Biomedical subjects

Woo Sung Min

Publications and source records attributed to Woo Sung Min.

16 recordsLinked to original sources

PubMed2006

Immunoregulatory effects of allogeneic mixed chimerism induced by nonmyeloablative bone marrow transplantation on chronic inflammatory arthritis and autoimmunity in interleukin-1 receptor antagonist-deficient mice.

OBJECTIVE: To investigate the immunoregulatory effects of allogeneic mixed chimerism induced by T cell-depleted, nonmyeloablative bone marrow transplantation (BMT) on chronic inflammatory arthritis and autoimmunity in mice deficient in interleukin-1 receptor antagonist (IL-1Ra). METHODS: IL-1Ra(-/-) mice (H-2K(d)) were treated with antibody to asialoganglioside G(M1) (anti-natural killer cell), total body irradiation (500 cGy), and T cell-depleted, nonmyeloablative BMT derived from C57BL/6 mice (H-2K(b)). Engraftment and chimerism were evaluated in peripheral blood, lymph nodes, and spleen by multicolor flow cytometry. The severity of arthritis was evaluated by clinical scoring and histopathologic assessment. Levels of IgG1 and IgG2a subtypes of anti-type II collagen (anti-CII) antibodies were measured in serum samples. After T cells were stimulated with CII, ovalbumin, and phytohemagglutinin, T cell proliferative responses and levels of cytokine production (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha], interleukin-10 [IL-10], and IL-17) were assayed in culture supernatants. RESULTS: All IL-1Ra(-/-) mice receiving BMT showed marked improvement in arthritis within 3 weeks, as well as successful induction of mixed chimerism. These mice showed higher levels of IgG1, and lower levels of IgG2a anti-CII antibodies and weaker T cell proliferative responses than did mice in the control groups (either no treatment or conditioning alone without bone marrow rescue). In mixed chimeras, the levels of IFNgamma, TNFalpha, and IL-17 produced from CII-stimulated T cells were significantly suppressed and IL-10 production was significantly higher as compared with controls. CONCLUSION: The introduction of allogeneic mixed chimerism showed a strong immunoregulatory potential to correct established chronic inflammatory arthritis and autoimmunity originating from a dysregulated proinflammatory cytokine network.

Animals↗

PubMed2006

Protective effect of irradiated renal carcinoma expressing hepatitis B surface antigen against renal-cell carcinoma-mediated tumors.

Radiation therapy and chemotherapy have little effect on renal-cell carcinomas (RENCAs). We investigated the effect of the tumor vaccination strategy on preventing tumor formation after a challenge with RENCA. The hepatitis surface antigen (HBsAg) was used to enhance the antitumor immunity and tumor vaccination efficiency. RENCA cells expressing HBsAg (RENCA/HBS) were completely susceptible to HBsAg vaccination, which implies that HBsAg vaccination induces specific antitumor immunity against HBsAg- expressing cancer cells. As with HBsAg vaccination, vaccination with irradiated RENCA/HBS retarded tumor formation following a RENCA/HBS challenge. After HBsAg vaccination, the irradiated RENCA/HBS tumor vaccine completely prevented the tumor formation by RENCA/HBS. Tumor vaccination with irradiated RENCA/HBS (5 x 10(4) cells), but not with RENCA, reduced the tumor rate after a challenge with 5 x 10(6) RENCA cells, whereas a lower tumor load was overcome by the RENCA vaccination alone. These results confirm the postulate that RENCA/HBS vaccination elicits an antitumor immune response to some putative antigens or enhances the general immune competence in immunosuppressed renal tumor patients.

Animals↗

PubMed2006

Current trends of infectious complications following hematopoietic stem cell transplantation in a single center.

This study was to analyze the infectious complications after hematopoietic stem cell transplantation (HSCT) according to the recent changes of HSCT. Medical records of 379 adult patients who underwent HSCT consecutively at Catholic HSCT Center from January 2001 to December 2002 were reviewed retrospectively. Allogeneic HSCT accounted for 75.7% (287/379) and autologous HSCT for 24.3% (92/379). During pre-engraftment period, bacterial infection was predominant, and E. coli was still the most common organism. After engraftment, viral infection was predominant. The incidence of invasive fungal infection showed bimodal distribution with peak correlated with neutropenia and graft-versus-host disease (GVHD). The overall mortality and infection-related mortality rates according to 3 periods were as follows; during pre-engraftment, 3.16% (12/379) and 1.8% (7/379); during midrecovery period, 7.9% (29/367) and 4.1% (15/367); during late-recovery period, 26.9% (91/338), and 15.9% (54/338). Risk factors for infection-related mortality were as follows; during pre-engraftment period, fungal infection and septic shock; during the mid-recovery period, hemorrhagic cystitis and delayed engraftment; during the late-recovery period, fungal infection, chronic GVHD, and relapse. In conclusion, infection was still one of the main complications after HSCT and highly contributes to mortality. The early diagnosis and the effective vaccination strategy are needed for control of infections.

