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Metastatic cancer is associated with a hypercoagulable state; tumor cells can generate thrombin on their surface. We study the biomolecular significance of thrombin receptors on tumor cells. Platelets are required for metastasis in vivo. We showed that treating platelets with thrombin enhanced the adhesion of naive tumor cells to platelets. Active thrombin was necessary on the platelet surface. Thrombin administration with murine tumor cells enhanced pulmonary metastasis via a tail-vein injection in syngeneic mice. The platelet GPIIb-lIla adhesive ligand receptor was important for platelet-tumor cell interaction in vitro and metastasis in vivo.
A unique seven-membrane spanning thrombin receptor was cloned by Vu and colleagues in 1991 which requires proteolysis to produce a tethered ligand capable of activating the thrombin receptor. The thrombin receptor activation peptide (TRAP) from the tethered end recapitulated the thrombin effect on transfected xenopus oocytes and human platelets. We demonstrated the presence of the cloned receptor by RT-PCR in human and murine tumor cells lines and human tumor samples. Thrombin or TRAP treatment of tumor cells supported enhanced adhesion to platelets and increased murine metastasis in syngeneic mice
Currrently were are developing clinical trials to assess the use of antithrombin agents as adjuvants to chemotherapy.
Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ hybridization analysis
Shvartsbeyn, Marianna; Meehan, Shane M; Gu, Ping; Nierodzik, Mary Lynn; Perle, Mary Ann. Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ hybridization analysis. Journal of cutaneous pathology. 2012 Nov;39(11):1026-1029 (180076)
The impact of interventions on provider and treatment delays in head and neck cancer patients
Lai, D W; Kim, J; Marciscano, A; Buckley, S A; Schmidt, B L; Cohen, R F; Nierodzik, M L R; Myssiorek, D; DeLacure, M D; Sanfilippo, N; Seetharamu, N. The impact of interventions on provider and treatment delays in head and neck cancer patients [Meeting Abstract]. Journal of clinical oncology. 2012 May 20;30(15):?-? (249342)
Cancer portal project: a multidisciplinary approach to cancer care among Hispanic patients
Gany, Francesca; Ramirez, Julia; Nierodzick, Mary Lynn; McNish, Thelma; Lobach, Iryna; Leng, Jennifer. Cancer portal project: a multidisciplinary approach to cancer care among Hispanic patients. Journal of oncology practice. 2011 Jan;7(1):31-38 (131970)
Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma
Wu, Jennifer; Henderson, Charles; Feun, Lynn; Van Veldhuizen, Peter; Gold, Philip; Zheng, Hui; Ryan, Theresa; Blaszkowsky, Lawrence S; Chen, Haobin; Costa, Max; Rosenzweig, Barry; Nierodzik, MaryLynn; Hochster, Howard; Muggia, Franco; Abbadessa, Giovanni; Lewis, Jonathan; Zhu, Andrew X. Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. Investigational new drugs. 2010 Oct;28(5):670-676 (138148)
Tumor growth and metastasis
Nierodzik, ML; Karpatkin, S. Tumor growth and metastasis IN: Platelets. Amsterdam ; Boston : Academic Press/Elsevier, 2007 2nd ed. p.769-778 (644422)