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)

Single nucleotide polymorphisms (SNPs) were searched for in 36 genes involved in diverse DNA repair pathways, and 50 nonsynonymous (associated with amino acid changes) SNPs identified were assessed for associations with lung cancer risk by a case-control study consisting of 752 adenocarcinoma cases, 250 squamous cell carcinoma cases and 685 controls. An SNP, Arg72Pro, of the TP53 gene encoding a DNA damage response protein showed the strongest association with squamous cell carcinoma risk (OR Pro/Pro vs. Arg/Arg = 2.2), while 2 other SNPs, Phe257Ser of the REV gene encoding a translesion DNA polymerase and Ile658Val of the LIG4 gene encoding a DNA double-strand break repair protein, also showed associations (OR Ser/Ser vs. Phe/Phe = 2.0 and OR Ile/Val vs. Ile/Ile = 0.4, respectively). An SNP, Thr706Ala, in the POLI gene encoding another translesion DNA polymerase was associated with adenocarcinoma and squamous cell carcinoma risk, particularly in individuals of ages < 61 years (OR Ala/Ala + Ala/Thr vs. Thr/Thr = 1.5 and 2.4, respectively). POLI is the human counterpart of PolI, a strong candidate for the Par2 (pulmonary adenoma resistance 2) gene responsible for adenoma/adenocarcinoma susceptibility in mice. The present results suggest that these 4 SNPs function as genetic factors underlying lung cancer susceptibility by modulating activities to maintain the genome integrity of each individual.
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PMID:Association of amino acid substitution polymorphisms in DNA repair genes TP53, POLI, REV1 and LIG4 with lung cancer risk. 1560 17

Whereas animal and in vitro studies support a role of unsaturated fatty acids in colon carcinogenesis, the epidemiologic evidence is inconclusive. Using a large sigmoidoscopy-based case-control study (753 cases and 799 controls) in Los Angeles County, we investigated possible associations between single-nucleotide polymorphisms in the XRCC1 (codons 194 Arg/Trp and codon 399 Arg/Gln) and XRCC3 (codon 241 Thr/Met) genes and colorectal adenoma risk and their possible role as modifiers of the effect of monounsaturated fatty acid, the ratio of omega-6/omega-3 polyunsaturated fatty acids, and antioxidant intake. We found no evidence of associations between the XRCC1 codon 194 Arg/Trp or Trp/Trp genotypes and the XRCC3 codon 241 Thr/Met or Met/Met genotypes. Subjects with the XRCC1 Gln/Gln genotype were inversely associated with adenoma risk (odds ratio, 0.6; 95% confidence interval, 0.4-0.9; P = 0.01) when compared with subjects with Arg/Arg and Arg/Gln genotypes combined. We found no evidence of gene-dietary fat interactions for the XRCC3 codon 241 polymorphism. However, our data suggest an XRCC1-unsaturated fat interaction. High monounsaturated fatty acid intake was associated with adenoma risk only among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln combined genotypes (P for interaction = 0.018). High omega-6/omega-3 polyunsaturated fatty acid ratios were associated with adenoma risk among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln or the codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.026). These interactions were not modified by antioxidant intake. However, low antioxidant intake was associated with an inverse association only among subjects with the XRCC1 codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.022), which was independent of unsaturated fat intake. Our data suggest that the XRCC1 codon 194 and codon 399 single nucleotide polymorphisms may modify the effect of unsaturated fatty acid and antioxidant intake and that this XRCC1 effect modification may explain, in part, previously reported inconsistencies on the role of unsaturated fatty acids and adenoma risk.
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PMID:XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. 1576 38

Several mutations of the TSH-receptor gene have been described in a variety of thyroid diseases. Particularly in children and adolescents, somatic or germ cell mutations may lead to hyperthyroidism. In these cases, molecular analysis of the TSHR gene provides important information for further clinical management. We report a 3-year-old boy with a rare somatic TSHR mutation causing autonomous adenoma of the thyroid gland in order to illustrate how the genetic analysis of the lesion impacted on the surgical strategy. The patient presented with a left neck mass, negative thyroid autoantibodies, and unifocal autonomy on thyroid scan. He underwent local resection of the adenoma. Genetic workup demonstrated a somatic mutation of TSHR. Exons 9 and 10 of the TSHR gene (chromosome 14q3) from peripheral blood DNA and toxic thyroid adenoma tissue DNA were amplified by PCR and analyzed by denatured gradient gel electrophoresis (DGGE). DGGE from the EDTA blood sample showed no difference compared to the wild-type, whereas material extracted from the tissue sample showed a mutation in exon 10. Direct sequencing of the PCR product from the tissue demonstrated a heterozygous mutation in codon 453 (ATG-->ACG), leading to a substitution of methionine by threonine. The genetic appraisal of resected thyroid tissue in cases with nonautoimmune hyperthyroidism is important to formulate surgical and medical treatment plans. In cases with somatic mutations of the TSHR, simple resection of the adenoma is sufficient, whereas total thyroidectomy should be considered in patients with germ cell mutations.
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PMID:Activating TSH-receptor mutation (Met453Thr) as a cause of adenomatous non-autoimmune hyperthyroidism in a 3-year-old boy. 1949 84

