A group of 20-member macrolactones in which there are three remotely substituted pyran rings that are linked by a methylene bridge and an E-disubstituted alkene, and have geminal dimethyls at C8 and C18 carbons. Some interact with PROTEIN KINASE C.
A phylum of small sessile aquatic animals living as small tufted colonies. Some appear like hydroids or corals, but their internal structure is more advanced. Most bryozoans are matlike, forming thin encrustations on rocks, shells, or kelp. (Storer & Stebbins, General Zoology, 6th ed, p443)
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.
Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
A group of the proteobacteria comprised of facultatively anaerobic and fermentative gram-negative bacteria.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The relationship between two different species of organisms that are interdependent; each gains benefits from the other or a relationship between different species where both of the organisms in question benefit from the presence of the other.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
It is a form of protection provided by law. In the United States this protection is granted to authors of original works of authorship, including literary, dramatic, musical, artistic, and certain other intellectual works. This protection is available to both published and unpublished works. (from Circular of the United States Copyright Office, 6/30/2008)
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.
The continuous sequential physiological and psychological maturing of an individual from birth up to but not including ADOLESCENCE.
Analog or digital communications device in which the user has a wireless connection from a telephone to a nearby transmitter. It is termed cellular because the service area is divided into multiple "cells." As the user moves from one cell area to another, the call is transferred to the local transmitter.
A heterogeneous group of disorders characterized by renal electrolyte transport dysfunctions. Congenital forms are rare autosomal disorders characterized by neonatal hypertension, HYPERKALEMIA, increased RENIN activity and ALDOSTERONE concentration. The Type I features HYPERKALEMIA with sodium wasting; Type II, HYPERKALEMIA without sodium wasting. Pseudohypoaldosteronism can be the result of a defective renal electrolyte transport protein or acquired after KIDNEY TRANSPLANTATION.
Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.
Presence of small calculi in the terminal salivary ducts (salivary sand), or stones (larger calculi) found in the larger ducts.
A deformed foot in which the foot is plantarflexed, inverted and adducted.
A genus of SPONGES in the family Axinellidae, comprised of a choanosomal skeleton differentiated in the axial and extra-axial region. The type species is Axinella polypoides.
Acridine antineoplastic agent used in mammary and ovarian tumors. It inhibits RNA synthesis.
The study of the origin, structure, development, growth, function, genetics, and reproduction of organisms which inhabit the OCEANS AND SEAS.
The assignment, to each of several particular cost-centers, of an equitable proportion of the costs of activities that serve all of them. Cost-center usually refers to institutional departments or services.
Organisms that live in water.
Dressings comprised of a self-adhesive matrix to which hydrophilic absorbent particles are embedded. The particles consist of CELLULOSE derivatives; calcium ALGINATES; PECTINS; or GELS. The utility is based on providing a moist environment for WOUND HEALING.
Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.
One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.
Biological processes, properties, and characteristics of the whole organism in human, animal, microorganisms, and plants, and of the biosphere.
Cells lacking a nuclear membrane so that the nuclear material is either scattered in the cytoplasm or collected in a nucleoid region.
Databases devoted to knowledge about specific chemicals.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Magnesium chloride. An inorganic compound consisting of one magnesium and two chloride ions. The compound is used in medicine as a source of magnesium ions, which are essential for many cellular activities. It has also been used as a cathartic and in alloys.
Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The study of the structure, preparation, properties, and reactions of carbon compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
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)
The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Chemical and physical transformation of the biogenic elements from their nucleosynthesis in stars to their incorporation and subsequent modification in planetary bodies and terrestrial biochemistry. It includes the mechanism of incorporation of biogenic elements into complex molecules and molecular systems, leading up to the origin of life.
Prolamins in the endosperm of SEEDS from the Triticeae tribe which includes species of WHEAT; BARLEY; and RYE.
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.
Anemia characterized by larger than normal erythrocytes, increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
A broad-specificity HLA-DR antigen that is associated with HLA-DRB1 CHAINS encoded by DRB1*11 and DRB1*12 alleles.
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.
Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.
A chronic malabsorption syndrome, occurring mainly in residents of or visitors to the tropics or subtropics. The failed INTESTINAL ABSORPTION of nutrients from the SMALL INTESTINE results in MALNUTRITION and ANEMIA that is due to FOLIC ACID deficiency.

Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic progenitors. (1/250)

Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the marine bryozoan Bugula neritina and is a potent activator of protein kinase C (PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro anti-leukaemic potential. In samples derived from chronic myeloid leukaemia (CML) patients, it has been demonstrated that bryostatin-1 induces a macrophage differentiation, suppresses colony growth in vitro and promotes cytokine secretion from accessory cells. We investigated the effect of bryostatin-1 treatment on colony-forming unit-granulocyte macrophage (CFU-GM) capacity in the presence of accessory cells, using mononuclear cells, as well as in the absence of accessory cells using purified CD34-positive cells. Cells were obtained from 14 CML patients as well as from nine controls. Moreover, CD34-positive cells derived from CML samples and controls were analysed for stem cell frequency and ability using the long-term culture initiating cell (LTCIC) assay at limiting dilution. Individual colonies derived from both the CFU-GM and LTCIC assays were analysed for the presence of the bcr-abl gene with fluorescence in situ hybridization (FISH) to evaluate inhibition of malignant colony growth. The results show that at the CFU-GM level bryostatin-1 treatment resulted in only a 1.4-fold higher reduction of CML colony growth as compared to the control samples, both in the presence and in the absence of accessory cells. However, at the LTCIC level a sixfold higher reduction of CML growth was observed as compared to the control samples. Analysis of the LTCICs at limiting dilution indicates that this purging effect is caused by a decrease in output per malignant LTCIC combined with an increase in the normal stem cell frequency. It is concluded that bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be explored as a purging modality in CML.  (+info)

Identification of sibling species of the bryozoan Bugula neritina that produce different anticancer bryostatins and harbor distinct strains of the bacterial symbiont "Candidatus Endobugula sertula". (2/250)

Although the cosmopolitan marine bryozoan Bugula neritina is recognized as a single species, natural products from this bryozoan vary among populations. B. neritina is the source of the anticancer drug candidate bryostatin 1, but it also produces other bryostatins, and different populations contain different bryostatins. We defined two chemotypes on the basis of previous studies: chemotype O contains bryostatins with an octa-2,4-dienoate substituent (including bryostatin 1), as well as other bryostatins; chemotype M lacks bryostatins with the octa-2,4-dienoate substituent. B. neritina contains a symbiotic gamma-proteobacterium "Candidatus Endobugula sertula," and it has been proposed that bryostatins may be synthesized by bacterial symbionts. In this study, B. neritina populations along the California coast were sampled for genetic variation and bryostatin content. Colonies that differ in chemotype also differ genetically by 8% in the mitochondrial cytochrome c oxidase subunit 1 (CO I) gene; this difference is sufficient to suggest that the chemotypes represent different species. Each species contains a distinct strain of "E. sertula" that differs at four nucleotide sites in the small subunit ribosomal RNA (SSU rRNA) gene. These results indicate that the chemotypes have a genetic basis rather than an environmental cause. Gene sequences from an Atlantic sample matched sequences from the California chemotype M colonies, suggesting that this type may be cosmopolitan due to transport on boat hulls.  (+info)

A Phase I trial of bryostatin-1 in children with refractory solid tumors: a Pediatric Oncology Group study. (3/250)

