BACKGROUND: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin-3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. METHODS: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. RESULTS: The number of CD41a+ cells were 0.54+/-0.05x10(4) (rhIL-11 100 ng/ml), 5.32+.-0.23x10(4) (rhIL-3 100 ng/ml), and 8.76+/-0.15x10(4) (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to 7.47+/-0.69x10(4) (rhIL-3 rhIL-11), 11.92+/-0.19x10(4) (rhTPO rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid media including various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. CONCLUSION: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically
Blood Platelets ; Fetal Blood* ; Humans ; Interleukin-11* ; Interleukin-3 ; Megakaryocytes ; Thrombopoietin ; Umbilical Cord*

PURPOSE: High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report. MATERIALS AND METHODS: We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals. RESULTS: Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths. CONCLUSION: HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders.
Autografts ; Bacteremia ; Disease-Free Survival ; Drug Therapy* ; Fever ; Hematopoietic Stem Cell Transplantation ; Hospitals, University ; Humans ; Korea ; Ovarian Neoplasms* ; Peripheral Blood Stem Cell Transplantation* ; Retrospective Studies ; Stem Cell Transplantation

Skeletal muscle is one of the most unusual metastatic sites for any malignancy. Duodenal cancer is extremely rare, and no cases of skeletal muscle metastasis from duodenal cancer have been reported. We report here in a case of metastasis to the skeletal muscle of the left thigh from duodenal cancer. Our patient was a 47-year-old man, exhibiting a painful mass in the posterior aspect of his left thigh over a 4 month period. An imaging study, and a biopsy, revealed a duodenal adenocarcinoma metastasize to the skeletal muscle. The patient refused chemotherapy and has followed up for 4 months.
Adenocarcinoma* ; Biopsy ; Drug Therapy ; Duodenal Neoplasms ; Duodenum* ; Humans ; Middle Aged ; Muscle, Skeletal* ; Neoplasm Metastasis* ; Thigh*

BACKGROUND: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-gamma) and TNF-alpha can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. METHODS: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-gamma, TNF-alpha, or macrophage inflammatory protein 1-alpha (MIP-1alpha). RESULTS: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-gamma, TNF-alpha, or MIP-1alpha increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-gamma, TNF-alpha, or MIP-1alpha mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-gamma enhanced apoptosis most strongly via Fas-caspase-3 pathway. CONCLUSION: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-gamma can induce apoptosis of bone marrow progenitors in part by Fas induction.
Anemia, Aplastic* ; Antigens, CD95* ; Apoptosis* ; Bone Marrow Cells* ; Bone Marrow* ; Caspase 3 ; Chemokine CCL3 ; Cytokines ; Hematopoietic Stem Cells ; Humans ; Immunity, Cellular ; Interferons ; Signal Transduction ; Tissue Donors ; Tumor Necrosis Factor-alpha

We experienced a case of atypical hairy cell leukemia in a 42-year-old woman. She showed marked splenomegaly without palpable lymphadenopathy. Complete blood cell count revealed leukocytosis at 44,000/micro L with lymphocytes 74% and peripheral blood smear showed abnormal lymphoid cells with cytoplasmic projections. The bone marrow was easily aspirated and also revealed the abnormal lymphocytes in up to 95%. Tartrate-resistant acid phosphatase reactivity was negative in the hairy cells. Immunophenotyping results of lymphoid cells were CD5(-), CD7(-), CD10(-), CD19(+), and HLA-DR(+). She was treated with an adenosine analogue, fludarabine at a daily dose of 30mg/m2 for 5 consecutive days, every four weeks. Immediately after treatment, the size of the spleen was normalized. Correct diagnosis was difficult due to insufficient laboratory and pathologic data. The differential diagnosis of mature B-cell neoplasms with cytoplasmic projections in patients with splenomegaly includes hairy cell leukemia and splenic lymphoma with villous lymphocytes. We herein described the present case with a brief review of the literature.
Acid Phosphatase ; Adenosine ; Adult ; B-Lymphocytes ; Blood Cell Count ; Bone Marrow ; Cytoplasm ; Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Immunophenotyping ; Leukemia, Hairy Cell* ; Leukocytosis ; Lymphatic Diseases ; Lymphocytes ; Lymphoma ; Spleen ; Splenomegaly