We investigated the effects of the AMPK activator AICAR as compared to somatostatin-14 on cell viability and GH secretion in human GH-secreting pituitary adenomas in vitro and in rat GH3 cells. Overnight treatment with AICAR increased phospho-(threonine-172) AMPK levels (activated AMPK) in cultured human adenomas. As to the effects on cell viability, four adenomas out of 15 were responsive to AICAR (0.4mM) and five adenomas were responsive to SS-14 (100 nM). One adenoma was responsive to both somatostatin and AICAR. The effects of cotreatment with SS-14 and AICAR were investigated in eight adenomas. In two adenomas, the effects of AICAR+SS-14 did not exceed the effect of AICAR. In two adenomas which were not responsive to either AICAR or SS-14, the cotreatment was able to reduce cell viability versus control. Two adenomas were not responsive to any treatment. As to the effects on GH secretion, nine adenomas out of 15 were responsive to AICAR. Twelve adenomas were responsive to SS-14. Eight adenomas were responsive to both AICAR and SS-14. Cotreatment exceeded the effect of single treatments in 4 out of 10 adenomas. In GH3 cells, AICAR reduced the activity of p70S6 kinase, which plays an important role in cell growth. SS-14 did not affect significantly AMPK phosphorylation and p70S6K activity but it was able to enhance the inhibitory effect of AICAR on phospho-S6 levels. Moreover, AICAR and SS-14 reduced ERK phosphorylation with a different time course. The combined treatment reduced phospho-ERK levels at any time point.
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PMID:Effects of AMPK activation and combined treatment with AMPK activators and somatostatin on hormone secretion and cell growth in cultured GH-secreting pituitary tumor cells. 2311 72

The molecular abnormalities leading to sporadic parathyroid adenomas, a common type of human endocrine neoplasm, are heterogeneous and incompletely understood. Using whole exome and direct sequencing of parathyroid adenoma DNA samples, we identified recurrent somatic mutations in the ZFX gene. ZFX is a member of Krueppel C2H2 type zinc finger protein family, was initially described as a homolog of ZFY, and has been implicated as a transcription factor regulating embryonic stem cell renewal. The ZFX mutations we identified were strikingly specific, focused in each tumor on one encoded residue in a hotspot of two consecutive highly conserved arginine residues (R786/787; arginine to glutamine, threonine or leucine) in a zinc finger domain near the C-terminus of the protein. The intragenic specificity of these recurrently selected mutations, their confirmed expression within the tumors, the absence of loss of heterozygosity, and the absence of these mutations among over 4000 ZFX alleles in the dbSNP137 database, strongly suggest a novel role for ZFX as a human proto-oncogene. Further, these observations highlight the mutated zinc-finger domain as a new focal point for understanding ZFX's normal and tumorigenic functions, and for development of molecularly-targeted therapeutics.
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PMID:Recurrent ZFX mutations in human sporadic parathyroid adenomas. 2582 39

Nowadays, people pay more and more attention to the natural products based on their multiple targets in the antitumor treatment. In our previous research, Rhizoma paridis saponins (RPS) were regarded as potent anticancer agent that elicits programmed cell death and inhibits metastases in murine lung adenocarcinoma in vivo. In the present study, we set up a rat model of diethylnitrosamine (DEN) induced pulmonary adenoma to evaluate the antitumor effects of RPS again. After 20 weeks treatment, rats were sacrificed in order to perform histopathological examinations, blood biochemistry, immunohistochemistry, western blot, PCR and metabonomics. As a result, DEN induced pulmonary adenoma generation in the lungs and damaged hepatocytes and hepatoma formation in the livers. RPS effectively attenuated hepatotoxic and inhibited pulmonary adenoma through down-regulating expression of MMP-9 and up-regulating level of TIMP-2 in DEN-induced rats. Meanwhile, RPS remarkably decreased energy metabolism, and glycine, serine and threonine metabolism to block the tumor growth. In conclusion, RPS would be a potent anticancer agent used in the prospective application.
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PMID:Inhibition of pulmonary adenoma in diethylnitrosamine-induced rats by Rhizoma paridis saponins. 2619 22

Studies suggest that gene mutation and carcinogen exposure contribute to lung tumorigenesis including a mutation of epidermal growth factor receptor (EGFR) and exposure to benzo[a]pyrene (BaP). However, the interaction between EGFR mutation and BaP exposure during lung tumorigenesis is unclear. Metabolomics has become an important tool in clinical research and has been utilized to help our understanding of mechanisms and to identify indicators of cancers. This study's aim was to identify the changes in metabolite profiles in mice associated with an EGFR exon 21 deletion and/or BaP treatment-induced lung tumorigenesis. While the EGFR mutation increased the incidence of lung adenoma in transgenic mice (EGFR mutant mice) at 32 weeks of age, exposure to BaP caused the onset of lung tumorigenesis in these mice as early as 16 weeks after exposure. Using a metabolomics strategy involving liquid chromatography-mass spectrometry in conjunction with principal component analysis and confirmation by liquid chromatography triple quadrupole tandem mass spectrometry, we demonstrated that the serum amino acid profiles of these mice were changed. A total of eight amino acid concentrations were lower in EGFR mutant mice than in wild-type mice at 32 weeks of age. Five amino acids were lower in tumor-bearing mice than in non-tumor-bearing EGFR mutant mice at 10th week post-treatment of BaP, namely phenylalanine, tyrosine, alanine, proline, and threonine. Our results suggest that gene mutation and carcinogen exposure-induced lung adenomas share some common mechanisms. Changes in serum amino acid profiles may be early indicators of lung tumorigenesis.
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PMID:Changes of serum amino acid profiles by an epidermal growth factor receptor mutation and benzo[a]pyrene in mouse lung tumorigenesis. 3009 Apr 24


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