Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.17 (PCE)
 1,301 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An oxygen dependent signal was detected, late in the 1950s by electron spin resonance (ESR) in a saline solution of hematoporphyrin (Hp) excited by light. This signal expressed a free radical consisting of 'some kind of an association between Hp and oxygen', that Smaller et al. called 'oxyradical' (HpOO.). It soon opened a new level of understanding in carcinogenesis triggered by photodynamic substances, including Hp itself, polycyclic hydrocarbons (PCHs), as well as any carcinogen involving molecular species activated by radiation and/or metabolic reaction. Early in the 1960s, this prompted the discovery of benzo(a)pyrene (BP) photocarcinogenic enhancement (BP-PCE) in mice, probably due to an increase in free oxygen radical generation following correct light exposure. This assumption was confirmed in 1980 by the fact that mice orally loaded with antioxidants and radical quenchers, such as beta-carotene (BC) and cantaxanthin (CX), were protected against BP-PCE at 100% and against total BP carcinogenicity at more than 60%. These achievements were presented as the bases of the current explosion of interest in biology and medicine in building up the new field of chemoprevention against cancer and other chronic diseases by supplementation with antioxidant vitamins, retinoids and especially carotenoids and their synergistic association. The relevant findings of this research obtained in the last decade in in vitro and in vivo experiments as well as human interventions are reported and discussed with personal contributions.
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PMID:Free radicals as carcinogens and their quenchers as anticarcinogens. 180 72

Seventy-four patients with non-small cell lung cancer were treated in a prospective, randomized trial either with a four-drug combination of cisplatin, doxorubicin, cyclophosphamide, and vindesine (PACE) or with a three-drug combination of cisplatin, cyclophosphamide, and vindesine (PCE). None of these patients had received prior chemotherapy, and all had a Karnofsky performance status of at least 60. Of 68 evaluable patients, 21 (31%) had complete or partial remissions. Response rates for PACE and PCE were similar, and there was no difference in response rates for patients with adenocarcinoma or epidermoid cancer. The median duration of remission was 10 months (range, 2-26+); five patients are still in remission (median, 18+ months; range, 17+ to 26+). The median duration of survival for responding patients (complete or partial) was 18 months. Toxic effects, including mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, were manageable in general. The response rates and remission durations for PACE and PCE are similar to those seen with the two-drug combination of cisplatin and vindesine, and toxic effects are similar. Thus, the addition of doxorubicin and/or cyclophosphamide adds no advantage to the use of the cisplatin and vindesine combination alone.
Cancer Treat Rep 1982 Feb
PMID:Cisplatin, doxorubicin, cyclophosphamide, and vindesine combination chemotherapy for non-small cell lung cancer. 703 32

The potential human carcinogenicity of PCE has been the subject of study for many years, yet the largest and most recent occupational studies have not reported any increased risk of leukemia in PCE-exposed groups, let alone a risk of the magnitude suggested by Aschengrau et al. The EPA's own Science Advisory Board concluded in 1991 that PCE is a chemical "for which there is no compelling evidence of human cancer risk, accompanied by animal data of carcinogenicity whose extrapolation to humans is ambiguous." Given this background, it is not plausible that a leukemia risk of the magnitude reported by Aschengrau et al. should exist but not have been found among highly exposed occupational groups. Aschengrau et al. could contribute to our understanding of this inconsistency by presenting the additional data analysis that I have suggested.
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PMID:Apparent increased risk of leukemia in their highest category of exposure to tetrachloroethylene (PCE) in drinking water. 821 91

The risk assessment process predicts the chances of adverse health effects that the toxicant possibly can do to the target organism under expected conditions of exposure. Regulators chose among several mathematical approaches to estimate the risk, but in each case it is necessary to link the dosemetrics of the toxicant with its predicted health effect. In this paper, a computer program is described that allowed us to link a physiologically based pharmacokinetic (PBPK) model for tetrachloroethylene (PCE) in the lactating mother with the estimate of extra cancer risk for breast-fed infants, according to the U.S. Environmental Protection Agency (EPA) methodology. When inhaled by a lactating woman, PCE may partition into breast milk and may be transferred to the breast-fed infant. We have developed and validated experimentally a PBPK model for lactational transfer of PCE in rats, including a quantitative description of a milk compartment and the nursing pup. Subsequently, the model has been scaled to describe human physiology, and was validated with literature data for human cases of PCE exposure. Finally, we linked the dosage predictions of the PBPK model with equations used by EPA to estimate the cancer risk from PCE. The model predictions are in good agreement with both the measured values and those reported in the literature for exposure to PCE. This comparison confirms the usefulness of PBPK modeling in risk assessments.
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PMID:A computer program linking physiologically based pharmacokinetic model with cancer risk assessment for breast-fed infants. 779 84