Bryostatin-1, a macrocyclic lactone, appears to elicit a wide range of biological responses including modulation of protein kinase C (PKC). PKC, one of the major elements in the signal transduction pathway, is involved in the regulation of cell growth, differentiation, gene expression, and tumor promotion. Because of the potential for a unique mechanism of interaction with tumorgenesis, a Phase I trial of bryostatin-1 was performed in children with solid tumors to: (a) establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); (b) establish the pharmacokinetic profile in children; and (c) document any evidence of antitumor activity. A 1-h infusion of bryostatin-1 in a PET formulation (60% polyethylene glycol 400, 30% ethanol, and 10% Tween 80) was administered weekly for 3 weeks to 22 children (age range, 2-21 years) with malignant solid tumors refractory to conventional therapy. Doses ranged from 20 to 57 microg/m2/ dose. Pharmacokinetics were performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. Twenty-two patients on five dose levels were evaluable for toxicities. At the 57 microg/m2/dose level dose-limiting myalgia (grade 3) was observed in three patients; two of those patients also experienced photophobia or eye pain, and one experienced headache. Symptoms occurred in all patients within 24-72 h after the second dose of bryostatin-1 with resolution within 1 week of onset. Other observed toxicities (grades 1 and 2) included elevation in liver transaminases, thrombocytopenia, fever, and flu-like symptoms. The bryostatin-1 infusion was typically well tolerated. Although stable disease was noted in several patients, no complete or partial responses were observed. The recommended Phase II dose of bryostatin-1 administered as a 1-h infusion weekly for 3 of every 4 weeks to children with solid tumors is 44 microg/m2/dose. Myalgia, photophobia, or eye pain, as well as headache, were found to be dose limiting.  (+info)

p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. (4/250)

Although activation of protein kinase C (PKC) is known to promote cell survival and protect against cell death, the PKC targets and pathways that serve this function have remained elusive. Here we demonstrate that two potent activators of PKC, 12-O-tetradecanoylphorbol-13-acetate and bryostatin, both stimulate phosphorylation of Bad at Ser(112), a site known to regulate apoptotic cell death by interleukin-3. PKC inhibitors but not PI 3-kinase/Akt inhibitors block 12-O-tetradecanoylphorbol-13-acetate-stimulated Bad phosphorylation. PKC isoforms tested in vitro were unable to phosphorylate Bad at Ser(112), suggesting that PKC acts indirectly to activate a downstream Bad kinase. p90(RSK) and family members RSK-2 and RSK-3 are activated by phorbol ester and phosphorylate Bad at Ser(112) both in vitro and in vivo. p90(RSK) stimulates binding of Bad to 14-3-3 and blocks Bad-mediated cell death in a Ser(112)-dependent manner. These findings suggest that p90(RSK) can function in a PKC-dependent pathway to promote cell survival via phosphorylation and inactivation of Bad-mediated cell death.  (+info)

Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein. (5/250)

Enzyme localization often plays a controlling role in determining its activity and specificity. Protein kinase C (PKC) has long been known to translocate in response to physiological stimuli as well as to exogenous ligands such as the phorbol esters. We report here that different phorbol derivatives and related ligands, selected for differences in chemical structure and profile of biological activity, induce distinct patterns of redistribution of PKC delta. Localization of a PKC delta-green fluorescent protein (GFP) fusion construct was monitored in living Chinese hamster ovary cells as a function of ligand, concentration, and time using confocal laser scanning microscopy. delta-PKC-GFP was expressed predominantly in the cytoplasm, with some in the nucleus and perinuclear region. Phorbol 12-myristate 13-acetate (PMA) induced plasma membrane translocation followed by slower nuclear membrane translocation. As the concentration of PMA increased, the proportion of nuclear to plasma membrane localization increased markedly. In contrast to PMA, bryostatin 1, a unique activator of PKC that induces a subset of PMA-mediated responses while antagonizing others, at all doses induced almost exclusively nuclear membrane translocation. Like PMA, the complete tumor promoter 12-deoxyphorbol 13-tetradecanoate induced plasma membrane and slower nuclear membrane translocation, whereas the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate, which differs only in its side chain, induced a distinctive distribution of PKC delta-GFP. Finally, the novel constrained diacylglycerol derivative B8-DL-B8 induced a slow Golgi localization. We speculate that differential control of PKC delta localization may provide an interesting strategy for producing ligands with differential biological consequences.  (+info)

Proteolytic cleavage of protein kinase Cmu upon induction of apoptosis in U937 cells. (6/250)

Treatment of U937 cells with various apoptosis-inducing agents, such as TNFalpha and beta-D-arabinofuranosylcytosine (ara-C) alone or in combination with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), bryostatin 1 or cycloheximide, causes proteolytic cleavage of protein kinase Cmu (PKCmu) between the regulatory and catalytic domain, generating a 62 kDa catalytic fragment of the kinase. The formation of this fragment is effectively suppressed by the caspase-3 inhibitor Z-DEVD-FMK. In accordance with these in vivo data, treatment of recombinant PKCmu with caspase-3 in vitro results also in the generation of a 62 kDa fragment (p62). Treatment of several aspartic acid to alanine mutants of PKCmu with caspase-3 resulted in an unexpected finding. PKCmu is not cleaved at one of the typical cleavage sites containing the motif DXXD but at the atypical site CQND378/S379. The respective fragment (amino acids 379-912) was expressed in bacteria as a GST fusion protein (GST-p62) and partially purified. In contrast to the intact kinase, the fragment does not respond to the activating cofactors TPA and phosphatidylserine and is thus unable to phosphorylate substrates effectively.  (+info)

Differential roles of the tandem C1 domains of protein kinase C delta in the biphasic down-regulation induced by bryostatin 1. (7/250)

Bryostatin 1 (Bryo), currently in clinical trials, has been shown to induce a biphasic concentration-response curve for down-regulating protein kinase C (PKC) delta, with protection of the enzyme from down-regulation at high Bryo doses. In our ongoing studies to identify the basis for this unique behavior of PKCdelta, we examined the participation of the two ligand binding sites (C1a and C1b) in the regulatory domain of the enzyme. Three mutants of PKCdelta prepared by introducing a point mutation in either C1a or Clb or both C1a and Clb were overexpressed in NIH 3T3 cells. All of the constructs retained a biphasic response to down-regulation assessed after 24-h treatment with Bryo. However, the roles of the individual C1 domains were different for the two phases of the response. For down-regulation, both the C1a and the C1b mutants displayed equivalent 3-4-fold reductions in their affinities for the ligand. For protection from down-regulation, a reduced protection was observed for the C1a mutant, which showed a broader biphasic curve compared with those for wild-type PKCdelta and the Clb mutant. Like wild-type PKCdelta, all of the mutants showed the same subcellular partitioning of the protected enzyme to the particulate fraction of the cells, arguing against changes in sensitivity to Bryo due to differences in localization. Likewise, relatively similar patterns of localization were observed using green fluorescent protein-PKCdelta constructs. We conclude that the C1 domains of PKCdelta do not have equivalent roles in inducing protection against Bryo-induced down-regulation. The C1a domain plays a critical role in conferring the degree of protection at high concentrations of Bryo. Elucidation of the differential effect of Bryo on PKCdelta may suggest strategies for the design of novel ligands with Bryo-like activities.  (+info)

Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. (8/250)

Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.  (+info)

