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In Vitro Stimulation of Murine Peritoneal Monocytes Induced by Alginates
Pasquali Paolo,Zalcman Amy,Murtas Susanna,Adone Rosanna,Brambilla Gianfranco,Marianelli Cinzia,Cagiola Monica,Ciuchini Franco The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.8
In this trial we assessed the effect of soluble alginates on murine cells. Mouse peritoneal monocytes were stimulated in vitro with a solution of alginate. The production of $TNF-\alpha$ and nitric oxide (NO), the expression of surface molecules CD80 and CD86, and the ability of monocytes to phagocyte bacteria were assessed, in order to evaluate the effect of alginate on cell functionality. We showed that mouse peritoneal monocytes stimulated with alginate produce NO and $TNF-\alpha$. In addition, alginate is able also to increase their phagocytic activity and to a lesser extent also to increase the expression of CD80. Even with different degrees, it implies that alginates per se act directly on immune response, being able to effectively stimulate proinflammatory activity. These findings corroborate the idea that alginates can represent interesting adjuvants to use to increase the efficacy of antigenic stimulation.
In Vitro Stimulation of Murine Peritoneal Monocytes Induced by Alginates
Paolo Pasquali,Amy Zalcman,Susanna Murtas,Rosanna Adone,Gianfranco Brambilla,Franco Ciuchini,Monica Cagiola,Cinzia Marianelli 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.8
In this trial we assessed the effect of soluble alginates on murine cells. Mouse peritoneal monocytes were stimulated in vitro with a solution of alginate. The production of TNF-α and nitric oxide (NO), the expression of surface molecules CD80 and CD86, and the ability of monocytes to phagocyte bacteria were assessed, in order to evaluate the effect of alginate on cell functionality. We showed that mouse peritoneal monocytes stimulated with alginate produce NO and TNF-α. In addition, alginate is able also to increase their phagocytic activity and to a lesser extent also to increase the expression of CD80. Even with different degrees, it implies that alginates per se act directly on immune response, being able to effectively stimulate proinflammatory activity. These findings corroborate the idea that alginates can represent interesting adjuvants to use to increase the efficacy of antigenic stimulation.
Cho, Byoung Chul,Dy, Grace K.,Govindan, Ramaswamy,Kim, Dong-Wan,Pennell, Nathan A.,Zalcman, Gerard,Besse, Benjamin,Kim, Joo-Hang,Koca, Goekben,Rajagopalan, Prabhu,Langer, Simon,Ocker, Matthias,Nogai, Elsevier 2018 Lung cancer Vol.123 No.-
<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>This phase Ib/II study evaluated safety, pharmacokinetics, maximum tolerated dose (MTD), and efficacy of the pan-cyclin-dependent kinase inhibitor roniciclib with cisplatin-etoposide (CIS-ETOP) or carboplatin-etoposide (CARBO-ETOP) in patients with extensive-disease small-cell lung cancer (ED-SCLC).</P> <P><B>Patients and methods</B></P> <P>In this open-label, non-randomized study, patients with previously untreated ED-SCLC received roniciclib twice daily (BID) in a 3 days on/4 days off schedule. Cisplatin 75 mg/m<SUP>2</SUP> or carboplatin (AUC5) dose was administered on day 1, and etoposide 100 mg/m<SUP>2</SUP> on days 1–3, of 21-day cycles. Phase Ib used a dose-escalation design to define the MTD for phase II. Pharmacokinetics were assessed.</P> <P><B>Results</B></P> <P>Forty-three patients received treatment (roniciclib 2.5 mg BID [+ CARBO-ETOP, n = 4; + CIS-ETOP, n = 3] and roniciclib 5 mg BID [+ CARBO-ETOP, n = 24; + CIS-ETOP, n = 12]). The MTD of roniciclib was 5 mg BID with CARBO-ETOP or CIS-ETOP. Common adverse events were nausea (90.7%) and vomiting (69.8%). Roniciclib was readily absorbed following oral administration at the MTD (median t<SUB>max</SUB> 0.5–1 h), with a 30–40% reduction in exposure when co-administered with CARBO-ETOP or CIS-ETOP; administration of roniciclib had no effect on etoposide or platinum pharmacokinetics. The response rate was 81.4% (35/43) overall and 86.1% (31/36) in the pooled roniciclib 5 mg BID population (all partial responses).</P> <P><B>Conclusion</B></P> <P>Roniciclib co-administered with chemotherapy in patients with ED-SCLC demonstrated tolerability, acceptable pharmacokinetics, and promising efficacy. An observed safety signal in a related phase II study resulted in discontinuation of the present study and termination of further roniciclib development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Phase Ib/II study of ED-SCLC patients treated with roniciclib plus chemotherapy. </LI> <LI> Combination was well tolerated and readily absorbed across all dose combinations. </LI> <LI> No clinically relevant PK interactions were observed upon concomitant treatment. </LI> <LI> Promising efficacy of roniciclib plus chemotherapy, despite low patient numbers. </LI> <LI> Unfavorable benefit/risk balance from another study led to study termination. </LI> </UL> </P>