Person: Gerbaudo, Victor
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Gerbaudo
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Victor
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Gerbaudo, Victor
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Publication Systemic chemotherapy decreases brain glucose metabolism(BlackWell Publishing Ltd, 2014) Horky, Laura L; Gerbaudo, Victor; Zaitsev, Alexander; Plesniak, Wen; Hainer, Jon; Govindarajulu, Usha; Kikinis, Ron; Dietrich, JorgObjective: Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients. Methods: Using sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer. Results: Significant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts. Interpretation Our data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients.Publication Autophagy Correlates with the Therapeutic Responsiveness of Malignant Pleural Mesothelioma in 3D Models(Public Library of Science, 2015) Barbone, Dario; Follo, Carlo; Echeverry, Nohemy; Gerbaudo, Victor; Klabatsa, Astero; Bueno, Raphael; Felley-Bosco, Emanuela; Broaddus, V. CourtneyMalignant pleural mesothelioma is a highly chemoresistant solid tumor. We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/mTOR inhibitors. Here, we investigate the activity of GDC-0980, a novel dual PI3K/mTOR inhibitor, which has been proposed to be effective in mesothelioma. In this work, we aimed to identify mechanisms and markers of efficacy for GDC-0980 by utilizing 3D models of mesothelioma, both in vitro multicellular spheroids and ex vivo tumor fragment spheroids grown from patient tumor samples. We found that a subset of mesothelioma spheroids is sensitive to GDC-0980 alone and to its combination with chemotherapy. Unexpectedly, this sensitivity did not correlate with the activation of the Akt/mTOR pathway. Instead, sensitivity to GDC-0980 correlated with the presence of constitutive ATG13 puncta, a feature of autophagy, a cellular program that supports cells under stress. In tumor fragment spheroids grown from 21 tumors, we also found a subset (n = 11) that was sensitive to GDC-0980, a sensitivity that also correlated with the presence of ATG13 puncta. Interference with autophagy by siRNA of ATG7, an essential autophagic protein, increased the response to chemotherapy, but only in the sensitive multicellular spheroids. In the spheroids resistant to GDC-0980, autophagy appeared to play no role. In summary, we show that GDC-0980 is effective in mesothelioma 3D models that display ATG13 puncta, and that blockade of autophagy increases their response to chemotherapy. For the first time, we show a role for autophagy in the response to chemotherapy of 3D models of mesothelioma and propose ATG13 as a potential biomarker of the therapeutic responsiveness of mesothelioma.Publication Intrathymic cyst: Clinical and radiological features in surgically resected cases(Elsevier BV, 2014) Araki, Tetsuro; Sholl, Lynette; Gerbaudo, Victor; Hatabu, Hiroto; Nishino, MichiyaAIM To investigate radiological and clinical characteristics of pathologically proven cases of intrathymic cysts. MATERIALS AND METHODS The study population consisted of 18 patients (five males, 13 females; median age 56 years) with pathologically confirmed intrathymic cysts who underwent thymectomy and had preoperative chest computed tomography (CT) available for review. The patient demographics, clinical presentation, and preoperative radiological diagnoses were reviewed. CT images were evaluated for shape, contour, location of the cysts and the presence of adjacent thymic tissue, mass effect, calcifications, and septa. The size and CT attenuations of the cysts were measured. RESULTS The most common CT features of intrathymic cysts included oval shape (9/18; 50%), smooth contour (12/18; 67%), midline location (11/18; 61%), the absence of visible adjacent thymic tissue (12/18; 67%), and the absence of calcification (16/18; 89%). The mean longest diameter and the longest perpendicular diameter were 25 mm (range 17–49 mm) and 19 mm (range 10–44 mm), respectively. The mean CT attenuation was 38 HU (range 6–62 HU) on contrast-enhanced CT, and was 45 HU (range 26–64 HU) on unenhanced CT (p=0.41). The CT attenuation was >20 HU in 15 of 18 patients (83%). Preoperative radiological diagnosis included thymoma in 11 patients. CONCLUSION In surgically removed, pathologically proven cases of intrathymic cyst, the CT attenuation was >20 HU in most cases, leading to the preoperative diagnosis of thymoma. Awareness of the spectrum of imaging findings of the entity is essential to improve the diagnostic accuracy and patient management.Publication Motion artifacts occurring at the lung/diaphragm interface using 4D CT attenuation correction of 4D PET scans(John Wiley and Sons Inc., 2011) Killoran, Joseph H.; Gerbaudo, Victor; Mamede, Marcelo; Ionascu, Dan; Park, Sang‐June; Berbeco, RossFor PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F‐FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT‐PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity “fixed activity volume” (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC‐ and CINE CTAC–corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios. PACS numbers: 87.57.qp, 87.57.cp