Role of Pertussis Toxin-sensitive G Protein-coupled Receptor Signaling in the Proliferation of Bone Marrow Mesenchymal Stem Cells / 대한혈액학회지

BACKGROUND: Bone marrow (BM) mesenchymal stem cells (MSCs) can be expanded over 20~30 cell doublings in vitro even in the absence of any growth factors. However, the mechanisms that govern MSC proliferation are not well understood. METHODS: We investigated the role of signaling of the pertussis toxin (PTX)-sensitive G protein-coupled receptor in the proliferation of BM MSCs. RESULTS: PTX inhibited the proliferation of human BM MSCs and murine BM stromal MS-5 cells in a dose-dependent manner. Among the chemokines produced by the BM stromal cells, stromal cell-derived factor-1 (SDF-1) enhanced the proliferation of BM MSCs, while MIP-1alpha, MCP-3 or RANTES did not. PTX also inhibited the proliferation of some fibroblasts, such as MRC-5 and NIH-3T3, but did not affect the proliferation of HeLa and HSF cells. HSF cells did not express CXCR4 mRNA, but did produce SDF-1. In contrast, HeLa cells expressed CXCR4 strongly on the cell surface, but did not produce SDF-1. BM MSCs, MS-5, MRC-5, and NIH-3T3 cells all expressed CXCR4 minimally on the cell surface. These cells, however, had abundant CXCR4 protein in their cytoplasm, which was demonstrated by flow cytometric analysis performed after permeabilization of the cells. In addition, an ELISA performed on the culture supernatants of the cells revealed that these cells constitutively produce and secrete SDF-1. CONCLUSION: These results indicate that the signaling through the PTX-sensitive G protein-coupled receptor, which is induced by autocrine factors, plays an important role in the proliferation of BM MSCs and in some fibroblasts, and that SDF-1 is the most probable candidate for the autocrine growth factor.

A Case of Recurrent Solid Pseudopapillary Tumor of the Pancreas with Involvement of the Spleen and Kidney / Journal of the Korean Cancer Association, 대한암학회지

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic tumor of an unknown etiology that is usually diagnosed in adolescent girls and young women. Most SPTPs are considered to be benign and only rarely metastasize. We report here on a 27-year old woman with recurrent SPTP with involvement of both the spleen and left kidney at the time of the initial diagnosis, and with aggressive behavior. In July 1995, she was admitted with abdominal discomfort and mass. She underwent exploratory laparotomy with distal pancrea tectomy, left nephrectomy and splenectomy, and was diagnosed with SPTP with invasion to both the spleen and left kidney. In June 2001, she again presented with abdominal pain and was diagnosed as having recurrence of the tumor. She underwent mass excision and omentectomy. Then she was lost to follow-up. In November 2005, she presented once again with an abdominal mass and was diagnosed with recurred SPTP, which formed a huge intraperitoneal mass with peritoneal seeding and the tumor showed multiple metastases in the liver. She is currently being treated conservatively.

Prognostic Significance of Biomarkers of Diffuse Large B-cell Lymphomas / 대한혈액학회지

BACKGROUND: Biomarkers of lymphomas identified by immunostaining of lymphoma tissues were recently found to have a prognostic value for diffuse large B-cell lymphoma (DLBL). Thus, it seems likely that the prognostic prediction of lymphomas might be improved by incorporating biological markers into well known prognostic systems. METHODS: To determine the clinical significance of the biological markers expressed in DLBL, 26 patients, with de novo DLBL, were retrospectively studied at the Chungnam National University Hospital. Archival specimens from the patients were stained with antibodies for the bcl-2, bcl-6, Ki-67, CD 10, IRF-4, Granzyme-B, MHC-II and p16 antigens. Two immunophenotypic patterns of DLBL were identified by the pattern of differentiation; the germinal center (GC, CD10+/-/Bcl-6+/IRF-4-)-like subgroup and the post germinal center (pGC, CD10+/-/bcl-6+/-/IRF4+)-like subgroup. RESULTS: The median age of the subjects was 56 years, ranging form 37 to 69. After a median follow up duration of 48 months, the median survival time was 44 month, ranging from 1~100 months. The five-year overall survival rate Using the Kaplan-Meier method was 32%. The only biomarker affecting the survival was bcl-2 (P=0.009). The survival of the GC-like subgroup was superior to that of the pGC-like subgroup, but without statistical significance (P=0.064). Among 18 patients with IPI scores 0~2, those expressing bcl-2 (P=0.002) and the pGC-like subgroup had a worse prognosis compared to the GC-like subgroup (P=0.049). CONCLUSION: The prognostic assessment of DLBL patients might be improved by the addition of immunohistochemical profiles, especially for bcl-2, to the traditional IPI system.