Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fresh organically grown pomegranates (Punica granatum L.) of the Wonderful cultivar were processed into three components: fermented juice, aqueous pericarp extract and cold-pressed or supercritical CO2-extracted seed oil. Exposure to additional solvents yielded polyphenol-rich fractions ('polyphenols') from each of the three components. Their actions, and of the crude whole oil and crude fermented and unfermented juice concentrate, were assessed in vitro for possible chemopreventive or adjuvant therapeutic potential in human breast cancer. The ability to effect a blockade of endogenous active estrogen biosynthesis was shown by polyphenols from fermented juice, pericarp, and oil, which inhibited aromatase activity by 60-80%. Fermented juice and pericarp polyphenols, and whole seed oil, inhibited 17-beta-hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at concentrations ranging from 100 to 1,000 microg/ml according to seed oil >> fermented juice polyphenols > pericarp polyphenols. In a yeast estrogen screen (YES) lyophilized fresh pomegranate juice effected a 55% inhibition of the estrogenic activity of 17-beta-estradiol; whereas the lyophilized juice by itself displayed only minimal estrogenic action. Inhibition of cell lines by fermented juice and pericarp polyphenols was according to estrogen-dependent (MCF-7) >> estrogen-independent (MB-MDA-231) > normal human breast epithelial cells (MCF-10A). In both MCF-7 and MB-MDA-231 cells, fermented pomegranate juice polyphenols consistently showed about twice the anti-proliferative effect as fresh pomegranate juice polyphenols. Pomegranate seed oil effected 90% inhibition of proliferation of MCF-7 at 100 microg/ml medium, 75% inhibition of invasion of MCF-7 across a Matrigel membrane at 10 microg/ml, and 54% apoptosis in MDA-MB-435 estrogen receptor negative metastatic human breast cancer cells at 50 microg/ml. In a murine mammary gland organ culture, fermented juice polyphenols effected 47% inhibition of cancerous lesion formation induced by the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The findings suggest that clinical trials to further assess chemopreventive and adjuvant therapeutic applications of pomegranate in human breast cancer may be warranted.
Breast Cancer Res Treat 2002 Feb
PMID:Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. 1200 40

Tamoxifen is primarily used in the treatment of breast cancer. It has been approved as a chemopreventive agent for individuals at high risk for this disease. Tamoxifen is metabolized to a number of different products by cytochrome P450 enzymes. The effect of tamoxifen on the enzymatic activity of bacterially expressed human cytochrome CYP2B6 in a reconstituted system has been investigated. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified CYP2B6 was inactivated by tamoxifen in a time- and concentration-dependent manner. Enzymatic activity was lost only in samples that were incubated with both tamoxifen and NADPH. The inactivation was characterized by a K(I) of 0.9 microM, a k(inact) of 0.02 min(-1), and a t(1/2) of 34 min. The loss in the 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity did not result in a similar percentage loss in the reduced carbon monoxide spectrum, suggesting that the heme moiety was not the major site of modification. The activity of CYP2B6 was not recovered after removal of free tamoxifen using spin column gel filtration. The loss in activity seemed to be due to a modification of the CYP2B6 and not reductase because adding fresh reductase back to the inactivated samples did not restore enzymatic activity. A reconstituted system containing purified CYP2B6, NADPH-reductase, and NADPH-generating system was found to catalyze tamoxifen metabolism to 4-OH-tamoxifen, 4'-OH-tamoxifen, and N-desmethyl-tamoxifen as analyzed by high-performance liquid chromatography analysis. Preliminary studies showed that tamoxifen had no effect on the activities of CYP1B1 and CYP3A4, whereas CYP2D6 and CYP2C9 exhibited a 25% loss in enzymatic activity.
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PMID:Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. 1202 23

