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https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#1
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#2
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
BACKGROUND: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment. Unexpectedly, a recent study indicates that CpG ODNs activate human platelets via the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor glycoprotein VI. OBJECTIVE: To further analyze the mechanisms of CpG ODN-induced platelet activation and identify potential inhibitory strategies...
March 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#3
Hiroshi Kono, Hideki Fujii, Katsue Suzuki-Inoue, Osamu Inoue, Shinji Furuya, Kazuyoshi Hirayama, Yasuhiro Akazawa, Yuuki Nakata, Chao Sun, Nagaharu Tsukiji, Toshiaki Shirai, Yukio Ozaki
BACKGROUND AND AIM: The aim of the present study was to investigate the role of CLEC-2 in liver regeneration following partial liver resection in mice. MATERIALS AND METHODS: Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT), CLEC-2 deleted (KO), or CLEC-2 deleted specifically from platelets (flKO) mice were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin...
March 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28288575/lactobacillus-derived-extracellular-vesicles-enhance-host-immune-responses-against-vancomycin-resistant-enterococci
#4
Ming Li, Kiho Lee, Min Hsu, Gerard Nau, Eleftherios Mylonakis, Bharat Ramratnam
BACKGROUND: Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells. RESULTS: Our previous work has shown that probiotic conditioning C...
March 14, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28209350/n-decyl-s-trityl-r-cysteine-a-new-chiral-selector-for-green-ligand-exchange-chromatography-applications
#5
Andrea Carotti, Federica Ianni, Emidio Camaioni, Lucia Pucciarini, Maura Marinozzi, Roccaldo Sardella, Benedetto Natalini
In search for new enantioselectivity profiles, the N-decyl-S-trityl-(R)-cysteine [C10-(R)-STC] was synthesized through a one-step procedure and then hydrophobically adsorbed onto an octadecylsilica surface to generate a stable chiral stationary phase for ligand-exchange chromatography (CLEC-CSP) applications. The CLEC analysis was carried out on underivatized amino acids, by using a Cu(II) sulphate (1.0mM) containing aqueous eluent system. Most of the analysed compounds (34 out of 45) were enantiodiscriminated by the C10-(R)-STC-based CSP, with resolution factor (RS) values up to 8...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28157429/chimeric-anti-human-podoplanin-antibody-nz-12-of-lambda-light-chain-exerts-higher-antibody-dependent-cellular-cytotoxicity-and-complement-dependent-cytotoxicity-compared-with-nz-8-of-kappa-light-chain
#6
Mika K Kaneko, Shinji Abe, Satoshi Ogasawara, Yuki Fujii, Shinji Yamada, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Yasuhiko Nishioka, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG2a, lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis...
February 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28104688/mice-with-a-deficiency-in-clec-2-are-protected-against-deep-vein-thrombosis
#7
Holly Payne, Tatyana Ponomaryov, Steve P Watson, Alexander Brill
Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#8
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28028907/c-type-lectin-like-receptor-2-promotes-hematogenous-tumor-metastasis-and-prothrombotic-state-in-tumor-bearing-mice
#9
T Shirai, O Inoue, S Tamura, N Tsukiji, T Sasaki, H Endo, K Satoh, M Osada, H Sato-Uchida, H Fujii, Y Ozaki, K Suzuki-Inoue
Essentials The role of C-type lectin-like receptor-2 (CLEC-2) in cancer progression is unclear. CLEC-2-depleted mouse model is generated by using a rat anti-mouse CLEC-2 monoclonal antibody. CLEC-2 depletion inhibits hematogenous tumor metastasis of podoplanin-expressing B16F10 cells. CLEC-2 depletion prolongs cancer survival by suppressing thrombosis and inflammation. SUMMARY: Background C-type lectin-like receptor 2 (CLEC-2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells...
March 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27999992/c-type-lectins-their-network-and-roles-in-pathogen-recognition-and-immunity
#10
REVIEW
Sabine Mayer, Marie-Kristin Raulf, Bernd Lepenies
C-type lectins (CTLs) represent the most complex family of animal/human lectins that comprises 17 different groups. During evolution, CTLs have developed by diversification to cover a broad range of glycan ligands. However, ligand binding by CTLs is not necessarily restricted to glycans as some CTLs also bind to proteins, lipids, inorganic molecules, or ice crystals. CTLs share a common fold that harbors a Ca(2+) for contact to the sugar and about 18 invariant residues in a phylogenetically conserved pattern...
February 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27960039/physiologic-and-pathophysiologic-roles-of-interaction-between-c-type-lectin-like-receptor-2-and-podoplanin-partners-from-in-utero-to-adulthood
#11
REVIEW
K Suzuki-Inoue, M Osada, Y Ozaki
A platelet activation receptor, C-type lectin-like receptor 2 (CLEC-2), has been identified as a receptor for a platelet-activating snake venom, rhodocytin. CLEC-2 protein is highly expressed in platelets/megakaryocytes, and at lower levels in liver Kupffer cells. Recently, podoplanin has been revealed as an endogenous ligand for CLEC-2. Podoplanin is expressed in certain types of tumor cells, fibroblastic reticular cells (FRCs) in lymph nodes, kidney podocytes, and lymphatic endothelial cells, but not in vascular endothelial cells...