All-trans retinoic acid (ATRA) therapy induces complete remission in acute promyelocytic leukemia (APL) via differentiation of the APL cells. Recent clinical trials in China and United states showed that arsenic trioxide (ATO) is an effective and relatively safe drug in the treatment of APL. The patient was 29-year-old woman with APL who had been treated heavily with allogeneic bone marrow transplantation (BMT) in 4 years ago and reinduction chemotherapy plus donor lymphocyte infusion (DLI) after relapse in 2 years ago. After diagnosis for relapse, she had been treated with ATRA, but unfortunately failed. She was treated with ATO at the dose of 10 mg/day intravenously for 6 weeks. Complete remission was achieved at 3 weeks and the cumulative dose of ATO during induction was 420mg. She had complete remission without severe adverse effects except mild impairment of liver function and is following up for 6 months. We report a case of remission induction by ATO in ATRA refractory APL patient who experienced multiple relapse after allogeneic BMT, chemotherapy and DLI.
Adult ; Arsenic* ; Bone Marrow Transplantation* ; Bone Marrow* ; China ; Diagnosis ; Drug Therapy ; Female ; Humans ; Leukemia, Promyelocytic, Acute* ; Liver ; Lymphocytes ; Recurrence ; Remission Induction* ; Tissue Donors ; Tretinoin ; United States

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8x6.5x4cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.
Adult ; Antineoplastic Agents, Combined/administration & dosage ; Biopsy, Needle ; Brain Neoplasms/therapy ; Brain Neoplasms/secondary* ; Brain Neoplasms/pathology ; Case Report ; Combined Modality Therapy ; Follow-Up Studies ; Head and Neck Neoplasms/therapy ; Head and Neck Neoplasms/surgery ; Head and Neck Neoplasms/pathology* ; Human ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Neoplasms, Basal Cell/therapy ; Neoplasms, Basal Cell/secondary* ; Neurosurgical Procedures/methods ; Reoperation ; Scalp* ; Skin Neoplasms/therapy ; Skin Neoplasms/surgery ; Skin Neoplasms/pathology* ; Tomography, X-Ray Computed

BACKGROUND: Several mechanisms have been proposed to account for bone marrow failure in aplastic anemia (AA), including deficiency in hematopoietic stem cells, a secondary stem cell defect involving immune regulation and defective marrow stroma, or microenvironment. We investigated the pathophysiology of AA through long-term bone marrow cultures (LTBMCs) using bone marrrow of AA patients before treatment and of patients responded to immunosuppressive therapy with anti-thymocyte globulin (ATG) and/or cyclosporine. METHODS: We investigated the hematopoietic defect in severe aplastic anemia (SAA) patients by using long-term bone marrow cultures (LTBMCs). Twenty patients with SAA have been studied. In these patients, 10 had been treated with ATG plus cyclosporine and the remainders were studied before therapy was begun. Subsequent assays of the production of negative-acting hematopoietic cytokines (TNF-alpha, IFN-gamma, MIP-1alpha and TGF-beta) by AA stroma in LTBMCs were performed. RESULTS: Initial assessment of CD34+ cells, CFU-GM and CFU-MK from LTBMCs in AA demonstrated severely reduced or absent in patients with SAA, even following hematologic recovery with immunosuppressive therapy,when compared with normal controls. Significant difference in concentrations of TNF-alpha, INF-gamma, and MIP-1alpha between the AA and control groups were apparent. Interestingly, the levels of those negative-acting hematopoietic cytokines were decreased in SAA patients receiving immunosuppressive therapy, but not the levels of controls. However, the mean TGF-beta concentrations in the AA patients and normal controls were not significantly different. The percent of CD34+ cells and CFU-MK in bone marrow was lower in SAA patients before immunosuppressive therapy was begun than that in SAA patients receiving immunosuppressive therapy and that in normal controls (mean 0.54+/-0.32% vs 0.96+/-0.32% vs 1.94+/-0.61%). CONCLUSIONS: These results indicate the presence of a in vitro functional deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment, and add to the available evidence for defect of microenvironment with hematopoeitic stem cell in some cases of AA.
Anemia, Aplastic* ; Antilymphocyte Serum ; Bone Marrow* ; Chemokine CCL3 ; Cyclosporine ; Cytokines ; Granulocyte-Macrophage Progenitor Cells ; Hematopoietic Stem Cells ; Hematopoietic System ; Humans ; Stem Cells ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