A single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA) has been shown to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances, including attenuation of the preovulatory Luteinizing Hormone surge and Gonadotropin-Releasing Hormone release and amplification of the preovulatory 17beta-Estradiol (E2) surge. In this study, we examined the hypothesis that a single administration of DMBA increases the E2 and Progesterone inhibition of the spontaneous and Isoproterenol-induced Melatonin (MT) secretion from the pineal gland, during the latency phase. Also, the incidence of mammary tumors, as well as the possible preventive effect of various doses of Melatonin, were recorded up to 6 months after daily administration. For all studies, Sprague-Dawley rats, 55-60 days of age, received, on the Estrous day of the Estrous cycle, a single dose of 15 mg DMBA delivered by intragastric intubation. For the study on ovarian steroids, they were ovariectomized 5 days later and then sacrificed by decapitation at 10 a.m., one month later. Pineal glands were removed and placed in perifusion chambers containing Hanks 199 medium. The medium was saturated with O2/CO2 (95%/5%) and its pH was 7.4. Ten independent chambers were immersed in a water bath at 37 degrees C. Each pineal gland received medium (flow rate: 0.16 ml/min) through a system of input lines. The fractions were collected every 10 min, and immediately frozen at -20 degrees C until Melatonin RIA. Experiments were repeated to obtain up to five experimental points for each treatment. E2 (10(-11)-10(-9) M) and Progesterone (10(-9)-10(-7) M) were applied during the entire perifusion period (7 h). Isoproterenol (10(-6) M) was applied for 20 min after 2.5 h in perifusion. Melatonin concentrations and Areas Under the Curves were compared using two-factor ANOVA as well as parametric or nonparametric two-sample methods after testing sample normality. For the study on the possible preventive effect of Melatonin, they were daily treated, by the intragastric route, with increasing doses of Melatonin for 6 months. The percentage of female rats having at least one mammary carcinoma were compared using the Fischer exact t-test. During the latency phase, in vehicle-treated rats, E2 and Progesterone treatments lead an almost significant inhibition of the Isoproterenol-induced stimulation of Melatonin secretion. In DMBA-treated rats, E2 treatment leads to a complete blunting of the Isoproterenol-induced stimulation of Melatonin and Progesterone treatment leads to a cyclic inhibition of the Isoproterenol-induced Melatonin secretion. During the promotion phase, there was a dose-dependent inhibitory effect (up to 65% inhibition) of the daily administration of Melatonin, on mammary tumors occurrence. In conclusion, the long term inhibition of DMBA upon Melatonin secretion from the pineal gland might accelerate the promotion of mammary tumors induced by the mammary carcinogen. Inversely, the daily administration of Melatonin for 6 months induces a long lasting protective effect against the formation of mammary tumors.
Breast Cancer Res Treat 2003 Jun
PMID:Long term inhibition by estradiol or progesterone of melatonin secretion after administration of a mammary carcinogen, the dimethyl benz(a)anthracene, in Sprague-Dawley female rat; inhibitory effect of Melatonin on mammary carcinogenesis. 1284 21

Sentinel lymphadenectomy was developed to reduce the extent of surgical interventions in cancer patients. The sentinel node (SN) concept was first established for melanoma and breast cancer; within some years, it also became increasingly popular for head and neck cancer. As soon as the required sensitivity of the method proves to be feasible in the daily clinical routine, the discussion about the best surgical approach to single or multiple SN(s) will arise. Different objectives may here compete with each other. The incision should render the best exposure of the operation site and should be expandable in case further lymph node regions have to be dissected. Finally, a good functional as well as a good cosmetic result is desirable. Endoscopic lymph node excisions were performed in patients suffering from squamous cell carcinoma of the upper aerodigestive tract located in different sites (1x uvula, 2x epiglottis, 1x glottis). In preoperatively performed ultrasonic imaging (B-mode-ultrasonography), N0 necks were assessed. In contrast to previously reported endoscopic techniques in humans, the presented method requires no insufflation of carbon dioxide or external retraction of the skin. Following laser surgical resection of the primary tumor, the SN and further lymph node(s) with accumulation of tracer substance were identified and resected endoscopically via an incision that was afterwards extended to a normal neck dissection incision. Reports of histopathologic examination of the sentinel node(s) were compared to the respective neck dissection specimens. The presented method may help to reduce the degree of invasiveness frequently attributed to sentinel lymphadenectomy once the method has been established for head and neck cancer.
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PMID:Endoscopic sentinel lymphadenectomy as a new diagnostic approach in the N0 neck. 1532 30