February 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27783896/continuous-sensing-photonic-lab-on-a-chip-platform-based-on-cross-linked-enzyme-crystals
#12
Mayte Conejero-Muriel, Isaac Rodríguez-Ruiz, Cristóbal Verdugo-Escamilla, Andreu Llobera, José A Gavira
Microfluidics or lab-on-a-chip technology offer clear advantages over conventional systems such as a dramatic reduction of reagent consumption or a shorter analysis time, which are translated into cost-effective systems. In this work, we present a photonic enzymatic lab-on-a-chip reactor based on cross-linked enzyme crystals (CLECs), able to work in continuous flow, as a highly sensitive, robust, reusable, and stable platform for continuous sensing with superior performance as compared to the state of the art...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27766053/new-horizon-in-platelet-function-with-special-reference-to-a-recently-found-molecule-clec-2
#13
REVIEW
Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27766044/anti-thrombotic-agents-derived-from-snake-venom-proteins
#14
REVIEW
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27578274/conservation-of-the-c-type-lectin-fold-for-accommodating-massive-sequence-variation-in-archaeal-diversity-generating-retroelements
#15
Sumit Handa, Blair G Paul, Jeffery F Miller, David L Valentine, Partho Ghosh
BACKGROUND: Diversity-generating retroelements (DGRs) provide organisms with a unique means for adaptation to a dynamic environment through massive protein sequence variation. The potential scope of this variation exceeds that of the vertebrate adaptive immune system. DGRs were known to exist only in viruses and bacteria until their recent discovery in archaea belonging to the 'microbial dark matter', specifically in organisms closely related to Nanoarchaeota. However, Nanoarchaeota DGR variable proteins were unassignable to known protein folds and apparently unrelated to characterized DGR variable proteins...
2016: BMC Structural Biology
https://www.readbyqxmd.com/read/27564251/lpmab-19-recognizes-sialylated-o-glycan-on-thr76-of-human-podoplanin
#16
Satoshi Ogasawara, Mika K Kaneko, Yukinari Kato
Human podoplanin (hPDPN) is expressed in lymphatic vessels, pulmonary type-I alveolar cells, and renal glomerulus. The hPDPN/C-type lectin-like receptor-2 (CLEC-2) interaction is involved in platelet aggregation and cancer metastasis. High expression of hPDPN in cancer cells or cancer-associated fibroblasts (CAFs) leads to a poor prognosis for cancer patients. In our previous research, we reported on several anti-hPDPN monoclonal antibodies (mAbs), including LpMab-2, LpMab-3, LpMab-7, LpMab-9, LpMab-12, LpMab-13, and LpMab-17 of mouse IgG1 subclass, which were produced using CasMab technology...
August 26, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27564117/high-clec-2-expression-associates-with-unfavorable-postoperative-prognosis-of-patients-with-clear-cell-renal-cell-carcinoma
#17
Ying Xiong, Li Liu, Yu Xia, Jiajun Wang, Wei Xi, Qi Bai, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
We enrolled a total of 277 patients who received nephrectomy due to clear cell renal cell carcinoma (ccRCC) in Zhongshan Hospital from Jan 2005 to Jun 2007. Immunohistochemistry was performed to evaluate the impact of CLEC-2 positive cell infiltration on the overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Kaplan-Meier analysis showed that high CLEC-2 positive cell infiltration in tumor tissue indicated poorer OS and RFS (OS, p < 0.001; RFS, p = 0.002). High CLEC-2 positive cell infiltration is also an independent risk factor for OS and RFS in multivariate analyses (OS, p = 0...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27559049/downregulation-of-the-syk-signaling-pathway-in-intestinal-dendritic-cells-is-sufficient-to-induce-dendritic-cells-that-inhibit-colitis
#18
Long Hang, Arthur M Blum, Sangeeta Kumar, Joseph F Urban, Makedonka Mitreva, Timothy G Geary, Armando Jardim, Mary M Stevenson, Clifford A Lowell, Joel V Weinstock
Helminthic infections modulate host immunity and may protect people in less-developed countries from developing immunological diseases. In a murine colitis model, the helminth Heligmosomoides polygyrus bakeri prevents colitis via induction of regulatory dendritic cells (DCs). The mechanism driving the development of these regulatory DCs is unexplored. There is decreased expression of the intracellular signaling pathway spleen tyrosine kinase (Syk) in intestinal DCs from H. polygyrus bakeri-infected mice. To explore the importance of this observation, it was shown that intestinal DCs from DC-specific Syk(-/-) mice were powerful inhibitors of murine colitis, suggesting that loss of Syk was sufficient to convert these cells into their regulatory phenotype...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27443248/e3-ubiquitin-ligase-chip-interacts-with-c-type-lectin-like-receptor-clec-2-and-promotes-its-ubiquitin-proteasome-degradation
#19
Miaomiao Shao, Lili Li, Shushu Song, Weicheng Wu, Peike Peng, Caiting Yang, Mingming Zhang, Fangfang Duan, Dongwei Jia, Jie Zhang, Hao Wu, Ran Zhao, Lan Wang, Yuanyuan Ruan, Jianxin Gu
C-type lectin-like receptor 2 (CLEC-2) was originally identified as a member of non-classical C-type lectin-like receptors in platelets and immune cells. Activation of CLEC-2 is involved in thrombus formation, lymphatic/blood vessel separation, platelet-mediated tumor metastasis and immune response. Nevertheless, the regulation of CLEC-2 expression is little understood. In this study, we identified that the C terminus of Hsc70-interacting protein (CHIP) interacted with CLEC-2 by mass spectrometry analysis, and CHIP decreased the protein expression of CLEC-2 through lysine-48-linked ubiquitination and proteasomal degradation...
October 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27385789/lymphovenous-hemostasis-and-the-role-of-platelets-in-regulating-lymphatic-flow-and-lymphatic-vessel-maturation
#20
REVIEW
John D Welsh, Mark L Kahn, Daniel T Sweet
Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation...
September 1, 2016: Blood
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