Quantitative study of cytotoxic T-lymphocyte immunotherapy for nasopharyngeal carcinoma.

BACKGROUND: In clinical practice, the common strategy for immunotherapy of nasopharyngeal carcinoma (NPC) is to infuse cytotoxic T-lymphocyte (CTL) lines several times by intravenous injection, but it is difficult by laboratory research to investigate the relationship between treatment time-point, the amount of CTL added and the therapeutic effect. The objective of this study is to establish a mathematical model to study the therapeutic effect of different treatment time-points and amounts of CTL, and to predict the change in therapeutic effect when the percentage of EBV LMP2-specific CTL is increased from 10% to 20%. RESULTS: The concentration of epidermal growth factor receptor (EGFR) in the tumor cell cytomembranes increases after CTL is added. Concurrently, there is a marked downward trend of the phosphorylated transforming growth factor-α (TGFα)-EGFR complex in the tumor cell cytomembranes, which indicates restriction of tumor growth after CTL immunotherapy. The relationships among the time of addition of CTL, the amount of CTL added, different CTL specificities for LMP2 and the increment rate k of the total number of tumor cells were evaluated. CONCLUSIONS: The simulation results quantify the relationships among treatment time-points, amount of CTL added, and the corresponding therapeutic effect of immunotherapy for NPC.

Changes and significance of IL-25 in chicken collagen II-induced experimental arthritis (CIA).

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. It is a systemic inflammatory disease, characterized by chronic, symmetrical, multi-articular synovial arthritis. IL-25 (IL-17E) is a member of the recently emerged cytokine family (IL-17s), which is expressed in Th2 cells and bone marrow-derived mast cells. Unlike the other members of this family, IL-25 is capable of inducing Th2-associated cytokines (IL-4, IL-5, and IL-13) and also promotes the release of some pro-immune factors (IL-6 and IL-8). IL-25 is also a pleiotropic factor, which constitutes a tissue-specific pathological injury and chronic inflammation. In this study, we used chicken collagen II-induced experimental arthritis (CIA) model in DBA/1 mice to investigate the relationship between IL-25 and other inflammatory factors, revealing the possible mechanism in CIA. Our results showed that the expression level of IL-25 was enhanced in the late stage of CIA, and IL-17 was increased in the early stage of the disease. It is well known that IL-17 has a crucial role in the development of RA pathogenesis, and IL-25 plays a significant role in humoral immune. For reasons given above, we suggested that the IL-25 inhibited IL-17 expression to some extent, while enhancing the production of IL-4. It was confirmed that IL-25 not only regulated the cellular immune, but also involved the humoral immune in rheumatoid arthritis.

Complication following gastric pull-up reconstruction for advanced hypopharyngeal or cervical esophageal carcinoma: a 20-year review in a Chinese institute.

OBJECTIVES: Carcinoma of the hypopharynx and cervical esophagus is a very aggressive cancer with a high incidence of multifocal mucosal involvement and a high incidence of submucosal lymphatic spread. Total pharyngolaryngoesophagectomy and gastric pull-up reconstruction are often the procedures of choice. The aim of this study is to review the complication after gastric pull-up reconstruction in patients with advanced hypopharyngeal or cervical esophageal cancer. MATERIALS AND METHODS: A total of 208 patients undergoing gastric pull-up reconstruction for squamous cell carcinoma of the hypopharynx invading the cervical esophagus and cervical esophagus at the Affiliated Provincial Hospital of Anhui Medical University in China from 1988 to 2007 were reviewed. Of 208 patients, 124 patients had hypopharyngeal carcinoma invading cervical esophagus; and 84 patients had cervical esophageal carcinoma. The analysis focused on the most common complications and the survival following gastric pull-up reconstruction. This study and its methods have been approved by the institutional review board. RESULTS: Of the 208 patients, 87 (41.8%) developed some complications, including anastomotic leak (19, 9.1%), pneumonitis (23, 11.1%), pleural effusion (15, 7.2%), wound infection (8, 3.9%), heart failure (4, 1.9%), anastomosis stricture (7, 3.4%), chylous fistula (4, 1.9%), hemothorax (3, 1.4%), hemoperitoneum (2, 1.0%), and burst abdomen (2, 1.0%); there was no gastric necrosis. In our cases, there was no immediate operative mortality; but there were 4 hospital deaths. The average hospital stay was 15 days. CONCLUSIONS: Gastric pull-up reconstruction is a relatively safe and effective method and can be performed with low mortality and acceptable morbidity and result in good quality of lives.

Corynebacterium pyruviciproducens promotes the production of ovalbumin specific antibody via stimulating dendritic cell differentiation and up-regulating Th2 biased immune response.

Corynebacterium pyruviciproducens (C. pyruviciproducens), a newly discovered Corynebacterium, is gram-positive, non-flagellate, non-spore-forming lipophilic rod. No known pathogenic components of Corynebacteria have been found in this new bacterium, such as diphtheria toxin and tuberculostearic acid. In the present study, referring to Propionibacterium acnes (P. acnes), a well-known bacterial adjuvant, the stimulation of dendritic cells by C. pyruviciproducens was analyzed through detecting the levels of cytokine-secretion, ability of cell-proliferation and expression of membrane molecules. In addition, the effect of C. pyruviciproducens in promoting antibody production in vivo was detected. Compared with P. acnes, C. pyruviciproducens more strongly enhanced cytokine secretion including inflammatory factor IL-6 and Th1-associated molecule IL-12, and more effectively induced proliferation, activation or maturation of D2SC/1 (a murine dendritic cell line) and bone marrow-derived dendritic cells (BMDC). Vaccination studies in mice using ovalbumin (OVA) as a model antigen showed that C. pyruviciproducens effectively promoted antigen-specific humoral immune response by increasing OVA-specific antibody, Th2-biased response in spleen and high IL-4/IFN-γ ratio in serum.