Based on a variety of maternal occupational and residential inhalation exposure scenarios, estimates of infant exposure to the dry-cleaning solvent tetrachlorothylene (perchloroethylene, PCE) in breastmilk were made. Physiologically based pharmacokinetic (PBPK) modeling indicates that infants may be exposed to elevated levels of PCE in breastmilk due to their mothers' inhalation of PCE. The PBPK-predicted breastmilk PCE concentrations agree very well with measured concentrations, where available. Based on this analysis, infants may be exposed to this workplace chemical via breastmilk at doses corresponding to rather high levels of risk. Predicted breastmilk doses provide the infant with little margin of exposure to doses associated with adverse health effects. In addition, the estimated increased cancer risks associated with these infant exposures are large under certain exposure scenarios. The actual concentrations of PCE in breastmilk of exposed mothers can only be known with certainty if monitoring is conducted. Due to the widespread exposure potential, monitoring studies should be undertaken so that the appropriate risk management alternatives can be better evaluated.
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PMID:Predicted infant exposure to tetrachloroethene in human breastmilk. 825 41

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are major metabolites of tetrachloroethylene (PCE) and trichloroethylene (TCE) and are found in chlorinated drinking water. All four chlorinated compounds are liver carcinogens in B6C3F1 mice. It has previously been reported that approximately 20% of hepatic tumors induced by PCE exhibited loss of heterozygosity (LOH) on chromosome 6, suggesting the presence of a tumor suppressor gene. In the current investigation, we determined whether TCA or DCA also induced LOH on chromosome 6. Liver tumors were initiated in 15 day old female B6C3F1 mice with N-methyl-N-nitrosourea (MNU) and promoted with 20 mmol/l DCA or TCA in their drinking water. Twenty-four and thirty-seven liver tumors promoted by DCA and TCA, respectively, were examined for LOH using 4 polymorphic loci on chromosome 6. Ten of 37 (27%) tumors (7 of 27 carcinomas and 3 of 10 adenomas) promoted by TCA exhibited LOH at least for two loci on chromosome 6. All 10 tumors that exhibited LOH, lost the C57BL/6J allele at both the D6mit9 loci, while two also lost at least one of the C3H/HeJ alleles. No LOH on chromosome 6 was observed in the 24 liver tumors promoted by DCA. The LOH on chromosome 6 in TCA but not in DCA-promoted tumors supports it as an active metabolite of PCE and demonstrates different pathogenesis at least for some of the DCA and TCA-promoted liver cancer.
Cancer Lett 1996 Nov 29
PMID:Loss of heterozygosity on chromosome 6 in dichloroacetic acid and trichloroacetic acid-induced liver tumors in female B6C3F1 mice. 897 3

We conducted a population-based case-control study to evaluate the relationship between cancer of the colon-rectum (n = 326), lung (n = 252), brain (n = 37), and pancreas (n = 37), and exposure to tetrachloroethylene (PCE) from public drinking water. Subjects were exposed to PCE when it leached from the vinyl lining of drinking-water distribution pipes. Relative delivered dose of PCE was estimated using a model that took into account residential location, years of residence, water flow, and pipe characteristics. Adjusted odds ratios (ORs) for lung cancer were moderately elevated among subjects whose exposure level was above the 90th percentile whether or not a latent period was assumed [ORs and 95% confidence intervals (CIs), 3.7 (1.0-11.7), 3.3 (0.6-13.4), 6.2 (1.1-31.6), and 19.3 (2.5-141.7) for 0, 5, 7, and 9 years of latency, respectively]. The adjusted ORs for colon-rectum cancer were modestly elevated among ever-exposed subjects as more years of latency were assumed [OR and CI, 1.7 (0.8-3.8) and 2.0 (0.6-5.8) for 11 and 13 years of latency, respectively]. These elevated ORs stemmed mainly from associations with rectal cancer. Adjusted ORs for rectal cancer among ever-exposed subjects were more elevated [OR and CI, 2.6 (0. 8-6.7) and 3.1 (0.7-10.9) for 11 and 13 years of latency, respectively] than were corresponding estimates for colon cancer [OR and CI, 1.3 (0.5-3.5) and 1.5 (0.3-5.8) for 11 and 13 years of latency, respectively]. These results provide evidence for an association between PCE-contaminated public drinking water and cancer of the lung and, possibly, cancer of the colon-rectum.
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PMID:Tetrachloroethylene-contaminated drinking water in Massachusetts and the risk of colon-rectum, lung, and other cancers. 1009 Jul 4

