Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.Mevalonic AcidAnticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Protein Prenylation: A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.Polyisoprenyl Phosphates: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Simvastatin: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Drug Incompatibility: The quality of not being miscible with another given substance without a chemical change. One drug is not of suitable composition to be combined or mixed with another agent or substance. The incompatibility usually results in an undesirable reaction, including chemical alteration or destruction. (Dorland, 27th ed; Stedman, 25th ed)Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES).Farnesol: A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Monascus: A genus in the family Monascaceae, order EUROTIALES. One species, Monascus purpureus, has multiple uses in traditional Chinese medicine (MEDICINE, CHINESE TRADITIONAL).Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels.Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae.Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent: Specific hydroxymethylglutaryl CoA reductases that utilize the cofactor NAD. In liver enzymes of this class are involved in cholesterol biosynthesis.Fatty Acids, Monounsaturated: Fatty acids which are unsaturated in only one position.Glutens: Prolamins in the endosperm of SEEDS from the Triticeae tribe which includes species of WHEAT; BARLEY; and RYE.Celiac Disease: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.Diet, Gluten-Free: A diet which is devoid of GLUTENS from WHEAT; BARLEY; RYE; and other wheat-related varieties. The diet is designed to reduce exposure to those proteins in gluten that trigger INFLAMMATION of the small intestinal mucosa in patients with CELIAC DISEASE.Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with CELIAC DISEASE.Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis.Jejunum: The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum.Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.Diabetic Neuropathies: Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)Hereditary Sensory and Motor Neuropathy: A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)Sural Nerve: A branch of the tibial nerve which supplies sensory innervation to parts of the lower leg and foot.Neural Conduction: The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus.Polyneuropathies: Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.Foods, Specialized: Foods and beverages prepared for use to meet specific needs such as infant foods.Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71.Hyperlipoproteinemia Type II: A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Homozygote: An individual in which both alleles at a given locus are identical.Hypercholesterolemia: A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Lipoproteins, LDL: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Lanosterol: A triterpene that derives from the chair-boat-chair-boat folding of 2,3-oxidosqualene. It is metabolized to CHOLESTEROL and CUCURBITACINS.SqualeneDictionaries, PharmaceuticDictionaries, MedicalRxNorm: A standardized nomenclature for clinical drugs and drug delivery devices. It links its names to many of the drug vocabularies commonly used in pharmacy management.National Cancer Institute (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research with the objective of cancer prevention, early stage identification and elimination. This Institute was established in 1937.Dictionaries as Topic: Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).

Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells. (1/983)

In the rat thyroid cell lines PC Cl3, FRTL- 5 and WRT, proliferation is mainly regulated by insulin or IGF, and TSH. However, the mechanism regulating cell mass doubling prior to division is still unknown. Our laboratory has shown that in dog thyroid cells insulin promotes growth in size while TSH in the presence of insulin triggers DNA replication. In the absence of insulin, TSH has no effect on cell growth. In this report we investigated insulin action on both cell mass and DNA synthesis and its modulation by TSH and insulin in PC Cl3 and FRTL-5 cells. In PC Cl3 cells, insulin activated not only DNA synthesis but also protein synthesis and accumulation. Although TSH potentiated the stimulation of DNA synthesis induced by insulin, enhancement of protein synthesis by both agents was additive. All TSH effects were reproduced by forskolin. Similar effects were also obtained in FRTL-5 cells. This suggests that insulin and TSH, via cAMP, modulate both growth in size and DNA replication in these cell lines. Lovastatin, which blocks 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreased the induction of DNA synthesis, but not of protein synthesis induced by insulin or TSH in PC Cl3 cells. In FRTL-5 cells, lovastatin reduced protein and DNA synthesis stimulated by insulin but not TSH-induced protein synthesis. Taking these data together, we propose that insulin and/or TSH both modulate cell mass doubling and DNA synthesis in these cell lines, presumably via different pathways, and that there are at least two pathways which regulate growth in size in FRTL-5 thyroid cells: one triggered by insulin, which is lovastatin sensitive, and the other activated by TSH, which is not sensitive to lovastatin.  (+info)

Role of cholesterol ester mass in regulation of secretion of ApoB100 lipoprotein particles by hamster hepatocytes and effects of statins on that relationship. (2/983)

