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BACKGROUND/AIMS@#Few studies have addressed whether there are differences in clinical efficacy between intravenous methylprednisolone (methyl-Pd) and intravenous immunoglobulin (IVIg) use.@*METHODS@#We retrospectively compared platelet responses and toxicities associated with these two treatments in adult patients with immune thrombocytopenia. Patients received intravenous methyl-Pd therapy followed by oral prednisolone (Pd) from 1993 to 2002 and IVIg together with oral Pd from 2003 to 2008.@*RESULTS@#Early response and maintenance of the response were assessed at 7 days and 6 months after treatment, respectively. Of the 87 patients enrolled, 77 (88.5%) were eligible for analysis. Early responses occurred in 30 of 39 patients (76.9%) receiving methyl-Pd versus 33 of 38 patients (86.6%) receiving IVIg (p = 0.187). The response was maintained in 28 patients (71.8%) in the methyl-Pd arm and in 23 patients (60.5%) in the IVIg arm (p = 0.187). The time to a complete response in the IVIg arm (6 days; range, 1 to 35) was shorter than that in the methyl-Pd arm (13.5 days; range, 2 to 29) (p = 0.002). Side effects were mild and tolerable in both arms. Five years after initiating treatment, 7 of 18 patients (38.9%) and five of 14 patients (35.7%) were still maintaining a response in the methyl-Pd and IVIg arms, respectively.@*CONCLUSIONS@#These results indicate that neither the early response rate nor the long-term outcome differed between the methyl-Pd and IVIg treatments. However, IVIg induced a complete response more rapidly than did methyl-Pd.
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BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Subject(s)
Humans , Colon , Colonic Neoplasms , Colorectal Neoplasms , Liver , Lung , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Rectal Neoplasms , Rectum , Republic of KoreaABSTRACT
No abstract available.
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PURPOSE: There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment. MATERIALS AND METHODS: We selected patients with advanced non-small cell lung cancer (NSCLC) who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Thirty-five patients were enrolled. Response rate was 22.9% (complete response, 0 patients [0%]; partial response, eight patients [22.9%]; stable disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2 months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41 months). Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles. CONCLUSION: Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.
Subject(s)
Humans , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Disease-Free Survival , Drug Therapy , NeutropeniaABSTRACT
BACKGROUND: Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro. METHODS: The effects of bortezomib on the survival and proliferation of the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane cell migration was evaluated using the Transwell system. A short interfering RNA strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the migration and localization of myeloma cells, MS-5 monolayers were treated with bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma cells. RESULTS: Bortezomib inhibited BMSC proliferation in a concentration-dependent manner, and induced cellular apoptosis. Bortezomib decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment of BMSC monolayers reduced the tendency of myeloma cells to locate to positions under the monolayers. CONCLUSION: Bortezomib inhibits the survival and growth of BMSCs via downregulation of CXCL12, which may contribute to the clinical effects of this agent.
Subject(s)
Humans , Apoptosis , Cell Line , Cell Movement , Down-Regulation , Mesenchymal Stem Cells , Multiple Myeloma , RNA, Messenger , RNA, Small Interfering , BortezomibABSTRACT
PURPOSE: The aim of this study is to determine the diagnostic and prognostic role of baseline spinal magnetic resonance imaging (MRI) in patients with multiple myeloma. MATERIALS AND METHODS: We enrolled patients newly diagnosed with multiple myeloma from 2004-2011 at a single center. Abnormal MRI findings that were not detected in radiographs have been analyzed and categorized as malignant compression fractures or extramedullary plasmacytoma. The bone marrow (BM) infiltration patterns on MRI have been classified into five categories. RESULTS: A total of 113 patients with a median age of 65 years (range, 40 to 89 years) were enrolled in the study. Malignant compression fractures not detected in the bone survey were found in 26 patients (23.0%), including three patients (2.6%) with no related symptoms or signs. Extramedullary plasmacytoma was detected in 22 patients (19.5%), including 15 (13.3%) with epidural extension of the tumor. Of these 22 patients, 11 (50.0%) had no relevant symptoms or signs. The presence of malignant compression fractures did not influence overall survival; whereas non-epidural extramedullary plasmacytoma was associated with poor overall survival in the multivariate analysis (hazard ratio, 3.205; 95% confidence interval [CI], 1.430 to 9.845; p=0.042). During the follow-up for a median of 21 months (range, 1 to 91 months), overall survival with the mixed BM infiltrative pattern (median, 24.0 months; 95% CI, 22.9 to 25.1 months) was shorter than those with other patterns (median 56 months; 95% CI, 48.9 to 63.1 months; p=0.030). CONCLUSION: These results indicate that spine MRI at the time of diagnosis is useful for detecting skeletal lesions and predicting the prognosis in patients with multiple myeloma.
