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

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.
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PMID:Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression. 798 6

An accredited laboratory means that its competence in performing particular tests and examinations is officially recognised. Requirements concerning testing laboratories are specified in the European Standard EN 45001 and in the Guide ISO/ICE-25. When applying for an accreditation laboratories of the State Sanitary Inspectorate have to develop new or adjust existing systems of quality assurance in accordance with the aforesaid recommendations. The system of laboratory quality assurance should be described thoroughly in the quality manual and backed up by an appropriate documentation. An application for accreditation should be preceded by the following steps: setting up of a team of persons responsible for quality assurance policy, drawing up criteria for assessing testing methods and procedures, promoting principles of quality assurance and introducing necessary corrections, formulating an accreditation application form which should comprise: the range of expected accreditation, kind of investigations to be performed and methods to be applied. An application together with the quality manual should be submitted to the Central Bureau for Product Quality Assurance in Warsaw--the only office which grants accreditation in Poland.
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PMID:[Quality assurance of examinations performed by laboratories of the State Sanitary Inspection Service]. 800 25

Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the precursor of the cytokine IL-1 beta to a mature, biologically active form in monocytes and macrophages. To further understand the role of ICE in regulating IL-1 beta-mediated biological functions, we have isolated several genomic clones encoding the full-length murine ICE gene. Southern blot comparison of murine genomic DNA and the clones indicates that ICE is a compact, single-copy gene 8616 bp in size. We sequenced the entire gene as well as 1.0-kb segment upstream of the coding region and determined that the gene consists of 10 exons whose organization parallels the functional organization of the ICE proenzyme in that the prodomain and p20 and p10 subunits of ICE are encoded by three clusters of exons. Two initiation sites, 37 and 32 nucleotides upstream of the initiator methionine, were identified by primer extension analysis. The 5' region of the ICE gene lacks a TATA box, a CAAT box, and SP1 sites. However, the presence of a completely conserved 14-bp sequence spanning the transcription initiation site of both the murine and the human ICE genes suggests that this sequence plays a role in transcription.
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PMID:The structure and complete nucleotide sequence of the murine gene encoding interleukin-1 beta converting enzyme (ICE). 803 21

A total of 25 patients with epithelial ovarian cancer were treated with second-line carboplatin, etoposide, and ifosfamide (ICE) following failure of first-line cisplatin-based combination chemotherapy. The combination carboplatin 35 mg/m2, etoposide 50 mg/m2, and ifosfamide 1,200 mg/m2 was administered intravenously daily for 3 consecutive days. Response was seen in 13 patients (52%) with 7 complete responses (28%) and 6 partial responses (24%). Median duration of response was 9+ months (range: 4-17+ months). Response rate to second-line ICE relates directly to prior response to first-line cisplatin-based chemotherapy: 12 patients (67%) responded to second-line ICE who responded to first-line cisplatin-based chemotherapy, while only 1 patient (14%) responded who progressed on first-line cisplatin-based chemotherapy. Median survival was 18+ months (range: 2-31+ months). There were six episodes (4%) of grade 4 neutropenia, seven episodes (4%) of grade 4 thrombocytopenia and no grade 3 or 4 nonhematologic toxicity. ICE has moderate activity with minimal toxicity as second-line treatment of advanced epithelial ovarian cancer.
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PMID:Carboplatin, etoposide, and ifosfamide as second-line treatment for ovarian cancer. 804 96

The cDNA coding for the precursor form of human interleukin-1 beta-converting enzyme (proICE) was expressed in Spodoptera frugiperda (Sf9) insect cells using a baculovirus expression system. The 45-kDa recombinant protein was further processed to several smaller forms of 32, 24, 20, 13 and 10 kDa. Active recombinant ICE derived from the baculovirus expression system (bvICE) was found to be present in soluble lysates of insect cells as an associated heterodimer consisting of 10- and 20-kDa subunits. The activity of bvICE was determined by conversion of precursor interleukin-1 beta (preIL-1 beta) to the mature form (mIL-1 beta) and via site-specific cleavage of a decapeptide which spans the ICE cleavage site in preIL-1 beta. The bvICE system was inhibited by an ICE inhibitor to the same extent as native ICE from the monocytic cell line THP-1. Expression of an active-site mutant (Cys285 to Ser) of proICE in insect cells resulted in the accumulation of partially processed (32-kDa) ICE. The availability of a facile expression system will permit further characterization of the biochemical properties and processing pathway of this unique protease.
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PMID:Production of active human interleukin-1 beta-converting enzyme in a baculovirus expression system. 805 42