Adolescent↗

PubMed2006

Clinical characteristics and outcomes of posttransplant lymphoproliferative disorders following allogeneic hematopoietic stem cell transplantation in Korea.

Between 1995 and 2003, seven cases of posttransplant lymphoproliferative disorder (PTLD) were identified among 1,116 patients who received allogeneic hematopoietic stem cell transplantations (HSCT) at Catholic HSCT Center (overall incidence 0.6%). Five (71.4%) patients had episodes of acute graft-versus-host-disease (GVHD) and were treated with steroids. Cervical lymphadenopathy was observed in most cases (71.4%), but clinical symptoms varied depending on the involved sites. Pathologic findings varied: 1 case of plasmacytic hyperplasia, 3 of polymorphic PTLD, 2 of diffuse large B-cell lymphoma, 1 of large T-cell lymphoma, which proved to be associated with Epstein-Barr virus (EBV). The proportion of EBV-negative PTLD was 33.3%. Five patients demonstrated a good response to treatment (treatment response rate 71.4%). The overall mortality was 42.8%, and one death was directly attributable to PTLD. The incidence of PTLD is expected to increase, based on the rising use of grafts from alternative donors and recent clinical features of PTLD manifested by a disseminated and fulminant nature. It is necessary to have a high level of suspicion when monitoring patients and readily adopt prompt and effective cellular immunotherapy for PTLD.

Adolescent↗

PubMed2006

Intracellular IL-4, IL-10, and IFN-gamma levels of leukemic cells and bone marrow T cells in acute leukemia.

The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-gamma (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 +/- 1056) and lowest in the dysplastic AML group (960 +/- 545). The IFN-gamma level was highest in the acute promyelocytic leukemia (APL) group (495 +/- 159), and lowest in the ALL group (252 +/- 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 +/- 1049) and lowest in the APL group (397 +/- 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-gamma are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.

Acute Disease↗

PubMed2005

Mutational analysis of the ARAF gene in human cancers.

Deregulation of RAS signal transduction has been implicated in the malignant growth of human cancer cells. The BRAF gene, encoding a RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers, raising the possibility that other RAF family members might be mutated in human cancers. In this study we analyzed the genomic DNAs for the detection of somatic mutations of the ARAF gene in 60 human cancer cell lines and 323 primary human cancer tissues, including colorectal carcinomas, gastric carcinomas, ovarian tumors and acute leukemias. The MOLT-4 leukemia cell line was found to harbor an ARAF gene mutation resulting in an amino acid substitution (A451T) at the activation segment in the kinase domain of ARAF. In the cancer tissues we could not detect any ARAF gene mutation. Our data indicate that, in contrast to the BRAF gene, the ARAF gene is rarely mutated in human cancers, and suggest that alterations of the RAS pathway by ARAF gene mutation may not play an important role in the pathogenesis of human cancers.

DNA↗

PubMed2005

Successful treatment with splenectomy and interferon alpha against recurred hemophagocytic syndrome in remission state of anaplastic large cell lymphoma following high-dose therapy and autologous peripheral blood stem cell transplantation.

A 25-yr-old man had been diagnosed as having CD30(+) anaplastic large cell lymphoma associated with hemophagocytic syndrome (HS). He received aggressive frontline chemotherapies and consolidation with autologous peripheral blood stem cell transplantation (PBSCT) following high-dose chemotherapy combined with splenic irradiation (720 cGy in fraction of 180 cGy). However, HS recurred on day 50 of PBSCT without radiologic evidence of lymphoma relapse. On day 56 of PBSCT, splenectomy was performed and pathology showed massive sinusoidal infiltration of histiocytes. On day 68 of PBSCT, administration of interferon alpha was started and maintained for 24 months. HS was completely resolved and he has been alive well and in complete remission (CR), 60 months after initial diagnosis.

Adult↗

PubMed2005

Retrospective multicenter study of allogeneic peripheral blood stem cell transplantation followed by reduced-intensity conditioning or conventional myeloablative regimen.