BACKGROUND: Initial treatment of chronic idiopathic thrombocytopenic purpura (ITP) is generally done with corticosteroid. In case of refractory to corticosteroid or dependency, splenectomy seems to be the most effective and definitive treatment. Partial splenic embolization is an easier procedure with minimal morbidity. We evaluated the efficacy and complications of partial splenic embolization as treatment of chronic ITP refractory to corticosteroid or corticosteroid dependency. METHODS: Eight patients with chronic ITP and two systemic lupus erythematosus (SLE) patients with immunothrombocytopenia underwent partial splenic embolization. Embolization of 70~80% of the splenic volume was performed with endocoils or gelform particles without anesthesia by selective arterial catheterization and followed up for 4~50 months. The therapeutic effect of partial splenic embolzation was defined on the basis of the platelet count at the last follow-up after partial splenic embolzation : complete response, >100,000/nL,partial response, 100,000~50,000/nL and no response, <50,000/nL without medication. RESULTS: Partial splenic embolization brought a complete response in six of ten patients, a partial response in three, and no response in one. With a follow-up of 4~50 months, these responses were maintained in all except three patients. One patient was treated by splenectomy and one by partial splenic embolization again. Tolerance was good in all patients. Abdominal pain and fever was observed in 8 and 4 patients, respectively. One patient had a left pleural effusion with spontaneous resolution. No serious infection occurred. All patients were discharged within 6 days after partial splenic embolization. CONCLUSION: We conclude that partial splenic embolization may be useful and safe procedure and a good alternative to splenectomy in chronic ITP refractory to medical treatment.
Abdominal Pain ; Anesthesia ; Catheterization ; Catheters ; Fever ; Follow-Up Studies ; Humans ; Lupus Erythematosus, Systemic ; Platelet Count ; Pleural Effusion ; Purpura, Thrombocytopenic, Idiopathic* ; Splenectomy

BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) been shown to be associated with human diseases including Kaposi's sarcoma, pleural effusion lymphoma, multicentric Castleman's disease. The IL-6 may both stimulate myeloma growth and prevent apoptosis of malignant plasma cells. Interestingly, viral IL-6(vIL-6), homolog to human interleukin-6(IL-6) in KSHV genome retains biologic activity. Thus, oncogenic role of the KSHV has been proposed as a pathogenesis of the multiple myeloma. We used ISH to determine the frequency of patients with multiple myeloma and plasmacytosis associated with KSHV-infected BM cells in fresh core biopsies and to determine the correlation between KSHV infection and clinical characteristics. METHODS: Bone marrow(BM) biopsy samples from 16 cases of multiple myeloma, 2 cases of monoclonal gammopathy of undetermined significance(MGUS) were obtained from the pathology division of Soon Chun Hyang University Hospital, Seoul, Korea. Biopsy sample of Kaposi's sarcoma for positive control and BM biopsy samples of myelodysplastic syndrome(MDS) and malignant lymphoma for negative control were obtained. Bitinylated probe to KSHV were prepared with the following sequences: 5' to 3' TGCAGCAGCTGTTGGTGTACCACATATCT. and in situ hybridization (ISH) was performed. RESULTS: Among the 18 patients. Two patients were MGUS and among 16 patients with multiple myeloma, 1 in stage IB disease, 1 stage IIB disease, 8 stage IIIA disease, 4 stage IIIB diseases and 2 in variant of multiple myeloma, extramedullary plasmacytoma. Strong positive signal was detected in nuclei and cytoplasm of the malignant cells of biopsy sample from 1 cases of Kaposi's sarcoma by ISH(positive control). Signal was not detected in BM biopsy samples of 7 cases from MDS and malignant lymphoma(negative control). Among 16 patients with multiple myeloma, 15 demonstrated viral positive cells and 2 cases with MGUS also showed viral positive cells by ISH. Signal was detected in nuclei and cytoplasm of stromal cells. Signal was strongly detected in MGUS than multiple myeloma. Positivity of the KSHV was not related with stage of the patients with multiple myeloma. One patients with multiple myeloma was studied at diagnosis and after chemotherapy. After chemotherapy KSHV was not detected. CONCLUSION: In MGUS and multiple myeloma, KSHV infects the stromal cells of BM rather than malignant plasma cells. On the basis of these data, we have supposed KSHV to play a role in transformation from MGUS to multiple myeloma. Particularly, due to the fact that signal of ISH was strongly detected in MGUS and was not detected in one case with multiple myeloma, it was presumed that KSHV was not major role in already advanced multiple myeloma but statistic significance was not demonstrated because of small numbers of cases. Further studies to reveal the correlation of KSHV and pathogenesis of multiple myeloma are needed.
Apoptosis ; Biopsy ; Cytoplasm ; Diagnosis ; Drug Therapy ; Genome ; Giant Lymph Node Hyperplasia ; Herpesvirus 8, Human ; Humans ; In Situ Hybridization ; Interleukin-6 ; Korea ; Lymphoma ; Multiple Myeloma* ; Paraproteinemias ; Pathology ; Plasma Cells ; Plasmacytoma ; Pleural Effusion ; Sarcoma, Kaposi ; Seoul ; Stromal Cells