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)

The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc(Min/+) mouse and correlate with a high relative risk of human colorectal cancer susceptibility, respectively. We examined the functional consequence of Igf2 allelic dosage (null, monoallelic, and biallelic) on intestinal adenoma development in the Apc(Min/+) by breeding with mice with either disruption of Igf2 paternal allele or H19 maternal allele and used these models to evaluate an IGF-II-specific therapeutic intervention. Increased allelic Igf2 expression led to elongation of intestinal crypts, increased adenoma growth independent of systemic growth, and increased adenoma nuclear beta-catenin staining. By introducing a transgene expressing a soluble form of the full-length IGF-II/mannose 6-phosphate receptor (sIGF2R) in the intestine, which acts as a specific inhibitor of IGF-II ligand bioavailability (ligand trap), we show rescue of the Igf2-dependent intestinal and adenoma phenotype. This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer.
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PMID:Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. 1648 92

We reviewed the cases of 32 patients with growth hormone (GH)-secreting macroadenoma who underwent short-term octreotide treatment before transsphenoidal surgery to determine which types of adenoma the preoperative treatment were sensitive and whether predictors of tumor shrinkage could be identified. The effects of preoperative octreotide treatment, endocrinologic effect and effect on tumor volume in 32 patients were evaluated retrospectively in relation to tumor features on magnetic resonance images and responses to endocrinologic challenge tests. At a daily dose of 300 microg for 2-3 weeks, octreotide reduced serum GH and insulin-like growth factor-1 (IGF-1) levels to 31.9 % and 51.6% of pretreatment values, respectively, and led to a mean tumor volume of 68% of pretreatment volume in 52% of the patients. The endocrinologic effect and the effect on tumor volume were larger in Knosp grades 0-2 than in Knosp grades 3-4. Tumor shrinkage occurred significantly more often among patients that had a good response to both octreotide and bromocriptine challenge tests. For surgical removal of the tumor, the effect of reducing tumor to 68% of pretreatment volume will be beneficial for the macroadenomas of Knosp grades 1-2. Preoperative short-term octreotide treatment is effective for GH-secreting macroadeomas of Knosp grades 1-2 and a good response to both octreotide and bromocriptine challenge tests is a predictor of subsequent tumor shrinkage. These results will lead to more effective selection of patients for preoperative octreotide treatment.
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PMID:Short-term preoperative octreotide treatment of GH-secreting pituitary adenoma: predictors of tumor shrinkage. 1654 82

There is growing evidence that the insulin-like growth factor-binding protein 3 (IGFBP-3) can have IGF-independent effects on cell growth. However, despite the fact that IGFBP-3 has been reported to be both antiproliferative and proapoptotic, the molecular mechanisms underlying the action of IGFBP-3 have not been elucidated. We report that although addition of IGFBP-3 (either synthetic or secreted protein) had no effect on cell survival, IGFBP-3 (100 ng/ml) significantly enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cell death in colonic carcinoma-derived cell lines (20-30% depending on cell line), whereas it had no effect on the survival of the TRAIL-resistant adenoma-derived cells. Both addition of IGFBP-3 protein to cell cultures or enforced expression of IGFBP-3 in the HT29 carcinoma cell line inhibited nuclear factor kappa B (NF-kappaB) activation in response to the induction of apoptosis by TRAIL. We propose that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an adjuvant in the treatment of colon cancer.
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PMID:Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. 1664 43

Acromegaly is a rare disease caused by excess secretion of growth hormone (GH), usually from a pituitary somatotrope adenoma. The prevalence of acromegaly is 38-40 cases/1,000,000 subjects, while the annual incidence is 3 new cases/1,000,000 subjects. The increase in morbidity and mortality associated with acromegaly is the result of GH and insulin-like growth factor (IGF)-I oversecretion and the direct mass effect of the pituitary tumor. Once the disease is clinically suspected, laboratory evaluation is mandatory to establish diagnosis. The standard method for the diagnosis of acromegaly has been the measuring of GH nadir (GHn) during an oral glucose tolerance test (OGTT) which in normal individuals is undetectable, while acromegalics failed to suppress GH levels. Determination of IGF-I levels is useful as they correlate with clinical features of acromegaly and with the 24-hour mean GH levels. According to the more recent consensus, a random GH <0.4 microg/l and IGF-I in the age- and gender-matched normal range exclude the diagnosis of acromegaly. If either of these levels are not achieved, an OGTT should be performed, and then GHn <1 microg/l during OGTT excludes acromegaly. The therapeutic goals for acromegaly include the relief of sings and symptoms, the control of the tumor mass, the correction of the biochemical markers to normal levels, and the reduction in morbidity and mortality to the expected rate for the normal population. According to the 2000 consensus criteria, biochemical control of acromegaly is achieved when circulating IGF-I is reduced to an age- and sex-adjusted normal range and GHn during OGTT is <1 microg/l. There is debate in the literature whether GHn or IGF-I levels are more reliable to evaluate treatment of acromegaly. It has been reported that 15% of acromegalics with GHn <1 microg/l after treatment demonstrate abnormal IGF-I levels, while 15% of patients with normal IGF-I fail to suppress GH levels <1 microg/l during the OGTT. Probably, GHn and IGF-I levels represent two different aspects of disease activity in acromegaly. While IGF-I evaluates the secretory function of the somatotropes, GHn provides evidence of the presence or absence of functional autonomy of these cells.
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PMID:Dynamic tests and basal values for defining active acromegaly. 1704 83

