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

Colon cancer is a common cause of cancer-related mortality. Complete surgical resection of the primary tumor and/or select metastatic lesions can be curative in many patients. The risk of recurrence after resection can be predicted by pathologic staging. Large prospective randomized trials over the past 2 decades have clearly shown an increased overall survival for patients with resected stage III colon cancer who are treated with adjuvant 5-fluorouracil-based chemotherapy. The benefit of adjuvant chemotherapy for patients with stage II disease remains controversial. There is indirect evidence to support adjuvant chemotherapy after resection of metastatic disease. Locoregional approaches such as radiation, hepatic arterial infusion, or portal vein chemotherapy remain investigational. Adjuvant immunotherapy with monoclonal antibodies is emerging as a therapeutic option that might complement chemotherapy. Future challenges include improving adjuvant chemotherapy with the addition and/or substitution of new agents, resolving which subset of patients with stage II and resected stage IV colon cancer might benefit from therapy, validating the benefit of immunotherapy, and investigating locoregional therapies compared with systemic therapy.
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PMID:Adjuvant therapy of colon cancer: a review. 1245 Apr 21

We report the use of video-assisted thoracic surgery (VATS) as a treatment or pulmonary metastases. Between July 1994 and March 2002, 75 patients were treated for metastatic lung tumor by VATS. These patients included 45 males and 30 females with an average age of 60.6 years. Their primary diseases were Colon cancer (38), renal cell carcinoma (12), breast cancer (6), seminoma (3), thyroid carcinoma (3), parotid cancer (2), pharyngeal cancer (2) and the others (9). Tumor size ranged from 6 to 62 mm in diameter. A preoperative high resolution spiral computed tomography (CT) scan was used to locate the nodule in all patients. Ten recurrence cases were performed re-resection by VATS approach with an average period was 22 month. We conclude that VATS is a good candidate for the resection of lung metastases in the selected cases.
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PMID:[Video-assisted thoracic surgery for the resection of pulmonary metastases]. 1260 48

Human colon cancer affects nearly 150,000 patients and results in 60,000 deaths in the United States per year. Despite significant advances in the management of the colon cancer patient, little change in survival rates has been appreciated over the past 50 years. The primary cause of death relates to the development of distant metastases to organs such as the liver and lungs. Colon cancer represents an important disease to study in order to better understand tumor progression and metastasis primarily because there is almost a stepwise advancement of the disease that is marked by measurable genetic and associated phenotypic alterations. Metastasis appears to be the end product of the development of 'Herculean' cell clones capable of independent growth, invasion, adhesion, avoidance of apoptosis, and angiogenesis. Although significant progress has been made in understanding the sequential genetic events leading to the development of cancer, the precise genes and the associated molecular pathways underlying the development of metastatic potential are still poorly understood. Moreover, our enhanced genetic knowledge has had relatively little trickle down effect on our clinical management of this deadly disease. For this reason, we undertook a comprehensive study to develop a molecular encyclopedia of new tumor markers and markers of tumor progression, some of which will hopefully prove useful in the clinical management of colon cancer patients by means of their capacity to detect and predict the stage and disease burden. This review will focus on the application of gene expression profiling technology to the problem of identifying new tumor markers and progression markers, and the discovery of osteopontin as the leading candidate clinical marker derived from a screen of approximately 12,000 named genes.
Clin Exp Metastasis 2003
PMID:Osteopontin and colon cancer progression. 1265 Jun 11

Colon cancer preferentially metastasizes to the liver. To determine cellular backgrounds of this preference, we generated an enhanced green fluorescent protein (eGFP)-expressing rat adenocarcinoma cell line (CC531s) that forms metastases in rat liver after administration to the portal vein. Intravital videomicroscopy (IVVM) was used to visualize early events in the development of tumors in livers of live animals from the time of injection of the cancer cells up to 4 days afterward. Based on information obtained with IVVM, tissue areas were selected for further analysis using confocal laser scanning microscopy (CLSM), electron microscopy (EM), and electron tomography. It was shown that initial arrest of colon cancer cells in sinusoids of the liver was due to size restriction. Adhesion of cancer cells to endothelial cells was never found. Instead, endothelial cells retracted rapidly and interactions were observed only between cancer cells and hepatocytes. Tumors developed exclusively intravascularly during the first 4 days. In conclusion, initial steps in the classic metastatic cascade such as adhesion to endothelium and extravasation are not essential for colon cancer metastasis in liver.
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PMID:Visualization of early events in tumor formation of eGFP-transfected rat colon cancer cells in liver. 1457 75

Colon cancer overexpresses insulin-like growth factor 1 (IGF1) and insulin-like growth factor 1 receptor (IGF1-R), as compared with normal or adenomatous mucosa, and it has been postulated that colorectal cancer cells depend on the IGF1/IGF1-R pathway for their growth and progression. In this study, using the human colon cancer cell line HCT116, we find that established HCT116/IGF1-R transfectants exhibit a more aggressive transformed phenotype than the parental cell line, as demonstrated by their higher proliferation rate in response to IGF1, higher degree of anchorage-independent growth, resistance to serum deprivation-induced apoptosis, and higher migratory capability in a monolayer "wounding assay." When injected into nude mice, HCT116/IGF1-R transfectants were highly invasive and produced distant metastases, whereas the parental cell did not. Moreover, the overexpression of IGF1-R in these cells was associated with IGF1-R-induced activation of Akt and up-regulation of the antiapoptotic protein Bcl-x(L). We also show that Akt pathway mediates IGF1-R-induced Bcl-x(L) expression at transcriptional level. Our data demonstrate, for the first time, that IGF1-R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype, in a subset of colorectal cancers.
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PMID:Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. 1463 95

