UMLS:C0027627 - FACTA Search

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

The survival of patients with hepatocellular carcinoma (HCC) has been improved with various diagnostic tools and treatment modalities. Consequently, spinal metastases from HCC are diagnosed more frequently. We investigated the clinical biomarkers of HCC patients presenting with spinal metastasis. Between January 2001 and December 2007, we recruited 30 consecutive HCC patients presenting with spinal metastasis. Their tissue samples were collected and analyzed by immunohistochemistry in a tissue microarray. A total of 16 proteins were assessed in the tissue microarray; we found that expression of p16(INK4) correlated with the survival time (log-rank test, P = 0.05), and loss of p16(INK4) was significantly associated with osteopontin overexpression (Fisher exact test: P = 0.045, logistic regression: P = 0.024, OR = 0.184, 95% CI 0.035-0.963). Patients with osteopontin (-) and with p16(INK4) (+) lived longer than patients with osteopontin (+) and with p16(INK4) (-). We found that p16(INK4) and osteopontin might be the biomarkers of patients with spinal metastasis from HCC, a more large-scaled randomized study might be required to confirm the result and study the mechanism.
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PMID:Loss of p16INK4, alone and with overexpression of osteopontin, correlates with survival of patients with spinal metastasis from hepatocellular carcinoma. 1981 7

Osteopontin (OPN) is a secreted glycoprotein implicated to function in cancer development and metastasis. Although elevated expression of OPN are observed in cancer cells of various types, in some cases, only the cells in the stromal region surrounding the tumor express OPN, suggesting distinct functional roles for this protein derived from host cells and from cancer cells. To provide a model for addressing the functions and mechanisms of host-derived OPN in cancer progression and metastasis, a cutaneous squamous cell carcinoma cell line (ONSC) that lacks the OPN gene, Spp1, was established. This line of cells was derived from a squamous cell carcinoma that developed in a female, OPN-null mouse subjected to two-stage skin carcinogenesis. Morphologically, ONSC cells resemble epithelial cells, and they express the epithelial markers, K1, K14, and p63, as confirmed by immunohistochemical analyses. Genomic analyses indicate the presence of mutated H-Ras and p53 genes. ONSC cells form colonies in soft agar and, subcutaneously injected into athymic nude mice, develop into squamous cell carcinomas that metastasize to the lungs. Lacking OPN expression, these squamous cell carcinoma cells provide a model to address the function of host OPN in the context of cancer progression and metastasis.
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PMID:Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line. 1991 34

The mouse polyoma virus induces a broad array of solid tumors in mice of many inbred strains. In most strains tumors grow rapidly but fail to metastasize. An exception has been found in the Czech-II/Ei mouse in which bone tumors metastasize regularly to the lung. These tumors resemble human osteosarcoma in their propensity for pulmonary metastasis. Cell lines established from these metastatic tumors have been compared with ones from non-metastatic osteosarcomas arising in C3H/BiDa mice. Osteopontin, a chemokine implicated in migration and metastasis, is known to be transcriptionally induced by the viral middle T antigen. Czech-II/Ei and C3H/BiDa tumor cells expressed middle T and secreted osteopontin at comparable levels as the major chemoattractant. The tumor cell lines migrated equally well in response to recombinant osteopontin as the sole attractant. An important difference emerged in assays for invasion in which tumor cells from Czech-II/Ei mice were able to invade across an extracellular matrix barrier while those from C3H/BiDa mice were unable to invade. Invasive behavior was linked to elevated levels of the metalloproteinase MMP-2 and of the transcription factor NFAT. Inhibition of either MMP-2 or NFAT inhibited invasion by Czech-II/Ei osteosarcoma cells. The metastatic phenotype is dominant in F1 mice. Osteosarcoma cell lines from F1 mice expressed intermediate levels of MMP-2 and NFAT and were invasive. Osteosarcomas in Czech-II/Ei mice retain functional p53. This virus-host model of metastasis differs from engineered models targeting p53 or pRb and provides a system for investigating the genetic and molecular basis of bone tumor metastasis in the absence of p53 loss.
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PMID:Polyoma virus-induced osteosarcomas in inbred strains of mice: host determinants of metastasis. 2010 4

