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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer (CRC) is the leading cause of cancer-related mortality in western countries. Adjuvant treatment does not seem to be highly effective and recurrent or metastatic disease occurs in half of the new cases within one year of diagnosis and median survival does not exceed 18 months. CRC represents an optimal model for primary and secondary prevention, given the availability of effective screening procedures and of a well defined multi-step carcinogenic pathway. Colon cancer is supposed to arise as the result of a series of genetic mutations, which parallel histopathologic and molecular changes, from normal colonic epithelium to invasive carcinoma, with adenomatous polyps as an intermediate step. A growing body of evidence has shown a wide variety of effective compounds, in vitro in animal models and in human clinical trials. The more studied agents are the non-steroidal anti-inflammatory drugs. Among those, aspirin has been shown, in two recent randomised trials, to lower the incidence on polyps vs. placebo. Intervention studies on diet showed disappointing results, but diet micronutrients are promising agents in CRC prevention. Calcium, vitamin D and folic acid in different proportions in different populations have been shown to have a certain degree of action in preventing cancer development in epidemiological studies and in randomised trials. Also oestrogens or, rather, hormone replacement therapy for the menopause can protect against CRC. In conclusion, the rapid growth of information and knowledge in chemoprevention, especially for CRC, is very encouraging and gives us hope that soon this approach will be applicable in a larger scale population.
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PMID:Chemoprevention of colorectal cancer: an update. 1566

High level expression of cyclooxygenase (COX)-2 is reported in 80-90% of colorectal adenocarcinomas. In the recent years, selective inhibitors of COX-2 have been developed, and are shown to effectively protect against cancer development and progression. Colon cancer cells, as well as the epithelial cells in general, are dependent on appropriate interactions with the extracellular matrix (ECM) proteins to achieve a number of important functions, such as proliferation, differentiation, invasion and survival. These interactions are mediated via a family of cell-surface receptors called integrins, which interact with cytoskeletal proteins on the cytoplasmic side of the plasma membrane and thereby provide a link between the ECM and the cytoskeleton. In the present study, a high-COX-2 (high level COX-2 expression) colon cancer cell line, HT-29, and a low-COX-2 (low level COX-2 expression), DLD-1, were used to investigate the anticolon cancer effect of the selective COX-2 inhibitor, JTE-522. Moreover, to clarify its mechanisms of action, we focused especially on the ability to adhere to and to migrate on ECM. We could clearly demonstrate that, in addition to the decrease of the proliferative activity, JTE-522 caused a dose-dependent decrease in both the ability of colon cancer cells to adhere to and to migrate on ECM. These effects were, at least in part, dependent on the down-regulation of beta1-integrin expression, which was evident in HT-29, the high-COX-2 colon cancer cells, but not the low-COX-2, DLD-1. In addition, prostaglandin E2 almost completely reversed the effect of JTE-522, strongly suggesting the involvement of a COX-2-dependent pathway. In conclusion, for the first time, we could demonstrate the down-regulation of beta1 integrin caused by COX-2 inhibition, with consequent impairment of the ability of cancer cells to adhere to and to migrate on ECM, which are crucial steps for cancer metastases to develop.
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PMID:Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to extracellular matrix by decreased expression of beta1 integrin. 1572 53

The clinical diagnosis of primary thyroid cancer is uncommon, constituting 1.5% of all cancers in the United States. Clinically diagnosed metastatic cancer to the thyroid gland is rare. Colon cancer is one of the most common cancers in the United States, with a high propensity to metastasize; 30% to 40% of patients have metastatic disease at the initial diagnosis. The most common sites of metastasis from colon cancer are the regional lymph nodes, the liver, the lung, and the peritoneum. Colon cancer metastasis to the thyroid gland is rare, with only a few reported cases, mainly in the pathology literature. These cases describe metastasis from colon cancer to the thyroid gland that became apparent years after the initial diagnosis of colon cancer and were usually associated with dissemination to the liver, the lung, or both. We report a case of colonic adenocarcinoma metastatic to the thyroid gland and lung without involvement of the liver. A review of the literature is also included.
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PMID:Colon cancer metastatic to the lung and the thyroid gland. 1641 18

