siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers

Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that lead to uncontrolled cell proliferation. RNA interference (RNAi) with short interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal processing in CTCL cells, but functional biomaterial carriers are needed to effectively deliver siRNAs intracellularly. Towards this goal, we explored the utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA, respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP) was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a high siRNA: carrier ratio used to assemble the complexes and centrifugation of cells in the presence of complexes were found effective. The toxicities of PEI-CA and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI and Lipofectamine^® RNAiMAX. This might have contributed to reduced siRNA delivery efficiency of the latter carriers. Screening several endogenous targets led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated cell growth inhibition. The results of this study identified promising polymeric carriers and molecular targets that could control proliferation of CTCL cells based on RNAi therapy.     

Sequestered disc herniation mimicking psoas abscess: A rare case report

Intervertebral disc herniation is common condition, with majority occurring in lumbar and cervical spine. Most lumbar disk herniations occur within the spinal canal, with approximately 7%-10% identified within the foramen or extraforaminal location. Extraforaminal disc herniation in extreme lateral, retroperitoneal or anterior terms are used when disc material is seen towards anterolateral or anterior to the spine. Disc herniation in these locations is easily mistaken for an abscess or a neoplasm especially when it is not connected to the parent disc (sequestered disc). We describe a case of 60-year male who initially was misdiagnosed as psoas abscess and subjected to invasive investigation which later turned out to be histologically confirmed disc sequestration in the retroperitoneum. Thus, knowledge of this condition is essential in avoiding unnecessary workup and treatment.