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)

This study aimed to investigate the relationship between clinicopathological factors and plasma brain natriuretic peptide (BNP) levels in non-small cell lung cancer (NSCLC) patients. A total of 133 patients with advanced NSCLC were included in this study. The level of BNP was determined at the time of diagnosis. The BNP plasma concentration was measured using a chemiluminescent enzyme immunoassay kit. The univariate relationship between each independent clinicopathological variable and plasma BNP was examined using the Chi-square test. The survival curves were determined using the Kaplan-Meier method. According to the cut-off value of plasma BNP levels (11.5 and 22.4 pg/ml), plasma BNP negatively correlated with the presence of metastases (Chi-square test, p=0.0374 and p=0.0098, respectively). However, no significant association between patient survival time and plasma BNP levels was found. Reduced plasma BNP levels in advanced NSCLC patients with metastases were noted and the possibility was raised that BNP decreases distant metastases of advanced NSCLC patients.
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PMID:Association between brain natriuretic peptide and distant metastases in advanced non-small cell lung cancer patients. 2286 73

The prognosis of patients with metastatic uveal melanoma is poor and there are limited therapeutic options. C-kit is expressed in the majority of patients with metastatic uveal melanoma. In this pilot trial, we examined the toxicity and efficacy of sunitinib malate, a multitarget tyrosine kinase inhibitor, in patients with metastatic uveal melanoma. Twenty patients with metastatic uveal melanoma expressing c-kit, 17 of whom failed previous treatments, were included in this study. Patients received sunitinib malate 37.5 mg daily continuously in 4-week cycles. The evaluation of response was carried out every 8 weeks. The overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier survival curves and differences in survivals were tested using the log-rank test. There was one partial response and 12 stable disease (SD) after sunitinib treatment. The median OS and PFS were 8.2 and 4.2 months, respectively. Three patients had SD for more than 12 months with sunitinib after failing previous treatments. The most common adverse events were fatigue (90%), diarrhea (60%), hemorrhage (55%), anorexia (45%), hand-foot syndrome (25%), hypothyroidism (25%), and rash (25%). Eleven patients required a dose reduction to 25 mg daily secondary to grade 3 adverse events. The degree of c-kit expression in melanoma cells was not associated with longer PFS or OS. Patients who developed systemic metastases after more than 5 years of their initial diagnosis had better PFS (median PFS: 5.8 vs. 2.6 months, P=0.005). Sunitinib was safely administered and showed potential clinical benefit in patients with metastatic uveal melanoma. The lack of a correlation between c-kit expression and clinical outcomes requires further investigation on the mechanism of sunitinib in metastatic uveal melanoma.
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PMID:A pilot study of sunitinib malate in patients with metastatic uveal melanoma. 2311 4

Mutation analysis of KRAS is needed before starting treatment with anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (CRC). In most of the cases, testing is performed on primary tumors, assuming that KRAS mutation status does not change in metastasis although correlation studies gave conflicting results. We evaluated the KRAS status concordance rate between primary tumors and related metastasis using a highly sensitive molecular assay. Forty-five primary tumors and related metastases from patients with CRC (28/45 male-62.2% and 17/45 female-37.8%; mean age 66.4 years) were analyzed by using TheraScreen: KRAS mutational kit. Metastatic samples were collected from lymph nodes (8/45-17.8%) and visceral sites (37/45-82.2%); 23 were synchronous (49%) and 22 were metachronous (51%), obtained after a mean of 30.8 months after the first diagnosis of CRC. Twenty-eight patients had KRAS mutations in both primary CRC and related metastases (62.2%). No differences in type and frequency of mutations were identified, despite different metastatic sites and time of onset of metastatic disease. Our results indicate that the mutation status of KRAS is the same in primary CRC and metastasis, suggesting that in clinical practice, KRAS testing can be performed on both tumor tissues when using a highly sensitive molecular assay.
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PMID:Mutation analysis of KRAS in primary colorectal cancer and matched metastases by means of highly sensitivity molecular assay. 2353 47

Myxopapillary ependymoma (MPE) is a rare tumor of the distal spinal cord. Despite benign histopathology, local recurrences occur in ~30 % of patients and distant metastases have been described in few cases. MPE tumor cells typically express glial fibrillary acidic protein (GFAP), which could be released to the circulation. In this current report, we investigated circulating plasma-GFAP in a series of MPE patients. We analyzed circulating plasma-GFAP using a commercially available ELISA kit in 3 patients with completely resected MPE, 1 patient with locally advanced MPE and 2 patients with pleuropulmonary metastases of MPE. As controls we used blood samples of age and gender-matched healthy volunteers (n = 3), 6 glioblastoma patients with known plasma-GFAP status (positive for 3 and negative for 3 patients) and 3 brain metastases patients with known plasma-GFAP negativity. We found very high concentrations of plasma-GFAP in two MPE patients with pleuropulmonary metastases, while in none of the other MPE patients circulating plasma-GFAP was detectable. Circulating GFAP could be useful as marker for early detection or follow-up of distant metastases in MPE patients.
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PMID:High plasma-GFAP levels in metastatic myxopapillary ependymoma. 2362 79

Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n=112; P=0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.
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PMID:Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification. 2374 29