Colon cancer is a leading cause of cancer and cancer deaths in Western countries. Although 5-fluorouracil is still the basis of adjuvant therapy, advances in drug development have led to increased efficacy with the addition of oxaliplatin and options for oral therapy with capecitabine. The benefit of adjuvant therapy for stage II disease is consistently small and not statistically significant. Future studies will evaluate the role of the biologic agents that have proved to be effective in metastatic disease and better delineate the population at risk by identifying prognostic and predictive markers.
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PMID:Adjuvant therapy for colon cancer. 1661 79

Irinotecan, a water-soluble, semisynthetic derivative of camptothecin, is a key component of first- and second-line treatment regimens for metastatic colorectal cancer (CRC). In the first-line treatment of metastatic CRC, the results of two prospective, multicenter phase III trials have shown that the combination of irinotecan with bolus or infusional 5-fluorouracil (5FU)/leucovorin (LV) can significantly prolong survival compared with 5FU/LV alone, with a manageable side effects profile. In addition, irinotecan-based regimens, with or without oxaliplatin, may improve resectability of metastases and further increase patient survival. Studies of irinotecan in the first-line setting in combination with newer agents, such as bevacizumab, have shown impressive overall survival. In the second-line setting, irinotecan has demonstrated efficacy superior to that of best supportive care. Initial studies of irinotecan plus bolus 5FU/LV, and the preliminary results from trials of irinotecan plus infusional 5FU/LV in the adjuvant setting, have been disappointing; however, for the largest trial, the Pan-European Trial in Adjuvant Colon Cancer, results with sufficient follow-up are pending. Irinotecan has an acceptable tolerability profile and is not associated with cumulative toxicities in patients with metastatic CRC; regimens containing irinotecan extend treatment duration and improve survival. New regimens and adjunctive therapies are being explored to reduce the incidence of common complications of irinotecan treatment, such as diarrhea and neutropenia.
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PMID:Irinotecan in the treatment of colorectal cancer. 1695 32

Colon cancer patients routinely undergo preoperative computed tomography (CT) scanning, but local staging is thought to be inaccurate. We aimed to determine if clinical outcome could be predicted from radiological features of the primary tumour. Consecutive patients at one hospital undergoing primary resection for colon cancer during 2000-2004 were included. Patients with visible metastases were excluded. Preoperative CT scans were reviewed independently by two radiologists blinded to histological stage and outcome. Images of the primary tumour were evaluated according to conventional TNM criteria and patients were stratified into 'good' or 'poor' prognosis groups. Comparison was made between prognostic group and actual clinical outcome. Hundred and twenty-six preoperative CT scans were reviewed. T-stage and nodal status was correctly predicted in only 60 and 62%, respectively. However, inter-observer agreement for prognostic group was 79% (kappa=0.59) and 3-year relapse-free survival was 71 and 43% for the CT-predicted 'good' and 'poor' groups, respectively (P<0.0066). This compared favourably with 75 vs 43% for histology-predicted prognostic groups. Computed tomography is a robust method for stratifying patients preoperatively, with similar accuracy to histopathology for predicting outcome. Recognition of poor prognosis tumours preoperatively may permit investigation into the future use of neo-adjuvant therapy in colon cancer.
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PMID:Preoperative computed tomography staging of nonmetastatic colon cancer predicts outcome: implications for clinical trials. 1735 25

Colon cancer arises through a multistep process involving inactivation of tumor suppressor proteins and activation of oncogene-encoded proteins. Development of colon cancer frequently involves mutation of the adenomatous polyposis coli (APC) tumor suppressor. The activity of the proto-oncogene-encoded Src tyrosine kinase is commonly elevated in colon cancer, with higher activity observed as tumors progress and metastasize. Both APC and Src are multifunctional proteins that have been implicated in the control of cell proliferation, but also as regulators of cytoskeletal changes associated with cell motility and invasion. To investigate the potential for biological cooperativity between APC partial loss-of-function and Src gain-of-function, oncogenic Src was stably expressed in mouse colon epithelial cell lines IMCE (APC(+/min)) and YAMC (APC(+/+)). Under permissive growth conditions, these lines are conditionally immortalized through inactivation of p53. Irrespective of the APC genotype or p53 status, oncogenic Src expression led to morphologic transformation associated with loss of cell-cell junctions, cytoskeletal disorganization, and acquisition of invasive properties. However IMCE cells that carry one copy of the mutant APC(min) allele exhibited increased capacity for Src-mediated anchorage-independent proliferation as compared to the YAMC cells, and this property was enhanced under permissive growth conditions. beta-catenin levels and transcriptional activity were also elevated in the Src-transformed IMCE cells. The selective Src inhibitor, AZD0530, was found to be effective in blocking both cell invasion and anchorage-independent proliferation. These findings suggest that the combined effects of elevated Src activity and APC partial loss-of-function may contribute to the growth of colon tumors.
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PMID:Src transformation of colonic epithelial cells: enhanced anchorage-independent growth in an Apc(+/min) background. 1861 32

