Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Woman 75-year-old treated 30 years for syndrome of acromegaly refused pituitary surgery and irradiation. Five years and nine months before death she had a colon carcinoma successfully removed. Multinodular hyperfunctional goitre was treated with carbimazole. For six last years of life corticosteroids were given as a replacement therapy. Her cause of death was the heart failure due to acromegalic heart disease. In autopsy a large intrasellar and extrasellar pituitary adenoma without rests of nonneoplastic tissue was found. Nevertheless the target peripheral endocrine glands except ovaries, were not atrophic. A multinodular goitre and diffuse adrenocortical hyperplasia were revealed. Histology, and immunohistochemistry demonstrated that mot neoplastic cells were producing GH and ACTH, dispersly Prl, scattered cells were positive for beta-subunit of FSH, LH, TSH. Electron microscopy proved most of the cells to be densely granulated. We classify the adenoma according to the newly proposed WHO pituitary tumours classification (1) as plurihormonal, hyperfunctional, extrasellar, typical adenoma from densely granulated cells. We conclude that in plurihormonal adenomas with dominant (in the case referred acromegalic) symptomatology the additional hormonal production should be monitored as a possible source of important complications.
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PMID:[Multihormonal and multifunctional hypophyseal adenoma and the acromegaly syndrome]. 1104 8

Expression of laminin-5 alpha3, beta3 and gamma2 protein subunits was investigated in colorectal adenocarcinomas using immunostaining and confocal microscopy. The laminin-5 heterotrimer was found in basement membranes and as extracellular deposits in tumor stroma. In contrast to the alpha3 subunit, which was under-expressed, the gamma2 and beta3 subunits were detected in the cytoplasm of carcinoma cells dissociating (budding) from neoplastic tubules, suggestive of focal alterations in laminin-5 assembly and secretion. Laminin-5 gamma2 or beta3 subunit-reactive budding carcinoma cells expressed cytokeratins but not vimentin; they did not proliferate and were not apoptotic. Furthermore, expression of laminin-5 gamma2 and beta3 subunits in budding cells was associated with focal under-expression of the E-cadherin-beta-catenin complex. Results from xenograft experiments showed that budding activity in colorectal adenocarcinomas could be suppressed when these tumors grew at ectopic s.c. sites in nude mice. In vitro, cultured colon carcinoma cells, but not adenoma-derived tumor cells, shared the laminin-5 phenotype expressed by carcinoma cells in vivo. Using colon carcinoma cell lines implanted orthotopically and invading the cecum of nude mice, the laminin-5-associated budding was restored, indicating that this phenotype is not only determined by tumor cell properties but also dependent on the tissue micro-environment. Our results indicate that both laminin-5 alpha3 subunit expression and cell-cell cohesiveness are altered in budding carcinoma cells, which we consider to be actively invading. We propose that the local tissue micro-environment contributes to these events.
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PMID:Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment. 1107 38

The progressive accumulation of genetic changes in both oncogenes and tumor-suppressor genes parallels the clinical and histopathologic progression from normal colonic epithelium through benign adenomas to frank colon cancer. A similar progression is postulated in the transition of normal squamous epithelium to metaplastic mucosa (Barrett's esophagus) and subsequently through dysplasia to adenocarcinoma of the esophagus. A common link between colorectal cancer and Barrett's esophagus or esophageal carcinoma might be explained by either genetic predisposition or common environmental risk factors. The multistep nature of oncogenesis is most directly illustrated by molecular experimental genetic studies which demonstrate that the progression from adenoma to colon carcinoma results from the accumulation of molecular genetic alterations involving mainly 3 factors: activation of oncogenes; inactivation of tumor-suppressor genes; and abnormalities in genes involved in DNA mismatch repair. Changes in oncogenes encoding four distinct groups of proteins (peptide growth factors, protein kinases, signal transducing proteins, and nuclear transcriptional regulatory proteins) can contribute to colon carcinogenesis. In addition, various carcinogens may act at different stages of this model, affecting somatic mutations and resulting in additional genetic alterations. Other promoters, including hormones, may enhance the likelihood of these events through the stimulation of the rate of cell turnover. Diseased detoxification processes may also play a role in carcinogenesis.
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PMID:New concepts of molecular biology for colon carcinogenesis. 1110 Mar 35

Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on alpha v beta 6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both alpha v beta 6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK). Furthermore, phosphorylated ERK was targeted to newly forming cell--matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK--tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK--ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK--ERK--dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression.
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PMID:The protrusive phase and full development of integrin-dependent adhesions in colon epithelial cells require FAK- and ERK-mediated actin spike formation: deregulation in cancer cells. 1149 15

Selective COX-2 inhibitors reduce adenoma formation and cancer progression in rodent models of colorectal cancer. To assess the therapeutic activity of selective COX-2 inhibitors, we tested the effect of SC-58125 treatment on the growth of human colon carcinoma cells in nude mice. Delaying treatment by 2, 4, or 7 weeks following implantation of the carcinoma cells resulted in a significant inhibition of tumor growth. Furthermore, short-term (48 hours) treatment with SC-58125 was sufficient to attenuate tumor growth for up to 15 days. SC-58125 treatment did not alter the rate at which cells underwent apoptosis, but did result in a delayed progression through the cell cycle at the G(2)/M transition. Accordingly, p34(cdc2) protein levels and activity were decreased following SC-58125 treatment. We conclude that SC-58125 primarily exerts a cytostatic effect in vivo, which is likely to be mediated through inhibition of progression through the G(2)/M phase of the cell cycle.
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PMID:A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. 1168 54

Arachidonic acid metabolism plays an important role in colon carcinogenesis. Cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the synthesis of prostaglandins from arachidonic acids, is known to be up-regulated in colon cancer, and multiple lines of evidence indicate that it is a critical early step in colon carcinogenesis. Recently, 15-lipoxygenase-1, the enzyme that converts arachidonic acid to 15(S)-HETE, was also found to be up-regulated in colon carcinoma. In our previous studies, we cloned a gene that encodes another arachidonic acid-using enzyme, fatty acid CoA ligase 4 (FACL4), and showed that overexpression of this enzyme prevents apoptosis. We have also showed that FACL4 and COX-2 synergistically inhibit apoptosis by reducing the intracellular level of free arachidonic acid. Here, we report that expression of FACL4 is significantly increased in colon adenocarcinoma compared with adjacent normal tissue at both the mRNA and protein levels by quantitative RT-PCR (paired t test, P < 0.015), immunoblot, and immunohistochemical staining. We found that the increase in expression level of FACL4 mRNA relative to control ranged between 2.4- and 54.5-fold; the average fold-increase was 13.4. The increase in FACL4 protein expression is between 2.4- and 65.0-fold. In addition, we found that a higher level of increased FACL4 expression was correlated with well and moderately differentiated adenocarcinoma, whereas no similar correlation was observed with COX-2 expression. The in situ hybridization results indicate that expression of FACL4 is localized predominantly in the colon epithelium but not in the stroma. The onset of FACL4 up-regulation appears to occur during the transformation from adenoma to adenocarcinoma because FACL4 expression was not increased above normal in the three colon adenomas examined. Finally, we observed that a tumor promoter significantly induced FACL4 expression. These findings suggest that the FACL4 pathway may be important in colon carcinogenesis, and that the development of selective inhibitors for FACL4 may be a worthy effort in the prevention and treatment of colon cancer.
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PMID:Fatty acid CoA ligase 4 is up-regulated in colon adenocarcinoma. 1173 23

We examined the expression of the putative tumor suppressor gene deleted in colorectal carcinoma (DCC) in human colon adenoma tissues and cell lines. One allele of DCC is deleted in 70% of human colon carcinomas, and DCC expression is undetectable in 90% of colon carcinoma cell lines. One DCC allele is also deleted in 50% of human colon adenomas, but results from protein expression studies have differed as to whether complete loss of DCC expression could occur in colon adenomas, or instead correlates with progression of colon adenoma to carcinoma. To further examine the timing of DCC expression loss in colon adenomas, we assayed DCC transcript levels in adenoma cell lines and tissues. We measured DCC expression by a sensitive assay using Southern blot detection of the RT-PCR-amplified DCC transcript. DCC expression was negligible or greatly reduced in 4 of 14 colon adenomas, including 2 of 2 adenoma cell lines and 2 of 12 adenoma tissue samples. These data are the first evidence that expression of DCC transcript can be silenced in colon adenoma cell lines and tissues. These data indicate that loss of DCC expression occurs in some colon adenomas, but is insufficient to drive the adenoma to carcinoma progression.
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PMID:Early loss of deleted in colorectal carcinoma gene transcript detected in a group of benign colon adenomas. 1243 38

