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Connor Ploug posted an update 6 days, 3 hours ago
In addition, this device shows excellent durability and flexibility with multiple optional outputs, demonstrating the potential as a transparent energy supply in planar electronics.Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4+ T cells, decreased numbers of regulatory T cells (Treg), and activation of the myeloid compartment. Importantly, the immunotherapy-enabling benefits of IL-12 are achieved with minimal systemic effects. Our findings thus show that local delivery of IL-12 may be an effective adjuvant for CAR-T cell therapy for GBM.
This case report details the surgical treatment of an RA patient who presented with concomitant AAI and subaxial spondylotic stenosis and was subsequently treated via a C1-2 screw-rod construct, semispinalis cervicis sparing C3 laminectomy, and C4-C7 laminoplasty. Our case report is the first to describe a surgical approach for treatment of concomitant AAI and subaxial spondylotic stenosis in a patient with RA.
A 66-year-old male with a history of rheumatoid arthritis and atlantoaxial instability presented to an outpatient spine clinic with complaints of neck pain and worsening gait imbalance. A flexion-extension MRI revealed compression of the posterior aspect of the C1 ring on the back of the spinal cord during flexion, resulting in cord deformation; subaxial spondylosis with moderate associated stenosis and congenital narrowing from C3-7; and central cord compression with T2 signal change at C5-6. A C1-2 arthrodesis was performed and the subaxial spinal cord was then decompressed by performing a seminspinalis-sparing C3 laminectomy, C4-6 laminoplasties, and C7 dome laminectomy. Follow-up flexion-extension radiographs demonstrated satisfactory hardware position at C1-2 and full range of motion at C3-7.
This is the first study to describe the surgical management of an RA patient with concomitant AAS and subaxial spondylotic stenosis. Patients with these simultaneous pathologies can be considered for decompression caudal to the C1-2 arthrodesis, though they should be adequately counseled regarding the risk of developing SAS requiring subsequent fusion.
This is the first study to describe the surgical management of an RA patient with concomitant AAS and subaxial spondylotic stenosis. Patients with these simultaneous pathologies can be considered for decompression caudal to the C1-2 arthrodesis, though they should be adequately counseled regarding the risk of developing SAS requiring subsequent fusion.WHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. In this study, we revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer (CRC). Our data showed that WHSC1 as well as H3K36me2 were highly expressed in clinical CRC samples, and high WHSC1 expression is associated with poorer prognosis in OS patients. WHSC1 reduction promoted colon cancer cell apoptosis both in vivo and in vitro. We found that B cell lymphoma-2 (BCL2) expression, an anti-apoptotic protein, is markedly decreased in after WHSC1 depletion. Mechanistic characterization indicated that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level. What’s more, our study indicated that WHSC1 depletion promotes chemosensitivity in CRC cells. Together, our results suggested that WHSC1 and H3K36me2 modification might be optimal therapeutic targets to disrupt CRC progression and WHSC1-targeted therapy might potentially overcome the resistance of chemotherapeutic agents.Hematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor-TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor-TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.
Ganglion cysts are benign soft tissue lesions, usually arising from periarticular connective tissue. see more These are very rarely reported in the spine, but when seen can cause radiculopathy or myelopathy.
A 68-year-old female patient presented with worsening radiculopathy and right foot drop and imaging noted a right L5-S1 foraminal mass. The lesion was gross totally resected. Histological analysis revealed myxoid degeneration and inflammation, without a synovial lining, consistent with ganglion cyst.
While uncommon, intra-foraminal ganglion cysts can be distinguished from synovial cysts through imaging and histology and are typically amenable to surgical resection. Greater knowledge and insight about differentiating ganglion versus synovial cyst may prevent resection of facet joints and prevent a fusion procedure.
While uncommon, intra-foraminal ganglion cysts can be distinguished from synovial cysts through imaging and histology and are typically amenable to surgical resection. Greater knowledge and insight about differentiating ganglion versus synovial cyst may prevent resection of facet joints and prevent a fusion procedure.