Previous researches have proved that Pueraria lobata up-regulates bone mineral contents and bone mineral density in bone-loss model, ovariectomized mice and orchidectomized rats. However, the precise effects and mechanisms of Pueraria lobata on osteoclast differentiation and bone resorbing activity of mature osteoclasts still remains unknown. Therefore, we investigated the effect and mechanism of Pueraria lobata on receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony stimulation factor (M-CSF)-induced osteoclast differentiation in bone marrow macro-phages (BMMs). First of all, we treated BMMs derived from mice with various concentrations of Pueraria lobata in order to perform screening by tartrate-resistant acid phosphatase (TRAP) staining. Also, we conducted western blotting and RT-PCR for the purpose of verifying the treatment mechanism of Pueraria lobata and lastly, we used hydroxyapatite-coated plate to evaluate the effects of Pueraria lobata on bone resorbing activity of mature osteoclasts. As a result, Pueraria lobata has inhibitory effect on phosphorylation of p38, Akt, c-Jun N-terminal kinase (JNK), and IkappaB which are essential early signaling pathway of osteoclastogenesis. Also, the inactivation of nuclear factor of activated T cells (NFAT)c1, and c-Fos which is caused by Pueraria lobata is followed by the suppression effects of Pueraria lobata on osteoclast-related various genes, osteoclast-associated receptor (OSCAR), TRAP, Integrin beta3, osteoclast stimulatory transmembrane protein (OC-STAMP), and dendritic cell-specific transmembrane protein (DC-STAMP). Particularly, Pueraria lobata blocks the formation of pit area on hydroxyapatite-coated plate in a dose-dependent manner as well as the mRNA expression of Cathepsin K, which is associated with bone resorbing activity. These results demonstrate the molecular mechanism relating to anti-osteoclastogenesis effect of Pueraria lobata as well as the inhibitory effect of Pueraria lobata on mature osteoclast formation and bone resorbing activity.
Acid Phosphatase ; Animals ; Blotting, Western ; Bone Density ; Bone Marrow ; Bone Remodeling ; Bone Resorption* ; Cathepsin K ; Integrin beta3 ; JNK Mitogen-Activated Protein Kinases ; Macrophages ; Mass Screening ; Mice ; Osteoclasts* ; Osteoporosis ; Phosphorylation ; Pueraria* ; RANK Ligand ; Rats ; RNA, Messenger ; T-Lymphocytes

Idiopathic retroperitoneal fibrosis is a relatively rare disease that is characterized by the proliferation of fibrous tissue with an inflammatory process in the retroperitoneal cavity. It can cause an obstruction and compression of the ureter, abdominal aorta, and finally progress to renal failure. During the initial stages, the histology shows active inflammation. However, in the late stages, fibrous scarring occurs and the tissue becomes relatively avascular and acellular. Increased 18F-FDG accumulation was observed in our patient at the time of disease onset, which was attributed to the presence of inflammatory cells and actively metabolizing fibroblasts. We describe two patients with idiopathic retroperitoneal fibrosis, who were examined by 18F-FDG-PET, and discuss the efficiency of positron emission tomography in the diagnosis and management of idiopathic retroperitoneal fibrosis patients.
Aorta, Abdominal ; Cicatrix ; Diagnosis ; Fibroblasts ; Fluorodeoxyglucose F18 ; Humans ; Inflammation ; Positron-Emission Tomography* ; Rare Diseases ; Renal Insufficiency ; Retroperitoneal Fibrosis* ; Ureter

BACKGROUND: Acute leukemias co-expressing myeloid and lymphoid antigens but does not meet the criteria for biphenotypic acute leukemia (BAL) is common, however its clinical significance is not fully defined. METHODS: In this study, clinical features of 68 co-expressing (myeloid and lymphoid) acute leukemias diagnosed between January 2000 and December 2006 were studied and compared with those of a control group of patients (pure AML or ALL). RESULTS: Age, gender, initial Lactate dehydrogenase (LDH) level and cytogenetics were not different between the co-expressing group and the control group. But, the initial bone marrow blast percent was significantly higher in the co-expressing group (70% vs. 54.5%, P=0.003). Fifty five percent (16/29) of ALL and 30% (52/172) of AML patients showed myeloid and lymphoid markers concomitantly. The lymphoid antigen positive AML (Ly+AML) patients showed significantly shorter survival rates than pure AML patients (4 year survival rate, 17.6% vs. 45.6%, P=0.002). However hematopoietic stem cell transplantation (HST) abrogated the difference (4 year survival rate, 54.7% vs. 50.6%, P=0.894). In ALL patients, survival rate was not affected by myeloid antigen co-expression (4 year survival rate 26.1% vs. 20%, P=0.954). CONCLUSION: Co-expression of lymphoid markers in AML should be regarded as a poor prognostic factor and more aggressive treatment such as HST should be considered.
Bone Marrow ; Cytogenetics ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunophenotyping ; L-Lactate Dehydrogenase ; Leukemia ; Leukemia, Biphenotypic, Acute ; Prognosis ; Survival Rate