Subject(s)
Humans , Bone Marrow , Diagnosis , Follow-Up Studies , Fractures, Compression , Magnetic Resonance Imaging , Multiple Myeloma , Multivariate Analysis , Plasmacytoma , Prognosis , SpineABSTRACT
BACKGROUND: The C-X-C chemokine receptor 7 (CXCR7) has been shown to be a decoy receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid leukemia (AML) cells in vitro. METHODS: CXCR7 mRNA was knocked down in AML cells by using small interfering RNA (siRNA) technology, and subsequent biological alterations in the cells were evaluated in vitro. RESULTS: All AML cell lines examined in this study (U937, K562, KG1a, HL-60, and MO7e) and primary CD34+ cells obtained from patients with AML expressed CXCR7 mRNA at various levels. Western blotting showed that all AML cells produced CXCR7. Furthermore, all AML cells expressed CXCR7 in both the cytoplasm and on the cell surface at various levels. Stromal cell-derived factor-1 (SDF-1; C-X-C motif ligand 12 (CXCL12)) induced internalization of cell surface CXCR7. However, neither hypoxia nor the examined hematopoietic growth factors (interleukin-1beta (IL-1beta), IL-3, IL-6, granulocyte-colony-stimulating factor, granulocyte, macrophage-colony-stimulating factor, and stem cell factor) and proinflammatory cytokines (interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha) were found to alter cell surface CXCR7 expression. The transfection of AML cells with CXCR4 siRNA, but not CXCR7 siRNA, significantly impaired the CXCL12-induced transmigration of the cells. The transfection of AML cells with CXCR7 siRNA did not affect the survival or proliferation of these cells. Knockdown of CXCR7, but not CXCR4, induced the upregulation of CXCL12 mRNA expression and CXCL12 production in AML cells. CONCLUSION: CXCR7 is involved in the regulation of autocrine CXCL12 in AML cells.
Subject(s)
Humans , Hypoxia , Apoptosis , Blotting, Western , Cell Line , Cell Proliferation , Cytokines , Cytoplasm , Granulocytes , Intercellular Signaling Peptides and Proteins , Interleukin-3 , Interleukin-6 , Leukemia, Myeloid, Acute , Necrosis , RNA, Messenger , RNA, Small Interfering , Stem Cells , Transfection , Up-RegulationABSTRACT
BACKGROUND: There has been no report on the clinical features or natural history of autoimmune hemolytic anemia (AIHA) in the Korean adult population. This study retrospectively analyzed the clinical characteristics and long-term outcomes of AIHA in the Korean adults. METHODS: Patients newly diagnosed with AIHA between January 1994 and December 2010 at Chungnam National University Hospital were enrolled. Patient characteristics at diagnosis, response to treatment, and the natural course of the disease were documented. RESULTS: Thirty-two patients (31 females and 1 male) with a median age of 48 years (range, 17-86) were enrolled. Of these, 21.9% were initially diagnosed with secondary AIHA. Thirteen patients (40.6%) were initially diagnosed with Evans' syndrome. Of the 29 patients who were placed on therapy, 27 (93.1%) showed a partial response or better. Nevertheless, 1 year after initiating treatment, 80% of the patients were still treatment-dependent. During follow-up (median length 14 months; range, 0.5-238), 14 of 25 patients (56.0%) who were initially diagnosed with primary warm antibody AIHA were found to have systemic lupus erythematosus (SLE). Median time to conversion to SLE was 8.0 months (95% CI, 4.3-11.7), and the probabilities of conversion at 12 and 24 months were 63% and 91%, respectively. Younger age (<60 years) and a positive fluorescent anti-nuclear antibody test were associated with a higher probability of SLE conversion (P=0.01 and P<0.001, respectively). CONCLUSION: Primary AIHA is rare. Regular, vigilant testing for SLE is required in patients initially diagnosed with AIHA.
