Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826.

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m  + cisplatin 50 mg/m or carboplatin AUC 5) with or without bevacizumab 15 mg/kg.

Involvement of the βγ subunits of G proteins in the cAMP response induced by stimulation of the histamine H1 receptor.

Stimulation of the histamine H1 receptor has been shown to enhance adenosine 3', 5'-cyclic monophosphate (cAMP) accumulation in various cell types but, to date, the mechanism by which this occurs is still unclear. In the present study, we examined the possibility that the betagamma subunits of G proteins (G betagamma) are involved in this process in cultured Chinese hamster ovary cells transfected with the human histamine H1 receptor (CHO-H1). Histamine increased intracellular cAMP levels in a concentration-dependent manner in CHO-H1 cells, and this histamine action was abolished by pyrilamine (1 microM).

MaxiK channel-triggered negative feedback system is preserved in the urinary bladder smooth muscle from streptozotocin-induced diabetic rats.

MaxiK channel, the large-conductance Ca2+-sensitive K+ channel, facilitates a negative feedback mechanism to oppose excitation and contraction in various types of smooth muscles including urinary bladder smooth muscle (UBSM). In this study, we investigated how the contribution of MaxiK channel to the regulation of basal UBSM mechanical activity is altered in streptozotocin-induced diabetic rats. Although the urinary bladder preparations from both control and diabetic rats were almost quiescent in their basal mechanical activities, they generated spontaneous rhythmic contractions in response to a MaxiK channel blocker, iberiotoxin (IbTx).

Influence of receptor number on the cAMP response to forskolin in Chinese hamster ovary cells transfected with human beta2-adrenoceptor.

We examined the basal adenosine 3',5'-cyclic monophosphate (cAMP) levels and forskolin-induced cAMP accumulation in cultured Chinese hamster ovary cells (CHO) expressing different levels of human beta(2)-adrenoceptors. Both the basal and forskolin-induced cAMP accumulation in the cells that express higher density of beta(2)-adrenoceptors (CHO-beta(2)/H; 560 fmol/mg protein) were larger than those in the cells that express lower density of beta(2)-adrenoceptors (CHO-beta(2)/L; 270 fmol/mg protein). In addition, isoproterenol-induced cAMP accumulation was also augmented as the number of beta(2)-adrenoceptors was increased.

Lidocaine attenuates muscarinic receptor-mediated inhibition of adenylyl cyclase in airway smooth muscle.

We examined how lidocaine affects muscarinic receptor-mediated inhibition of adenylyl cyclase in bovine tracheal smooth muscles. Lidocaine (100 microM) augmented the relaxant responses to forskolin in the bovine tracheal smooth muscle contracted with methacholine (0.3 microM).

Relaxant effect of YM976, a novel phosphodiesterase 4 inhibitor, on bovine tracheal smooth muscle.

Effects of 4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one (YM976), a novel and selective phosphodiesterase type 4 inhibitor, on tension and adenosine 3',5'-cyclic monophosphate (cAMP) content of bovine tracheal smooth muscle were compared with those of rolipram and theophylline. YM976, rolipram and theophylline relaxed the tracheal preparations contracted with histamine in a concentration-dependent manner. The relaxant effects of YM976 and rolipram were more potent than those of theophylline.

Possible involvement of Ca2+-independent phospholipase A2 in protease-activated receptor-2-mediated contraction of rat urinary bladder.

Possible involvement of Ca(2+)-independent phospholipase A2 (iPLA2) was examined in protease-activated receptor-2 (PAR-2)-mediated contraction of the rat urinary bladder. Both PAR-2 activating peptide (PAR-2 AP; SLIGRL-NH2) and trypsin produced a concentration-dependent contractile response in the urinary bladder preparations. These contractions were significantly (p<0.

Augmentation of rat urinary bladder relaxation mediated by beta1-adrenoceptors in experimental diabetes.

We examined how diabetes affects the beta-adrenoceptor subtypes mediating relaxation of rat urinary bladder smooth muscle contracted with carbachol. The relaxant responses to isoproterenol were larger in muscles from rats 8 to 10 weeks after induction of diabetes with streptozotocin (80 mg/kg, i.p.

Protease-activated receptor-2-mediated contraction in the rat urinary bladder: the role of urinary bladder mucosa.

The role of protease-activated receptor-2 (PAR-2) in the regulation of the rat urinary bladder contractility was investigated. Both trypsin and PAR-2 activating peptide (SLIGRL-NH(2)) produced a concentration-dependent contractile response in the urinary bladder preparations. These contractions were abolished by removal of the urinary bladder mucosa and were significantly reduced by indomethacin (10 microM).

Inhibitory mechanism of BRL37344 on muscarinic receptor-mediated contractions of the rat urinary bladder smooth muscle.

We examined the inhibitory mechanism of BRL37344, a beta-adrenoceptor agonist that is considered to be specific to beta(3)-subtype, on muscarinic receptor-mediated contraction of the rat urinary bladder smooth muscle. BRL37344 produced apparently biphasic concentration-relaxation curves in the urinary bladder smooth muscle contracted with carbachol (0.6 microM).