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

Nodal staging is an integral part of the pretreatment staging of any patient with malignancy and has therapeutic and prognostic implications. Currently used imaging techniques used for nodal evaluation are limited in accuracy because they rely on size criteria for the detection of metastases. This has led to the emergence of lymphotropic nanoparticle enhanced magnetic resonance imaging as a promising tool for nodal characterization. This article reviews the properties of lymphotropic iron oxide nanoparticles and the technique, image interpretation, and initial clinical experience with lymphotropic nanoparticle enhanced magnetic resonance imaging.
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PMID:Lymphotrophic nanoparticle enhanced MR imaging (LNMRI) for lymph node imaging. 1668 May 6

Targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) could facilitate their accumulation in metastatic cancer cells in peripheral tissues, lymph nodes and bones and enhance the sensitivity of magnetic resonance imaging (MRI). The specificities of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone/chorionic gonadotropin (LH/CG)- bound SPIONs were tested in human breast cancer cells in vitro and were found to be dependent on the receptor expression of the target cells, the time of incubation and showed saturation kinetics. In incubations with MDA-MB-435S.luc cells, the highest iron accumulation was 452.6 pg Fe/cell with LHRH-SPIONs, 203.6 pg Fe/cell with beta-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 degrees C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (betaCG or LHRH) decreased the iron accumulation in each case. LHRH-SPIONs were poorly incorporated by macrophages. Tumors and metastatic cells from breast cancer xenografts were targeted in vivo in a nude mouse model. LHRH-SPION specifically accumulated in cells of human breast cancer xenografts. The amount of LHRH-SPION in the lungs was directly dependent on the number of metastatic cells and amounted to 77.8 pg Fe/metastastic cell. In contrast, unconjugated SPIONs accumulated in the liver, showed poor affinity to the tumor, and were not detectable in metastatic lesions in the lungs. LHRH-SPION accumulated in the cytosolic compartment of the target cells and formed clusters. LHRH-SPIONs did not accumulate in livers of normal mice. In conclusion, LHRH conjugated SPIONs may serve as a contrast agent for MR imaging in vivo and increase the sensitivity for the detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs.
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PMID:LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases. 1675 77

Tumor metastasis is an important clinical problem, contributing to the majority of cancer-related deaths. The recent discovery of metastasis suppressor genes, such as N-myc downstream-regulated gene-1 (Ndrg-1), has introduced a novel approach to treating cancer and preventing metastasis. Ndrg-1 has been identified as a protein involved in the differentiation of epithelial cells. In addition, Ndrg-1 expression can be regulated by androgens and is involved in the pathology of the disease, Hereditary Motor and Sensory Neuropathy-Lom (HMSNL). However, one of the most well documented links between Ndrg-1 and pathophysiology is its association with inhibition of tumor metastasis. The expression of Ndrg-1 was found to be significantly downregulated in a variety of different neoplasms including breast, colon and prostate cancer. Furthermore, Ndrg-1 expression was shown to be negatively correlated with tumor metastasis. Studies in vitro and in vivo have demonstrated a significant reduction in the metastatic ability of cells overexpressing Ndrg-1. The ability of these cells to invade was also compromised. The Gleason grade of prostate and breast cancers was found to correlate with Ndrg-1 expression, with more advanced and poorly differentiated tumors having lower Ndrg-1 levels. Recently, Ndrg-1 expression was demonstrated to be regulated by cellular iron levels and induced by iron chelators. These latter compounds were recently identified as potential anticancer agents as they selectively prevent cancer cell proliferation and lead to apoptosis. The discovery that iron chelators also increase Ndrg-1 expression further augments their antitumor activity and provides a novel strategy for the treatment of cancer and its metastasis.
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PMID:The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. 1692 Jul 33

Endothelin expression is increased in breast tumors and is associated with invasion and metastasis, whereas CCR7 expression by breast tumor cells may have a role in the organ specificity of breast cancer spread. In this article, we have analyzed whether endothelins influence breast tumor cell expression of the chemokine receptor CCR7. Stimulation of human breast tumor cell lines with endothelins increased cell surface expression of CCR7 via endothelin receptor A. The iron chelators desferrioxamine and cobalt chloride, which induce hypoxia-inducible factor (HIF)-mediated transcription, also increased CCR7 expression; transfection of a dominant-negative version of the HIF regulatory subunit, HIF-1alpha, into MCF-7 cells abolished CCR7 induction by endothelins, indicating that increased expression is due to HIF-1 stabilization. Endothelin stimulation promoted invasion toward the CCR7 ligands CCL19 and CCL21. Endothelin-mediated chemokine-independent invasion itself is dependent on CCR7 activity and could be abolished using a CCR7-neutralizing monoclonal antibody. In human breast carcinomas, mRNA expression of endothelins correlated with the level of CCR7 expression, both of which were associated with the presence of lymph node metastases. Expression of the CCR7 ligands CCL19 and CCL21 was also higher in breast cancer patients with lymph node involvement compared with those without, but expression of these chemokines did not correlate with endothelin expression. These data show that CCR7 may be regulated by the breast tumor microenvironment and further support the use of endothelin receptor antagonists in the treatment of invasive and metastatic breast cancer.
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PMID:Endothelins induce CCR7 expression by breast tumor cells via endothelin receptor A and hypoxia-inducible factor-1. 1728 12

