The hepatic niche leads to aggressive natural killer cell leukemia proliferation through the transferrin-transferrin receptor 1 axis.

Aggressive natural killer cell leukemia (ANKL) is a rare lymphoid neoplasm frequently associated with Epstein-Barr virus, with a disastrously poor prognosis. Owing to the lack of samples from patients with ANKL and relevant murine models, comprehensive investigation of its pathogenesis including the tumor microenvironment (TME) has been hindered. Here we established 3 xenograft mice derived from patients with ANKL (PDXs), which enabled extensive analysis of tumor cells and their TME. ANKL cells primarily engrafted and proliferated in the hepatic sinusoid. Hepatic ANKL cells were characterized by an enriched Myc-pathway and proliferated faster than those in other organs. Interactome analyses and in vivo CRISPR-Cas9 analyses revealed transferrin (Tf)-transferrin receptor 1 (TfR1) axis as a potential molecular interaction between the liver and ANKL. ANKL cells were rather vulnerable to iron deprivation. PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a noncanonical hematopoietic organ in adults, serves as a principal niche for ANKL and the inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.

Microcervical Foraminotomy for Cervical Juxtafacet Cysts: Case Series and Literature Review.

BACKGROUND: Juxtafacet cysts are located near or contiguous with the facet joints, and their occurrence is rare in the cervical spine. We report 4 cases of cervical juxtafacet cysts operated by microcervical foraminotomy (MCF) or a combination of MCF and laminoplasty. We simultaneously review previously reported cases in terms of location, clinical findings, and surgical technique. METHODS: Among the patients who underwent spine surgery at our hospital from 2015 to 2019, 4 had cervical juxtafacet cysts. The images and clinical records of the patients were retrospectively assessed. Relevant previous English literature was searched and reviewed using PubMed. RESULTS: In our series, all 4 patients presented with unilateral upper extremity muscle weakness preoperatively. Two patients underwent MCF, and the other 2 underwent a combination of MCF and laminoplasty with resection of the cyst. All showed improvement in muscle strength. In previously reported cases, the rate of muscle weakness was high. A review of previous cases showed that 75 of 139 patients had cysts at C7-T1. The most common surgical techniques consisted of a hemilaminectomy or laminectomy with the addition of posterior fusion in 28 patients. The number of male patients was twice that of female patients; however, the male-to-female ratio was almost the same in patients with cysts in C7-T1. On pathological diagnosis, there were 3 times more synovial cysts than ganglion cysts. The percentage of synovial cysts was higher in patients with radiculopathy, and the percentage of ganglion cysts was higher in patients with myelopathy. CONCLUSIONS: Cervical juxtafacet cysts tend to occur in C7-T1 and cause muscle weakness. Surgical therapy is strongly recommended due to good postoperative improvement. CLINICAL RELEVANCE: The results of this study suggest that microcervical foraminotomy for cervical juxtafacet cysts can provide favorable symptomatic improvement.

Ponatinib Improved the Prognosis of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Japanese Single-Center Cohort Study.

Introduction The overall survival (OS) of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has improved with the combination of tyrosine kinase inhibitor (TKI) with intensive chemotherapy. In recent years, there has been increased interest in the possibility of long-term survival without allogeneic hematopoietic stem cell transplantation (HSCT) or maintenance therapy. The aim of this study was to determine the effectiveness of treatment and the resultant outcomes in Ph+ALL patients using real-world data. Methods We performed a single-center retrospective analysis utilizing Akita University Hospital data (Akita, Japan) from November 2000 to June 2023 to evaluate the outcomes of TKI with intensive chemotherapy for Ph+ALL. Results Twenty-three patients with Ph+ALL were treated with intensive chemotherapy combined with TKI, including six imatinib, four dasatinib, and 13 ponatinib. The median patient age was 53 years (range; 28-67). Eighteen patients (78%) achieved complete molecular remission (CMR) within three months. HSCT was performed in 16 patients (70%), all of whom did not receive post-transplant TKI maintenance therapy. Six of the seven patients who did not undergo HSCT received maintenance therapy with ponatinib after intensive chemotherapy. The three-year OS was 81%. Ponatinib treatment resulted in a much higher OS rate than imatinib/dasatinib (100% vs. 60%; P=0.011). CMR within three months was identified as a prognostic factor for molecular relapse-free survival (hazard ratio (HR)=0.22; P=0.027). CD20 positivity was identified as a risk factor for hematological relapse (HR=5.2, P=0.032). Conclusion Even in a single-center cohort study, ponatinib, as a combination TKI with intensive chemotherapy or maintenance therapy, may improve the prognosis of Ph+ALL. Patients with CMR within three months might not necessarily need to receive HSCT, but a subsequent treatment-free status could have been achieved only by HSCT. Furthermore, CD20 positivity may be a useful biomarker for future treatment decisions in patients with Ph+ALL.

Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia.

Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are "fluctuate" patients who have BCR-ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8+ T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR.

The BCRP inhibitor febuxostat enhances the effect of nilotinib by regulation of intracellular concentration.

Nilotinib is a substrate of the breast cancer resistance protein (BCRP), which is a drug efflux transporter encoded by ABCG2 and regulates the pharmacokinetics of its substrates. We investigated the interaction between nilotinib and BCRP in chronic myeloid leukemia (CML) cells. An imatinib-resistant K562 cell line (K562/IM-R) treated with nilotinib was analyzed for BCRP expression, proliferation, apoptosis, and intracellular nilotinib concentration. K562/IM-R cells cultured with tyrosine kinase inhibitors (TKIs) showed an increased cell count and retained viability, whereas the growth of parental K562 cells was severely inhibited, suggesting that BCRP is involved in developing resistance to TKIs. Nilotinib-treated K562/IM-R cells showed a reduction in apoptosis; however, febuxostat pretreatment resulted in increased apoptosis. The intracellular concentration of nilotinib in K562/IM-R cells was significantly reduced compared to that in parental K562 cells, and febuxostat-pretreated K562/IM-R cells showed an increased intracellular nilotinib level compared to cells without pretreatment. The reduction in nilotinib levels caused by BCRP in CML cells might play a crucial role in resistance to TKIs. Moreover, febuxostat, as a BCRP inhibitor, could enhance nilotinib sensitivity, and combination therapy with nilotinib and febuxostat may represent a promising strategy for treatment of CML.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.

Basics of cancer immunotherapy.

The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19+ acute lymphocytic leukemia. In sharp contrast to conventional anti-cancer reagents which directly kill cancer cells, cancer immunotherapy activates various types of immune effector cells to attack cancer cells. However, more than half of the treated patients showed no activation of anti-tumor CD8+ killer T cells and CD4+ helper T cells and failed to respond to immune therapies such as immune checkpoint blockade, even when administered in combination regimens. Thus, development of novel immunotherapies to achieve more effective activation of anti-cancer immunity and immuno-monitoring of biomarkers, allowing proper evaluation of immune responses in cancer patients in order to detect responders, are urgent issues. Additionally, we must pay attention to characteristic immunological side effects not observed following treatment with conventional anti-cancer reagents. Herein, we present a summary outline and discuss the future direction of cancer immunotherapy.

Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut.

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.

Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner.

BACKGROUND: During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown. QUESTIONS/PURPOSES: In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes. METHODS: A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naïve, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array(®) quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2. RESULTS: Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037). CONCLUSIONS: Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted. CLINICAL RELEVANCE: This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may contribute to the development of more and better treatment options for patients with disc herniation and sciatica.

Clinical results of microsurgical bilateral decompression via unilateral approach for lumbar canal stenosis with multiple-level involvement.

OBJECT: Microsurgical decompression of the lumbar spine is a beneficial approach for selected patients of lumbar spinal stenosis (LSS). The purpose of this prospective study was to describe the clinical results of surgical treatment for microsurgical bilateral decompression via unilateral approach on patients with LSS with multiple-level involvement. MATERIALS AND METHODS: Seventy-three consecutive patients who had microsurgical bilateral decompression via unilateral approach of more than two spinal levels were included in this study. Seventy-seven patients who had surgery at a single level over the same time periods were compared as a single-level LSS group. RESULTS: The preoperative Japanese Orthopaedic Association scores averaged 11.7 points, and the postoperative scores averaged 21.2 points with an average recovery rate (RR) of 56% in the multiple-level LSS group. There was no significant difference in the RR between the groups. There were no major complications related to the surgery in the both groups. CONCLUSION: Microsurgical bilateral decompression via unilateral approach was a useful and safe operative procedure for LSS patients. Sufficient clinical results that were comparable to single-level LSS patients were obtained even in the patients with multiple-level LSS, if the patient were correctly selected and the microsurgical decompression surgery were carefully performed.

