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)

It has been recognized since the turn of the century that cell motility by non-muscle cells requires virtually continuous restructuring of the cytoskeleton (see refs [1-4]). It is also clear that cell motility requires a mechanism for converting chemical energy into mechanical work. The proteins actin and myosin, two important constituents of the cytoskeleton, have been postulated to act as the chemicomechanical transducer in motile cells. Central to their role as a force generating mechanism in motile cells is the ability of myosin (a) to hydrolyze ATP when it interacts with actin and (b) to form filaments. Recent studies on mammalian cells and on the cellular slime mold Dictyostelium discoideum have shed light and at the same time raised questions regarding the involvement of myosin in cell motility. Moreover, they have demonstrated the presence of two types of myosins, called myosin II and myosin I, that have unique biochemical and regulatory properties and that may play different roles in mediating cell motility. In this chapter we will discuss the properties of these two myosins and then describe what is known about their involvement in Dictyostelium and mammalian cell motility.
Cancer Metastasis Rev 1992 Mar
PMID:The role of myosin I and II in cell motility. 151 99

Tangeretin, a flavonoid from citrus plants, was found to inhibit the invasion of MO4 cells (Kirsten murine sarcoma virus transformed fetal mouse cells) into embryonic chick heart fragments in vitro. The flavonoid appeared to be chemically stable in tissue culture medium, and the anti-invasive effect was reversible on omission of the molecule from the medium. Unlike (+)-catechin, another anti-invasive flavonoid, tangeretin bound poorly to extracellular matrix. It did not alter fucosylated surface glycopeptides of MO4 cells. Tangeretin seemed not to act as a microtubule inhibitor, as immunocytochemistry revealed no disturbance of the cytoplasmic microtubule complex. However, at anti-invasive concentrations of tangeretin, cell proliferation and thymidine incorporation appeared to be inhibited. When cultured on an artificial substrate, treated MO4 cells were less elongated, covered a larger surface area and exhibited a slower directional migration than untreated cells. From the decrease in ATP content in MO4 cells after tangeretin treatment, we deduce that this flavonoid inhibits a number of intracellular processes, which leads to an inhibition of cell motility and hence of invasion.
Clin Exp Metastasis
PMID:The flavonoid tangeretin inhibits invasion of MO4 mouse cells into embryonic chick heart in vitro. 292 47

The role of oncogene expression in tumor metastasis was examined using the Abelson leukemia virus-transformed murine large cell lymphoma RAW117. Cell sublines of low and high metastatic potential expressed equally abl oncogene-coded mRNA and its phosphoprotein product p160, and the capacity of p160 to become autophosphorylated with gamma-[32P]ATP was the same among low and high metastatic cells. The expression of other oncogene-coded mRNAs (fos, myc, myb), if present, was also similar in low and high metastatic RAW117 cells. Although oncogene expression is thought to be important in initiating, and in some cases maintaining, the transformed phenotype, its expression in RAW117 lymphoma cells appears to be unrelated to metastatic phenotype.
Clin Exp Metastasis
PMID:Expression of abl and other oncogenes is independent of metastatic potential in Abelson virus-transformed malignant murine large cell lymphoma. 404 63

Twenty-four patients with various types of tumors and without evidence of consumption coagulopathy (normal routine coagulation tests) were investigated for intraplatelet ATP, ADP, serotonin, beta-thromboglobulin and platelet factor 4; the percentage of light circulating platelets was also determined. Evidence for an acquired storage pool defect was found in seven patients (29%) without any correlation with the clinical status, the presence of metastases, platelet count or fibrinogen level. These results show that exhausted platelets are commonly encountered in cancerous patients even in the absence of consumption coagulopathy. The precise mechanism of this abnormality remains to be established.
 ...
PMID:Exhausted platelets in patients with malignant solid tumors without evidence of active consumption coagulopathy. 623 14

