Objective To study the growth inhibitory effect of chemotherapeutic drugs on the pancreatic cancer cell line Aspc-1 and Bxpc-3, and the relations to the varied concentration and exposere time of chemotherapeutic drugs administrated in single or in combination. Methods Four chemotherapeutic drugs included 5-fluorouracil (5-FU), epirubicin (E-ADM), mitomycin(MMC) or cisplatin (DDP) administrating in single or in combination and using varied concentrations(d1、d2、d3 and d4) and exposure times(24、28 and 72 hours); and then the growth inhibitory effect on the two cell lines. resulted from these drugs were assayed by MTT colorimetry and analysed by “ t ” test. Results The growth inhibitory rate of two cell lines was increased, with the increment of drug concentration and/or the prolongation of exposure time ( P

BACKGROUND:More and more evidence suggests that macrophages and inflammation reactions are involved in the formation and development of nephrolithiasis. Previous studies have found that calculi crystals can stimulate macrophages to release high mobility group protein B1.
OBJECTIVE:To investigate the synergistic effect of high mobility group protein B1 in calcium phosphate induced release of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages.
METHODS:(1) The induced U937 cells were respectively stimulated with RPMI (blank), 100 mg/L calcium phosphate, 100μg/L high mobility group protein B1 and 100 mg/L calcium phosphate+100μg/L high mobility group protein B1 for 1, 2 and 4 hours to col ect cellsupernatant. (2) The induced U937 cells were respectively stimulated with 100 mg/L calcium phosphate, 100 mg/L calcium phosphate+10μg/L high mobility group protein B1, 100 mg/L calcium phosphate+50μg/L high mobility group protein B1, 100 mg/L calcium phosphate+100μg/L high mobility group protein B1 for 4 hours to col ect cellsupernatant. Levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 were determined by ELISA.
RESULTS AND CONCLUSION:The levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 in the cellculture supernatant of 100 mg/L calcium phosphate group and 100μg/L high mobility group protein B1 group were both higher than those in the blank group in a time-dependent manner (P<0.05). The levels of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 in the cellculture supernatant of different concentrations of high mobility group protein B1 groups were al higher than those in the 100 mg/L calcium phosphate group in a concentration-dependent manner (P<0.05). The results suggest that both calcium phosphate and high mobility group protein B1 can induce the release of interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages and the high mobility group protein B1 has the synergistic effect with calcium phosphate to induce interleukin-1β, interleukin-6, tumor necrosis factorαand monocyte chemotactic factor 1 from human macrophages.

G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
Bias (Epidemiology)* ; Felodipine ; GTP-Binding Proteins ; Humans ; Ligands ; Pathology* ; Physiology* ; Transducers