Loss of Chemerin in Rhabdomyosarcoma Cells Polarizes Adjacent Monocytes to an Immunosuppressive Phenotype.

Chemerin is a multifunctional adipokine that regulates adipogenesis, insulin signaling and blood pressure and has thus a central function in metabolism. Mounting evidence confirmed a function of chemerin in various cancers. In this study, we investigated the role of chemerin in rhabdomyosarcoma (RMS), an aggressive soft tissue cancer that affects mainly children and young adults. We found chemerin expression in 93.8% (90 of 96) of RMS cases, with a range of 86.7-96.7% for the four RMS subgroups. While chemerin is uniformly expressed in normal skeletal muscle, its expression in RMS is patchy with interspersed areas that are devoid of chemerin. This variable chemerin expression is reflected by RMS cell lines as two of them (Rh41 and Rd18) were found to secrete chemerin while the two other ones (JR1 and RD) were negative. Deletion of chemerin in Rh41 and Rd18 cells did not alter their growth rate or morphology. We investigated the potential influence of chemerin on immune surveillance by coculturing parental and chemerin-deficient RMS cells with resting- or lipopolysaccharide (LPS)-activated human peripheral monocytes. The absence of chemerin in the RMS cells led to increased expression levels of the coinhibitory molecules PD-L1 and PD-L2 while levels of the costimulatory molecule CD86 were not changed. Further, the absence of chemerin enhanced the secretion of cytokines (IL-1ß, IL-6, IL-10 and TNF) that have been shown to support RMS pathogenesis. These data indicate that the loss of chemerin expression by RMS cells repolarizes monocytes in the tumor microenvironment to supporting tumor progression.

Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting.

Rhabdomyosarcoma (RMS) is a heterogeneous soft tissue neoplasm most frequently found in children and adolescents. As the prognosis for recurrent and metastatic RMS remains poor, immunotherapies are hoped to improve quality of life and survival. CD137 is a member of tumor necrosis factor receptor family and a T cell costimulatory molecule which induces potent cellular immune responses that are able to eliminate malignant cells. Therefore, it was puzzling to find expression of CD137 on an RMS tissue microarray by multiplex staining. CD137 is not only expressed by infiltrating T cells but also by malignant RMS cells. Functional in vitro experiments demonstrate that CD137 on RMS cells is being transferred to adjacent antigen-presenting cells by trogocytosis, where it downregulates CD137 ligand, and thereby reduces T cell costimulation which results in reduced killing of RMS cells. The transfer of CD137 and the subsequent downregulation of CD137 ligand is a physiological negative feedback mechanism that is likely usurped by RMS, and may facilitate its escape from immune surveillance. In addition, CD137 signals into RMS cells and induces IL-6 and IL-8 secretion, which are linked to RMS metastasis and poor prognosis. However, the ectopic expression of CD137 on RMS cells is an Achilles' heel that may be utilized for immunotherapy. Natural killer cells expressing an anti-CD137 chimeric antigen receptor specifically kill CD137-expressing RMS cells. Our study implicates ectopic CD137 expression as a pathogenesis mechanism in RMS, and it demonstrates that CD137 may be a novel target for immunotherapy of RMS.

[The effect of Tai Chi movement in patients with rheumatoid arthritis].

PURPOSE: This study was performed to verify the effect of Tai Chi exercise on patients with rheumatoid arthritis particularly their level of pain, fatigue, sense of balance and daily life performance (ADL). METHOD: It employed a non-equivalent control group pre- and post-test design. The research instruments used in this study were pain, fatigue, sense of balance and ADL. Thirty-two patients in the experimental group carried out 50 minutes of Tai Chi exercise for 12 weeks, and 29 patients in the control group did not. Before and after the experiment, both groups were tested for pain, fatigue, sense of balance and ADL. Collected data were processed using the SPSS/WIN 10.0 program analyzed by the frequency, percentage, chi2-test, and t-test. RESULTS: Pain and fatigue significantly decreased in the experimental group. However the improvement in ADL of the rheumatoid arthritis patients was not statistically significant but their sense of balance was enhanced significantly. CONCLUSION: Tai Chi exercise is an effective nursing intervention that can be used for rheumatoid arthritis patients.

Distribution of trkA in cerebral cortex and diencephalon of the mongolian gerbil after birth.

TrkA is essential components of the high-affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF. Here we report on the expression of trkA in the cerebral cortex and diencephalon of mongolian gerbils during postnatal development. The expression of trkA was identified by immunohistochemical method. In parietal cortex and piriform cortex, higher levels of trkA IR (immunoreactivity) were detected at 3 days postnatal (P3) and at P9. Although trkA was not expressed till P3 in the parietal cortex, it was detectable at birth in the piriform cortex. Several regions, such as Layers I, IV & VI, did not show much expression. Layer I showed especially weak labeling. In the hippocampus, thalamus, and hypothalamus, higher levels of trkA IR were detected at P6 and P12 than earlier days. But trkA was not expressed at birth in the hippocampus, at P3 in the reticular thalamic nucleus (Rt), or neonatally in the dorsomedial hypothalamic nucleus (DM). This data shows that expression of trkA is developmentally regulated and suggests that high affinity neurotrophin-receptors mediate a transient response to neurotrophines in the cerebral cortex and diencephalon during mongolian gerbil brain ontogeny.

Immunohistochemical localization of nerve growth factor, glial fibrillary acidic protein and ciliary neurotrophic factor in mesencephalon, rhombencephalon, and spinal cord of developing mongolian gerbil.

The distribution of the nerve growth factor (NGF), the glial fibrillary acidic protein (GFAP) and the ciliary neurotrohic factor (CNTF) was performed in coronal sections of the mesencephalon, rhombencephalon and spinal cord in the developing Mongolian gerbils. Generally, NGF specifically recognizes neurons with the NGF receptor, whereas GFAP does the glia, and CNTF does the motor neurons. The receptor expression was examined separately in gerbils between embryonic days 15 (E15) and postnatal weeks 3 (PNW 3). The NGF-IR was first observed in the spinal cord at E21, which might be related to the maturation. The GFAP reactivity was peaked at the postnatal days 2 (PND2), while the highest CNTF-reaction was expressed at PNW 2. The GFAP stains were observed in the aqueduct and the spinal cord, which appeared to project laterally at E19. The CNTF was observed only after the birth and found in both the neurons and neuroglia of the substantia nigra, mesencephalon, cerebellum and the spinal cord from PND1 to PNW3. These results suggest that NGF, GFAP and CNTF are important for the development of the neurons and the neuroglia in the central nervous system at the late prenatal and postnatal stages.