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 aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 micrograms, as i.v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing's disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNF alpha concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 mumol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alpha levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 mumol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNF alpha concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH-secreting adenomas.
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PMID:Tumor necrosis factor-alpha increases after corticotropin-releasing hormone administration in Cushing's disease. In vivo and in vitro studies. 893 Sep 39

We report a case of a 35-year-old man with secondary amyloidosis chiefly involving the kidney and heart. The patient showed severe proteinuria and ischemic heart damage and had hepatic adenoma at the age of 33. Biopsy specimens from the kidney, heart, stomach and rectum showed extensive deposition of amyloid. After the surgical resection of a 300-gram hepatic adenoma, highly elevated c-reactive protein (CRP) levels decreased and the serum amyloid A (SAA) level was completely normalized. Normal liver cells were immunostained with rabbit anti-SAA antibody, but the cells in adenoma tissue and kidney were not. Electron microscopic examination revealed extracellular deposition of amyloid fibrils in the hepatic adenoma and kidney tissue. The concentration of tumor necrosis factor-alpha (TNF-alpha) (312 pg/mg tissue protein) was 7-fold higher in adenoma tissue than in normal liver tissue. Moreover, SAA (2.8 ng/mg tissue protein) was 2-fold higher in normal liver tissue than in adenoma tissue. Since TNF-alpha has been known to induce SAA production in target cells, the present results suggest that the hepatic adenoma produced TNF-alpha, which then caused mainly secondary amyloidosis in the kidney and heart. Currently, 2 years after surgical resection, urinary excretion of protein has been markedly reduced (from 3.5 to 0.8 g/day) and renal and cardiac functions are normal without specific medical treatment.
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PMID:A case of renal amyloidosis associated with hepatic adenoma: the pathogenetic role of tumor necrosis factor-alpha. 906 59

Apoptosis seems to be the predominant type of active cell death in the liver (type I), while in other tissues cells may die via biochemically and morphologically different pathways (type II, type III). Active cell death is under the control of growth factors and death signals. In the liver, endogenous factors, such as transforming growth factor beta 1 (TGF-beta 1), activin A, CD95 ligand, and tumor necrosis factor (TNF) may be involved in induction of apoptosis. Release and action of these death factors seems to be triggered by exogenous signals such as withdrawal of hepato-mitogens, food restriction, etc. During stages of hepatocarcinogenesis, not only DNA synthesis but also apoptosis gradually increase from normal to preneoplastic to adenoma and carcinoma tissue. Also, in human carcinomas, birth and death rates of cells are several times higher than in surrounding liver. (Pre)neoplastic liver cells are more susceptible than normal hepatocytes to stimulation of cell replication and of cell death. Consequently, tumor promoters may act as survival factors, i.e., inhibit apoptosis preferentially in preneoplastic and even in malignant liver cells, thereby stimulating selective growth of (pre)neoplastic lesions. On the other hand, regimens favoring apoptosis and lowering cell replication may result in selective elimination of (pre)neoplastic cell clones from the liver. Finally, we have studied the first stage of carcinogenesis, namely the appearance of putatively initiated cells after a single dose of the genotoxic carcinogen N-nitrosomorpholine (NNM). Most of these cells were found to be eliminated by apoptosis, suggesting that initiation, at the organ level, can be reversed at least partially by preferential elimination of initiated cells. These events may be regulated by autocrine or paracrine actions of survival factors.
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PMID:Apoptosis in the liver and its role in hepatocarcinogenesis. 929 54

In order to know more about the in vivo secretion of various cytokines from the human pituitary, this study measured the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-6, tumor necrosis factor-alpha and IL-1 receptor antagonist (ra) in both the peripheral blood and the cavernous sinus (CS) plasma from six patients with Cushing's disease before and after an intravenous bolus injection of human corticotropin-releasing hormone (CRH, 100 microg). As a routine procedure for the diagnosis of Cushing's disease, adrenocorticotropin (ACTH) levels were also determined in the same samples. In four of the six patients, unstimulated levels of IL-1ra in the CS ipsilateral to the ACTH-secreting adenoma were higher than those in the peripheral blood, with a ratio of > or = 1.5:1, even though CRH was without effect on the cytokine's concentration in the CS. In contrast, no consistent data were obtained for any of the remaining five cytokines. These results demonstrate for the first time that the in vivo release of IL-1ra is detectable in at least some corticotroph adenomas, and also suggest a possible role of the cytokine in physiological and pathophysiological processes occurring in the human pituitary.
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PMID:Measurement of cytokines in the cavernous sinus plasma from patients with Cushing's disease. 963 49

