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)

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.
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PMID:c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas. 195 73

Cyclopenta[cd]pyrene (CPP) is a ubiquitous cyclopenta-fused polycyclic aromatic hydrocarbon. CPP is highly genotoxic in bacterial and mammalian systems inducing gene mutations, sister chromatid exchanges and morphological transformation. CPP is a mouse skin carcinogen, a mouse skin tumor initiator and induces pulmonary tumors in newborn mice. We have examined the tumorigenic activity of CPP in strain A/J mice, have determined the formation and persistence of CPP-induced DNA adducts in lung tissue, and analyzed the mutational spectrum in the Ki-ras oncogene from CPP-induced tumors. CPP dissolved in tricaprylin was administered by i.p. injection to male A/J mice (20 mice/dose) at 0, 10, 50, 100 and 200 mg/kg. Animals were killed 8 months later and the lungs removed, fixed, and surface adenomas enumerated. CPP proved to be highly tumorigenic in A/J mice in terms of inducing lung adenomas. The observed tumor multiplicities (lung adenomas/mouse) were: 97.7 +/- 28.7 at 200 mg/kg, 32.8 +/- 15.4 at 100 mg/kg, 4.63 +/- 2.11 at 50 mg/kg and 0.58 +/- 0.82 at 10 mg/kg. Tricaprylin-treated controls produced 0.60 +/- 0.58 lung adenomas/mouse. Groups of mice treated under the same dosing conditions as those in the tumor studies were killed 1, 3, 7, 14 and 21 days after treatment. The lungs were removed, and the DNA was subjected to DNA adduct analysis by the 32P-postlabeling method. Total CPP-DNA adducts in mouse lung peaked at day 3 with 5870 amol CPP adducts/micrograms DNA after a single dose of 200 mg/kg. DNA adduct levels decreased to 1800 amol CPP adducts/micrograms DNA at day 21. Qualitative DNA adduct analysis revealed four major adducts and one minor adduct. Co-chromatography of the lung DNA from CPP-treated mice with calf thymus DNA treated with CPP-3,4-oxide indicated that all DNA adducts were oxide derived and comparison with CPP-3,4-oxide-treated polydeoxyguanylic acid suggests that almost all of these adducts are CPP-3,4-oxide-2'-deoxyguanosine adducts. Ki-ras codon 12 mutation analysis of the DNA from tumors taken from the 100 and 200 mg/kg CPP dose groups demonstrated the following patterns: GGT-->CGT (50%); GGT-->GTT (15%); GGT-->TGT (25%); GGT-->GAT (10%). We conclude that CPP is highly tumorigenic in the A/J mouse lung adenoma model, being five times more active than benzo[a]pyrene. This is unlike the result of CPP as a mouse skin tumorigen or tumor initiator in which CPP is considerably less potent than benzo[a]pyrene.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclopenta[cd]pyrene-induced tumorigenicity, Ki-ras codon 12 mutations and DNA adducts in strain A/J mouse lung. 814 68

Twenty-four sporadic colorectal adenomas were analysed for the presence of allelic loss on the short arm of chromosome 17 as well as mutations in the K-ras and p53 genes. Chromosome 17p13 allelic loss was not present in 14 out of 14 informative cases. K-ras mutations were observed in 15 out of 24 cases. A p53 gene mutation (GGC-->GAC at codon 245) was detected in two biopsies taken at a four year interval from a recurrent rectal villous adenoma. Both biopsies also contained the same K-ras gene mutation (GGT-->GTT at codon 12). The data from the recurrent rectal adenoma provide in vivo evidence that K-ras and p53 heterozygous mutations confer a proliferative advantage but together are not sufficient for malignant transformation.
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PMID:Genetic events in sporadic colorectal adenomas: K-ras and p53 heterozygous mutations are not sufficient for malignant progression. 831 95

To elucidate genetic alteration in relation to morphology and also to confirm more directly the proposed adenoma-carcinoma sequence, we analyzed thirty-eight colorectal "cancer in adenoma" lesions exhibiting areas of different atypia, in terms of K-ras codon 12 point mutation. The mutation incidence was 26.3% (10/38) for all cancerous areas. Well-differentiated and very well-differentiated carcinoma exhibited values of 17.6% (3/17) and 30.4% (7/23), respectively (statistically not significant). Positive cases of adenoma with severe atypia and adenoma with moderate or slight atypia were 26.7% (8/30) and 8.3% (3/36) respectively (statistically significant). Thus, K-ras point mutation, as indicated previously, may play an important role in the early stages of colorectal tumorigenesis. As for the nature of the mutation, GGT(Gly) to GAT(Asp) was the most frequent (80%). Eight cases had mutations concurrently in different areas of the same tumor and in all of these the mutation was homogeneous (6 cases to GAT, 1 case to TGT and 1 case to GTT). This provides genetic support for the "adenoma-carcinoma sequence" theory proposed on the basis of morphological considerations. All lesions with a mutation were of polypoid type, and no mutation was found in the flat type.
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PMID:Variation in K-ras codon 12 point mutation rate with histological atypia within individual colorectal tumors. 851 5

