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Topic: Bryostatin

In the News (Thu 24 Dec 09)

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	Synthetic conversion of bryostatin 2 into bryostatin 1 - Patent 5072004 (Site not responding. Last check: 2007-10-14)
		The method according to claim 2 in which said bryostatin 2 is converted to bryostatin 2 26-tert-butyldimethylsilyl ether by admixing said bryostatin 2 with tert-butyldimethylsilyl chloride in the presence of 4-(N,N-dimethyl) aminopyridine and triethylamine in dimethylforamide.
		Bryostatin 2 is admixed with tert-butyldimethylsilyl chloride in the presence of 4-(N,N-dimethyl) aminopyridine and triethylamine in dimethylforamide at 25.degree.
		Bryostatin 2 was allowed to react at room temperature with excess tert-butyldimethylsilyl TBDMS) chloride in the presence of 4-(N,N-dimethyl) aminopyridine (and triethylamine in dimethylformamide) to produce the 26-tert-butyldimethylsilyl ether of bryostatin 2.
	www.freepatentsonline.com /5072004.html (1743 words)

	Blistering barnacles - bryostatin 2 is totally synthesised (Site not responding. Last check: 2007-10-14)
		Harvard University chemists have devised the first synthetic route to the potential anticancer drug bryostatin 2, which could also make it easier to produce the archetypal member of the group bryostatin 1 made as a defence chemical by marine barnacles.
		The first bryostatin was discovered by George Pettit and his team at Cancer Research Institute at Arizona State University in 1982.
		David Evans and his colleagues at Harvard realised that bryostatin 1 has remained a rare and costly substance and so began to look for a simple synthesis to make its chemical cousin bryostatin 2.
	www.acdlabs.com /webzine/1/1_1f.html (373 words)

	Creatures from the deep fight cancer and warn of environmental hazards: 4/00
		Bryostatin is being tested in more than 40 clinical trials in the United States, and so far, many cancer patients have shown marked improvement with relatively minor side effects.
		The ultimate answer, he argued, is for chemists to create a simplified version of the bryostatin molecule that would be easier to manufacture in bulk and would perform better in the clinic.
		The goal, he said, is to redesign bryostatin by removing segments of the molecule that have nothing to do with blocking tumors.
	www.stanford.edu /dept/news/pr/00/oceanmeds45.html (1041 words)

	ISAC XX Abstracts (Site not responding. Last check: 2007-10-14)
		Bryostatin - differentiation and apoptosis in B-cell chronic lymphocytic leukaemia
		Bryostatin, a macrocyclic lactone with the ability to activate protein kinase C, has been shown to induce differentiation and increased drug sensitivity in a B-CLL cell line (WSU-CLL).
		This had the effect of raising the Bcl-2/Bax ratio of the viable B-CLL cell population indicating that short-term exposure to Bryostatin may potentiate a drug resistant phenotype in B-CLL cells and as such Bryostatin should be used with caution in clinical settings.
	www.wiley.com /legacy/products/subject/life/cytometry/isac2000/6707.htm (184 words)

	Bryostatin 1 protects protein kinase C-delta from down-regulation in mouse keratinocytes in parallel with its ...
		Bryostatin 1 protects protein kinase C-delta from down-regulation in mouse keratinocytes in parallel with its inhibition of phorbol ester-induced differentiation.This protected portion of PKC-delta retained kinase activity.
		Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation.
		Bryostatin 1 at 100 nM to 1 microM, on the other hand, failed to induce down-regulation, and these high (100 nM to 1 microM) doses of bryostatin 1 showed noncompetitive inhibition of PKC-delta down-regulation by 1 microM PMA after coapplication.
	www.pdg.cnb.uam.es /UniPub/iHOP/gp/140989.html (340 words)