To evaluate the associations of phosphorylated c-Jun NH2-terminal kinase (p-JNK) expression with clinicopathological features in patients with papillary thyroid carcinoma, p-JNK expression were immunohistochemically measured in 121 thyroid samples. p-JNK was overexpressed in papillary thyroid carcinomas with respect to matched nontumorous tissues (P=0.000), which was supported by western blot analysis. Increased p-JNK expression was significantly associated with the presence of lymph node metastases (P=0.001) and advanced TNM stages (P=0.02). Furthermore, p-JNK expression was positively correlated with osteopontin (OPN) expression (r=0.58, P<0.001). Activation of p-JNK may play a role in the carcinogenesis and lymph node metastasis of papillary thyroid carcinoma, and may be a molecular target for therapeutic intervention.
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PMID:Phosphorylated c-Jun NH2-terminal kinase is overexpressed in human papillary thyroid carcinomas and associates with lymph node metastasis. 2013 24

FANCD2, a pivotal protein in the Fanconi anemia and BRCA pathway/network, is monoubiquitylated in the nucleus in response to DNA damage. This study examines the subcellular location and relationship with prognostic factors and patient survival of FANCD2 in breast cancer. Antibodies to FANCD2 were used to immunocytochemically stain 16 benign and 20 malignant breast specimens as well as 314 primary breast carcinomas to assess its association with subcellular compartment and prognostic factors using Fisher's Exact test or with patient survival over 20 years using Wilcoxon-Gehan statistics. Immunoreactive FANCD2 was found in the nucleus and cytoplasm of all 16 benign tissues, but nuclear staining was lost from a significant 19/20 malignant carcinomas (P < 0.0001). Antibodies to FANCD2 stained the cytoplasm of 196 primary carcinomas, leaving 118 as negatively stained. Negative cytoplasmic staining was significantly associated with positive staining for the metastasis-inducing proteins S100A4, S100P, osteopontin, and AGR2 (P < or = 0.002). Survival of patients with FANCD2-negative carcinomas was significantly worse (P < 0.0001) than those with positively stained carcinomas, and only 4% were alive at the census date. Multivariate regression analysis identified negative staining for cytoplasmic FANCD2 as the most significant indicator of patient death (P = 0.001). Thus FANCD2's cytoplasmic loss in the primary carcinomas may allow the selection of cells overexpressing proteins that can induce metastases before surgery.
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PMID:Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer. 2036 22

The molecular triad, which includes the receptor activator of nuclear factor kappa-B ligand (RANKL), its receptor RANK, and the endogenous soluble RANKL decoy receptor osteoprotegerin (OPG), has emerged as an important determinant of bone metabolism. We aimed to evaluate the effect of treatment with the biphosphonate zoledronic acid (ZA) on biochemical markers of bone remodeling and to detect possible correlations of markerlevel changes with skeletal morbidity and clinical outcomes in patients with solid tumors and osseous metastases. The following serum markers were measured at the onset of skeletal metastases and after 6 months of treatment with ZA (4 mg intravenously monthly) in 70 patients with breast (n = 30), lung (n = 18), or prostate (n = 22) cancer: RANKL, OPG, C-terminal cross-linking telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), bone-specific alkaline phosphatase (bALP), and osteopontin (OPN). Logistic regression models were applied to assess the correlation between marker-level changes and skeletal related events (SRE, primary endpoint), recurrence or progression, and death. Within a median follow-up of 32 months, 34 patients (48.6%) presented with at least 1 SRE and 48 patients (68.6%) relapsed. The RANKL/OPG ratio was upregulated in patients with breast and lung cancer, and it tended to decline after treatment with ZA, whereas prostate cancer patients presented with profound elevation of OPG only that persisted after treatment. CTX levels were significantly reduced after treatment in the whole study population (P = 0.003). None of the markers was able to predict skeletal morbidity or clinical outcomes independently of well-established prognostic clinical parameters.
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PMID:Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid. 2040 80

Pancreatic cancer stem-like cells are described by membrane expression of CD24, CD44 and ESA (epithelial-specific antigen) and their capacity to grow as spheres in a serum-free medium containing well-defined growth factors. The capacity of a panel of four pancreatic cancer cell lines (PANC-1, CFPAC-1, PancTu-1 and PSN-1) to form spheres was tested. All cell lines with the exception of PancTu-1 developed spheres. Phenotypically, the sphere-growing cells showed an increased in vitro invasion capability. Both gene and protein expressions of markers of metastases [CXCR4 (CXC chemokine receptor 4), OPN (osteopontin) and CD44v6] and components of active hedgehog pathway signalling were assessed. Spheres clearly demonstrated increased expression of the above-mentioned markers when compared with their adherent counterpart. With the aim of identifying a minimum set of markers able to separate cells that have the capacity to form spheres from those incapable of forming spheres, a PCA (principal component analysis) of the multidimensional dataset was performed. Although PCA of the 'accepted' stemness genes was unable to separate sphere-forming from sphere-incapable cell lines, the addition of the 'aggressiveness' marker CD44v6 allowed a clear differentiation. Moreover, inoculation of the spheres and the adherent cells in vivo confirmed the superior aggressiveness (proliferation and metastasis) of the spheres over the adherent cells. In conclusion, the present study suggests that the sphere-growing cell population is not only composed of cells displaying classical stem membrane markers but also needs CD44v6-positive cells to successfully form spheres. Our results also emphasize the potential therapeutic importance of pathways such as CXCR4 and hedgehog for pancreatic cancer treatment.
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PMID:Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells. 2042 68

