DF/HCC Program Affiliation

Breast Cancer
Cancer Cell Biology

Research Abstract

Our research covers two related areas: cellular responses to localized oxidative stress and mechanisms for stress-induced bystander effects. The studies on localized oxidative stress involve a team approach for use of state-of-the-art methods such as ionizing radiation microbeams, in collaboration with a group in the UK, and subcellularly localized photosensitizers to study biochemical pathways involved in triggering of apoptosis, mutagenesis, and DNA damage and repair after subcellularly localized stress induction, e.g., in nuclear versus non-nuclear regions including plasma membranes and mitochondria. Cells containing genetic mutations or knock-downs in apoptosis and DNA repair pathways are used, and cellular responses are followed, among other approaches, by use of sophisticated time-lapse microscopy. The studies on stress-induced bystander effects involve investigation of the signaling pathways whereby a cell that is damaged by ionizing radiation, photosensitizers or other oxidative stresses sends a signal to neighboring undamaged cells which then show a biological response. These studies include use of a unique heavy ion irradiation facility at Brookhaven National Laboratory.

Publications

• Lawenda BD, Smith DE, Xu L, Niemierko A, Silverstein JR, Boucher Y, Kashiwagi S, Held KD, Jain RK, Loeffler JS, Eisenberg DM, Blumberg JB.Do the dietary supplements epigallocatechin gallate or vitamin e cause a radiomodifying response on tumors in vivo? A
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• Prise KM, Schettino G, Folkard M, Held KD.New insights on cell death from radiation exposure.Lancet Oncol 2005 Jul;6(7):520-8.
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• Yang H, Asaad N, Held KD.Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts.Oncogene 2005 Mar 17;24(12):2096-103.
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• Held KD.Radiation-induced apoptosis and its relationship to loss of clonogenic survival.Apoptosis 1997;2(3):265-82.
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• Schettino G, Folkard M, Prise KM, Vojnovic B, Held KD, Michael BD.Low-dose studies of bystander cell killing with targeted soft X rays.Radiat Res 2003 Nov;160(5):505-11.
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• Tartier L, McCarey YL, Biaglow JE, Kochevar IE, Held KD.Apoptosis induced by dithiothreitol in HL-60 cells shows early activation of caspase 3 and is independent of mitochondria.Cell Death Differ 2000 Oct;7(10):1002-10.
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