Description: Bacillus cereus strains harboring a pXO1-like virulence plasmid cause respiratory anthrax-like disease in humans, particularly in welders. We developed mouse models for intraperitoneal as well as aerosol challenge with spores of B. cereus G9241, harboring pBCXO1 and pBC218 virulence plasmids. Compared to wild-type B. cereus G9241, spores with a deletion of the pBCXO1-carried protective antigen gene ( pagA1 ) were severely attenuated, whereas spores with a deletion of the pBC218-carried protective antigen homologue ( pagA2 ) were not. Anthrax vaccine adsorbed (AVA) immunization raised antibodies that bound and neutralized the pagA1 -encoded protective antigen (PA1) but not the PA2 orthologue encoded by pagA2 . AVA immunization protected mice against a lethal challenge with spores from B. cereus G9241 or B. cereus Elc4, a strain that had been isolated from a fatal case of anthrax-like disease. As the pathogenesis of B. cereus anthrax-like disease in mice is dependent on pagA1 and PA-neutralizing antibodies provide protection, AVA immunization may also protect humans from respiratory anthrax-like death.

Description: In order to identify possible predictive markers, this study aimed to characterize miRNA profiles of responder and non-responder in the multimodality therapy of locally advanced esophageal cancer. Initially a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pre-therapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (pre- and post-neoadjuvant therapy). Selected miRNAs were than analyzed on pre- and posttherapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pre-therapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194, and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194, and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pre-therapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pre-therapeutic biopsies are considered as indicators of major histopathologic regression. © 2013 Wiley Periodicals, Inc.