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#28939555   2017/09/23 Save this To Up

A novel therapeutic strategy for pancreatic cancer: targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC).

Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumour-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin-glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin-drug conjugate (LDC), and its safety and anti-tumour effects were evaluated. A specific affinity between rBC2LC-N (a recombinant bacterial C-type lectin) and Capan-1 was identified, and its positivity was confirmed in 69 human samples. In contrast to the belief that all lectins mediate harmful haemagglutination, rBC2LC-N did not cause haemagglutination with human erythrocytes and was safely administered to mice. The 50% inhibitory concentration of LDC to Capan-1 (1.04 pg/ml=0.0195 pmol/l) was 1/1000 lower than that reported for conventional immunotoxins. The intraperitoneal administration of LDC reduced the tumour weight from 390 mg to 130.8 mg (P<0.01) in an orthotopic model, and reduced the number of nodules from 48 to 3 (P<0.001) and improved survival from 62 to 105 days in a peritoneal dissemination model (P<0.0001). In addition, the effect of LDC was reproduced in nodules from patient-derived PDAC xenografts through intravenous injection. Herein, we show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments.

1676 related Products with: A novel therapeutic strategy for pancreatic cancer: targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC).

Lung non small cell cance Multiple lung carcinoma ( Oral squamous cell cancer Multiple pancreatic cance High density (69 cases 20 High density (69 cases 20 High density pancreatic c Pancreatic cancer test ti Multiple pancreatic cance Multiple pancreatic cance Multiple pancreatic cance Multiple pancreatic cance

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#28933966   2017/09/21 Save this To Up

Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

This study aims to evaluate and standardize the reliability of a mobile laser indirect ophthalmoscope in the induction of choroidal neovascularization (CNV) in a mouse model.

2840 related Products with: Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

Mouse Anti P. aeruginosa Mouse Anti P.aeruginosa s Mouse Anti P.aeruginosa s Mouse AntiSerratia marces Mouse AntiMRSA Target Ant Mouse Anti Salmonella typ Mouse AntiLegionella pneu Mouse Anti Shigella boydi MOUSE ANTI BOVINE ROTAVIR Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon HIV1 integrase antibody,

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#28931755   2017/09/21 Save this To Up

Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.

Blockade of immune checkpoint proteins (e.g., CTLA-4, PD-1) improves overall survival in advanced melanoma; however, therapeutic benefit is limited to only a subset of patients. Because checkpoint blockade acts by "removing the brakes" on effector T cells, the efficacy of checkpoint blockade may be constrained by the limited pool of melanoma-reactive T cells in the periphery. In the thymus, autoimmune regulator (Aire) promotes deletion of T cells reactive against self-antigens that are also expressed by tumors. Thus, while protecting against autoimmunity, Aire also limits the generation of melanoma-reactive T cells. Here, we show that Aire deficiency in mice expands the pool of CD4+ T cells capable of melanoma cell eradication and has additive effects with anti-CTLA-4 antibody in slowing melanoma tumor growth and increasing survival. Moreover, pharmacologic blockade of central T cell tolerance and peripheral checkpoint blockade in combination enhanced antimelanoma immunity in a synergistic manner. In melanoma patients treated with anti-CTLA-4 antibody, clinical response to therapy was associated with a human Aire polymorphism. Together, these findings suggest that Aire-mediated central tolerance constrains the efficacy of peripheral checkpoint inhibition and point to simultaneous blockade of Aire and checkpoint inhibitors as a novel strategy to enhance antimelanoma immunity.

2900 related Products with: Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.

Anti VGLUT 1 Rat, polyclo Anti Rat VGLUT 2, Rabbit REASTAIN® Quick Diff Kit Androgen Receptor (Phosph Androgen Receptor (Phosph Rabbit Anti-Human Androge Rabbit Anti-Human Androge Androgen Receptor (Ab 650 Anti beta3 AR Human, Poly AZD-3514 Mechanisms: Andr 17β-Acetoxy-2α-bromo-5 (5α,16β)-N-Acetyl-16-[2

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#28928458   2017/09/20 Save this To Up

Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer.

The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. This effect is dependent upon increased downstream p38/JNK pathway activation. Taken together, our data suggest that although Ras/MAPK pathway inhibition can increase tumor immunogenicity, the negative impact on T-cell activity is functionally important. This undesirable impact is effectively prevented by combination with T-cell immune agonist immunotherapies resulting in superior therapeutic efficacy.MEK inhibition in breast cancer is associated with increased tumour infiltrating lymphocytes (TILs), however, MAPK activity is required for T cells function. Here the authors show that TILs activity following MEK inhibition can be enhanced by agonist immunotherapy resulting in synergic therapeutic effects.

1569 related Products with: Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer.

Breast cancer tissue arra Breast cancer (IDC) tissu Breast cancer and adjacen Breast cancer tissue arra Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer and matched Tissue microarray of brea Breast cancer and matched Breast cancer tissue arra Breast cancer, carcinoma

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#28928164   2017/09/20 Save this To Up

ImmunoPET of malignant and normal B cells with (89)Zr- and (124)I-labeled obinutuzumab antibody fragments reveals differential CD20 internalization in vivo.

The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.

2328 related Products with: ImmunoPET of malignant and normal B cells with (89)Zr- and (124)I-labeled obinutuzumab antibody fragments reveals differential CD20 internalization in vivo.

