Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.

Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-ß, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As2O3. These findings suggested that anti-angiogenesis may be an underlying mechanism of As2O3 anticancer activity in lung cancer.

A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia.

The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non-inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.

Clinical aspects and cytokine response in adults with seasonal influenza infection.

Cytokine responses play an important role in the pathogenesis of influenza infection. Previous studies found that cytokine expressions in patients infected with the novel A (H1N1) influenza virus (nvA (H1N1)) could reflect the severity of the disease. But the patterns of cytokine response in patients infected with seasonal influenza virus and the correlations between cytokine responses and clinical data are still unknown. Seventy-two outpatients for laboratory-confirmed seasonal influenza infection were studied: twenty-four seasonal influenza A patients and forty-eight seasonal influenza B patients. Thirty healthy volunteers were enrolled as a control group. Serum samples from influenza patients obtained on the admission day and 6 days later were measured for eight cytokines using enzyme-linked immunosorbent assay (ELISA). The clinical variables were recorded prospectively. The levels of interleukin (IL)-6, IL-33 and tumor necrosis factor (TNF)-α were significantly higher in influenza A patients than those in the control group while IL-6, IL-17A, IL-29, interferon (IFN)-γ and interferon gamma-induced protein (IP)-10 were significantly higher in influenza B patients than those in the control group. Furthermore, IL-17A, IL-29 and IP-10 were increased in seasonal influenza B patients when comparing with those in the seasonal influenza A patients. A positive correlation of IL-29 levels with fever (Spearman's rho, P-values < 0.05) and a negative correlation of IFN-γ and IP-10 levels with lymphocyte count (Spearman's rho, P-values < 0.05) were found in seasonal influenza infection. While a hyperactivated proinflammatory cytokine responses were found in seasonal influenza infection, a higher elevation of cytokines (IL-17A, IL-29 and IP-10) were found in seasonal influenza B infection versus influenza A. IL-29, IFN-γ and IP-10 were important hallmarks in seasonal influenza infection, which can help clinicians make timely treatment decision for severe patients.

Applications of platelet antigen gene typing and matching in the platelet transfusion / 中国实验血液学杂志

The aim of this study was to establishment of known HPA genotype platelet donor data base and carry out the platelet antigen gene typing and matching in the platelet transfusion so as to prevent the production of the antibody and to avoid the platelet transfusion refractoriness. HPA of the donors and the patients were genotyped by PCR-SSP. The platelet transfusion with the same ABO type and HPA genotypes as the patient was selected and infused if the solid-phase agglutination matching was consistent. The results showed that the distribution of HPA types in Chinese Mudanjiang area had its own characteristics. HPA-15 had the greatest heterozygosity, and then HPA-3. The effective rate was 94.4% if both the HPA types and the ABO types were coincident while the effective rate was 77.8% when only ABO types were coincident. It is concluded that the distribution of HPA types in Chinese Mudanjiang area presents genetic polymorphism. The platelet transfusion with genetic typing and matching of both HPA and ABO types is an effective way to avoid production of the antibody and platelet transfusion refractoriness.

Interleukin-10 promoter polymorphisms and asthma risk: a meta-analysis.

Several studies assessed the associations of interleukin-10 (IL-10) polymorphisms with asthma in different populations. However, the results were inconclusive. The aim of the present study was to further assess the associations by the method of meta-analysis. Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched. Data were extracted independently by two authors. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Seventeen potentially eligible articles were identified (4478 cases and 4803 controls). Significant associations between -1082A/G and -592A/C polymorphisms and asthma were observed. However, there was no significant association between -819T/C polymorphism and asthma risk. In addition, there were significant associations of the IL-10 haplotypes with asthma. In summary, this meta-analysis suggested that IL-10 promoter polymorphisms were associated with asthma risk.

Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma.

BACKGROUND: Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting ß(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775). METHODS: A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life. RESULTS: Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated. CONCLUSIONS: In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

Repressor of GATA-3 can negatively regulate the expression of T cell cytokines through modulation on inducible costimulator.

