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1.
Experimental & Molecular Medicine ; : 293-302, 2012.
Article Dans Anglais | WPRIM | ID: wpr-186640

Résumé

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.


Sujets)
Animaux , Cricetinae , Humains , Souris , Anticorps monoclonaux/génétique , Cytotoxicité à médiation cellulaire dépendante des anticorps , Conduits biliaires intrahépatiques/effets des médicaments et des substances chimiques , Cellules CHO , Adhérence cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Cholangiocarcinome/traitement médicamenteux , Modèles animaux de maladie humaine , Endocytose/effets des médicaments et des substances chimiques , Immunoglobuline G/génétique , Tumeurs du foie/traitement médicamenteux , Souris nude , Transplantation tumorale , Molécule d'adhérence cellulaire neurale L-1/génétique , Liaison aux protéines , Structure tertiaire des protéines , Protéines de fusion recombinantes/immunologie
2.
Experimental & Molecular Medicine ; : 343-352, 2007.
Article Dans Anglais | WPRIM | ID: wpr-201420

Résumé

Asthma was induced by the sensitization and challenge with ovalbumin (OVA) in mice. B-cell activating factor (BAFF) plays a role in mature B cell generation and maintenance. Here, we investigated whether, BAFF expression was changed in OVA-induced mice and whether the control of BAFF expression level alleviates the symptom of bronchial asthma. BAFF expression was detected in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues. BAFF protein was also increased in OVA-induced mouse serum. The increased BAFF transcripts was detected in OVA-induced mouse splenocytes. OVA-induced asthma was associated with the increased number of eosinophils in bronchoalveolar lavage fluid (BALF). When TACI:Fc scavenging soluble BAFF was injected to OVA-induced mice, a significant inhibition was detected in the thickness of airway smooth muscle and glycol-containing cellular elements in airway that were visualized by hematoxylin/eosin Y and periodic acid-Schiff staining, respectively. In addition, when mice were treated with TACI:Fc protein, BAFF protein level was decreased in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues compared to control mice. When compared to OVA-induced control, TACI:Fc treatment reduced the percentage of non-lymphoid cells and no changes were detected in lymphoid cell population. Hypodiploid cell formation in BALF was decreased by OVA-challenge but it was recovered by TACI:Fc treatment. Collectively, data suggest that asthmatic symptom could be alleviated by scavenging BAFF and then BAFF could be a novel target for the develpoment of anti-asthmatic agents.


Sujets)
Animaux , Femelle , Humains , Souris , Apoptose , Asthme/induit chimiquement , Facteur d'activation des lymphocytes B/biosynthèse , Bronches/métabolisme , Liquide de lavage bronchoalvéolaire/cytologie , Granulocytes éosinophiles/anatomopathologie , Fragments Fc des immunoglobulines/génétique , Immunoglobuline G/génétique , Lymphocytes/anatomopathologie , Souris de lignée BALB C , Ovalbumine , Alvéoles pulmonaires/métabolisme , Protéines de fusion recombinantes/génétique , Rate/métabolisme , Protéine TACI/génétique
3.
Southeast Asian J Trop Med Public Health ; 2004 Jun; 35(2): 408-15
Article Dans Anglais | IMSEAR | ID: sea-34197

Résumé

A study of epidemic transmission of Chikungunya virus (CHIK) was initiated in April 1999 in Yogyakarta, Indonesia. Three hundred seventeen volunteers from three kelurahans (sub-districts) were recruited. Anti-CHIK IgG antibodies were detected in 68% to 74% of cases and 28% to 32% of controls. In the kelurahan with no reported CHIK illness, 29% of cases and 28% of controls had anti-CHIK IgG antibodies. None of these cases demonstrated anti-CHIK IgM antibodies. In the two kelurahans with disease activity, anti-CHIK IgM antibodies were detected in 3% to 36% of cases, with the highest percentage from the kelurahan with recently reported cases. Ten percent of controls from Gowok had anti-CHIK IgM detected in their serum. Twelve acutely ill volunteers were later included from the kelurahan Pilahan for virus identification. Samples from two volunteers were culture- and RT-PCR-positive for CHIK. This is the first documentation of epidemic transmission of CHIK in Indonesia since 1982.


Sujets)
Adulte , Infections à alphavirus/sang , Anticorps antiviraux/génétique , Virus du chikungunya/immunologie , Épidémies de maladies , Femelle , Humains , Immunoglobuline G/génétique , Immunoglobuline M/génétique , Indonésie/épidémiologie , Mâle , RT-PCR , Études séroépidémiologiques
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