Treatment options for acromegaly include surgical removal of the adenoma, radiotherapy, or pharmacological reduction of growth hormone (GH) levels by dopamine agonists or somatostatin analogs. Whether such treatment can truly cure acromegaly is debatable. A problem with evaluating efficacy of treatment is the lack of consensus of what constitutes a cure. Despite modern neurosurgical techniques for resecting GH-secreting pituitary adenomas, more than 50% of patients may have persistent GH hypersecretion; radiotherapy may take years to produce an effect. There is thus interest in pharmacological relief of symptoms and reduction in GH secretion. We report on eight patients with a biochemical diagnosis of acromegaly (failure of suppression of GH levels to < 2.5 micrograms/L following a glucose tolerance test [GTT]). The use of Sandostatin-LAR (Sandoz Pharma Ltd, Basel, Switzerland) in doses of 20 to 30 mg intramuscularly at 4 week intervals produced consistent and therapeutic serum octreotide concentrations, suppressed GH secretion to 5 micrograms/L in all eight subjects, lowered insulin-like growth factor-1 (IGF-1) levels in all and normalized values in seven of eight, improved or led to disappearance of symptoms and signs, and was not associated with an increase in adverse events as compared with subcutaneous treatment.
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PMID:Treatment options for acromegaly. 876 85

Point mutations at codon 12 of the c-Ki-ras gene were investigated in 103 biopsy tissues from 38 patients with gastric adenoma. DNA from minute specimens of formalin-fixed paraffin-embedded tissue was amplified by nested polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) method was used to detect mutations of the c-Ki-ras gene. Mutations were detected in 4 of the 38 gastric adenomas (10.5%), but were not detected in intestinal metaplasias and gastric adenocarcinomas. Of the 4 mutation-positive gastric adenomas, the GGT sequence in codon 12 changed to GAT in 2 cases, to GTT in 1 case and to TGT in 1 case. We classified gastric adenomas into three degrees of atypia; mutations were detected only in biopsy tissues with moderate and severe atypia but were not detected in biopsy tissues with mild atypia. When different biopsy tissues from a mutation-positive gastric adenoma were examined, the mutation was not always detected in every tissue sample examined. This suggests that mutations are not homogeneously distributed, even in the same adenoma. It is possible to follow up the mutation of biopsy materials of gastric adenoma by this method.
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PMID:Detection of c-Ki-ras oncogene mutation in gastric adenomas with formalin-fixed, paraffin-embedded biopsy materials. 905 92

The prognostic significance of a diffusely infiltrative intramyometrial growth pattern was evaluated in 110 cases of low-stage (stages I and II) endometrial adenocarcinoma. Fifty cases were associated with diffuse infiltration (DI group), and 50 cases had more conventional granulation tissue type intramyometrial infiltration (GTT group). Ten cases with carcinomatous involvement of deeply situated adenomyosis (ADMY group) were also studied. The diffusely infiltrative "adenoma malignum" growth pattern featured typically round, regular individual glands, clearly within myometrium but with minimal or absent stromal or inflammatory cell response. Myoinvasion of the conventional sort was characterized by irregular, sharply angulated abnormal glands within myometrium without interposed normal glands or endometrial stroma. The abnormal glands were surrounded, at least focally, by edematous stroma with granulation tissue type reaction and/or an inflammatory cell infiltrate. Mean follow-up was 77.8 months (range 3-219 months) for the patients with diffusely infiltrative myoinvasion and deep adenomyosis and 86.9 months (range 1-206 months) for the patients with conventional myoinvasion. Recurrence-free survival for patients with stage I disease and conventional myoinvasion (94%) was similar to that of patients with diffuse adenoma malignum infiltration (98%; p = 0.13). Survival rates for both groups were also similar. Two (4%) of the 50 patients with diffusely infiltrative adenoma malignum pattern of myoinvasion died of endometrial carcinoma 36 and 72 months after hysterectomy, and 2 (4%) of the 50 patients with conventional myoinvasion died 34 and 67 months after hysterectomy (p = 0.41). Survival in these patients correlated with depth of myometrial invasion and stage. There were no recurrences in the patients with deep adenomyosis. These results suggest that although endometrial carcinomas with diffuse myometrial infiltration are fully capable of aggressive clinical behavior, they do not appear to behave any more aggressively than those with conventional myometrial invasion. Prognostic indicators of clinically aggressive disease are similar to those that have been previously identified for endometrial carcinomas with the more conventional pattern of myometrial infiltration. They include cervical involvement, deep myometrial invasion, higher histologic grade, and lymph-vascular space invasion. Endometrial carcinomas with extensive involvement of adenomyosis and adjacent foci of minimal myometrial infiltration appear to have very low malignant potential, but the number of cases with this finding and adequate clinical follow-up is limited. This finding needs to be confirmed in a much larger series of cases.
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PMID:Diffusely infiltrative endometrial adenocarcinoma: an adenoma malignum pattern of myoinvasion. 988 5