The widespread use and storage of volatile organic compounds (VOCs) in the United States has led to releases of these chemicals into the environment, including groundwater sources of drinking water. Many of these VOCs are commonly found in public drinking water supplies across the nation and are considered by state or federal agencies to be potentially carcinogenic to humans. In this paper, we evaluate the detection frequencies, detected concentrations, and relative cancer risks of six VOCs in drinking water sources in California from 1995 to 2001. We find that during this 7-year period, the most frequently detected VOCs in sampled drinking water sources were chloroform (12-14%), PCE (11-13%), and TCE (10-12%). Detection frequencies in water were lower for 1,1-DCE (3-6%), MTBE (1-3%), and benzene (<1%). Mean detected concentrations were also consistently above California's primary maximum contaminant level for some VOCs, including benzene, PCE, and TCE. Although none of the six VOCs necessarily poses a significant public health threat from drinking water exposures, 1,1-DCE and benzene werefound to pose the greatest cancer risk relative to the other VOCs. However, after adjusting for the occurrence of each VOC in drinking water, chloroform and PCE were found to pose the greatest relative cancer risk. Despite media reports about significant MTBE contamination of drinking watersupplies in California, MTBE detections were infrequent and this chemical was found to pose the least cancer risk relative to the other VOCs.
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PMID:Comparative risk analysis of six volatile organic compounds in California drinking water. 1248 91

Peritoneal metastases are a common sequela of gastrointestinal malignancy. The treatment of peritoneal metastases through use of aggressive surgical cytoreduction including peritonectomy, coupled with IPHC has now been reported in several large single institution series. The available literature suggests that in experienced hands and with appropriate patient selection, cytoreduction, and IPHC can be an effective therapy, particularly when all macroscopic tumor deposits are removed. Different techniques involving the administration of intraperitoneal chemotherapy have been reported including early postoperative, closed intraoperative, the open or coliseum technique, and the open technique using a PCE device. All techniques have been associated with low mortality and morbidity that is significant, but generally consistent with other major surgical procedures. Commonly reported complications of IPHC include prolonged ileus, fistula, abscess, and thrombosis. In theory, the coliseum and PCE techniques may have less associated morbidity due to improved heat distribution, however, this remains to be definitively proven in a controlled clinical trial. Such controlled studies are critical to defining the best techniques of IPHC administration and the appropriate role for this treatment regimen in patients with peritoneal metastases.
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PMID:Technology of intraperitoneal chemotherapy administration: a survey of techniques with a review of morbidity and mortality. 1456 36

Extracorporeal photochimiotherapy (ECP) is based on the exposure of peripheral blood mononuclear cells to the photosensitizing agent (psoralen or 8MOP) and UVA radiation. Mononuclear cells are harvested by cytapheresis and reinfused to the patient after irradiation. This cell therapy has been shown to be effective in the treatment of selected diseases mediated by clonal T cells proliferation such as Sezary T cells lymphoma, rejection after solid organ transplantation and graft-versus-host disease but results obtained in autoimmune diseases are less convincing. ECP is well tolerated with very few side effects and can be combined with immunosuppressive drugs. Two methods of ECP are currently used: in the first one, the whole procedure is performed with the same equipment whereas in the second one, the cytapheresis is performed on a conventional cell separator and treated with an independent UVA irradiation: Experimental data and clinical results suggest that PCE might induced an immune response against pathological T cells clones. However, technical differences in the methods of PCE and weak knowledge on its mechanism of action impair the standardization and evaluation of this cell therapy process as well as its clinical development.
Bull Cancer
PMID:[Extracorporeal photochemotherapy for treatment of clonal T cell proliferations]. 1460 67


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