This retrospective study compared the results of reduced-intensity conditioning stem cell transplantation (RIST) and a conventional myeloablative regimen (CST) followed by allogeneic peripheral blood stem cell transplantation. In this respect, 63 RISTs and 41 CSTs were performed at 5 transplantation centers in Korea between April 1998 and December 2002. The RIST group had more adverse pretransplant characteristics. More aggressive diseases, like acute myeloid or lymphoblastic leukemia, were included in the CST group, while the RIST group included more indolent diseases, like chronic myeloid leukemia or myeloma (p < 0.001). The incidence of acute graft-versus-host disease (GVHD) grades 2-4 was 29.1 and 57.9% for the RIST and CST groups, respectively (p = 0.010), yet the incidence of chronic GVHD was similar in the two groups (57.4 vs. 71.9%). With a median follow-up of 13 months (0.5-61 months, 17 months in 52 survivors), the 3-year overall (OS) and disease-free survival (DFS) was similar in the RIST and CST groups (p = 0.965 for OS, p = 0.545 for DFS). In a multivariate analysis, RIST (p = 0.010), good performance status (p = 0.006) and a higher CD34+ cell dose (p = 0.008) were all identified as independent favorable prognostic factors for OS. Accordingly, in the current study, RIST produced equivalent or acceptable results compared with CST in terms of OS. Therefore, a prospective randomized trial of RIST and CST is warranted.

Adolescent↗

PubMed2004

Spontaneous pneumothorax developed in patients with bronchiolitis obliterans after unrelated hematopoietic stem cell transplantation: case report and review of the literature.

Spontaneous pneumothorax following unrelated hematopoietic stem cell transplantation developed in our 2 patients with bronchiolitis obliterans. Bronchiolitis obliterans is a form of obstructive airway disease and is considered a manifestation of chronic graft-versus-host disease (GVHD). Both of the patients were the recipients of marrow from HLA-matched unrelated donors after a preparative regimen with total body irradiation. Chronic GVHD after transplantation is a common feature in these cases. In contrast to other patients with pneumothorax described in the literature, our patients did not develop bullae. We describe a pneumothorax secondary to bronchiolitis obliterans that complicated the posttransplantation course.

Adult↗

PubMed2004

High dose chemotherapy and autologous stem cell transplantation for poor risk and recurrent non-Hodgkin's lymphoma: a single-center experience of 50 patients.

BACKGROUND: The long-term survival of patients with non-Hodgkin's lymphoma after conventional chemotherapy is about 35%, with the remaining 65% of patients tending to be refractory or experience relapse. As such, primary refractory patients responding to salvage chemotherapy, and sensitive relapsed patients and primary high-risk patients are recommended to receive high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT). We evaluated the role of HDC and autologous PBSCT in patients with primary refractory, primary high risk, and sensitive relapsed non-Hodgkin's lymphoma. METHODS: We performed a retrospective analysis of the data from 50 patients with non-Hodgkin's lymphoma who were treated with HDC and autologous PBSCT in the Catholic Hematopoietic Stem Cell Transplantation Center between 1997 and 2002. RESULTS: Of the 50 patients, the conditioning regimen was BEAM in 20, CMT (cyclophosphamide, melphalan and thiotepa) in 19, fludarabine- and total body irradiation (TBI)-based regimen in 8, and cyclophosphamide and TBI in 2. There were 3 (6%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Twenty-five patients remain alive at a median follow-up duration of 40.5 months (range 9-61). Among the patients with partial response before transplantation, 76% showed further response after transplantation. In half of these responders, the disease state was changed into complete response (CR) after transplantation. 2-year overall survival was 52% and 2-year progression free survival was 36.8%. Median overall survival was 34 months (range 8-60), and median progression-free survival was 8 months (range 1-14). Median overall survival was 14 months (range 9-19) in the primary high-risk group (n=13), 7 months (range 4-10) in the resistance relapse group (n=5), and 6 months (range 0-14) in the primary refractory group (n=10). Overall survival in the sensitive relapse group (n=22) did not reach the median; the mean overall survival in this group was 33 months. The disease status before transplantation was the only significant prognostic factor in determining overall survival (p=0.032) and progression- free survival (p=0.001). CONCLUSION: HDC and autologous PBSCT appears to produce high response rate. Primary high-risk group and sensitive relapse group had good prognosis, while refractory and resistance relapse group had poor prognosis. And the pre-transplantation disease status was the only significant prognostic factor in multivariate analysis.