BACKGROUND: The transcription factor, repressor of GATA-3 (ROG), can simultaneously suppress the expression of T helper cells (Th1 and Th2) cytokines. Since the suppression of Th2 cytokines by GATA-3 is well understood, it is postulated that there are other molecular targets of ROG that can suppress the expression of the Th1 cytokines. We hypothesized that ROG might suppress the stimulators of T lymphocyte cytokines such as CD3, CD28, and inducible costimulator (ICOS), or indirectly enhance the expression of cytokine suppressors such as T lymphocyte-associated antigen-4 (CTLA-4) and CD45. The objective of this study was to clarify the molecular targets of ROG involved in suppressing Th1 or Th2 cytokines. METHODS: Real-time quantitative PCR (RT-PCR) and Western blotting were performed to evaluate the mRNA and protein levels of CD3, CD28, ICOS, CTLA-4, and CD45 in Th1 and Th2 cells during various levels of ROG expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interferon-γ (IFN-γ) and interleukin (IL)-4 in culture media of Th1 and Th2 cells. RESULTS: The results showed that the mRNA and protein levels of ROG were relatively low in Th1 and Th2 cells (P < 0.01). After ROG-pcDNA3.1 transfection, the mRNA and protein level of ROG was significantly elevated, while the expression of ICOS, IFN-γ, and IL-4 was markedly down-regulated (P < 0.01). Conversely, transfection of ROG-siRNA led to inhibition of ROG expression and up-regulation of ICOS, IFN-γ and IL-4 (P < 0.01). However, the expression levels of CD3, CD28, CTLA-4 and CD45 did not change in either ROG-pcDNA3.1 or ROG-siRNA-transfected Th1 and Th2 cells (P > 0.05). CONCLUSION: It is concluded that ROG can inhibit the expression of Th1 and Th2 cytokines by down-regulating the expression of ICOS, which might be a potential molecular target for asthma treatment.

The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

BACKGROUND: A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. RESULTS: Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008). CONCLUSIONS: This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

HPA distribution characteristics of platelet donor population in Mudanjiang area of China and establishment of its database / 中国实验血液学杂志

This study was aimed to explore the distribution characteristics of the human platelet antigen (HPA) gene of human platelet donors and its polymorphism in Mudanjiang area of Heilongjiang Province in China, to determine platelet antigen system with clinical significance by judging the rate of incompatibility of HPA, as well as to establish a database of donors' HPA. The genotyping of 154 unrelated platelet donors was performed by means of PCR-SSP. The frequencies of gene and genotype were calculated and compared with that in other areas. The results showed that the genes 1a-17a of HPA-a were all expressed in the 154 healthy and unrelated platelet donors. Only genes 1b, 2b, 3b, 5b, 6b and 15b of HPA-b were expressed while genes 4b, 7b-14b, 16b were not expressed. Among the genotypes, aa homozygosity was predominant and HPA15 had the greatest heterozygosity, while HPA3 had lower heterozygosity. There were 23 combined types of HPA, 5 of them had a rate higher than 10%, and the frequencies of the other 18 were lower than 8%. HPA genotype frequencies showed a good consistency to Hardy-Weinberg equilibrium. It is concluded that the distribution of the allele polymorphism of HPA1-HPA17 in Mudanjiang area has its own characteristics, compared with other areas and some countries, the local HPA genotype database of platelet donors is established in Mudanjiang area, which can provide the matching donors for clinical use with immunological significance.

[A multi-center, randomized, controlled, double blind and double dummy clinical trial of antofloxacin hydrochloride tablet versus levofloxacin tablet for the treatment of acute bacterial infections].

OBJECTIVE: To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. METHODS: A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups. RESULTS: A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05). CONCLUSIONS: Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].

OBJECTIVE: To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS: The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS: Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia.

