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)

Multiple genetic and epigenetic alterations in oncogenes, tumour-suppressor genes, cell-cycle regulators, cell adhesion molecules, DNA repair genes and genetic instability as well as telomerase activation are implicated in the multistep process of human stomach carcinogenesis. However, particular combinations of these alterations differ in the two histological types of gastric cancer, indicating that well-differentiated or intestinal-type and poorly differentiated or diffuse-type carcinomas have distinct carcinogenetic pathways. In the multistep process of well-differentiated-type carcinogenesis, the genetic pathway can be divided into three subpathways: an intestinal metaplasia-->adenoma-->carcinoma sequence, an intestinal metaplasia-->carcinoma sequence and de novo. In the multistep process of well-differentiated-type or intestinal-type gastric carcinogenesis, infection with Helicobacter pylori may be a strong trigger for hyperplasia of hTERT-positive 'stem cells' in intestinal metaplasia. Genetic instability and hyperplasia of hTERT-positive stem cells precede replication error at the D1S191 locus, DNA hypermethylation at the D17S5 locus, pS2 loss, RARbeta loss, CD44 abnormal transcripts and p53 mutation, all of which accumulate in at least 30% of incomplete intestinal metaplasias. All of these epigenetic and genetic alterations are common events in intestinal-type gastric cancer. An adenoma-->carcinoma sequence is found in about 20% of gastric adenomas with APC mutations. In addition to these events, p53 mutation and loss of heterozygosity (LOH), reduced p27 expression, cyclin E expression and the presence of c-met 6.0-kb transcripts allow malignant transformation from the above precancerous lesions to intestinal-type gastric cancer. DCC loss, APC mutations, 1q LOH, p27 loss, reduced tumour growth factor (TGF)-beta type I receptor expression, reduced nm23 expression and c-erbB gene amplification are frequently associated with an advanced stage of intestinal-type gastric cancer. The de-novo pathway for carcinogenesis of well-differentiated gastric cancer involves LOH and abnormal expression of the p73 gene that is responsible for the development of foveolar-type gastric cancers with pS2 expression. On the other hand, LOH at chromosome 17p, mutation or LOH of p53 and mutation or loss of E-cadherin are preferentially involved in the development of poorly differentiated gastric cancers. In addition to these changes, gene amplification of K-sam, and c-met and p27 loss as well as reduced nm23 obviously confer progression, metastasis and diffusely productive fibrosis. Mixed gastric carcinomas composed of well-differentiated and poorly differentiated components exhibit some but not all of the molecular events described so far for each of the two types of gastric cancer. Besides these genetic and epigenetic events, well-differentiated and poorly differentiated gastric cancers also organize different patterns of interplay between cancer cells and stromal cells through the growth factor/cytokine receptor system, which plays an important role in cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. Meta-analysis of epidemiological studies and animal models show that both intestinal and diffuse types of gastric cancer are equally associated with H. pylori infection. However, H. pylori infection may play a role only in the initial steps of gastric carcinogenesis. Differences in H. pylori strain, patient age, exogenous or endogenous carcinogens and genetic factors such as DNA polymorphism and genetic instability may be implicated in two distinct major genetic pathways for gastric carcinogenesis.
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PMID:Genetic pathways of two types of gastric cancer. 1505 5

Pleomorphic adenomas (PAs) of salivary glands are characterized by the mixed appearance of epithelial and mesenchymal-like components such as myxoid and chondroid tissues. Although various studies have examined PAs, thus far it is not clear how PAs make these multiple components. Thus, clarification of the histodifferentiation of this unique salivary gland tumor using not only tissues in vivo but also PA cells cultured in vitro is necessary. However, no in vitro model of PA has been reported, because normal and benign tumor cells tend to grow slowly and senesce quickly in culture. Therefore, we immortalized cells using transfection of the hTERT gene without otherwise altering the nature of those cells. The immortalized PA cells expressed mRNA of the pleomorphic adenoma gene 1 and showed epithelial and neoplastic myoepithelial characteristics by immunohistochemical immunofluorescence analyses and ultrastructural study. Our findings suggest that these cells will be a useful model to study the cellular differentiation of PA.
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PMID:Immortalization and characterization of pleomorphic adenoma cells by transfection with the hTERT gene. 1761 90