Metastases are the most common malignant liver lesions and the most common indication for hepatic imaging. Specific characterization of liver metastases in patients with primary non-hepatic tumors is crucial to avoid unnecessary diagnostic work-up for incidental benign liver lesions. Magnetic resonance (MR) is rapidly emerging as the imaging modality of choice for detection and characterization of liver lesions due to the high specificity resulting from optimal lesion-to-liver contrast and no radiation exposure. Improvements in breath-hold T1-weighted fast spoiled gradient echo and rapid T2-weighted single shot echo-train acquisition enable imaging of the liver in a single breath-hold with high spatial resolution. Most metastases are hypo- to isointense on T1 and iso- to hyperintense on T2-weighted images. MR contrast agents provide critical tumor characterization and can be safely used in patients with iodine contrast allergy and renal failure. Other agents, including newly developing gadolinium-chelates or iron oxide agents may provide additional benefits in selected applications. The degree and nature of tumor vascularity form the basis for liver lesion characterization based on enhancement properties. Liver metastases may be hypovascular or hypervascular. Colon, lung, breast and gastric carcinomas are the most common tumors causing hypovascular liver metastases, and typically show perilesional enhancement. Neuroendocrine tumors including carcinoid and islet cell tumors, renal cell carcinoma, breast, melanoma, and thyroid carcinoma are tumors most commonly causing hypervascular hepatic metastases, which may develop early enhancement with variable degrees of washout and peripheral rim enhancement.
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PMID:Imaging of liver metastases: MRI. 1729 3

Preoperative imaging in rectal cancer is very important, as accurate staging determines optimal treatment strategy. In this review, imaging modalities for locoregional and distant staging in rectal cancer are discussed. For local staging, superficial tumors are best staged using endorectal US (EUS), as EUS is the most accurate modality for assessment of tumor ingrowth into the rectal wall layers. The more advanced tumors are best imaged using MRI, because MRI accurately predicts the distance from tumor to mesorectal fascia, and thus the circumferential resection margin (CRM), as well as possible invasion into surrounding organs. For the prediction of the nodal status none of the three imaging modalities - EUS, MRI and CT - can be reliably used for clinical decision-making. Only MRI using lymph node specific contrast (such as ultrasmall paramagnetic iron oxide-enhanced MRI) seems promising for the detection of nodal disease. For the detection of distant metastases transabdominal ultrasound and chest X-ray are used as a primary screening tool. However, for the high prevalence group (stage III) both methods are insufficiently sensitive, and CT of the chest plus abdomen is preferred.
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PMID:Role of preoperative local and distant staging in rectal cancer. 1734 2

Glioblastoma multiforme are highly invasive brain tumors. Experimental approaches focus on unravelling the mechanisms of invasion, this being a major reason for the poor prognosis of these tumors. Our previous results hinted towards involvement of the iron metabolism in invasion. In this study, we examined the effect of iron depletion on the invasive phenotype of glioblastoma cells. Transwell Matrigel invasion assays were used to monitor iron-dependent invasion of human glioblastoma cell lines U373MG and DBTRG05MG. Intracellular iron concentrations were modulated by applying desferrioxamine (DFO) and ferric ammonium citrate (FAC). We detected enhanced invasion of glioblastoma cells upon DFO-induced iron depletion. Treatment of cells with FAC strongly inhibited invasion. DFO treatment resulted in hypoxia-inducible factor 1 (Hif-1)-mediated induction of urokinase plasminogen activator receptor and matrix metalloproteinase 2. Further, RNA interference-mediated repression of urokinase plasminogen activator receptor inhibited DFO-induced invasion. Our data demonstrate a direct effect of DFO on Hif-1 expression resulting in activation of factors associated with ECM degradation and invasion of glioma cells. These findings caution on utilization of DFO and other iron chelators in the treatment of tumors with invasive potential.
Clin Exp Metastasis 2007
PMID:Involvement of Hif-1 in desferrioxamine-induced invasion of glioblastoma cells. 1735 15

Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells.
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PMID:Brain metastases of breast cancer. 1747 72

Endorectal MRI, now a fast and reliable examination, is an essential part of the local work-up for prostate cancer, regardless of the treatment envisioned. MRI spectroscopy, an actively maturing technique, makes it possible to combine anatomical and metabolic information that can be used for detection, staging, and posttreatment follow-up of prostate cancer. In patients with repeated negative biopsies, spectroscopy and dynamic gadolinium injection will be able to detect atypical cancer sites that escape routine biopsies. MRI of lymph nodes with ultrasmall superparamagnetic iron oxide (USPIO) injection will improve diagnostic performance in the detection of lymph node metastases. In the planning of conservative treatment, MRI and especially spectroscopic MRI will increasingly replace computed tomography. Finally, endorectal MRI of the prostate, spectroscopy, and dynamic injection will show local recurrences.
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PMID:[MRI of prostate cancer]. 1755 16

Antibody-conjugated iron oxide nanoparticles offer a specific and sensitive tool to enhance magnetic resonance (MR) images of both local and metastatic cancer. Prostate-specific membrane antigen (PSMA) is predominantly expressed on the neovasculature of solid tumors and on the surface of prostate cells, with enhanced expression following androgen deprivation therapy. Biotinylated anti-PSMA antibody was conjugated to streptavidin-labeled iron oxide nanoparticles and used in MR imaging and confocal laser scanning microscopic imaging studies using LNCaP prostate cancer cells. Labeled iron oxide nanoparticles are internalized by receptor-mediated endocytosis, which involves the formation of clathrin-coated vesicles. Endocytosed particles are not targeted to the Golgi apparatus for recycling but instead accumulate within lysosomes. In T(1)-weighted MR images, the signal enhancement owing to the magnetic particles was greater for cells with magnetic particles bound to the cell surface than for cells that internalized the particles. However, the location of the particles (surface vs internal) did not significantly alter their effect on T(2)-weighted images. Our findings indicate that targeting prostate cancer cells using PSMA offers a specific and sensitive technique for enhancing MR images.
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PMID:Targeting and cellular trafficking of magnetic nanoparticles for prostate cancer imaging. 1771 83


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