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#33521616   2021/01/06 To Up

Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab.

Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.
Nicholas Agresti, Jacob P Lalezari, Phillip P Amodeo, Kabir Mody, Steven F Mosher, Harish Seethamraju, Scott A Kelly, Nader Z Pourhassan, C David Sudduth, Christopher Bovinet, Ahmed E ElSharkawi, Bruce K Patterson, Reejis Stephen, Jonah B Sacha, Helen L Wu, Seth A Gross, Kush Dhody

2860 related Products with: Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab.

5/100 Packing /sleeve/bo5/200 Packing /sleeve/bo5/100 Packing /sleeve/bo5/200 Packing /sleeve/bo1 mg.5 per Sleeve, 100 Flasks/16 Arrays/Slide100 ug 5 G

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#33437400   // To Up

Carbohydrate antigen 19-9 - tumor marker: Past, present, and future.

Carbohydrate antigen 19-9 (CA 19-9) is a cell surface glycoprotein complex most commonly associated with pancreatic ductal adenocarcinoma (PDAC). Koprowski first described it in 1979 using a mouse monoclonal antibody in a colorectal carcinoma cell line. Historically, it is one of the most commonly used tumor markers for diagnosing, managing, and prognosticating PDAC. Additionally, elevated CA 19-9 levels are used as an indication for surgery in suspected benign pancreatic conditions. Another common application of CA 19-9 in the biliary tract includes its use as an adjunct in diagnosing cholangiocarcinoma. However, its clinical value is not limited to the hepatopancreatobiliary system. The reality is that the advancing literature has broadened the clinical value of CA 19-9. The potential value of CA 19-9 in patients' workup extends its reach to gastrointestinal cancers - such as colorectal and oesophageal cancer - and further beyond the gastrointestinal tract - including urological, gynecological, pulmonary, and thyroid pathologies. Apart from its role in investigations, CA 19-9 presents a potential therapeutic target in PDAC and acute pancreatitis. In a bid to consolidate its broad utility, we appraised and reviewed the biomarker's current utility and limitations in investigations and management, while discussing the potential applications for CA 19-9 in the works for the future.
Tsinrong Lee, Thomas Zheng Jie Teng, Vishal G Shelat

2474 related Products with: Carbohydrate antigen 19-9 - tumor marker: Past, present, and future.

96tests20 96tests0.1 mg96tests1x107 IFU/ml x 200ul96tests50ul (1mg/ml)1 kit(96 Wells)100 25 mg100ul

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#33352782   2020/12/19 To Up

G Cell Cycle Arrest and Extrinsic Apoptotic Mechanisms Underlying the Anti-Leukemic Activity of CDK7 Inhibitor BS-181.

In vitro antitumor activity of the CDK7 inhibitor BS-181 against human T-ALL Jurkat cells was determined. Treatment of Jurkat clones (JT/Neo) with BS-181 caused cytotoxicity and several apoptotic events, including TRAIL/DR4/DR5 upregulation, c-FLIP down-regulation, BID cleavage, BAK activation, ΔΨ loss, caspase-8/9/3 activation, and PARP cleavage. However, the BCL-2-overexpressing Jurkat clone (JT/BCL-2) abrogated these apoptotic responses. CDK7 catalyzed the activating phosphorylation of CDK1 (Thr161) and CDK2 (Thr160), and CDK-directed retinoblastoma phosphorylation was attenuated in both BS-181-treated Jurkat clones, whereas only JT/BCL-2 cells exhibited G cell cycle arrest. The G-blocker hydroxyurea augmented BS-181-induced apoptosis by enhancing TRAIL/DR4/DR5 upregulation and c-FLIP down-regulation. BS-181-induced FITC-annexin V-positive apoptotic cells were mostly in the sub-G and G phases. BS-181-induced cytotoxicity and mitochondrial apoptotic events (BAK activation/ΔΨ loss/caspase-9 activation) in Jurkat clones I2.1 (FADD-deficient) and I9.2 (caspase-8-deficient) were significantly lower than in A3 (wild-type). Exogenously added recombinant TRAIL (rTRAIL) markedly synergized BS-181-induced apoptosis in A3 cells but not in normal peripheral T cells. The cotreatment cytotoxicity was significantly reduced by the DR5-blocking antibody but not by the DR4-blocking antibody. These results demonstrated that the BS-181 anti-leukemic activity is attributed to extrinsic TRAIL/DR5-dependent apoptosis preferentially induced in G-arrested cells, and that BS-181 and rTRAIL in combination may hold promise for T-ALL treatment.
Shin Young Park, Ki Yun Kim, Do Youn Jun, Su-Kyeong Hwang, Young Ho Kim

2250 related Products with: G Cell Cycle Arrest and Extrinsic Apoptotic Mechanisms Underlying the Anti-Leukemic Activity of CDK7 Inhibitor BS-181.