This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or cancer or that are in strong linkage disequilibrium with colorectal adenoma and/or cancer causing variants. A pooled analysis was performed for 30 polymorphisms in 20 different genes that have been reported in more than one colorectal adenoma or cancer study. An association with colorectal cancer was found for seven polymorphisms in seven genes reported in more than one study; no associations were found with colorectal adenoma. Four of the polymorphisms exhibited an increased colorectal cancer risk [GSTT1, NAT2 (phenotype), HRAS1, and ALDH2]. Two others [MTHFR, Tp53 (intron 3)] exhibited a decreased risk. For the tumor necrosis factor (TNF)a polymorphism of the TNF-alpha gene, one allele was associated with an increased risk (a2 allele) and two other TNFa alleles with decreased risks (a5 and a13 allele). No association with colorectal adenoma and/or cancer was detected for 23 other polymorphisms in 15 genes. However, of all 30 polymorphisms, only three pooled analyses had sufficiently large samples to confirm (MTHFR) or to exclude (GSTM1 and NAT2 genotype) the association with a P < 0.0026 and a power of 90%. Eighteen polymorphisms in 15 genes were each described in only one study, all with very small sample sizes. For 11 polymorphisms in 10 of these genes, an association with colorectal adenoma and/or cancer was found. Only simultaneous genotyping and combined analysis of different polymorphisms in large numbers of patients and controls, stratified by ethnicity, gender, and tumor localization and taking relevant dietary and lifestyle habits into account, will make it possible to describe the exact relations between polymorphisms and colorectal cancer susceptibility with an adequate power.
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PMID:Low-penetrance genes and their involvement in colorectal cancer susceptibility. 1243 10

The evaluation of postoperative peritoneal drainage fluid tumor necrosis factor (TNF)alpha and interleukin (IL)-6 was studied prospectively over a 7-day period in 25 patients operated on for neoplastic colorectal diseases. In 22 cases, colon or rectum carcinoma was the reason for surgery, and in 3 patients resection was performed because of colonic adenoma. All patients received either an end-to-end colo-colonic or colorectal anastomosis. Of this group, 22 patients were free of complications defined as uneventful postoperative course without any signs of anastomotic leakage until the 14th postoperative day. All of these patients showed a significant rise in peritoneal TNFalpha with maximum on the 7th day during the study period (p <.05). In contrast, peritoneal IL-6 levels remained constant without significant change in time (p >.05). Three patients underwent relaparotomy because of anastomotic leakage. In these patients, peritoneal TNFalpha concentrations showed a rise until the day of operative confirmation of anastomotic leakage. This rise preceded the day of operative confirmation by at least 1 day but did not change significantly in time (p =.59). Peritoneal IL-6 concentrations in patients with anastomotic leakage remained constant and also did not change significantly in time (p =.21). After elective colorectal surgery, neither postoperative abdominal drainage fluid TNFalpha nor IL-6 monitoring is helpful to decide on the need for revision in patients with anastomotic leakage.
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PMID:Peritoneal release of TNFalpha and IL-6 after elective colorectal surgery and anastomotic leakage. 1274 89

The acquisition of antiapoptotic properties is one of the essential mechanistic steps in colorectal carcinogenesis and is closely correlated with a loss of chemosensitivity and radiosensitivity. Human ring finger homologous to inhibitor of apoptosis protein type (hRFI) is a newly discovered gene encoding a ring finger domain highly homologous to that of X chromosome-linked inhibitor of apoptosis protein. Immunohistochemistry has revealed that the expression of hRFI increased in transition from normal colorectal mucosas to adenomas and from adenomas to carcinomas, suggesting an essential role in the early stage of colorectal carcinogenesis. However, the function role of hRFI in colorectal carcinoma has not been elucidated. To determine whether hRFI possesses an antiapoptotic function in colorectal cancer cells, HCT116 colorectal cancer cells stably overexpressing hRFI were established. The hRFI transfectant exhibited significant resistance to apoptosis induced by tumor necrosis factor-alpha or tumor necrosis factor-related apoptosis-inducing ligand compared with control. This antiapoptotic response was associated with decreased activity of caspase-3, -8, and -9. We also established an antisense down-regulation of hRFI, which effectively reversed the antiapoptotic activity of the hRFI transfectant. This confirmed that the antiapoptotic property of the hRFI transfectant was not due to the clonal effect but in fact dependent on hRFI function. In conclusion, hRFI possesses an antiapoptotic function in HCT116 colorectal cancer cells. Considering the progressive increase of hRFI expression in the advance of the colorectal adenoma-carcinoma sequence, hRFI is one of the important players in colorectal carcinogenesis through its effect on apoptosis regulation.
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PMID:Overexpression of hRFI (human ring finger homologous to inhibitor of apoptosis protein type) inhibits death receptor-mediated apoptosis in colorectal cancer cells. 1589 38

Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to be a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4+ CD45RB(hi) (T(E)) cells to induce inflammatory bowel disease (IBD) in mice, to investigate roles of inflammation on carcinogenesis in the Apc(Min/+) mouse model of intestinal polyposis. We find that transfer of T(E) cells significantly increases adenoma multiplicity and features of malignancy in recipient Apc(Min/+) mice. Surprisingly, we find that female Apc(Min/+) recipients of T(E) cells also rapidly develop mammary tumors. Both intestinal polyposis and mammary adenocarcinoma are abolished by cotransfer of anti-inflammatory CD4+ CD45RB(lo) regulatory lymphocytes or by neutralization of key proinflammatory cytokine tumor necrosis factor-alpha. Lastly, down-regulation of cyclooxygenase-2 and c-Myc expression is observed coincident with tumor regression. These findings define a novel mouse model of inflammation-driven mammary carcinoma and suggest that epithelial carcinogenesis can be mitigated by anti-inflammatory cells and cytokines known to regulate IBD in humans and mice.
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PMID:Proinflammatory CD4+ CD45RB(hi) lymphocytes promote mammary and intestinal carcinogenesis in Apc(Min/+) mice. 1639 16

Cytokines have been suggested to be key factors in modulating immune response against tumorigenesis in the microenvironment. Therefore, characterization of cytokine expression along the colorectal adenoma-carcinoma sequence may add important information for understanding the immune-related mechanisms of the development of colorectal carcinoma (CRC). In this study, biopsies from 32 patients with colorectal adenoma (CRA), 20 patients with CRC and 18 healthy controls were examined. Cytokine gene expressions of interleukin-4 (IL-4), IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and its upstream inducers (IL-12A and IL-18) were measured at messenger RNA (mRNA) level with quantitative real-time PCR (Q-PCR). Cytokine expressing cells were characterized using immunohistochemistry (IHC). A distinct different cytokine profile between adenoma and CRC was observed: the Th1 cytokines (IFN-gamma, TNF-alpha, IL-12A and IL-18) were increased in local tissues of CRA and decreased in CRC. Consistent with the quantitative cytokine data, IHC examinations revealed slightly increased densities of Th1 cytokine-expressing cells in CRA and a remarkably decreased density of the Th1 cells in CRC. In CRA, the cytokine-expressing cells were highly polarized to the subepithelial stroma while the cells were evenly distributed through the stroma in CRC. In conclusion, distinct changes in the Th1 cytokine profile appear along the colorectal adenoma-carcinoma sequence. This may reflect a change in the host immune regulatory function in the adenoma-carcinoma sequence.
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PMID:Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum. 1716 Apr 10

The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-alpha in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-alpha were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between known risk factors for colorectal neoplasia and circulating levels of inflammatory cytokines and associations between inflammatory cytokines and colorectal adenomas. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines, including older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-alpha and, to a lesser degree, with CRP. For IL-6, adjusted odds ratios (OR) for colorectal adenomas were 1.79 [95% confidence interval (CI), 1.19-2.69] for the second highest plasma level and 1.85 (95% CI, 1.24-2.75) for the highest level compared with the reference level. A similar association was found with TNF-alpha, with adjusted ORs of 1.56 (95% CI, 1.03-2.36) and 1.66 (95% CI, 1.10-2.52), respectively. Our findings indicate that systemic inflammation might be involved in the early development of colorectal neoplasia.
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PMID:Circulating levels of inflammatory cytokines and risk of colorectal adenomas. 1817 26


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