Our understanding of the factors that regulate the secretion of apoB100 lipoproteins remains incomplete with considerable debate as to the role, if any, for cholesterol ester in this process. This study examines this issue in primary cultures of hamster hepatocytes, a species in which both cholesterol and apoB100 metabolism are very similar to man. Addition of oleate to medium increased the mass of triglyceride and cholesterol ester within the hepatocyte and also increased the secretion of triglycerides, cholesterol ester, and apoB100 into the medium. Next, the responses of hamster hepatocytes to addition of either an HMG-CoA reductase inhibitor (lovastatin) or an acyl-CoA cholesterol acyltransferase inhibitor (58-035) to the medium, with or without added oleate, were determined. Effects of either agent were only evident in the oleate-supplemented medium in which cholesterol ester mass had been increased above basal. If oleate was not added to the medium, neither agent reduced apoB100 secretion; equally important, over the 24-hour incubation, neither agent, at the concentration used, produced any detectable change in intracellular cholesterol ester mass. However, in contrast to the estimates of mass, which were unchanged, under the same conditions radioisotopic estimates of cholesterol ester synthesis were markedly reduced. Any conclusion as to the relation of cholesterol ester mass to apoB100 secretion would therefore depend on which of the 2 methods was used. Overall, the data indicate a close correlation between the mass of cholesterol ester within the hepatocyte and apoB100 secretion from it and they go far to explain previous apparently contradictory data as to this relation. More importantly, though, taken with other available data, they indicate that the primary response of the liver to increased delivery of lipid is increased secretion rather than decreased uptake. These results point, therefore, to a hierarchy of hepatic responses to increased flux of fatty acids and increased synthesis of cholesterol that in turn suggests a more dynamic model of cholesterol homeostasis in the liver than has been appreciated in the past.  (+info)

Effect of inhibition of cholesterol synthetic pathway on the activation of Ras and MAP kinase in mesangial cells. (3/983)

Intermediary metabolites of cholesterol synthetic pathway are involved in cell proliferation. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, blocks mevalonate synthesis, and has been shown to inhibit mesangial cell proliferation associated with diverse glomerular diseases. Since inhibition of farnesylation and plasma membrane anchorage of the Ras proteins is one suggested mechanism by which lovastatin prevents cellular proliferation, we investigated the effect of lovastatin and key mevalonate metabolites on the activation of mitogen-activated protein kinase (MAP kinase) and Ras in murine glomerular mesangial cells. The preincubation of mesangial cells with lovastatin inhibited the activation of MAP kinase stimulated by either FBS, PDGF, or EGF. Mevalonic acid and farnesyl-pyrophosphate, but not cholesterol or LDL, significantly prevented lovastatin-induced inhibition of agonist-stimulated MAP kinase. Lovastatin inhibited agonist-induced activation of Ras, and mevalonic acid and farnesylpyrophosphate antagonized this effect. Parallel to the MAP kinase and Ras data, lovastatin suppressed cell growth stimulated by serum, and mevalonic acid and farnesylpyrophosphate prevented lovastatin-mediated inhibition of cellular growth. These results suggest that lovastatin, by inhibiting the synthesis of farnesol, a key isoprenoid metabolite of mevalonate, modulates Ras-mediated cell signaling events associated with mesangial cell proliferation.  (+info)

Posttranslational regulation of the retinoblastoma gene family member p107 by calpain protease. (4/983)

The retinoblastoma protein plays a critical role in regulating the G1/S transition. Less is known about the function and regulation of the homologous pocket protein p107. Here we present evidence for the posttranslational regulation of p107 by the Ca2+-activated protease calpain. Three negative growth regulators, the HMG-CoA reductase inhibitor lovastatin, the antimetabolite 5-fluorouracil, and the cyclic nucleotide dibutyryl cAMP were found to induce cell type-specific loss of p107 protein which was reversible by the calpain inhibitor leucyl-leucyl-norleucinal but not by the serine protease inhibitor phenylmethylsulfonylfluoride, caspase inhibitors, or lactacystin, a specific inhibitor of the 26S proteasome. Purified calpain induced Ca2+-dependent p107 degradation in cell lysates. Transient expression of the specific calpain inhibitor calpastatin blocked the loss of p107 protein in lovastatin-treated cells, and the half-life of p107 was markedly lengthened in lovastatian-treated cells stably transfected with a calpastatin expression vector versus cells transfected with vector alone. The data presented here demonstrate down-regulation of p107 protein in response to various antiproliferative signals, and implicate calpain in p107 posttranslational regulation.  (+info)