TY - JOUR. T1 - Differential Effects of Bryostatins and Phorbol Esters on Arachidonic Acid Metabolite Release and Epidermal Growth Factor Binding in C3H 10T1/2 Cells. AU - DellAquila, Marie L.. AU - Herald, Cherry L.. AU - Kamano, Yoshiaki. AU - Pettit, George R.. AU - Blumberg, Peter M.. N1 - Copyright: Copyright 2016 Elsevier B.V., All rights reserved.. PY - 1988. Y1 - 1988. N2 - The bryostatins, a group of macrocyclk lactones isolated on the basis of their antineoplastic activity, activate protein kinase C in vitro and block phorbol ester binding to this enzyme. In some cellular systems, bryostatins mimic phorbol ester action. In other systems, however, the bryostatins display only marginal agonistic action and, instead, inhibit phorbol ester-induced responses. At least in primary mouse epidermal cells, a transient duration of action of bryostatin 1 could rationalize these differences. To determine whether this model of transient activation could explain the dual actions of bryostatin 1 in ...
Angewandte Chemie DOI: 10.1002/anie.200900109 Bryostatins Catalysis in the Total Synthesis of Bryostatin 16** Aubry K. Miller* bryostatins · homogeneous catalysis · lactones · macrocycles · total synthesis M acrocyclic secondary metabolites, perhaps best exemplified by the polyketide macrolactones, hold a special place in the history of natural product total synthesis. The exquisite biological potency and novel modes of action that many of these natural products possess, coupled with the fact that they often cannot be obtained in sufficient quantities for complete testing, has provided a clear need to develop efficient syntheses from robust chemical feedstocks. Notwithstanding the medicinal importance of these natural products, synthetic chemists have been awed by their intricate and imposing beauty, and inspired to recreate these compounds in the laboratory. Virtually all conceivable syntheses of a polyketide macrolactone require a macrocyclization step. In spite of the numerous methods ...
The main purpose of this study is find out how safe a single dose of bryostatin 1 is in patients with Alzheimers Disease (AD). This study is also being done 1) to determine how effective a single dose of bryostatin 1 is in the treatment of AD, 2) to find out what happens to bryostatin 1 once it enters the body by measuring the levels of bryostatin 1 in blood, and 3) to measure a substance in the blood (protein kinase C) that may help to better understand how bryostatin 1 works ...
A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3. Results show that prostratin and bryostatin-1 can significantly damage the integrity of an endothelial monolayer. Moreover, prostratin and bryostatin-1 induce secretion of some proinflammatory cytokines and an increase of ICAM-1 expression. Additional studies demonstrated that ...
TY - JOUR. T1 - Effects of exercise and bryostatin-1 on serotonin dynamics after cerebral infarction. AU - Mizutani, Kenmei. AU - Sonoda, Shigeru. AU - Wakita, Hideaki. AU - Okazaki, Hideto. AU - Katoh, Yoshimitsu. AU - Chihara, Takeshi. AU - Shimpo, Kan. PY - 2016/6/15. Y1 - 2016/6/15. N2 - Although it has been suggested that the combination of exercise and bryostatin-1 administration may induce greater functional recovery than exercise alone, the detailed molecular mechanisms are not well known. Here, we examined the relationship between this combination treatment and monoamine dynamics in the cerebral cortex peri-infarction area to promote our understanding of these molecular mechanisms. Experimental cerebral cortex infarctions were produced by photothrombosis in rats. Voluntary exercise was initiated 2 days after surgery. Motor performance was then measured using the rotarod test. Monoamine concentrations in the perilesional cortex were analyzed by high-performance liquid chromatography. In ...
Abstract. We have examined the in vivo radioprotective effects of the macrocyclic lactone protein kinase C (PK-C) activator, bryostatin 1, administered either
OBJECTIVES:. I. Determine the response to bryostatin 1 (BRYO) administered weekly for 3 weeks in patients with relapsed non-Hodgkins lymphoma.. II. Assess the toxic effects of this treatment. III. Establish the correlation between PKC isoenzyme activity and BRYO function in lymphoma cells and normal lymphocytes.. IV. Determine the pharmacokinetic profile of BRYO and its relationship to pharmacodynamics.. OUTLINE:. Single-Agent Chemotherapy/Differentiation Therapy. Bryostatin 1, BRYO, NSC-339555.. ...
Phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit the growth of A549 human lung carcinoma cells at non-toxic concentrations, whereas 1-oleoyl-2-acetylglycerol and 1,2-dioctanoylglycerol, synthetic analogues of the physiological ligands of protein kinase C (PKC), do not. Exper …
Researchers at the Blanchette Rockefeller Neurosciences Institute (BRNI) and the Marshall University Joan C. Edwards School of Medicine announced their findings from a new study entitled, PSEN1 Variant in a Family with Atypical AD. An Alzheimer patient with very severe disease, genetically confirmed to have a known variant of PSEN1, showed promising benefits during treatment with the drug Bryostatin 1. Genetically confirmed Alzheimers patients as severely advanced as patient IV-18 have not shown this level of clinical improvement previously with other treatment(s). We are very encouraged by the clinical improvements observed in patient IV-18. Nevertheless, controlled clinical trials are necessary to demonstrate safety and efficacy. BRNI believes, however, that this patients response is supportive evidence that activation of Protein Kinase C (PKC) by potent activators such as Bryostatin, with both pre-clinical synaptogenic and anti-amyloid efficacies, could be a viable therapeutic approach ...
We have been able to demonstrate in this patient that infusion of Bryo-1 for 72 h induces peripheral blood lymphocyte HC morphology and increases the sensitivity of cells to 2-CdA. Moreover, there was a significant reduction of lymphocyte count from 37.1 × 103/μl before the treatment to 3.4 × 103/μl, and partial remission was achieved 2 months after the treatment. Sequential treatment with Bryo-1 followed by 2-CdA induced the initiation of apoptosis.. Bryo-1 has been reported to induce differentiation of CLL cells of B-cell origin to a HC stage in vitro (2) . We have previously documented that Bryo-1-treated CLL cells exhibit increased sensitivity to 2-CdA, a drug active in treating de novo HCL but not active in fludarabine-resistant CLL. In WSU-CLL cells in vitro as well as the xenograft model in SCID mice, the efficacy of 2-CdA was enhanced when the cells were first exposed to Bryo-1 (6 , 7) . Administration of Bryo-1 followed by 2-CdA appeared to be sequence-dependent because neither ...
Để khích lệ tinh thần của những thành viên tâm huyết và những người có bài viết hay, hoặc những bài viết sưu tầm chất lượng, BQT quyết định : -- Những bài viết đó sẽ đc trang trọng đưa lên phần đầu diễn đàn, và đc dán lên cao tại Box có bài viết đó. -- Chủ nhân của những bài viết đó sẽ đc cộng điểm thưởng từ 1-|5 (tùy theo chất lượng bài viết). -- Người tìm và giới thiệu bài viết đó (nếu bài viết đó đc công nhận) sẽ đc cộng 2 điểm. -- Cuối tháng sẽ có đợt tổng kết và người có nhiều bài
Fingerprint Dive into the research topics of Activation and Growth of Murine Tumor-specific T-Cells Which Have in Vivo Activity with Bryostatin l. Together they form a unique fingerprint. ...
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NF-κB作用机制。在此图中,将以Rel与p50蛋白组成的NF-κB异质二聚体为例。当处于激活状态时,NF-κB位于细胞质中且与抑制蛋白IκBα形成复合体。通过内在膜受体的介导,一些胞外信号物质可激活一种称为IκB激酶(IKK)的酶。IKK转而磷酸化IκBα蛋白,这将导致后者的泛素化,使得IκBα从NF-κB上脱离下来,最终IκBα被蛋白酶体所降解。被激活的NF-κB接下来转移到细胞核内,在这里会结合到DNA上被称为反应元件(RE)的特异性序列上。DNA/NF-κB 复合体接下来会招募其它蛋白,如辅激活物与RNA聚合酶,这些蛋白将下游的DNA转录为mRNA并转而被翻译为蛋白质,这些蛋白最终导致细胞功能发生改变[1][2][3] ...
