Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect.
Cancer Lett 1995 Oct 20
PMID:Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth. 758 74

To identify the so-called toxohormone, which is a tumor-derived factor with activity to induce cancer cachexia syndrome in tumor-bearing animals, 5 human cancer cell lines with this activity were studied for cytokine production. Tumor cell products with activity to inhibit lipoprotein lipase (LPL) were shown to play an important role in the development of the cancer cachexia syndrome. All culture media conditioned by the 5 cell lines possessed LPL-inhibitory activity. However, the activity differed with the cell line. In order to characterize the activity, we examined whether the cultured cells produced cytokines with activity to inhibit LPL. A melanoma cell line, SEKI, and a neuroepithelioma cell line, NAGAI, were found to express a large amount of leukemia inhibitory factor (LIF) mRNA. Furthermore, both of these cell lines were demonstrated to produce a large amount of LIF protein, and plasma levels of LIF were extremely elevated in SEKI- and NAGAI-bearing nude mice, indicating that LIF produced by the tumor cells induced cancer cachexia syndrome in the animals. Thus, LIF fulfills the requirements for a toxohormone, except for suppressive activity on liver catalase. In contrast, the mechanisms responsible for cachexia in the MKN-1-, LX-1- and LS180-bearing mice remain unknown. These findings suggest that various types of bioactive substances produced by cancer cells could be toxohormones.
Jpn J Cancer Res 1995 Jun
PMID:Cytokine production in five tumor cell lines with activity to induce cancer cachexia syndrome in nude mice. 762 21

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.
Cancer Res 1993 Sep 01
PMID:Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. 768 19

Polymorphic alleles at loci such as LPL (lipoprotein lipase) and MSR (macrophage scavenger receptor) in chromosome band 8p22 are frequently lost during the genesis of several types of human cancer, including colorectal, non-small cell lung, hepatocellular, and prostatic carcinomas. A physical map of 31 published or novel probes and sequence-tagged sites in this genetic region was constructed using a radiation hybrid panel and the CEPH (Centre d'Etude du Polymorphisme Humain) yeast artificial chromosome (YAC) library. Thirty-six overlapping YACs defined a physical order for the following polymorphic markers: tel-D8S26-D8S511-D8S549-MSR-D8S254-D8S233- D8S261-D8S21-LPL-D8S258-cen. These maps unify small consensus regions of allelic loss on chromosome 8p defined by restriction fragment length polymorphisms with more informative PCR-based polymorphisms and widely available YAC mapping resources.
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PMID:Yeast artificial chromosome and radiation hybrid map of loci in chromosome band 8p22, a common region of allelic loss in multiple human cancers. 769 54

Aqueous extracts of acetone/ether powders of surgically obtained specimens of human tumors hydrolyzed 3H-labeled triolein in a dose-dependent manner. The lipolytic activity in these extracts was inhibited by anti-lipoprotein lipase (LPL) IgG dose-dependently, 25 micrograms of anti-LPL IgG causing 95% inhibition of the activity. Thus, LPL accounts for most of the lipolytic activity in extracts of acetone/ether powders of the tumors. All sarcomas and carcinomas examined contained LPL activity. Western blotting showed that they gave a band corresponding to that of human adipose tissue LPL (M(r) = 57,000). Immunocytochemical studies showed that LPL was present in cultured human osteosarcoma cells and distributed throughout the cells. We determined the proliferating cell nuclear antigen (PCNA)-labeling index as an indicator of the proliferative activity of tumor cells and measured LPL activity in extracts of tumors in areas corresponding to those used for determining the PCNA-labeling index. In malignant fibrous histiocytomas, the PCNA-labeling index in area a, which corresponds to the subcapsular region, was higher than that in area b, which corresponds to the central region. The LPL activity in area a was 10 times that in area b. In rectal cancer, the index in area c, which corresponds to the subserosal region, was higher than that in area d, which corresponds to the submucosal region. The LPL activity in area c was 1.9 times that in area d. These findings indicate heterogeneity in the distributions of LPL activity within tumors and higher levels of LPL activity in tumors that are proliferating actively.
Jpn J Cancer Res 1994 May
PMID:Existence of lipoprotein lipase in human sarcomas and carcinomas. 791 39

