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#35020859   2021/12/05 To Up

Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T cell subpopulations in rheumatoid arthritis using flow-cytometry based peptide-MHC class-II tetramer staining.

Antigen-specific T cells can serve as a response biomarker in non-clinical or clinical immunotherapy studies in autoimmune disease. There are protocols with optimized multimer staining methods to detect peptide (p)MHCII+ CD4+ T cells, and some qualified and validated protocols for pMHCI+ CD8+ T cells. However, no protocol is fully or partially qualified to enumerate and characterise antigen-specific pMHCII+ CD4+ T cells from patient samples. Implementing such an assay requires a desired level of specificity and precision, in terms of assay repeatability and reproducibility. In transgenic type II collagen (CII)-immunised HLA-DR1/DR4 humanised mouse models of collagen-induced arthritis (CIA), CII259-273-specific T cells dominantly expand. Therefore antigen-specific T cells recognising this epitope presented by rheumatoid arthritis (RA)-associated risk HLA-DR allomorphs are of interest to understand disease progression and responses to immunotherapy in RA patients. Using HLA-DRB1*04:01 or *01:01-collagen type II (CII)259-273 tetramers, we evaluated parameters influencing precision and reproducibility of an optimized flow cytometry-based method for antigen-specific CD4+ T cells and eight specific subpopulations with and without tetramer positivity. We evaluated specificity, precision, and reproducibility for research environments and non-regulated laboratories. The assay has excellent overall precision with %CV<25% for intra-assay repeatability, inter-analyst precision, and inter-assay reproducibility. The precision of the assay correlated negatively with the cell viability after thawing, indicating that post-thaw viability is a critical parameter for reproducibility. This assay is suitable for longitudinal analysis of treatment response and disease activity outcome in RA patients, and adaptable for translational or immunotherapy clinical trial settings.
Swati Patel, Nishta Ramnoruth, Pascale Wehr, Jamie Rossjohn, Hugh H Reid, Kim Campbell, Hendrik J Nel, Ranjeny Thomas

1804 related Products with: Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T cell subpopulations in rheumatoid arthritis using flow-cytometry based peptide-MHC class-II tetramer staining.

1 kit1 kit1 kit1 kit(96 Wells)0.1ml (1mg/ml)1 kit1 kit(96 Wells)1 kit1 kit(96 Wells)1 kit(96 Wells)24 tests

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#35003898   2022/01/05 To Up

Identification of Claudin 6-specific HLA class I- and HLA class II-restricted T cell receptors for cellular immunotherapy in ovarian cancer.

Adoptive cell therapy (ACT) is one of promising immunotherapies for cancer patients by providing a large amount of cancer antigen-specific effector T cells that can be manufactured rapidly by ex vivo gene engineering. To provide antigen-specificity to patients' autologous T cells in a short-term culture, T-cell receptors (TCRs) or chimeric antigen receptors (CARs) are transduced to bulk T cells. Because of intra- and inter-tumoral heterogeneity in tumor antigen expression, a repertoire of TCR or CAR genes targeting a wide range of tumor antigens are required for a broad and effective treatment by ACT. Here, we characterized immunogenicity of claudin 6 (CLDN6) in ovarian cancer patients and identified specific TCR genes from CD8 and CD4 T cells. CLDN6 protein was frequently expressed on EpCAM ovarian cancer cells but not CD45 lymphocytes in tumor ascites of ovarian cancer patients. Spontaneous CLDN6-specific CD4 and CD8 T-cell response was detected in peripheral blood mononuclear cells (PBMCs) from 1 out of 17 ovarian cancer patients. HLA-A*02:01 (A2) and DR*04:04 (DR4)-restricted TCR genes were isolated from CLDN6-specific CD8 and CD4 T cells, respectively. T cells that were engineered with A2-restricted TCR gene recognized and killed A2CLDN6 cancer cells. DR4-restricted TCR-transduced T cells directly recognized DR4CLDN6-overexpressed cancer cells. Our results demonstrate that these CLDN6-specific TCR genes are useful as therapeutic genes for ACT to patients with ovarian and other solid tumors expressing CLDN6.
Junko Matsuzaki, Shashikant Lele, Kunle Odunsi, Takemasa Tsuji

2869 related Products with: Identification of Claudin 6-specific HLA class I- and HLA class II-restricted T cell receptors for cellular immunotherapy in ovarian cancer.



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#34990076   2022/01/06 To Up

Epidemiology and surveillance of autoimmune hepatitis in Asia.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that mainly injures the hepatocytes. The autoimmune disease might be involved in its aetiology, but this remains to be confirmed. Recently epidemiological studies of AIH in Asia have been broadly conducted, revealing characteristics and management of AIH patients in Asia. In East Asia, most AIH patients are type 1, and type 2 AIH is very rare. However, type 2 AIH in South Asia is as frequent as in Europe and the USA. HLA-DR4 is associated with the characteristics of type 1 AIH in East Asia, whereas HLA-DR3 occurs in AIH patients from South Asia. AIH prevalence worldwide is increasing, and several studies have reported a prevalence of 19.44, 22.80 and 12.99 per 100 000 people in Europe, the USA and Asia respectively. A meta-analysis of studies on AIH showed similar annual incidence rates for all regions, with 1.31, 1.37 and 1.00 per 100 000 people in Asia, Europe and the USA respectively. The increase in the rates could be attributable to the increased awareness of disease concepts and diagnosis. In South Asia, most cases were diagnosed as AIH only after having progressed to cirrhosis, which may cause a higher mortality rate in South Asia than in East Asia. Therefore, the early diagnosis and treatment of AIH patients can improve the current situation in Asia.
Tomohiro Katsumi, Yoshiyuki Ueno

2256 related Products with: Epidemiology and surveillance of autoimmune hepatitis in Asia.