Kornax er lei andi v rumerki slandi til margra ra mj li fyrir b i bakstursi na inn og neytendamarka inn kk s traustum vi skiptavinum. Kornax er
TY - JOUR. T1 - Phase II trial of the combination of bryostatin-1 and cisplatin in advanced or recurrent carcinoma of the cervix. T2 - A New York Gynecologic Oncology Group study. AU - Nezhat, Farr. AU - Wadler, Scott. AU - Muggia, Franco. AU - Mandeli, John. AU - Goldberg, Gary. AU - Rahaman, Jamal. AU - Runowicz, Carolyn. AU - Murgo, Anthony J.. AU - Gardner, Ginger J.. N1 - Funding Information: Supported by N01-CM-07003 from the National Cancer Institute, NIH. Previously presented in part at the American Society of Clinical Oncology, May 2002. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2004/4. Y1 - 2004/4. N2 - Objective. Bryostatin-1 is a macrocyclic lactone that has been shown to regulate protein kinase C (PKC) activity and thereby potentially inhibit tumor invasion, angiogenesis, cell adhesion, and multidrug resistance. In preclinical experiments, bryostatin-1 induces tumor growth inhibition and enhances cytotoxicity when combined with other agents including ...
TY - JOUR. T1 - A phase I study of intravenous bryostatin 1 in patients with advanced cancer. AU - Prendiville, J.. AU - Crowther, D.. AU - Thatcher, N.. AU - Woll, P. J.. AU - Fox, B. W.. AU - McGown, A.. AU - Testa, N.. AU - Stern, P.. AU - McDermott, R.. AU - Potter, M.. AU - Pettit, George. PY - 1993/8. Y1 - 1993/8. N2 - Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginning of each 2 week treatment cycle. A maximum of three treatment cycles were given. Doses were escalated in steps from 5 to 65 micrograms m-2 in successive patient groups. The maximum tolerated dose was 50 micrograms m-2. Myalgia was the dose limiting toxicity and was of WHO grade 3 in all three patients treated at 65 micrograms m-2. Flu-like symptoms were ...
Read The Composition of fatty acids and aldehydes of the marine bryozoans Berenicea meandrina and Dendrobeania flustroides (Bryozoa: Gymnolaemata), Russian Journal of Marine Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
We sought to determine the res ponse rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced eso phageal cancer
Health,...Bryostatin may also work in patients with Alzheimers and traumatic in...WEDNESDAY Sept. 3 (HealthDay News) -- A little-used cancer drug calle... Current stroke treatments must be administered within three hours and... Todays stroke patient has precious minutes to receive care without s...,Drug,Given,24,Hours,After,Stroke,Helps,Repair,Brain,Tissue,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
The results of the present study indicate that although bryostatin 1 and UCN-01 share the capacity to interrupt the PKC signal transduction pathway and to promote ara-C-induced apoptosis, the mechanisms by which these two agents act differ fundamentally. There is abundant evidence that in hematopoietic cells, PKC exerts a cytoprotective function. For example, PKC activators such as PMA protect hematopoietic cells from growth factor deprivation-induced cell death (Lotem et al., 1991); in addition, pharmacologic PKC inhibitors are highly potent inducers of apoptosis in hematopoietic and nonhematopoietic cells (Jarvis et al., 1996). Moreover, PKC inhibitors have been shown to potentiate apoptosis induced by various cytotoxic drugs, including ara-C (Jarvis et al., 1994). Although bryostatin 1 acutely activates PKC, on long-term exposure it down-regulates the enzyme, a phenomenon that involves proteasomal degradation (Lee et al., 1997). Thus, under these circumstances, bryostatin 1 functions as a PKC ...
Our research program involves studies in chemistry, biology, and medicine. We place special emphasis on both the design of novel therapeutic drug candidates, and the development of new strategies for the efficient synthesis and evaluation of these molecules. The research supported by this grant is focused on molecules that are selected because of their unique biological activities and consequently their potential to lead to new therapeutics for treating cancer and other diseases.. One part of this program is directed at bryostatin, a marine natural product that is now in human clinical trials. Bryostatin has a unique range of activities, including the ability to trigger a programmed cell death pathway called apoptosis in cancer cells, providing a means to achieve selective elimination of cancer cells in the presence of normal cells. Bryostatin also reverses a cellular process called multidrug resistance that can allow cancer cells to neutralize the effects of entire classes of drugs; ...
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug ma
Fenestella, genus of extinct bryozoans, small colonial animals, especially characteristic of the Early Carboniferous Period (360 to 320 million years ago). Close study of Fenestella reveals a branching network of structures with relatively large elliptical openings and smaller spherical openings
krzem z borem silor b i inne produkty invex remedies - sklep - Sklep internetowy z naturalnymi suplementami diety w niskich cenach. Medycyna naturalna Immunocal, witaminy, krzem, vilcacora, noni itp. Promocja zdrowia - doradztwo zdrowotne i dietetyczne.
Pocket-sized and portable, Instant Work-ups: A Clinical Guide to Medicine offers all of the critical information physicians need to know in order to evaluate and diagnose a patient. The content is uniquely presented as a patient would present his or her case: with symptoms and abnormalities, as opposed to a diagnosis. Practical and easy to use, it provides clear work-up plans for the most commonly encountered medical conditions, providing quick, focused guidance with the flexibility to adapt to each unique patient.
G998B Dr.Ketan ROM ROM Features ROM Features varies with version of ROM. For more details, read changelog post. Link available in post #3 for...
Problem 11. Back and Forth Rows function b = back_and_forth(n) for i = 1:2:n b(i,:) = (i-1)*n+1:i*n; end for j = 2:2:n b(j,:) = j*n : -1 : (j-1)*n+1; end end Problem 12. Fibo
Bryostatin 1, a macrocyclic lactone isolated from a marine bryozoan, has significant antineoplastic activity against the murine cell line P388. Like phorbol esters, bryostain 1 is capable of binding to and activating protein kinase C, but these two compounds differ in the ability of bryostain 1 to act as a tumor promoter. We have investigated whether bryostatin 1 can modulate the differentiated phenotype of fresh samples of human myeloid leukemia. We find that six of seven samples responded to bryostatin treatment with changes associated with a more differentiated phenotype including increases in macrophage-like morphology and an increase in adherence and OKM1 and α-naphthyl acetate esterase activity positivity. The percentage of cells within each sample evidencing these changes varied markedly among the seven patients cells examined.. Because of the effects of bryostatin on fresh samples we examined the ability of bryostatin to differentiate four HL-60 cell sublines obtained from different ...
Technical Summary of BIMECTIN PLUS Injection for CATTLE - BIMEDA - ivermectin 1% + clorsulon 10%, macrocyclic lactone, benzenesulphonamide for the control of gastrointestinal roundworms, lungworms, eyeworms, liver flukes, lice, mites and grubs on cattle, cows, heifers, calves, bulls, bovine, Indications, spectrum of activity, recommended dose, safety, toxicity, LD50, withholding period, ingredientes, composición, administration, characteristics, features.
