Browsing by Author "Cardona, Diana M"
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Item Open Access A Fluorescence-Guided Laser Ablation System for Removal of Residual Cancer in a Mouse Model of Soft Tissue Sarcoma.(Theranostics, 2016) Lazarides, Alexander L; Whitley, Melodi J; Strasfeld, David B; Cardona, Diana M; Ferrer, Jorge M; Mueller, Jenna L; Fu, Henry L; Bartholf DeWitt, Suzanne; Brigman, Brian E; Ramanujam, Nimmi; Kirsch, David G; Eward, William CThe treatment of soft tissue sarcoma (STS) generally involves tumor excision with a wide margin. Although advances in fluorescence imaging make real-time detection of cancer possible, removal is limited by the precision of the human eye and hand. Here, we describe a novel pulsed Nd:YAG laser ablation system that, when used in conjunction with a previously described molecular imaging system, can identify and ablate cancer in vivo. Mice with primary STS were injected with the protease-activatable probe LUM015 to label tumors. Resected tissues from the mice were then imaged and treated with the laser using the paired fluorescence-imaging/ laser ablation device, generating ablation clefts with sub-millimeter precision and minimal underlying tissue damage. Laser ablation was guided by fluorescence to target tumor tissues, avoiding normal structures. The selective ablation of tumor implants in vivo improved recurrence-free survival after tumor resection in a cohort of 14 mice compared to 12 mice that received no ablative therapy. This prototype system has the potential to be modified so that it can be used during surgery to improve recurrence-free survival in patients with cancer.Item Open Access Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D.(Scientific reports, 2019-11-20) Huang, Jianguo; Chen, Mark; Xu, Eric S; Luo, Lixia; Ma, Yan; Huang, Wesley; Floyd, Warren; Klann, Tyler S; Kim, So Young; Gersbach, Charles A; Cardona, Diana M; Kirsch, David GCooperating gene mutations are typically required to transform normal cells enabling growth in soft agar or in immunodeficient mice. For example, mutations in Kras and transformation-related protein 53 (Trp53) are known to transform a variety of mesenchymal and epithelial cells in vitro and in vivo. Identifying other genes that can cooperate with oncogenic Kras and substitute for Trp53 mutation has the potential to lead to new insights into mechanisms of carcinogenesis. Here, we applied a genome-wide CRISPR/Cas9 knockout screen in KrasG12D immortalized mouse embryonic fibroblasts (MEFs) to search for genes that when mutated cooperate with oncogenic Kras to induce transformation. We also tested if mutation of the identified candidate genes could cooperate with KrasG12D to generate primary sarcomas in mice. In addition to identifying the well-known tumor suppressor cyclin dependent kinase inhibitor 2A (Cdkn2a), whose alternative reading frame product p19 activates Trp53, we also identified other putative tumor suppressors, such as F-box/WD repeat-containing protein 7 (Fbxw7) and solute carrier family 9 member 3 (Slc9a3). Remarkably, the TCGA database indicates that both FBXW7 and SLC9A3 are commonly co-mutated with KRAS in human cancers. However, we found that only mutation of Trp53 or Cdkn2a, but not Fbxw7 or Slc9a3 can cooperate with KrasG12D to generate primary sarcomas in mice. These results show that mutations in oncogenic Kras and either Fbxw7 or Slc9a3 are sufficient for transformation in vitro, but not for in vivo sarcomagenesis.Item Open Access Metastatic Renal Cell Carcinoma as Solitary Subcentimeter Polypoid Gastric Mucosal Lesions: Clinicopathologic Analysis of Five Cases.(Gastroenterology research, 2018-02-23) Hemmerich, Amanda; Shaar, Mohanad; Burbridge, Rebecca; Guy, Cynthia D; McCall, Shannon J; Cardona, Diana M; Zhang, Xuchen; Lai, Jinping; Zhang, XuefengThe stomach is an uncommon site for metastatic carcinoma. Approximately 6% of renal cell carcinomas (RCCs) may metastasize to the stomach. The majority of the reported metastatic RCCs in the stomach presented as large masses or ulcers greater than a centimeter in size. It is very rare to encounter metastatic RCC as a solitary small polypoid gastric mucosal lesion.In this study, we collected surgical pathology cases of gastric metastasis from RCC that measured 1.0 cm or less at the time of endoscopy. The clinicopathological characteristics were analyzed.Five patients with subcentimeter metastatic RCC involving the gastric mucosa were identified. The clinical presentation for upper endoscopic examination was non-specific. Two of the five patients did not have a known history of RCC. In the three patients with a previous history of RCC, the interval from primary RCC diagnosis to the detection of gastric mucosal metastasis was 5, 6, and 10 years, respectively. Endoscopically, all the lesions were solitary, ranging in size from 0.4 to 1 cm. Histologically, all five cases were of the clear cell type consisting of a bland clear cell proliferation within the lamina propria. Although the tumor cells were relatively bland, the presence of clear cytoplasm, nuclear membrane irregularity, occasional enlarged hyperchromatic atypical nuclei, and destructive growth in the center of the lesion should promote immunohistochemical workup. Immunohistochemically, the RCC cells exhibited at least patchy immunoreactivity for cytokeratin and RCC markers. In two cases, there were many CD68 positive foamy histiocytes intermingled with the tumor cells.Metastatic RCC can rarely present as subcentimeter polypoid gastric mucosal lesions. The remote or unknown history of RCC, the non-specific endoscopic appearance, and the bland histological features may lead to a potential diagnostic pitfall. It is of importance to raise the awareness of such an unusual presentation of metastatic RCC in the stomach and to include metastatic RCC in the differential diagnosis for gastric mucosal polyps with clear cell morphology.Item Open Access Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.(Transplantation direct, 2022-11) Abraham, Nader; Ludwig, Elsa K; Schaaf, Cecilia R; Veerasammy, Brittany; Stewart, Amy S; McKinney, Caroline; Freund, John; Brassil, John; Samy, Kannan P; Gao, Qimeng; Kahan, Riley; Niedzwiecki, Donna; Cardona, Diana M; Garman, Katherine S; Barbas, Andrew S; Sudan, Debra L; Gonzalez, Liara MSuccessful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model.Methods
Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice.Results
In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function.Conclusions
This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.Item Open Access Retroperitoneal dermoid cyst presenting with radiculopathy symptoms: a case report.(Journal of surgical case reports, 2022-12) Kelly-Hedrick, Margot; Frerich, Jason M; Peairs, Emily M; Cardona, Diana M; Arcot, Rohith; Smith, Brandon; Abern, Michael; Miller, Chad; Abd-El-Barr, Muhammad MDermoid cysts rarely present in the retroperitoneal space or during adulthood. In this case report, we describe the clinical presentation, operative and post-operative course of a 31-year old with a retroperitoneal dermoid cyst. The patient presented with buttock and leg pain/paresthesia found to have a retroperitoneal mass between the psoas muscle and L5/S1 disk space. We describe the operative approach, including intra-operative images, of the resection by a team of urologists and neurosurgeons. The histology is also presented. Finally, we discuss the benefits of use of intra-operative ultrasound and neuromonitoring.