Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeic acid phenethyl ester (CAPE) was isolated from propolis (a product of honeybee hives) that has been used in folk medicine as a potent antiinflammatory agent. CAPE is cytotoxic to tumor and virally transformed but not to normal cells. Our main goal was to establish whether CAPE inhibits the tumor promoter (12-O-tetradecanoylphorbol-13-acetate)-induced processes associated with carcinogenesis. Topical treatment of SENCAR mice with very low doses (0.1-6.5 nmol/topical treatment) of CAPE strongly inhibits the following 12-O-tetradecanoylphorbol-13-acetate-mediated oxidative processes that are considered essential for tumor promotion: (a) polymorphonuclear leukocyte infiltration into mouse skin and ears, as quantified by myeloperoxidase activity; (b) hydrogen peroxide (H2O2) production; and (c) formation of oxidized bases in epidermal DNA, as measured by 5-hydroxymethyluracil and 8-hydroxylguanine. A 0.5-nmol dose of CAPE suppresses the oxidative burst of human polymorphonuclear leukocytes by 50%. At higher doses (1-10 mumol), CAPE inhibits edema and ornithine decarboxylase induction in CD-1 and SENCAR mice. Interestingly, we discovered that 12-O-tetradecanoylphorbol-13-acetate-induced H2O2 production in bovine lenses also is inhibited by CAPE. Cumulatively, these findings point to CAPE as being a potent chemopreventive agent, which may be useful in combating diseases with strong inflammatory and/or oxidative stress components, i.e., various types of cancer and possibly cataract development.
Cancer Res 1993 Mar 15
PMID:Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester. 768 Feb 81

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one course of treatment, and none revealed any human anti-mouse antibody (HAMA) response. Clinical side-effects of patients treated with ch14.18 were abdominal and joint pains, pruritus and urticaria. One patient presented with a transient pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve that was probably attributable to prior therapies. A complete remission was seen in 2 patients, partial remission in 2 patients, a minor response in 1 patient and stable disease in 1 patient. 3 patients showed tumour progression. Thus, our results indicate that treatment with chimeric MAb ch14.18 can elicit some complete and partial tumour responses in neuroblastoma patients.
Eur J Cancer 1995
PMID:A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. 771 35

Thirteen patients with relapsed or refractory Non-Hodgkin's Lymphoma were treated with 131I-Lym-1 during the course of a dose escalation trial. Principal aims were to establish the maximum tolerated single dose (MTD), as well as to assess clinical and dosimetric effects of the MTD. Patients were eligible if > 25% of tumor cells bound Lym-1 on immunohistochemistry, stain intensity was +2/4 or greater and human anti-mouse antibody (HAMA) assay was negative. Radioimmunotherapy was performed with escalating doses at levels of 50 mCi, 65 mCi/m2 and 80 mCi/m2 (50-139 mCi total). Patients were eligible for retreatment after 6-10 weeks if there was no severe toxicity, their disease was at least stable and HAMA remained negative. Three were retreated. Four have achieved partial responses which lasted 11, 11, 18 and 22 weeks. Acute toxicities included rigors (69%), fever (62%), nausea (46%), vomiting (46%), pruritus (23%), urticaria (23%), chest pain (23%) and bronchospasm (15%). HAMA developed in 3 patients. Myelosuppression, manifested as thrombocytopenia and neutropenia, was dose-limiting and defined the single dose MTD at 65 mCi/m2. Plasma radioactivity clearance was biphasic, with a 0.9 hr alpha-T1/2 and a 19.8 hr beta-T1/2. At completion of Lym-1 infusion, a mean of 45% of the injected dose was recoverable in the circulation. Images obtained within the first 2 hours indicated mean hepatic and splenic uptake was 29% and 11%, respectively. Radiation absorbed doses to tumor ranged from 18-61 rads; mean doses to whole body ranged from 17 to 71 rads.
Cancer Biother 1993
PMID:A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1. 781 46

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.
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PMID:Phase I trial of cisplatin, WR-2721, and the murine monoclonal antibody R24 in patients with metastatic melanoma: clinical and biologic effects. 806

We present the case of a 27-year-old Caucasian woman who suffered from Langerhans cell histiocytosis with axillary and scalp involvement. She also developed diabetes insipidus after 2 years of skin lesions. Topical nitrogen mustard therapy was performed for the skin lesions, but we had to stop this therapy because of severe local irritation and systemic urticaria. Afterwards, we administered etoposide systemically, but no improvement appeared in 6 weeks. Finally we used methotrexate for 3 months and the result was very good at the end of the first month.
Cancer Lett 1994 Sep 15
PMID:Langerhans cell histiocytosis in an adult. 807 73

