Distinct roles of cholinergic receptors in small cell lung cancer cells.

BACKGROUND: Cholinergic receptors are expressed in small cell lung cancer (SCLC); however, the distinct functions of muscarinic cholinergic receptor 3 (mAChR3) and the nicotinic cholinergic receptor (nAChR) in SCLC have not yet been completely elucidated. MATERIALS AND METHODS: RT-PCR and Western blotting were used to investigate the expression of cholinergic receptors. Flow cytometry was used to detect the integrin expression. Cell proliferation, adhesion and migration assays were carried out in vitro to determine the roles of the cholinergic receptors in SBC3 human SCLC cells. RESULTS: Both mAChR3 and nAChR were expressed in the SBC3 cells. Acetylcholine iodide (Ach) stimulated SBC3 cell proliferation, adhesion and migration toward fibronectin (Fn). The mAChR3 antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), or the nAChR antagonist, mecamylamine hydrochloride (Meca), inhibited SBC3 cell proliferation in the presence or the absence of exogenous Ach. 4-DAMP abrogated cell adhesion and migration toward Fn induced by Ach, while Meca had no effect. Interestingly, Ach did not alter Fn receptor (alphavbeta1 or alpha5beta1 integrin) expression, while anti-beta1 integrin antibody or anti-alphav and anti-alpha5 integrin antibody completely abrogated cell adhesion to Fn induced by Ach. CONCLUSION: Both mAChR3 and nAChR are expressed in SCLC. SBC3 cell proliferation is regulated in vitro through both cholinergic receptors. In contrast, SBC3 cell migration and adhesion toward Fn are modulated only by mAChR. Moreover, the stimulatory effects of Ach on cell adhesion and migration through mAChR3 are presumably modulated by functional alteration of alphavbeta1 and alpha5beta1 integrin, but not by any variation in their expression. The mAChR3 antagonist may therefore be a beneficial therapeutic modality for SCLC patients, especially those with chronic obstructive pulmonary disease (COPD) as a comorbidity.

[Clinical study of teicoplanin in the treatment of patients with gram-positive cocci: the Chinese experience].

OBJECTIVE: To evaluate the efficacy and safety of Teicoplanin (TEC) in the treatment of Chinese patients with moderate and severe Gram positive (G(+)) coccus infections. METHODS: A prospective, multicenter, non-comparator control, open-label drug clinical trial of phase IV was conducted. RESULTS: Totally 156 cases with established and highly suspected G(+) coccus infections are enrolled. Mean age was 53.6 +/- 20.9 (9-93). The infections included: lower respiratory tract infections (66.0%), sepsis (9.0%), catheters-associated infections (5.1%), endocarditis (1.9%), leucopenia with fever (14.1%), bone-joint infections (1.3%), skin-soft tissue infections (7.7%), and other infections (10.9%). Eighty seven point eight percent of the patients suffered from severe underlying diseases, 28.2% (44/156) had immunocompromised conditions. 69.2% had received antibiotics previously (57.4% with cephalosporins and 28.7% with carbapenem, respectively). One hundred and thirty strains of G(+) cocci were isolated from 123 patients (78.8%). Among them methicillin-resistant Staphylococcus aureus (MRSA) accounted for 90.7% (49/54) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) 88.2% (30/34). The TEC susceptibility test for 105 strains showed that all of the Staphylococci and Enterococci were susceptible. In 121 strains tested for vancomycin, all of the Staphylococci but only 78.3% (18/23) of the Enterococci were susceptible. There were 18 strains of Gram negative bacilli and 1 strain of Candida A. isolated concomitantly with G(+) cocci from 17 cases. The total clinical effectiveness was 82.1% by ITT (156 cases) analysis and 85.2% by PP (135 cases) analysis, respectively. Bacteriologic eradication rate was 87.7%. Thirty three patients with negative culture result were empirically treated with TEC and had 96.8% of clinical effectiveness. The efficacy of TEC to different infections was similar. The total adverse effects, such as decrease in blood cells and transient abnormal liver functions, accounted only for 1.28%. CONCLUSIONS: Teicoplanin was a very effective antibiotic for G(+) coccus infections and safe for patients. In highly suspected infections with methicillin-resistant Staphylococci or Enterococci, TEC may be a choice for initial empirical treatment.