Current and future disease‐modifying therapies in multiple sclerosis

The development of disease‐modifying therapies (DMT) in multiple sclerosis (MS) has rapidly evolved over the last few years and continues to do so. Prior to the United States Food and Drug Administration approval of the immunomodulatory agent, interferon‐β1b in 1993, no other drug had been shown to alter the course of the disease in a controlled study of MS. At present, there are five licenced disease‐modifying agents in MS – interferon‐β1b, interferon‐β1a, glatiramer acetate, natalizumab and mitoxantrone. All have shown significant therapeutic efficacy in large controlled trials. However, current therapies are only partially effective and are not free from adverse effects. Moreover, available DMTs are overwhelmingly biased in favour of those with relapsing‐remitting disease. Effective treatment for progressive MS is severely limited, with only interferon‐β1b and mitoxantrone having licenced use in secondary progressive, but not primary progressive disease. Monoclonal antibodies, such as natalizumab selectively target immune pathways involved in the pathogenic process of MS. Alemtuzumab, daclizumab and rituximab are other notable monoclonal antibodies currently undergoing phase II and III trials in MS. Alemtuzumab has so far shown promising therapeutic benefit in relapsing disease, although immunological adverse effects have been a problem. Oral therapies have the benefit of improved tolerability and patient compliance compared with current parenteral treatments. Cladribine and fingolimod (FTY720) have shown encouraging results in their phase III clinical trials. It is also worth noting the evidence for starting DMT in patients with clinically isolated syndrome, whereby early treatment has shown to delay the onset of clinically definite MS in separate phase III studies.     

Giant Mesenteric Lipoma As an Unusual Cause of Abdominal Pain: A Case Report and a Review of the Literature

We report a rare case of giant mesenteric lipoma presenting with colicky abdominal pain. A 29-yr-old woman underwent laparoscopic resection for a giant mesenteric lipoma causing compression of the ileal loop. The resected ileal segment was encased by a giant fatty tissue, and normal mucosal fold patterns of the resected ileum were effaced by the mass. Microscopically, the mass was characterized by homogenous mature adipose tissue without cellular atypia, which was compatible with the diagnosis of a mesenteric lipoma. Despite the benign nature of this tumor, total excision with or without the affected intestinal loop should be considered if intestinal symptoms such as abdominal pain are present.     

hMSC-mediated Concurrent Delivery of Endostatin and Carboxylesterase to Mouse Xenografts Suppresses Glioma Initiation and Recurrence

Glioma stem cells (GSCs) are known to be maintained within a “vascular niche” thereby, disruption of this microenvironment using antiangiogenesis agents is a promising therapeutic modality. However, this regimen leads to treatment failure and tumor recurrence in patients with glioblastoma multiforme (GBM). Therefore, more effective therapeutic approaches that can eradicate GSCs and the bulk tumors are needed. Toward this goal, we examined the antitumor effects of an antiangiogenesis approach combined with conventional chemotherapy on suppressing glioma xenograft growth. We established three genetically engineered mesenchymal stem cell (MSC) lines (GE-AF-MSCs) by stably transducing the gene encoding endostatin (an antiangiogenesis factor), the gene encoding secretable form of carboxylesterase 2 (sCE2, a prodrug-activating enzyme), or a mixture of both genes. Among the three GE-AF-MSC cell lines, injection of amniotic fluid (AF)-MSCs-endostatin-sCE2 cells into U87MG-EGFRvIII-driven orthotopic brain tumor and postsurgery tumor recurrence models, and subsequent CPT11 treatment yielded the strongest antitumor responses, including diminished angiogenesis, increased cell death, and a reduced Nestin-positive GSC population. Therefore, our antitumor strategy provides a novel basis for designing stem cell-mediated therapeutic approaches to target and eradicate GSCs and the bulk tumors.     

Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum Contributes to Activation of Endothelial Nitric Oxide Synthase

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.     

Region-based diagnostic performance of multidetector CT for detecting peritoneal seeding in ovarian cancer patients

Purpose  

To determine the accuracy of multi-detector CT (MDCT) compared with the surgical findings, such as peritoneal seeding and metastatic lymph nodes, in ovarian cancer patients.