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)

Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic agents active in treating many malignant diseases. The ICE combination (ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer, small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other malignancies with promising results. We conducted a dose-escalation study of paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide 1.25 g/m2/d days 1 to 3, carboplatin 300 mg/m2 day 1, and etoposide 80 mg/m2/d days 1 to 3. Paclitaxel was given at a dose of 120 mg/m2 to five patients, 135 mg/m2 to five patients, 150 mg/m2 to three patients, and 175 mg/m2 to 11 patients. All patients received granulocyte colony-stimulating factor support. The most common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever occurring during 14% of cycles. No treatment-related death or sepsis occurred due to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other toxicities were mostly mild to moderate and did not require dose modification, although alopecia was universal. Nine patients (100%) with metastatic breast cancer and four (67%) with soft tissue sarcoma have attained documented objective responses with four complete remissions (one breast cancer and three sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been defined, and the study is ongoing. In conclusion, this pilot study showed that ICE-T is safe and tolerable. The response to ICE-T is encouraging and warrants further study with this regimen.
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PMID:Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: a dose-escalation study. 867 54

Five patients with metastatic testicular cancer of advanced extent according to the Indiana University criteria were enrolled into this study. All tumors were non-pretreated non-seminomas. Initially all patients were treated with standard dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the five patients showed a good response to VIP and subsequently achieved a pathological complete response (pCR) following surgical resection of residual masses after 3 or 5 courses of VIP. However, they suffered from severe myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT) following the final course of VIP. The remaining three patients unlikely to be cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10 g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400 mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial response (PR) with marker-negative and two PR with marker-positive. Residual masses were removed in all three patients and viable tumor cells were found in two. Of the five patients enrolled, four patients (80%) remain disease-free with minimal follow-up of 20 months, and the remaining one died of cancer 10 months after PBSCT. No serious side effects or complications were encountered. This study shows that standard dose induction therapy of VIP followed by early salvage chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the treatment of advanced poor-risk testicular cancer.
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PMID:[High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer]. 965 1

Spermatogenesis is a phenomenon where two main processes proliferation and apoptosis, meet. Slight changes in their activities could lead to different pathologies, such as fertility disorder (excessive apoptosis) or testicular cancer (overproliferation). The IL-1 gene family includes genes which play important roles in both these processes and consists of IL-1?, IL-1ss, IL-18, the IL-1 receptor antagonist (IL-1RA), two IL-1 receptors (IL-1RI, IL-1RII), the IL-18 receptor (IL-18R?), and the receptor-associated proteins - IL-1RAcP and IL-18Rss. Caspase-1 (ICE - interleukin-1 converting enzyme), directly connected with apoptosis and responsible for the cleavage of IL-1b and IL-18, is also a member of the IL-1 family. The system of the numerous IL-1 receptors and their signal transduction involving protein cascades provokes a range of gene expressions necessary for the initiation and maintenance of inflammatory reaction. In the testis, IL-1 is constitutively expressed, where it creates a unique microenvironment for diploid gametogenic cell conversion into specialized haploid spermatozoa. It may also be an element of the physiological protection from autoimmune attack by host testicular antigens and a part of immune privilege. This review is to summarize the knowledge of the local control of spermatogenesis and immunomodulation in the male gonad. As infertility is one of the main problems of industrialized countries, study of the pathophysiology of the male genital tract appears essential in future clinical practice.
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PMID:[Function of the interleukin-1 gene system in immunomodulation, apoptosis and proliferation in the male gonad]. 1576 87