Resveratrol is a bioflavonoid which is known to inhibit cell proliferation and induce apoptosis in cancer cell lines at concentrations above 50uM. It also has colon cancer prevention activity in mouse models and possibly in humans. We have examined the effects of low concentrations of resveratrol on a specific signaling pathway, the Wnt pathway, which is activated in over 85% of sporadic colon cancers. Two colon cancer (HT29 and RKO) and one normal mucosa-derived (NCM460) cell lines were utilized. Cell proliferation was not affected by resveratrol at ≤40uM for HT29 and NCM460 and <20uM for RKO though Wnt signal throughput, as measured by a reporter construct, was reduced in RKO and NCM460 at concentrations as low as 10uM (p<0.001). This effect was most easily appreciated following Wnt pathway stimulation with Wnt3a conditioned medium and LEF1 or LEF1/ β-catenin transfection. Resveratrol did not inhibit Wnt throughput in mutationally activated HT29. Low concentrations of resveratrol significantly decreased the amount and proportion of β-catenin in the nucleus in RKO (p=0.002) and reduced the expression of lgs and pygoI, regulators of β-catenin localization in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular β-catenin localization.

Malignant gliomas continue to have a dismal prognosis despite all available treatments and advances made in understanding molecular mechanisms and signaling pathways. Conventional treatments, such as surgery, chemotherapy and radiation, have been used with limited success. Bevacizumab is a recently described molecule, which inhibits endothelial proliferation and prevents formation of new blood vessels in tumor. However, this treatment confers increased hemorrhage risk and impairs wound healing. Therefore, the timing of surgery for patients receiving bevacizumab, who are in need of surgery, is critical. We performed a literature review to establish the appropriate timing between the cessation of bevacizumab therapy and surgical intervention. Our literature review indicated that the optimum time between cessation of bevacizumab therapy and surgery was 4 weeks. The timing for re-initiation of bevacizumab post-surgery was at least 2 weeks. The duration of preoperative cessation of bevacizumab treatment is critical in preventing life threatening surgical complications. The interval between the surgery and re-initiation of bevacizumab can be shortened. However, more studies are needed to ascertain the exact timing of preoperative and postoperative therapy.

When healthy subjects undergo brain imaging, incidental findings are not rare. The optimal response to such findings has been the focus of considerable discussion. The current report describes the operations and results of a system that provides review of incidental findings by an appropriate medical professional. A web-based system was created whereby investigators performing brain MRI scans on healthy subjects could refer images with suspected concerns to a board certified radiologist who had a Certificate of Added Qualification in Neuroradiology. The specific details of this system are described. Among 27 scans suspected by an investigator of having a significant finding, all but one were referred by a researcher with a PhD. The most common concerns described by these investigators were for the possible presence of a cyst or of enlarged ventricles. The most common findings reported by the radiologist were Virchow-Robin spaces and cysts. Findings were generally of low clinical significance, with 1 major exception. Identifying the optimal response to incidental findings in neuroimaging research remains a challenge. The current report describes a system for providing expert assistance and so addresses these issues in the setting of suspected incidental findings. To our knowledge the current system is the first to provide a specific means for evaluation of incidental findings in neuroimaging research.

Primary intraocular lymphoma (PIOL) is a relatively rare form of Non-Hodgkin's Lymphoma arising in the lymphoid tissues of the eye. It is highly correlated with primary CNS lymphoma (PCNSL) and it is estimated that up to 80% of patients presenting with PIOL will eventually manifest intracranial malignancy, which is the largest contributor to mortality. Most patients present with nonspecific visual symptoms, including floaters and blurry vision, and are often initially diagnosed with uveitis or retinitis. Definitive diagnosis requires biopsy of malignant tissues with demonstration of malignant lymphoid cells. Optimal therapy is to this point undefined, and the available literature is limited to case reports and retrospective series. Currently employed therapies include the use of localized external beam radiation therapy (EBRT), whole brain radiation therapy (WBRT), systemic chemotherapy, intrathecal chemotherapy, and, most recently, direct intravitreal (IVT) chemotherapy. While radiation therapy and chemotherapy can produce a high response rate, they have not been shown to effectively prevent relapse or the incidence of CNS spread. Methotrexate has been the most popular therapy used for the treatment of intraocular lymphoma. It has been administered systemically, intrathecally or intravitreally. However due to multiple mechanisms of resistance developed by lymphoma cells against methotrexate, this drug has been unable to prevent disease recurrence. The newest, and perhaps most promising, reported therapy includes the use of rituximab anti-CD20 monoclonal antibody either alone or in combination chemotherapy via intrathecal or IVT administration. Most cases in the literature employ combinations of available therapies, and there are no comparative studies of significant power to date. Multicenter collaboration will be required to determine the true relative efficacy and adversity of the therapeutic options available.