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)

Long-term ulcerative colitis (UC) patients are at increased risk for developing colorectal cancer. In order to develop strategies for preventing UC-associated carcinogenesis, we studied the effect of the antioxidant N-acetylcysteine (NAC) on UC-associated cancer development in a mouse model. Female C57BL/6J mice were subjected to long-term administration of dextran sulfate sodium (DSS) in the drinking fluid and 2-fold iron-enriched AIN76A diet, with or without NAC. In the DSS-plus-2-fold iron positive control group, gross tumor incidence was 88.5% (23/26 mice) after 12 DSS cycles (1 DSS cycle = 7 day DSS treatment period followed by 10 day recovery period). The tumor multiplicity was 2.1 +/- 0.2 tumors/tumor-bearing mouse, and the tumor volume was 0.054 +/- 0.019 cm3. With 0.2% NAC administration, tumor incidence was significantly reduced (68%, 17/25 mice; P < 0.05), as was the tumor multiplicity (1.5 +/- 0.1 tumors/tumor-bearing mouse; P < 0.05). The tumor volume was lower (0.014 +/- 0.004 cm3), but not significantly decreased. The proliferation index was significantly decreased in non-cancerous epithelia (48.5 +/- 6.0% vs 32.0 +/- 3.7%; P < 0.05), but not in tumor cells. NAC significantly induced apoptosis in both non-cancerous epithelia and colorectal adenocarcinoma. The number of cells immunostained-positive for nitrotyrosine was markedly decreased in the non-cancerous mucosa of NAC-treated mice (102.4 +/-16.6 positive cells/mm2 mucosa vs 53.6 +/- 14.9 cells/mm2; P < 0.05). In addition, the number of inducible nitric oxide synthase (iNOS)-positive inflammatory cells in the non-cancerous mucosa of the distal colon was markedly decreased by NAC. This study indicates that the antioxidant NAC has the potential to serve as a preventive agent for UC-associated colorectal cancer, possibly via inhibition of cellular proliferation and nitrosative stress-caused cellular damage.
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PMID:Inhibition of chronic ulcerative colitis-associated colorectal adenocarcinoma development in a murine model by N-acetylcysteine. 1208 21

Atrophic chronic gastritis and Helicobacter pylori infection are considered possible causes of iron deficiency anemia, and sideropenic anemia is also frequent after subtotal gastrectomy. In this study, thirty-three patients who underwent subtotal gastrectomy for primary adenocarcinoma of stomach were follow-up for at least 3 years, and included in this analysis. The presence of atrophic gastritis and H. pylori infection were detected by biopsy sampling and endoscopy every year after surgery. The iron status was evaluated by the assay of serum ferritin, serum iron and hemoglobin level. Statistical analysis revealed that atrophic gastritis was associated with lower iron serum levels, and gastric stump H. pylori infection was related to lower serum ferritin levels; on the contrary, no correlation of these factors with sex, age, malabsorption symptoms and stage of tumor was found. Atrophic chronic gastritis and Helicobacter pylori infection seem to play an important role as possible causes of post gastrectomy anaemia.
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PMID:[Correlation between chronic gastritis of the gastric stump, Helicobacter pylori infections and iron deficiency after gastrectomy for gastric cancer]. 1242 77

