Search

Background To investigate the relationship between hematologic test results and the predictive effect of regression of esophageal cancer after neoadjuvant chemotherapy (NACT), we analyzed pre- NACT hematologic data and their relationship to tumor regression. Methods Thirty-eight consecutive patients with locally advanced squamous cell esophageal carcinoma who had undergone two cycles of paclitaxel/carboplatin NACT were enrolled. On the day prior to the first cycle of chemotherapy, hematologic tests, including routine blood test and biochemical examinations, were recorded. All patients were confirmed to have no history of hepatitis. Surgical resection was performed when clinical restaging showed effective regression. Histopathological examination was routinely performed to evaluate the postoperative effects of chemotherapy. Results After two cycles of NACT, tumor imaging evaluation showed that 27 of the 38 patients had CR and PR, including 25 patients who underwent radical esophagectomies. Six patients had stable disease and five patients had progressive disease. According to the hematologic test results before NACT, patients with higher white blood cell counts, lymphocyte percentages, mononuclear cell counts, neutrophilic granulocyte counts, and eosinophilic granulocyte counts and lower alanine aminotransferase (ALT) level had a significantly greater opportunity for an effective response. Conclusion Basal host immunologic function and hepatic function are associated with tumor response to NACT in patients with esophageal cancer. These parameters may have a certain predictive efficacy on NACT for esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to be participated in tumor development. The association between hnRNP A1 and liver cancer and the functional role of hnRNP A1 in liver cancer have never been reported. Herein, hnRNP A1-specific single-stranded DNA aptamer, BC15, was used to (a) evaluate hnRNP A1 expression in liver cancer, and (b) treat hepatocarcinoma by acting as an inhibitor of hnRNP A1. Results showed that there is high hnRNP A1 expression in liver cancer including serum a-feto- protein--negative liver cancer tissues compared with either para-cancer or benign controls. Down regulation of hnRNP A1 expression by RNA interference inhibits the proliferation and migration of cancerous HepG2 cells, while overexpression of hnRNP A1 in normal HL-7702 cells increased the proliferation and migration of the cells. Importantly, BC15 showed a stronger inhibiting effect on the proliferation of cultured hepatoma cells than hnRNP A1 small interfering RNA, strongly suggesting that BC15 could also be a potential drug candidate for an hnRNP A1 inhibitor besides its prospect utility in in situ histological examination. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is one of the major cariogenic bacteria in the oral environment. Small non-coding RNAs (sRNAs) play important roles in the regulation of bacterial growth, stress tolerance, and virulence. In this study, we experimentally verified the existence of sRNA, L10-Leader, in S. mutans for the first time. Our results show that the expression level of L10-Leader was growth-phase dependent in S. mutans and varied among different clinical strains of S. mutans. The level of L10-Leader in S. mutans UA159 was closely related to the pH value, but not to the concentrations of glucose and sucrose in culture medium. We predicted target mRNAs of L10-Leader bioinformatically and found that some of these mRNAs were related to growth and stress response. Five predicted mRNA targets were selected and detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and we found that the expression levels of these mRNAs were closely related to the level of L10-Leader at different growth phases of the bacteria. Our results indicate that L10-Leader may play an important role in the regulation of responses in S. mutans, especially during its growth phase and acid adaption response. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus ribonuclease III belongs to the enzyme family known to degrade double-stranded RNAs. It has previously been reported that RNase III cannot influence cell growth but regulates virulence gene expression in S. aureus. Here we constructed an RNase III inactivation mutant (Δrnc) from S. aureus 8325-4. It was found that the extracellular proteins of Δrnc were decreased. Furthermore, we explored how RNase III regulated the production of the extracellular proteins in S. aureus. We found during the lag phase of the bacterial growth cycle RNase III could influence the extracellular protein secretion via regulating the expression of secY2, one component of accessory secretory (sec) pathway. After S. aureus cells grew to exponential phase, RNase III can regulate the expression of extracellular proteins by affecting the level of RNAIII. Further investigation showed that the mRNA stability of secY2 and RNAIII was affected by RNase III. Our results suggest that RNase III could regulate the pathogenicity of S. aureus by influencing the level of extracellular proteins via two different ways respectively at different growth phases. [ABSTRACT FROM AUTHOR]

The Hfq protein is reported to be an RNA chaperone, which is involved in the stress response and the virulence of several pathogens. In E. coli, Hfq can mediate the interaction between some sRNAs and their target mRNAs. But it is controversial whether Hfq plays an important role in S. aureus. In this study, we found that the deletion of hfq gene in S. aureus 8325-4 can increase the surface carotenoid pigments. The hfq mutant was more resistant to oxidative stress but the pathogenicity of the mutant was reduced. We reveal that the Hfq protein can be detected only in some S. aureus strains. Using microarray and qRT-PCR, we identified 116 genes in the hfq mutant which had differential expression from the wild type, most of which are related to the phenotype and virulence of S. aureus. Among the 116 genes, 49 mRNAs can specifically bind Hfq protein, which indicates that Hfq also acts as an RNA binding protein in S. aureus. Our data suggest that Hfq protein of S. aureus is a multifunctional regulator involved in stress and virulence. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor alpha (TNF-α) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-α (hTNF-α) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-α. We performed screening peptide library against anti-hTNF-α antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-α. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80-91 aa) of hTNF-α proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-α biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-α. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-α and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a major human pathogen. Pathogenic effects are largely due to production of bacterial toxins, whose synthesis is controlled by an mRNA molecule termed RNAIII. The S. aureus protein called RAP (RNAIII-activating protein) is secreted and activates RNAIII production by inducing the phosphorylation of its target protein TRAP (target of RAP). Antibodies to TRAP have been shown to suppress exotoxin production by S. aureus in vitro, suggesting that TRAP may be a useful vaccine target site. Here we showed that a peptide TA21 was identified by screening a phage display library using anti-TRAP antibodies. Mice vaccinated with Escherichia coli engineered to express TA21 on their surface (FTA21) were protected from S. aureus infections, using sepsis and cellulitis mice models. By sequence analysis, it was found that the TA21 is highly homologous to the C-terminal sequence of TRAP which is conserved among S. aureus and Staphylococcus epidermidis, suggesting that peptide TA21 may be a useful broad vaccine to protect from infection caused by various staphylococcal strains. [ABSTRACT FROM AUTHOR]