Colon cancer metastases rarely involve the spleen; in the literature only 29 cases of isolated splenic metastasis of colon cancer are reported (9 in the English literature and 29 in the Japanese literature). In this paper, a further case of isolated splenic metastasis in a 73 year- old woman, treated six years before with left emicolectomy for a mucinous colon cancer (Dukes B) is reported. A survey of the English literature shows that most of the cases had a significant period between the first original resection and the diagnosis of spleen metastasis (2-11 years). Splenectomy was performed in all the cases reported. No long-term follow-up has been published; therefore, it is not possible to define if spleen metastases of colon cancer have a better clinical behaviour than hepatic metastases and if splenectomy can prevent metastatic spreading of the disease leading to a potential survival benefit.
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PMID:[Metachronus splenic metastasis of colon cancer. A case report]. 1466 9

The HER-2/neu oncogene encodes a 185 kD protein that is phosphorylated upon ligand binding to other HER/erbB members and regulates cell growth and differentiation. Given that HER-2 receptor blockade can inhibit the growth of colon cancer cell lines and tumor xenografts, we investigated the frequency, localization and phosphorylation status of HER-2 in colon cancer cell lines and in human tumors. Protein expression was analyzed in relation to mRNA levels, HER-2 amplification, and clinicopathological variables. Colon cancer cell lines constitutively expressed HER-2 proteins and none showed HER-2 amplification by fluorescence in situ hybridization. Cell fractionation and immunoblotting showed HER-2 in both the membrane and cytosolic compartments. Primary colorectal carcinomas (n = 96) and their metastases (n = 25) were examined by immunohistochemistry. Strong membrane HER-2 staining was detected in 5 (5%) of primaries and in 3 (12%) metastases (p = 0.36). Membrane but not cytoplasmic localization was strongly associated with HER-2 gene amplification (p = 0.007). Cytoplasmic HER-2 staining was found in 61 (63.5%) of primary tumors and localization was confirmed by immunoelectron microscopy that also showed plasma membrane HER-2. Using real-time quantitative RT-PCR, HER-2 mRNA was increased in tumors with membrane compared to cytoplasmic staining (r = 0.66, p = 0.001). Cytoplasmic HER-2 was associated with tumor differentiation (p = 0.018), but not other clinicopathological variables. By immunoblotting, heterogeneity was seen in HER-2 levels with downregulation in 4 of 7 tumors relative to normal epithelia that uniformly expressed HER-2. Phosphorylated HER-2 was detected in approximately 50% of tumors and in normal mucosa. In conclusion, HER-2 is expressed constitutively in colon cancer cell lines and demonstrates relatively distinct localization patterns in human tumors. Strong membrane immunoreactivity is associated with high levels of HER-2 mRNA and gene amplification whereas cytoplasmic HER-2 is detected frequently and seems to be a marker of tumor differentiation.
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PMID:HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. 1469 18

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.
Cancer Metastasis Rev
PMID:Mucins and mucin binding proteins in colorectal cancer. 1500 Jan 51

Transforming growth factor (TGF) beta mediates a tumor suppressor pathway in human colon epithelial cells. We were interested in identifying and characterizing novel genes regulated by the TGF beta pathway in the colon. We employed expression microarrays to identify transcripts induced by TGF beta in Vaco 330, a colon adenoma cell line. We then used expression microarrays to determine which of these TGF beta induced transcripts are down-regulated in metastatic colon cancer. Northern analysis and real-time reverse transcription PCR confirmed and quantified our findings from the microarrays. These analyses highlighted C8orf4 as induced by TGF beta in colon cells. Moreover, C8orf4 is expressed in most normal colon mucosa samples, and is not expressed in most colon cancer metastases or colon cancer cell lines. Colon cancer primary tumors showed reduced expression of C8orf4 relative to normal mucosa, possibly reflecting contributions of C8orf4 expression in stromal cells. C8orf4 is a gene regulated by TGF beta signaling and loss in advanced colon cancer suggests C8orf4 may play a role in colon cell differentiation or growth regulation.
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PMID:C8orf4 is a transforming growth factor B induced transcript downregulated in metastatic colon cancer. 1518 45

Colon cancer is the third most common cancer globally. The risk of developing colon cancer is influenced by a number of factors that include age and diet, but is primarily a genetic disease, resulting from oncogene over-expression and tumour suppressor gene inactivation. The induction and progression of the disease is briefly outlined, as are the cellular changes that occur in its progression. While colon cancer is uniformly amenable to surgery if detected at the early stages, advanced carcinomas are usually lethal, with metastases to the liver being the most common cause of death. Oncogenes and genetic mutations that occur in colon cancer are featured. The molecules and signals that act to eradicate or initiate the apoptosis cascade in cancer cells, are elucidated, and these include caspases, Fas, Bax, Bid, APC, antisense hTERT, PUMA, 15-LOX-1, ceramide, butyrate, tributyrin and PPARgamma, whereas the molecules which promote colon cancer cell survival are p53 mutants, Bcl-2, Neu3 and COX-2. Cancer therapies aimed at controlling colon cancer are reviewed briefly.
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PMID:Colon cancer: genomics and apoptotic events. 1525 76


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