An impressive body of epidemiologic data collected over the past decade indicates that the risk of colon cancer is elevated in those with metabolic syndrome. This evidence includes studies that examined the risk of colon cancer or adenoma in relation to determinants of the metabolic syndrome (obesity, abdominal distribution of adiposity, and physical inactivity), clinical consequences of this syndrome (type 2 diabetes and hypertension), plasma or serum components of the definition of metabolic syndrome (hypertriglyceridemia, hyperglycemia, and low HDL cholesterol), and markers of hyperinsulinemia or insulin resistance (insulin and C-peptide), which is the underlying metabolic defect of the metabolic syndrome. The mechanism underlying these associations is unknown but may involve the influence of hyperinsulinemia in enhancing free or bioavailable concentrations of insulin-like growth factor-1. Future studies should also be based on better measurements of insulin resistance, beta-cell depletion, and insulin responses to better assess which aspects of insulin resistance are most closely related to the risk of colon neoplasia.
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PMID:Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. 1826 77

Silibinin, a flavonolignan from milk thistle seeds, possesses cancer chemopreventive properties in rodent models of carcinogenesis. We tested the hypotheses that silibinin or silipide, silibinin formulated with phospholipids, delays tumour development in TRAMP or Apc(Min) mice, genetic models of prostate or intestinal malignancies, respectively. Mice received silibinin or silipide with their diet (0.2% silibinin equivalents) from weaning. Intervention with silipide reduced the size of well differentiated TRAMP adenocarcinomas by 31%. Silipide and silibinin decreased the incidence of poorly differentiated carcinomas by 61% compared to mice on control diet. Silipide decreased plasma levels of insulin-like growth factor (IGF)-1 by 36%. Levels of circulating IGF binding protein (IGFBP)-3 in mice on silipide or silibinin were 3.9- or 5.9-fold, respectively, elevated over those in control TRAMP mice. In Apc(Min) mice silibinin, but not silipide, had only a marginal adenoma number-reducing effect. The results cautiously support the advancement of silipide to the stage of clinical investigation in prostate cancer.
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PMID:Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels. 1834 54

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.
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PMID:Study of growth factors and receptors in carcinoma ex pleomorphic adenoma. 2014 60

Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery.
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PMID:Excess body weight and obesity--the link with gastrointestinal and hepatobiliary cancer. 2138 10

In the veterinary literature there are few data concerning the expression of insulin-like growth factor type I (IGF-IR) in the canine mammary gland tumors. The aim of the present study was the evaluation of IGF-IR expression and its correlation to the expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR), proteins: Bcl-2, Bax, p53 in canine mammary gland tumors, and also a correlation with other features: bitch's age, tumor diameter, histologic type of tumor, degree of histologic malignancy, proliferate activity. The study was done on 112 epithelial neoplasms: 21 (19%) were adenoma, 38 (34%) complex carcinoma (adenocarcinoma), 47 (42%) simple carcinoma (adenocarcinoma) and 6 (5%) solid carcinoma. Histochemistry and immunohistochemistry methods were employed. It was shown that more common and/or higher IGF-IR expression in cells of canine mammary gland tumors was related to the histologic type of cancer of worse prognostic (solid and simple carcinoma), high histologic degree of malignancy (III degrees) but the statistical analysis did not reveal any significant differences. We observed the high degree of IGF-IR expression in tumors which displayed the high ERalpha and PR expression. These results suggest the involvement of IGF-IR in the development of hormonosensitive canine mammary tumors. Additionally, the significant positive correlation between expression of IGF-IR and p53, Bax was found. Our study provides some evidence that interactions exist between the IGF-IR and these apoptosis-associated proteins may contribute to the development and progression of canine mammary gland tumors. These results require further investigations.
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PMID:Relationship between receptors for insulin-like growth factor- I, steroid hormones and apoptosis-associated proteins in canine mammary tumors. 2172 9

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C>A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.
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PMID:Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation. 2174 88


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