Objective To systematically review the effect and safety of bevacizumab as salvage treatment for Her-2 negative recurrent or metastatic breast cancer. Methods The stage III randomized controlled trials (RCTs) on chemotherapy plus bevacizumab vs. chemotherapy alone for Her-2 negative recurrent or metastatic breast cancer were collected from PubMed, EMbase, The Cochrane Library, SCI citation database and CBM. Conference abstracts in ASCO and ESMO during last three years, NCCN guideline (2012), as well as relevant Chinese journals were also retrieved manually. The retrieved literature was published from the inception of databases to February 2012. Two reviewers independently screened the literature according to inclusion and exclusion criteria, evaluated and cross-checked methodological quality, and resolved discrepancy by discussion or according to expert opinion. Then meta-analysis was conducted using STATA SE 12.0 software. Results Of 132 articles collected, a total of 4 RCTs involving 3 131 patients were included. The results of meta-analyses showed that: compared with chemotherapy alone, bevacizumab plus chemotherapy could improve the progression-free survival (PFS) for patients with Her-2 negative breast cancer (HR=0.67, 95%CI 0.57 to 0.79, P=0.001), but it could not prolong the overall survival (OS) (HR=0.92, 95%CI 0.82 to 1.02, P=0.121). Adverse effects such as hypertension, proteinuria and bleeding significantly increased in the bevacizumab group, but no statistical significance was found in thrombo-embolic event, neutropenia and sensory neuropathy between the two groups. Conclusion Bevacizumab can improve PFS rather than OS for patients with Her-2 negative recurrent or metastatic breast cancer, and it increases the Grade 3 to 4 adverse effects. It is necessary to identify the best indications of bevacizumab as salvage treatment for breast cancer.
ObjectiveTo study the effect of intercellular adhesion (ica) operon of Staphylococcus epidermidis on the inflammation associated with mixed biofilm of Staphylococcus epidermidis and Candida albicans on endotracheal tube material in rabbits. MethodsThe standard strains of Staphylococcus epidermidis RP62A (ica operon positive, positive group) and ATCC12228 (ica operon negative, negative group) were taken to prepare a bacterial solution with a concentration of 1×106 CFU/mL, respectively. Then, the two bacterial solutions were mixed with the standard strain of Candida albicans ATCC10231 of the same concentration to prepare a mixed culture solution at a ratio of 1∶1, respectively. The mixed culture solution was incubated with endotracheal tube material for 24 hours. The formation of mixed biofilm on the surface of the material was observed by scanning electron microscope. Thirty New Zealand rabbits, aged 4-6 months, were divided into two groups (n=15), and the endotracheal tube materials of the positive group and the negative group that were incubated for 24 hours were implanted beside the trachea. The body mass of rabbits in the two groups was measured before operation and at 1, 3, and 7 days after operation. At 1, 3, and 7 days after operation, the levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and monocytechemotactic protein 1 (MCP-1) were detected by using an ELISA test kit. At 7 days after operation, the formation of mixed biofilm on the surface of the endotracheal tube materials was observed by scanning electron microscope, the inflammation and infiltration of tissues around the materials were observed by HE staining, and the bacterial infections in heart, lung, liver, and kidney were observed by plate colony counting method.ResultsScanning electron microscope observation showed that the mixed biofilm structure was obvious in the positive group after 24 hours in vitro incubation, but no mixed biofilm formation was observed in the negative group. In vivo studies showed that there was no significant difference in body mass between the two groups before operation and at 1, 3, and 7 days after operation (P>0.05). Compared with the negative group, the levels of MCP-1 and IL-1β at 1 day, and the levels of IL-1β, MCP-1, IL-6, and TNF-α at 3 and 7 days in the positive group all increased, with significant differences (P<0.05). Scanning electron microscope observation showed that a large amount of Staphylococcus epidermis and mixed biofilm structure were observed in the positive group, and a very small amount of bacteria was observed in the negative group with no mixed biofilm structure. HE staining of surrounding tissue showed inflammatory cell infiltration in both groups, and neutrophils and lymphocytes were more in the positive group than in the negative group. There was no significant difference in the number of bacterial infections in heart and liver between the two groups (P>0.05). The number of bacterial infections in lung and kidney in the positive group was higher than that in negative group (P<0.05).ConclusionIn the mixed infection of Staphylococcus epidermidis and Candida albicans, the ica operon may strengthen the structure of the biofilm and the spread of the biofilm in vivo, leading to increased inflammatory factors, and the bacteria are difficult to remove and persist.