Histochemically (including the determination of RNA, acid and alkaline phosphatase, 5-nucleotidase and ATP-ase) the kinetics of the T-and B-cell region representation in regional lymph nodes has been studied in 54 gastric cancer patients. Four types of regional immune reactions were distinguished with regard to which the frequency of regional metastases and the survival rate in 30 patients were followed up. Metastatic involvement of the lymph nodes with morphohistochemical signs typical for the first type of immune response was found to occur in 2 of 14 cases, in 12 of 20 cases according to the second and in 4 of 16 cases according to the third one. If the group comprising 8 patients with activization of the regional immune protection according to the cell type showed an average survival of 8.7 months, in 22 patients with a predominance of the 2-4 types of regional immune reactions a shorter survival was noted, on average 5.1, 4.3 and 0.7 months correspondingly.
 ...
PMID:[Histochemical studies of the immunomorphological state of the regional lymph nodes in stomach cancer]. 696 99

Visualization of lactate dehydrogenase (LDH) activity with Neotetrazolium as final electron acceptor under anaerobic conditions and an incubation medium containing polyvinyl alcohol showed that under normal physiological conditions a zonal distribution of LDH activity is present in the liver lobule of male rats. Periportal hepatocytes contain more LDH activity than pericentral hepatocytes. This difference is due to the role of LDH both in gluconeogenesis (periportal cells) and glycolysis (pericentral cells). In livers containing metastases from colon carcinoma, areas of the parenchyma which are not affected by tumour growth maintain such zonation in the lobule, whereas areas close to metastatic foci show increased activity which is distributed uniformly over the lobule. This change may be explained by a Cori's cycle-like relationship between malignant cells and the surrounding hepatocytes due to glucose consumption and lactate production by the tumour cells. Within the metastatic foci, a zonation of LDH activity was also observed. Malignant cells close to the edge of the tumours contained the lowest activity, whereas activity increased inwards. Cancer cells directly surrounding necrotic areas showed the highest activity. Such patterns are in line with increasing anaerobic glycolysis towards the inner metastatic regions. Anaerobic glycolysis supplies limited amounts of ATP with concomitant lactate production but also large amounts of metabolites for RNA, DNA, lipid and complex carbohydrate synthesis. Lactate that is produced by the metastases induces adaptive changes in surrounding hepatocytes to convert this excess of lactate effectively.
 ...
PMID:Changes in the zonation of lactate dehydrogenase activity in lobules of rat liver after experimentally induced colon carcinoma metastases. 787 78

Multidrug resistance represents a major obstacle to successful chemotherapy of metastatic disease. Elevated levels in cancer cells of the product of the multidrug resistance gene, P-glycoprotein or the multidrug transporter, have been associated with the development of simultaneous resistance to a great variety of amphiphilic cytotoxic drugs. P-glycoprotein is an integral plasma membrane protein which contains 12 putative transmembrane regions and two ATP binding sites. It confers multidrug resistance by functioning as an energy-dependent drug efflux pump. Here we describe recent studies on the biosynthesis, structure, function, and mechanism of action of P-glycoprotein which have provided insights into the complexity of this multifunctional transport system and revealed an additional chloride channel activity. The physiological role of P-glycoprotein, however, still remains to be elucidated.
 ...
PMID:P-glycoproteins: mediators of multidrug resistance. 809 27

