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Barth B.M.,Pennsylvania State University | Cabot M.C.,John Wayne Cancer Institute at Saint Johns Health Center | Kester M.,Pennsylvania State University
Anti-Cancer Agents in Medicinal Chemistry

The bioactive sphingolipid, ceramide, has garnered major interest as a principle regulator of cellular stress, proliferation, senescence, and death. Of particular interest to cancer biologists and clinical oncologist, dysregulated ceramide metabolism has been documented in both solid and non-solid malignancies. Moreover, most anticancer chemotherapeutics stimulate ceramide accumulation through increased ceramide synthesis or through the inhibition of ceramide catabolism. In fact, neutralization of ceramide via glycosylation or phosphorylation in malignant cells has been linked to multidrug chemoresistance. New therapeutic strategies to overcome chemoresistance focus on increasing endogenous ceramide levels by stimulating ceramide synthesis, by inhibiting ceramide neutralization, or by the direct delivery of exogenous ceramide. This review will discuss new therapeutic strategies designed specifically to modulate ceramide metabolism, as well as nanoscale delivery systems engineered to selectively deliver ceramide to cancerous cells and tissues. © 2011 Bentham Science Publishers. Source

Barkhoudarian G.,John Wayne Cancer Institute at Saint Johns Health Center

Three-dimensional (3-D) endoscopy is a recent addition to augment the transsphenoidal surgical approach for anterior skull-base and parasellar lesions. We describe our experience implementing this technology into regular surgical practice. Retrospective review of clinical factors and outcomes. All patients were analyzed who had endoscopic endonasal parasellar operations since the introduction of the 3-D endoscope to our practice. Over an 18-month period, 160 operations were performed using solely endoscopic techniques. Sixty-five of these were with the Visionsense VSII 3-D endoscope and 95 utilized 2-dimensional (2-D) high-definition (HD) Storz endoscopes. Intraoperative and postoperative findings were analyzed in a retrospective fashion. Comparing both groups, there was no significant difference in total or surgical operating room times comparing the 2-D HD and 3-D endoscopes (239 minutes vs 229 minutes, P = .47). Within disease-specific comparison, pituitary adenoma resection was significantly shorter utilizing the 3-D endoscope (surgical time 174 minutes vs 147 minutes, P = .03). These findings were independent of resident or fellow experience. There was no significant difference in the rate of complication, reoperation, tumor resection, or intraoperative cerebrospinal fluid leaks. Subjectively, the 3-D endoscope offered increased agility with 3-D techniques such as exposing the sphenoid rostrum, drilling sphenoidal septations, and identifying bony landmarks and suprasellar structures. The 3-D endoscope is a useful alternative to the 2-D HD endoscope for transnasal anterior skull-base surgery. Preliminary results suggest it is more efficient surgically and has a shorter learning curve. As 3-D technology and resolution improve, it should serve to be an invaluable tool for neuroendoscopy. Source

Parker W.H.,John Wayne Cancer Institute at Saint Johns Health Center | Einarsson J.,Harvard University | Istre O.,Harvard University | Dubuisson J.-B.,Hopitaux Universitaires Of Geneva
Journal of Minimally Invasive Gynecology

Case reports for uterine rupture subsequent to laparoscopic myomectomy were reviewed to determine whether common causal factors could be identified. Published cases were identified via electronic searches of PubMed, Google Scholar, and hand searches of references, and unpublished cases were obtained via E-mail queries to the AAGL membership and AAGL Listserve participants. Nineteen cases of uterine rupture after laparoscopic myomectomy were identified. The removed myomas ranged in size from 1 through 11 cm (mean, 4.5 cm). Only 3 cases involved multilayered closure of uterine defects. Electrosurgery was used for hemostasis in all but 2 cases. No plausible contributing factor could be found. It seems reasonable for surgeons to adhere to techniques developed for abdominal myomectomy including limited use of electrosurgery and multilayered closure of the myometrium. Nevertheless, individual wound healing characteristics may predispose to uterine rupture. © 2010 AAGL. Source

Steen S.,John Wayne Cancer Institute at Saint Johns Health Center
ILAR journal / National Research Council, Institute of Laboratory Animal Resources

We postulated that a surgical shunt between the portal and hepatic veins (portohepatic shunt) could improve the function and regeneration of the liver remnant after extensive hepatic resection. Using a canine model, we designed a survival study to test the feasibility of 90% hepatectomy with a portohepatic shunt. Of eight mixed-hound canines, it was necessary to sacrifice two animals for postmortem study of hepatic anatomy; we used the results to design a procedure for removing all of the liver except portions of two lobes. We tested this 90% hepatectomy procedure under general anesthesia in the remaining animals, with (N=3) or without (N=3) a portohepatic shunt. We monitored animals postoperatively with serial liver biochemical testing, and sacrificed on postoperative day 48. Assessment of liver regeneration was by weight after complete postmortem hepatectomy. Extended hepatectomy removed four complete lobes and portions of the right lateral and caudate lobes. For the portohepatic shunt, we anastomosed the left portal vein branch to the left hepatic vein branch. All procedures were performed successfully. One no-shunt animal expired on the second postoperative day. We thus confirmed the feasibility of 90% hepatectomy with portohepatic shunt in the canine model. If the efficacy of shunting is validated in a larger study population, it may increase the indications for extensive resection in patients with advanced hepatic malignancy. Source

Asaga S.,John Wayne Cancer Institute at Saint Johns Health Center | Kuo C.,John Wayne Cancer Institute at Saint Johns Health Center | Nguyen T.,John Wayne Cancer Institute at Saint Johns Health Center | Terpenning M.,Santa Monica Hematology Oncology Consultant | And 2 more authors.
Clinical Chemistry

BACKGROUND: MicroRNAs (miRs) are a class of small noncoding RNAs whose expression changes have been associated with cancer development and progression. Current techniques to isolate miRs for expression analysis from blood are inefficient.Wedeveloped a reversetranscription quantitative real-time PCR (RT-qPCR) assay for direct detection of circulating miRs in serum. We hypothesized that serum concentrations of miR- 21, a biomarker increased in breast tumors, would correlate with the presence and extent of breast cancer. METHODS: The RT-qPCR applied directly in serum (RT-qPCR-DS) assay for circulating miR-21 was tested in sera from 102 patients with different stages of breast cancer and 20 healthy female donors. RESULTS: The assay was sensitive for detection of miR-21 in 0.625 7mu;L of serum from breast cancer patients. For differentiation of samples from patients with locoregional breast cancer from those from healthy donors, the odds ratio was 1.796 and the area under the curve was 0.721. In a multivariate analysis that included standard clinicopathologic prognostic factors, high circulating miR-21 concentrations correlated significantly (P<0.001) with visceral metastasis. CONCLUSIONS: A novel RT-qPCR-DS can improve the efficiency of miR assessment. Use of this assay to detect circulating miR-21 has diagnostic and prognostic potential in breast cancer. © 2010 American Association for Clinical Chemistry. Source

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