Immune Regulation in Breast Cancer Metastasis and Immunotherapy

There are significant alterations in the tumor surrounding stromal cells in addition to the cancer cells in tumor microenvironment. Tumor cells can metastasize by acquiring the ability to escape immune control and surveillance. A decline in the ability of the immune cells to recognize and kill the tumor leads to tumor relapse or metastasis after primary treatment. Comprehensive review in this chapter will be conducted to further investigate into the mechanism of immune evasion in metastatic tumor microenvironment. The immune cells, stromal cells, extracellular matrix protein/component, and their interaction will be reviewed and summarized. Breast cancer has not been previously viewed as a particularly immunogenic type of tumor. Nevertheless, immune parameters have been increasingly studied in breast cancer, and accumulating data show that they are relevant for the development and progression of this tumor type. Consequently, immunotherapies of breast cancer are now tested in different clinical trials. The prospect of immunotherapy in metastatic breast cancer will be introduced. The importance of host‐targeted modulation/therapy will be increased in addition to cancer‐targeted strategies. We have to better define subpopulations of breast cancer patients to optimize the immunological way to overcome the cancer metastasis

An escherichia coli vaccine co-expressing listeriolysin-O and tumour antigen in cancer immunotherapy and the mechanisms of immune regulation

PhDSome recombinant bacterial strains have been shown to be very efficient in experimental therapies against cancer in rodent models. Amongst them is an E. coli that expresses the Listeriolysin-O protein (LLO) and a model tumour antigen ovalbumin (OVA). I have demonstrated the efficacy of E. coli-LLO/OVA in preventive or therapeutic models against OVA-expressing tumours. This effect is mediated by specific cytotoxic T-lymphocytes (CTL) against OVA antigen and inhibition of the suppressive function of Foxp3+ T-regulatory (Treg) cells. When applying a “real” and clinically-relevant tumour antigen, Wilms’ tumour-1 antigen (WT1), this vaccine (E. coli-LLO/WT1) is capable of inducing an anti-tumour effect. Furthermore, we have characterised the immunodominant epitope involved in E. coli-LLO/WT1- immunisation (pWT130-138, NAPYLPSCL) through screening of a peptide library of the WT1 protein by cytokine ELISpot, lymphocyte stimulation effects, MHC stability, and specific cytotoxicity. Also, the effect on Treg when applying a real tumour antigen is still preserved. Co-injection of pWT130-138 with E. coli-LLO resulted in an anti-tumour effect equivalent to that obtained with E. coli-LLO/WT1, demonstrating that the adjuvant properties of the E. coli-LLO vaccine can be exploited in conjunction with peptides. Treg are recognised as playing important roles in immunotherapy. An ideal vaccine for cancer would stimulate specific cytotoxic responses and suppress Treg function. This study showed that E. coli-LLO vaccine suppresses Treg cell function and the Treg RNA microarray analysis revealed expression differences of some cytokine/chemokine genes which could be relevant to the reversal of Treg suppression. This may have important implications for developing anti-tumour vaccine strategies in humans. Overall, this study demonstrated that an E. coli-LLO vaccine is effective in cancer immunotherapy, either co-expressed with a real tumour antigen or co-injected with a peptide. The efficacy of this vaccine was due to its ability to dampen Treg suppressive function

Malignant mesenchymal tumor with leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, and osteosarcoma differentiation: case report and literature review

A case of malignant mesenchymoma of the bladder containing leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, and myxomatous components is described. The primary pedunculated tumor measuring 14 × 13 × 7 cm and weighing 343 g arose from the left trigone of the bladder and was treated by total cystectomy. The histogenesis of malignant mesenchymomas and their optimal management strategy and prognosis remain uncertain. Herein, we present the fifth case of malignant mesenchymoma of the urinary bladder to be reported in the literature, which presented five unrelated differentiated tissues more than did previously reported cases

HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial fibroblasts via p38 MAPK and NF-

