Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoreactive-adrenomedullin concentrations and the expression of adrenomedullin mRNA were studied in the tumor tissues of adrenocortical tumors. Northern blot analysis showed the expression of adrenomedullin mRNA in tumor tissues of adrenocortical tumors, including aldosterone-producing adenomas, cortisol-producing adenomas, a non-functioning adenoma and adrenocortical carcinomas, as well as normal parts of adrenal glands and pheochromocytomas. On the other hand, immunoreactive-adrenomedullin was not detected in about 90% cases of adrenocortical tumors (<0.12 pmol/g wet weight (ww)). Immunoreactive-adrenomedullin concentrations ranged from 0.44 to 198.2 pmol/g ww in tumor tissues of pheochromocytomas and were 9.2 +/- 1.2 pmol/g ww (mean +/- SD, n = 4) in normal parts of adrenal glands. Adrenomedullin mRNA was expressed in an adrenocortical adenocarcinoma cell line, SW-13 and immunoreactive-adrenomedullin was detected in the culture medium of SW-13 (48.9 +/- 1.8 fmol/10(5) cells/24h, mean +/- SEM, n = 4). On the other hand, immunoreactive-adrenomedullin was not detectable in the extract of SW-13 cells (<0.09 fmol/10(5) cells), suggesting that adrenomedullin was actively secreted from SW-13 cells without long-term storage. These findings indicate that adrenomedullin is produced and secreted, not only by pheochromocytomas, but also by adrenocortical tumors. Undetectable or low levels of immunoreactive-adrenomedullin in the tumor tissues of adrenocortical tumors may be due to very rapid secretion of this peptide soon after the translation from these tumors.
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PMID:Expression of adrenomedullin mRNA in adrenocortical tumors and secretion of adrenomedullin by cultured adrenocortical carcinoma cells. 988 77

Obesity and diet affect the incidence and severity of various types of cancer, including colon cancer. It is not known whether obesity, independent of diet, is a risk factor for colon adenocarcinoma. We used azoxymethane (AOM) to induce colon cancer in mature genetically obese male Zucker rats (fa/fa) on low-fat crude diet (LFC, 10% fat) and their lean counterparts (Fa/fa and Fa/fa) on high-fat crude diet (HFC, 40% fat) for three months. At death visible tumors, histopathology, and colonic aberrant crypt (AC) formation were studied by blinded investigators. At death the obese animals were heavier (719 +/- 19 g; mean +/- SEM) than lean animals regardless of diet or genotype (Fa/fa-LFC:451 = 6 g; Fa/fa-HFC:441 +/-10 g; Fa/Fa-HFC:412 +/- 9 g; P < 0.001 vs fa/fa by ANOVA). All AOM-treated rats developed AC, compared to none of the saline-injected controls. Macroscopic adenocarcinoma developed in 8/9 obese rats on LFC (P < 0.001), compared to none in lean rats regardless of diet. Obese rats had significantly more AC (876 +/- 116) than any of the lean rats (Fa/fa-LFC:550 +/- 99; Fa/fa-HFC:325 +/- 37; Fa/Fa-HFC:360 +/- 36; P < 0.05 vs fa/fa). We conclude that obesity more than exposure to high-fat diet was associated with colon carcinogenesis in these rats.
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PMID:Obesity potentiates AOM-induced colon cancer. 1079 50