It is known that the interruption of normal iron metabolism with chelators of iron, toxic metals, toxic metals bound to transferrin, or anti-transferrin receptor antibodies leads to significant inhibition of tumor cell growth in cell culture systems and animal models. In the present study, we found that iron depletion was produced by the iron chelator deferoxamine mesylate, the free toxic metals gallium or indium, and the toxic metals gallium or indium bound to transferrin in the MCF-7 human breast cancer cell line, and this induced the condensation and fragmentation of chromatin, and the formation of DNA fragments characteristic of apoptosis. The induction of apoptosis was quantitated with acridine orange and ethidium bromide staining of apoptotic cells, separation of fragmented DNA from radiolabeled cells, and in situ terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assays. The apoptosis, caused by deferoxamine mesylate, and gallium or indium bound to transferrin in the MCF-7 cells, can be completely inhibited by excess ferric chloride or equimolar iron-loaded transferrin. Gallium-transferrin and indium-transferrin complexes induced more apoptosis than their respective salts in the MCF-7 cells. Deferoxamine mesylate induced a small increase in the endogenous expression of both the bcl-2 and bax genes in the MCF-7 cells and this can be prevented by ferric chloride. In the 13762NF rat mammary adenocarcinoma model, in situ TUNEL assays showed that the iron-deficiency following a low iron diet or intravenous injection of deferoxamine mesylate produced 5.32 +/- 3.90% and 6.46 +/- 3.58% of apoptotic cells, respectively, compared to 2.01 +/- 1.20% of apoptotic cells in the control rats maintained on a normal diet (p < 0.05 and p < 0.01, respectively, Student's t-test). This is the first report of iron depletion caused by a low iron diet or deferoxamine mesylate treatment inducing apoptosis in rats bearing the 13762NF marnmary adenocarcinoma.
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PMID:Induction of apoptosis by iron depletion in the human breast cancer MCF-7 cell line and the 13762NF rat mammary adenocarcinoma in vivo. 1252 82

CDKN2A is regarded as a major melanoma susceptibility gene. A 19 bp deletion has been detected within Dutch families with familial atypical multiple mole-melanoma syndrome. Genetic analysis revealed two individuals with germline deletions in both copies of CDKN2A. One of them did not develop atypical naevi or melanoma, but died of adenocarcinoma at the age of 54 years. This report describes the results of the investigation of the second p16-null individual, who was also found to have glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and who has developed many atypical naevi and seven melanomas. Using electron microscopic techniques, striking alterations in melanosomal structures and deviations in their sulphur, iron and calcium composition indicating a strong preference for phaeomelanogenesis and increased oxidative stress were found in the naevus cells of the patient. Using an in vitro model, we demonstrated that leaking melanin precursors may strongly enhance oxidative DNA damage through iron release from ferritin. We conclude that the homozygous p16 deletion is not sufficient for the development of a dysplastic naevus phenotype and melanoma. However, when an additional modifying factor, such as G-6-PD deficiency, increases the level of oxidative DNA damage in melanin-producing cells, the risk of developing atypical naevi and their malignant transformation may increase significantly.
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PMID:Homozygous germline mutation of CDKN2A/p16 and glucose-6-phosphate dehydrogenase deficiency in a multiple melanoma case. 1269 Mar 1

Wireless-capsule-endoscopy is a new painless method that is able both to visualize the entire small bowel and to detect even small lesions. We report here the case of a patient in whom a locally advanced small-bowel adenocarcinoma was initially missed on capsule endoscopy, but was diagnosed by subsequent push enteroscopy. Capsule endoscopy was carried out in a 47-year-old patient with a history of obscure gastrointestinal bleeding, iron-deficiency anemia, and a lack of symptoms suggestive of stenosis. The capsule imaging revealed angiodysplasias in the jejunum, but no other abnormalities. Push enteroscopy was carried out to allow argon plasma coagulation treatment of the angiodysplasias that had been detected; it revealed a polypoid tumor 20 mm in diameter at 150 cm from the incisors, with the capsule endoscope still located proximal to the tumor and with its optical dome turned towards the push enteroscope. Clinical staging and subsequent surgical resection showed a locally advanced adenocarcinoma (pT4, pN0 (0/7), pMx, G3).[nl]Small-bowel tumors within the reach of push enteroscopy may be missed by capsule endoscopy. Although wireless capsule endoscopy is a major advance in the investigation of the small bowel, well-designed clinical studies still need to define the precise algorithm for diagnostic work-up of suspected small-bowel diseases.
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PMID:Locally advanced small-bowel adenocarcinoma missed primarily by capsule endoscopy but diagnosed by push enteroscopy. 1455 67

