Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoid tumours (DT) are slow-growing tumours that consist of proliferations of well-differentiated fibroblasts. Although the typical characteristics of malignant tumours, such as distant metastases, are absent, the tumours are locally aggressive and grow into neighbouring structures. The prevalence of desmoid tumours in patients with FAP is 7-12%. The lifetime risk of developing desmoid tumours is about 20%. In FAP, most tumours are intra-abdominal or located in the abdominal wall. Next to colorectal cancer, desmoid tumours are the most frequent cause of death in FAP. Possible risk factors for the development of desmoid tumours are previous surgical procedures, pregnancy, female sex, a family history of desmoid tumours, and specific mutations in the APC-gene. Both CT scanning and MRI can be used to detect the tumours. An excision biopsy is needed to establish the diagnosis. Medicinal treatment with NSAIDs is the treatment of first choice, followed by hormonal treatment (e.g., tamoxifen) in combination with NSAIDs. Both forms of treatment lead to a response in about 30-50% of the patients. Surgery is the preferred treatment for extra-abdominal tumours or tumours located in the abdominal wall. Surgical treatment of intra-abdominal tumours is only indicated in patients with obstruction of the bowel or ureter. Chemotherapy is indicated in patients with progressive desmoid tumours when non-cytotoxic treatment has failed. Radiotherapy may play a role in the treatment of irresectable extra-abdominal or abdominal wall tumours, or as adjuvant treatment of tumours with positive margins.
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PMID:[Desmoid tumors in patients with familial adenomatous polyposis]. 1216 72

The E-cadherin/catenin complex plays a major role in epithelial cell-cell adhesion. Both beta-catenin and gamma-catenin bind directly to the cytoplasmic domain of E-cadherin whereas alpha-catenin links the bound beta-catenin or gamma-catenin to the actin microfilament network of the cellular cytoskeleton. Significant changes in the expression and/or structure of members of the complex can occur in neoplasia. Several studies have reported on the nuclear localization of beta- and gamma-catenin and on their role in influencing the transcriptional activity of several proto-oncogenes. The cellular localization of alpha-catenin has not been studied in detail. The aim of this study was to investigate the cellular localization of alpha-catenin in colorectal carcinoma both in vitro and in vivo and to assess whether it might be relevant to tumor behavior. The expression of alpha-catenin was examined in a panel of colorectal carcinoma cell lines (SW480, SW620, HCT116, HT29, and Caco-2) using a combination of immunohistochemistry, confocal fluorescence microscopy, and Western blotting. The expression of alpha-catenin was also studied by immunohistochemistry in 15 sporadic colorectal adenomas, 30 sporadic colorectal adenocarcinomas, and their 13 lymph node metastases. From familial adenomatous polyposis patients, 20 adenomas and 5 adenocarcinomas were studied. Nuclear localization of alpha-catenin was detected in the colorectal carcinoma cell lines when the cells were dispersed rather than confluent. alpha-catenin was not detected in the nuclei in any of the sporadic or familial adenomas. However, it was detected in one sporadic and one familial adenocarcinoma but not in any of the lymph node deposits. alpha-catenin can localize to the nuclei of colorectal tumor cells, and this may be related to lack of perception of connection to adjacent cells.
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PMID:Variable nuclear localization of alpha-catenin in colorectal carcinoma. 1221 77

