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)

Patients with pancreatic cancer frequently suffer from thrombosis due to excess thrombin generation. Yet, the effects of thrombin on pancreatic cancer are still poorly understood. The thrombin receptor PAR-1 is responsible for cellular effects of thrombin. PAR-1 plays an important role in the progression of different solid tumours in vitro. In breast cancer the level of PAR-1 expression correlates with invasiveness. Our aim was to correlate PAR-1 mRNA and protein expression level with the grade of differentiation of pancreatic tissue and cancer cell lines. PAR-1 protein was not detectable in the epithelium of healthy pancreas. Analysis of PAR-1 protein expression by immunofluorescence staining of pancreatic cancer cell lines revealed a correlation to the grade of differentiation. Quantitative analysis of PAR-1 protein expression by Western Blot analysis confirmed these observations. Analysis of PAR-1 mRNA expression showed low levels in healthy pancreas compared to pancreatic cancer tissue and the pancreatic cancer cell line MIA PaCa-2. The level of PAR-1 mRNA differed up to 25 fold between the respective pancreatic cancer cell lines. The eminent differences in PAR-1 expression, both protein and mRNA, between healthy pancreatic tissue and pancreatic cancer in vivo and in vitro emphasise the putative role of PAR-1 in pancreatic cancer progression.
Clin Exp Metastasis 2002
PMID:Expression of the thrombin receptor PAR-1 correlates with tumour cell differentiation of pancreatic adenocarcinoma in vitro. 1196 83

In this study we demonstrate the ability of a novel, p.o.-administered cytosine analogue, CS-682, to effectively prolong survival and inhibit metastatic growth in an imageable orthotopic mouse model of pancreatic cancer. MIA-PaCa-2-RFP pancreatic cancer cells were transduced with the Discosoma red fluorescent protein (RFP) and orthotopically implanted onto the pancreas of nude mice. Tumor RFP fluorescence facilitated real-time, sequential imaging, and quantification of primary and metastatic growth and dissemination in vivo. Mice were treated with various p.o. doses of CS-682 on a five times per week schedule until death. At a dose of 40 mg/kg, CS-682 prolonged survival compared with untreated animals (median survival 35 days versus 17 days; P = 0.0008). At nontoxic doses, CS-682 effectively suppressed the rate of primary tumor growth. CS-682 also decreased the development of malignant ascites and the formation of metastases, which were reduced significantly in number in the diaphragm, lymph nodes, liver, and kidney. Selective RFP tumor fluorescence enabled noninvasive real-time comparison between groups during treatment and facilitated identification of micrometastases in solid organs at autopsy. Thus, we have demonstrated that CS-682 is an efficacious antimetastatic agent that significantly prolongs survival in an orthotopic model of pancreatic cancer. The antimetastatic efficacy of CS-682 and its p.o. availability confer significant advantages and clinical potential to this agent for pancreatic cancer.
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PMID:Selective antimetastatic activity of cytosine analog CS-682 in a red fluorescent protein orthotopic model of pancreatic cancer. 1450 Mar 89

In order to investigate the antitumor and antimetastatic efficacy of new chemotherapeutic agents, a novel, red-fluorescent, orthotopic model of pancreatic cancer was constructed in nude mice. MIA-PaCa-2 human pancreatic cancer cells were transduced with red fluorescent protein (RFP) and initially grown subcutaneously. Fluorescent tumor fragments were then transplanted onto the pancreas by surgical orthotopic implantation (SOI), facilitating high-resolution, real-time visualization of tumor and metastatic growth and dissemination in vivo. Tumor growth at the primary site was visible within the first postoperative week, while distant metastasis and the development of ascites became visible over the following week. This MIA-PaCa-2-RFP model produced extensive local disease and metastases to the retroperitoneum (100%), spleen (100%), intestinal and periportal lymph nodes (100%), liver (40%) and diaphragm (80%), and gave rise to malignant ascites and peritoneal carcinomatosis in 80% of cases. Growth and metastasis of tumor was more rapid and frequent than in previously described orthotopic pancreatic cancer models, leading to a median survival of only 21 days after tumor implantation. This unique, red fluorescent model rapidly and reliably simulates the highly aggressive course of human pancreatic cancer and can be easily non-invasively visualized in the live animal. The model can therefore be used for the discovery and evaluation of novel therapeutics for the treatment of this devastating disease.
Clin Exp Metastasis 2004
PMID:An imageable highly metastatic orthotopic red fluorescent protein model of pancreatic cancer. 1506 97

