Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen,multiple myeloma HM1.24

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per week) cytotoxic T-lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system, we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.     

Computer-aided morphometry of liver inflammation in needle biopsies

AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation. METHODS: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation, and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent. RESULTS: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%. CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.     

Mast Cells as a Potential Prognostic Marker in Prostate Cancer

Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men''s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs), infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.     

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor： A case report

Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.     

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

Background  

Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver.