Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal inflammatory diseases that can present as bloody diarrhea, abdominal pain, and malnutrition. Collectively, these disorders are referred to as inflammatory bowel disease (IBD). All patients with IBD share a common pathophysiology. However, there are a number of developmental, psychosocial, and physiologic issues that are unique to the approximate, equals 20% of patients that present during childhood or adolescence. These include the possibility of disease-induced delays in linear growth or physical development, differences in drug dosing, and the changes in social and cognitive development that occur as children move from school-age years into adolescence and early adulthood. Gastroenterologists caring for these children must therefore develop an optimal regimen of pharmacologic therapies, nutritional management, psychologic support, and properly timed surgery (when necessary) that will maintain disease remission, minimize disease and drug-induced adverse effects, and optimize growth and development. This article reviews current approaches to the management of patients with UC and CD and highlights issues specific to the treatment of children with IBD. The principal medical therapies used to induce disease remission in patients with UC are aminosalicylates (for mild disease), corticosteroids (for moderate disease), and cyclosporine (ciclosporin) (for severe disease). If a patient responds to the induction regimen, maintenance therapies that are used to prevent disease relapse include aminosalicylates, mercaptopurine, and azathioprine. Colectomy with creation of an ileal pouch anal anastomosis (J pouch) has become the standard of care for patients with severe or refractory colitis and results in an improved quality of life in most patients. Therefore, the risks associated with using increasingly potent immunosuppressant agents must be balanced in each case against a patient's desire to retain their colon and avoid a temporary or potentially permanent ileostomy. Decisions about drug therapy in the management of patients with CD are more complex and depend on both the location (e.g. gastroduodenal vs small intestinal vs colonic), as well as the behavior of the disease (inflammatory/mucosal vs stricturing vs perforating) in a given patient. Induction therapies for CD typically include aminosalicylates and antibiotics (for mild mucosal disease), nutritional therapy (including elemental or polymeric formulas), corticosteroids (for moderate disease), and infliximab (for corticosteroid-resistant or fistulizing disease). Aminosalicylates, mercaptopurine, azathioprine, methotrexate, and infliximab can be used as maintenance therapies. Because surgical treatment of CD is not curative, it is typically reserved for those patients either with persistent symptoms and disease limited to a small section of the intestine (e.g. the terminal ileum and cecum) or for the management of complications of the disease including stricture or abdominal abscess. When surgery is necessary, maintenance medications administered postoperatively will postpone recurrence. Patients with UC and CD are at risk for the development of micronutrient deficiencies (including folate, iron, and vitamin D deficiencies) and require close nutritional monitoring. In addition, patients with UC and CD involving the colon are at increased risk of developing colon cancer, and should be enrolled into a colonoscopy surveillance program after 8-10 years of disease duration.
 ...
PMID:Current therapy of inflammatory bowel disease in children. 1703 46

Iron could be a relevant risk factor for carcinogenesis since it catalyses the formation of reactive oxygen species (ROS), which damage DNA. We previously demonstrated genotoxic effects by ferric iron using the human colon cancer cell line HT29. Here we investigated ferric iron in primary non-transformed colon cells and in a preneoplastic colon adenoma cell line (LT97), which both are suitable models to study effects of carcinogens during early stages of cell transformation. Genetic damage was determined using the Comet assay. Comet FISH (fluorescence in situ hybridization) was used to assess specific effects on TP53. Fe-NTA (0-1000 microM, 30 min, 37 degrees C) significantly induced single strand breaks in primary colon cells (500 microM Fe-NTA: Tail intensity [TI] 22.6%+/-5.0% versus RPMI control: TI 10.6%+/-3.9%, p<0.01) and in LT97 cells (1000 microM Fe-NTA: TI 26.8%+/-7.3% versus RPMI control: TI 11.1%+/-3.7%, p<0.01). With the Comet FISH protocol lower concentrations of Fe-NTA significantly increased DNA damage already at 100 and 250 microM Fe-NTA in primary colon and LT97 adenoma cells, respectively. This damage was detected as an enhanced migration of TP53 signals into the comet tail in both cell types, which indicates a high susceptibility of this tumor relevant gene towards Fe-NTA. In conclusion, Fe-NTA acts genotoxic in non-transformed and in preneoplastic human colon cells, in which it also enhances migration of TP53 at relatively low concentrations. Translated to the in vivo situation these results suggest that iron overload putatively contributes to a genotoxic risk during early stages of colorectal carcinogenesis on account of its genotoxic potential in non-tumorigenic human colon cells.
 ...
PMID:Ferric iron is genotoxic in non-transformed and preneoplastic human colon cells. 1715 27

In three patients, aged 79, 58 and 59 years, respectively, iron-deficiency anaemia (IDA) was diagnosed. All three had a right-sided colonic adenocarcinoma. In the first patient, a cardiologic cause was looked for instead of a simple laboratory investigation of the anaemia. The second patient received iron supplementation without sufficient diagnostic evaluation, and in the third patient the abdominal X-ray was inadequate for evaluation of the ascending colon; moreover, she responded well to iron supplementation therapy. IDA is a common problem in clinical practice that may have various causes. In the Netherlands, gastrointestinal bleeding is the major cause of IDA in men and women over 50 years of age. The three patients described illustrate that IDA should be considered a clinical sign. An accurate evaluation of the IDA to detect a convincing explanation is therefore necessary. Various causes can be found on duodenoscopy and colonoscopy, e.g. neoplasms, ulcers, angiodysplasia or polyps. Carcinoma of the ascending colon is a frequent cause of IDA, especially in those over 50 years of age and without upper gastrointestinal symptoms. Evaluation to exclude a right-sided carcinoma of the colon has a high priority in these cases.
 ...
PMID:[Iron-deficiency anaemia: a sign that requires an adequate explanation]. 1755 74

A series of trans-2-alkyl-4-halopiperidines and 2-alkyl-4-halo-1,2,5,6-tetrahydropyridines were prepared by means of an iron(III) catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780 (ovarian cancer), SW1573 (non-small cell lung cancer), and WiDr (colon cancer). The results on the biological activity revealed that, in general, the 2-alkyl-4-halo-1,2,5,6-tetrahydropyridine analogs are more potent than the trans-2-alkyl-4-halopiperidine derivatives. A remarkable selectivity of the aza compound 5f for the resistant cell line WiDr was observed. Cell cycle studies revealed a G(2)/M phase arrest for 5f.
 ...
PMID:Antiproliferative activity of 2-alkyl-4-halopiperidines and 2-alkyl-4-halo-1,2,5,6-tetrahydropyridines in solid tumor cell lines. 1737 81

Different proteins ensure the fine control of iron metabolism at the level of various tissues. Among these proteins, it was discovered a second transferrin receptor (TfR2), that seems to play a key role in the regulation of iron homeostasis. Its mutations are responsible for type 3 hemochromatosis (Type 3 HH). Although TfR2 expression in normal tissues was restricted at the level of liver and intestine, we observed that TfR2 was frequently expressed in tumor cell lines. Particularly frequent was its expression in ovarian cancer, colon cancer and glioblastoma cell lines; less frequent was its expression in leukemic and melanoma cell lines. Interestingly, in these tumor cell lines, TfR2 expression was inversely related to that of receptor 1 for transferrin (TfR1). Experiments of in vitro iron loading or iron deprivation provided evidence that TfR2 is modulated in cancer cell lines according to cellular iron levels following two different mechanisms: (i) in some cells, iron loading caused a downmodulation of total TfR2 levels; (ii) in other cell types, iron loading caused a downmodulation of membrane-bound TfR2, without affecting the levels of total cellular TfR2 content. Iron deprivation caused in both conditions an opposite effect compared to iron loading. These observations suggest that TfR2 expression may be altered in human cancers and warrant further studies in primary tumors. Furthermore, our studies indicate that, at least in tumor cells, TfR2 expression is modulated by iron through different biochemical mechanisms, whose molecular basis remains to be determined.
 ...
PMID:Transferrin receptor 2 is frequently expressed in human cancer cell lines. 1742 3

Elevated levels of phospholipases, prostaglandin synthases and lipoxygenases in colonic cells at various stages of malignancy indicate a strong link between dietary lipids and colon cancer. Lipoxygenase-catalysed arachidonic acid metabolism plays a key role in colorectal carcinogenesis and has the potential to be modulated by phenolic compounds. Plant-based foods are rich sources of phenolic compounds and in the human colon they are predominantly available as simple phenolics such as the benzoic acids. Benzoic acids were determined in faecal waters from four volunteers consuming a western-style diet. Structure-activity relationships were established for the lipoxygenase-catalysed oxygenation of arachidonic acid using an oxygen electrode. All compounds studied inhibited this reaction (21-73%; p<0.001) and many of the structural features could be rationalised by computational modelling. No correlation was observed with the ability to act as reductants, supporting the hypothesis that their mode of inhibition may not be by a direct redox effect on the non-haem iron.
 ...
PMID:Inhibition of 15-lipoxygenase-catalysed oxygenation of arachidonic acid by substituted benzoic acids. 1831 36

Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-kappaB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer's disease.
 ...
PMID:Curcumin: from ancient medicine to current clinical trials. 1832 53

Iron depletion, using iron chelators targeting transferrin receptor (TfR) and ribonucleotide reductase (RR), is proven to be effective in the treatment of cancer. We synthesized and evaluated novel polyaminocarboxylate-based chelators NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-NETA, C-NE3TA, and N-NE3TA for use in iron depletion tumor therapy. The cytotoxic activities of the novel polyaminocarboxylates were evaluated in the HeLa and HT29 colon cancer cell lines and compared to the clinically available iron depletion agent DFO and the frequently explored polyaminocarboxylate DTPA. All new chelators except C-NETA displayed enhanced cytotoxicities in both HeLa and HT29 cancer cells compared to DFO and DTPA. Incorporation of the nitro functional unit for conjugation to a targeting moiety into the two potent non-functionalized chelators NE3TA and NE3TA-Bn (C-NE3TA and N-NE3TA) was well-tolerated and resulted in a minimal decrease in cytotoxicity. Cellular uptake of C-NE3TA, examined using a confocal microscope, indicates that the chelator is taken up into HT29 cancer cells.
 ...
PMID:Synthesis and evaluation of novel polyaminocarboxylate-based antitumor agents. 1834 10

Colon and rectal cancers are both associated with genetic as well as nutritional, occupational, and environmental factors. Aromatic amines and heterocyclic amines are established colorectal carcinogens. The polymorphic enzyme N-acetyltransferase 1 (NAT1) contributes to heterocyclic amine metabolism in the human colon. Thereby, NAT1 may influence the risk for development of colorectal cancer. The distribution of NAT1 genotypes was determined in 107 colon cancer cases, 77 rectal cancer cases, and 185 controls (suffering from nonmalignant diseases) by standard methods. In addition, possible occupational and nonoccupational risk factors were determined by a personal interview. Cancer cases and controls were derived from an area of former coal, iron, and steel industries, which is known for elevated colon cancer mortality. The proportions of NAT1*4/*4 genotype were 72% in controls, 75% in rectal cancer cases, and 72% in colon cancer cases. The proportions of the NAT1*4/*10 genotype were 17.8% in controls, 12.9% in rectal cancer cases, and 14% in colon cancer cases. Combinations of the determined NAT1 alleles *3/*3, *3/*10, *4/*3, *4/*11, *10/*10 and *11/*11 contributed to 10.2% of the genotypes in controls, 12.1% in rectal cancer cases, and 14% in colon cancer cases. In contrast to another study on healthy German volunteers, the NAT1*4/*4 genotype (wild type) is overrepresented. This might be due to the variation in the proportion of NAT1 alleles in the general population. The present study does not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area.
 ...
PMID:N-acetyltransferase 1 in colon and rectal cancer cases from an industrialized area. 1856 93

The usual form of presentation of celiac disease is chronic diarrhoea and deficiencies of vitamin D, vitamin K, iron and vitamin B12, due to malabsorption. Intestinal obstruction secondary to an intussusception is rare in adults and usually is a complication of carcinoma of the colon or post-operative adhesions. We report a 45 year-old female consulting for diarrhoea and vomiting lasting one week and progressive abdominal bloating. A plain abdominal X ray showed air fluid levels in the small bowel and a CT scan showed an intussusception. She was operated and discharged but continued with diarrhoea. She was admitted again and a new CT scan showed three intussusceptions that were resolved with the administration of oral contrast media. Antiendomisial antibodies were positive and a celiac disease was diagnosed. After one year with a gluten free diet, the patient remains asymptomatic.
 ...
PMID:[Celiac disease presenting as an intestinal intussusception. Report of one case]. 1903 Jun 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>