PURPOSE: The events of cell stress and cell death are linked, with the heat shock proteins (Hsps) induced in response to stress appearing to function at key regulatory points in the control of apoptosis. The purpose of this study was to investigate the effect of arisostatins A on the Hsp70 expression and signal mechanism of its transcription. MATERIALS AND METHODS: We used natural arisostatins A produced by Actinomycete, in Caki cells. We measured the growth rate of cell using trypan blue staining, and the induction of the transcriptional levels of Hsp70 with arisostatins, which was quantified by reverse transcript-polymerase chain reaction (RT-PCR) and transiently transfecting cells with a Hsp70. The induction of the transcriptional levels of Hsp70 with arisostatins A was quantified by RT-PCR and transiently transfecting cells with a Hsp70 promoter-luciferase reporter plasmid. RESULTS: Arisostatins A-induced Hsp70 up-regulation was not prevented by the overexpression of peroxiredoxinI (PrxI), PrxII or treatment of superoxide dismutase and catalase. However, the arisostatins A-mediated expression of Hsp70 was reduced significantly in Caki cells treated by the antioxidant, N-acetylcystein. Inhibition of the Janus tyrosine kinase (JAK) activity with AG490 did not inhibit the arisostatins A-induced Hsp70 up-regulation, suggesting that JAK is not associated with the arisostatins A-mediated Hsp70 expression. The mechanism of Hsp70 induction depends on the activation of heat shock factor-1. However, arisostatins A did not effect the change in the expression levels of heat shock factor-1. CONCLUSIONS: These findings suggested that Hsp directly regulates specific stress-responsive signaling pathways, which may antagonize the signaling cascades that result in apoptosis.
Apoptosis ; Carcinoma, Renal Cell* ; Catalase ; Cell Death ; Cell Line* ; Heat-Shock Proteins* ; Hot Temperature* ; HSP70 Heat-Shock Proteins* ; Plasmids ; Protein-Tyrosine Kinases ; Shock ; Superoxide Dismutase ; Trypan Blue ; Up-Regulation

No abstract available.
Apoptosis* ; Carcinoma, Renal Cell* ; Cell Line* ; Interferon-gamma*

PURPOSE: Curcumin is the major constitute of turmeric powder extracted from the rhizomes of the plant Curcuma longa. We investigated that the effect of curcumin on regulatory protein of cell cycle, induction of apoptosis and metalloproteinase (MMP) activity in Caki cells, renal cell carcinoma (RCC) line. MATERIALS AND METHODS: The Caki cells were treated with curcumin for 24 h and cells were visually monitored and photographed. The cell viability was determined by trypan blue exclusion staining. The expression levels of cell cycle regulatory proteins and apoptosis regulatory proteins were determined by Western blot. To address the significance of caspase activation in curcumin-induced apoptosis, we used a general and potent inhibitor of caspases, z-VAD-fmk. The expression and secretion of MMP were determined by gelatin zymography. RESULTS: Treatment with curcumin produced morphological changing and DNA fragmentation in Caki cells. It also inhibited cellular growth and reduced cell viability in Caki cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Reduction of cell viability was associated with caspase 3 activation. The elevated caspase 3 activity in curcumin treated Caki cells are correlated with down-regulation of XIAP and cIAP1. Caspase inhibitor co-treated cells abolished curcumin-induced caspase 3 activity. The release of cytochrome c in curcumin-induced Caki cells was dose-dependent manners. Although MMP-2 expression levels were not significantly altered, however, the expression and secretion levels of MMP-9 were induced by PMA dose-dependent manners. CONCLUSIONS: Curcumin induces apoptosis and inhibit invasion by down regulation of regulatory protein of cell cycle, apoptosis related protein and MMP activity. These findings have implications for developing curcumin-based anticancer prevention or therapy of RCC.
Apoptosis Regulatory Proteins ; Apoptosis* ; Blotting, Western ; Carcinoma, Renal Cell ; Caspase 3 ; Caspases ; Cell Cycle ; Cell Cycle Proteins ; Cell Line* ; Cell Survival ; Curcuma ; Curcumin* ; Cytochromes c ; DNA Fragmentation ; Down-Regulation ; Gelatin ; Kidney Neoplasms* ; Plants ; Rhizome ; Trypan Blue

BACKGROUND: Malignant gliomas are the most common primary tumors in the central nervous system. METHODS: We investigated the combined effect of PG490 and LPS on the induction of the apoptotic pathway in human astroglioma cells. RESULTS: Treatment of U87 cells with combination of 50 nM of PG490 and 50microgram/ml of LPS resulted in increased internucleosomal DNA fragmentation, cleavage of PLC-gamma1, and down- regulation of cIAP1 and XIAP. The combination of LPS and PG490 treatment-induced apoptosis is mediated through the activation of caspase, which is inhibited by the caspase inhibitor, z-VAD-fmk. Also, release of cytochrome c was found in PG490 and LPS- cotreated U87 cell. CONCLUSION: Taken together, combination of PG490 and LPS appears to be a potent inducer of apoptosis in astrogliaoma cells, and might have some benefit in the treatment of glioma patients.
Apoptosis* ; Astrocytoma* ; Central Nervous System ; Cytochromes c ; DNA Fragmentation ; Glioma ; Humans*