Murine monoclonal antibody (MAb) R-24 reacts with the ganglioside GD3 that is highly expressed on malignant melanoma. 2 patients with melanosis of the meninges received MAb R-24 intrathecally. Regressive changes in tumour cells were observed in both patients after intrathecal application of MAb R-24 (1-10 mg, 8-10 h, over 5-6 weeks). The first patient suffered from brain metastases and died a few weeks later, whereas the second achieved a complete remission with no evidence of disease 6 years after intrathecal R-24 treatment. No R-24-related neurotoxicity has occurred to date. The administration of MAb R-24 caused an increase of inflammatory cells in the cerebrospinal fluid (CSF) of both patients. Cytotoxic lymphocytes, cultured from the CSF, showed high cytolytic activity against allogeneic melanoma cells in vitro. In addition, 15 patients with advanced melanoma, in which the brain was not affected, were treated with R-24 intravenously using high dose R-24 (5 or 10 mg/m2) or low dose R-24 (1 mg/m2). No remissions were registered in the high dose group, with only 1/6 patients experiencing a mixed response. In contrast, 2/9 patients treated with low dose R-24 achieved a partial remission, one achieving a minor response and the other a mixed response. Toxicity was related to the dose of R-24 administered. Urticaria, burning and pruritus were the prominent side-effects, mostly occurring at the high dose level. Immunological monitoring during and after intravenous treatment showed no significant changes in peripheral blood lymphocytes, natural killer cell activity or antibody-dependent cellular cytotoxicity, although transient changes were observed. There was no correlation between immunological parameters and clinical response.
Eur J Cancer 1994
PMID:Immunological response to intrathecal and systemic treatment with ganglioside antibody R-24 in patients with malignant melanoma. 815 84

Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.
Cancer Res 1993 Sep 15
PMID:Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. 836 13

In order to assess the association between atopy and cancer risk, a cohort of 6593 skin-prick-tested patients was established. Among atopic subjects, no overall increased cancer risk was found, but the incidence of both breast cancer (standardized incidence ratio (SIR) 2.50, 95% CI 1.01-5.16) and malignant lymphomas (SIR 4.40, 95% CI 1.20-11.3) was significantly enhanced. Atopic subjects with asthma showed a decreased overall cancer risk (SIR 0.73, 95% CI 0.27-1.60), as compared with the other asthmatic subjects (SIR 1.46, 95% CI 1.03-2.04). The cancer risk for subjects with rhinitis was near unity (SIR 1.11), irrespective of whether the subjects were atopic or not. An almost significant risk increase for cancer was observed among subjects with urticaria (SIR 1.70, 95% CI 0.99-2.80). Our results support neither the original hypothesis of an overall cancer protective effect of atopy, nor that of an opposite effect; rather, they strengthen the view that the association between atopic diseases and cancer is complex.
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PMID:A prospective study of cancer incidence in a cohort examined for allergy. 854 65

The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose escalation trial in patients with refractory Hodgkin's lymphoma. The IT was constructed by linking the monoclonal antibody RFT5 via a sterically hindered disulfide linker to deglycosylated ricin-A. All patients in this trial were heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies, including autologous bone marrow transplantation in 8 of 15. The mean age was 29 years (range, 19 to 34 years). Thirteen of 15 patients had advanced disease (stage IV) with massive tumor burdens and 6 of 15 had B symptoms. The IT was administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses per cycle of 5, 10, 15, or 20 mg/m2. Patients received one to four cycles of treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7 micrograms/mL. The serum half life (T1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours). Side effects were related to vascular leak syndrome (VLS), ie, decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2 allergic reaction with generalized urticaria and mild bronchospasm. At 15 mg/m2, 1 patient experienced a grade 3 myalgia. All 3 patients receiving 20 mg/m2 experienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal tolerated dose was 15 mg/m2. Seven of 15 patients made human antiricin antibodies (> or = 1.0 microgram/mL) and 6 of 15 developed human antimouse antibodies (> or = 1.0 microgram/mL). Clinical response included 2 partial remissions, 1 minor response, 3 stable diseases, and 9 progressive diseases. As has been predicted from the preclinical tests, these data seem to indicate clinical efficacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting further clinical investigation.
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PMID:A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. 900 41

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant derived from the propolis of honeybee hives. CAPE was shown to inhibit the formation of intracellular hydrogen peroxide and oxidized bases in DNA of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated HeLa cells and was also found to induce a redox change that correlated with differential growth effects in transformed cells but not the nontumorigenic parental ones. Mediated via the electrophile or human antioxidant response element (hARE), induction of the expression of NAD(P)H quinone oxidoreductase (NQO1) and glutathione S-transferase Ya subunit genes by certain phenolic antioxidants has been correlated with the chemopreventive properties of these agents. Here, we determined by Northern analysis that CAPE treatment of hepatoma cells stimulates NQO1 gene expression in cultured human hepatoma cells (HepG2), and we characterized the effects of CAPE treatment on the expression of a reporter gene either containing or lacking the hARE or carrying a mutant version of this element in rodent hepatoma (Hepa-1) transfectants. A dose-dependent transactivation of human hARE-mediated chloramphenicol acetyltransferase (cat) gene expression was observed upon treatments of the Hepa-1 transfectants with TPA, a known inducer, as well as with CAPE. The combined treatments resulted in an apparent additive stimulation of the reporter expression. To learn whether this activation of cat gene expression was effected by protein kinase C in CAPE-treated cells, a comparison was made of cat gene activity after addition of calphostin, a protein kinase C inhibitor. Calphostin reduced the cat gene induction by TPA but not by CAPE, suggesting that stimulation of gene expression in this system by these agents proceeds via distinct mechanisms. Band-shift experiments to examine binding of transactivator proteins from nuclear extracts of treated and untreated cells to a hARE DNA probe showed that TPA exposure increased the binding level. In contrast, binding of factors to this probe was inhibited after either in vivo treatment of cells with CAPE or in vitro addition of this compound to the nuclear extract. In view of the clear stimulation by CAPE of gene expression mediated by hARE, possible explanations of this result are discussed.
Cancer Res 1997 Feb 01
PMID:Caffeic acid phenethyl ester stimulates human antioxidant response element-mediated expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene. 901 71


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