To investigate the potential efficacy of calcium and vitamin D in reducing risk for colorectal neoplasms and to develop "treatable" phenotypic biomarkers of risk for colorectal neoplasms, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of these agents on cell cycle markers in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2 g/day calcium and/or 800 IU/day vitamin D(3) versus placebo over 6 months. Overall expression and distributions of p21(waf1/cip1) (marker of differentiation), MIB-1 (marker of short-term proliferation), and hTERT (marker of long-term proliferation) in colorectal crypts in the normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. In the calcium, vitamin D, and calcium plus vitamin D groups relative to the placebo, p21 expression increased by 201% (P = 0.03), 242% (P = 0.005), and 25% (P = 0.47), respectively, along the full lengths of colorectal crypts after 6 months of treatment. There were no statistically significant changes in the expression of either MIB-1 or hTERT in the crypts overall; however, the proportion of hTERT, but not MIB-1, expression that extended into the upper 40% of the crypts was reduced by 15% (P = 0.02) in the vitamin D plus calcium group relative to the placebo. These results indicate that calcium and vitamin D promote colorectal epithelial cell differentiation and may "normalize" the colorectal crypt proliferative zone in sporadic adenoma patients, and support further investigation of calcium and vitamin D as chemopreventive agents against colorectal neoplasms.
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PMID:Effects of vitamin d and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial. 1986 11

The differential diagnosis of parathyroid carcinoma from benign adenoma is often difficult when its typical clinicopathological features are absent, even with the aid of various molecular markers. We recently demonstrated that telomerase activation through hTERT expression is a unique characteristic that is limited to parathyroid carcinoma and not seen in benign tumors. In the present study, we investigated hTERT expression in parathyroid tumors using immunohistochemistry in an attempt to determine its clinical utility. There was no evidence of immunoreactivity in the 4 normal parathyroid glands and the 18 typical adenomas. In contrast, one atypical adenoma stained positively and homogeneously, and the disease recurred three times clinically. All of the 6 carcinomas demonstrated a clear positive nuclear staining of hTERT. Every hTERT-positive tumor showed a high Ki-67 index, i.e., greater than 4%. Nucleolin, an hTERT-binding protein, was abundantly and homogeneously expressed in all specimens examined independent of the pathological diagnosis and hTERT or Ki-67 expression. Therefore, it is possible that immunostaining with an anti-hTERT antigen (NCL-L-hTERT) individually may distinguish parathyroid carcinoma from benign tumors.
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PMID:Diagnosis of parathyroid carcinoma using immunohistochemical staining against hTERT. 1988 12

Pathologists are usually readily able to diagnose parathyroid tissues and diseases, particularly when they have knowledge of the clinical information, laboratory findings, and radiographic imaging studies. However, the identification of parathyroid tissue or lesions can be difficult in small biopsies, ectopic locations, supranumerary glands, and in some oxyphil/oncocytic lesions. Widely available immunohistochemical studies such as chromogranin-A, synaptophysin, keratin, parathyroid hormone, thyroglobulin, and thyroid transcription factor-1 can help in difficult cases. One of the most difficult diagnostic aspects faced by the pathologist in evaluating parathyroid is distinguishing between parathyroid adenoma, particularly atypical adenoma, and parathyroid carcinoma. Many markers have and continue to be evaluated for diagnostic utility, and are even beginning to be studied for prognostic utility. Single immunohistochemical markers such as parafibromin and Ki-67 are among the most studied and most utilized, but many additional markers have and continue to be evaluated such as galectin-3, PGP9.5, Rb, bcl2, p27, hTERT, mdm2, and APC. Although not widely available in many laboratories, a panel of immunohistochemical markers may prove most useful as an adjunct in the evaluation of challenging parathyroid tumors.
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PMID:Immunohistochemistry in Diagnostic Parathyroid Pathology. 2962 76

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.
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PMID:Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias. 2968 98