Technical Summary of MASTERMECTIN 10 mg/ml Solution for Injection for CATTLE, SHEEP & PIGS - C-CORP - ivermectin, macrocyclic lactone, for the control of gastrointestinal roundworms, lungworms, eyeworms, lice, mites and grubs on cattle, cows, heifers, calves, sheep, lambs, ewes, goats, swine, pigs, piglets. Indications, spectrum of activity, recommended dose, safety, toxicity, LD50, withholding period, ingredientes, composición, administration, characteristics, features.
SuperFluids™ CXP technology can be utilized to manufacture nutraceutical products such as saw palmetto for the treatment of mild to moderate benign prostate enlargement and St. Johns Wort for mild to moderate depression. Other candidate products include: ginseng used to boost mental and physical resistance to stress; ginkgo biloba used for increasing concentration and attention span as well as helping those suffering from Alzheimers; kava kava used to combat anxiety; and echinacea used for the prevention and treatment of colds and flu; as well as specialty flavors and fragrances. The technology can also be utilized to manufacture natural pharmaceuticals such as taxols, bryostatins and camptothecins ...
We selected and characterized a 30-fold etoposide (VP-16)-resistant subline of K562 human leukemia cells (K/VP.5) that exhibits quantitative and qualitative changes in topoisomerase II, including hypophosphorylation of this drug target. The initial rate of topoisomerase II phosphorylation was reduced 3-fold in K/VP.5 compared with K562 cells, but the rate of dephosphorylation was similar. Analysis of potential topoisomerase II protein kinases revealed a 3-fold reduction in the level of the beta II protein kinase C (PKC) in K/VP.5 cells, whereas levels of alpha- and epsilon PKC, casein kinase II, p42map kinase, and p34cdc2 kinase were comparable for both cell lines. The PKC activator, bryostatin 1, together with K562 nuclear extracts potentiated VP-16-induced topoisomerase II/DNA covalent complex formation in nuclei isolated from K/VP.5 cells but not from K562 cells. Bryostatin 1 effects were blocked by the PKC inhibitor 7-O-methyl-hydroxy-staurosporine. Bryostatin 1 also up-regulated ...
Background Regression of established tumors can be induced by adoptive immunotherapy with tumor draining lymph node lymphocytes activated with bryostatin and ionomycin. We hypothesized that tumor regression is mediated by a subset of the transferred T lymphocytes, which selectively infiltrate the tumor draining lymph nodes and proliferate in vivo. Results Adoptive transfer of B/I activated tumor draining lymphocytes induces regression of advanced 4T1 tumors, and depletion of CD8, but not CD4 T cells, abrogated tumor regression in mice. The predominant mediators of tumor regression are CD8+ and derived from CD62L- T cells. Transferred lymphocytes reached their peak concentration (10.5%) in the spleen 3 days after adoptive transfer and then rapidly declined. Adoptively transferred cells preferentially migrated to and/or proliferated in the tumor draining lymph nodes, peaking at day 5 (10.3%) and remained up to day 28. CFSE-stained cells were seen in tumors, also peaking at day 5 (2.1%). Bryostatin and
Free Online Library: Evolutionary and structural diversification of the larval nervous system among marine bryozoans.(Report) by The Biological Bulletin; Biological sciences Bryozoa Physiological aspects Research Bryozoans Larval development Nervous system
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On a day trip to walk to the wonderful hermitage in Perthshire, a watery wonderland where the autumn leaves are a bit past their best. The bryophytes, though, are luscious, and I couldnt resists snagging a couple even though I was off duty. Favourite of the day was Bazzania trolobata, which I have wanted to see for a while. One of those things you see in the field guide and look forward to meeting it ...
A seaweed-like marine invertebrate contains a molecule that has piqued interest as a drug but is in short supply: Collecting 14 tons of the critters, a type of bryozoan, yields just 18 grams of the potential medicine. Now, an efficient lab recipe might make bryostatin 1 easier to get.. Making more of the molecule could help scientists figure out whether the drug - which has shown mixed.... ...
Trepostomata, extinct order of bryozoans (moss animals) found as fossils in marine rocks of Ordovician to Triassic age (200 million to 488 million years old). The trepostomes are characterized by colonies in long, curved calcareous tubes, the interiors of which are intersected by partitions. The
Bài Tập Về Đại Từ Nhân Xưng - Free download as Word Doc (.doc / .docx), PDF File (.pdf), Text File (.txt) or read online for free. kjkk
Bài viết liên quan đến Rêu này vẫn còn sơ khai. Bạn có thể giúp Wikipedia bằng cách mở rộng nội dung để bài được hoàn chỉnh hơn. ...
Bài viết tông cúc Heliantheae này vẫn còn sơ khai. Bạn có thể giúp Wikipedia bằng cách mở rộng nội dung để bài được hoàn chỉnh hơn. ...
I have no problems with my face. But |b|I am very fond of attractive jaw lines|/b|. My jawline is very normal. Can I undergo surgery for those awesome looks, with the hot jawlines? How much would such a surgery cost?
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positive variable xplus(j), xneg(j); obj.. z=e=sum(j, xplus(j) + xneg(j)); cons(i).. sum(j, a(i,j)*(xplus(j) - xneg(j))) =l= b(i); model foo /all/; solve foo minimizing z using lp ...
Nemadectin is a macrocyclic lactone antibiotic with a broad-spectrum endectocidal and nematocidal activity [1]. In dogs, oral administration of 0.2-0.4 mg/kg nemadectin (a liquid formulation administered in gelatin capsules) was effective in eliminating
Stereotypic cleavage patterns play a crucial role in cell fate determination by precisely positioning early embryonic blastomeres. Although misplaced cell divisions can alter blastomere fates and cause embryonic defects, cleavage patterns have been modified several times during animal evolution. However, it remains unclear how evolutionary changes in cleavage impact the specification of blastomere fates. Here, we analyze the transition from spiral cleavage - a stereotypic pattern remarkably conserved in many protostomes - to a biradial cleavage pattern, which occurred during the evolution of bryozoans. Using 3D-live imaging time-lapse microscopy (4D-microscopy), we characterize the cell lineage, MAPK signaling, and the expression of 16 developmental genes in the bryozoan Membranipora membranacea. We found that the molecular identity and the fates of early bryozoan blastomeres are similar to the putative homologous blastomeres in spiral-cleaving embryos. Our work suggests that bryozoans have retained
Coloured scanning electron micrograph (SEM) of Bryozoan, lophophorate animals that consist of microscopic zooids that form colonies. A thin crust is formed around each zooid consisting of a protein and mucopolysaccharide material than can be calcified. Magnification x16 when shortest axis printed at 25 millimetres. - Stock Image C032/4244
Tập hợp những bài báo về lĩnh vực y học hay và nổi bật mới xuất bản trong tháng 5 năm 2019, Đặc biệt là dịch sởi, dịch tay chân miệng và các bệnh khác như dại, zika, sốt xuất huyết,viêm não nhật bản,ứng dụng trí thông minh nhân tạo trong lĩnh vực y tế..
Dưới đây là 101 từ vựng tiếng Anh bạn nên thuộc nằm lòng để làm bài thi IELTS Reading đạt kết quả tốt. Những từ vựng được liệt kê này có tính ứng dụng cao, phổ biến trong ngôn ngữ khoa học và báo chí, bởi vậy mà 96% bạn sẽ gặp phải khi đọc đề thi IELTS Reading.. Download file full PDF ở cuối bài.. ...