Serum protein S100 and melanoma-inhibitory protein (MIA) have been described as useful tumor markers for malignant melanoma. In this study, these two serum proteins were compared in 48 patients with melanoma at different stages of disease. Serum concentrations of S100 and MIA were measured by immunoradiometric and enzyme-linked immunosorbent assays, respectively. We found that the cut-off values were 17.4 ng/ml for MIA and 0.09 microg/l for S100. Five patients had stage I-II, 22 had stage III, and 21 had stage IV disease. Serum levels of two markers were elevated with metastatic disease (p < 0.05). Sensitivities of the MIA were found higher compared with S100 in patients with extensive (M1c) metastatic disease and with chemotherapy nonresponders (p > 0.05). We showed a trend for worsened outcome in patients with elevated MIA level in univariate analysis. MIA was found to be more sensitive and is a potential prognostic marker for patients with metastatic malignant melanoma in comparison with S100.
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PMID:Clinical value of protein S100 and melanoma-inhibitory activity (MIA) in malignant melanoma. 1517 Jan 38

Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in end-stage renal disease (ESRD) patients treated with dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with earlier stages of chronic kidney disease as compared to the general population. Although traditional risk factors are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in this patient group are warranted.
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PMID:Systemic inflammation in dialysis patients with end-stage renal disease: causes and consequences. 1546 2

Tumor markers in the serum of cancer patients have an important role in clinical diagnosis and in prognosis, and also in the monitoring of the patients' disease and response to therapy over time. The serum markers currently available for melanoma have only limited clinical use. Those most widely used in clinical applications are S100-beta, melanoma inhibitory activity, and lactate dehydrogenase; there are close correlations between the serum concentrations of these and tumor load. Regular determination of S100-beta and MIA levels during follow-up can therefore be used for early detection of a tumor relapse in melanoma patients, increased serum concentrations of these marker proteins being indicative of tumor growth. Patients with distant metastases from melanoma who present with elevated serum levels of S100-beta, MIA, or LDH have poorer overall survival than do patients whose serum concentrations are within normal ranges. These three markers can also be used to monitor the course of disease and therapy outcome in patients with distant metastases. Since there are no marker proteins for melanoma that are not dependent on tumor load, it is not currently possible to forecast the survival of patients who are tumor free after surgery. Serum markers are also not suitable for screening or for the diagnosis of primary melanomas.
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PMID:[Serum markers for melanoma]. 1565 26

Despite marked improvements in dialysis technology during the last 20 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients treated by dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with early stages of chronic kidney disease as compared to the general population. Although traditional risk factors for CVD are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause progressive atherosclerotic CVD and malnutrition, itself an important risk factor for the development of CVD, by several pathogenetic mechanisms. The causes of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also cause vascular damage by several pathogenic mechanisms. Indeed, it seems logical to speculate that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) in ESRD would improve survival and decrease co-morbidity in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, more studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status, as well as outcome in this patient group, are clearly warranted and will be helpful in identifying precisely which pathways are most involved in the pathogenic process.
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PMID:Chronic systemic inflammation in dialysis patients: an update on causes and consequences. 1567 81