CA (carbonic anhydrase) catalyses the reversible hydration of carbon dioxide into bicarbonate, and at least 14 isoforms have been identified in vertebrates. The role of CA type II in maintaining the fluid and pH balance has made it an attractive drug target for the treatment of glaucoma and cancer. 667-coumate is a potent inhibitor of the novel oncology target steroid sulphatase and is currently in Phase 1 clinical trials for hormone-dependent breast cancer. It also inhibits CA II in vitro. In the present study, CA II was crystallized with 667-coumate and the structure was determined by X-ray crystallography at 1.95 A (1 A=0.1 nm) resolution. The structure reported here is the first for an inhibitor based on a coumarin ring and shows ligation of the sulphamate group to the active-site zinc at 2.15 A through a nitrogen anion. The first two rings of the coumarin moiety are bound within the hydrophobic binding site of CA II. Important residues contributing to binding include Val-121, Phe-131, Val-135, Leu-141, Leu-198 and Pro-202. The third seven-membered ring is more mobile and is located in the channel leading to the surface of the enzyme. Pharmacokinetic studies show enhanced stability of 667-coumate in vivo and this has been ascribed to binding of CA II in erythrocytes. This result provides a structural basis for the stabilization and long half-life of 667-coumate in blood compared with its rapid disappearance in plasma, and suggests that reversible binding of inhibitors to CA may be a general method of delivering this type of labile drug.
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PMID:Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex with 667-coumate, a novel anti-cancer agent. 1545 28

Cyclopentenone prostaglandins (cyPGs) are produced by dehydration of precursor molecules. The cyPGs are reported to have proapoptotic effects in a variety of cell types. However, cyPGs, particularly 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), can also exert cytoprotective effects at relatively low concentrations. The cytoprotective activity of cyPGs appears to be mediated by the reactive alpha,beta-unsaturated carbonyl group located in the cyclopentene ring. In this study, we investigated the effect of cyPGs on the expression of heme oxygenase-1 (HO-1), a ubiquitous stress-responsive enzyme that catalyzes oxidative cleavage of heme to form iron, carbon monoxide, and biliverdin. Treatment of the human breast cancer cell line (MCF-7) with 15d-PGJ(2) resulted in a concentration- and time-dependent increase in the expression of HO-1, whereas prostaglandin A(2) (PGA(2)) and the non-PG derivative 2-cyclopenten-1-one failed to induce HO-1 expression at the protein level. RT-PCR revealed that the expression of HO-1 mRNA was induced at 6 h by 15d-PGJ(2) at 10 microM. However, PGA(2) induced HO-1 mRNA expression at a higher concentration (30 microM). 2-Cyclopenten-1-one did not induce the expression of HO-1 mRNA at all. Likewise, 15d-PGJ(2) treatment for 6 h led to phosphorylation of Akt/protein kinase B (PKB) to a greater extent than that achieved with PGA(2). Thus, the induction of HO-1 expression and the activation of Akt/PKB by 15d-PGJ(2) and PGA(2) are likely to confer cytoprotective or antiapoptotic effects exerted by these cyPGs.
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PMID:Effects of cyclopentenone prostaglandins on the expression of heme oxygenase-1 in MCF-7 cells. 1565 34

Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins, preferentially recognizes Galbeta1-4GlcNAc (LacNAc) sequences of oligosaccharides associated with several cell surface glycoconjugates. As demonstrated histochemically, gal-1 recognizes appropriate glycoepitopes on human breast cancer cells (MCF7) and on human chorionic carcinoma cells (BeWo). Gal-1 is expressed in many malignant and normal tissues. A high level of expression is found in lymphatic organs, which feature high rates of apoptosis. Furthermore, it is known that galectin-1 can initiate T cell apoptosis. In this study, we examined the apoptotic potential of gal-1 in vitro on MCF7 and BeWo cells. After growing both cell lines on chamber-slides for three days, apoptosis was induced by incubation with 30 microg gal-1 per ml serum-free medium for 6, 9 and 20 hours. To avoid false increased rates of apoptosis by deletion of FCS, all approaches were done with and without FCS. Apoptotic cells were detected by in situ nick translation. The rate of apoptosis was determined by counting 1500 cells per chamberslide. The normal rate of apoptosis ranged between 0.1% and 0.3%. The incubation of both cell lines with 30 microg/ml gal-1 in serum-free medium for 6 and 9 hours marginally raised the number of apoptotic cells. An increase of apoptosis was only shown by additional stimuli like hyperthermia, removal of CO2 and FCS for 20 hours. Impressing findings were manifested in an older passage of BeWo cells, in which only omission of FCS caused apoptotic rates for up to 25% after 6 hours. The presence of mycoplasma in this BeWo passage was shown by PCR. Our results demonstrated, that galectin-1 shows apoptotic potential in both the epithelial tumour cell lines examined only with additional stress stimuli.
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PMID:Induction of apoptosis in human breast cancer and trophoblast tumor cells by galectin-1. 1603 63