	ASH: Bryostatin Less Than Impressive in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma (Site not responding. Last check: 2007-10-14)
		Bryostatin, a cytotoxic agent derived from a single-cell sea organism, has both cytotoxic and immunomodulatory properties in in-vivo and in-vitro models.
		Though it never showed much activity as a single agent, bryostatin has been of interest to scientists as a potential modulator of other cytotoxic drugs, Dr. Roberts said.
		The trials continued escalation to 50 micrograms/m2 of bryostatin followed by 25 mg/m2 of fludarabine.
	www.pslgroup.com /dg/225872.htm (529 words)

	[No title] (Site not responding. Last check: 2007-10-14)
		The drug may be further diluted with 0.9% sodium chloride, USP, or Dextrose 5% in Water, USP, to a concentration of 0.15 mcg/mL to 0.75 mcg/mL in a glass or polyolefin container.
		Extended infusion: When bryostatin is aseptically mixed in a single polypropylene bag and diluted with benzyl alcohol preserved normal saline to a drug concentration between one and ten mcg/mL, the solution is suitable for a continuous intravenous infusion of up to 14 days.
		The diluted solution of bryostatin was physically and chemically stable under normal laboratory lighting for at least 24 hours at room temperature.
	www.dtp.nci.nih.gov /docs/static_pages/pharm_data/339555phrm.html (313 words)

	Cancer Cell International \| Full text \| Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC ... (Site not responding. Last check: 2007-10-14)
		Bryostatin 1 may be considered for further investigation of IFNg-dependent MHCII induction in resistant tumors in vivo.
		Bryostatin 1 is a potent PKC activator that has undergone extensive clinical testing for the treatment of hematological malignancies and solid tumors [27].
		Animal studies show that the concentration of Bryostatin 1 in various tissues after a single intraveneous injection stays in a range of 10–50 ng/g for a period of more than 72 hr [28].
	www.cancerci.com /content/3/1/4 (6050 words)

	Bryostatin and CD40-ligand enhance apoptosis resistance and induce expression of cell survival genes in B-cell chronic ...
		Bryostatin and CD40-ligand enhance apoptosis resistance and induce expression of cell survival genes in B-cell chronic lymphocytic leukaemia.
		Apoptosis resistance was associated with CD40L- and Bryostatin- induced elevations in the anti-apoptotic Bcl-2 family protein Mcl-1.
		This Fas-resistance was associated with increased expression of the Fas-antagonist Flip in CD40L-treated, and with elevations in the caspase inhibitor XIAP in Bryostatin-treated B-CLLs.
	www.pdg.cnb.uam.es /UniPub/iHOP/gp/8326232.html (199 words)

	The Effect of Protein Kinase C Modulation with Bryostatin 1 on Paclitaxel-Induced Growth Inhibition and Apoptosis in ...
		The combination of bryostatin 1 and paclitaxel was studied in four breast cancer cell lines utilizing multiple treatment schedules and no synergistic combination was identified.
		No synergistic combinations of bryostatin 1 and paclitaxel (as well as the other drugs tested) were identified even though several breast cancer cell lines and multiple treatment schedules were evaluated.
		These studies suggest that bryostatin 1 in combination with paclitaxel and the other drugs evaluated may not be a promising combination for the treatment of breast cancer.
	www.stormingmedia.us /32/3218/A321873.html (254 words)

	Protein Kinase C-dependent Activation of the Tumor Necrosis Factor Receptor-mediated Extrinsic Cell Death Pathway ...
		bryostatin was an ineffective inducer of maturation, and in
		FP, or bryostatin 1 + FP (B/FP) in the presence or absence of TNFSRs [(SR) 100 ng/ml] for 24 h.
		TNF Receptor-related Pathways Contribute to the Synergistic Induction of Apoptosis by Bryostatin 1 and FP in Promyelocytic Leukemia Cells (HL-60).
	mct.aacrjournals.org /cgi/content/full/2/1/83 (7156 words)