PURPOSE: Expression levels of tumor necrosis factor (TNF)-alpha expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-alpha has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. METHODS: Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-alpha, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. RESULTS: TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P=0.043). TNF-alpha (P=0.0001) and DR4 (P=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. CONCLUSION: These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-alpha expression and DR4 pathway may have an important role in apoptosis.
Apoptosis ; Atrophy ; Cell Death ; Enterocolitis ; Epithelial Cells ; Fas Ligand Protein ; Humans ; Infant ; Intestine, Small ; Mucous Membrane ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha ; Up-Regulation

Forty two patients were diagnosed as having subcortical(lobar) intracerebral hemorrhage among 407 consecutive patients presenting with spontaneous intracerebral hemorrhage. Brain CT and MRI or angiography were performed in 39 patients. The authors analyzed clinical features, brain CT, etiological factors, and outcome. Headache(69%) and vomiting(55%) were most common symptoms. The incidence of seizure was 14%. The volume of hematoma on CT was below 20cc in 21 patients, between 20cc and 40cc in 16 patients, and aove 40cc in 5 patients. The most common site of hemorrhage was parietal lobe in 32 of 42 patients. The mortality rate was 9.5% and the functional outcome of the patients was generally better than in other forms of intracerebral hemorrhage. Thirty one patients had arterial hypertension which was the leading cause. Two patients had AVMs and two patients had blood dyscrasias. Unknown etiology occurred in 7 patients. Neither brain MRI nor cerebral angiography showed abnormal vascular lesion in all of the pa tients who had arterial hypertension. We conclude that no further evaluation if recommended in patients with subcortical hemorrhage who were definitely diagnosed as having arterial hypertension.
Angiography ; Brain ; Cerebral Angiography ; Cerebral Hemorrhage ; Hematoma ; Hemorrhage ; Humans ; Hypertension ; Incidence ; Magnetic Resonance Imaging ; Mortality ; Parietal Lobe ; Seizures

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.
Apoptosis* ; Caspase 3 ; Cell Cycle Proteins ; Cell Cycle* ; Cell Death ; Complementary Therapies ; Curcuma ; Curcumin* ; Cytochromes c ; Cytosol ; Down-Regulation ; Gelatin ; Neoplasm Metastasis* ; Plants ; Plants, Medicinal ; Reactive Oxygen Species ; Rhizome ; Vitis

Presented here in are two cases of chronic subdural hematoma in children which were spontaneously resolved. The first case has developed as the complication of a ventriculoperitoneal shunt in bilateral cerebral convexities of a 14-year-old boy while in the other case, the hematoma was developed in the posterior fossa of a 19 days-old neonate are complication of delivery. The etiology, clinical couse, treatment and mechanism of spontaneous resolution of chronic subdural hematomas in children and adult are discussed.
Adolescent ; Adult ; Child* ; Hematoma ; Hematoma, Subdural, Chronic* ; Humans ; Infant, Newborn ; Male ; Ventriculoperitoneal Shunt

PURPOSE: The prognosis of patients with advanced non-small-cell lung cancer (NSCLC) is extremely poor. Many prospective randomized trials on patients with advanced NSCLC suggested systemic chemotherapy improves both the survival and quality of life. A phase II trial was conducted to evaluate the efficacy and safety profile of the combination chemotherapy of gemcitabine and cisplatin in advanced NSCLC. MATERIALS AND METHODS: Forty-four patients with locally advanced or metastatic NSCLC were enrolled. The patients received a cisplatin, 75 mg/m(2), infusion over 30 minutes on days 1, followed by a gemcitabine, 1, 250 mg/m(2), infusion over 30 minutes on days 1 and 8 every 3 weeks. RESULTS: The median age of the patients was 64 years (range: 27~75). Forty-one patients were assessable for response and toxicity analyses. The overall response rate was 53.6%, but with no complete remissions. The median time to progression was 5.6 months (range: 1~15.4). The median survival was 14.2 months (95% confidence interval (CI), 13.8~22.5). A total of 179 cycles were administered, with a median of 4 cycles of chemotherapy, ranging from 2 to 9 cycles. The most common hematological toxicities were NCI grades 3/4 neutropenia (24%) and thrombocytopenia (7.8%). The most common non-hematological toxicity was fatigue (42.4%). There were no life-threatening toxicity or treatment related mortalities. The median duration of follow up was 9.4 months, ranging from 1.6 to 30.3 months. CONCLUSION: In this trial, the combination of gemcitabine and cisplatin showed significant activity, with acceptable and manageable toxicities as a first-line regimen for patients with advanced NSCLC.
Cisplatin* ; Drug Therapy ; Drug Therapy, Combination ; Fatigue ; Follow-Up Studies ; Humans ; Lung Neoplasms* ; Lung* ; Mortality ; Neutropenia ; Prognosis ; Prospective Studies ; Quality of Life ; Thrombocytopenia

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