Through the rigorous application of polypectomy, the colon carcinoma rate can be clearly reduced (66%). The term "polyp" comprises epithelial (hyperplastic or neoplastic) and nonepithelial causes. The majority of carcinomas in the colon develop from adenomatous tissue (adenoma-carcinoma sequence). Pedunculated adenomas (90% of all polyps) are removed with the high-frequency diathermy snare. In some cases, flat (sessile) polyps can be elevated by injections placed below them, and then removed with the diathermy snare (strip biopsy). In the event of larger or large-area flat polyps that cannot be removed with the snare, piecemeal resection is applied. The excision alone of adenomas with a stage I carcinoma is carried out only in so-called low-risk situations. Flat neoplasms make particular demands of the endoscopist, since they often appear merely as a reddish area, but may already have invaded the submucosa when diagnosed. For classification and, where indicated, endoscopic resection, the recommendations of the Japanese Society of Gastroenterological Endoscopy are applied.
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PMID:[Cancer prevention with the endoscope. Search not only for polyps!]. 1259 80

The Authors deal with a rare case of 'meta-metachronous' carcinoma of the colon. A seventy years old man was admitted to ward after being diagnosed an adenocarcinoma of the transverse colon. The anamnestic data pointed out that the patient had already been operated twice for the colon carcinoma, which had been diagnosed in the left colon and in the cecum respectively seven and two years before. A colonoscopy performed sixteen months before did not show any lesion of the residual colon. It is likely that tiny lesions, which were still in the adenoma phase, were not diagnosed by the endoscopy; it is also possible that the adenoma-carcinoma sequence was extremely fast. On the basis of this experience the Authors recommend that patients with metachronus carcinoma undergo either frequent controls or a preventive subtotal colectomy.
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PMID:[Metachronous carcinoma of the colon: report of a clinical case]. 1466 83

The aim of this study was to evaluate the potential application of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) for colorectal cancer screening in asymptomatic individuals. The subjects consisted of 3210 physical check-up examinees (1736 men, 1474 women; mean age +/- SD, 53.2 +/- 8 y) with non-specific medical history. In the control group, 12 patients who had gastrointestinal symptoms with biopsy-proved colon carcinoma were recruited. Whole-body FDG PET was performed on all patients. Focal hypermetabolic areas with an intensity equal to or exceeding the level of FDG uptake in the brain and bladder were considered abnormal and interpreted as intraluminal neoplasia. Among the 3210 FDG PET examinations, advanced neoplasm was present in 20 examinations, including 2 tubular adenomas larger than 1 cm, 12 villous adenomas and 6 cancers. Of 6 examinees diagnosed with cancer, one had a Dukes stage A lesion, four had Dukes stage B lesion and one had a Dukes stage C lesion. In the control group, of 12 patients with biopsy-proved carcinoma followed by FDG PET scan, six had a Dukes stage B lesion, four had Dukes stage C lesion and two had a Dukes stage D lesion. The mean and standard deviation of standard uptake value (SUV) in colonic adenoma and carcinoma is 3.56 +/- 0.68 and 5.74 +/- 2.26, respectively. The sensitivity of using FDG PET in the detection of primary colorectal cancer is high. Primary colorectal cancer can be detected with FDG PET in a resectable stage. FDG PET could detect large size (> 0.7 cm) and pre-malignant change of colonic adenoma. It is possible to differentiate adenoma from carcinoma of colon by an increased rate of glycolysis (SUV) in carcinoma.
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PMID:Colorectal cancer screening in asymptomatic adults: the role of FDG PET scan. 1466 51


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