Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) (DPDP) was evaluated as a contrast agent for magnetic resonance (MR) imaging (1.5 T) of focal liver lesions in 40 patients. Doses of 5 and 10 mumol/kg were administered intravenously. Mn-DPDP-enhanced T1-weighted images were compared quantitatively and subjectively with standard T1- and T2-weighted nonenhanced images. Use of Mn-DPDP resulted in a statistically significant increase in signal intensity of liver parenchyma in T1-weighted images at both doses. No enhancement was seen in metastases, cholangiocarcinomas, or lymphomas, while all hepatocellular carcinomas were enhanced. Enhancement was seen in focal nodular hyperplasia and in regenerative nodules. The lesion-to-liver contrast in Mn-DPDP-enhanced gradient-recalled-echo images was superior to that of all precontrast images (P less than .01). The number of nonenhancing malignant liver lesions detected in spin-echo (SE) images was increased (272 in T2-weighted SE images vs 390 in T1-weighted Mn-DPDP-enhanced SE images). Image interpretation (eg, visualization and demarcation of the lesions) was markedly better in Mn-DPDP-enhanced images than in all precontrast images (P less than .001).
 ...
PMID:Focal liver lesions: MR imaging with Mn-DPDP--initial clinical results in 40 patients. 172 73

Our laboratory has previously reported that the adoptive transfer of highly purified lymphokine-activated killer cells (adherent-LAK, A-LAK) into Fischer 344 (F344) rats bearing established lung or liver micrometastases effectively reduced the resultant tumor growth more than 90%, leading to significant increases in animal survival (Cancer Res. 49, 1441, 1989). To begin to investigate the mechanism(s) by which A-LAK cells mediate this anti-tumor effect, we studied their migration patterns in F344 rats bearing experimentally induced lung and liver metastases as well as subcutaneous tumors. A-LAK cells which were phenotypically 95 to 100% natural killer cells/large granular lymphocytes were labeled with either 51Chromium or fluorescein diacetate (so as to be visualized microscopically). Intravenous injection of such labeled A-LAK cells did not show significant differences in their tissue distribution patterns in tumor-bearing versus normal rats, even when high levels of exogenous recombinant interleukin-2 (rIL-2) was administered. A-LAK cells first migrated to the lungs and then subsequently migrated to the liver and spleen as early as 2 to 6 hr following iv injection. The kinetics of exit of A-LAK cells from the pulmonary capillary beds was not significantly different in rats bearing 3-day micrometastases or 14-day macrometastases compared to normal rats. Moreover, the presence of metastases in the liver did not alter the extent or kinetics of entry of A-LAK cells into the liver even in the presence of exogenously administered rIL-2. Finally, in rats bearing subcutaneous tumors, no evidence could be obtained that A-LAK cells were selectively localized to the tumor site. Tissue sections of livers from metastases-bearing animals injected with fluorescein diacetate labeled A-LAK cells did not demonstrate significant numbers of A-LAK cells infiltrating tumor nests with or without the administration of exogenous IL-2. These data suggest that A-LAK cells may mediate tumor regression in vivo by direct and indirect mechanisms, possibly through the secretion of cytokines and/or the recruitment of secondary effector cells.
 ...
PMID:In vivo migration and tissue localization of highly purified lymphokine-activated killer cells (A-LAK cells) in tumor-bearing rats. 238 92

Fourteen pharmacologic agents reported to have biological activities which are directly or indirectly antineoplastic, were assayed for their ability to inhibit the growth of a mouse neoplasia (M5076) and a rat mammary adenocarcinoma (13762) implanted beneath the renal capsule of the host. Ascorbic acid, cimetidine hydrochloride. Corynebacterium parvum, dimethylsulfoxide, naloxone hydrochloride, indomethacin, muramyl-dipeptide, Protein A from Staphylococcus aureus, theophylline, tilorone (analog R11, 877DA), tuftsin diacetate and sodium ibuprofen were completely inactive as antineoplastic agents for these 2 tumors. In fact, theophylline and dimethylsulfoxide seemed to enhance the formation of 13762 metastases. Blue tongue virus and polyinocinic-polycytidylic acid were marginally effective antineoplastic agents for 13762. Polyinocinic-polycytidylic acid was an excellent antineoplastic agent for M5076; this agent not only prevented the growth of M5076, it was oncolytic.
 ...
PMID:In vivo antineoplastic activity of various biological response modifiers for tumors of the ovary and breast. 632 38

