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)

Although positron emission tomography (PET) detects occult metastatic disease in approximately 20% of patients with isolated hepatic colorectal metastases, it is associated with false negative results in up to 16%. We hypothesized that patients with a poorer prognosis (as defined by clinical risk score [CRS]) would have a higher yield from PET. All patients with colorectal liver metastases who were imaged by means of PET between 1998 and 2002 were identified from a prospective PET database. All patients were assigned a CRS, with one point added for each of five preoperative factors (disease-free interval <1 year, tumor size >5 cm, tumor number >1, carcinoembryonic antigen >200, and node-positive primary lesion). A total of 85 PET scans were reviewed. In half the patients (53%), PET provided no additional information over conventional imaging. Occult extrahepatic disease was detected or questionable findings seen on conventional imaging were confirmed in 20% of PET scans, whereas PET readings were inaccurate in 27%. PET findings were correlated with CRS in a subset of 63 patients presenting with a first occurrence of hepatic colorectal metastases. Among patients with a CRS of 0, no patient had extrahepatic disease detected by PET and 57% had false positive readings, whereas among patients with a CRS of 1 or more, 14% were found to have additional disease that was detected only by PET, and there were no false positive readings (P<0.001, Fisher's exact test). Patients with isolated hepatic colorectal metastases and a CRS of 0 should undergo conventional imaging alone prior to surgical exploration.
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PMID:Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases. 1503 90

The aim of the study was to analyse the prognostic factors for long-term outcome of liver resections for metastases from colorectal cancer. The retrospective analysis included 297 liver resections for colorectal carcinoma liver metastases. The following prognostic factors were considered: age, gender, stage and grade of differentiation of the primary tumour, node metastases, site of the primary colorectal cancer, number and diameter of the hepatic lesions, time interval from primary cancer to liver metastases, preoperative CEA level, adjuvant chemotherapy after hepatic resection, type of hepatic resection, use of intraoperative ultrasound and portal triad clamping, blood loss and transfusions, postoperative complications and hospital stay, tumour-free surgical margins, clinical risk score (as defined by the Memorial Sloan-Kettering Cancer Centre group, MSKCC-CRS). Overall survival rates were estimated according to the Kaplan-Meier method and were compared at univariate analysis using the log-rank test. Multivariate analysis was performed including significant variables at univariate analysis using the Cox regression model. Differences were considered significant at p < 0.05. The 1, 3, 5 and 10-year overall survival rates were 90.6%, 51%, 27.5%, and 16.9%, respectively. The univariate analysis revealed a statistically significant difference (p < 0.05) in overall survival in relation to: grade of differentiation of the primary cancer (5-year survival of grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), preoperative CEA level > 5 and > 200 ng/ml (5-year survival of CEA < 5 ng/ml vs CEA > 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; 5-year survival of CEA < 200 ng/ml vs CEA > 200 ng/ml: 27.9% vs 17.4%, p = 0.0001), diameter of major lesions > 5 cm (5-year survival of diameter < or = 5 cm vs > 5 cm: 30.0% vs 18.8%, p = 0.0074), disease-free interval between primary tumour and liver metastases longer than 12 months (5-year survival of patients with disease-free interval < or = 12 months vs > 12 months: 23.0% vs 36.1%, p = 0.042), high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: 36.4% vs 1 6.3%, p = 0.017). The multivariate analysis showed three independent negative prognostic factors: G3-G4 primary cancer, CEA level > 5 ng/ml, and high MSKCC-CRS class. No single prognostic factor turned out to be associated with such disappointing outcomes after hepatic surgery for colorectal liver metastases as to permit the identification of specific subgroups of patients to be excluded on principle from undergoing liver resection. However, in the presence of a number of specific prognostic factors (G3-G4 grade of differentiation of the primary tumour, preoperative CEA level > 5 ng/ml, high MSKCC-CRS) enrolment of the patient in trials exploring new diagnostic tools or new adjuvant treatments may be suggested to improve the preoperative staging of the disease and reduce the incidence of tumour recurrence after liver resection.
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PMID:[Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases]. 1624 Oct 86