In Barrett's esophagus, the precursor to esophageal adenocarcinoma, the squamocolumnar junction (SCJ) between the normal esophagus and the stomach like mucosa is proximally displaced. Currently it can be detected only by an expensive upper GI endoscopic procedure. We have developed a minimally invasive and easy to operate colorimetric instrument for the low-cost detection of Barrett's esophagus. The instrument is based on a flexible, narrow diameter, fiber-optic probe that performs a colorimetric scan of the esophageal lumen. The instrument was clinically evaluated in 50 subjects. The instrument could identify both symmetric and asymmetric SCJ's. The SCJ locations determined by the colorimetric instrument correlated strongly (R2 = 0.89) with those determined by endoscopy. The instrument identified the SCJ locations accurately (Mean of difference +/- SEM: 0.97 +/- 1.72 cm) and reproducibly (Mean of absolute difference +/- SEM: 1.33 +/- 1.40 cm). The instrument has a 90% sensitivity of identifying patients with Barrett's esophagus, based on the clinical algorithm that if the SCJ is located at a distance less than 37 cm from the teeth, then the subject has Barrett's esophagus, otherwise the subject does not have Barrett's esophagus. In conclusion, the colorimetric instrument has the potential of being a cost-effective way of determining patients likely to have Barrett's esophagus in the population.
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PMID:A low-cost fiber-optic instrument to colorimetrically detect patients with Barrett's esophagus for early detection of esophageal adenocarcinoma. 1139 99

The clinical value of pre- and post-operative serum carcinoembryonic antigen (CEA) concentration (mean +/- SEM, ng/ml) in surgically treated primary lung cancer patients with adenocarcinoma (n=97) was studied. Preoperative CEA in pT2 patients (18.3+/-8.0) was higher than in pT1 (10.5+/-6.4, p<0.05) but was not different from pT3 patients (19.7+/-6.7). Preoperative CEA in pN1 patients (5.9+/-1.6) was lower than in pN2 (28.2+/-13.2, p<0.05) but not different from pN0 patients (8.8+/-3.8); p-stage II patients (8.2+/-4.7) had lower values than p-stage III patients (26.7+/-10.5, p<0.05), but not p-stage I patients (7.9+/-3.9). The CEA was not different between p-stages IA and IIA (3.5+/-0.6, 6.1+/-3.2) and IB and IIB (17.0+/-11.8, 11.7+/-7.8), but was different between IA and IB (p<0.05) and IIA and IIB (p<0.05). Preoperative CEA did not differ between patients who received complete (12.7+/-4.7) versus incomplete (9.5+/-6.0) resections, nor between patients who developed recurrence after surgery (21.9+/-10.4) versus those who were disease-free (30.9+/-21.7). CEA obtained 2 months after surgery in patients who recurred or metastasized after surgery (63.1+/-47.0) was higher than in disease-free patients (4.8+/-1.6, p<0.05). The post-/pre-operative CEA ratio in patients who recurred or metastasized after surgery (146.6+/-53.3%) was also higher than in disease-free patients (91.0+/-10.9%, p=0.05). In conclusion, CEA reflected tumor size but not the tumor invasion nor hilar lymph node disease; patients with mediastinal lymph node involvement had higher CEA values. Preoperative CEA did not reflect the likelihood of complete resection nor postoperative metastasis, but postoperative CEA obtained 2 months after surgery did reflect postoperative metastasis.
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PMID:Pre- and post-operative serum carcinoembryonic antigen in primary lung adenocarcinoma. 1556 62

