Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous investigations increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects, including cancer. In this investigation transferrin C (TF C) subtypes were studied in lung cancer patients and controls from the Stockholm area in central Sweden. There was a significant difference between patients and controls with respect to the distribution of TF C alleles and genotypes, which was mainly due to a low frequency of the TF C3 allele among the patients (P = 3 x 10(-6). However, in adenocarcinoma the frequency of TF C3 types was almost identical to that among the controls, whereas in the smoking-related (squamous and small cell) tumor types the TF C3 frequency was remarkably low (OR = 0.03, 95% CI = 0.00-0.22). Thus individuals with the TF C3 variant appear to enjoy an almost complete protection against smoking-related lung cancer. The frequency of individuals carrying the protective TF C3 variant is approximately 17% in central Sweden and 25% in Finland, which has the highest TF C3 frequency found so far. The mechanism behind the observed association, which appears to be independent of iron binding and body iron stores, remains to be elucidated.
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PMID:Transferrin C3 offers protection against smoking-associated lung cancer? 870 47

Human adenocarcinoma cells of the line WiDr and Chinese hamster lung fibroblasts of the line V79 were treated with 5-aminolaevulinic acid (5-ALA) and exposed to light. The effects of the iron chelators ethylenediaminetetraacetic acid (EDTA) and desferrioxamine (DEF) were assessed. Both cell lines were treated with various concentrations of 5-ALA in the presence or absence of the iron chelators for 4 h in serum-free medium. The accumulation of protoporphyrin IX (PpIX) reached a maximum level at 1 mM 5-ALA in WiDr cells [280 ng PpIX (mg protein x 4 h-1] and at 0.1 mM 5-ALA in V79 cells [55 ng PpIX (mg protein x 4 h)-1]. PpIX was the only fluorescing porphyrin in these cells after 5-ALA treatment alone or in combination with the chelators. The iron chelators did not influence the intracellular localisation pattern of PpIX in 5-ALA-treated cells. While both chelators enhanced the accumulation of PpIX in 5-ALA-treated cells, DEF was found to be superior at equal concentrations. A linear relationship between the applied concentration of DEF and the DEF-induced increase in PpIX accumulation was observed in double-reciprocal plots. The intercepts of the regression lines with the ordinate indicate that the ferrochelatase is saturated with PpIX when the 5-ALA concentration exceeds 0.3 mM and 0.05 mM in WiDr and V79 cells respectively. The DEF-induced enhancement of PpIX accumulation in 5-ALA-treated cells was cell line and 5-ALA concentration dependent. At a 5-ALA concentration inducing a maximum level of PpIX accumulation, inhibition of ferrochelatase activity enhanced the PpIX accumulation 3- and 1.4-fold in V79 and WiDr cells respectively. The relative gain in PpIX accumulation increased with decreasing concentration of 5-ALA. In cells treated with the lowest concentrations of 5-ALA used in this study, DEF enhanced PpIX accumulation 44- and 3.5-fold in V79 and WiDr cells respectively. The iron chelator-induced increase in cellular PpIX accumulation was followed by a similar increase in sensitivity to photoinactivation. The ferrochelatase inhibitor dihydropyridine 3,5-diethoxycarbonyl-1,4-dihydrocollidine reduced the accumulation of PpIX in both cell lines.
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PMID:The influence of iron chelators on the accumulation of protoporphyrin IX in 5-aminolaevulinic acid-treated cells. 879 69

Platinum and trace metal distributions of a human ovarian adenocarcinoma cell line, IGROV1, and a subline resistant to the antitumor agent cisplatin were compared using nuclear microprobe analysis. The cisplatin-resistant cell line IGROV1-DDP exhibited a cytologically heterogeneous cell population. Two subpopulations were distinguished, small mononuclear cells, morphologically similar to the parental cells IGROV1, and enlarged polynuclear cells. Quantitative mapping of platinum and essential trace metal such as manganese, iron, copper and zinc was performed at the cellular level. Elemental maps were obtained with 2 mu m spatial resolution. Platinum appeared uniformly distributed within the cells, in all cell types. The same was true for copper and zinc. In some cases, iron maps showed preferential localization in the perinuclear region, especially in IGROV1-DDP polynuclear cells. Cisplatin resistance was associated with decreased platinum and iron concentrations and increased levels of copper and zinc. Decreased drug accumulation was encountered in both subpopulations of the resistant cell line. In contrast, high inter-individual variation of copper content was noticed in this cell line suggesting that in vitro cisplatin selection of human ovarian adenocarcinoma resistant cells can bring about the emergence of distinct cellular phenotypes.
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PMID:Quantitative mapping of platinum and essential trace metal in cisplatin resistant and sensitive human ovarian adenocarcinoma cells. 883 69

Mucin production, when heavily sialylated, can promote cancer cell invasion and metastasis, and modulate the immune recognition system of the host. To explore the prognostic implication of sialomucin expression in lung cancer, we studied 116 patients with non-small-cell lung cancer (NSCLC). Tumor specimens were stained immunohistochemically with monoclonal antibodies (mAbs) against mucin glycoprotein (17Q2, HMFG2, SM3), and histochemically with periodic acid-Schiff/alcian blue to differentiate neutral mucin from acid mucin, and with high-iron diamine/alcian blue to differentiate sialomucin from sulfomucin. The expression status of two established molecular prognostic factors, the p53 and erbB-2 oncoproteins, were evaluated immunohistochemically. The staining was performed on two separately archived, paraffin-embedded tumor blocks for each patient, with normal lung as a control. Correlations were subsequently made among stains and various clinicopathologic factors. All analyses were blinded, and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Associations were established among adenocarcinoma histotype and erbB-2 overexpression, sialomucin expression, and 17Q2 and HMFG2 immunohistochemical positivity (p < 0.05). Sialomucin expression was closely linked to erbB-2 overexpression (p = 0.01). Significant univariate predictors (p < 0.05) of recurrence and cancer death were surgical stage, p53 expression, erbB-2 overexpression, and sialomucin expression. These four factors remained as independent predictors of early recurrence (p < 0.05) after multivariate analysis. For cancer death prediction, p53 and sialomucin expression had a marginal effect. We concluded that sialomucin expression is also a poor indicator of prognosis, which is associated with erbB-2 oncoprotein overexpression, early postoperative recurrence, and cancer death in NSCLC.
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PMID:Sialomucin expression is associated with erbB-2 oncoprotein overexpression, early recurrence, and cancer death in non-small-cell lung cancer. 910 88