Yesterday I received my Retina MacBook Pro. I went a little nuts and bought the top of the line config: 16 gigs of RAM (!) and a 750GB SSD. This thing is a screamer. The Retina MacBook Pro replaces my trusty 13 MacBook Air Some observations: This display is under hyped. Its absolutely beautiful. Its…
Google has taken another major step toward making Google Translates Pinyin converter decent. Finally, apostrophes. Not long ago 陂爼巷尻亚焼耔仆愗蓱藚普洳茿 would have yielded Āěrbāníyǎ ránér rénài liánǒu pǔěr chá. But now Google produces the correct Āěrbāníyǎ ránér rénài liánǒu pǔěr chá. (Well, one could debate whether that last one should be pǔěr chá, pǔěrchá, Pǔěr chá, Pǔěr Chá, or Pǔěrchá. But the apostrophe is undoubtedly correct regardless.). Also, the -men suffix is now solid with words (e.g., 有叏倓 -> péngyoumen and 孨孑倓 -> háizimen). This is a small thing but nonetheless welcome. The most significant remaining fundamental problem is the capitalization and parsing of proper nouns.. And numbers are still wrong, with everything being written separately. For example, 三匿乢白囙匿三萩亏匿公白亏匿公 should be rendered as qīqiān jiǔbǎi sìshísān wàn wǔqiān liùbǎi wǔshíbā. But ...
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[b]MITCH LUCKER[/b] i dont need efes.. i dont need pokemones, i dont need rawrs, and nothing like that, so please.. GET THE F*CK OUT OF HE... - Fotolog
Upplýsingar og aðrar lýsingar um sjúkdómsgreiningar eru yfirleitt fengnar með tengingu við utanaðkomandi síður (utan rarelink) A. Greining getur verið listuð nokkuð víða, undir mismunandi nöfnum, bæði á íslensku, ensku og öðrum norrænum tungumálum ...
國立臺北教育大學 96 學年度碩士班招生入學考試 請以 2B 鉛筆於答案卡上畫記作答,作答前請務必詳閱答案卡上之「畫記說明」 I. Vocabulary (每小題 2 分,共 20 分) Please choose the option that is closest in meaning to the word underlined. 1. I noticed a peculiar grin on the face of my eleven-year-old boy as I kissed him goodbye. 3. I e ...
Am I indanger of myself?? [i][color=red>Annie, [b][i] it and decided I would but I would say very little. I think a lot of us have had feelings of despair and sadness. That [i][color=#ff0000>s] . It is up to us to try very.... ...
Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti ... Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided ... As of 2010 20 different bryostatins had been isolated. The low concentration in bryozoans (to extract one gram of bryostatin, ... Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16. Among them, Wender's total synthesis of bryostatin 1 ...
Bryostatins were first isolated from Bryozoa. Salinosporamides are derived from Salinispora tropica. Ziconotide is derived from ...
... produces the bryostatins, a group of around twenty bioactive natural products. The bryostatins are under investigation for ... Ruan BF, Zhu HL (2012). "The chemistry and biology of the bryostatins: potential PKC inhibitors in clinical development". Curr ...
A group of chemicals called bryostatins can be extracted from the marine bryozoan Bugula neritina. In 2001 pharmaceutical ...
The Saksena-Evans reduction has since been used in the synthesis of several products, particularly the bryostatins. Evans- ...
Certain antineoplastic agents, bryostatins 4 and 5, have been extracted from Aplidium californicum and are being evaluated. ...
... neritina attracted interest as a source of cytotoxic chemicals, bryostatins, under clinical investigation as anti-cancer ... B The Bryostatins' Tale Chemical and Engineering News, Vol 89, No 43 PP. 10 - 17 Oct 24, 2011 accessed Dec 19, 2017 "Bryostatin ...
... and the bryostatins (from the bryozoan Bugula neritina). Natural products sometimes have pharmacological activity that can be ...
"The Bryostatins' Tale", Chemical and Engineering News 89.43, October 24, 2011, pp. 10-17 Gordon, R. Sharov, AA Eds. (2017). ... "Identifying bryostatins and potential precursors from the bryozoan 'Bugula neritina'", Natural Product Research 19.5 (2005) 467 ...
One species of bryozoan, Bugula neritina, is of interest as a source of chemicals, bryostatins, which are under investigation ...
The bryostatins not only interfere with A549 cell growth but can also counter the growth-inhibitory effect of PKC activators, ... Effects of activators of protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells Int ... At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of ... mezerein or the bryostatins. The extent of inhibition changed little during the subsequent 5 hr of incubation, after which it ...
Bryostatins are complex macrolactones isolated from marine organisms Bryozoan Bugula neritina. They are potent modulators of ... Bryostatins, Bryostatin-1, Protein kinase C, Clinical trials, Cancer, Alzheimers disease. Affiliation:. Medicinal Chemistry ... Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal ... Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review [ Vol. 20 ...
In some cellular systems, bryostatins mimic phorbol ester action. In other systems, however, the bryostatins display only ... In some cellular systems, bryostatins mimic phorbol ester action. In other systems, however, the bryostatins display only ... In some cellular systems, bryostatins mimic phorbol ester action. In other systems, however, the bryostatins display only ... In some cellular systems, bryostatins mimic phorbol ester action. In other systems, however, the bryostatins display only ...
... synthetic cell permeant dioleins and bryostatins isolated from the marine bryozoan Bugula neritina. Bryostatins 1 and 2 (B1 and ... synthetic cell permeant dioleins and bryostatins isolated from the marine bryozoan Bugula neritina. Bryostatins 1 and 2 (B1 and ... synthetic cell permeant dioleins and bryostatins isolated from the marine bryozoan Bugula neritina. Bryostatins 1 and 2 (B1 and ... synthetic cell permeant dioleins and bryostatins isolated from the marine bryozoan Bugula neritina. Bryostatins 1 and 2 (B1 and ...
The Bryostatins. David J. Newman. The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic ...
The Bryostatins. David J. Newman. The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic ...
Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti ... Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided ... As of 2010 20 different bryostatins had been isolated. The low concentration in bryozoans (to extract one gram of bryostatin, ... Total syntheses have been published for bryostatins 1, 2, 3, 7, 9 and 16. Among them, Wenders total synthesis of bryostatin 1 ...
Bryostatins were first isolated from Bryozoa. Salinosporamides are derived from Salinispora tropica. Ziconotide is derived from ...
This updated edition in the long standing series provides the latest information on many individual drugs, including the most complete coverage of their adverse reactions and interactions.
Pettit G. The bryostatins. Fortschr. Chem. Org. Naturst., 57: 153-195, 1991. ...
Mutter, R; Wills, M. Chemistry and Clinical Biology of the Bryostatins. Bioorg. Med. Chem 2000, 8, 1841-1860. [Google Scholar] ... Evidence for the biosynthesis of bryostatins by the bacterial symbiont "Candidatus Endobugula sertula" of the bryozoan Bugula ... Substitution on the A-ring confers to bryopyran analogues the unique biological activity characteristic of bryostatins and ... 20 natural Bryostatins are a part of our knowledge today [60]. Their low toxicity and antineoplastic nature makes them ...
Modeling of the bryostatins to the phorbol ester pharmacophore on protein kinase C. Proc. Natl. Acad. Sci. USA 85, 7197-7201 ( ...
