This project is focused on the clinical study of patients with AIDS-related malignancies. Much of the work is focused on tumors associated with Kaposis sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8). This virus is the cause of Kaposis sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castlemans disease (MCD). We are also studying antibody to VEGF (bevacizumab) as a therapeutic agent in KS as well as BAY 43-9007 (sorafineb). This latter agent is of interest because it can downregulate several receptors for VEGF. We have also initiated a trial of bevacizumab in combination with liposomal doxorubicin in patients with severe KS. We have initiated a clinical trial to study the natural history of MCD and to explore the treatment of MCD using a combination of AZT and valganciclovir, a pro-drug of ganciclovir as well as several other approaches (including liposomal doxorubicin and rituxuimab). In addition, we are studying other patients with KSHV infection to assess factors that may be linked to malignancy. We are exploring methotrexate-based therapy for primary central nervous system lymphoma (PCNSL). We are also studying infusional chemotherapy as therapy for AIDS-associated lymphoma in collaboration with the Metabolism Branch. We have identified a group of patients with a new KSHV-related syndrome, called KSHV inflammatory cytokine syndrome (KICS), and have just opened a protocol to study this new disease. Finally, as part of this effort, we are collaborating with a number of other investigators to conduct translational studies related to HIV, AIDS-malignancies, and also xenotropic murine leukemia-virus related virus (XMRV).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Cancer Institute Division of Basic Sciences
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Lurain, Kathryn; Yarchoan, Robert; Uldrick, Thomas S (2018) Treatment of Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease. Hematol Oncol Clin North Am 32:75-88
Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha et al. (2017) Corrigendum: Clinical manifestations of Kaposi sarcoma herpesvirus lytic activation: multicentric Castleman disease (KSHV-MCD) and the KSHV inflammatory cytokine syndrome. Front Microbiol 8:1572
Roshan, Romin; Labo, Nazzarena; Trivett, Matthew et al. (2017) T-cell responses to KSHV infection: a systematic approach. Oncotarget 8:109402-109416
Sanchez-Martin, David; Uldrick, Thomas S; Kwak, Hyeongil et al. (2017) Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas. J Natl Cancer Inst 109:
Yu, Li; Tu, Meifeng; Cortes, Jorge et al. (2017) Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood 129:1658-1668
Gonçalves, Priscila H; Uldrick, Thomas S; Yarchoan, Robert (2017) HIV-associated Kaposi sarcoma and related diseases. AIDS 31:1903-1916
Uldrick, Thomas S; Gonçalves, Priscila H; Wyvill, Kathleen M et al. (2017) A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma. Oncologist 22:505-e49
Polizzotto, Mark N; Uldrick, Thomas S; Wyvill, Kathleen M et al. (2016) Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS). Clin Infect Dis 62:730-738
Goncalves, Priscila H; Montezuma-Rusca, Jairo M; Yarchoan, Robert et al. (2016) Cancer prevention in HIV-infected populations. Semin Oncol 43:173-188
Bhutani, Manisha; Polizzotto, Mark N; Uldrick, Thomas S et al. (2015) Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. Semin Oncol 42:223-46

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