Electrophysiological evidence of functional improvement in the corticospinal tract after laminoplasty in patients with cervical compressive myelopathy: clinical article.

OBJECT: Cervical laminoplasty is a surgical procedure for cervical compressive myelopathy (CCM), and satisfactory outcomes have been reported. However, few reports have examined the pathophysiology of improvements in spinal cord function. The aim of this study was to investigate the variation in central motor conduction time (CMCT) before and after cervical laminoplasty in patients with CCM. METHODS: Motor evoked potentials (MEPs) following transcranial magnetic stimulation and compound muscle action potentials (CMAPs) and F-waves following electrical stimulation of the ulnar and tibial nerves at the wrist and ankle were measured from the abductor digiti minimi muscle (ADM) and abductor hallucis muscle (AH) in 42 patients with CCM before and 1 year after cervical laminoplasty. The peripheral conduction time (PCT) was calculated as follows: (latency of CMAPs + latency of F-waves - 1)/2. The CMCT was calculated by subtracting the PCT from the onset latency of the MEPs. The CMCT recovery ratio was defined and calculated as the ratio of CMCT values 1 year after surgery to those before surgery. The CMCT data were analyzed as longer or shorter CMCT between the patients' right and left ADMs and AHs. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was obtained as a clinical outcome before and 1 year after surgery. The recovery rate (RR) 1 year after surgery was calculated using the following formula: (postoperative JOA score 1 year after surgery - preoperative JOA score)/(17 - preoperative JOA score) × 100. Correlations among CMCT parameters, patient age, JOA score, and RR were determined. RESULTS: The longer and shorter CMCTs from the ADM (longer, p = 0.000; shorter, p = 0.008) and the longer CMCT from the AH (longer, p = 0.000) before surgery decreased significantly 1 year after surgery; the shorter CMCT from the AH did not significantly differ (shorter, p = 0.078). The mean JOA score before surgery was 10.1 ± 3.0 and improved significantly to 12.9 ± 2.7 at 1 year after surgery (p = 0.000). The mean CMCT recovery ratio and RR were 0.91 ± 0.18 and 0.43 ± 0.27, respectively. The longer/shorter CMCT parameters in the ADM and AH before or 1 year after surgery correlated significantly with the JOA score both before and 1 year after surgery. The CMCT recovery ratio from the longer CMCT in the ADM correlated significantly with the RR (r = - 3090, p = 0.011). There were no significant correlations between age and any CMCT parameters or CMCT recovery ratios. CONCLUSIONS: These results suggest that cervical laminoplasty improves corticospinal tract function 1 year after surgery, which may be one of the reasons for the JOA score improvements in patients with CCM. The degree of improvement in corticospinal tract function did not correlate with patient age in this case series. The results demonstrated quantitative evidence of the pathophysiology of functional recovery in the corticospinal tract following cervical laminoplasty in patients with CCM.

Surgical treatment of high-grade dysplastic spondylolisthesis using intraoperative electrophysiological monitoring: report of two cases and review of the literature.

Treatment of high-grade dysplastic spondylolisthesis in adolescents remains challenging. Surgical treatment of spondylolisthesis has been recommended in adolescents with pain refractory to conservative treatment, slippage progression, or severe slippage on presentation. Controversy exists as to the optimal surgical approach for high-grade spondylolisthesis. Moreover, some authors reported the incidence of L5 root palsy during the reduction procedure. We performed 2 cases of surgical treatment using intraoperative electrophysiological monitoring for patients with high-grade dysplastic spondylolisthesis in adolescence. Each patient received treatment consisting of decompression of nerve with surgical microscope, reduction, and circumferential fusion with transpedicular and monosegmental fixation surgery with intraoperative neurological monitoring with transcranial electric motor evoked potentials and continuous spontaneous electromyography recording. Intraoperative monitoring did not show any abnormal changes. The patients got well after surgery, and they showed no postoperative motor paralysis of the extremities. A postoperative radiogram showed reduction of the slippage, and computed tomogram showed bone union between L5 and S1 vertebral body. This report describes 2 cases of surgical treatment using intraoperative electrophysiological monitoring with transcranial electric motor evoked potentials and continuous spontaneous electromyography for patients with high-grade dysplastic spondylolisthesis in adolescence. We successfully perform the surgery without any neurological deficit using intraoperative electrophysiological monitoring.

