Harrison Kim1,2,3,4, Donald J Buchsbaum5, Kurt R Zinn6,7. 1. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. hyunkikim@uabmc.edu. 2. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. hyunkikim@uabmc.edu. 3. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. hyunkikim@uabmc.edu. 4. , G082C5 Volker Hall, 1670 University Blvd., Birmingham, AL, 35294-0019, USA. hyunkikim@uabmc.edu. 5. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. 6. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. 7. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Abstract
PURPOSE: The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in human breast and pancreatic cancer mouse models. PROCEDURES: Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10(5) cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (×20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R (2)) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R (2) value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC50) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models. RESULTS: Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R (2) value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p < 0.05). The novel imaging biomarker was significantly correlated with either log10(IC50) or %TGI (p < 0.001). CONCLUSION: The imaging biomarker extracted from the cellular distribution pattern of Cy5.5-TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancer patients.
PURPOSE: The aim of the study was to develop a reliable quantitative imaging biomarker from fluorescence microscopic imaging of TRA-8/death receptor 5 (DR5) oligomer to predict TRA-8 therapeutic efficacy in humanbreast and pancreatic cancermouse models. PROCEDURES: Two breast (2LMP, SUM159) and two pancreatic (MIA PaCa-2, PANC1) cancer cell lines were used. 10(5) cells per cell line were placed in a culture dish and treated with Cy5.5-labeled TRA-8 overnight in vitro. Three fluorescence microphotographs (×20) were acquired from randomly selected areas, and about 300 cells were analyzed per cell line. Two-dimensional (2D) fluorescence signal distribution of Cy5.5-TRA-8 on each cell was measured. Gaussian curve fitting to the distribution was determined by the least square regression method, and the coefficient of determination (R (2)) of the fitting was found. In addition, two features of the best fitting Gaussian curve such as peak amplitude and the volume under the curve (VUC) were retrieved. A novel image biomarker was extracted by correlating the combination of R (2) value, peak amplitude, and the VUC with the logarithmic values of the half maximal inhibitory concentrations (IC50) of TRA-8 for the four cell lines or the percentage of tumor growth inhibition (%TGI) at a week of TRA-8 treatment in animal models. RESULTS:Cy5.5-TRA-8 binding to DR5 receptors resulted in an oligomer on each cell membrane, and its fluorescence signal distribution followed Gaussian curve. Peak amplitude of fluorescence signal in the oligomeric region, R (2) value of the Gaussian fitting, and the VUC in TRA-8-sensitive cells were significantly higher than those in resistant cells (p < 0.05). The novel imaging biomarker was significantly correlated with either log10(IC50) or %TGI (p < 0.001). CONCLUSION: The imaging biomarker extracted from the cellular distribution pattern of Cy5.5-TRA-8 may serve as a predictive biomarker of TRA-8 therapy for cancerpatients.
Authors: Patsy G Oliver; Albert F LoBuglio; Tong Zhou; Andres Forero; Hyunki Kim; Kurt R Zinn; Guihua Zhai; Yufeng Li; Choo H Lee; Donald J Buchsbaum Journal: Breast Cancer Res Treat Date: 2011-09-07 Impact factor: 4.872
Authors: Hyunki Kim; Sharon L Samuel; Guihua Zhai; Samir Rana; Marie Taylor; Heidi R Umphrey; Denise K Oelschlager; Donald J Buchsbaum; Kurt R Zinn Journal: Cancer Biol Ther Date: 2014-08 Impact factor: 4.742
Authors: Andres Forero-Torres; Jeffrey R Infante; David Waterhouse; Lucas Wong; Selwyn Vickers; Edward Arrowsmith; Aiwu Ruth He; Lowell Hart; David Trent; James Wade; Xiaoping Jin; Qiang Wang; Tashara Austin; Michael Rosen; Robert Beckman; Reinhard von Roemeling; Jonathan Greenberg; Mansoor Saleh Journal: Cancer Med Date: 2013-10-25 Impact factor: 4.452
Authors: Fiona L Scott; Boguslaw Stec; Cristina Pop; Małgorzata K Dobaczewska; JeongEun J Lee; Edward Monosov; Howard Robinson; Guy S Salvesen; Robert Schwarzenbacher; Stefan J Riedl Journal: Nature Date: 2008-12-31 Impact factor: 49.962
Authors: Romone M Fancy; Harrison Kim; Tong Zhou; Kurt R Zinn; Donald J Buchsbaum; Yuhua Song Journal: J Cell Biochem Date: 2017-04-12 Impact factor: 4.429
Authors: Romone M Fancy; Harrison Kim; Tiara Napier; Donald J Buchsbaum; Kurt R Zinn; Yuhua Song Journal: J Cell Biochem Date: 2018-04-16 Impact factor: 4.429