The detection of circulating tumor cells (CTC) in breast cancer is strongly associated with disease relapse. Since it is unclear whether all CTCs are capable of generating metastasis, we investigated their apoptotic and proliferative status in 56 CTC-positive (29 early and 27 metastatic) patients with breast cancer. Double-staining immunofluorescence experiments were carried out in peripheral blood mononuclear cells (PBMC) cytospins, using the pancytokeratin A45-B/B3 antibody and either M30 (apoptotic marker) or Ki67 (proliferation marker) antibodies. Apoptosis was also evaluated using a polycaspase detection kit. Patients with metastatic disease had significantly lower numbers of apoptotic CTCs compared with patients with early breast cancer (polycaspase kit: 8.1% vs. 47.4% of the total CTC number; P = 0.0001; M30-antibody: 32.1% vs. 76.63%; P = 0.002). The median percentage of apoptotic CTCs per patient was also lower in patients with advanced compared with those with early disease (polycaspase kit: 0% vs. 53.6%; M30-antibody: 15% vs. 80%). Ki67-positive CTCs were identified in 51.7% and 44% of patients with early and metastatic disease, respectively. Adjuvant chemotherapy reduced both the number of CTCs per patient and the number of proliferating CTCs (63.9% vs. 30%). In conclusion, apoptotic CTCs could be detected in patients with breast cancer irrespective of their clinical status, though the incidence of detection is higher in early compared with metastatic patients. The detection of CTCs that survive despite adjuvant therapy implies that CTC elimination should be attempted using agents targeting their distinctive molecular characteristics.
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PMID:Apoptotic circulating tumor cells in early and metastatic breast cancer patients. 2377 53

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer. The aim of the present study was to elucidate the potential use of EGCG as chemotherapy targeting liver metastases of human colorectal cancer. To assess the effect of EGCG on human colorectal cancer cell lines, RKO and HCT116, cell viability, cell proliferation and apoptosis were measured by cell counting kit-8, BrdU assay and TUNEL staining, respectively. Protein and gene expression were measured by western blot analysis and RT-PCR analysis, respectively. EGCG inhibited cell proliferation and induced apoptosis. EGCG dephosphorylated constitutively activated Akt and increased the activation of p38. EGCG also decreased the expression of vascular endothelial growth factor receptor 2. Additionally, the ability of EGCG to prevent the development of liver metastases of RKO tumors was evaluated in SCID mice. EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration. Our findings indicate that EGCG may be useful in the treatment of liver metastases of human colorectal cancer.
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PMID:(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer. 2433 1

Malignant melanoma is a highly aggressive cancer with a very poor prognosis after the onset of metastasis. We have previously demonstrated that the protein melanoma inhibitory activity (MIA) is involved in the metastasis of and immunosuppression in malignant melanoma. Recently, we further established MIA as a therapeutic target to inhibit metastatic spread in malignant melanoma. We could show that an inhibition of MIA by a synthetic peptide decreased both the number of metastases as well as immunosuppression in a murine model of malignant melanoma. To control recurrence after surgical resection of a primary lesion, it is paramount to have diagnostic tools available that can detect a relapse due to the strong metastatic potential of melanoma. This follow-up is maintained with periodic re-examinations. Due to high cost and the associated radiation exposure, radiology examinations are avoided if possible. The analysis of prognostic markers in patient serum is therefore attractive. In this review, we focus on the quantitative analysis of the MIA protein as a prognostic tool because it has proven to be a useful serum marker for documenting disease progression of malignant melanoma. The MIA quantification assay itself is readily performed using an ELISA kit and common laboratory equipment. Because analysing MIA serum levels in combination with other established markers such as S100B improves their prognostic value, we feel that the quantification of MIA in the serum, among other markers, should be performed as a general standard of care in patients at risk of developing metastatic melanoma.
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PMID:Melanoma inhibitory activity in melanoma diagnostics and therapy - a small protein is looming large. 2437 47

Metastasis-associated in colon cancer 1 (MACC1) is a newly identified gene that has been shown to promote tumor cell invasion and metastasis. The present study investigated the effect of MACC1 downregulation on the biological characteristics of the ovarian cancer OVCAR3 cell line. In this study, MACC1 expression was blocked using the RNA interference technique. The downregulation of MACC1 mRNA and protein expression was confirmed using quantitative polymerase chain reaction and western blot analysis. The proliferative activity and adhesion rate of the cells were detected using cell counting kit-8 and a cell adhesion assay, while cell invasion was determined using a Matrigel invasion assay and migration capacity was observed using migration and wound-healing assays. A tube formation assay was also used to examine the angiogenic capacity of cells, and a luciferase assay was performed to assess whether MACC1 binds to the c-MET gene. The MACC1 mRNA and protein expression levels were significantly downregulated using sequence-specific small interfering RNA (siRNA). The inhibition of MACC1 expression markedly decreased the invasive, metastatic and angiogenic capacities of the cells, but only slightly inhibited growth and adhesion. In addition, a putative MACC1-binding site was identified in the 3'-untranslated region of c-MET. MACC1-siRNA was also found to significantly reduce the expression of the c-MET protein and a luciferase reporter assay confirmed that c-MET was the target gene of MACC1. These results demonstrated that the attenuation of MACC1 suppresses cell invasion and migration and that MACC1 may regulate cell metastasis through targeting the expression of c-MET. Inhibition of the function of MACC1 may represent a new strategy for treating ovarian cancer.
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PMID:MACC1 induces metastasis in ovarian carcinoma by upregulating hepatocyte growth factor receptor c-MET. 2500 63

Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.
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PMID:Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy. 2537 77


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