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#34948260   2021/12/15 To Up

Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells.

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21 and, inhibition of the NF-κB pathway.
Irene Rodríguez, Ester Saavedra, Henoc Del Rosario, Juan Perdomo, José Quintana, Filippo Prencipe, Paola Oliva, Romeo Romagnoli, Francisco Estévez

1055 related Products with: Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells.

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#34903991   // To Up

Effect of Zebularine in Comparison to Trichostatin A on the Intrinsic and Extrinsic Apoptotic Pathway, Cell Viability, and Apoptosis in Hepatocellular Carcinoma SK-Hep 1, Human Colorectal Cancer SW620, and Human Pancreatic Cancer PaCa-44 Cell Lines.

Aberrant histone modifications or promoter region hypermethylation of tumor suppressor genes (TSGs) have been recognized as the important epigenetic molecular mechanism in cancer induction. The potential anticancer activities of histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMTIs) have been investigated in recent years. The current study was assigned to investigate the effect of trichostatin A (HDACI) in comparison to zebularine (DNMTI) on the intrinsic pro-apoptotic () and anti-apoptotic () genes and extrinsic ( genes) pathways, DNA methyltransferase 1, 3a, and 3b, histone deacetylase inhibitors 1, 2, and 3, cell viability, and apoptosis in hepatocellular carcinoma (HCC) SK-Hep 1, colorectal cancer SW620, and pancreatic cancer PaCa-44 cell lines. The SK-Hep 1, SW620, and PaCa-44 cells were cultured and treated with TSA and zebularine. To determine cell apoptosis, cell viability, and the relative gene expression level, flow cytometry assay, MTT assay, and qRT-PCR were done respectively. The result indicated that zebularine and TSA changed the expression level of the , by which induced cell apoptosis and inhibit cell growth in all three cell lines. Concluding, TSA induced its role through both extrinsic and intrinsic apoptotic pathways in three cell lines, whereas, zebularine played its role via both pathways in the SK-Hep 1cell line, it had no significant effect on gene expression in SW620 and PaCa-44 cell lines.
Masumeh Sanaei, Fraidoon Kavoosi

2756 related Products with: Effect of Zebularine in Comparison to Trichostatin A on the Intrinsic and Extrinsic Apoptotic Pathway, Cell Viability, and Apoptosis in Hepatocellular Carcinoma SK-Hep 1, Human Colorectal Cancer SW620, and Human Pancreatic Cancer PaCa-44 Cell Lines.

100 μg100ug Lyophilized100ug Lyophilized1.00 flask1.00 flask2 Pieces/Box

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#34853027   // To Up

Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes.

We assessed whether Index60, a composite measure of fasting C-peptide, 60-min C-peptide, and 60-min glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody-positive (Ab+) individuals with normal 2-h glucose values (<140 mg/dL).
Brandon M Nathan, Maria J Redondo, Heba Ismail, Laura Jacobsen, Emily K Sims, Jerry Palmer, Jay Skyler, Laura Bocchino, Susan Geyer, Jay M Sosenko

1231 related Products with: Index60 Identifies Individuals at Appreciable Risk for Stage 3 Among an Autoantibody-Positive Population With Normal 2-Hour Glucose Levels: Implications for Current Staging Criteria of Type 1 Diabetes.

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#34850014   2021/11/27 To Up

Association of high-affinity autoantibodies with type 1 diabetes high-risk HLA haplotypes.

ECL assays are high-affinity autoantibody (Ab) tests that are more specific than Abs detected by traditional radiobinding assays (RBA) for risk screening and prediction of progression to type 1 diabetes. We sought to characterize the association of high-risk HLA haplotypes and genotypes with electrochemiluminescence (ECL) positivity and levels in relatives of individuals with type 1 diabetes.
Taylor M Triolo, Laura Pyle, Hali Broncucia, Taylor Armstrong, Liping Yu, Peter A Gottlieb, Andrea K Steck

1617 related Products with: Association of high-affinity autoantibodies with type 1 diabetes high-risk HLA haplotypes.

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#34843580   2021/11/29 To Up

Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis.

Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker's organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL.
Yushi Hayashi, Hidenori Suzuki, Wataru Nakajima, Ikuno Uehara, Atsuko Tanimura, Toshiki Himeda, Satoshi Koike, Tatsuya Katsuno, Shin-Ichiro Kitajiri, Naoto Koyanagi, Yasushi Kawaguchi, Koji Onomoto, Hiroki Kato, Mitsutoshi Yoneyama, Takashi Fujita, Nobuyuki Tanaka

2041 related Products with: Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis.

100ug Lyophilized1.00 flask1 mg2 Pieces/Box100ug Lyophilized2ug96 assays10 rxns1x10e7 cells100ug Lyophilized100ug Lyophilized1.00 flask

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#34733271   2021/10/18 To Up

Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With and Smoking.

Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four SNPs, four SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in (OR: 0.82, p=0.04). rs74058715(T) in conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In -positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and (p=0.004 and p=0.008, respectively) Thus, polymorphisms associate with ACPA-positive RA, particularly in -positive individuals, and with ACPA-negative RA independently of -.
Laura Massarenti, Christian Enevold, Dres Damgaard, Niels Ødum, Peter Garred, Morten Frisch, Miriam A Shelef, Søren Jacobsen, Claus Henrik Nielsen

1544 related Products with: Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With and Smoking.

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