Search results for: monoclonal
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A Proposed Treatment Approach to Treat Lethal Mutating Cancers.A proposed treatment using dual-peptide ligand masks, that are functional extensions to existing analogous mammalian immune system structures, to bind to cancer cell surface proteins and stop mutating cancers that could evade presently used engineered immune cell therapies. One treatment injects the dual-peptide ligand masks into the blood stream of patients, and another treatment injects the dual-peptide ligand masks into localized cancers to bind to cancer cell surface proteins. The mammalian immune system has long used analogous, but more complex structures called pentraxins to physically link various types of pathogens to immune cells for neutralization. This treatment approach offers potential advantages in increased binding adaptability to mutations in the surface proteins of cancer cells, and potentially lower treatment cost compared to engineered immune cell treatments against cancer, especially against mutating cancer cells, even compared to extremely specific and costly monoclonal antibody treatments or engineered T cell treatments.
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Detection of Rhizopus-specific antigen in human and murine serum and bronchoalveolar lavage.Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.
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RNA sequencing profiles and diagnostic signatures linked with response to ramucirumab in gastric cancer.Gastric cancer (GC) is the fifth cancer type by associated mortality. Proportion of early diagnosis is low, and most patients are diagnosed at the advanced stages. First line therapy standardly includes fluoropyrimidines and platinum compounds with trastuzumab for HER2-positive cases. For the recurrent disease there are several alternative options including ramucirumab, a monoclonal therapeutic antibody that inhibits VEGF-mediated tumor angiogenesis by binding with VEGFR2, alone or in combination with other cancer drugs. However, control over disease rate following ramucirumab or its combinations is 30-80% of the patients, suggesting that personalization of drug prescription is needed to increase efficacy of treatment. We report here original tumor RNA sequencing profiles for 15 advanced GC patients linked with data on clinical response to ramucirumab or its combinations. Three genes showed differential expression in the tumors-responders vs non-responders: CHRM3, LRFN1 and TEX15. Of them, CHRM3 was upregulated in the responders. Using bioinformatic platform Oncobox we simulated ramucirumab efficiency and compared output model results with actual tumor response data. An agreement was observed between predicted and real clinical outcomes (AUC ≥ 0.7). These results suggest that RNA sequencing may be used to personalize prescription of ramucirumab for GC and indicate on potential molecular mechanisms underlying ramucirumab resistance. The RNA sequencing profiles obtained here are fully compatible with the previously published Oncobox Atlas of Normal Tissue Expression (ANTE) data.
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The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases.Zinc fingers and homeoboxes (ZHX) proteins are heterodimeric transcriptional factors largely expressed at the cell membrane in podocytes in vivo. We found ZHX2-based heterodimers in podocytes, with ZHX2-ZHX1 predominantly at the cell membrane of the podocyte cell body, and ZHX2-ZHX3 at the slit diaphragm. In addition to changes in overall ZHX2 expression, there was increased podocyte nuclear ZHX3 and ZHX2 in patients with focal segmental glomerulosclerosis, and increased podocyte nuclear ZHX1 in patients with minimal change disease. Zhx2 deficient mice had increased podocyte ZHX1 and ZHX3 expression. Zhx2 deficient mice and podocyte specific Zhx2 overexpressing transgenic rats develop worse experimental focal segmental glomerulosclerosis than controls, with increased nuclear ZHX3 and ZHX2, respectively. By contrast, podocyte specific Zhx2 overexpressing transgenic rats develop lesser proteinuria during experimental minimal change disease due to peripheral sequestration of ZHX1 by ZHX2. Using co-immunoprecipitation, the interaction of ZHX2 with aminopeptidase A in the podocyte body cell membrane, and EPHRIN B1 in the slit diaphragm were noted to be central to upstream events in animal models of minimal change disease and focal segmental glomerulosclerosis, respectively. Mice deficient in Enpep, the gene for aminopeptidase A, and Efnb1, the gene for ephrin B1 developed worse albuminuria in glomerular disease models. Targeting aminopeptidase A in Zhx2 deficient mice with monoclonal antibodies induced albuminuria and upregulation of the minimal change disease mediator angiopoietin-like 4 through nuclear entry of ZHX1. Thus, podocyte ZHX2 imbalance is a critical factor in human glomerular disease, with minimal change disease disparities mediated mostly through ZHX1, and focal segmental glomerulosclerosis deviations through ZHX3 and ZHX2.
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A small-molecule inhibitor of PCSK9 transcription ameliorates atherosclerosis through the modulation of FoxO1/3 and HNF1α.Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that down-regulates hepatic low-density lipoprotein receptor (LDLR) by binding and shuttling LDLR to lysosomes for degradation. The development of therapy that inhibits PCSK9 has attracted considerable attention for the management of cardiovascular disease risk. However, only monoclonal antibodies of PCSK9 have reached the clinic use. Oral administration of small-molecule transcriptional inhibitors has the potential to become a therapeutic option.
