Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-alpha. No dose response effect for IFN-alpha was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-alpha and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans. 844 8

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.
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PMID:Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients. 927 42

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.
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PMID:Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer. 1074 53

A 79-year-old woman was admitted to a nearby hospital for seven days due to low-grade fever, loss of appetite and general fatigue. She was diagnosed with normal condition and discharged. She was admitted to our hospital one week later with disturbed consciousness. Laboratory findings upon admission revealed anemia, elevated alanine amino transferase, elevated total birirubin and thrombocytopenia. Abdominal CT demonstrated multiple low intensity lesions in the liver. Enhanced brain CT revealed multiple lesions with increased signal intensity lesions in the white matter and cortex. The value of soluble IL-2 receptor antibody was 16,000U/ml. Intravascular lymphoma was suspected because of brain CT finding and IL-2 receptor antibody titer. Methylprednisolone pulse therapy was started considering her age and general condition, but she was died thirteen days after admission. Postmorten examination revealed widespread intravascular aggregation of malignant lymphoma cells in the liver, spleen, bone marrow, bladder, ovary and stomach indicating a diagnosis of an Asian variant of intravascular large B cell lymphoma (AIVL). Neurological abnormalities are not usually associated with AIVL, but this patient had rare AIVL presenting with initial progressive nonspecific neurological symptoms.
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PMID:[A case of intravascular malignant lymphoma with initial progressive non-specific neurological symptoms]. 2201 66