The activation of Myc induces apoptosis of human ovarian adenocarcinoma N.1 cells when serum factors are limited. However, the downstream mechanism that is triggered by Myc is unknown. Myc-activation and treatment with the proapoptotic ligands TNFalpha, FasL, and TRAIL induced H-ferritin expression under serum-deprived conditions. H-ferritin chelates intracellular iron and also intracellular iron sequestration by deferoxamine-induced apoptosis of N.1 cells. Supplementation of serum-free medium with holo-transferrin blocked apoptosis of N.1 cells that was induced by Myc-activation or by treatment with TNFalpha, FasL, and TRAIL, whereas apotransferrin did not prevent apoptosis. This suggests that intracellular iron depletion was a trigger for apoptosis and that transferrin-bound iron rescued N.1 cells. Furthermore, apoptosis of primary human ovarian carcinoma cells, which was induced by TNFalpha, FasL, and TRAIL, was also inhibited by holo-transferrin. The data suggest that Myc-activation, FasL, TNFalpha, and TRAIL disturbed cellular iron homeostasis, which triggered apoptosis of ovarian carcinoma cells and that transferrin iron ensured survival by re-establishing this homeostasis.
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PMID:Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFalpha, FasL, TRAIL, or Myc. 1461 58

An unusual case of synchronous gastric carcinomas occurred in a 28-year-old man with a family history of gastric disease. Two tumor foci were identified: a well-differentiated advanced carcinoma with the phenotypic properties of complete intestinal metaplasia and an early intestinal-type carcinoma. Histochemical and immunohistochemical stains to demonstrate complete intestinal metaplasia, ie, Alcian blue pH 2.5/periodic acid-Schiff, high iron diamine/Alcian blue pH 2.5, CD10, and MUC2, were all positive in the advanced adenocarcinoma. Of all markers used, only high iron diamine/Alcian blue pH 2.5 and Alcian blue pH 0.5 were positive in the early carcinoma. In these cases, mistakes frequently are made during examination of endoscopic biopsies. Fortunately, the advanced adenocarcinoma was low grade (the patient has shown no signs of disease at 6 years postsurgery). Histopathologic, histochemical, and immunohistochemical findings suggest that an extensive substrate of complete intestinal metaplasia (corpus) and of complete and incomplete intestinal metaplasia (antrum) can be associated with two independent tumors with different phenotypes.
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PMID:Advanced gastric carcinoma with a complete intestinal metaplasia phenotype associated with early intestinal-type carcinoma. 1473 79

We observed the sequential development of columnar lined epithelium associated with adenocarcinoma, squamous dysplasia related with squamous cell carcinoma and adenosquamous carcinoma which were induced by duodeno-esophageal or gastro-duodeno-esophageal reflux in rats. Wistar male rats, weighing approximately 250 g were employed. Animals received total gastrectomy and were reconstructed with esophago-jejunostomy, which causes unavoidable duodeno-esophageal reflux. The animals were sacrificed every 10 weeks after surgery until 50 weeks. Erosions and basal cell hyperplasia were observed in the lower esophageal squamous epithelium at 10 weeks after surgery. At 20 weeks, glandular structures featured with galactose oxidase-Schiff-positive staining (foveolar metaplasia) appeared in the basal layer of esophageal squamous epithelium. At 30 weeks, the glands developed and formed cysts which were stained with concanavalin A (pyloric glandular metaplasia) or/and high iron diamine and alcian blue (intestinal metaplasia). Since 40 weeks after surgery, esophageal carcinomas were found. As adenocarcinomas were surrounded by the columnar-lined epithelium, squamous cell carcinoma and adenosquamous carcinoma were accompanied by squamous dysplasia. Persistent duodeno-esophageal reflux can change the stem cells of squamous epithelium to make columnar-lined cells. As part of the sequence of events leading to the development of columnar-lined epithelium, foveolar metaplasia was observed followed by the appearance of pyloric glandular metaplasia and intestinal metaplasia. Chronic duodenal reflux induces the development of esophageal carcinoma not only adenocarcinoma also squamous cell carcinoma and adenosquamous carcinoma. These pathways of carcinogenesis were different dual patterns.
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PMID:[Reflux of duodenal or gastroduodenal contents induces esophageal carcinoma in rats]. 1534 31