Bryostatins: biological context and biotechnological prospects. Curr Opin Biotech 21: 834-842. [ Links ]. ... Evidence for the biosynthesis of bryostatins by the bacterial symbiont Candidatus Endobugula sertula of the bryozoan Bugula ... For example, the development of bryostatins for biomedical and biotechnological applications included the cultivation of the ... bryostatins from the bryozoan Bugula neritina, or the halichondrins from the sponge Lissodendoryx, can be isolated only in ...
Bryostatins were first isolated from the marine organism Bugula neritina. Currently, ,20 natural bryostatins are known. ... Bryostatins are macrolactones isolated from marine organisms. Of the ,20 known bryostatins, bryostatin-1 is the best ... The involvement of bryostatins in the SDF-1/CXCR4 signaling process has never been reported. In this study, we found that ... S1A) and found a class of macrolactones, bryostatins, with potent inhibitory activity against SDF-1-induced chemotaxis in a ...
Pettit, G. R., The bryostatins. In progress in the chemistry of organic natural products. Herz, W., Kirby, G.W., Steglich, W. ...
Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review. , 20(12 ... Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review. ...
... partial bryostatins or new relatives of bryostatins in the laboratory and, ultimately, on an industrial scale. ... "If we could get the whole cluster properly expressed in a single cell, you could make bryostatins as simply as you make beer. ... "The larvae are covered with a skin of bryostatins," said Haygood, whose research was described recently in the Journal of ... We also discovered there are bryostatins on the root structures of the adults, perhaps to help them maintain their territory. ...
This pathway may be exploited to give potent inhibitors, such as the bryostatins, now in clinical trial. A summary is given of ...
A. Gupta Total Synthesis of Bryostatins. Feb. 13, 2009. Y. Guan Synthesis of Polyfluorinated and Polychlorinated ...
Some limitations of an approach to the assembly of bryostatins by ring-closing metathesis. Raphaël Dumeunier, Thomas Gregson, ...
It is the source of bioactive polyketide metabolites, the bryostatins. Evidence suggests that an uncultured vertically ... Endobugula sertula" and, subsequently, defensive bryostatins; their documented northern distribution was consistent with ... the source of the bryostatins and the tunicate Ecteinascidia turbinata (the source of ET-743. Another strategy involves partial ... and larvae from these colonies are endowed with defensive bryostatins and contain "Ca. Endobugula sertula". Molecular analysis ...
Bugula and Bryostatins Often mistaken for seaweed, bugula is actually colonies of small animals, likeRead more ...
The bryostatins, exemplified by bryostatin 8 (4), are of increasing clinical importance as anticancer agents. Zhenlei Song of ...
... diacylglycerol and bryostatins. ...
One species of bryozoan, Bugula neritina, is of interest as a source of chemicals, bryostatins, which are under investigation ...
... of the bryostatins. Subsequent direct probing of this question led to the discovery that a symbiotic organism, named Candidatus ... Bryostatins were among the first marine isolates to demonstrate significant anticancer activity, and this family of compounds ... Endobugula neritina, actually biosynthesizes the bryostatins. This observation bears some significance to the question of large ...
... and the bryostatins (from the bryozoan Bugula neritina). Natural products sometimes have pharmacological activity that can be ...
1989). Action of phorbol esters, bryostatins, and retinoic acid on cholesterol sulfate synthesis: Relation to the multistep ...
Natural products chemists and organic synthesis fans will perk up their ears at that name, because the bryostatins are well ... Two: Anybody know what dosages were used? The Bryostatins are, as was previously mentioned, a famously complex family of ...
One species of bryozoan, Bugula neritina, is of current interest as a source of cytotoxic chemicals, bryostatins, under ...
  • Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal chemists and clinicians. (currenttopicsinmedicinalchemistry.com)
  • Scientists have long known bryostatins, particularly a type of the compound called bryostatin 1, have anti-cancer properties, including activity against pancreatic and renal cancer, leukemia, non-Hodgkin's lymphoma and melanoma that involves flipping a switch that makes the cancer cells behave like normal cells. (ohsu.edu)
  • By sequencing the genes from two closely related strains of the Endobugula sertula bacterium found in different Bugula neritina bryozoan species - one living in deep waters, the other in shallow waters - they isolated a gene cluster "proposed to code for the biosynthetic machinery to make a common precursor" of the 20 known bryostatins, called bryostatin 0, according to the study. (ohsu.edu)
  • The bryostatins, exemplified by bryostatin 8 ( 4 ), are of increasing clinical importance as anticancer agents. (organic-chemistry.org)
  • Angewandte Chemie DOI: 10.1002/anie.200900109 Bryostatins Catalysis in the Total Synthesis of Bryostatin 16** Aubry K. Miller* bryostatins · homogeneous catalysis · lactones · macrocycles · total synthesis M acrocyclic secondary metabolites, perhaps best exemplified by the polyketide macrolactones, hold a special place in the history of natural product total synthesis. (docme.ru)
  • The target molecule of Trosts synthesis, bryostatin 16 (1), belongs to a family of related macrolactones known collectively as the bryostatins. (docme.ru)
  • The isolation of bryA represents a significant step forward in understanding bryostatin biosynthesis and eventually harnessing bry genes to produce bryostatins and derivatives inexpensively and in abundant quantities,' the authors write in the paper, one of the first studies that describes such a cloning achievement from a marine symbiont organism. (ucsd.edu)
  • This invention relates to pharmaceutical compositions, particularly pharmaceutical compositions comprising a Bryostatin 1, other bryostatins and substituted derivatives of bryostatins for use in treating inflammation, and for use in combating arteriosclerosis, diseases of the cardiovascular system and the central nervous system, prior to and following organ transplantation, and ischemia [United States Patent Pending]. (aphios.com)
  • The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. (elsevier.com)
  • Bryostatins are complex macrolactones isolated from marine organisms Bryozoan Bugula neritina. (currenttopicsinmedicinalchemistry.com)
  • We have examined several actions on GH 4 C 5 cells of TPA and two other classes of protein kinase C activators, synthetic cell permeant dioleins and bryostatins isolated from the marine bryozoan Bugula neritina. (elsevier.com)
  • Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided to JL Hartwell's anticancer drug discovery group at the National Cancer Institute (NCI) by Jack Rudloe. (wikipedia.org)
  • Bryostatins were first isolated from the marine organism Bugula neritina . (aacrjournals.org)
  • One species of bryozoan, Bugula neritina , is of interest as a source of chemicals, bryostatins , which are under investigation as anti-cancer agents. (wikipedia.org)
  • In 2001, Haygood and other scientists in her Scripps laboratory found that such bacteria living in Bugula neritina were the source of bryostatins, a family of chemical compounds being closely studied for their potential as anticancer pharmaceuticals in leukemia, lymphoma and several cancers including colon, breast, ovarian and prostate. (ucsd.edu)
  • Bryostatins are a group of macrocyclic lactones first discovered in the late 1960s in a species of bryozoan, Bugula neritina . (chemeurope.com)