Until recently, the signal transduction pathways involved in the processes of tumor growth have been poorly understood. In the present study, we investigated cell surface receptors which utilize phosphatidylinositol (Pl) turnover/Ca2+ mobilization as a signal transduction pathway to regulate cell growth in a metastatic human lung carcinoma cell line, PG. We found that purinoceptor agonists, including ATP and its analogs, and bombesin, an amphibian tetradeca-peptide of mammalian homology gastrin-releasing peptide, induced rapid transient increase of cytoplasmic-free Ca2+ in PG cells loaded with fura-2. The Ca2+ responses were derived both from release from internal stores and the opening of plasma membrane Ca2+ channels. HPLC analysis of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) and its isomers showed a receptor-linked phospholipase C activation by ATP and bombesin. Although ATP and bombesin were both able to induce Pl turnover and Ca2+ mobilization in PG cells, they had differential growth regulatory effects on PG cells. Treatment with bombesin stimulated PG cell growth while treatment with ATP inhibited significantly PG cell growth. Pharmacological studies showed that the purinoceptors on PG cells were of the P2 subtype. Other hydrolysis-resistant P2 purinoceptor agonists, including ATP gamma S and AMP-PNP, were as effective as ATP in stimulating Pl turnover and Ca2+ mobilization as well as in inhibiting PG cell growth in vitro, suggesting the potential usefulness of such ATP analogs in clinical trials. Preliminary results suggest G protein involvement in the differential regulation of ATP and bombesin signal transduction pathways.
Clin Exp Metastasis 1993 Jul
PMID:Differential growth regulation of a metastatic human lung carcinoma cell line through activation of phosphatidyl inositol turnover signal transduction pathway. 831 79

B16-F10 and B16-BL6 are B16 mouse melanoma sublines that preferentially metastasize to the lung following i.v. and s.c. injections, respectively. To study molecular mechanisms underlying the different metastatic behaviors exhibited by the B16 melanoma sublines, we performed differential hybridization of the genes transcribed in these cells and compared their expression levels. We isolated four genes that were highly expressed in B16-F10 cells but not in B16-BL6 cells: TI-225 (polyubiquitin), TI-229 (pyruvate kinase), TI-241 (LRF-1 homologue), and TI-227 (novel gene). Triosephosphate isomerase, 10-formyltetrahydrofolate dehydrogenase, tyrosinase-related protein 2, cytochrome c oxidase, ATP synthetase alpha subunit, RNA helicase, and ribosomal protein (L37, J1, acidic phosphoprotein), however, showed higher expression in B16-BL6 cells than in B16-F10 cells. Among these clones, transfection of TI-241 into the low metastatic clone F1 converted the parental cells from low- into high-metastatic cells. TI-241 may regulate the expression of various genes as a transcription factor in the complex process of metastasis.
 ...
PMID:Identification of genes differentially expressed in B16 murine melanoma sublines with different metastatic potentials. 863 Oct 27

This trial was conducted to compare the cytotoxic efficacy of epirubicin (EPI) and mitoxantrone (MX) in clinical tumor samples derived from 34 chemotherapy-native women suffering from breast cancer by utilizing an in vitro ATP tumor chemosensitivity assay (ATP-TCA). An assay evaluability rate of 32/34 (94 %) was achieved. There was no significant difference between EPI and MX when regarding the mean IC90 and IC50 values corresponding to nearly identical overall in vitro response rates observed for both drugs (EPI: 62.5 %; MX 59.4 %). Individual IC90 values showed a weak correlation which was lacking for IC50. Accordingly, a lack of cross-resistance was found in 11/32 tumors (34 %) with 6 tumors showing sensitivity to EPI and resistance to MX and 5 tumors showing resistance to EPI and sensitivity to MX. At lower drug concentrations, a steep slope of the cumulative dose response curves for IC50 could be observed for both cytostatics with an apparent shift to higher concentrations at the IC90 level. For both drugs, a loss of linearity of the IC90 and IC50 dose-response curves was found at maximum concentrations. In conclusion, our results demonstrated an overall equality of EPI and MX in previously untreated breast cancers which already has been found clinically in metastatic disease. Nevertheless, we were able to show that approximately one third of chemotherapy-naive breast carcinomas are not cross-resistant to both EPI and MX. These findings could have implications on planning adjuvant chemotherapy for an individual breast cancer patient.
 ...
PMID:[Comparison of the cytostatic effect of epirubicin and mitoxantrone on native breast carcinoma cells using the ATP tumor chemosensitivity assay]. 870 23


1 2 3 4 5 6 7 8 9 10 Next >>