Loss of E-cadherin triggers peritoneal dissemination, leading to an adverse prognosis for most patients with epithelial ovarian carcinoma (EOC). Because TWIST mainly regulates the epithelial-to-mesenchymal transition and is one of the E-cadherin repressors, we investigated the possibility that TWIST expression affects peritoneal metastasis of EOC using siRNA technique. In the present study, we showed a correlation between TWIST expression and EOC cellular morphology. Furthermore, we demonstrated that the suppression of TWIST expression in EOC cells (HEY) alters the cellular morphology from a fibroblastic and motile phenotype to an epithelial phenotype, and inhibits the adhesion of these cells to mesothelial monolayers. To investigate the mechanism by which down-regulation of TWIST leads to inhibition of adhesion to mesothelial cells (MCs), expression of adhesion molecules (CD29, CD44 and CD54) were observed. Moreover, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. This findings suggests that reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to MCs and invasion of MCs) and may be a potential therapeutic target for the treatment of this carcinoma.
Clin Exp Metastasis 2007
PMID:Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma. 1748 58

TWIST, a helix-loop-helix transcription factor, is highly expressed in many types of human cancer. We have previously found that TWIST confers prostate cancer cells with an enhanced metastatic potential through promoting epithelial-mesenchymal transition (EMT) and a high TWIST expression in human prostate cancer is associated with an increased metastatic potential. The predilection of prostate cancer cells to metastasize to bone may be due to two interplaying mechanisms (i) by increasing the rate of bone remodeling and (ii) by undergoing osteomimicry. We further studied the role of TWIST in promoting prostate cancer to bone metastasis. TWIST expression in PC3, a metastatic prostate cancer cell line, was silenced by small interfering RNA and we found that conditioned medium from PC3 with lower TWIST expression had a lower activity on stimulating osteoclast differentiation and higher activity on stimulating osteoblast mineralization. In addition, we found that these effects were, at least partly, associated with TWIST-induced expression of dickkopf homolog 1 (DKK-1), a factor that promotes osteolytic metastasis. We also examined TWIST and RUNX2 expressions during osteogenic induction of an organ-confined prostate cancer cell, 22Rv1. We observed increased TWIST and RUNX2 expressions upon osteogenic induction and downregulation of TWIST through short hairpin RNA reduced the induction level of RUNX2. In summary, our results suggest that, in addition to EMT, TWIST may also promote prostate cancer to bone metastasis by modulating prostate cancer cell-mediated bone remodeling via regulating the expression of a secretory factor, DKK-1, and enhancing osteomimicry of prostate cancer cells, probably, via RUNX2.
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PMID:TWIST modulates prostate cancer cell-mediated bone cell activity and is upregulated by osteogenic induction. 1845 41

Phosphatase PRL-3 has been involved in different types of cancer, especially in metastases from colorectal carcinoma (CRC). In this study, we explored both isoforms of PRL-3 as a biomarker to predict the recurrence of stage IIIB-C CRC. Overexpression of PRL-3 was investigated in primary human colorectal tumours (n=20) and hepatic metastases (n=36) xenografted in nude mice, samples characterised by absence of human non-tumoral cells, showing a high degree of expression in metastases (P=0.001). In 27 cases of matched normal colonic mucosa/primary tumour/hepatic metastases, PRL-3 overexpression occurs in primary tumours vs normal mucosa (P=0.001) and in hepatic metastases vs primary tumours (P=0.045). Besides, our results in a series of 80 stage IIIB-C CRC primary tumours showed that high levels of PRL-3 were an independent predictor of metastasis (P<0.0001; OR: 9.791) in multivariate analysis of a binary logistic regression and that PRL-3 expression tightly correlates with parameters of bad outcome. Moreover, PRL-3 expression associated with poor outcome in univariate (P<0.0001) and multivariate Cox models (hazard ratio: 3.322, 95%, confidence interval: 1.405-7.852, P=0.006). In conclusion, PRL-3 is a good marker of aggressiveness of locally advanced CRS and a promising predictor of distant metastases. Nevertheless, for prognosis purposes, it is imperative to validate the cutoff value of PRL-3 expression in a larger and consecutive series and adjuvant setting.
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PMID:PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness. 1900 88

