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

Advanced renal cell carcinoma (RCC) has a poor prognosis and is characterized by an unpredictable clinical course. The aim of this study was to assess the systemic phospholipid distribution as a possible marker of tumor stage and tumor spread beyond the kidney. To this end, the effect of renal cell carcinoma (RCC) on phospholipid concentrations in blood plasma using 31P NMR spectroscopy was studied in: (a) 29 patients with RCC prior to nephrectomy; (b) 19 healthy volunteers; (c) three patients with other renal tumors (renal metastases of bronchial carcinoma and of renal pelvic carcinoma, and a benign renal tumor). Furthermore, the phospholipid concentrations of eight patients of group (a) were determined 6 months after nephrectomy, when they were in remission. We found considerable deviations in the concentrations of the lysophosphatidylcholines (LPC1, LPC2) in both male and female patients with RCC compared to healthy volunteers (male--LPC1 0.217+/-0.062 vs 0.297+/-0.049 mmol/l, LPC2 0.036+/-0.014 vs 0.068+/-0.024 mmol/l; female--LPC1 0.195+/-0.071 vs 0.296+/-0.044 mmol/l, LPC2 0.037+/-0.027 vs 0.044+/-0.014 mmol/l). In addition, female patients with RCC showed lower concentrations of phosphatidylcholines (PC; 1.409+/-0.268 vs 1.947+/-0.259 mmol/l). The low phospholipid concentrations normalized for patients in remission. Phospholipid concentrations were found to depend on tumor stage and metastatic spread. The deviations in phospholipid concentrations (LPC1, LPC2, PC) observed may be attributable to systemic effects caused by the tumor as well as changes in enzyme activities.
NMR Biomed 2002 Feb
PMID:31P NMR spectroscopy of blood plasma: determination and quantification of phospholipid classes in patients with renal cell carcinoma. 1184 May 54

Angiogenesis is a process of development and of growth of new capillary blood vessels from pre-existing vessels. When pathological, it contributes to the development of numerous types of tumors, and the formation of metastases. In order to grow, carcinoma need new blood vessels to form so that they can feed themselves. Therefore, nowadays the concept according to which the development of cancer is angiogenesis dependent is generally recognized. This concept makes the control of tumoral angiogenesis one of the promising therapeutic ways in cancerology. The transition from the latent phase to the invasive and metastatic phase of a cancer is linked to what is called the angiogenic switch. It implies complex cellular and molecular interactions between cancerous cells, endothelial cells and the components of the extra-cellular matrix and namely the existence of specific proteins secreted by the tumoral cells able to stimulate the proliferation of capillary endothelial cells. Among them, VEGF, Vascular Endothelial Growth Factor was found in several types of tumors. It has shown a tumoral angiogenic activity in vitro and in vivo, and thus is a privileged target for the control of angiogenesis in an anti-tumoral goal. The role of VEGF in tumoral angiogenesis has been extensively studied. It has been proved to undergo as well autocrine as paracrine stimulation of tumoral angiogenesis. During the last few years, several members of the VEGF family have been described namely the VEGF-A, B, C, D, E and placenta growth factor (PlGF) among which VEGF-A (121 aminoacids) plays a role of prime importance in angiogenesis. VEGF is a 45 kDA glycoprotein, homodimeric, basic, and able to bind heparin. The three-dimensional structure of VEGF has been recently determined, by X-rays diffraction, and NMR spectroscopy. The different forms of the VEGF bind to receptors that exhibit a tyrosine-kinase activity (RTK). The specific action of the VEGF on the endothelial cells is mainly regulated by two types of RTK of the VEGF family, VEGFR1, or Flt-1, and VEGFR2, or KDR/Flk-1. Mutagenesis studies have shown that only a small number of VEGF residues are important and essential for the binding with RTK. Data described to date from the studies of VEGF/RTK interactions agree to the hypothesis that KDR receptor is the main human receptor responsible for the VEGF activity in both physiological and pathological vascular development, and VEGF-KDR signalling pathway has been validated as a priority target for the development of anti- and pro- angiogenic agents. Therefore angiogenesis mediated by VEGF constitutes a new target for anti-cancer therapy which has explored through different ways of intervention aiming at the blocking of the tumoral angiogenesis. The main ones are: -Struggle against the stroma degradation and invasion by the neo-vessels -Inhibition of activated endothelial cells. -Inhibition of angiogenic factors production and of their receptors. -Inhibition of the VEGF signal pathway, by peptides blocking the bond between VEGF and its receptors through the inhibition of intracellular transduction of VEGF signal. In conclusion, this bibliographic study allows to situate works of medicinal chemistry in the context of present knowledge concerning the vascular endothelial growth factor (VEGF) and its role in angiogenesis.
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PMID:Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. 1267 5