Subject(s)
Adult , Female , Humans , Anemia, Hemolytic, Autoimmune , Follow-Up Studies , Lupus Erythematosus, Systemic , Natural History , Retrospective Studies , ThrombosisABSTRACT
BACKGROUND: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. METHODS: The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34+ cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. RESULTS: AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10-5 M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. CONCLUSION: The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.
Subject(s)
Humans , Annexin A5 , Apoptosis , Cell Count , Cell Line , Cell Proliferation , Flow Cytometry , Hematopoietic Stem Cells , Heterocyclic Compounds , Leukemia , Leukemia, Myeloid , Oligopeptides , Pertussis Toxin , Phosphorylation , Receptors, CXCR4ABSTRACT
BACKGROUND: Hypocellularity of bone marrow (BM), not associated with significant dyshematopoiesis, is often found in patients with isolated thrombocytopenia, but its clinical implications have not been studied. We prospectively studied the clinical features and natural history of these patients. METHODS: Adults with isolated thrombocytopenia (platelet counts 50x10(9)/L in 16 patients (80%). BM cellularity ranged from 5% to 25% (median, 15%) and was 150x10(9)/L) after 12, 56 and 66 months. Three patients developed pancytopenia after 11, 70 and 90 months. Two patients were consistent with moderate aplastic anemia, and 1 was confirmed as having refractory cytopenia with multilineage dysplasia. In the remainder of the patients, platelet counts remained unchanged. CONCLUSION: Isolated thrombocytopenia accompanied by hypocellular marrow encompasses a group of heterogeneous conditions.
Subject(s)
Adult , Aged , Humans , Male , Anemia, Aplastic , Bone Marrow , Chromosome Aberrations , Follow-Up Studies , Hyperplasia , Myelodysplastic Syndromes , Natural History , Pancytopenia , Platelet Count , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic , ThrombocytopeniaABSTRACT
BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/blood , Chi-Square Distribution , Glucocorticoids/therapeutic use , Lupus Coagulation Inhibitor/blood , Prednisolone/therapeutic use , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/blood , Thrombocythemia, Essential/blood , ThrombosisABSTRACT
PURPOSE: AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro. MATERIALS AND METHODS: The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay). RESULTS: AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions. CONCLUSION: AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.
Subject(s)
Humans , Annexin A5 , Apoptosis , Cell Line , Cell Proliferation , Flow Cytometry , GTP-Binding Proteins , Hematopoietic Stem Cells , Heterocyclic Compounds , Interleukin-6 , Multiple Myeloma , Oligopeptides , Pertussis Toxin , PhosphorylationABSTRACT
Osteosclerotic myeloma is a rare entity, characterized by single or multiple osteosclerotic bone lesions and usually accompanied by a polyneuropathy syndrome (POEMS). Multiple myeloma with osteosclerotic lesions without polyneuropathy is exceedingly rare. We report a case of multiple myeloma associated with multifocal osteosclerotic lesions without any evidence of POEMS. A 48-year-old woman presented with incidentally found osteosclerosis of 8th thoracic vertebra on a plain chest film. Bone survey, CT scan, MR scan, and radioisotope scintigraphy revealed multiple localized osteoclerosis; serum protein immunofixation showed IgG, lambda monoclonal gammopathy. A biopsy of T8 vertebral body disclosed plasma cell myeloma. Given that there was no organ or tissue damage other than multifocal osteosclerosis, the patient was placed on close observation with regular examination. This case indicates that although rare, multiple myeloma should be included in the differential diagnosis of sclerotic bone lesions.