Effects of alpha-chymotrypsin and deoxyribonuclease I (DNase I) on the early phase of blood-borne lung metastasis in rats were studied using confocal laser scanning microscopy and AH-109A cells labeled either with carboxyfluorescein diacetate succinimyl ester or with 51Cr. Intravenous administration of alpha-chymotrypsin or DNase I appeared to enhance or inhibit, respectively, the tumor cell arrest in lung microvasculature as a reflection of reduction or promotion of the tumor cell clearance in the microvasculature. These results suggest that the effects of alpha-chymotrypsin and DNase I are related to induction of tumor cell aggregation and disaggregation in the blood stream, respectively.
Invasion Metastasis 1995
PMID:Effects of serine protease and deoxyribonuclease on intravascular tumor cell arrest in rat blood-borne lung metastasis. 767 31

Twenty-nine patients with known or suspected focal hepatic disease were evaluated in a retrospective multi-institutional study comparing T1-weighted manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis (phosphate) (DPDP) enhanced magnetic resonance imaging (MRI) with dynamic sequential bolus contrast enhanced computed tomography (DBCT) for the detection of focal liver lesions. The patients were divided into four dose groups, receiving 3, 5, 8, or 10 mumol/kg of Mn-DPDP, delivered either via intravenous bolus (0.25 ml/sec) or infusion (1 ml/sec). Each of three readers, with varying levels of expertise in interpreting hepatic MRI and CT studies, identified more lesions on the Mn-DPDP enhanced MRI than the contrast enhanced CT images. Mn-DPDP enhanced MRI depicted the presence of extensive metastatic disease not seen with DBCT in three patients with fatty liver. The most experienced MRI reader saw more lesions per patient on the Mn-DPDP enhanced MRI than with DBCT, while the opposite held true for the most experienced CT reader. The best single exam for detection of hepatic lesions may be determined by the experience of the reader.
 ...
PMID:Comparison of contrast enhanced CT and Mn-DPDP enhanced MRI for detection of focal hepatic lesions. Initial findings. 818 Aug 55

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N' diacetate 5,5'-bis(phosphate) (MnDPDP) is a hepatobiliary agent that is incorporated into the hepatocyte. We retrospectively reviewed our experience with 39 focal liver lesions in 20 patients studies with MnDPDP-enhanced hepatic magnetic resonance (MR) imaging to determine whether hepatocellular carcinoma (HCC) could be differentiated from tumors of nonhepatocyte origin (metastases, cavernous hemangiomas, etc.) For all cases, liver parenchyma enhanced significantly following MnDPDP administration. All HCCs (6) showed significant tumor enhancement resulting in decreased tumor conspicuity compared to precontrast images [average 37% decrease in tumor-liver contrast to noise ratio (C/N)]. In contradistinction, other focal liver lesions showed little or no tumor enhancement resulting in increased lesion conspicuity (average 100% increase in tumor-liver C/N ratio). Our preliminary data suggest that MnDPDP-enhanced MR images may enable differentiation of HCC from other focal liver masses of nonhepatocyte origin.
 ...
PMID:Differentiation of hepatomas from nonhepatomatous masses: use of MnDPDP-enhanced MR images. 829 10

We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.
 ...
PMID:The compound 14-keto-stypodiol diacetate from the algae Stypopodium flabelliforme inhibits microtubules and cell proliferation in DU-145 human prostatic cells. 978 57