  • The bryostatins, a group of macrocyclk lactones isolated on the basis of their antineoplastic activity, activate protein kinase C in vitro and block phorbol ester binding to this enzyme. (elsevier.com)
  • Int. Ed. 2009, 48, 3221 - 3223 From a structural viewpoint, the bryostatins are extraordinarily beautiful and dauntingly complex 26-membered lactones. (docme.ru)
  • The most famous of compounds obtained from these organisms are macrolide lactones of Bryostatins. (ac.ir)
  • Silva AE, Lim-Fong GE, Sharp KH, Haygood MG. Bryostatins: biological context and biotechnological prospects. (innovareacademics.in)
  • Haygood said the next step is moving the bacterial genes into a host organism that can process them properly and go on to produce bryostatins, partial bryostatins or new relatives of bryostatins in the laboratory and, ultimately, on an industrial scale. (ohsu.edu)
  • To identify antagonists of this signaling pathway, we screened a small library of compounds derived from marine organisms (Supplementary Fig. S1 A ) and found a class of macrolactones, bryostatins, with potent inhibitory activity against SDF-1-induced chemotaxis in a human acute T-cell leukemia cell line (Jurkat). (aacrjournals.org)
  • The bryostatins not only interfere with A549 cell growth but can also counter the growth-inhibitory effect of PKC activators, presumably via interaction with a target separate from the phorbol ester receptor site. (nih.gov)
  • In some cellular systems, bryostatins mimic phorbol ester action. (elsevier.com)
  • In other systems, however, the bryostatins display only marginal agonistic action and, instead, inhibit phorbol ester-induced responses. (elsevier.com)
  • Bryostatins 2, 3, 4,10, and several of their derivatives caused variable arachidonic acid metabolite release (10 to 60% of phorbol ester control) and correspondingly variable inhibition of phorbol ester action. (elsevier.com)
  • They indicate, moreover, differences in the structure-activity relations of the bryostatins for the phorbol ester-mimetic and phorbol ester-inhibitory actions. (elsevier.com)
  • Modeling of the bryostatins to the phorbol ester pharmacophore on protein kinase C. (nature.com)
  • We propose that different activators of protein kinase C (such as bryostatins, dioleins, and phorbol esters) may elicit different cellular responses by altering the substrate specificity or activating multiple forms of the kinase. (elsevier.com)
  • Bryostatins 1 and 2 (B1 and B2, respectively) competed for [ 3 H]phorbol 12,13-dibutyate binding to the protein kinase C complex in intact cells nearly equipotently with TPA. (elsevier.com)
  • We conclude that the bryostatins, phorbol esters, and dioleins bind to the same site on the protein kinase C complex to activate the enzyme, but they alter three biological responses in GH 4 C 5 cells with selectivities and efficacies that differ. (elsevier.com)
  • Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti-AIDS/HIV agents and in people with Alzheimer's disease. (wikipedia.org)
  • In vitro trials have shown bryostatins to act synergistically with other anti-cancer drugs and to modulate protein kinase C (PKC) activity, with a potent antileukemic effect and action against lung, prostate and non-Hodgkin's lymphoma tumor cells. (chemeurope.com)
  • The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. (elsevier.com)
  • This pathway may be exploited to give potent inhibitors, such as the bryostatins, now in clinical trial. (springer.com)
  • At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of DNA synthesis and the anti-replicative effect of TPA and mezerein. (nih.gov)
  • This finding is essential for the formulation of the combination therapy using low nanomolar concentrations of bryostatins. (aphios.com)
  • Bryostatins 1 and 2 were able to induce transient growth arrest of A549 cells in a manner similar to phorbol esters at nanomolar concentrations, but at higher concentrations blocked both their own antiproliferative action and also that of phorbol esters and mezerein. (aston.ac.uk)
  • A complete loss of PKC activity was also observed on treatment with growth-inhibitory concentrations of bryostatins. (aston.ac.uk)
  • Measurement of intracellular Ca2+ concentrations using A549 cells cultured on Cytodex 1 microcarrier beads revealed that TPA, mezerein and the bryostatins induced a similar rapid rise in intracellular Ca2+ levels. (aston.ac.uk)
  • Inhibition of DNA synthesis to between 90 and 75% of control values developed during the first hour of incubation of the cells with TPA, mezerein or the bryostatins. (nih.gov)
  • Treatment with TPA, mezerein or bryostatins resulted in a concentration-dependent shift of PKC activity from the cytosol to cellular membranes within 30 min. (aston.ac.uk)
  • Here, we propose a hypothesis for the biosynthesis of the bryostatins. (elsevier.com)
  • Dr. Eduardo Muñoz, lead inventor and Chief Scientific Officer of VivaCell Biotechnology España states that: "From our experiments using a specific and suitable model for HIV-1 reactivation, we determined which combinations of bryostatins and HDACs inhibitors synergize to antagonize HIV-1 latency. (aphios.com)
  • Natural products chemists and organic synthesis fans will perk up their ears at that name, because the bryostatins are well known as examples of complex marine natural products. (sciencemag.org)
  • The bryostatins have been challenging chemists since their discovery more than 25 years ago, and until Trosts recent synthesis, only three total syntheses had been reported. (docme.ru)
  • But the problem has been getting the bryostatins in the large quantities needed for pharmaceutical development. (ohsu.edu)
  • As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical. (elsevier.com)
  • Blumberg, Peter M. / Differential Effects of Bryostatins and Phorbol Esters on Arachidonic Acid Metabolite Release and Epidermal Growth Factor Binding in C3H 10T1/2 Cells . (elsevier.com)
  • In a nutshell, the natural as well as synthetic bryostatins have generated a strong hope to emerge as treatment for cancer along with many other diseases. (currenttopicsinmedicinalchemistry.com)
  • Human clinical trials have been less promising, but suggest bryostatins to have a potentially useful synergistic action with other chemotherapeutic agents. (chemeurope.com)
  • These post-β-Branching steps generate the vinyl methylester moieties which are found in all natural product bryostatins. (wikipedia.org)
  • The larvae are covered with a skin of bryostatins," said Haygood, whose research was described recently in the Journal of Natural Products. (ohsu.edu)
  • Se analizó la toxicidad natural, mediante Microtox®, de cnidarios, briozoos y tunicados de dos cuevas, en primavera y otoño. (worldwidescience.org)
  • The technology can also be utilized to manufacture natural pharmaceuticals such as taxols, bryostatins and camptothecins. (aphios.com)
  • 7] [*] Dr. A. K. Miller Medicinal Chemistry in Preclinical Target Development Deutsches Krebsforschungszentrum (DKFZ) Im Neuenheimer Feld 517, 69120 Heidelberg (Germany) Fax: (+ 49) 6221-42-4323 E-mail: [email protected] Homepage: http://www.dkfz.de/en/drugs/G0404medi.html [**] I thank Dr. Jean-Philip Lumb for valuable comments. (docme.ru)
  • 2. Which source has been particularly fruitful in finding novel anti-tumour agents such as bryostatins and dolostatins? (sscportal.in)
  • The structure-activity relationship of bryostatins has been well established, with the identification of key pharmacophoric features important for PKC modulation. (currenttopicsinmedicinalchemistry.com)
  • The involvement of bryostatins in the SDF-1/CXCR4 signaling process has never been reported. (aacrjournals.org)