The present study investigated the changes of quality of life, mood, and the tumor marker CA 15-3 associated with a 3-week inpatient breast cancer rehabilitation program incorporating spa therapy. One hundred forty-nine women, 32 to 82 years, participated in the study 3 to 72 months after breast cancer surgery. Quality of life (QoL, EORTC QLQ-C30), anxiety, and depression (HADS) were measured 2 weeks before, at the end, and 6 months after rehabilitation; CA 15-3 at the beginning, end, and at 6 months follow-up. Patients received an individualized rehabilitation program incorporating manual lymph drainage, exercise therapy, massages, psychological counseling, relaxation training, carbon dioxide baths, and mud packs. Quality of life and mood improved significantly, the greatest short-term improvements found for mood-related aspects of quality of life, the most lasting improvements found for physical complaints (eg, fatigue). Also, the tumor marker CA 15-3 declined significantly to follow-up. Patient characteristics, as well as the time since surgery, moderated rehabilitation outcome to a limited extent. Older patients, nonobese patients, patients with a greater lymphedema, and patients with an active coping style showed slightly greater improvements. Hot mud packs inducing hyperthermia did not affect CA 15-3. In conclusion, the combination of inpatient rehabilitation with spa therapy provides a promising approach for breast cancer rehabilitation.
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PMID:Combined inpatient rehabilitation and spa therapy for breast cancer patients: effects on quality of life and CA 15-3. 1619 31

The single exhalation analysis of carbon monoxide, acetylene, and methane allows the determination of intrabreath (regional) DL, pulmonary capillary blood flow and ventilation inhomogeneities during rest and exercise. We reasoned that this technique might be more sensitive in detecting regional pulmonary capillary abnormalities than resting single breath DL (DL(sb)). We selected a group of breast cancer patients in high-dose chemotherapy (HDCT) protocols who were at risk for pulmonary injury. We grouped the patients into pre-HDCT and post-HDCT, and used resting DL(sb) to further categorize the latter into those with and without pulmonary injury. We found that exercise DL increases were blunted in post-HDCT patients with low resting DL(sb). More importantly, even in post-HDCT patients with normal resting DL(sb), exercise DL response was reduced in the slowest emptying lung units along with evidence for ventilation inhomogeneities (increased methane slope). We conclude that exercise assessments of DL at low lung volumes and gas mixing properties may be sensitive indicators of lung injury.
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PMID:Intrabreath analysis of carbon monoxide uptake during exercise in patients at risk for lung injury. 1631 83

A 44-year-old woman, ASA I, with breast cancer was scheduled for mastectomy. The anesthetic induction was performed by inhalation of 5% sevoflurane and 66% nitrous oxide in oxygen. After the loss of eyelash reflex assisted ventilation was initiated. At this point, the capnograph indicated inspired carbon dioxide tension of 18mmHg. Anesthetic machine check was soon carried out again. A visual check of non-return valves detected a plastic film, 18 x 21mm large, caught in the expiratory valve. This plastic film impaired complete occlusion of the orifice for the expiratory gas flow. As a result, the patient was rebreathing carbon dioxide. After removing it, the wave form of the capnograph was normalized and end-tidal carbon dioxide tension decreased immediately from 45mmHg to 33mmHg. As we did not detect any foreign matters at the non-return valves on anesthetic machine check before use, the plastic film might have already existed in the disposable corrugated tube before use. The capnograph is a useful device for detecting anesthetic circle system failure in such a case. It is important that the patients' airway is separated from the anesthetic circle system through the use of a filter to prevent foreign matter from being inhaled.
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PMID:[Anesthetic circle system failure caused by a plastic film--a case report]. 1649 2


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