	The Antineoplastic Agent Bryostatin-1 Induces Proinflammatory Cytokine Production in Human Monocytes: Synergy With ...
		Berkow RL, Kraft AS: Bryostatin, a non-phorbol macrocyclic lactone, activates intact human polymorphonuclear leukocytes and binds to the phorbol ester receptor.
		Smith JB, Smith L, Pettit GR: Bryostatins: Potent, new mitogens that mimic phorbol ester tumor promotors.
		Mohr H, Pettit GR, Plessing-Menze A: Co-induction of lymphokine synthesis by the antineoplastic bryostatins.
	www.bloodjournal.org /cgi/content/full/89/9/3402 (6380 words)

	Phase I study of bryostatin 1 in patients with relapsed non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
		Phase I study of bryostatin 1 in patients with relapsed non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
		PATIENTS AND METHODS: Bryostatin 1 was delivered by 72-hour continuous infusion every 2 weeks to patients with relapsed NHL or CLL, at doses that ranged from 12 microg/m2 to 180 microg/m2 per course.
		An in vitro assay for total PKC evaluation in patient peripheral-blood samples demonstrated activation within the first 2 hours with subsequent downregulation by 24 hours, which was maintained throughout the duration of the 72-hour infusion.
	www.aegis.com /pubs/medline/1998/jan/m9816415.html (460 words)

	Synthesis of the First Members of a New Class of Biologically Active Bryostatin Analogues
		The bryostatins are a novel family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa on the basis of their significant activity against murine P388 lymphocytic leukemia.
		While their molecular mode of action is not known, the bryostatins potently inhibit the binding of the tumor-promoting phorbol esters to protein kinase C (PKC) and stimulate enzymatic activity both in vitro and in vivo.
		and analogy to diacylglycerol, the endogenous activator of PKC, suggest that the binding of bryostatin to PKC could be attributed to substituents at C1, C19, and C26 (boxed in Figure 1), whose orientations are remotely controlled by a lipophilic spacer (shaded in Figure 1).
	pubs.acs.org /cgi-bin/sample.cgi/jacsat/1998/120/i18/html/ja9727631.html (1431 words)

	A Proposed Semi-Synthesis of Bryostatin 1 (Site not responding. Last check: 2007-10-14)
		Valdosta State University, Valdosta, GA Bryostatin 1, one of several members of the bryostatin family, has received FDA approval for treating several types of cancer.
		In addition to poor harvesting yields, laboratory synthesis of bryostatin 1 is complex and expensive resulting in a drug cost of $2.3 million per gram.
		The process involves using acid catalysis for converting alcohols to esters, acid catalysis, addition of acid chlorides, or acetylation to convert carboxyl groups to esters, converting amines into leaving groups, nitrosonium ions for converting amines into leaving groups, and reduction of alcohols with active metals to develop ethers.
	acs.confex.com /acs/56serm/techprogram/P13963.HTM (250 words)

	Clinical Trial: Bryostatin 1 Plus Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed ... (Site not responding. Last check: 2007-10-14)
		Determine the toxic effects and maximum tolerated dose of bryostatin 1 and fludarabine in patients with symptomatic or advanced chronic lymphocytic leukemia or relapsed indolent non-Hodgkin's lymphoma.
		Monitor apoptosis, differentiation, and protein kinase C activity in leukemic lymphocytes exposed in vivo to bryostatin 1 and fludarabine.
		Once the MTD for fludarabine is determined, the dose of bryostatin 1 is escalated.
	clinicaltrials.gov /show/NCT00005580 (488 words)

	Progress in the development and acquisition of anticancer agents from marine sources -- Amador et al. 14 (11): 1607 -- ...
		The action of bryostatin on normal human hematopoietic progenitors is mediated by accessory cell release of growth factors.
		Bryostatin 1 induces apoptosis and augments inhibitory effects of vincristine in human diffuse large cell lymphoma.
		Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60.
	annonc.oupjournals.org /cgi/content/full/14/11/1607 (5385 words)

