In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

Summary.  Background:  We developed a fibrinogen γ‐chain (dodecapeptide HHLGGAKQAGDV [H12])‐coated, ADP‐encapsulated liposome (H12‐[ADP]‐liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb–IIIa and augments platelet aggregation by releasing ADP. Objective:  To evaluate the efficacy of H12‐(ADP)‐liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. Methods:  Thrombocytopenia (platelets < 50 000 μL−1) was induced in rabbits by repeated blood withdrawal (100 mL kg−1 in total) and isovolemic transfusion of autologous washed red blood cells. H12‐(ADP)‐liposomes with platelet‐poor plasma (PPP), platelet‐rich plasma (PRP), PPP, ADP liposomes with PPP or H12‐(PBS)‐liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. Results:  Administration of H12‐(ADP)‐liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24 h. Administration of H12‐(ADP)‐liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12‐(phosphate‐buffered saline)‐liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25 000 platelets μL−1), the hemostatic effects of H12‐(ADP)‐liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12‐(ADP)‐liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12‐(ADP)‐liposomes. Conclusions:  H12‐(ADP)‐liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

To identify genes that are associated with progression of malignant lymphoma, the expression profiles of 18 432 genes were analyzed in diffuse large B-cell lymphomas at early (stages I and II, 6 cases) and advanced stages (stages III and IV, 9 cases) by means of cDNA microarrays. By comparing expression profiles between localized and advanced lymphomas, a number of genes that were differentially expressed were identified: 48 genes with increased expression and 30 genes with reduced expression in advanced-stage diffuse large B-cell lymphomas. Increased expression of MPHOSPH1, RUVBL1, CHN2, PSA and CDC10 genes, and reduced expression of COL1A2, COL4A1, FBLN5, CLECSF6, MIC2, CAV1 and S100A10 genes in the advanced lymphoma group were confirmed by semi-quantitative reverse transcription-PCR. RUVBL1 and PSA expression was further confirmed by real-time quantitative PCR, whose results paralleled the microarray data. The highly expressed genes encode proteins that promote cell proliferation and the genes with reduced expression encode adhesion proteins and target protein for cytotoxic T-lymphocytes. These findings suggested that analysis with cDNA microarrays is a useful approach for identifying genes related to tumor progression and their products could be potential tumor markers or diseasespecific targets for anti-tumor therapy.

H12-(ADP)-liposomes might be a safe and effective therapeutic tool during damage control surgery for trauma patients with acute thrombocytopenia and massive bleeding.

Pyothorax-associated lymphoma (PAL) is a unique lymphoma developing in the pleural cavity after long-standing pyothorax. They are diffuse large B-cell lymphomas (DLBCLs), frequently with immunoblastic morphology, and show a strong association with Epstein-Barr virus (EBV) infection. In this study, cDNA microarray analysis was performed in six cases with PAL and 12 with nodal DLBCL. Among 5516 informative genes, 348 displayed more than 2-fold difference (higher or lower) of expression level between PAL and nodal DLBCL (P < < < <0.001). These genes are known to be involved in apoptosis, interferon response, and signal transduction. One of the most differentially expressed genes, IFI27 (interferon-α α α α-inducible protein 27) was subjected to quantitative RT-PCR analysis, and increased expression of IFI27 was confirmed. Overexpression of IFI27 was also found in cell lines derived from PAL, but not in other lymphoid cell lines. This study shows that PAL is a distinctive subtype of DLBCL not only in its clinical presentation, but also in its molecular profile. alignant lymphoma develops in the pleural cavity affected by long-standing pyothorax, usually resulted from artificial pneumothorax for the treatment of lung tuberculosis or tuberculous pleuritis.