Effects of LY295427, a low-density lipoprotein (LDL) receptor up-regulator, on LDL receptor gene transcription and cholesterol metabolism in normal and hypercholesterolemic hamsters. (5/983)

The action of LY295427 [(3alpha,4alpha, 5alpha)-4-(2-propenylcholestan-3-ol)], a compound that derepresses low-density lipoprotein receptor (LDL-R) expression in a cell-based model, was examined in hamsters. It was found that the compound does not have an effect in normal chow-fed hamsters, in which LDL-R levels are not repressed, but exerts a marked hypocholesterolemic effect (>70% decrease) in cholesterol-coconut oil-fed hamsters, in which LDL-R is repressed. In this model, there is a dose-response for cholesterol lowering with an approximate ED50 value of 40 mg/kg/day and an inverse relationship between serum cholesterol and serum LY295427 levels. LDL-R mRNA is increased (2-fold) and liver cholesterol ester content is decreased (>90%). Unlike the 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor lovastatin, the decreased serum cholesterol is confined to the non-high-density lipoprotein fraction. Furthermore, LY295427 does not affect cholesterol biosynthesis, and it does not have a significant effect on cholesterol absorption. These data suggest that LY295427 acts in the hypercholesterolemic hamster by derepressing LDL-R transcription, thereby enhancing cholesterol clearance from the blood. The results with LY295427 suggest that compounds that act to increase LDL-R may represent a novel approach in the pharmacotherapy for hypercholesterolemia.  (+info)

Lovastatin-induced proliferation inhibition and apoptosis in C6 glial cells. (6/983)

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol biosynthesis. HMG-CoA reductase converts HMG-CoA to mevalonate, which is then converted into cholesterol or various isoprenoids through multiple enzymatic steps. In this study, we examined the cytotoxic effects of lovastatin, an HMG-CoA reductase inhibitor, in C6 glial cells. Lovastatin at concentrations higher than 10 microM suppressed cell proliferation and induced cell death, which were prevented completely by mevalonate (300 microM). The data from lactate dehydrogenase assay and fluorescence microscopic assay using Hoechst 33342 and propidium iodide showed that mevalonate at a concentration of 100 microM could prevent lovastatin-induced cell death, whereas it could not prevent lovastatin-induced inhibition of cell proliferation. These data suggest that the lovastatin-induced interruption of cell cycle transition was not sufficient to induce cell death in C6 glial cells. In the presence of lovastatin at concentrations higher than 10 microM, DNA laddering, the typical finding of apoptosis, was identified. Lovastatin-induced apoptosis was prevented by mevalonate (100 microM). Both cycloheximide (0.5 microgram/ml) and actinomycin D (0.1 microgram/ml) prevented lovastatin-induced DNA laddering. In this study, we demonstrated that the cytotoxic effects of lovastatin fall into two categories: suppression of cell growth and induction of apoptosis in C6 glial cells.  (+info)

Postmarketing analysis of lovastatin use in the VA Northern California System of Clinics: a retrospective, computer-based study. (7/983)

Prevention of coronary heart disease is a major public health goal. The efficacy of lovastatin in lowering serum cholesterol has been proven in research studies, but its efficacy in practice is unclear. To evaluate our practice patterns and outcome in the Veterans Administration Northern California System of Clinics, we reviewed computer-based records of 203 unselected patients issued lovastatin; 193 (95%) were men, and the average patient age was 66 +/- 9 years. The average daily dose of lovastatin was 24 +/- 10 mg, and average duration of therapy was 22 +/- 11 months. Only 72 patients (35%) were instructed on the prescription to take their medication with the evening meal, and only 59 patients (29%) had seen a dietitian during the observed (1 to 3 years) treatment period. Nevertheless, among the 124 patients with pretreatment lipid data, total serum cholesterol decreased by 18% from 271 +/- 45 to 221 +/- 41 mg/dL (P < 0.001), and low density lipoprotein (LDL)-cholesterol decreased by 23% from 185 +/- 43 to 143 +/- 37 (P < 0.001) mg/dL. High density lipoprotein-cholesterol and triglycerides were unchanged. Of the 168 patients with LDL-cholesterol data during the treatment period, only 74 (44%) achieved an LDL-cholesterol level of less than 130 mg/dL, the minimum goal for a population of older males with a high incidence of other cardiac risk factors. Safety surveillance with liver function testing was performed at least once in 192 patients (95%), but with creatine phosphokinase (CPK) testing in only 123 patients (61%) during the survey period. Enzyme elevations were minor, but occurred at least intermittently in approximately one quarter of patients. Only 5.7% of patients on lovastatin manifested an increase in transaminases on therapy. Due to incomplete baseline data, it is unclear how many patients had elevated CPK as a result of lovastatin. We conclude that: (1) lovastatin is effective in lowering total and LDL-cholesterol in practice, but is often used in dosage insufficient to lower LDL-cholesterol to goal levels; (2) patients are not being adequately educated on dosing schedules; (3) toxicity may be underestimated by infrequent and inconsistent surveillance; and (4) nonpharmacologic therapy is underutilized.  (+info)