We compared the sensitivity and specificity of S-100 and MIA in advanced melanoma, in 96 patients with no evidence of disease (NED) and 86 patients with metastatic melanoma. Abnormal S100 (>0.2 microg/l) and MIA (>14 ng/ml) results were found in 1.1% and 3.2% of NED patients and in 59.3% and 54.6% of the patients with active melanoma (p<0.001). Using both tumor markers simultaneously, the sensitivity increased up to 69.8% with the same specificity 96.8%. S100 serum levels were not related to growth patterns. By contrast, MIA levels seemed to be related to the growth pattern, with higher levels in nodular melanoma (60.6+/-87.1 ng/ml) compared with acral-lentigous melanoma (11.9+/-5.4 ng/ml) (p=0.02). Likewise, S100 was related to the metastases site with significantly higher sensitivity and mean concentrations in patients with brain metastases (p=0.01) with the lowest in those with lung MI. MIA was related to the same metastases locations but without statistical significance. In summary, both S100 and ML4 are useful markers related to prognostic factors, being more effective when used in combination.
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PMID:S-100beta and MIA in advanced melanoma in relation to prognostic factors. 1603 99

Pancreatic cancer has a dismal prognosis due to the fact that patients present late when metastatic disease is already present. Previous studies have demonstrated that pancreatic cancer cells have decreased levels of MnSOD, which correlates well with increased rates of tumor cell proliferation. Recently, we have found that nude mice injected with MIA PaCa-2 human pancreatic cancer cells in the flank occasionally develop ascites and intra-abdominal metastatic deposits. Mice that developed ascites were sacrificed and the ascites cultured. Necropsy demonstrated metastatic tumors in the retroperitoneum, which were excised, digested, and cultured. Western blots, enzyme activity and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc (CuZnSOD), catalase, and glutathione peroxidase (GPx) in the ascites cell line, metastatic tumor cell line, MIA PaCa-2 primary pancreatic cancer cell line, and the Capan-1, a metastatic pancreatic cancer cell line. Cell growth, plating efficiency, growth in soft agar and growth in nude mice were determined in the ascites, metastatic tumor, and MIA PaCa-2 cell lines. MnSOD, CuZnSOD, and GPx protein and activity were increased in the ascites, metastatic tumor, and Capan-1 cell lines compared to MIA PaCa-2. The ascites and metastatic tumor cell lines had decreased cell growth, plating efficiency, and growth in soft agar, but the ascites cell line had increased cell growth in 4 and 1% O(2) concentrations in vitro and more rapid growth in vivo. Metastatic disease is associated with changes in the content and activity of antioxidant enzymes with an associated change in growth characteristics depending on the O(2) concentrations.
Clin Exp Metastasis 2005
PMID:Metastatic progression of pancreatic cancer: changes in antioxidant enzymes and cell growth. 1647 22

Most of the melanoma markers used today are melanocytic markers or pigmentation pathway-associated genes driven by the microphthalmia transcription factor, MITF, and include among others, tyrosinase, dopachrome tautomerase, DCT, melan-A and S100B. Genomic studies repeatedly revealed several novel melanoma marker genes including those of the transcription factor NOTCH2, WNT5A, proliferation-associated genes TOPO2A and CDC2, membrane receptors FGFR and EphA3, adhesion molecules N-cadherin, beta3 integrin and syndecan-4, and the cell surface antigens CD59/protectin and MIA. Other genomic analyses tried to define the gene signature of the metastatic disease but failed to find a consistent one except the gold standard genes of beta3 integrin, syndecan-4 and WNT5a. Studies on the gene signatures of chemoresistance and cytokine sensitivity of melanoma clearly defined apoptosis-resistance as one of the key elements of the above biological properties, but the data are controversial, mostly because of the use of inappropriate model systems and the lack of confirmation on clinical samples. Accordingly, application of genomic technologies must be more "translational" to provide breakthrough in melanoma diagnosis and therapy.
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PMID:Melanoma genomics reveals signatures of sensitivity to bio- and targeted therapies. 1743 76


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