A large number of epidemiological studies have shown that regular use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) results in a 40-50% reduced risk of colorectal cancer (CRC). Furthermore, NSAIDs cause the regression of preexisting adenomas in patients with familial adenomatous polyposis and significantly inhibit tumor growth in animal models of CRC. To establish a CRC liver metastasis model, we implanted mouse colon tumor MC-26 cells into the splenic subcapsule of BALB/c mice, after which mice were given either standard chow or chow containing the cyclooxygenase (COX)-2-specific inhibitor rofecoxib, alone or in combination with the standard antineoplastic agents, 5-fluoruracil or irinotecan. After 14 days, mice that were given rofecoxib or irinotecan, but not 5-fluoruracil, had significantly smaller primary tumors and fewer metastases. Rofecoxib, at clinical anti-inflammatory plasma concentrations, enhanced the effects of both antineoplastic agents when used in combination. Biochemical analyses of the primary splenic tumor in rofecoxib-treated mice showed no alteration in COX-1 expression, but significant decreases in the expression of the tumor-promoting proteins COX-2, cyclin D1, cytosolic beta-catenin, matrix metalloproteinases-2 and -9, and vascular endothelial cell- derived growth factor. Rofecoxib also decreased growth-enhancing prostaglandin E(2) and tumor-suppressive interleukin-10, whereas antineoplastic interleukin-12 was increased. Two separate survival studies were performed. When mice were fed chow containing 0.01% rofecoxib beginning on day 0 after tumor cell implantation, which achieved clinical anti-inflammatory plasma concentrations, survival time was significantly longer compared with mice given control chow. After 30 days, mortality in the control group was 90%, whereas only one mouse (5%) treated with rofecoxib had died after 30 days. In the second survival study, all of the mice were initially fed with regular chow after tumor cell implantation. On day 7, mice were randomly divided into three dietary groups: control chow, low-dose (0.01%) rofecoxib chow, and high-dose (0.025%) rofecoxib chow. After 28 days, mortality was 100%, 20%, and 10% in control, low-, and high-dose rofecoxib fed groups, respectively. These studies demonstrate that rofecoxib decreases the growth and metastatic potential of CRC in mice through multiple mechanisms. These studies in mice also provide important information that supports the benefit of COX-2 inhibition, not only in the prevention of CRC, but also potentially in the treatment of this common malignancy. Clinical trials will be necessary to assess the utility of COX-2 inhibitors as adjuvant therapy for early-stage disease and as potential agents, either alone or in combination, with more established drugs, for the treatment of refractory CRC.
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PMID:Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. 1256

The putative oncogene, integrin-linked kinase (ILK) is a protein serine/threonine kinase that has been reported to regulate a number of biological properties including anchorage-independent cell cycle progression, tumour cell invasion and apoptosis. Overexpression of ILK has been documented in a wide variety of human malignancies including Ewing's sarcoma (ES), primitive neural ectodermal tumours (PNETs) and prostate tumours (PT). We recently reported that ILK signalling was also dysregulated in patients with the genetic condition familial adenomatous polyposis (FAP), a precursor to colon cancer. In this study, we extended our previous work by investigating the ILK-signalling pathway in sporadic human colon cancer and representative lymph node metastases. The data indicate that the ILK protein is significantly hyperexpressed in malignant acini in relation to normal crypts. Moreover, overexpression of ILK not only coincided with increased MBP phosphotransferase activity but as well with effects on downstream targets like GSK3beta. Based upon the presented data, we propose that ILK signalling is dysregulated early during the development of human colon cancer, and that selective inhibition of this molecule alone or in combination with the standard therapeutic modality might be a more effective means of treating colon cancer.
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PMID:Characterisation of integrin-linked kinase signalling in sporadic human colon cancer. 1467 16

Deeply seated aggressive fibromatosis also termed as desmoid tumors are rare tumors that invade surrounding structures. Although they never metastasize mortality rate may be as high as 10% due to their aggressive local behavior. Intraabdominal desmoid tumors are usually associated with familial poliposis coli and have a high recurrence rate regardless of the therapy instituted. Sporadic cases are very rare and generous surgical excision may be of benefit. We hereby report 2 siblings with sporadic pancreatic desmoid tumors who also harbor additional fibrotic masses in the pelvis. Although in previously reported cases there is usually a triggering event such as trauma, in the present cases there was no inciting event. Furthermore, the cases are without an associated FAP history, which provides the first clinical clue of a possible genetic determinant in this rare disorder.
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PMID:Sporadic hereditary pancreatic desmoid tumor: a new entity? 1286 94