Synovial fibroblasts (SF) play a central role in the inflammatory and destructive process in rheumatoid arthritis (RA). High-mobility group box chromosomal protein 1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS (HMGB1-LPS) significantly facilitated SF proliferation. HMGB1 alone failed to induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS-induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels. HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation endproducts (RAGE) expression on the surface of SF. Both blockers of TLR4 and RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the production of IL-6 and MMPs, but blocking antibodies to TLR2 failed. HMGB1-LPS synergistically increased intracellular levels of phosphorylated p38 and phosphorylated I B. Furthermore, both NF-B inhibitor Bay11-7085 and p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6 and MMPs induced by HMGB1-LPS. In conclusion, HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGE expression on the surface of SF in RA and then to augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-B activation

Autophagy regulation in heme-induced neutrophil activation is associated with microRNA expression on transfusion-related acute lung injury

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of death after transfusion therapy. The pathogenesis of TRALI is associated with neutrophil activation in the lungs, causing endothelial damage and capillary leakage, and thus neutrophil extravasation. Heme-related molecules derived from the hemolysis of red blood cell components have been recognized as a stimulator, inducing neutrophil activation at TRALI. To investigate post-transcriptional changes of the neutrophil at TRALI, we performed heme-related molecules induced reactive oxygen species production in the neutrophil as a model. Neutrophils were isolated from heparinized peripheral blood and stimulated with heme-related molecules. After stimulation, reactive oxygen species production, degranulation, phagocytosis activity, and miRNA expression profile of neutrophil were analyzed by luminol assay, flow cytometry, and real-time polymerase chain reaction. The expression of miRNA targeting NADPH oxidase and autophagy in the neutrophil activation of TRALI was explored. The expression profile of miRNAs will be a useful predictor of disease severity and for the grading of patients for transfusion

Flexible Nanopaper Composed of Wood-Derived Nanofibrillated Cellulose and Graphene Building Blocks

Nanopaper has attracted considerable interest in the fields of films and paper research. However, the challenge of integrating the many advantages of nanopaper still remains. Herein, we developed a facile strategy to fabricate multifunctional nanocomposite paper (NGCP) composed of wood-derived nanofibrillated cellulose (NFC) and graphene as building blocks. NFC suspension was consisted of long and entangled NFCs (10–30 nm in width) and their aggregates. Before NGCP formation, NFC was chemically modified with a silane coupling agent to ensure that it could interact strongly with graphene in NGCP. The resulting NGCP samples were flexible and could be bent repeatedly without any structural damage. Within the NGCP samples, the high aspect ratio of NFC made a major contribution to its high mechanical strength, whereas the sheet-like graphene endowed the NGCP with electrical resistance and electrochemical activity. The mechanical strength of the NGCP samples decreased as their graphene content increased. However, the electrical resistance and electrochemical activity of the NGCP samples both rose with increasing content of graphene. The NGCPs still kept advantageous mechanical properties even at high temperatures around 300°C because of the high thermal stability of NFCs and their strong entangled web-like structures. In view of its sustainable building blocks and multifunctional characteristics, the NGCP developed in this work is promising as low-cost and high-performance nanopaper

The new genetic environment of cfr on plasmid pBS-02 in a Bacillus strain

Sir, The gene cfr, encoding a 23S rRNA methyltransferase, confers resistance to five chemically unrelated antimicrobial classes, including phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A (PhLOPSA), and has been observed mainly in staphylococcal isolates over the past decade.1–3 Our previous study reported a cfr-carrying plasmid, pBS-01, in a novel strain (BS-01) of a Bacillus species isolated from a pig farm in China.4 In our routine surveillance study on antimicrobial resistance in farm animals in 2010, another florfenicol and chloramphenicol-resistant Bacillus species strain (named BS-02) from swine faeces was identified. Gram staining, sequence analysis of the 16S rRNA and API 50CH testing associated with the API 20E system (bioMérieux, France) showed that BS-02 had an identical profile to that of strain BS-01, which suggested that BS-02 also belongs to a novel Bacillus species. Despite their identical profiles, more than six PFGE band differences were observed between BS-01 and BS-02 (data not shown), indicating that they belong to different clonal types of the same species