Use of prone position magnetic resonance imaging for detecting the terminal filum in patients with occult tethered cord syndrome.

OBJECT: The pathophysiology of occult tethered cord syndrome (OTCS) with no anatomical evidence of a caudally shifted conus and a normal terminal filum is hard to understand. Therefore, the diagnosis of OTCS is often difficult. The authors hypothesized that the posterior displacement of the terminal filum may become prominent in patients with OCTS who are in a prone position if filum inelasticity exists, and they investigated prone-position MRI findings. METHODS: Fourteen patients with OTCS and 12 control individuals were examined using T2-weighted axial MRI with the patients in a prone position on a flat table. On each axial view, the distance between the posterior and anterior ends of the subarachnoid space (A), the distance between the posterior end of the subarachnoid space and the terminal filum (B), the distance between the posterior end of the subarachnoid space and the dorsal-most nerve among the cauda equina (C), and the distance between the posterior end of the subarachnoid space and the ventral-most nerve (D) were measured. The location ratios of the terminal filum, the dorsal-most nerve, and the ventral-most nerve were calculated by the ratio of A to B (defined as TF = B/A), A to C (defined as DN = C/A), and A to D (defined as VN = D/A), respectively. Patients underwent sectioning of the terminal filum with the aid of a surgical microscope. The low-back pain Japanese Orthopaedic Association score was obtained before surgery and at the final follow-up visit. RESULTS: On prone-position axial MRI, the terminal filum was separated from the cauda equina and was shifted caudally to posterior in the subarachnoid space in all patients with OTCS. The locations of the caudal cauda equina shifted to ventral in the subarachnoid space. The TF values in the OTCS group were significantly lower than those in the control group at the L3-4 (p = 0.023), L-4 (p = 0.030), L4-5 (p = 0.002), and L-5 (p < 0.001) levels. In contrast, the DN values in the OTCS group were significantly higher than those of the control group at the L-2 (p = 0.003), L2-3 (p = 0.002), L-3 (p < 0.001), L3-4 (p < 0.001), L-4 (p = 0.007), L4-5 (p = 0.003), and S-1 (p = 0.014) levels, and the VN values in the OTCS group were also significantly higher than those of the control group at the L2-3 (p = 0.022), L-3 (p = 0.027), L3-4 (p = 0.002), L-4 (p = 0.011), L4-5 (p = 0.019), and L5-S1 (p = 0.040) levels. Sections were collected during surgery for histological evaluation, and a decreased elasticity within the terminal filum was suggested. Improvements in the Japanese Orthopaedic Association score were observed at the final follow-up in all patients. CONCLUSIONS: The authors' new method of using the prone position for MRI shows that the terminal filum is located significantly posterior and the cauda equina is located anterior in patients with OTCS, suggesting a difference in elasticity between the terminal filum and cauda equina.

Medium-term clinical results of microsurgical lumbar flavectomy that preserves facet joints in cases of lumbar degenerative spondylolisthesis: comparison of bilateral laminotomy with bilateral decompression by a unilateral approach.