Helicobacter pylori infection is acquired primarily during childhood and carries a significant lifetime risk for morbidity. In developing countries, approximately 70% of children are infected with the bacterium by their 15th birthday. In the United States, the rate of H pylori infection among children varies widely--approximately 10% of all 10-year-olds are infected; however, this figure is substantially higher among populations of immigrant children and children born of recent immigrants to the United States. H pylori transmission is primarily "person-to-person" via fecal-oral, gastric-oral, or oral-oral routes, with evidence suggesting contaminated water as a potential source of infection. Risk factors for infection in childhood include an infected family member, having > or =2 siblings, crowded living conditions, lower socioeconomic means, and attendance at a daycare facility. The natural history of H pylori infection includes an increased lifetime risk for peptic ulcer and gastric adenocarcinoma or lymphoma. In children and adults who develop H pylori-related peptic ulcer, cure of the infection is associated with a <5% rate of ulcer recurrence. The ideal mode of H pylori detection among children is unclear--currently available serology and whole blood tests are unreliable, while the urea breath test and stool antigen tests have not been studied adequately. Children with confirmed H pylori-related peptic ulcer disease, iron-deficiency (sideropenic) anemia, or a first-degree relative with gastric cancer should be treated for the infection using 1 of 3 available 10- to 14-day triple therapy regimens recommended by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
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PMID:Appropriate strategies for testing and treating Helicobacter pylori in children: when and how? 1547 50

In this three-phase study we first compared the availability of fourteen Fe forms in a wheat-based ready-to-eat breakfast cereal using an in vitro digestion/human colonic adenocarcinoma (CaCo-2) cell model. We then investigated the effect of milk and/or coffee on those fortified cereals found in phase 1 to show promising increases in Fe availability. The Fe forms assessed in phase 1 were reduced (control), carbonyl, electrolytic, FePO(4), FeSO(4), FeCO(3), Na(2)FeEDTA, Ferrochel (Albion Laboratories, Clearfield, UT, USA; ferrous bis-glycinate), encapsulated ferrous fumarate, FeSO(4), ferrous lactate and Biofer (LipoTech, Britwell Salome, Oxfordshire; FeSO(4)), SQM (Sea-Questra-Min Iron; Quali Tech, Chaska, MN, USA; polysaccharide-complexed FeSO(4)) and Sun Active (Taiyo Kagaku, Yokkaichi, Japan). All these forms increased Fe uptake compared with the unfortified cereal. Relative to the control, the following increases in Fe availability were observed: electrolytic, 52 %; ferrous fumarate, 30-35 %; Sun Active, 78 %; Ferrochel, 125 %; Na(2)FeEDTA, 291 %. Recent human studies have shown similar data with regard to Ferrochel, FeSO4 and Na(2)FeEDTA, with the latter being more bioavailable. Our phase-2 studies indicated that the addition of milk to FeSO(4)-fortified cereal increased Fe availability, but this availability was markedly decreased by the addition of coffee to the digest. Conversely, a loss in availability from Na(2)FeEDTA was observed with the addition of milk; however, the addition of coffee did not markedly affect Fe availability from this form. In phase-3 studies we observed increased Fe availability upon the addition of milk to cereals containing Ferrochel, FeSO(4), Sun Active, a mixture of reduced Fe and Na(2)FeEDTA or reduced Fe. For these forms we did not assess the behaviour after the addition of coffee. In conclusion, when considering possible fortificants for optimizing Fe bioavailability within a foodstuff, it is of paramount importance to consider the interaction between the fortified foodstuffs and other components of the meal (such as milk and coffee with a breakfast).
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PMID:Iron availability of a fortified processed wheat cereal: a comparison of fourteen iron forms using an in vitro digestion/human colonic adenocarcinoma (CaCo-2) cell model. 1570 27


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