Arsenic trioxide (As(2)O(3)) has been established to be an effective agent for treating acute promyleocytic leukemia. Laboratory data suggest that As(2)O(3) induces apoptosis of several solid tumor cells including lung cancer cells. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we studied the cytotoxic effect of As(2)O(3) on human lung adenocarcinoma cell lines A549 and A549/R (resistant to vincristine, adriamycin and mitomycin etc.) grown under normoxic and hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 5, 10 and 15 microM As(2)O(3) induced evident growth inhibition and apoptosis in A549 cells as well as A549/R cells after 48 hours of exposure. In contrast, the conventional chemotherapeutic drug vincristine showed lowered efficiency in hypoxic A549 cells. As(2)O(3) induced G(2)/M cell cycle arrest in both normoxic and hypoxic A549 cells. As(2)O(3) significantly decreased the messenger RNA (mRNA) levels of Cyclin B(1) and survivin and the protein levels of Cyclin B(1), phospho-CDC(2) (Thr 161) and survivin in both normoxic and hypoxic A549 cells. Together, our findings indicated that As(2)O(3) significantly inhibited the proliferation of lung cancer cells via G(2)/M cell cycle arrest and induction of apoptosis at both normoxia and hypoxia, and the induction of apoptosis was associated with down regulation of survivin.

[Effects of arsenic trioxide on apoptosis and proliferation of human lung cancer cells under hypoxia].

OBJECTIVE: To observe the effects of different concentrations of arsenic trioxide (As(2)O(3)) on apoptosis and proliferation of human lung cancer cell line A549 in vitro under hypoxia and normoxia. METHODS: A549 cells were treated with 0, 1, 2, 4 micromol/L As2O3 for 12, 24 and 48 h under hypoxia (5% O(2)) and normoxia (21% O(2)). The proliferative inhibition rate of A549 cells was measured with methyl thiazolyl tetrazolium assay, and the apoptotic rate of A549 cells was detected by Annexin V/propidium iodide (PI) double staining. RESULTS: Under normoxia and hypoxia, 1, 2, 4 micromol/L As(2)O(3) could significantly inhibit the proliferation of A549 cells and induce the apoptosis of A549 cells. The results depended on the drug concentration and action time. And the hypoxia couldn't influence the effects of As(2)O(3). CONCLUSION: As(2)O(3) can inhibit the proliferation and induce the apoptosis of A549 cells under hypoxia and normoxia.

Case report: dramatic recovery of lung adenocarcinoma-associated dermatomyositis with targeted lung cancer therapy alone.

This case report details the sudden onset of severe dermatomyositis (DM) symptoms followed by rapid progression of adenocarcinoma of the lung and an obvious diminution of the primary tumor with the administration of lung cancer targeted drug therapy alone, followed by nearly complete disappearance of the DM symptoms, with no conspicuous improvement in the DM symptoms when using corticosteroids.

[A multicentre study on the pathogenic agents in 665 adult patients with community-acquired pneumonia in cities of China].

OBJECTIVE: To investigate the pathogenic causes of community-acquired pneumonia (CAP) in adult patients in China, the relation of previous antibiotic use and the Pneumonia Patient Outcome Research Team (PORT) classification to microbial etiology, and the prevalence of drug resistance of common CAP bacteria. METHODS: A prospective study was performed on 665 consecutive adult patients with CAP at 12 centers in 7 Chinese cities during one year. The etiology of pneumonia was considered if one of the following criteria was met: (1) valid sputum sample yielding one or more predominant strains; (2) blood cultures yielding a bacterial pathogen; (3) seroconversion, a > or = 4-fold increase or decrease titers of antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila. Minimum inhibitory concentration (MIC) of respiratory tract isolates was determined using the agar dilution method. RESULTS: Pathogens were identified in 324/610 patients (53.1%) with valid serum samples and sputum cultures as follows: Mycoplasma pneumoniae (126, 20.7%), Streptococcus pneumoniae (63, 10.3%), Haemophilus influenzae (56, 9.2%), Chlamydia pneumoniae (40, 6.6%), Klebsiella pneumoniae (37, 6.1%), Legionella pneumophila (31, 5.1%), Staphylococcus aureus (23, 3.8%), Escherichia coli (10, 1.6%), Moraxella catarrhalis (8, 1.3%), Pseudomonas aeruginosa (6, 1.0%). Of 195 patients with a bacterial pathogen, an atypical pathogen was identified in 62 (10.2%) cases. The non-susceptibility rate of Streptococcus pneumoniae to penicillin, azithromycin, and moxifloxacin was 20.3%, 75.4% and 4.3% respectively. CONCLUSIONS: Atypical pathogens have important role in CAP, with Mycoplasma pneumoniae being the most common pathogen, and mixed infection of atypical pathogens with bacteria was found in 10.2% of the cases. Streptococcus pneumoniae and Haemophilus influenzae remain the most important bacteria for CAP. More than 75.0% of Streptococcus pneumoniae was resistant to macrolides and 20.3% was resistant to penicillin.

