tissue micro-array XML data exchange specification, In Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2004): Scientific Session and E-Poster Abstracts. Arch Pathol Lab Med. 2005 Jun;129(6):811-834.
  42. Lamers SL, Salemi M, McGrath MS. HIV-1 envelope domains derived from AIDS related lymphoma tissues display unique substitution patterns as compared to published envelope domains. The 3rd IAS Conference on HIV Pathogenesis and Treatment, 2005 Abstract no. MoPe14.2B17.
  43. McGrath MS, Lamers SL, Salemi M. HIV sequence evolution in the brain: Distinctly different evolutionary pathways between HAD and primary CNS lymphoma associated strains of HIV. The 3rd IAS Conference on HIV Pathogenesis and Treatment, 2005 Abstract no. WePe8.13B04.
  44. Nohle DG, Hackman BA, Ayers LW. Adding style to the API Tissue Micro-array Data Exchange Specification, In Advancing Practice, Instruction, and Innovation Through Informatics (APIII 2005): Scientific Session and E-Poster Abstracts. Arch Pathol Lab Med. in press.
  45. Dittmer DP, Staudt MR, Fakhari FD, Hilscher C, Sin S, Chaput A. Regulation of KSHV Latent gene expression. Abstracts from the 9th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Marriott Bethesda North Hotel & Conference Center, North Bethesda, MD, September 26-27, 2005. [http://www.cancer.gov/dctd/aids/conference] in press.
  46. Levine AL, Seaberg EC, Hessol NA, Preston-Martin S, Li M, Silver S, Cohen M, Anastos K, Minkoff H, Black J, Watts DH. HIV is not a risk factor for lung cancer in women: data from the women’s interagency HIV study (WIHS). Abstracts from the 9th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Marriott Bethesda North Hotel & Conference Center, North Bethesda, MD, September 26-27, 2005. [http://www.cancer.gov/dctd/aids/conference] in press.
  47. Mbulaiteye SM, Katabira ET, Wabinga H, Parkin DM, Virgo P, Ochai R, Workneh M, Coutinho A, Engels EA. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-cancer registry match study. Abstracts from the 9th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Marriott Bethesda North Hotel & Conference Center, North Bethesda, MD, September 26-27, 2005. [http://www.cancer.gov/dctd/aids/conference] in press.
  48. McGrath MS, Lamers S, Salemi M. Evolutionary distinct forms of HIV in AIDS lymphoma and dementia. Abstracts from the 9th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Marriott Bethesda North Hotel & Conference Center, North Bethesda, MD, September 26-27, 2005. [http://www.cancer.gov/dctd/aids/conference] in press.
  49. Shikuma CM, Shiramizu B, McGrath M, Shagrun L, Chow D, Gerschenson M. HIV Infected Monocytes and Macrophages in Adipose Tissue Contribute to the Development of Lipatrophy. 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 13-16 Nov 2005 in Dublin, Ireland.
  50. Zhang RZ, Gascon R, Miller RG, Gelinas DF, Mass J, Lancero M, Narvaez A, McGrath MS. MCP-1 Chemokine Receptor CCR2 Is Absent on Circulating Monocytes in Sporadic ALS. Poster presentation at the 16th International Symposium on ALS/MND in Dublin, Ireland, Dec 8-10, 2005.
  51. Do H, Hadlock KG, Miller RG, Yu S, Mass J, Zhang RZ, Gascon R, Narvaez A, Katz J, McGrath, MS. Transcriptional Program of Peripheral Blood Cells in ALS: Evidence for Systemic Immune Activation. Poster presentation at the 16th International Symposium on ALS/MND in Dublin, Ireland, Dec 8-10, 2006.
  52. Jin X, Hadlock KG, Yu S, Do H, Miller R, Mass J, Katz J, Zhang RZ, Gascon R, McGrath MS. Mutational Recovery of Viral Open Reading Frames in Selected HERV-K-Related Endogenous Retro Viruses in ALS Patients. Poster presentation at the 16th International Symposium on ALS/MND in Dublin, Ireland, Dec 8-10, 2005.
  53. Yu S, Hadlock KG, Miller RG, Do H, Mass J, Zhang RZ, Gascon R, Lancero M, Narvaez A, Katz J, McGrath MS. Detection of ALS by Quantitative Real Time RT-PCR of Peripheral Blood Cells. Poster presentation at the 16th International Symposium on ALS/MND in Dublin, Ireland, Dec 8-10, 2005.
  54. McGrath MS, Galligan D, Lamers S, Salemi M. HIV Infected Macrophages Associated with Lymphoma (ARL) Show Distinct Patterns of Evolution in Vivo. Accepted for poster presentation at 13th Conference on Retroviruses and Opportunistic Infections, Denver CO, Feb 5-9, 2006.
  55. Galligan D, Lamers SL, de Oliveira T, Salemi, M, McGrath MS. HIV-1 Molecular Dynamics in Multisite Lymphoma Biopsies. Accepted for poster presentation at HIV Pathogenesis Symposium, Keystone CO, Mar 27-Apr 2, 2006.
  56. Lamers SL, Salemi T, de Oliveria T, Beason S, Compton R, Goodenow M, McGrath MS. A Protocol for HIV-1 env Alignments Assists in Determining the Evolutionary Dynamics of the V1, V2 and V4 Hypervariable Domains. Submitted to HIV Pathogenesis Symposium, Keystone CO, Mar 27-Apr 2, 2006