Colon cancer is a public health problem worldwide. Although potentially curable at early stages, a substantial number of patients will inevitably present with or eventually develop metastatic disease, which is often incurable. Despite the progress achieved with the introduction of new cytotoxic agents, recurrence rates for patients with resected stage II/III disease remain > 20%. Therefore, a great deal of effort and resources have been put into improving early diagnosis and prevention tools as well as the efficacy of adjuvant treatment. Oxaliplatin-based chemotherapy is now considered the standard of care in node-positive colon cancer, but there remains controversy with regard to the indication and type of adjuvant treatment in patients with nodenegative disease. Oral fluoropyrimidines play a growing role in the management of colorectal cancer and can be currently considered an alternative to 5-fluorouracil. Numerous reports have suggested that elderly patients benefit equally from chemotherapy, but the growing numbers of octogenarian and nonagenarian patients in our clinics, many of whom occasionally struggle through treatment, are a reminder of the challenges ahead. Finally, as we might have reached a plateau in terms of cytotoxic chemotherapy, numerous clinical trials are now focusing on the role of biologic agents in the adjuvant setting.
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PMID:Colon cancer: update on adjuvant therapy. 1862 35

Colon cancer is still the second most frequent malignancy in the Western world. Despite major efforts in diagnosis and treatment it is one of the leading causes of cancer related deaths. The metastatic dissemination of primary tumors is directly linked to patient's survival and accounts for about 90% of all colon cancer deaths. Current clinical predictions on whether colon cancer will metastasize are mainly defined by histopathological staging, describing the tumor spread within a surgical specimen. This review focuses on the need for molecule-based staging as essential prerequisite for individualized diagnosis, prognosis and therapy. Molecular determinants for progression and metastasis of colon cancer are discussed. Moreover, a newly identified molecule playing a decisive role in colon cancer metastasis is highlighted: MACC1. MACC1 acts as a key regulator of the metastasis-inducing HGF/Met pathway, predicts the risk for metastasis in early cancer stages, and represents a novel target to attack metastasis.
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PMID:Colon cancer metastasis: MACC1 and Met as metastatic pacemakers. 1966 36

Colorectal cancer is the third most common malignancy in men and women and accounts for 10% of all cancer deaths. The primary risk factor for colorectal cancer is advancing age, but other factors also play a role in its development, including genetic predisposition, smoking, alcohol consumption, obesity, and high-fat, low-fiber diet. Colon cancer survival is primarily related to the stage of disease at diagnosis. The main screening tests for colon cancer are fecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy. The pre-operative evaluation should include a complete blood count, carcinoembryonic antigen (CEA), colonoscopy, and chest radiograph. Other preoperative evaluations are patient specific or of unproven benefit. The operative procedure should include a bowel preparation, parenteral antibiotics, and deep venous thrombosis prophylaxis. The procedure performed must be tailored to the location of the colon cancer but should include complete, en bloc resection of the cancer and its lymphatic drainage, including locally invaded structures. The bowel margins of resection should be at least 5 cm from the tumor to minimize anastomotic recurrences. Laparoscopic colectomy has been shown to be as safe and effective as open colectomy for the treatment of colon cancer. The use of sentinel lymph node biopsy is feasible but has not yet been proved clinically useful. Surveillance after surgery for colon cancer is necessary to monitor for metastatic disease or local recurrence. Several groups have made surveillance recommendations including office visits, colonoscopy, and CEA monitoring.
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PMID:Preoperative evaluation and oncologic principles of colon cancer surgery. 2001 Dec 99


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