MarkerGeneTM in vivo lacZ Normal Antibody Diluent Normal Antibody Diluent Normal Antibody Diluent Normal Antibody Diluent Normal Antibody Diluent Normal Antibody Diluent Normal Antibody Diluent Anti C Reactive Protein A anti CD20 monoclonal anti Mouse Anti-Human Interleu TGF beta induced factor 2

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#28924242   2017/09/19 Save this To Up

A new mouse expressing human Fcγ receptors to better predict therapeutic efficacy of human anti-cancer antibodies.

Leukemia accepted article preview online, 19 September 2017. doi:10.1038/leu.2017.293.

2090 related Products with: A new mouse expressing human Fcγ receptors to better predict therapeutic efficacy of human anti-cancer antibodies.

Mouse Anti-Human CA19-9 ( Mouse anti Human IgA anti Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Human IgG anti Mouse anti Human IgG anti Mouse anti Human IgG anti Mouse anti Human IgM anti Mouse anti Human IgM anti Goat Anti-Human, Mouse PS

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#28923896   2017/09/19 Save this To Up

Experimental and theoretical approaches to investigate the immunogenicity of Taenia solium-derived KE7 antigen.

Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides, with proven protective capacity against cysticercosis, are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated to membrane processes and may participate in several vital cell pathways.This study is aimed to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. TsKE7 was recombinantly expressed in Escherichia coli Rosetta 2 (rTsKE7) and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune-proteomic analysis. These Abs were then used to screen a phage-displayed 7-random peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides with the consensus motif YF/YPS sequence, which includes YYYPS (named GK-1M for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of sera from cysticercotic pigs with 100% of specificity, but induced a weak protection against murine cysticercosis.In silico analysis revealed universal T cell epitope(s) in nTsKE7, potentially capable of stimulating CTL and helper T lymphocytes under different MHC class I and class II mouse haplotypes.Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines.

2345 related Products with: Experimental and theoretical approaches to investigate the immunogenicity of Taenia solium-derived KE7 antigen.

HIV type O envelope antig Toxoplasma gondii MIC 3 r Toxoplasma gondii P24 (GR Toxoplasma gondii P29 (GR Toxoplasma gondii P30 (SA FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Human Antithrombin III to Human Plasminogen Total A Total Human uPA Antigen A

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#28923838   2017/09/19 Save this To Up

Syngeneic Mouse Models of Oral Cancer are Effectively Targeted by anti-CD44-based NIR-PIT.

Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAbs) are a potential therapy against CD44 expressing OSCC, however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber, IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic). Binding of the anti-CD44-IR700 conjugate was shown to be specific and cell-specific cytotoxicity was observed after exposure of the cells to NIR in vitro. The anti-CD44-IR700 conjugate, when assessed in vivo, demonstrated deposition within the tumor with a high tumor-to-background ratio. Tumor-bearing mice were separated into four cohorts: no treatment; 100µg of anti-CD44-IR700 i.v. only; NIR light exposure only; and 100µg of anti-CD44-IR700 i.v. with NIR light exposure. NIR-PIT therapy, compared with the other groups, significantly inhibited tumor growth and prolonged survival in all three cell model systems. In conclusion, these data reveal that anti-CD44 antibodies are suitable as mAb-photoabsorber conjugates for NIR-PIT in MOC cells.

1978 related Products with: Syngeneic Mouse Models of Oral Cancer are Effectively Targeted by anti-CD44-based NIR-PIT.

Goat Anti-Human, Mouse AR Mouse Anti-Human CA19-9 ( Mouse Anti-Human CD44 Mouse Anti-Human CD44 Rat Anti-Mouse CD44 Rat Anti-Mouse CD44 Mouse Anti-Human CD44, Bi Mouse Anti-Human CD44, Bi Rat Anti-Mouse CD44, Biot Rat Anti-Mouse CD44, Biot Mouse Anti-Human CD44 [+F Mouse Anti-Human CD44 [+F

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#28922396   2017/09/18 Save this To Up

Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1.

Leukotriene B4 (LTB4) receptor 1 (BLT1) is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1) has not been reported because a mBLT1 monoclonal antibody (mAb) has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8) that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1. Clone 7A8 did not cross-react with human BLT1 or other G protein-coupled receptors, including human chemokine (C-X-C motif) receptor 4. The 7A8 mAb binds to the second extracellular loop of mBLT1 and did not affect LTB4 binding or intracellular calcium mobilization by LTB4. The 7A8 mAb positively stained Gr-1-positive granulocytes, CD11b-positive granulocytes/monocytes, F4/80-positive monocytes, CCR2-high and CCR2-low monocyte subsets in the peripheral blood and a CD4-positive T cell subset, Th1 cells differentiated in vitro from naïve CD4-positive T cells. This mAb was able to detect Gr-1-positive granulocytes and monocytes in the spleens of naïve mice by immunohistochemistry. Finally, intraperitoneal administration of 7A8 mAb depleted granulocytes and monocytes in the peripheral blood. We have therefore succeeded in generating a high-affinity anti-mBLT1 mAb that is useful for analyzing mBLT1 expression in vitro and in vivo.

2983 related Products with: Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1.

Anti-Human, Mouse Monoclo Monoclonal Anti-c-kit SCF Monoclonal Anti-dEGF Rece Monoclonal Anti-dEGF Rece Leukotriene B4 Receptor(B Androgen Receptor , Mouse MOUSE ANTI BOVINE ROTAVIR Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Mouse, Monoclon

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#28920928   2017/09/18 Save this To Up

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

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