International journal of molecular sciences
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In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. ⋯ PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials.
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A syndrome of multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia due to somatic mosaic gain-of-function mutation of EPAS1, encoding HIF-2α, was previously described. HIF-2α has been implicated in endochondral and intramembranous ossification. Abnormal bone growth of the skull base may lead to Chiari malformation type I. ⋯ Both patients were confirmed for characteristics of EPAS1 gain-of-function mutation syndrome by complete blood count (CBC), plasma biochemistry, and computed tomography (CT) of the abdomen and pelvis. Chiari malformation type I and abnormal bony development of the posterior fossa was found on MRI and CT of the head. The present study implicates EPAS1 mutations in abnormal posterior fossa development resulting in Chiari malformation type I.
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Uterine leiomyoma is found in ~50-80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine leiomyomas. In this study, miR microarray analysis of leiomyomas and paired myometrial tissue revealed numerous aberrantly expressed miRs, including miR-150. ⋯ As a result, the Akt/p27Kip1 pathway was presumed to be one of the target pathways of miR-150. After transfecting cultured leiomyoma cells with the miR-150 mimic, expression levels of its target gene Akt decreased, whereas those of p27Kip1 increased significantly. Our results suggest that miR-150 affects the cell cycle regulation in uterine leiomyoma through the Akt/p27Kip1 pathway.
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Mesenchymal stem cells (MSCs) are emerging as a potential therapeutic intervention for brain injury due to their neuroprotective effects and safe profile. However, the homing ability of MSCs to injury sites still needs to be improved. Fibroblast Growth Factor 21 (FGF21) was recently reported to enhance cells migration in different cells type. ⋯ Magnetic resonance imaging (MRI) revealed that FGF21 significantly enhances the homing of MSC toward injury site. Histological analysis further confirmed the MRI findings. Taken together, these results show that FGF21 overexpression and MIEG labeling of MSC enhances their homing abilities and enables non-invasive real time tracking of the transplanted cells, provides a promising approach for MSC based therapy and tracking in TBI.
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Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. ⋯ The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.