Three different types of liposomes containing superparamagnetic iron oxide particles (SPIOs) as the contrast agent were tested for intratumoral enrichment by magnetic resonance imaging (MRI). The liposome-encapsulated SPIOs were investigated in comparison with AMI-227, dextran-coated SPIOs in two different dosages using the CC531 adenocarcinoma in the liver of WAG/RIJ rats as a model. Reduction of the relative signal intensity (SI) in the tumor in T2-weighted MR images was assumed as a measure of the liposome enrichment in the tumor or adjacent tissue. The samples were tested at dosages with isomolar iron content and at dosages producing the same MR relaxivity R2. For reverse phase evaporation vesicles and small unilamellar vesicles behavior differed remarkably according to the applied dosage. A steady, strong reduction in SI, starting immediately after injection and extending up to 48 h, was observed for small unilamellar vesicles sterically stabilized with polyethylene glycol.
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PMID:Liposome-encapsulated superparamagnetic iron oxide particles as markers in an MRI-guided search for tumor-specific drug carriers. 911 67

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.
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PMID:Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen. 939 30

CA-125 is abundantly secreted from ovarian endometriotic cysts, but is not specific to endometriosis. In order to develop a new, more specific diagnostic marker for endometriosis, the iron concentrations in various ovarian cysts were assayed. The ovarian cysts were punctured and the contents aspirated laparoscopically, laparotomically, or transvaginally. The iron concentration in the ovarian cystic fluid was assayed using a spectrophotometer after protein precipitations and chromogen treatment. The iron concentrations in ovarian cysts were 69.5+/-10.4 micromol/l in serous cystadenomas, 73.5+/-29.3 in mucinous cystadenomas, 65.4+/-12.4 in dermoid cysts, and 92.5+/-18.2 micromol/l in adenocarcinomas. On the other hand, high iron concentrations were demonstrated in endometriotic cysts (1,749.6+/-41.5 micromol/l), a lutein cyst (1,393.8), hemorrhagic corpus luteum (1,957.5) and endometrioid adenocarcinomas (1,860.9+/-157.9 micromol/l). Cytological smear tests of the contents as well as histological examination allowed differential diagnosis between endometriosis and endometrioid adenocarcinoma. In conclusion, assay of the ovarian cystic iron concentration is a useful diagnostic tool for the evaluation of ovarian endometriotic cysts.
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PMID:Chemical assay of iron in ovarian cysts: a new diagnostic method to evaluate endometriotic cysts. 969 45

The passage of nickel across monolayers of intestinal epithelial Caco-2 cells, originally derived from a human colonic adenocarcinoma, was studied in bicameral chambers. The results showed that the transport and accumulation of nickel were depressed in iron-loaded monolayers, indicating that the metal participates in an absorptive process for iron in the Caco-2 cells. No detectable transport of nickel in either the apical to basal or basal to apical direction occurred at 4 degreesC. Since cellular metabolism is inhibited at 4 degreesC, these data indicate that there is no passive transcellular or paracellular passage of the nickel across the monolayers. Studies in ATP-depleted monolayers showed an increased permeability of nickel, and concomitantly there was a similar increase in the permeability of the paracellular marker mannitol. These results indicate that the metabolic inhibition results in a loosening of the junctional complexes between the Caco-2 cells, resulting in a paracellular leakage of the nickel. Additional experiments showed that the transport of nickel in the basal to apical direction occurred at a higher rate than in the apical to basal direction. This indicates the presence of an extrusion mechanism that secretes the nickel from the basal to the apical side of the Caco-2 cells. Studies with Caco-2 cells and in vivo studies by other authors have shown similar results for other metals, indicating that colonic epithelial cells may have the ability to secrete some metals.
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PMID:Transport of nickel across monolayers of human intestinal Caco-2 cells. 970 94

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.
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PMID:Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. 974 41

We report herein the unusual case of a 59-year-old woman with Plummer-Vinson syndrome who developed gastric cancer. The patient had a longstanding history of dysphagia and iron deficiency anemia, for which she had sporadically taken iron supplements that improved the dysphagia to some extent, but not completely. Owing to her tolerance of the dysphagia, she had not been taking iron supplements for the past 17 years. On admission, she was in fair nutritional condition and not anemic. Blood chemistry results were all normal, including the serum iron level. Gastrointestinal radiographic series demonstrated cervical esophageal webs and advanced gastric cancer. Her dysphagia was successfully treated by endoscopic bougienage through the webs, and a distal partial gastrectomy with nodal dissection was performed. Histology of the resected stomach revealed atrophic mucosal change and, by chance, an adenomatous lesion in addition to adenocarcinoma. Her postoperative course was uneventful and she is now well, without any signs of recurrence. Although Plummer-Vinson syndrome is known to be associated with upper alimentary tract cancers, gastric cancer is extremely rare. A discussion on the etiology of Plummer-Vinson syndrome and its link with potential carcinogenesis follows this case report.
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PMID:Gastric cancer occurring in a patient with Plummer-Vinson syndrome: report of a case. 978 78


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