0.1ml (1mg/ml)1 kit100ul100 μg100 μg1 kit100 μg1 kit12 ml

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#33251159   2020/11/05 To Up

Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis.

Microglia initiates and sustains the inflammatory reaction that drives the pathogenesis of pneumococcal meningitis. The expression of the G-protein cannabinoid receptor type 2 (CB2) in the brain is low, but is upregulated in glial cells during infection. Its activation down-regulates pro-inflammatory processes, driving microglia towards an anti-inflammatory phenotype. CB2 agonists are therefore therapeutic candidates in inflammatory conditions like pneumococcal meningitis. We evaluated the effects of JWH-133, a specific CB2 agonist on microglial cells, inflammation, and damage driven by and in experimental pneumococcal meningitis.
Steven D Pan, Denis Grandgirard, Stephen L Leib

2428 related Products with: Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis.

50ul100 μg200ul100ug100 μg96 wells (1 kit)100ug100.00 ug100ug200ul200ul

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#32820271   2020/08/20 To Up

A phase 1b/2 study of duvelisib in combination with FCR (DFCR) for frontline therapy for younger CLL patients.

Fludarabine, cyclophosphamide, and rituximab (FCR) is highly effective initial therapy for younger patients with chronic lymphocytic leukemia (CLL); however, most eventually relapse. Duvelisib is a delta/gamma PI3K inhibitor approved for relapsed/refractory CLL. We conducted an investigator-initiated, phase 1b/2 study of duvelisib + FCR (DFCR) as initial treatment for CLL patients aged ≤65. A standard 3 + 3 design included two dose levels of duvelisib (25 mg qd and 25 mg bid). Duvelisib was given for 1 week, then with standard FCR added for up to six 28-day cycles, then up to 2 years of duvelisib maintenance. Thirty-two patients were enrolled. The phase 2 dose of duvelisib was identified as 25 mg bid. Hematologic toxicity was common, and all-grade non-hematologic toxicities included transaminitis (28%), febrile neutropenia (22%), pneumonia (19%), and colitis (6%). The best overall response rate by ITT was 88% (56% CR/CRi and 32% PR). The best rate of bone marrow undetectable minimal residual disease (BM-uMRD) by ITT was 66%. The rate of CR with BM-uMRD at end of combination treatment (primary endpoint) was 25%. Three-year PFS and OS are 73 and 93%, respectively. DFCR is active as initial therapy of younger CLL patients. Immune-mediated and infectious toxicities occurred and required active management.
Matthew S Davids, David C Fisher, Svitlana Tyekucheva, Mikaela McDonough, John Hanna, Brandon Lee, Karen Francoeur, Josie Montegaard, Oreofe Odejide, Philippe Armand, Jon Arnason, Jennifer R Brown

2838 related Products with: A phase 1b/2 study of duvelisib in combination with FCR (DFCR) for frontline therapy for younger CLL patients.

1 G250 mg100Tests 1 G 500 G250 ml 1 G10 mg100ug 1 G

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#32817707   2020/08/20 To Up

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome.
Malgorzata Mikulska, Laura Ambra Nicolini, Alessio Signori, Antonio Di Biagio, Chiara Sepulcri, Chiara Russo, Silvia Dettori, Marco Berruti, Maria Pia Sormani, Daniele Roberto Giacobbe, Antonio Vena, Andrea De Maria, Chiara Dentone, Lucia Taramasso, Michele Mirabella, Laura Magnasco, Sara Mora, Emanuele Delfino, Federica Toscanini, Elisa Balletto, Anna Ida Alessandrini, Federico Baldi, Federica Briano, Marco Camera, Ferdinando Dodi, Antonio Ferrazin, Laura Labate, Giovanni Mazzarello, Rachele Pincino, Federica Portunato, Stefania Tutino, Emanuela Barisione, Bianca Bruzzone, Andrea Orsi, Eva Schenone, Nirmala Rosseti, Elisabetta Sasso, Giorgio Da Rin, Paolo Pelosi, Sabrina Beltramini, Mauro Giacomini, Giancarlo Icardi, Angelo Gratarola, Matteo Bassetti

2444 related Products with: Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

5 mg100 μg5 mg100 μg1 ml100 μg10 Inserts of 96 Tips/Uni200ug

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#32795349   2020/08/14 To Up

Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial.

Sintilimab blocks the interaction between programmed death-1 (PD-1) and its ligands. The safety and efficacy of sintilimab combined with oxaliplatin/capecitabine (CapeOx) as first-line treatment were evaluated in patients with gastric (G)/gastroesophageal junction (GEJ) adenocarcinoma in a phase Ib clinical trial.
Haiping Jiang, Yulong Zheng, Jiong Qian, Chenyu Mao, Xin Xu, Ning Li, Cheng Xiao, Huan Wang, Lisong Teng, Hui Zhou, Shuyan Wang, Donglei Zhu, Bo Peng, Lin Shen, Nong Xu

1423 related Products with: Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial.



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