Photodynamic therapy (PDT) is based on the cytotoxic effect induced by a photosensitizer in the presence of light and molecular oxygen, with production of reactive oxygen species which cause cell death and tumor destruction. Here we describe the response of the murine mammary adenocarcinoma, LM3, to repeated PDT treatments using the synthetic porphyrin derivative, meso-tetra (4-N-methylpyridinium) porphine (TMPyP). Intradermal LM3 tumors in BALB/c mice were left untreated, only treated with light, only injected with 0.9% NaCl solution, or with TMPyP alone (10 microg in 0.1 ml of 0.9% NaCl). For PDT, the intratumoral TMPyP injection was followed 1 h later by blue-red light irradiation for 50 min (80 mW/cm2 total dose: 240 J/cm2). In all cases, control and PDT treatments were performed on the depilated and glycerol-covered skin over the tumor of anesthetized mice and repeated four times (every two days). In a pilot experiment, no significant differences were found in the growth rate of untreated tumors (n=4) and tumors only treated with light (n=4), 0.9% NaCl (n=3) or TMPyP (n=3). PDT-treated tumors (n=3) showed transitory regression and growth delay. In a second approach, the average diameter (mean, mm +/- SEM) of control (drug alone, n=15) vs PDT tumors (n=17) was 2.13+/-0.11 vs 2.02+/-0.10 at day 0, and 4.00+/-0.17 vs 0.20+/-0.07 at day 9, p<0.0001. At day 37 the average diameter of tumors from control vs the PDT group was 10.98+/-0.59 vs 6.31+/-0.82, p<0.0001. PDT caused partial regression of tumors in one from a total of 17 mice, long-term regression in 15, and cure in one animal. Significant differences in the survival and tumor size at death were found between control and PDT-treated mice. Histopathological analysis of LM3 tumors one day after a unique PDT treatment showed extensive hemorrhage and necrotic areas. These results indicate the considerable potential of intratumoral injection of photosensitizers and repeated PDT protocols.
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PMID:Long-term regression of the murine mammary adenocarcinoma, LM3, by repeated photodynamic treatments using meso-tetra (4-N-methylpyridinium) porphine. 1614 23

Modulation of drug metabolizing enzymes, leading to facilitated elimination of carcinogens represents a successful strategy for cancer chemoprevention. Nitric oxide-donating aspirin (NO-ASA) is a promising agent for the prevention of colon and other cancers. We studied the effect of NO-ASA on drug metabolizing enzymes in HT-29 human colon adenocarcinoma and Hepa 1c1c7 mouse liver adenocarcinoma cells and in Min mice treated with NO-ASA for 3 weeks. In these cell lines, NO-ASA induced the activity and expression of NAD(P)H:quinone oxireductase (NQO) and glutathione S-transferase (GST). Compared with untreated Min mice, NO-ASA increased in the liver the activity (nmol/min/mg; mean+/-SEM for all) of NQO (85+/-6 versus 128+/-11, P<0.05) and GST (2560+/-233 versus 4254+/-608, P<0.005) and also in the intestine but not in the kidney; the expression of NQO1 and GST P1-1 was also increased. NO-ASA had only a marginal effect on P450 1A1 and P450 2E1, two phase I enzymes. The release of NO from NO-ASA, determined with a selective microelectrode was paralleled by the induction of NQO1 and abrogated by NO scavengers; an exogenous NO donor also induced the expression of NQO1. NO-ASA induced concentration-dependently the translocation of Nrf2 into the nucleus as documented by immunofluorescence and immunoblotting; this paralleled the induction of NQO1 and GST P1-1. Thus NO-ASA induces phase II enzymes, at least in part, through the action of NO that it releases and by modulating the Keap1-Nrf2 pathway; this effect may be part of its mechanism of action against colon and other cancers.
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PMID:NO-donating aspirin induces phase II enzymes in vitro and in vivo. 1626 95

The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean +/- SEM, v/v) were 0.40 +/- 0.02, 0.39 +/- 0.02, 0.94 +/- 0.05, and 0.65 +/- 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 +/- 0.27, 1.35 +/- 0.20, and 0.85 +/- 0.18 cm(3) after injection with 10, 30, or 50 microL per 72 h (six times), respectively, as opposed to 3.88 +/- 0.50 cm(3) for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 +/- 4, 18 +/- 4, and 8 +/- 3%, respectively, while the control animals showed 75 +/- 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.
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PMID:Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy. 1793 50

