Browsing by Author "Stantz, Keith"

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    Development of Follicle-Stimulating Hormone Receptor Binding Probes to Image Ovarian Xenografts
    (2015-09) Lee, Chung-Wein; Guo, Lili; Matei, Daniela; Stantz, Keith; Department of Medicine, IU School of Medicine
    The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells in vitro and tumors xenograft model in vivo. The in vitro binding curve and the average number of FSHR per cell are obtained for OVCAR-3 cells by a high resolution flow cytometer. For the decapeptide, the measured EC50 was 160 μM and the average number of receptors per cell was 1.7 × 10(7). The decapeptide molecular imaging probe reached a maximum tumor to muscle ratio five hours after intravenous injection and a dose-dependent plateau after 24-48 hours. These results indicate the potential application of a small molecular weight imaging probe specific to ovarian cancer through binding to FSHR. Based on these results, multimeric constructs are being developed to optimize binding to ovarian cells and tumors.
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    Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer
    (Springer Nature, 2013-04-17) Yip-Schneider, Michele T.; Wu, Huangbing; Stantz, Keith; Agaram, Narasimhan; Crooks, Peter A.; Schmidt, C. Max; Surgery, School of Medicine
    Background: Pancreatic cancer remains one of the deadliest cancers due to lack of early detection and absence of effective treatments. Gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has limited clinical benefit. Treatment of pancreatic cancer cells with gemcitabine has been shown to induce the activity of the transcription factor nuclear factor-kappaB (NF-κB) which regulates the expression of genes involved in the inflammatory response and tumorigenesis. It has therefore been proposed that gemcitabine-induced NF-κB activation may result in chemoresistance. We hypothesize that NF-κB suppression by the novel inhibitor dimethylaminoparthenolide (DMAPT) may enhance the effect of gemcitabine in pancreatic cancer. Methods: The efficacy of DMAPT and gemcitabine was evaluated in a chemoprevention trial using the mutant Kras and p53-expressing LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mouse model of pancreatic cancer. Mice were randomized to treatment groups (placebo, DMAPT [40 mg/kg/day], gemcitabine [50 mg/kg twice weekly], and the combination DMAPT/gemcitabine). Treatment was continued until mice showed signs of ill health at which time they were sacrificed. Plasma cytokine levels were determined using a Bio-Plex immunoassay. Statistical tests used included log-rank test, ANOVA with Dunnett's post-test, Student's t-test, and Fisher exact test. Results: Gemcitabine or the combination DMAPT/gemcitabine significantly increased median survival and decreased the incidence and multiplicity of pancreatic adenocarcinomas. The DMAPT/gemcitabine combination also significantly decreased tumor size and the incidence of metastasis to the liver. No significant differences in the percentages of normal pancreatic ducts or premalignant pancreatic lesions were observed between the treatment groups. Pancreata in which no tumors formed were analyzed to determine the extent of pre-neoplasia; mostly normal ducts or low grade pancreatic lesions were observed, suggesting prevention of higher grade lesions in these animals. While gemcitabine treatment increased the levels of the inflammatory cytokines interleukin 1α (IL-1α), IL-1β, and IL-17 in mouse plasma, DMAPT and DMAPT/gemcitabine reduced the levels of the inflammatory cytokines IL-12p40, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 beta (MIP-1β), eotaxin, and tumor necrosis factor-alpha (TNF-α), all of which are NF-κB target genes. Conclusion: In summary, these findings provide preclinical evidence supporting further evaluation of agents such as DMAPT and gemcitabine for the prevention and treatment of pancreatic cancer.
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    Monte Carlo Simulation to Study Propagation of Light through Biological Tissues
    (2012-09-20) Prabhu Verleker, Akshay; Berbari, Edward J.; Stantz, Keith; Yoshida, Ken
    Photoacoustic Imaging is a non-invasive optical imaging modality used to image biological tissues. In this method, a pulsating laser illuminates a region of tissues to be imaged, which then generates an acoustic wave due to thermal volume expansion. This wave is then sensed using an acoustic sensor such as a piezoelectric transducer and the resultant signal is converted into an imaging using the back projection algorithm. Since different types of tissues have different photo-acoustic properties, this imaging modality can be used for imaging different types of tissues and bodily organ systems. This study aims at quantifying the process of light conversion into the acoustic signal. Light travels through tissues and gets attenuated (scattered or absorbed) or reflected depending on the optical properties of the tissues. The process of light propagation through tissues is studied using Monte Carlo simulation software which predicts the propagation of light through tissues of various shapes and with different optical properties. This simulation gives the resultant energy distribution due to light absorption and scattering on a voxel by voxel basis. The Monte Carlo code alone is not sufficient to validate the photon propagation. The success of the Monte Carlo code depends on accurate prediction of the optical properties of the tissues. It also depends on accurately depicting tissue boundaries and thus the resolution of the imaging space. Hence, a validation algorithm has been designed so as to recover the optical properties of the tissues which are imaged and to successfully validate the simulation results. The accuracy of the validation code is studied for various optical properties and boundary conditions. The results are then compared and validated with real time images obtained from the photoacoustic scanner. The various parameters for the successful validation of Monte Carlo method are studied and presented. This study is then validated using the algorithm to study the conversion of light to sound. Thus it is a significant step in the quantification of the photoacoustic effect so as to accurately predict tissue properties.