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)

It has been shown that angiogenesis plays an important role not only in tumor growth, but also in early carcinogenesis. The expression of a potent angiogenic factor, vascular endothelial growth factor (VEGF), increased during the early stage of carcinogenesis. In this study, the effects of the neutralizing monoclonal antibodies R1 mAb and R2 mAb of the VEGF receptors Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), respectively, on murine hepatocarcinogenesis induced by diethylnitrosamine (DEN) were examined. The effects of R1 mAb and R2 mAb on spontaneous lung metastasis from hepatocellular carcinoma (HCC) were also investigated. VEGF expression and neovascularization in the tumor increased stepwise during hepatocarcinogenesis. Treatment with both R1 mAb and R2 mAb markedly inhibited the development of HCC and adenoma in the liver. The inhibitory effect of R2 mAb was more potent than that of R1 mAb, and the combination treatment with both mAbs almost completely attenuated hepatocarcinogenesis. Both R1 mAb and R2 mAb treatment significantly suppressed the development of angiogenesis in HCC. The suppressive effects against angiogenesis R1 mAb and R2 mAb were similar in magnitude to their inhibitory effects against hepatocarcinogenesis. Furthermore, spontaneous lung metastasis from HCC was also significantly suppressed by R1 mAb and R2 mAb treatment. In conclusion, these results suggest that VEGF and receptor interaction plays an important role in hepatocarcinogenesis and in spontaneous lung metastasis from HCC.
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PMID:Halting the interaction between vascular endothelial growth factor and its receptors attenuates liver carcinogenesis in mice. 1518 88

Discerning malignancy in adrenal tumors largely influences disease management and is, therefore, of utmost importance to both patient and physician. Clinical presentation (e.g. virilization) and baseline hormonal evaluation (e.g. high serum DHEAS) are occasionally of great value but usually provide only limited help in predicting malignancy. The probability of malignancy is clearly related to tumor size, as almost all lesions <3 cm are benign whereas a diameter of >6 cm indicates a high risk of malignancy. Computed tomography (CT) and magnetic resonance imaging (MRI) both contribute significantly to the characterization of adrenal masses. If the attenuation of a homogeneous mass with smooth border is 10 Hounsfield units or less in unenhanced CT the diagnosis of a lipid rich adenoma is established. Similarly, enhancement washout of more than 50% in CT at 10-15 min suggests a benign lesion. In MRI both rapid contrast enhancement after gadolinium followed by rapid washout and signal intensity loss using opposed-phase image in chemical shift analysis also indicate the presence of an adenoma. In contrast, adrenal carcinomas--but also pheochromocytomas--typically present as inhomogeneous lesion with intermediate-to-high intensity on T2 images in MRI. Margins and enhancement after contrast media in CT are irregular in adrenal carcinoma. Other imaging techniques either offer little additional information (NP-59 scintigraphy) or have not yet been fully established (positron emission tomography). Fine needle aspiration/cut biopsy is at present restricted to patients with a known extra-adrenal malignancy and suspected adrenal metastasis as the only evidence of disseminated disease. Adrenal tumors classified as benign undergo follow-up imaging to assess tumor growth. If an increase in diameter of >1 cm is seen, surgical removal is recommended. Even after tumor removal the diagnosis of dignity may remain difficult. Diagnostic scores together with new immunohistological markers are the methods of choice to assess malignancy. In conclusion, an interdisciplinary approach with a structured use of available diagnostic tools is needed to classify adrenal tumors correctly.
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PMID:Adrenal tumors: how to establish malignancy ? 1523 62

In vitro, the growth inhibiting effect of ACTH on adrenocortical cells is well documented, even though there are reports of opposite effects under defined cell culture conditions. In vivo, activation of the ACTH receptor (ACTHR) has a trophic effect on the adrenal cortex, while the effects on proliferation are still under discussion, especially since other POMC derived peptides have been characterized. However, ACTH is thought to act as a differentiation factor with inhibiting effects on tumor growth. In undifferentiated adrenocortical carcinomas, ACTHR expression is frequently lost, which is associated with extensive tumor growth. We describe a new microsatellite marker within the intron of the ACTHR gene termed ACTHRint1. In a series of 114 patients with various adrenal and non-adrenal tumors, the rate of heterozygosity was 100 %. Only one out of 57 patients with adrenocortical adenoma showed LOH at the ACTHR locus, whereas 4 of 10 carcinomas had loss of one allele. Patients suffering from tumors with LOH showed a more aggressive disease course and had earlier recurrences with poor prognosis. These data confirm earlier findings that adrenocortical carcinomas frequently show loss of ACTHR expression, which is associated with a more aggressive tumor growth. However, whether the ACTHR is directly involved in tumor growth or acts a marker of differentiation that is lost in more advanced tumor stages is still not clear.
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PMID:The role of the ACTH receptor in adrenal tumors: identification of a novel microsatellite marker. 1524 32

Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.
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PMID:Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. 1538 May 19

Previous studies indicate that the arachidonic acid-metabolizing enzymes COX-2 and 5-LOX are overexpressed during the process of colonic adenoma formation promoted by cigarette smoke. The aims of the present study were to investigate whether there exists a relationship between COX-2 and 5-LOX, and whether dual inhibition of COX-2 and 5-LOX has an anticarcinogenic effect in the colonic tumorigenesis promoted by cigarette smoke. Results showed that pretreating colon cancer cells with cigarette smoke extract (CSE) promoted colon cancer growth in the nude mouse xenograft model. Inhibition of COX-2 or 5-LOX reduced the tumor size. In the group treated with COX-2-inhibitor, the PGE2 level decreased while the LTB4 level increased. In contrast, in the 5-LOX-inhibitor treated group, the LTB4 level was reduced and the PGE2 level was unchanged. However, combined treatment with both COX-2 and 5-LOX inhibitors further inhibited the tumor growth promoted by CSE over treatment with either COX-2-inhibitor or 5-LOX-inhibitor alone. This was accompanied by the downregulation of PGE2 and LTB4. In an in vitro study, we found that the action of CSE on colon cancer cells was mediated by 5-LOX DNA demethylation. In summary, these results indicate that inhibition of COX-2 may lead to a shunt of arachidonic acid metabolism towards the leukotriene pathway during colonic tumorigenesis promoted by CSE. Suppression of 5-LOX did not induce such a shunt and produced a better response. Therefore, 5-LOX inhibitor is more effective than COX-2 inhibitor, and blocker of both COX-2 and 5-LOX may present a superior anticancer profile in cigarette smokers.
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PMID:Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. 1563 91

Cushing's disease caused by a microadenoma located near the pituitary stalk is infrequent and spontaneous remission caused by necrosis of a corticotropinoma in such location has not been reported. A 42-year-old woman with ACTH-dependent Cushing's syndrome presented on magnetic resonance imaging (MRI) a 3-mm microadenoma attached to the pituitary stalk. Treatment with ketoconazole normalized urinary free cortisol (UFC) from 433.0 to 66.0 microg/day, although it failed to reduce elevated serum androgen levels (DHEAS 4770 ng/ml). After one year, treatment was stopped and UFC rose again to 936.0 microg/day but one month later the patient presented acute headache and signs of steroid withdrawal syndrome. Endocrine evaluation showed glucocorticoid and androgen deficiency (UFC 5.0 microg/day; DHEAS < 300 ng/ml); control MRI revealed disappearance of the microadenoma. Cushingoid signs subsided and steroid replacement was initiated, proving still necessary over two years after the episode. Infarction or hemorrhage of a corticotrope adenoma could be a probable underlying mechanism although its precipitating factor is unclear. Ketoconazole withdrawal, through abrupt increase in cortisol production and/or the interruption of a hypothetical inhibitory action on cell replication followed by tumor growth and compromise of vascular supply, may be considered as possible triggering factors. To the best of our knowledge, this is the first report of spontaneous remission of Cushing's disease caused by presumed infarction of a microadenoma, unusually located in the superior rim of the pituitary, attached to the stalk.
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PMID:Spontaneous remission of Cushing's disease after disappearance of a microadenoma attached to the pituitary stalk. 1563 98