The local progression of primary tumors is extrinsically controlled by type 1 immune responses, particularly via the cytokine IFN-gamma, whose secretion is highly dependent on helper T cells. The T-box transcription factor T-bet (Tbx21) plays a critical role in the development of type 1 helper T cells and is essential for the production of IFN-gamma. Here, the T-bet pathway in the autochthonous transgenic adenocarcinoma mouse prostate model is demonstrated to have only a modest effect on the characteristics of primary prostate cancers but rather exerts a significant suppressor function in the development of metastatic disease.
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PMID:T-bet regulates metastasis rate in a murine model of primary prostate cancer. 1474 55

Accumulating evidence indicates that the formation of tumor cell platelet emboli complexes in the blood stream is a very important step during metastases and that the anti-metastasis effects of heparin are partially due to a blockade of P-selectin on platelets. In this study, heparin and chemically modified heparins were tested as inhibitors of three human colon carcinoma cell lines (COLO320, LS174T, and CW-2) binding to P-selectin, adhering to CHO cells expressing a transfected human P-selectin cDNA, and adhering to surface-anchored platelets expressing P-selectin under static and flow conditions. The aim was to screen for heparin derivatives with high anti-adhesion activity but negligible anticoagulant activity. In this study, four modified heparins with high anti-adhesion activity were identified including RO-heparin, CR-heparin, 2/3ODS-heparin, and N/2/3DS-heparin. NMR analysis proved the reliability of structure of the four modified heparins. Our findings suggested that the 6-O-sulfate group of glucosamine units in heparin is critical for the inhibition of P-selectin-mediated tumor cell adhesion. Heparan sulfate-like proteoglycans on these tumor cell surfaces are implicated in adhesion of the tumor cells to P-selectin. Some chemically modified heparins with low anticoagulant activities, such as 2/3ODS-heparin, may have potential value as therapeutic agents that block P-selectin-mediated cell adhesion and prevent tumor metastasis.
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PMID:Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions. 1513 30

The purpose of this study was to evaluate clinically T1-weighted spin-echo imaging (T1-SE) and T1-weighted opposed-phase gradient-echo (T1-opposed GRE) in medical examinations for vertebral metastases using 0.2 Tesla MRI. Twenty-one patients (9 males and 12 females, 105 vertebrae) with non-neoplastic lesions were assigned to the normal group (Group N), whereas 27 patients (16 males and 11 females, 133 vertebrae) with malignant metastatic vertebral lesions were assigned to the metastatic group (Group M). Using quantitative analysis, the contrast to noise ratio (CNR) for bone marrow to muscle in the region of interest (ROI) defined by the operator were determined with both groups, whereas the CNR for lesion to bone marrow was determined with Group M. In the subjective analysis, 275 vertebrae of 27 patients in Group M were evaluated. There were significant differences in the Group M between CNR values, T1-SE and T1-opposed GRE. The evaluation by T1-SE image alone was rated as 85.0% for sensitivity, 99.3% for specificity, respectively. On the other hand, evaluation rate only by T1-opposed GRE was 98.5% for sensitivity, 82.4% for specificity, respectively. T1-opposed GRE image is an effective tool for 0.2 Tesla MRI to examine metastatic bone marrow tumors. These findings indicate the necessity of both T1-SE and T1-opposed GRE in diagnostic imaging of vertebral metastases using 0.2 Tesla MRI.
Physiol Chem Phys Med NMR 2003
PMID:MR imaging of vertebral metastases at 0.2 Tesla: clinical evaluation of T1-weighted opposed-phase gradient-echo imaging. 1555 25

Tumors express MMP-2 and MMP-9 gelatinases, which are involved in the formation of tumor vasculature. This suggests that a tumor and its surrounding neovasculature can be visualized by a sensitive gelatinase recognition method. We have studied tumor radioimaging using a gelatinase inhibitory peptide CTTHWGFTLC (CTT), which in a mouse model targets the tumor site following an intravenous injection. We determined a solution NMR structure of CTT and its retro-inversion peptide, and prepared 125I and 99mTc-labelled CTT peptide derivatives. Radiolabelled CTT inhibited gelatinases in vitro, and homed to a tumor xenograft in mice. In normal mice, CTT was instead rapidly cleared from the circulation mainly through the kidney and, after 24 h, no significant radioactivity was accumulated in healthy tissues. Gamma camera imaging of a primary tumor in live mice was obtained with double-labelled liposomes, which were coated with 99mTc-CTT and encapsulated with 125I albumin. CTT also targeted liposomes to the lungs of tumor-bearing mice, which may indicate the existence of non-visible lung micrometastases. Our studies suggest that selective gelatinase-targeting compounds could be useful in the early detection and imaging of primary tumors and metastases.
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PMID:Radionuclide imaging of tumor xenografts in mice using a gelatinase-targeting peptide. 1581 16