STUDY DESIGN: A retrospective study of medium-term results. OBJECTIVE: To describe a technique for posterior decompression using microsurgical lumbar flavectomy (MLF) without facetectomy, which is based on the anatomic features of the ligamentum flavum, and to examine the clinical outcomes of patients with lumbar spinal spondylolisthesis with lower extremity symptoms rather than low back pain, who underwent this procedure by 2 different approaches. SUMMARY OF BACKGROUND DATA: Posterior decompression with fusion has been the optimal and standard operative treatment for lumbar degenerative spondylolisthesis. Alternatively, minimally invasive procedures have been used for the treatment of lumbar degenerative spondylolisthesis with favorable outcomes. METHODS: A bilateral laminotomy (BL group) was performed on 44 consecutive patients, and bilateral decompression by a unilateral approach (BDU group) was performed on 23 consecutive patients. The mean follow-up period was 7.0 years. The Japanese Orthopaedic Association score and recovery rate were obtained, and radiographic assessment was performed using plain radiograms on the lateral view while standing in flexion, neutral, and extension postures before surgery and at the final follow-up. RESULTS: The Japanese Orthopaedic Association score at the final follow-up was improved in the BL and BDU groups, compared with that before MLF. The mean recovery rate was 72.4% and 68.4%, respectively. The mean % slip increased at the final follow-up, compared with that before surgery in both groups, except for the % slip in the extension posture in the BDU group. However, there was no significant difference in the dynamic % slip in the flexion-extension posture between before surgery and at the final follow-up. CONCLUSIONS: Clinical and radiologic parameters were not significantly different between the 2 groups. This technique of MLF using either approach did not increase the dynamic % slip and showed favorable medium-term clinical results in cases of lumbar degenerative spondylolisthesis.

Magnetic field-based delivery of human CD133⁺ cells promotes functional recovery after rat spinal cord injury.

STUDY DESIGN: Experimental animal study of spinal cord injury (SCI), using a cell delivery system. OBJECTIVE: To investigate the therapeutic effects of transplantation of peripheral blood-derived CD133 cells, with a magnetic delivery system in a rat SCI model. SUMMARY OF BACKGROUND DATA: There are no reports on intrathecal transplantation of peripheral blood-derived CD133 cells, with a magnetic cell delivery system to treat SCI. METHODS: Magnetically isolated peripheral blood-derived CD133 cells were used as the cell source. Contusion SCI was induced by an Infinite Horizon impactor in athymic nude rats. CD133 cells or phosphate-buffered saline was administered via a lumbar puncture immediately after SCI, and a magnetic field was applied to rats for 30 minutes. Animals were analyzed at specific times after transplantation by several methods to examine cell tracking, functional recovery, and histological angiogenesis and neurogenesis. RESULTS: A combination of cell transplantation and application of a magnetic field at the site of injury caused significant functional recovery. Transplantation of the cells alone in the absence of the magnetic field showed no effect beyond that observed in control rats. CONCLUSION: The combination of intrathecal transplantation of CD133 cells and application of a magnetic field at the site of injury is a possible therapeutic strategy to treat rat SCI and may therefore find application in clinical settings.

MicroRNA-223 expression in neutrophils in the early phase of secondary damage after spinal cord injury.

MicroRNA (miR)s are short non-coding RNAs that suppress the translation of target genes, and play an important role in gene regulation. Despite this prominence, there are few reports that refer to the expression of miRs after spinal cord injury (SCI). Previously, we reported on miR-223 expression after SCI in mice. The purpose of this study is to reveal the distribution of miR-223 and identify the cells that express miR-223 in the injured spinal cord. Quantitative polymerase chain reaction analysis revealed high expression of miR-223 at 12h after SCI. Double staining of in situ hybridization and immunohistochemistry showed that the signals of miR-223 merged with Gr-1 positive neutrophils. Our data indicate that miR-223 might regulate neutrophils in the early phase after SCI.

Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human.

c-Maf translocation or overexpression has been observed in human multiple myeloma. Although c-maf might function as an oncogene in multiple myeloma, a role for this gene in other cancers has not been shown. In this study, we have found that mice transgenic for c-Maf whose expression was direct to the T-cell compartment developed T-cell lymphoma. Moreover, we showed that cyclin D2, integrin beta(7), and ARK5 were up-regulated in c-Maf transgenic lymphoma cells. Furthermore, 60% of human T-cell lymphomas (11 of 18 cases), classified as angioimmunoblastic T-cell lymphoma, were found to express c-Maf. These results suggest that c-Maf might cause a type of T-cell lymphoma in both mice and humans and that ARK5, in addition to cyclin D2 and integrin beta(7), might be downstream target genes of c-Maf leading to malignant transformation.