Adolescent↗

PubMed2004

Plasma soluble interleukin-2 receptor (sIL-2R) levels in patients with acute leukemia.

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.

Acute Disease↗

PubMed2003

Expression of functional markers in acute lymphoblastic leukemia.

We analyzed surface antigens, multidrug resistance (MDR) parameters (PGP, MRP, LRP), tissue infiltration parameters (CD18, CD44, VCAM, MMP2), receptors for colony stimulating factors (G-CSFr, GM-CSFr) and cell cycle parameters (Ki-67, topoisomerase IIalpha) in 86 patients with acute lymphoblastic leukemia (ALL). LRP, PGP and CD18 were associated with poor clinical outcome, and LRP expression was related with CD18, CD44 and G-CSFr. Of the cell cycle parameters, Ki-67 (+) fraction was increased in ALL with hepato-splenomegaly and extramedullary involvement. In conclusion, analysis of LRP, PGP, CD18 and Ki-67 could be helpful to predict the clinical behavior of ALL.

ATP-Binding Cassette Transporters↗

PubMed2003

Very severe aplastic anemia appearing after thymectomy.

Aplastic anemia is a rare complication of thymoma and is extremely infrequent after thymectomy. We present a case of a 60-year-old woman with very severe aplastic anemia appearing sixteen months after thymectomy for a thymoma. She underwent thymectomy for a thymoma in April 2000. Preoperative examination revealed no hematologic abnormality. About sixteen months after the operation, she was readmitted because of pancytopenia with cough and fever. Bone marrow aspiration revealed a very severe hypoplasia in all the three cell lines with over 80% fatty tissue, and chest CT revealed no recurrence of thymoma. Her aplastic anemia had responded to cyclosporine A and granulocyte-colony stimulating factor (G-CSF).

Anemia, Aplastic↗

PubMed2002

Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia.

Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+) enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was 83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44) months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients.

Adolescent↗

PubMed2002

The association of HLA antigen and GVHD in allogeneic hemopoietic stem cell transplantation with histocompatible sibling donor: a single-center experience in Korea.

We analyzed the association of HLA antigens with incidence of organ-specific graft-versus-host disease (GVHD) after allogeneic hemopoietic stem cell transplantation (allo-HSCT) from an HLA-matched sibling donor. We retrospectively reviewed the clinical records of allo-HSCT recipients and found 389 patients who had received matched-sibling HSCT. HLA types, GVHD grades, and the development of acute or chronic GVHD, factors that reflect a certain immunological impact associated with involved organs, were investigated. The overall incidence of acute and chronic GVHD was 24.8% (96 cases) and 21.2% (82 cases), respectively. The incidence of acute GVHD with grades II through IV was higher among patients who had HLA-B61 (P = .0153) and HLA-Cw3 (P = .0208). The donor sex (P = .0040) and the conditioning regimen (P = .0010) were also associated with severe acute GVHD. The extensive-type chronic GVHD incidence was higher in patients who had HLA-B54 (P = .0159). The donor sex (P = .0406) and the pretransplantation diagnosis (P = .0184) were other factors associated with the development of extensive-type chronic GVHD. Furthermore, HLA-B35 (P = .0226) and HLA-B54 (P = .0091) were associated with a higher incidence of severe acute skin GVHD and chronic skin and oral GVHD (in descending order of incidence rates). HLA-B7,27 was associated with chronic liver GVHD (P = .0476) in addition to other parameters including patient (P = .0246) and donor sex (P = .0019). This study shows that these remarkable HLA antigens may be potent transplantation immune regulators, but there is a need for further evaluation using larger study samples.

Adolescent↗

PubMed2002

Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial.

BACKGROUND: Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia (AML) patients receiving chemotherapy. Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased. This study aimed to access the effectiveness of antimicrobial prophylaxis (AP) with orally absorbable antibiotics. METHODS: Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were randomly divided into the AP group (250 mg ciprofloxacin twice a day, 150 mg roxithromycin twice a day, 50 mg fluconazole once a day) and the control group for a prospective analysis. RESULTS: The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0.15). Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance. The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC < 1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups. Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs. 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs. 8% in the control group). Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90-100% resistance to erythromycin, regardless of the presence of AP. CONCLUSION: The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy. On considering increased gram-positive infection and resistance to fluoroquinolone and macrolide, routine prescription of AP should be reconsidered. Further studies that assess the effectiveness of AP in other malignancies, aplastic anemia and bone marrow transplantation are required.

Adult↗