2873 related Products with: A small-molecule inhibitor of PCSK9 transcription ameliorates atherosclerosis through the modulation of FoxO1/3 and HNF1α.AZD-3514 Mechanisms: Andr Rabbit Anti-Human Bcl-2 I ∆1-Androstene-3α,17β- 1-(6-Amino-9-β-D-ribofur 4 (p Acetoxyphenyl) 2 but Androsta-3,5,16-trien-17- Caspase 4 Inhibitor Drug Avanafil C23H26ClN7O3 CAS 2-Amino-4'-fluorobenzophe Ofloxacin CAS Number [824 5-Acetyl-2-aminobenzonitr Opiate-2000 test strip, S
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Blocking the CGRP Pathway for Acute and Preventative Treatment of Migraine - The Evolution of Success.The pivotal role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology was identified over 30 years ago, but the successful clinical development of targeted therapies has only recently been realized. This perspective traces the decades long evolution of medicinal chemistry required to advance small molecule CGRP receptor antagonists, also called gepants, including the current clinical agents: rimegepant, vazegepant, ubrogepant and atogepant. Providing clinically effective blockade of CGRP signaling required surmounting multiple challenging hurdles, including defeating a sizeable ligand with subnanomolar affinity for its receptor, designing antagonists with an extended confirmation and multiple pharmacophores while retaining solubility and oral bioavailability, and achieving circulating free plasma levels that provided near maximal CGRP receptor coverage. The clinical efficacy of oral and intranasal gepants and the injectable CGRP monoclonal antibodies (mAbs) are described, as are recent synthetic developments which have benefited from new structural biology data. The first oral gepant was recently approved and heralds a new era in the treatment of migraine.
1762 related Products with: Blocking the CGRP Pathway for Acute and Preventative Treatment of Migraine - The Evolution of Success.FDA Standard Frozen Tissu Normal rat multiple organ CSL Gradient Thermal Cycl Recombinant Thermostable Thermostable TDG Kit *DIS Rabbit anti PKC theta (Ab Theophylline CAS Number [ Normal mouse multiple org MyGenie 96 Gradient Therm MultiGene OptiMax Thermal Thermostable TDG Enzyme & Recombinant Human PKC the
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Analytical artifacts in characterization of recombinant monoclonal antibody therapeutics.A battery of analytical methods is used to analyze recombinant monoclonal antibodies for lot release to ensure consistent product quality, safety, and efficacy. Additionally, state-of-the-art analytical methods have been used to thoroughly characterize various post-translational modifications and degradation pathways of those molecules. Scientifically sound and robust analytical methods are essential to providing reliable results for defining control strategy, including setting phase-appropriate specifications. Analytical artifacts can substantially impact analytical method performance, causing either overestimation or underestimation of the impacted attributes. However, these artifacts are often overlooked due to lack of the fundamental understanding of analytical methods. This review discusses several regularly encountered artifacts and provides a guidance on assessment and prevention of these artifacts. Understanding and preventing artifacts can help establish scientifically sound and robust methods with reliable performance throughout the method life cycle.
1777 related Products with: Analytical artifacts in characterization of recombinant monoclonal antibody therapeutics.Mouse Anti-Insulin(1D4:) Mouse Anti-Insulin(1D4 ) HIV1 integrase antibody, Mouse Anti-Insulin(1G11) Mouse Anti-Insulin(1G11) Mouse Anti-Insulin(1D4 ) Mouse Anti-Insulin(1G11) Mouse Anti-Insulin(1G11) Monoclonal anti-human CD5 Mouse Anti-Insulin(1D4:) Mouse Anti-Insulin(1D4 ) Mouse Anti-Insulin(1D4 )
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Vedolizumab therapy in common variable immune deficiency associated enteropathy: A case series.A number of gastrointestinal complications occur in common variable immunodeficiency (CVID). Infections are one cause, but various forms of severe non-infectious enteropathy also lead to substantial morbidity. The presence of T cell lymphocytic infiltrates in the mucosa have suggested that vedolizumab, a humanized monoclonal antibody which binds to alpha4 beta7 integrin and inhibits the migration of effector T-lymphocytes into gastrointestinal tissues, would be an effective treatment. A previous report of 3 CVID cases suggested benefit in 2 subjects. In this study 7 CVID patients with severe enteropathy were treated with vedolizumab. Four of the 7 completed vedolizumab induction therapy but 3 subjects had acute decompensation during induction and treatment was stopped. While one subject showed improvement, 6 of the 7 patients were withdrawn from therapy. While vedolizumab may be of use in some CVID subjects, it was not ultimately found helpful in most of these patients.
1445 related Products with: Vedolizumab therapy in common variable immune deficiency associated enteropathy: A case series.Rectum adenocarcinoma tis High density breast cance Liver cancer and normal t Multiple organ cancer and Kidney cancer test tissue Breast cancer and normal Bone marrow tumor and nor Endocrine cancer tissue a Lung cancer survey tissue Malignant melanoma tissue Skin tumor tissue array, Bladder cancer tissue arr
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