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In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level. Copyright © 2020 the Author(s). Published by PNAS.Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection.Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as PET tracer for T-cell imaging. However, production is complex and time-consuming. Therefore, we developed two radiolabeled interleukin-2 (IL-2) variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL-2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL-2 (68Ga-Ga-NODAGA-IL2) and compared their in-vitro and in-vivo characteristics with 18F-FB-IL2. Methods Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex-vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60 and 90 min after tracer injection. In-vivo binding characteristics were studied in severe combined immune-deficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMrast PET images of target lymph nodes. Conclusion Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than 18F-FB-IL2. Both tracers showed good in-vitro and in-vivo characteristics with high uptake in lymphoid tissue and hPBMC xenografts. Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.Background Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following 177Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes 1) response ≥30% decline, 2) progression ≥25% increase and 3) stable less then 30% decline and less then 25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results We identified 124 eligible patients with PSA vle center experience. Conclusion PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA. Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.The accuracy of lutetium-177 (177Lu) radiotracer concentration measurements using quantitative clinical software was determined by comparing in vivo results for a digital solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography / x-ray computed tomography) system to in vitro sampling. First, image acquisition parameters were assessed for an International Electrotechnical Commission (IEC) body phantom emulating clinical count rates loaded with a "lung" insert and 6 hot spheres with a 121 target-to-background ratio of 177Lu solution. Then, the data of 28 whole-body SPECT/CT scans of 7 patients who underwent 177Lu prostate membrane antigen (177Lu-PSMA) radioligand therapy was retrospectively analyzed. Three users analyzed SPECT/CT images for in vivo urinary bladder radiotracer uptake using quantitative software (Q.Metrix, GE Healthcare). In vitro radiopharmaceutical concentrations were calculated using urine sampling obtained immediately after each scan, scaled to standardized uptaotentially improve diagnosis, improve patient management and treatment response assessment, and provide data essential to 177Lu dosimetry. Fetuin clinical trial Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.Overexpression of somatostatin receptors in patients with neuroendocrine neoplasms (NEN) is utilized for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Non-invasive visualization and quantification of somatostatin receptor density is possible by somatostatin receptor imaging (SRI) using positron emission tomography (PET). Recently, we introduced 64Cu-DOTATATE for SRI and we hypothesized that uptake of this tracer could be associated with overall (OS) and progression-free survival (PFS). Methods We evaluated patients with NEN that had a 64Cu-DOTATATE PET/CT SRI performed in two prospective studies. Tracer uptake was determined as the maximal standardized uptake value (SUVmax) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of 64Cu-DOTATATE SUVmax for OS and PFS. Specificity, sensitivity and accuracy was calculated for prediction of outcome at 24 months after 64Cu-DOTATATE PET/CT. Results A total of 128 patients with NEN were included and followed for a median of 73 (1-112) months.
Website: https://www.selleckchem.com/products/fetuin-fetal-bovine-serum.html
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