The establishment of metastasis depends on the ability of cancer cells to acquire a migratory phenotype combined with their capacity to recreate a secondary tumor in a distant tissue. In epithelial cancers, such as those of the breast, the epithelial-mesenchymal transition (EMT) is associated with basal-like breast cancers, generates cells with stem-like properties, and enables cancer cell dissemination and metastasis. However, the molecular mechanism(s) that connects stem cell-like characteristics with EMT has yet to be defined. Using an orthotopic model of human breast cancer metastasis to lung, we identified a poor prognosis gene signature, in which several components of the wnt signaling pathway were overexpressed in early lung metastases. The wnt genes identified in this signature were strongly associated with human basal-like breast cancers. We found that inhibiting wnt signaling through LRP6 reduced the capacity of cancer cells to self-renew and seed tumors in vivo. Furthermore, inhibition of wnt signaling resulted in the reexpression of breast epithelial differentiation markers and repression of EMT transcription factors SLUG and TWIST. Collectively, these results provide a molecular link between self-renewal, EMT, and metastasis in basal-like breast cancers.
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PMID:A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer. 1954 13

TWIST, a basic helix-loop-helix transcription factor, has been recently reported to play an important role in tumorigenesis of human cancer through converting the early stage tumors into invasive malignancies. Upregulation of TWIST is often found in cancer patients, especially those with shorter survival period and poor response to chemotherapy. Here we studied the functions of TWIST on regulating migration rate, apoptosis, and gene expression in gastric cancer cells. TWIST expression is elevated in MGC-803 and HGC-27 cells that exhibit high invasive potential; whereas it is reduced in BGC-823 and SGC-7901 cells that possess relatively low invasive content. To evaluate functional consequences of TWIST induction, we examined the effect of TWIST on cell migration and apoptosis. Overexpression of TWIST in BGC-823 cells resulted in increased migration content and decreased sensitivity to the arsenic oxide-induced cell death. Moreover, small interference RNA-mediated TWIST ablation in MGC-803 and HGC-27 cells showed suppressed migration ability, increased induction of apoptosis in response to arsenic oxide, and elevated cell cycle arrest. Furthermore, we found a negative correlation between the TWIST level and p53 level, probably due to transcriptional regulation. Our results have identified TWIST as a critical regulator of gastric cancer cell proliferation and migration, suggesting a potential therapeutic approach to inhibit the growth and metastasis of gastric cancer through inactivation of TWIST.
Clin Exp Metastasis 2009
PMID:Metastasis-induction and apoptosis-protection by TWIST in gastric cancer cells. 1980 64

Epithelial-mesenchymal transition (EMT) is a morphogenetic program essential for embryonic development and wound healing, but can adversely cause fibrosis and metastatic cancer progression when deregulated. Here, we established a model of efficient EMT induction in normal finite lifespan human mammary epithelial cells (HMEC) using transforming growth factor beta (TGFbeta). We demonstrate that EMT in HMEC occurs in three distinctive phases that are governed by a hierarchy of EMT-activating transcription factors (TFs). Loss of epithelial cell polarity (ZO-1), and acquisition of mesenchymal marker (Vimentin, Fibronectin) expression are immediate-early events, whereas switching from E-cadherin to N-cadherin protein expression occurs only after EMT-like morphological changes become apparent. The kinetics of TF induction suggests that ZEB1 and SNAIL mediate early EMT induction reinforced by ZEB2, while GOOSECOID and FOXC2 may play a role in EMT maintenance. TWIST and SLUG were not significantly induced in this system. Furthermore, we show for the first time that normal HMEC acquire a CD44(+)/CD24(-/low) stem cell phenotype during a third phase of EMT that is characterized by maximum TF expression levels. Our results may have important implications for understanding potential changes that might occur in normal breast epithelium under pathological conditions triggering elevated TGFbeta levels.
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PMID:Molecular characterization of TGFbeta-induced epithelial-mesenchymal transition in normal finite lifespan human mammary epithelial cells. 2069 61

The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis.
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PMID:The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. 2071 42

Peritoneal carcinomatosis (PC) had long been regarded as a terminal disease, characterized by a very poor survival and worth treating with palliative therapy. A new strategy combining maximal surgery (cytoreductive surgery, CRS), with maximal regional chemotherapy (hyperthermic intraperitoneal chemotherapy, HIPEC), has been proposed to treat PC, resulting in long-term survival rates in selected patients. The emerging trend is to view localised peritoneal carcinomatosis, in the absence of other metastases, as a regional metastatic disease that is amenable to locoregional therapy. In spite of the need for more high quality studies, many international experts now agree that the use of this new strategy is a gold standard for treating selected patients with PC with the intent of curing. The best results are achieved in patients with limited disease who have completed macroscopic tumor removal. To offer a comprehensive review, we summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcome.
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PMID:Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: state of the art and future developments. 2088 55


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