Alterations in lipid metabolism characterized in major part by a decrease in lipoprotein lipase (LPL) activity in adipose tissue are a central feature of cachexia from chronic infection or malignancy. These metabolic derangements may be mediated in large part through endogenous host proteins produced in response to various pathological stimuli. Differentiation factor/leukaemia inhibitory factor (D-factor) is a cytokine whose functions overlap those of tumour necrosis factor-alpha (TNF), IL-6 and IL-1. Recombinant murine D-factor produced a dose- and time-dependent inhibition of heparin-releasable LPL activity in differentiated 3T3-L1 adipocytes. Although 2-10 fold less potent than recombinant murine TNF, D-factor inhibited LPL activity at concentrations of 1-10 ng/ml. When added together, D-factor and TNF produced a synergistic inhibition of LPL activity. Interleukin 6 (IL-6) was 100-fold less potent than D-factor; 0.1 ng/ml of D-factor or 10 ng/ml of IL-6 caused a 50% inhibition of LPL activity. D-factor and TNF increased IL-6 production in 3T3-L1 cells. Ten ng/ml of D-factor or 1.0 ng/ml of TNF stimulated the release of < 1 ng/ml of IL-6 and inhibited LPL activity to 11 +/- 3% and 3 +/- 2% of control, respectively, whereas 50 ng/ml of recombinant IL-6 was required to decrease LPL activity to 24 +/- 19% of control. TNF produced a marked decrease in LPL mRNA, whereas D-factor had minimal or no effect at doses which inhibited LPL activity almost completely. Western blot analysis of cell extracts showed that TNF caused a greater decrease in LPL protein production than D-factor.2+ with TNF, may contribute to the manifestations of cachexia.
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PMID:Characterization of differentiation factor/leukaemia inhibitory factor effect on lipoprotein lipase activity and mRNA in 3T3-L1 adipocytes. 794 51

Cytokines induce a number of changes in lipid metabolism that can produce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently discovered cytokine, has been suggested to play a role in the cancer cachexia syndrome through its ability to decrease lipoprotein lipase (LPL) activity. This study explores the mechanism by which LIP decreases LPL activity in cultured adipocytes and determines its effects on fatty acid synthesis and lipolysis to see if it shares the same catabolic effects on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent decrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokines are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL activity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF caused a small increase in lipolysis, whereas TNF increased lipolysis by greater than 2-fold. These results demonstrate that the catabolic effects of LIF are weaker than those of TNF and are predominantly directed toward decreasing LPL activity, which may contribute to the hyperlipidemia associated with infection, inflammation, and cancer.
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PMID:Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes. 801 46

Inbred rat strains vary in their susceptibilities to mammary carcinogenesis. The Copenhagen (COP) and Wistar-Kyoto (WKY) rats are tumor resistant, whereas the Wistar-Furth (WF), Fischer (F344), and outbred Sprague-Dawley (SD) rats are susceptible. A dominant pattern of inheritance acting via the mammary carcinoma suppressor (Mcs) gene(s), which is mainly responsible for mammary tumor resistance, has been defined in the COP and WKY rats. In order to understand the basis of the phenotype, COP and WF mammary mRNAs were used for subtractive hybridization to isolate genes associated with the activity of the Mcs gene(s). Three genes, alpha-casein, lipoprotein lipase, and an unidentified gene, were found to be overexpressed in the mammary gland of the COP rat. In addition to alpha-casein overexpression, Northern analysis demonstrated that beta- and gamma-casein genes were also highly expressed in the mammary glands of tumor-resistant WKY and COP virgin rats but not the susceptible F344, WF, and SD strains. The association of casein gene expression with the tumor-resistant phenotype was further investigated by determining the functional site of the strain-specific casein gene regulation by using a mammary cell transplantation assay. In contrast to its normal endocrine control during pregnancy and lactation, casein gene overexpression was found to be controlled within the mammary epithelial cells of virgin rats. This is also the site of production and action of the Mcs gene product. Comparison of polymerase chain reaction-amplified beta-casein precursor RNA levels with the use of reverse transcription-polymerase chain reaction revealed that the regulation of this gene is likely at the transcriptional level. These data suggest an association of overexpression of casein genes, with the Mcs phenotype. The biological significance of this association is under investigation.
Cancer Res 1993 Dec 01
PMID:Cloning and characterization of overexpressed genes in the mammary gland of rat strains carrying the mammary carcinoma suppressor (Mcs) gene. 824 34

The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK-432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosphoenolpyruvate carboxykinase activity in the liver was significantly increased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) and increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing cancer cachexia is not yet clearly understood, OK-432 was not able to revert the tumor-induced metabolic alterations which lead to tissue wasting and cancer cachexia.
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PMID:The effects of a biological response modifier, OK-432, on tumor-induced alterations in the host metabolism. 836 14

The expression of genes coding for regulatory enzymes involved in the uptake, synthesis and mobilisation of lipid was measured in adipose tissue of cancer patients. Total RNA was isolated from subcutaneous adipose tissue of control and cancer patients and the various mRNAs measured by Northern blot analysis. The total lipoprotein lipase enzymic activity and the relative levels of the mRNAs for lipoprotein lipase and for fatty acid synthase were not significantly different between cancer patients and control patients. However, there was a significant two-fold increase in the relative level of mRNA for hormone-sensitive lipase (HSL) in adipose tissue of cancer patients compared with control patients. The cancer patients also exhibited a two-fold elevation in serum triacylglycerol levels and serum free fatty acid levels. There was a significant correlation between the serum free fatty acid level and expression of HSL mRNA in the adipose tissue. The serum levels of insulin and tumour necrosis factor-alpha were not different between cancer and control patients. The results suggest that at least one of the mechanisms for depletion of lipid from adipose tissue in cancer patients operates at the level of increased expression of mRNA of the lipolytic regulatory enzyme, hormone-sensitive lipase.
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PMID:Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients. 842 28


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