Subject(s)
Female , Humans , Middle Aged , Biopsy , Diagnosis, Differential , Immunoglobulin G , Multiple Myeloma , Osteosclerosis , Paraproteinemias , Polyneuropathies , Spine , ThoraxABSTRACT
Central nervous system (CNS) myelomatosis, which is the presence of monoclonal plasma cells in the cerebrospinal fluid (CSF), is extremely rare. We report a case of CNS myelomatosis developed in a 45-year-old woman with multiple myeloma in complete response, which was achieved by allogeneic peripheral blood stem cell transplantation using a reduced-intensity conditioning regimen consisting of melphalan, fludarabine, and antithymocyte globulin. Two months after the transplant, she developed a moderate motor and sensory weakness in both lower extremities. Atypical plasma cells were found in the CSF, and immunofixation revealed monoclonal light chain in the CSF. She was given three courses of weekly intra-thecal chemotherapy consisting of methotrexate, cytarabine, and dexamethasone, which cleared the CSF. This case indicates that the allogeneic transplantation could not control CNS myelomatosis, despite successfully treating the bone marrow myeloma.
Subject(s)
Female , Humans , Middle Aged , Antilymphocyte Serum , Bone Marrow , Central Nervous System , Cytarabine , Dexamethasone , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Light , Lower Extremity , Melphalan , Methotrexate , Multiple Myeloma , Nervous System , Peripheral Blood Stem Cell Transplantation , Plasma Cells , Transplantation, Homologous , Transplants , VidarabineABSTRACT
BACKGROUND: The question as to whether stromal cell-derived factor-1 (SDF-1) stimulated myeloma cell growth has been controversial. We explored the possibility that SDF-1 may function as an autocrine growth factor of myeloma cells. METHODS: CD138+ primary bone marrow myeloma cells and myeloma cell lines (RPMI8226, U266, and ARH77) were used. Chemotaxis in response to SDF-1 of the cells was analyzed using Transwells(TM). Cell proliferation was measured by a colorimetric assay. SDF-1 mRNA expression was analyzed by RT-PCR (reverse-transcription-polymerase chain reaction). SDF-1 and interleukin-6 (IL-6) receptor expression as well as signaling molecule phosphorylation levels, were examined using Western blot analysis. Concentrations of SDF-1 in the cell culture supernatants were measured by ELISA assay. RESULTS: SDF-1 alone had no discernible effect on the proliferation of CD138+ primary myeloma cells or myeloma cell lines. In contrast, SDF-1 significantly enhanced IL-6-induced proliferation of these cells. SDF-1 up-regulated the expression of IL-6 receptor and enhanced phosphorylation of AKT in an additive manner with IL-6. Co-culture of the myeloma cells with umbilical vein endothelial cells over-expressing the SDF-1 gene revealed that SDF-1 played an important role in not only the migration of the cells underneath the stromal cells but also the proliferation of the cells in contact with stromal cells. All the myeloma cell lines expressed SDF-1 mRNA, and SDF-1 was detected in the culture supernatants of the cells. The G protein-coupled receptor inhibitor, pertussis toxin, inhibited the proliferation of these cells in suspension cultures. CONCLUSION: SDF-1, most likely in concert with IL-6, enhanced the proliferation of myeloma cells in a both paracrine and autocrine manner.
Subject(s)
Blotting, Western , Bone Marrow , Cell Culture Techniques , Cell Line , Cell Proliferation , Chemotaxis , Coculture Techniques , Endothelial Cells , Enzyme-Linked Immunosorbent Assay , Interleukin-6 , Mesenchymal Stem Cells , Multiple Myeloma , Pertussis Toxin , Phosphorylation , Receptors, Interleukin-6 , RNA, Messenger , Stromal Cells , Umbilical VeinsABSTRACT
PURPOSE: The chemokine receptor CXCR4 plays a role in the metastasis and progression of a broad range of malignant tumors; however, its influence on hepatocellular carcinoma (HCC) is not well defined. Thus, we analyzed the expression of CXCR4 and its functions in HCC cell lines in vitro. MATERIALS AND METHODS: Five HCC cell lines (HepG2, Hep3B, SK-HEP-1, NCI-H630 and PLC/PRF5) were investigated. The CXCR4 expression was analyzed by RT-PCR, Western blotting, flow cytometry and immunofluorescence staining. In addition, the effects of stromal cell-derived factor-1 (SDF-1) on the migration, proliferation and survival of the cells were investigated, as well as the SDF-1-induced phosphorylation of signaling molecules. RESULTS: All five cell lines had abundant CXCR4 in their cytoplasm, whereas a cell surface CXCR4 expression was only detected in a very small population of PLC/ PRF5 cells. In contrast, SDF-1 bound to all the cells. SDF-1 induced the phosphorylation of AKT and ERK1/2 in the PLC/PRF5 cells and the phosphorylation of Stat3, AKT and ERK1/2 in the Hep3B cells. Nonetheless, SDF-1 did not induce migration or proliferation in any of the cells, nor did it rescue the cells from serum deprivation-induced apoptosis. Recruitment of CXCR4 from the cytoplasm to the cell surface was not elicited by dexamethasone, proinflammatory cytokines or VEGF. Hypoxia increased both the cytoplasmic and cell surface expressions of CXCR4 in only the PLC/PRF5 cells. CONCLUSIONS: CXCR4 is trapped in the cytoplasm and it is not recruited to the cell surface by standard extrinsic stimuli in the majority of HCC cell lines, and the result of this is a negligible response to SDF-1.