Metastatic cancer cells seed the lung via blood vessels. Because endothelial cells generate nitric oxide (NO) in response to shear stress, we postulated that the arrest of cancer cells in the pulmonary microcirculation causes the release of NO in the lung. After intravenous injection of B16F1 melanoma cells, pulmonary NO increased sevenfold throughout 20 minutes and approached basal levels by 4 hours. NO induction was blocked by N(G)-nitro-L-arginine methyl ester (L-NAME) and was not observed in endothelial nitric oxide synthase (eNOS)-deficient mice. NO production, visualized ex vivo with the fluorescent NO probe diaminofluorescein diacetate, increased rapidly at the site of tumor cell arrest, and continued to increase throughout 20 minutes. Arrested tumor cells underwent apoptosis with apoptotic counts more than threefold over baseline at 8 and 48 hours. Neither the NO signals nor increased apoptosis were seen in eNOS knockout mice or mice pretreated with L-NAME. At 48 hours, 83% of the arrested cells had cleared from the lungs of wild-type mice but only approximately 55% of the cells cleared from eNOS-deficient or L-NAME pretreated mice. eNOS knockout and L-NAME-treated mice had twofold to fivefold more metastases than wild-type mice, measured by the number of surface nodules or by histomorphometry. We conclude that tumor cell arrest in the pulmonary microcirculation induces eNOS-dependent NO release by the endothelium adjacent to the arrested tumor cells and that NO is one factor that causes tumor cell apoptosis, clearance from the lung, and inhibition of metastasis.
 ...
PMID:Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells. 1254 99

Several inhibitors of angiogenesis have been identified in bovine and shark cartilage. One of them is troponin I, which is the molecule responsible for the inhibition of the actomyosin ATPase during muscle contraction. In this study we sought to investigate if the active site of troponin I (peptide Glu94-Leu123; pTnI) is also the one responsible for the antiangiogenic properties of this protein. The effects of pTnI on endothelial cell tube formation and endothelial cell division were investigated using human umbilical vein endothelial cells, Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and production of vascular endothelial growth factor by pancreatic cancer cells (CAPAN-1) were also investigated, as was its efficacy in a mouse model of pancreatic cancer metastases. Our results show that concentrations as low as 1 pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that endothelial cell division was inhibited at 96 hours by 3 microg/ml pTnI (P=0.0001). No effects were seen using troponin peptide 124-181 as a control. pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1 downregulated ICAM-1 expression on human umbilical vein endothelial cells up to 10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor production was seen by treating CAPAN-1 cells with up to 1 microg/ml pTnI. After intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P=0.03). The active region of troponin I is the one responsible for its antiangiogenic effect. The mechanism of action of this peptide is probably multifactorial.
 ...
PMID:Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in vitro and in vivo effects on human endothelial cells and on pancreatic cancer. 1467 5

Metastases rarely occur in human livers with cirrhosis in clinical studies. We postulated that this phenomenon would also occur in experimental cirrhosis. Cirrhosis was established in C57BL/6 mice by carbon tetrachloride (CCl(4)) gastrogavage. B16F1 melanoma cells were injected into the mesenteric vein to induce hepatic metastases. Contrary to our postulate, there was greater than 4-fold increase in metastasis in animals with cirrhosis compared to controls. Intravital videomicroscopy showed that the hepatic sinusoids were narrower and more tumor cells were retained in the terminal portal vein (TPV) in cirrhotic livers. Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis. Using confocal microscopy and the fluorescent nitric oxide (NO) probe 4,5-diaminofluorescein diacetate, a significantly lower level of NO release was detected in livers with cirrhosis both in basal conditions and after tumor cell arrest. Eight hours after mesenteric vein tumor cell injection, the percentage of apoptotic tumor cells in the sinusoids was 17% +/- 2% in livers with cirrhosis and 30% +/- 5% in normal livers. More mitotic and Ki-67 labeled tumor cells were seen in livers with cirrhosis. In conclusion, the changes in architecture and adhesion molecule expression in livers with cirrhosis may cause more tumor cells to arrest in the TPV. Lower levels of NO production may reduce apoptosis of B16F1 cells in livers with cirrhosis. As a result, these changes may promote the growth of metastasis in this cirrhotic model.
 ...
PMID:Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice. 1538 52


1 2 Next >>