Three years of private urban practice of ICE with implantation of IOL in the AC, made us think this technique should be extended to the rural populations. Conclusions about the indications and the technique have been stressed so that better results can be reached.
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PMID:[Reflections on our experience of pseudophakia in Cameroon. Apropos of 26 cases]. 809 Oct 35

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. One of the principal control elements within the enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as the insulin control element [ICE]) and is regulated by both positive- and negative-acting transcription factors in the helix-loop-helix (HLH) family. It was previously shown that the c-jun proto-oncogene can repress insulin gene transcription. We have found that c-jun inhibits ICE-stimulated transcription. Inhibition of ICE-directed transcription is mediated by sequences within the carboxy-terminal region of the protein. These c-jun sequences span an activation domain and the basic leucine zipper DNA binding-dimerization region of the protein. Both regions of c-jun are conserved within the other members of the jun family: junB and junD. These proteins also suppress ICE-mediated transcription. The jun proteins do not appear to inhibit insulin gene transcription by binding directly to the ICE. c-jun and junB also block the trans-activation potential of two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results suggests that the jun proteins may be common transcription control factors used in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity. We discuss the possible significance of these observations to insulin gene transcription in pancreatic beta cells.
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PMID:c-jun inhibits transcriptional activation by the insulin enhancer, and the insulin control element is the target of control. 826 34

The insulin gene is expressed exclusively in pancreatic islet beta cells. The principal regulator of insulin gene transcription in the islet is the concentration of circulating glucose. Previous studies have demonstrated that transcription is regulated by the binding of trans-acting factors to specific cis-acting sequences within the 5'-flanking region of the insulin gene. To identify the cis-acting control elements within the rat insulin II gene that are responsible for regulating glucose-stimulated expression in the beta cell, we analyzed the effect of glucose on the in vivo expression of a series of transfected 5'-flanking deletion mutant constructs. We demonstrate that glucose-induced transcription of the rat insulin II gene is mediated by sequences located between -126 and -91 bp relative to the transcription start site. This region contains two cis-acting elements that are essential for directing pancreatic beta-cell-type-specific expression of the rat insulin II gene, the insulin control element (ICE; -100 to -91 bp) and RIPE3b1 (-115 to -107 bp). The gel mobility shift assay was used to determine whether the formation of the ICE- and RIPE3b1-specific factor-DNA element complexes were affected in glucose-treated beta-cell extracts. We found that RIPE3b1 binding activity was selectively induced by about eightfold. In contrast, binding to other insulin cis-acting element sequences like the ICE and RIPE3a2 (-108 to -99 bp) were unaffected by these conditions. The RIPE3b1 binding complex was shown to be distinct from the glucose-inducible factor that binds to an element located between -227 to -206 bp of the human and rat insulin I genes (D. Melloul, Y. Ben-Neriah, and E. Cerasi, Proc. Natl. Acad. Sci. USA 90:3865-3869, 1993). We have also shown that mannose, a sugar that can be metabolized by the beta cell, mimics the effects of glucose in the in vivo transfection assays and the in vitro RIPE3b1 binding assays. These results suggested that the RIPE3b1 transcription factor is a primary regulator of glucose-mediated transcription of the insulin gene. However, we found that mutations in either the ICE or the RIPE3b1 element reduced glucose-responsive expression from transfected 5'-flanking rat insulin II gene constructs. We therefore conclude that glucose-regulated transcription of the insulin gene is mediated by cis-acting elements required for beta-cell-type-specific expression.
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PMID:Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression. 828 26

A series of compounds containing a hydroxyethyl-based dipeptide surrogate have been prepared as probes to evaluate the possibility of ICE being an aspartic protease. The aldehyde t-BocAsp(beta-t-butyl)H reacted with the organochromium species derived from phenethyl bromide and CrCl2 to give the expected addition product. Lactonization, reprotection of the amine and oxidation with RuCl3 gave the two protected dipeptide surrogates 7a and 7b. These were incorporated into tetra-, penta- and hexapeptide-like molecules and evaluated as inhibitors of the enzyme. The failure of these compounds to inhibit ICE indicated that this enzyme was very unlikely to be an aspartic protease.
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PMID:Interleukin-1 beta converting enzyme. Synthesis of hydroxyethyl dipeptide surrogate-containing compounds as potential ICE inhibitors. 832 40

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.
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PMID:Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group. 842 73


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