The prenylation status of a novel plant calmodulin directs plasma membrane or nuclear localization of the protein. (8/983)

Post-translational attachment of isoprenyl groups to conserved cysteine residues at the C-terminus of a number of regulatory proteins is important for their function and subcellular localization. We have identified a novel calmodulin, CaM53, with an extended C-terminal basic domain and a CTIL CaaX-box motif which are required for efficient prenylation of the protein in vitro and in vivo. Ectopic expression of wild-type CaM53 or a non-prenylated mutant protein in plants causes distinct morphological changes. Prenylated CaM53 associates with the plasma membrane, but the non-prenylated mutant protein localizes to the nucleus, indicating a dual role for the C-terminal domain. The subcellular localization of CaM53 can be altered by a block in isoprenoid biosynthesis or sugar depletion, suggesting that CaM53 activates different targets in response to metabolic changes. Thus, prenylation of CaM53 appears to be a novel mechanism by which plant cells can coordinate Ca2+ signaling with changes in metabolic activities.  (+info)

  • Lovastatin (sold under the trade name Mevacor) is one fat-soluble "statin" drug available by prescription. (lifeextension.com)
  • While maintaining intensive dietary therapy, administration of lovastatin was instituted at a dosage of 20 mg/day, which was increased by 20-mg increments monthly, as necessary, to a maximum of 80 mg/day. (mcw.edu)
  • One patient failed to demonstrate lowering of these serum lipids, despite receiving the maximum recommended dosage of lovastatin of 80 mg/day. (mcw.edu)
  • Therapy with lovastatin should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease. (myhealthbox.eu)
  • Dose response effects of lovastatin (0, 15,30 muM) in DMEM and 10% FCS were examined on myofibroblast kinetics, total collagen synthesis, collagen I lattice contraction and actin filament rearrangement. (edu.au)
  • The scientists related a case history of a patient with acute myeloid leukemia treated at their institution using lovastatin at the high dose of 2 milligrams per kilogram of body weight per day for 52 consecutive days. (lifeextension.com)
  • For a person weighing 154 pounds, this would mean a daily dose of lovastatin of 140 mg. (lifeextension.com)
  • The patient taking this high-dose lovastatin demonstrated control of leukemic blast counts that lasted more than six months after cessation of treatment. (lifeextension.com)
  • There are now Phase I clinical trials scheduled to evaluate the toxicity and efficacy of low-dose lovastatin in the treatment of recurrent acute myeloid leukemia, head and neck squamous cell carcinomas, and cervical cancer. (lifeextension.com)
  • The Life Extension Foundation does not recommend that members enter these Phase I clinical trials, as they will restrict the use of other synergistic cancer therapies and may use a dose of lovastatin too low to provide optimal benefit. (lifeextension.com)
  • Instead, members should ask there doctor to prescribe a higher dose lovastatin and have a complete blood chemistry test performed every two weeks for the first two months of therapy to make sure lovastatin is not causing liver or muscle damage. (lifeextension.com)
  • Monthly blood chemistry tests should be done as long as high dose lovastatin is used. (lifeextension.com)
  • Lovastatin is a lactone which is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a strong inhibitor of HMG-CoA reductase. (nih.gov)
  • Serum levels of very-low-density lipoprotein cholesterol (VLDL-C) and triglycerides decreased slightly during lovastatin therapy, but the changes were not statistically significant. (mcw.edu)
  • In addition to the active ingredient lovastatin, each tablet contains the following inactive ingredients: D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, lactose anhydrous, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized corn starch. (nih.gov)
  • To determine whether this temporal difference is due to a simple delay in the action of retinoids on a common site or to different sites of action within the G1 phase, we studied the cell cycle effects of retinoic acid (RA) and the anti-estrogen ICI 164384 (ICI) in T-47D cells partially synchronized by mevalonic acid rescue of lovastatin-induced cell cycle arrest. (garvan.org.au)
  • In addition, cells rescued from cell cycle arrest induced by either RA, ICI or lovastatin entered S phase with the same kinetics. (garvan.org.au)
  • Homozygous Familial Hypercholesterolemia: Use of lovastatin for this rare genetic disorder (increased cholesterol levels) is not sufficient enough for treatment. (rxwiki.com)
  • Lovastatin should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total-C and LDL-C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk. (myhealthbox.eu)
  • Lovastatin is indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels. (myhealthbox.eu)
  • increased catabolism of LDL-C. Apolipoprotein B also falls during treatment with lovastatin. (myhealthbox.eu)
  • All patients were unresponsive to a six-week program of intensive dietary therapy and other nonpharmacologic treatment to lower their blood cholesterol levels before receiving lovastatin. (mcw.edu)
  • this was demonstrated after the first month of therapy with lovastatin and was maintained throughout the six-month treatment period. (mcw.edu)
  • In this study published in Clinical Cancer Research , the scientists noted that "lovastatin has the potential as an immediate, novel therapeutic approach in the treatment of these responsive tumors. (lifeextension.com)
  • We found that cells entering the cell cycle semi-synchronously after mevalonic acid rescue of lovastatin treatment were immediately susceptible to ICI but not RA. (garvan.org.au)
  • Consistent with this, cells recommencing cell cycle progression after RA treatment were susceptible to the effects of lovastatin, while cells pre-treated with ICI then rescued with estradiol were not. (garvan.org.au)
  • Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. (nih.gov)
  • Previous studies have indicated that lovastatin and other fat-soluble "statin" drugs are also effective against pancreatic, colon, liver and thyroid tumors. (lifeextension.com)
  • Lovastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. (rxwiki.com)
  • In 1997, The Life Extension Foundation published a protocol suggesting that cancer patients ask their oncologist to consider prescribing the drug lovastatin (80 mg a day) as an adjuvant therapy. (lifeextension.com)
  • Lovastatin induced a specific apoptotic response in these tumor cells within achievable therapeutic range and it (lovastatin) has a proven record in the clinic as a safe and effective drug. (lifeextension.com)
  • This anti-inflammatory activity of lovastatin was associated with a shift from a Th1 to a Th2 immune response, as well as an increase in the percentage of regulatory T cells at the inflammation site and in the regional draining lymph node. (jimmunol.org)
  • The scientists suggested that these findings indicated that lovastatin may prevent certain types of cancer from developing in the first place. (lifeextension.com)
  • Our findings suggest, first, that within G1, RA acts before and ICI acts after the point of lovastatin action and, second, that despite these differences in the initiation of cell cycle arrest, the final nature of the cell cycle arrest is similar. (garvan.org.au)
  • In this model, lovastatin administration reduced the acute inflammatory response elicited by C. albicans challenge. (jimmunol.org)
  • The scientists who conducted this study showed that lovastatin worked particularly well in the following cancer cells: acute myeloid leukemia, neuroblastoma, squamous cell carcinoma of the cervix, juvenile monomyelocytic leukemia, head and neck squamous cell carcinoma, medullobastoma and rhabdomyosarcoma. (lifeextension.com)
  • This recommendation was based on scientific studies indicating that lovastatin interfered with the cancer cell growth cycle and might be synergistic with conventional therapies in inducing apoptosis (programmed cell death). (lifeextension.com)
  • In discussing the results of their most recent research, the scientists pointed to a previous five-year study on 745 people taking lovastatin (to reduce their high cholesterol) that showed that these subjects had a lower than expected incidence of cancer. (lifeextension.com)
  • Likewise, collagen I lattice contraction and actin filament rearrangement were partially inhibited when lovastatin was added at 30 M In addition, lovastatin decreased both collagen and collagenase synthesis. (edu.au)
  • The lovastatin-induced increase in regulatory T cells in the inflamed skin was dependent on expression of CCL1, a chemokine that is locally up-regulated by statin administration. (jimmunol.org)
  • Since 1997, a number of studies have substantiated the potential benefit of lovastatin in treating a wide range of cancers. (lifeextension.com)