Inhibition of metastasis of syngeneic murine melanoma in vivo and vasculogenesis in vitro by monoclonal antibody C11C1 targeted to domain 5 of high molecular weight kininogen

Abstract We have shown that human high molecular weight kininogen is proangiogenic due to release of bradykinin. We now determined the ability of a murine monoclonal antibody to the light chain of high molecular weight kininogen, C11C1, to inhibit tumor growth compared to isotype-matched murine IgG. Monoclonal antibody C11C1 efficiently blocks binding of high molecular weight kininogen to endothelial cells in a concentration-dependent manner. The antibody significantly inhibited growth of human colon carcinoma cells in a nude mouse xenograft assay and was accompanied by a significant reduction in the mean microvascular density compared to the IgG control group. We also showed that a hybridoma producing monoclonal antibody C11C1 injected intramuscularly exhibited markedly smaller tumor mass in a syngeneic host compared to a hybridoma producing a monoclonal antibody to the high molecular weight kininogen heavy chain or to an unrelated plasma protein. In addition, tumor inhibition by purified monoclonal antibody C11C1 was not due to direct antitumor effect because there was no decrease of tumor cell growth in vitro in contrast to the in vivo inhibition. Our results indicate that monoclonal antibody C11C1 inhibits angiogenesis and human tumor cell growth in vivo and has therapeutic potential for treatment of human cancer. (Blood. 2004;104:2065-2072)

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Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor

Biological Chemistry ◽

10.1515/hsz-2012-0291 ◽

2013 ◽

Vol 394 (3) ◽

pp. 385-391 ◽

Cited By ~ 11

Author(s):

Thomas Kryza ◽

Gilles Lalmanach ◽

Marion Lavergne ◽

Fabien Lecaille ◽

Pascale Reverdiau ◽

...

Keyword(s):

Molecular Weight ◽

Endothelial Cells ◽

High Molecular Weight ◽

High Molecular Weight Kininogen ◽

Kinin Receptor ◽

Angiogenic Effect ◽

Lung Endothelial Cells ◽

Carboxy Terminal

Abstract Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway. We studied whether KLK12 had an impact on angiogenesis and the activation of kinin receptor B2 results from the KLK12-dependent generation of kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating a fragment containing the carboxy-terminal end of kinins. The kininogenase activity of KLK12 was poor, however, due to the cleavage resistance of the N-terminal side of the kinin sequence. A very low amount of kinins was accordingly released after in vitro incubation of high molecular weight kininogen with KLK12 and thus the proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release.

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In Vitro and in Vivo Antigen-Induced Release of High-Molecular Weight Neutrophil Chemotactic Activity from Human Nasal Tissue

American Journal of Rhinology ◽

10.2500/105065888781693221 ◽

1988 ◽

Vol 2 (1) ◽

pp. 7-11 ◽

Cited By ~ 4

Author(s):

T. Nagakura ◽

T. Onda ◽

Y. likura ◽

T. Endo ◽

H. Nagakura ◽

...

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Nasal Polyps ◽

Gel Filtration ◽

Chemotactic Activity ◽

Nasal Tissue ◽

Nasal Secretions ◽

Neutrophil Chemotactic Activity

High molecular weight neutrophil chemotactic activity has been identified in resected human nasal polyps, inferior turbinates, and nasal secretions following antigen challenge. The estimated molecular weight, by gel filtration chromatography, was approximately 600,000. However, a heterogeneity of molecular weight in some patients was recognized. Our results suggest a possible role for high molecular weight-neutrophil chemotactic activity in the pathogenesis of hypersensitivity in the human nasal cavity.

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An Assessment of the Bioactivity of Coffee Silverskin Melanoidins

Foods ◽

10.3390/foods8020068 ◽

2019 ◽

Vol 8 (2) ◽

pp. 68 ◽

Cited By ~ 6

Author(s):

Silvia Tores de la Cruz ◽

Amaia Iriondo-DeHond ◽

Teresa Herrera ◽

Yolanda Lopez-Tofiño ◽

Carlos Galvez-Robleño ◽

...

Keyword(s):

Molecular Weight ◽

Dietary Fiber ◽

High Molecular Weight ◽

Research Work ◽

Weight Fraction ◽

High Molecular Weight Fraction ◽

Total Dietary Fiber ◽

Coffee Silverskin

Melanoidins present in coffee silverskin, the only by-product of the roasting process, are formed via the Maillard reaction. The exact structure, biological properties, and mechanism of action of coffee silverskin melanoidins, remain unknown. This research work aimed to contribute to this novel knowledge. To achieve this goal, melanoidins were obtained from an aqueous extract of Arabica coffee silverskin (WO2013004873A1) and was isolated through ultrafiltration (>10 kDa). The isolation protocol was optimized and the chemical composition of the high molecular weight fraction (>10 kDa) was evaluated, by analyzing the content of protein, caffeine, chlorogenic acid, and the total dietary fiber. In addition, the structural analysis was performed by infrared spectroscopy. Antioxidant properties were studied in vitro and the fiber effect was studied in vivo, in healthy male Wistar rats. Melanoidins were administered to animals in the drinking water at a dose of 1 g/kg. At the fourth week of treatment, gastrointestinal motility was evaluated through non-invasive radiographic means. In conclusion, the isolation process was effective in obtaining a high molecular weight fraction, composed mainly of dietary fiber, including melanoidins, with in vitro antioxidant capacity and in vivo dietary fiber effects.