Due to the development of more effective medications, those infected with HIV are living longer. Consequently, more tumors and infections have been added to the AIDS-defining criteria in the last decade. Our aim was to review the occurrence and clinical course of colorectal (CR) malignancies in HIV infected/AIDS patients from a single institution. A retrospective review of HIV/AIDS patients with colorectal malignant tumors was undertaken. We included adult patients, with ELISA and Western blot test positive for HIV, and primary malignant tumors located in the colon or rectum. Malignant neoplasms of the anus were excluded for the purposes of this study. Twelve patients (9 males and 3 females), mean age 41 years, were identified with the following neoplasm: 6 adenocarcinomas (ACA), 5 non-Hodgkin lymphomas (NHL), and 1 small-cell carcinoma. Intravenous drug abuse was the main risk factor for HIV. No patient had identified risk factors for colorectal neoplasm. Five out of six patients with ACA had metastatic disease at the time of diagnosis. One patient with stage II ACA developed early liver metastases after colonic resection. Seven out of 12 patients underwent surgery. Six (85.7%) of these sustained postoperative complications, primarily wound infection. The overall survival in our series was dismal, averaging 20 months. For NHL average survival was 29 months, and 12 months for CR-ACA. This is the largest series of cases of colorectal cancer in the HIV/AIDS patient population published in the English language and the largest number of colorectal ACA reported in this unique population. Early in our experience, tumors frequently found in immunoincompetent patients were detected (NHL). More recently, we have only treated patients with colorectal ACA; none of them had no risk factors for colorectal cancer (family history, IBD, FAP, HNPCC). These patients developed tumors at earlier ages and were diagnosed at an advanced stage. Therefore, these tumors may be associated with the grade of immunosuppression induced during the course of the HIV infection and with a tumorigenic effect of the HIV on the colonic epithelium. Consequently, a high index of suspicion when evaluating chronic abdominal complaints in such patients is warranted. The use of the new antiretroviral therapy regimens should be further evaluated to know its impact in the survival.
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PMID:Colorectal malignancies in HIV-positive patients. 1462 61

Epidemiological studies have found that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal cancer (CRC). Cyclooxygenase (COX)-2 expression is present in colorectal cancer and overexpression is associated with metastases and poorer prognosis in multivariate analysis. NSAID treatment results in a reduction of the incidence of colorectal adenoma in patients with familial adenomatous polyposis, in patients with a history of colorectal adenomas and in patients with a history of CRC. Pre-clinical research shows that COX-2 expression is associated with cell proliferation, angiogenesis, apoptosis inhibition and local immune-down modulation. An anticarcinogenic effect has been shown specifically in selective COX-2 inhibitors in animal models. Selective COX-2 inhibitors have fewer adverse effects than the non-selective NSAIDs and are promising chemopreventative and chemotherapeutical agents. The effects of selective COX-2 inhibition in the prevention of and treatment for colorectal carcinoma will be investigated in clinical randomized multicentre trials.
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PMID:[Cyclooxygenase(COX)-2-inhibition in the prevention and treatment of colorectal carcinoma]. 1464 56

Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.
Cancer Metastasis Rev
PMID:Role of cyclooxygenase-2 in colorectal cancer. 1500 Jan 50

Adenomatous polyposis coli gene (APC) defects have been demonstrated for the first time in familial adenomatous polyposis. Recent reports indicate that the APC gene is an intermediary between cell adhesion molecules and the cytoskeleton and that it may function as a gatekeeper of colonic epithelial proliferation. The objective of this study was to analyse APC's presence in lentigos, primary melanomas and melanoma metastases. By immunohistochemistry, APC was demonstrated in all lentigos, in 75 out of 88 primary melanomas and in 16 out of 28 melanoma lymphatic metastases. The percentage of immunolabelled tumour cells (APC index) in lentigos ranged between 5 and 69%, in primary melanomas between 0 and 98% and in melanoma metastases between 0 and 52%. Statistically significant differences between lentigos and primary melanomas and between lentigos and metastases in APC expression were found. In a multivariate analysis, APC showed an independent prognostic impact. Analysis of microsatellite instability in the APC locus was performed on 29 melanomas. Microsatellite instability was found in 5/29 melanomas and loss of heterozygosity in 1/29 melanomas. Promoter methylation of APC was found in 6/10 APC-negative primary melanomas and in 9/10 APC-negative melanoma lymphatic metastases investigated. We conclude about important role of APC alterations for melanoma progression.
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PMID:Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours. 1525 16

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.
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PMID:Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM). 1533 Jan 88


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