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle. RESULTS: Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively. CONCLUSION: Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed.

[A study of interferon-gamma induced airway mucous cell apoptosis and its mechanisms].

OBJECTIVE: To investigate the effect of interferon-gamma (IFN-gamma) on airway mucous cells and its mechanisms. METHODS: (1) Normal human bronchial epithelial cells (NHBEs) were cultured under specific conditions, and treated by IFN-gamma for 3 days. The cells were analyzed with fluorescein isothiocyanate (FITC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. (2) Twenty wild type C57BL/6J mice were immunized and divided into 4 groups, and treated with IFN-gamma (50 ng and 100 ng, respectively), interleukin-13 (IL-13, 5 microg) and saline by nostril instillation. The mice were sacrificed and the airway mucous cells were analyzed by morphometry and TUNEL assay. RESULTS: (1) IFN-gamma induced apoptosis in NHBEs, which showed condensed nuclei, nuclear and DNA fragmentaion, and were positive by TUNEL assay. Bax was upregulated and translocated from cell plasma to mitochondria under the treatment. (2) Airway mucous cell account in 100 ng IFN-gamma instillation immunized mice group (28 +/- 6 mucous cells/mm basal lamina) was significantly decreased as compared to that in saline (58 +/- 12) and IL-13 (59 +/- 6) instillation groups (all < 0.05). There was no difference among the IFN-gamma 50 ng (48 +/- 11), saline (58 +/- 12) and IL-13 (59 +/- 6) instillation groups (all P > 0.05). TUNEL assay was also positive in airway mucous cells from IFN-gamma instillation mice as compared to saline instillation mice. CONCLUSIONS: IFN-gamma leads to airway mucous cell apoptosis by Bax upregulating and translocation into mitochondria. This might be of significance in the new therapies of asthma.

[Treatment of spontaneous metastatic lung cancer with interleukin-12 gene-modified dendritic cells vaccine].

BACKGROUND & OBJECTIVE: Although many works have been done in treatment of metastatic lung cancer, effective method is lacked. This study was designed to investigate the treatment of spontaneous metastatic lung cancer by interleukin-12 (IL-12) gene-modified dendritic cells (DC) vaccine. METHODS: The spontaneous metastatic lung cancer model, prepared by injection of the 3LL Lewis lung cancer cells into the footpads of C57BL/6 mice, were treated by subcutaneous vaccination with tumor antigen peptide Mut1-pulsed, IL-12 gene-modified dendritic cells (DC-IL-12/Mut1) derived from the normal bone marrow. After treatment, the lung weight, the number of lung metastatic nodes, the survival time of the tumor-bearing mice were observed, and the NK and CTL activities were respectively determined. RESULTS: Compared with mice treated with Mut1-pulsed, control LacZ gene modified DC and untreated DC, tumor-bearing mice treated with DC-IL-12/Mut1 had the lightest lung weights (P < 0.01), the least lung metastatic node numbers (P < 0.01), the longest survival time (P < 0.01), also with the induction of potent CTL activity (P < 0.01) and NK activity (P < 0.01). CONCLUSION: Tumor antigen-pulsed, IL-12 gene-modified dendritic cells have significant therapeutic effects on the spontaneous metastatic lung cancer, the possible mechanism involved with induction of CTL activity and enhancement of NK activity.