Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-five patients with CML (chronic phase (CP): 15 patients; accelerated phase (AP): 10 patients) at a median of 40 months after diagnosis and ineligible for allogeneic BMT, received an intensive chemotherapy regimen consisting of idarubicin, intermediate-dose ara-C and etoposide (ICE protocol). All patients had previously received alpha-interferon and only two patients had had partial cytogenetic response. During recovery from chemotherapy-induced aplasia, blood progenitors cells (BPC) were harvested by leukapheresis. All metaphases were found to be Ph-negative in the collection of 12 of 25 (48%) patients (CP: 9 of 15 (60%), AP: 3 of 10 (30%)) and a decrease of < 50% Ph-positive metaphases was seen in an additional five (CP: 4 patients; AP: 1 patient). The percentage of complete Ph-disappearance was 66% in patients receiving this procedure within the first 2 years of diagnosis and 30% in those treated after the second year of diagnosis. So far, the Ph-negative collections have been used in 9 patients (CP: 8 patients; AP: 1 patient) as autograft after conditioning with total body irradiation/etoposide/CY. Seven of 9 patients engrafted and 5 are alive and well, Ph-negative at 2+, 3+, 6+, 10+ and 18+ months.
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PMID:Collection of 'normal' blood repopulating cells during early hemopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukemia. 769 24

Many anticancer agents induce apoptosis in human leukemia cells. Among the various leukemia cells, especially HL-60 cells and U937 cells are very sensitive to apoptosis upon anticancer agents treatment. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage in human myeloid leukemia HL-60 and U937 cells. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on anticancer agent-induced internucleosomal DNA cleavage. Our data indicate that serine and ICE-like proteases may be involved in anticancer agent-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in human myeloid leukemia HL-60 and U937 cells.
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PMID:[The mechanism of apoptosis induced by anticancer agents in human leukemia cells]. 874 73

The present study was designed to investigate the contribution of proteases in anticancer agents-induced apoptosis of human leukemia HL-60 cells. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on etoposide-induced internucleosomal DNA cleavage. We found that cell lysates prepared from etoposide-treated HL-60 cells undergoing apoptosis contain the significant activity to induce internucleosomal DNA fragmentation in isolated nuclei. On the other hand, we could not detect such activity in the cell lysates from untreated HL-60 cells. Treatment of the cell lysates with a serine protease inhibitor TPCK abrogated the DNA fragmenting activity. An ICE-like protease inhibitor VAD-FMK had no effect on this DNA fragmenting activity in vitro. However, the formation of TPCK-sensitive DNA fragmenting activity in etoposide-treated cells was blocked by the VAD-FMK. These data indicate that serine and ICE-like proteases may be involved in etoposide-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in HL-60 cells.
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PMID:[The mechanism of apoptosis induced by anticancer agents in human leukemia HL-60 cells]. 877 71

Expression and functional activity of P-glycoprotein (P-gp) were measured in 182 acute myelogenous leukemia (AML) patients: 136 patients were treated with the AML-6 protocol (EORTC), containing daunorubicin, vincristine, and conventional-dose cytarabine (ara-C), and 21 patients received idarubicin, vepeside, and conventional-dose ara-C (ICE-AML-10 protocol/EORTC). An additional 25 patients were treated with a dose of idarubicin and ara-C, modified as compared with the ICE protocol, but with the same dose of etopside (ICE-I protocol). P-gp was determined using monoclonal antibody 4E3.16 and functional activity using the rhodamine 123 accumulation test. P-gp positivity was defined as a Kolmogorov Smirnov (KS) D value > or = 0.15, P-gp negativity as a KS D value < 0.15. P-gp activity was defined as a ratio of mean rhodamine 123 accumulation with/without verapamil. In AML patients at primary diagnosis and early relapse/refractoriness a significant (p < 0.05) difference between P-gp-positive and P-gp-negative patients was ascertained using the AML-6 protocol; the difference corresponded to the complete remission rate. For ICE- and ICE-I-treated AML patients at primary diagnosis this significance was not shown. Compared with AML patients at primary diagnosis and patients at early relapse or refractoriness, a significantly (p < 0.05) increased incidence of non-pumping P-gp and a trend (p = 0.054) to a higher percentage of non-P-gp-related mechanisms in AML patients at late relapse was determined. When the AML-6 protocol is used, age, activated P-gp, and CD34 expression are independent prognostic factors in AML patients. A test system which determines a functional P-gp overexpression is a major tool for identifying a group of AML patients with a poor prognosis. In order to effectively use so-called P-gp modulator substances, the degree of P-gp expression, the activated or nonactivated P-gp condition, and detection of non-P-gp-related resistance mechanisms are of utmost interest for optimal design and analysis of P-gp modulator trials and for understanding the complexity of chemotherapy-related resistance mechanisms in patients.
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PMID:Expression and functional activity of P-glycoprotein in adult acute myelogenous leukemia patients. 932 79

The multicentre phase III CORAL study aims to guide choice of salvage chemotherapy in diffuse large B-cell lymphoma (DLBCL) and assess the role of rituximab maintenance after autologous stem cell transplantation (ASCT). Patients are first randomised between ICE (ifosfamide, carboplatin, etoposide) and DHAP (dexamethasone, ara-C and cisplatin), both combined with rituximab (R-ICE or R-DHAP). After three courses, responders are treated by ASCT with BEAM. A second randomisation then allocates patients to maintenance treatment with rituximab 375 mg/m(2), one injection every 2 months six times, or observation. Accrual to the study is now proceeding well and the planned 400 patients are likely to be enrolled within the next 1.5 years. Results to date are very preliminary but suggest encouraging rates of response. However, they also indicate that initial exposure to rituximab may increase the difficulty of salvaging patients who fail first-line therapy.
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PMID:Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. 1670 82