Subject(s)
Hypoxia , Apoptosis , Blotting, Western , Carcinoma, Hepatocellular , Cell Line , Cytokines , Cytoplasm , Dexamethasone , Flow Cytometry , Fluorescent Antibody Technique , Neoplasm Metastasis , Phosphorylation , Vascular Endothelial Growth Factor AABSTRACT
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.
Subject(s)
Humans , Bone Marrow , Cell Proliferation , Chemokine CCL3 , Chemokine CCL5 , Chemokines , Cytoplasm , Enzyme-Linked Immunosorbent Assay , Fibroblasts , HeLa Cells , Intercellular Signaling Peptides and Proteins , Mesenchymal Stem Cells , NIH 3T3 Cells , Pertussis Toxin , RNA, Messenger , Stromal Cells , Whooping CoughABSTRACT
Lymphomatoid granulomatosis (LG) is a potentially malignant lymphoproliferative disorder. The lung is the most common involved site, followed by the skin and nervous system. However, LG of the central nervous system presenting with Parkinsonism is very rare. We report a patient with LG who presented with parkinsonian features such as bilateral rigidity, bradykinesia, and agitation. Brain magnetic resonance imaging showed multifocal punctuate enhanced lesions in both supra- and infratentorial areas. Steroid pulse therapy resulted in a dramatical improvement in the symptoms and MRI abnormalities.
Subject(s)
Humans , Brain , Central Nervous System , Dihydroergotamine , Hypokinesia , Lung , Lymphomatoid Granulomatosis , Lymphoproliferative Disorders , Magnetic Resonance Imaging , Nervous System , Parkinsonian Disorders , SkinABSTRACT
Limbic encephalitis is a rare neurological syndrome, which develops after stem cell transplantation, and is characterized by a series of neurological symptoms, including retrograde amnesia, behavioral disturbance, and progressive intellectual deterioration and high signal intensity in the hippocampus on magnetic resonance imaging (MRI). Herein is described the case of a patient with limbic encephalitis, which developed after allogeneic bone marrow transplantation, and was possibly due to HHV-6 infection. An 18-year-old man, with acute lymphoid leukemia, who underwent HLA-matched unrelated donor bone marrow transplantation, developed a fever and chill accompanied by neurological symptoms, including behavioral disturbance and retrograde amnesia, during the bone marrow recovery phase. A brain MRI revealed bright signal-intensity in both hippocampi. Examination of his cerebrospinal fluid suggested viral encephalitis. Based on these findings, a diagnosis of viral limbic encephalitis was highly suspected. Tests for casual causes of viral limbic encephalitis, including the CMV, HZV and HSV-1 and 2, in serum or CSF were all negative. The encephalitis responded well to ganciclovir therapy.
Subject(s)
Adolescent , Humans , Amnesia, Retrograde , Bone Marrow , Bone Marrow Transplantation , Brain , Cerebrospinal Fluid , Diagnosis , Encephalitis , Encephalitis, Viral , Fever , Ganciclovir , Herpesvirus 1, Human , Herpesvirus 6, Human , Hippocampus , Limbic Encephalitis , Magnetic Resonance Imaging , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Stem Cell Transplantation , Stem Cells , Unrelated DonorsABSTRACT
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.