We have synthesized a series of novel phenylester compounds and present our assessment of such a derivative of aspirin, 3-((diethoxyphosphoryloxy)methyl)phenyl 2-acetoxybenzoate, provisionally named phosphoaspirin. We determined its anticancer activity both in vitro and in vivo. Phosphoaspirin inhibited the growth of HT-29 human colon adenocarcinoma cells (IC(50) = 276.6+/-12.3 microM (mean +/- SEM)] through a combined antiproliferative and mainly proapoptotic effect. Phosphoaspirin (100 mg/kg body weight intraperitoneally daily for 21 days) also inhibited the growth of HT-29 tumors grown as xenografts in nude mice. The size of the tumors decreased progressively in the phosphoaspirin treated group, compared to controls, being reduced by 57% (p<0.001) on day 21. Phosphoaspirin achieved this effect by modulating cell kinetics; the proliferation index of cancer cells was reduced by 18.13% compared to controls (p<0.001) and the apoptosis index was increased by 94.6% (p<0.003). There was no apparent toxicity from phosphoaspirin. We conclude that phosphoaspirin is a promising agent for the control of cancer that deserves further evaluation.
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PMID:The novel phenylester anticancer compounds: Study of a derivative of aspirin (phoshoaspirin). 1809 47

Dehydroxylated MCM-41 and SBA-15 surfaces were modified by the grafting of two different titanocene complexes ([Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] and [Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)]) to give new materials, which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, MAS-NMR spectroscopy, thermogravimetry, SEM, and TEM. The toxicity of the resulting materials toward human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells, such as peripheral blood mononuclear cells PBMC has been studied. Estimation of the number of particles per gram of material led to the calculation of Q(50) values for these samples, which is the number of particles required to inhibit normal cell growth by 50%. In addition, M(50) values (quantity of material needed to inhibit normal cell growth by 50%) of the studied surfaces is also reported. Nonfunctionalized MCM-41 and SBA-15 did not show notable antiproliferative activity, whereas functionalization of these materials with different titanocene based anticancer drugs led to very promising antitumoral activity. The best Q(50) values correspond to titanocene functionalized MCM-41 surfaces (MCM-41/[Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] (1) and MCM-41/[Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (2)) with Q(50) values between 3.8+/-0.6x10(8) and 24.5+/-3.0x10(8) particles. Titanocene functionalized SBA-15 surfaces (SBA-15/[Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] (3) and SBA-15/[Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (4)) gave higher Q(50) values, showing lower activity from 73.2+/-9.9x10(8) to 362+/-7x10(8) particles. The best response of the studied materials in terms of M(50) values was observed against Fem-x (309+/-42 microg for 4) and K562 (338+/-18 microg for 2), whereas moderate activities were observed in HeLa cells (from 508+/-63 microg of 2 to 912+/-10 microg of 1). In addition, the analyzed surfaces presented only marginal activity against unstimulated and stimulated PBMC, showing a slight selectivity on human cancer cells. Comparison of the in vitro cytotoxicity in solution of the titanocene complexes [Ti(eta(5)-C(5)H(4)Me)(2)Cl(2)] and [Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] and the corresponding titanocene functionalized materials is also described.
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PMID:A new generation of anticancer drugs: mesoporous materials modified with titanocene complexes. 1937 Jul 42

Fe(III)-carboxylate nanoscale metal-organic frameworks (NMOFs) with the MIL-101 structure were synthesized using a solvothermal technique with microwave heating. The approximately 200 nm particles were characterized using a variety of methods, including SEM, PXRD, nitrogen adsorption measurements, TGA, and EDX. By replacing a percentage of the bridging ligand (terephthalic acid) with 2-amino terephthalic acid, amine groups were incorporated into the framework to provide sites for covalent attachment of biologically relevant cargoes while still maintaining the MIL-101 structure. In proof-of-concept experiments, an optical contrast agent (a BODIPY dye) and an ethoxysuccinato-cisplatin anticancer prodrug were successfully incorporated into the Fe(III)-carboxylate NMOFs via postsynthetic modifications of the as-synthesized particles. These cargoes are released upon the degradation of the NMOF frameworks, and the rate of cargo release was controlled by coating the NMOF particles with a silica shell. Potential utility of the new NMOF-based nanodelivery vehicles for optical imaging and anticancer therapy was demonstrated in vitro using HT-29 human colon adenocarcinoma cells.
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PMID:Postsynthetic modifications of iron-carboxylate nanoscale metal-organic frameworks for imaging and drug delivery. 1980 79


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