Colorectal cancer accounts for 11% of all cancers and is the second most frequent cause of cancer-related death, with the majority of deaths attributable to hepatic metastasis. The main aim of the study was to investigate changes which occur in CC531 rat colon adenocarcinoma cells and are instrumental to the metastatic phenotype after homing to the liver. RT-PCR and Western blotting were used to detect the expression of certain proteins, transcription factors and enzymes, which are intimately linked to colorectal metastasis. These included osteopontin (OPN), bone sialoprotein ll (BSP ll), Runx2, Hoxc8, matrix metalloprotease-7 (MMP-7) and matrix-metalloprotease-9 (MMP-9). Subsequently, in order to detect the role of the hepatocytes in these changes seen in tumor cells, two models of co-culturing hepatocytes with CC531 cells were established. OPN, Runx2 and MMP-7 were found to be highly expressed in CC531 metastases explanted from the liver, but showed subsequent down-regulation and/or disappearance in cell culture. The inverse regulation of Hoxc8, OPN and Runx2 suggests that these genes may be regulated in a feed-back loop manner. MMP-9 mRNA and active MMP-7 protein were expressed in tumor cells themselves. The presence of hepatocytes was insufficient to induce induction of OPN and Runx2 in tumor cells in vitro, so was the addition of OPN or TGF-beta1. Whereas TGF-beta1 induced over-expression of OPN and Runx2 in hepatocytes, it did not exert the same effect on hepatocytes co-cultured with CC531 cells, indicating that this response was abrogated by CC531 cells.
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PMID:Regulation of osteopontin and related proteins in rat CC531 colorectal cancer cells. 2059 51

Vascular endothelial cells (ECs) are key players in leukocyte recruitment into tissues and metastatic dissemination of tumor cells. ECs express B7h, which is the ligand of the ICOS T cell costimulatory molecule. The aim of this work was to assess the effect of B7h triggering by a soluble form of ICOS (ICOS-Fc) on the adhesion of colon carcinoma cell lines to HUVECs. We found that B7h triggering inhibited HUVEC adhesiveness to HT29 and DLD1 cells (by 50 and 35%, respectively) but not to HCT116 cells. The effect was dependent on the ICOS-Fc dose and was detectable as early as 30 min after treatment and was still present after 24 h. It was inhibited by soluble anti-ICOS reagents (mAb and B7h-Fc) and silencing of B7h on HUVECs, and it was not displayed by an F119S mutated form of ICOS-Fc that does not bind B7h. HUVEC treatment with ICOS-Fc did not modulate expression of adhesion molecules and cytokines, but it substantially downmodulated ERK phosphorylation induced by E-selectin triggering or osteopontin, which may influence HUVEC adhesiveness. Moreover, HUVEC treatment with ICOS-Fc also inhibited adhesion of polymorphonuclear cells and several tumor cell lines from different origins. Therefore, the B7h-ICOS interaction may modulate spreading of cancer metastases and recruitment of polymorphonuclear cells in inflammatory sites, which opens a view on the use of ICOS-Fc as an immunomodulatory drug.
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PMID:B7h triggering inhibits umbilical vascular endothelial cell adhesiveness to tumor cell lines and polymorphonuclear cells. 2081 64

Both vascular endothelial growth factor A (VEGF) and osteopontin (OPN) can directly induce tumor angiogenesis, which is essential for the growth and metastasis of solid tumors. Here we engineered a bispecific antibody (VEGF/OPN-BsAb) using the anti-VEGF-A antibody bevacizumab and the anti-OPN antibody hu1A12. Compared with hu1A12 alone and bevacizumab alone, VEGF/OPN-BsAb was significantly more effective in inhibiting tumor angiogenesis in a highly metastatic human hepatocellular carcinoma nude mouse model. Further study demonstrated that VEGF/OPN-BsAb could effectively suppress primary tumor growth and metastasis to lungs, suggesting that it might be a promising therapeutic agent for treatment of metastatic cancer.
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PMID:A bispecific antibody effectively inhibits tumor growth and metastasis by simultaneous blocking vascular endothelial growth factor A and osteopontin. 2082 49

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