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma.
Adult ; Aged ; Antigens, CD34/biosynthesis ; Antineoplastic Agents, Alkylating/*therapeutic use ; C-Reactive Protein/biosynthesis ; Cell Survival ; Combined Modality Therapy ; Cytogenetics ; Disease-Free Survival ; Female ; Human ; Korea ; L-Lactate Dehydrogenase/biosynthesis ; Male ; Melphalan/*therapeutic use ; Middle Aged ; Multiple Myeloma/*therapy ; Peripheral Blood Stem Cell Transplantation/*methods ; Time Factors ; Transplantation, Autologous/*methods ; beta 2-Microglobulin/blood

BACKGROUND: Horse antithymocyte globulin (ATG) is a useful treatment for aplastic anemia and for bone marrow transplantation from HLA-mismatched donors. Mortality due to anaphylactic reaction to horse ATG has been reported. We evaluated the clinical significance of skin test and specific IgE measurement for the prediction of immediate type hypersensitivity reaction to horse ATG. SUBJECTS AND METHODS: The study subjects consisted of 25 patients who received horse ATG. Underlying diseases of the 25 patients included aplastic anemia (n=20), leukemia (n=3), lymphoma (n=1), and Gaucher's disease (n=1). Skin prick test was done on these patients using undiluted ATG solution (Upjohn, USA) with duplication. Specific IgE to ATG was detected by enzyme-linked immunosorbent assay and immunoblot analysis. RESULTS: Skin prick test was positive in 7 (28%) of 25 patients. None of the patients showing negative skin prick test experienced immediate type hypersensitivity reaction to ATG. All patients showing positive skin prick test received desensitization before the administration of a full dose of ATG. However, 3 of 7 patients showing positive skin prick test experienced immediate type hypersensitivity reaction; one of them died of anaphylaxis. Specific IgE measurement using enzyme-linked immunosorbent assay was not useful in predicting immediate type hypersensitivity reaction to ATG because of nonspecific bindings. Specific IgE measurement using immunoblot analysis was only positive in the one patient who died of anaphylaxis. CONCLUSION: Skin prick test was clinically useful in the prediction of immediate type hypersensitivity reaction to horse ATG, but specific IgE measurement was not. Further studies might be needed to develop an in vitro test for the prediction of immediate type hypersensitivity reaction to horse ATG.
Anaphylaxis ; Anemia, Aplastic ; Antilymphocyte Serum* ; Bone Marrow Transplantation ; Enzyme-Linked Immunosorbent Assay ; Gaucher Disease ; Horses* ; Humans ; Hypersensitivity* ; Immunoglobulin E* ; Leukemia ; Lymphoma ; Mortality ; Skin Tests* ; Skin* ; Tissue Donors

PURPOSE: Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. Patients and Methods: The treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) were retrospectively compared with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In the induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/ cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in the concurrent group. RESULTS: The clinicopathological characteristics, including age, weight loss, histological types and clinical stage, showed no significant differences between the two groups, with the exception of a higher proportion of patients with an ECOG performance status of 2 in the concurrent group (3% vs. 27%, p=0.015). The overall toxicity was generally acceptable with only 1 treatment-related death from tracheoesophageal fistula in the induction group. The response rates after concurrent CRT were 41 and 54% for the induction and concurrent groups, respectively, which showed no significant difference (p=0.560). With a median follow-up of 13 (1~86) months, there was a trend toward an advantage in the concurrent group in relation to the median progression-free (6 months vs. 8.3 months, p=0.051) and overall survivals (12 months vs. 14.5 months, p=0.056). From a multivariate analysis, only a weight loss of more than 10% within 6 months was significantly associated with a poor survival (p=0.001). CONCLUSIONS: The addition of induction chemotherapy to concurrent CRT showed no any advantage over concurrent CRT alone in locally advanced NSCLC
Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Cisplatin ; Follow-Up Studies ; Humans ; Induction Chemotherapy* ; Multivariate Analysis ; Retrospective Studies ; Tracheoesophageal Fistula ; Weight Loss