6 results on '"Sexton, Sandra"'
Search Results
2. PET imaging with FAPI-ligands for non-cirrhotic hepatocellular carcinoma.
- Author
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Lee, Zhenghong, Lu, Zheng-Rong, Sexton, Sandra, and Xin, Wei
- Subjects
POSITRON emission tomography ,HEPATOCELLULAR carcinoma ,CHRONIC active hepatitis - Published
- 2023
- Full Text
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3. [18F] Clofarabine for PET Imaging of Hepatocellular Carcinoma.
- Author
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Sergeeva, Olga, Kepe, Vladimir, Zhang, Yifan, Miller-Atkins, Galen A., Keynon, Jonathan D., Iyer, Renuka, Sexton, Sandra, Awadallah, Amad, Xin, Wei, Saunthararajah, Yogen, Chan, E. Ricky, and Lee, Zhenghong
- Subjects
CELL proliferation ,ANIMAL experimentation ,HEPATOCELLULAR carcinoma ,HETEROCYCLIC compounds ,LIVER tumors ,MOLECULAR structure ,NUCLEOTIDES ,PHOSPHOTRANSFERASES ,RODENTS ,POSITRON emission tomography ,PROBENECID (Drug) ,PHYSIOLOGICAL effects of radiation - Abstract
Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management. This study investigated
18 F-labeled clofarabine ([18 F]CFA) targeting deoxycytidine kinase (dCK) for PET imaging of dCK-dependent proliferation in HCC. Since clinical PET scans showed a high liver background uptake of [18 F]CFA, the aim of this study was to reduce this liver background uptake. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for imaging experiments. Several modifiers were tested and compared with the baseline PET scan: Forodesine, probenecid, and cold clofarabine, all applied before the hot [18 F]CFA injection to evaluate the reduction in liver background uptake. Application of forodesine before hot [18 F]CFA injection did not reduce the background uptake. Instead, it increased the background by 11.6–36.3%. Application of probenecid also increased the liver background uptake by 16.6–32.1%. Cold CFA application did reduce the liver background uptake of [18 F]CFA, comparing to the baseline scan. Combining cold CFA with [18 F]CFA for PET imaging of liver cancers is a promising strategy, worthy of further clinical evaluation. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
4. PET imaging of hepatocellular carcinoma with anti-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in comparison with l-[S-methyl-11C]methionine.
- Author
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Sergeeva, Olga, Zhang, Yifan, Kenyon, Jonathan D., Miller-Atkins, Galen A., Wu, Chunying, Iyer, Renuka, Sexton, Sandra, Wojtylak, Patrick, Awadallah, Amad, Xin, Wei, Chan, E. Ricky, O'Donnel, James K., and Lee, Zhenghong
- Subjects
POSITRON emission tomography ,METHIONINE ,HEPATOCELLULAR carcinoma ,AMINO acid transport ,LIVER cancer ,CARRIER proteins ,PROTEIN synthesis - Abstract
Purpose: [
11 C]methionine ([11 C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of11 C decay limited further clinical development of [11 C]Met. Synthetic amino acid analog anti-1-amino-3-[18 F]fluoro-cyclobutyl-1-carboxylic acid ([18 F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated "repurposed" [18 F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [11 C]Met. Methods: [11 C]Met was synthesized in the lab, and [18 F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [11 C]Met and [18 F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging. Results: Higher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [11 C]Met and [18 F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [18 F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative. Conclusion: Both [18 F]FACBC and [11 C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [18 F]FACBC and [11 C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters. [ABSTRACT FROM AUTHOR]- Published
- 2019
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- View/download PDF
5. Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells.
- Author
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Iyer, Renuka V., Maguire, Orla, Kim, Minhyung, Curtin, Leslie I., Sexton, Sandra, Fisher, Daniel T., Schihl, Sarah A., Fetterly, Gerald, Menne, Stephan, and Minderman, Hans
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CELL proliferation ,APOPTOSIS ,CELL lines ,GENE expression ,HEPATOCELLULAR carcinoma ,IMMUNOLOGICAL tolerance ,IMMUNOSUPPRESSION ,LIVER ,T cells ,TRANSCRIPTION factors ,IN vitro studies ,IN vivo studies ,SORAFENIB ,PHARMACODYNAMICS - Abstract
The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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6. A Translational Hepatic Artery Infusion (HAI) Model for Hepatocellular Carcinoma in Woodchucks.
- Author
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Kim, Minhyung, Powers, Colin A., Curtin, Leslie I., Fisher, Daniel T., Sexton, Sandra, Gurova, Katerina V., Skitzki, Joseph J., and Iyer, Renuka V.
- Subjects
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HEPATIC artery , *HEPATOCELLULAR carcinoma , *LIVER enzymes , *ANATOMICAL variation , *TUMOR growth - Abstract
Woodchucks (Marmota monax) are a well-accepted animal model for the investigation of spontaneous hepatocellular carcinoma (HCC). As HCC tumors obtain nutrient blood supply exclusively from the hepatic artery, hepatic artery infusion (HAI) has been applied to HCC. However, there is a scarcity of experimental animal models to standardize drug regimens and examine novel agents. The purpose of this study was to establish an HAI model in woodchucks. HAI ports were placed in the gastroduodenal artery (GDA) of 11 woodchucks. The ports were infused with either a vehicle (dextrose 5% in water) or an experimental drug, CBL0137, once a week for 3 wk. Technical success rates, anatomical variation, morbidity and mortality, and tumor responses between groups were analyzed. The GDA access was feasible and reproducible in all woodchucks (11/11). The average operation time was 95 ± 20 min with no increase in the levels of liver enzymes detected from either infusate. The most common morbidity of CBL0137 therapy was anorexia after surgery. One woodchuck died due to hemorrhage at the gallbladder removal site from hepatic coagulopathy. Significantly higher CBL0137 concentrations were measured in the liver compared with blood after each HAI. Tumor growth was suppressed after multiple CBL0137 HAI treatments which corresponded to greater T cell infiltration and increased tumor cell apoptosis. HAI via GDA was a feasible and reproducible approach with low morbidity and mortality in woodchucks. The described techniques serve as a reliable platform for the identification and characterization of therapeutics for HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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