A large body of clinical, genetic, and biochemical evidence indicates that cyclooxygenase-2 (COX-2), a key enzyme for prostanoid biosynthesis, contributes to the promotion of colorectal cancer. COX-2-derived prostaglandin E2 (PGE2) is the most abundant prostaglandin found in several gastrointestinal malignancies. Although PGE2 enhances intestinal adenoma growth in Apcmin mice, the mechanism(s) by which it accelerates tumor growth is not completely understood. Here we investigated how PGE2 promotes intestinal tumor growth and the signaling pathways responsible for its effects. We observed that PGE2 treatment leads to increased epithelial cell proliferation and induces COX-2 expression in intestinal adenomas. Furthermore, we show that PGE2 regulation of COX-2 expression is mediated by activation of a Ras-mitogen-activated protein kinase signaling cascade. One intriguing finding is that COX-2-derived PGE2 mimics the effects of constitutively active Ras through a self-amplifying loop that allows for a distinct growth advantage.
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PMID:Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade. 1575 80

A 38-year-old man presented with a recurrent pleomorphic adenoma in the parapharyngeal space invading the skull base 19 years after the first operation for a parotid gland tumor. Stereotactic radiotherapy was performed to control the tumor growth using a marginal dose of 8 Gy and maximum dose of 18 Gy with care taken to minimize the dose to nearby structures. The symptoms were reduced within a few months. Magnetic resonance imaging over 5 years showed that the tumor was controlled with no regrowth. Stereotactic radiotherapy is a therapeutic option for the treatment of pleomorphic adenomas.
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PMID:Stereotactic radiosurgery for recurrent pleomorphic adenoma invading the skull base--case report--. 1578 9

A 23-year-old female rhesus macaque presented with a 2.5-cm diameter, firm, moveable, lobulated subcutaneous mass associated with a supranummary teat on the right side of the chest. This animal was a retired breeder, currently in an aging study. No exogenous hormone treatments were noted in the animal's history. Chest radiographs were within normal limits. Blood screens showed no noteworthy variations from normal. Needle aspirate cytology showed clusters of neoplastic cells. Grossly the mass was well circumscribed, firm, and homogeneously tan, with a glandular appearance. Differential diagnoses included sebaceous or mammary adenoma, carcinoma in situ, and lobular or ductular carcinoma. Histopathology was consistent with a mammary ductal carcinoma with comedo pattern. Subsequent needle aspirate cytology from an adjacent right axillary lymph node showed tumor cells with a few lymphoid cells, interpreted as lymphatic spread. Chest radiographs 2 and 6 weeks postbiopsy showed no evidence of pulmonary metastasis. After 1 year, there was no marked change on chest radiographs, but a small cluster of new nodules was palpable in the right axillary region. Histopathology of an excisional biopsy of the new nodules indicated tumor growth subjacent to regional lymph nodes. Further treatment was not performed and the animal remained clinically normal five years after the initial diagnosis. Spontaneous mammary neoplasia is a major concern in human medicine, yet it rarely has been reported to occur in nonhuman primates. This case is important in documenting an additional case of spontaneous mammary tumor development.
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PMID:Mammary ductal carcinoma with comedo pattern in a rhesus macaque. 1605 Jun 65

Substantial evidence indicates that significant exposure to cigarette smoke is associated with an elevated risk for colorectal cancer. However, the mechanisms underlying the causal relationship between cigarette smoking and colorectal cancer remain to be investigated. Our previous study showed that cigarette smoke promotes the formation of inflammation-associated colonic adenoma in mice through an angiogenic pathway. Therefore, in the present study, we used the human colon adenocarcinoma cell line, SW1116, and human umbilical vascular endothelial cells (HUVECs) to elucidate the possible mechanisms in vitro. Results showed that cigarette smoke extract enhanced cell proliferation and the expression of 5-lipoxygenase (5-LOX), vascular endothelium growth factor (VEGF), matrix metalloproteinases (MMPs) 2 and 9 in SW1116 cells. Inhibition of 5-LOX decreased cell proliferation and expressions of VEGF, MMP-2 and MMP-9 induced by cigarette smoke extract. In addition, cigarette smoke extract indirectly stimulated HUVEC proliferation, a biological activity closely related to angiogenesis during tumor growth. This was again blocked by the 5-LOX inhibitor. Taken together, the results of the present study demonstrate the central role of 5-LOX and its relationship with angiogenic mediators in the actions of cigarette smoke in the promotion of angiogenesis during colon cancer growth.
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PMID:A mechanistic study of colon cancer growth promoted by cigarette smoke extract. 1612 68


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