Assessment of tumour vascularity may characterize malignancy as well as predict responsiveness to anti-angiogenic therapy. Non-invasive measurement of tumour perfusion and blood vessel permeability assessed as the transfer constant, K(trans), can be provided by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Using the orthotopic murine tumour model B16/BL6 melanoma, the small contrast agent GdDOTA (DOTAREM(R); Guerbet, Paris) was applied to assess the vascular transfer constant, K(trans), and interstitial leakage space, whereas intravascular iron oxide nanoparticles (Endorem(R); Guerbet, Paris) were used to detect relative tumour blood volume (rTBV), and in one experiment blood flow index (BFI). No correlations were observed between these four parameters (r(2) always <0.05). The B16/BL6 primary tumour and lymph-node cervical (neck) metastases produced high levels of the permeability/growth factor, VEGF. To probe the model, the novel VEGF receptor (VEGF-R) tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK) was tested for anti-tumour efficacy and its effects on DCE-MRI measured parameters of tumour vascularity. Data from the non-invasive measure of tumour vascularity were compared with a histological measurement of vasculature using the DNA-staining dye H33342. PTK/ZK inhibited growth of the primary and, particularly, cervical tumour metastases following chronic treatment for 2 weeks (50 or 100 mg/kg daily) of 1-week-old tumours, or with 1 week of treatment against more established (2-week-old) tumours. After chronic treatment with PTK/ZK, DCE-MRI detected significant decreases in K(trans) and interstitial leakage space, but not rTBV of both primary tumours and cervical metastases. Histological data at this time-point showed a significant decrease in blood vessel density of the cervical metastases but not the primary tumours. However, in the cervical metastases, the mean blood vessel width was increased by 38%, suggesting overall no marked change in blood volume. After acute (2-4 day) treatment, DCE-MRI of the cervical metastases demonstrated a significant decrease in K(trans) and interstitial leakage space and also in the initial area under the enhancement curve for GdDOTA (IAUC), but no change in the rTBV or BFI. Thus, significant changes could be detected in the DCE-MRI measurement of tumour uptake of a small contrast agent prior to changes in tumour size, which suggests that DCE-MRI could be applied in the clinic as a rapid and sensitive biomarker for the effects of VEGF-R inhibition on tumour blood vessel permeability and thus may provide an early marker for eventual tumour response.
NMR Biomed 2005 Aug
PMID:PTK787/ZK222584, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, reduces uptake of the contrast agent GdDOTA by murine orthotopic B16/BL6 melanoma tumours and inhibits their growth in vivo. 1591 78

Despite presumed curative operation almost one-third of patients with prostatic carcinoma relapse. One obvious reason is that the preoperative lymph node staging is not sufficiently effective. Imaging modalities (CT and NMR) have not resolved the problem. Presently lymphadenectomy is not recommended in patients with Gleason score <7 and PSA <20 ng/ml owing to the low frequency of positive nodes. However, these data are based on experience with limited dissection. Results from extended dissection reveal a higher rate of metastases than previously found. The results from extended dissections showed that more than half of the diagnosed lymph node metastases were found outside the generally recommended regions. The drawback is the higher complication rate that follows. Thus the staging can be improved but if this translates into a survival benefit it needs to be addressed in controlled trials. Alternative techniques for lymph node staging have recently been developed. The sentinel lymph node (SLN) method has been tested and proved feasible. The results corroborated those of extended dissection, namely that the obturator region is insufficient to reflect the field of metastases. High-resolution MRI with magnetic nanoparticles can detect small and otherwise undetectable lymph-node metastases. Positron emission tomography (PET), using acetate or choline as tracers, has performed better than fluoro-2-deoyglucose for detection of relapsing prostate cancer after radical prostatectomy. Studies have also started to assess its role for lymph node staging. In summary, lymph node staging has to cover a larger anatomical field than routinely used. Whether surgical dissection can be replaced by the new imaging modalities is presently under investigation.
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PMID:Lymph node staging in prostatic carcinoma revisited. 1616 18

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patients general status deteriorated considerably and he was referred to the Oncology Service. There was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patients survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.
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PMID:[Ophthalmoplegia in a patient with prostate cancer and bone metastases]. 1623 78

A computer-based decision support system to assist radiologists in diagnosing and grading brain tumours has been developed by the multi-centre INTERPRET project. Spectra from a database of 1H single-voxel spectra of different types of brain tumours, acquired in vivo from 334 patients at four different centres, are clustered according to their pathology, using automated pattern recognition techniques and the results are presented as a two-dimensional scatterplot using an intuitive graphical user interface (GUI). Formal quality control procedures were performed to standardize the performance of the instruments and check each spectrum, and teams of expert neuroradiologists, neurosurgeons, neurologists and neuropathologists clinically validated each case. The prototype decision support system (DSS) successfully classified 89% of the cases in an independent test set of 91 cases of the most frequent tumour types (meningiomas, low-grade gliomas and high-grade malignant tumours--glioblastomas and metastases). It also helps to resolve diagnostic difficulty in borderline cases. When the prototype was tested by radiologists and other clinicians it was favourably received. Results of the preliminary clinical analysis of the added value of using the DSS for brain tumour diagnosis with MRS showed a small but significant improvement over MRI used alone. In the comparison of individual pathologies, PNETs were significantly better diagnosed with the DSS than with MRI alone.
NMR Biomed 2006 Jun
PMID:Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. 1676 71


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