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Arabidopsis Dynamin-Like 2 That Binds Specifically to Phosphatidylinositol 4-Phosphate Assembles into a High-Molecular Weight Complex in Vivo and in Vitro

PLANT PHYSIOLOGY ◽

10.1104/pp.010450 ◽

2001 ◽

Vol 127 (3) ◽

pp. 1243-1255 ◽

Cited By ~ 26

Author(s):

Yong-Woo Kim ◽

Dae-Sup Park ◽

Seung-Cheol Park ◽

Sung Hee Kim ◽

Gang-Won Cheong ◽

...

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

High Molecular Weight Complex ◽

Phosphatidylinositol 4

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MEKK1 activates both IκB kinase α and IκB kinase β

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.95.16.9319 ◽

1998 ◽

Vol 95 (16) ◽

pp. 9319-9324 ◽

Cited By ~ 293

Author(s):

Frank S. Lee ◽

Robert T. Peters ◽

Luan C. Dang ◽

Tom Maniatis

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Mitogen Activated Protein Kinase ◽

Site Specific ◽

Iκb Kinase ◽

Mitogen Activated Protein ◽

Bona Fide ◽

Factor Α

A critical step in the signal-induced activation of the transcription factor NF-κB is the site-specific phosphorylation of its inhibitor, IκB, that targets the latter for degradation by the ubiquitin–proteasome pathway. We have previously shown that mitogen-activated protein kinase/ERK kinase kinase 1 (MEKK1) can induce both this site-specific phosphorylation of IκBα at Ser-32 and Ser-36 in vivo and the activity of a high molecular weight IκB kinase complex in vitro. Subsequently, others have identified two proteins, IκB kinase α (IKK-α) and IκB kinase β (IKK-β), that are present in a tumor necrosis factor α-inducible, high molecular weight IκB kinase complex. These kinases are believed to directly phosphorylate IκB based on the examination of the kinase activities of IKK immunoprecipitates, but more rigorous proof of this has yet to be demonstrated. We show herein that recombinant IKK-α and IKK-β can, in fact, directly phosphorylate IκBα at Ser-32 and Ser-36, as well as homologous residues in IκBβ in vitro, and thus are bona fide IκB kinases. We also show that MEKK1 can induce the activation of both IKK-α and IKK-β in vivo. Finally, we show that IKK-α is present in the MEKK1-inducible, high molecular weight IκB kinase complex and treatment of this complex with MEKK1 induces phosphorylation of IKK-α in vitro. We conclude that IKK-α and IKK-β can mediate the NF-κB-inducing activity of MEKK1.

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High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613897 ◽

2000 ◽

Vol 83 (05) ◽

pp. 709-714 ◽

Cited By ~ 11

Author(s):

T. Mauron ◽

B. Lämmle ◽

W. A. Wuillemin

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Coagulation Factor ◽

Cleavage Sites ◽

High Molecular Weight Kininogen ◽

Surface Binding ◽

Amino Acid Sequence Analysis ◽

Sds Page ◽

System Activation

SummaryWe investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligandblotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels. Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326.In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.

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FRACTIONATION OF LIVER SOMATOMEDIN ACTIVITY BY ULTRAFILTRATION

Journal of Endocrinology ◽

10.1677/joe.0.0620355 ◽

1974 ◽

Vol 62 (2) ◽

pp. 355-361 ◽

Cited By ~ 4

Author(s):

JENNIFER M. DEHNEL ◽

P. D. McCONAGHEY ◽

M. J. O. FRANCIS

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Weight Fraction ◽

Low Molecular Weight ◽

High Molecular Weight Fraction ◽

Cartilage Growth ◽

The Relationship ◽

Somatomedin Inhibitors

SUMMARY Plasma somatomedin is the intermediary through which growth hormone (GH) exerts its effects on the growing skeleton. Somatomedin activity may be produced in vitro by perfusion of the liver and kidneys of rats with Waymouth's medium containing GH. The relationship between the activity of plasma somatomedin and somatomedin of hepatic and renal origin has yet to be clarified. Somatomedin from plasma can be separated into active fractions of both high and low molecular weight. Similarly, ultrafiltration of medium containing somatomedin of hepatic origin indicates the existence of two active fractions, one of high molecular weight (greater than 50000) and one of low molecular weight (less than 1000). The latter can be attributed to the release of amino acids, such as serine and glutamine, by the perfused tissue. The high molecular weight fraction is believed to represent GH-dependent somatomedin. Fractions that inhibit production of cartilage matrix are present in liver perfusates as well as in plasma. These results provide further evidence that the liver is a source of GH-dependent somatomedin in vivo. Furthermore, cartilage growth may be controlled not only by the GH-stimulated release of somatomedin by the liver, but also by its release of acid-labile somatomedin inhibitors.

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