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)

Seventeen patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with the ICE regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells (PSC) in the setting of an autotransplant program. Fifteen patients had CML in first chronic phase (CP), and two in accelerated phase (AP). Three patients had been previously treated with interferon alpha 2a (IFN). Twelve patients underwent leukaphereses and a mean of 4.7 x 10(8)/kg mononuclear cells were obtained. Four CP patients did not show a significant mobilization peak of CD34+ cells and leukapheresis was not performed; finally, one patient died before apheresis could be performed. Six of the 12 who underwent leukaphereses obtained more than 1.0 x 10(6)/kg CD34+ cells. Eight of the 12 mobilized patients (67%) obtained a major cytogenetic response, including two complete and six partial; in the remaining four patients minimal or absent cytogenetic responses were observed. A higher rate of Ph purging was obtained in patients mobilized early or showing residual Ph-negative cells before mobilization, even if they were in AP. Infectious complications were frequent with a 38% rate of bacteremia recorded and one case of pulmonary aspergillosis resulting in a toxicity similar to that occurring in acute myeloid leukemia-induction chemotherapy. The ICE regimen can promote 'in vivo' purging of the Ph+ cells in 67% of CML mobilized patients (8/12). Failure of mobilization occurs in 65% of patients (11/17), mainly because of poor CD34+ cell yield.
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PMID:Mobilization of peripheral stem cells with intensive chemotherapy (ICE regimen) and G-CSF in chronic myeloid leukemia. 893 40

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1beta release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K(+) efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1beta expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1beta. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1beta; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine.
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PMID:Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. 2036

Intestinal aspergillosis is an infection with a very high death rate especially in leukemic patients. Here we describe a case of a 46 years old woman with acute myeloid leukemia (LAM M5) who developed intestinal primary aspergillosis. This patient was diagnosed with LAM M5 through bone marrow aspiration and bone biopsy in March 2004. Symptoms of the disease were slight persistent fever, weight loss, asthenia, anemia, thrombocytopenia,and leukocytosis with high number of blasts in peripheral blood. After induction chemotherapy with ICE (Ifosfamide, Carboplatin, Etoposide), she developed neutropenia and high fever without apparent infective foci. She was treated with empiric antibiotic therapy, nevertheless she developed an intense diarrhea and ileo-cecal distention. Diagnostic exams didn't show signs of a focal lesion. Despite the change in antibiotic treatment and the transfusions of granulocytes and blood cells, the patient developed extremely critical conditions with persistence of neutropenia and abdominal distention. A surgical treatment was decided at the time. We treated the patient with a two steps surgical procedure. The first step was a right abdominal ileostomy followed by improvement of general conditions and then the second step a right colectomy. The histological morphology confirmed necrotizing colitis with Aspergillus ife. At that time , treatment with voriconazole was started. The general conditions of the patient improved rapidly and we were able to treat the patient with other medical anti-leukemic therapies. The patient is now cured and in healthy state. We obtained a good clinical result as only in other few cases described in literature.
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PMID:Emergency hemicolectomy for intestinal primary aspergillosis in acute myeloid leukemia. 2252 50