	Bryostatin-1 and IL-2 Synergize to Induce IFN-{gamma} Expression in Human Peripheral Blood T Cells: Implications for ...
		Bryostatin, a non-phorbol macrocyclic lactone, activates intact human polymorphonuclear leukocytes and binds to the phorbol ester receptor.
		Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1 correlates with the dephosphorylation of cyclin-dependent kinase 2.
		In vivo administration of the anticancer agent bryostatin 1 activates platelets and neutrophils and modulates protein kinase C activity.
	www.jimmunol.org /cgi/content/full/167/9/4828 (6265 words)

	Articles - Bryostatin (Site not responding. Last check: 2007-10-14)
		Bryostatins are a group of macrocyclic lactones first discovered in the late 1960s in a species of bryozoan, Bugula neritina.
		Believed to be produced by symbiont bacteria to protect the bryozoan larva from predation, they have cytotoxic properties and are under investigation as anti-cancer agents.
		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.
	www.poncier.com /articles/Bryostatin (171 words)

	Synergistic induction of apoptosis in human leukemia cells (U937) exposed to bryostatin 1 and the proteasome inhibitor ...
		Comparative effects of polymyxin B, phorbol ester and bryostatin on protein phosphorylation, protein kinase C translocation, phospholipid metabolism and differentiation of HL60 cells.
		Bryostatin 1 and phorbol ester down-modulate protein kinase C-alpha and -epsilon via the ubiquitin/proteasome pathway in human fibroblasts.
		The role of protein kinase C isoenzymes in the growth inhibition caused by bryostatin 1 in human A549 lung and MCF-7 breast carcinoma cells.
	www.bloodjournal.org /cgi/content/full/97/7/2105 (7155 words)

	Biological Sciences / Research / Publication
		Background: Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts.
		Purpose: The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo.
		Implications: The recommended dosage of bryostatin 1 for phase II studies is 25 mug/m2 by intravenous infusion for 1 hour once a week for 3 weeks, with no treatment in the 4th week.
	biology.bangor.ac.uk /research/publication/A1993MG53000010 (375 words)

	News - Bryostatin Less Than Impressive in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma: Presented ...
		Bryostatin Less Than Impressive in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma: Presented at ASH
		evidence of synergy between bryostatin and fludarabine has not been borne out in clinical phase-I studies of the combination in chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (NHL).
		Bryostatin, a cytotoxic agent derived from a single-cell sea organism, has both cytotoxic and immunomodulatory properties in
	www.docguide.com /news/content.nsf/news/8525697700573E1885256C91006DD422 (547 words)

	Clinical Trial: Bryostatin 1 Plus Cladribine in Treating Patients With Relapsed Chronic Lymphocytic Leukemia (Site not responding. Last check: 2007-10-14)
		Determine the maximum tolerated dose of cladribine when administered after bryostatin 1 in patients with relapsed chronic lymphocytic leukemia.
		Patients receive bryostatin 1 IV continuously on days 1-3 immediately followed by cladribine IV continuously on days 4-8.
		Sequential treatment of a resistant chronic lymphocytic leukemia patient with bryostatin 1 followed by 2-chlorodeoxyadenosine: case report.
	clinicaltrials.gov /show/NCT00003174 (577 words)

	Bryostatin 1 Increases 1-beta -D-Arabinofuranosylcytosine-Induced Cytochrome c Release and Apoptosis in Human Leukemia ...
		Bryostatin 1 Increases 1-beta -D-Arabinofuranosylcytosine-Induced Cytochrome c Release and Apoptosis in Human Leukemia Cells Ectopically Expressing Bcl-xL -- Wang et al.
		of bryostatin 1 (e.g., 10 nM), the extent of cell death was not
		B, cells were treated with ara-C + bryostatin 1 (A + B) in the presence or absence of oligomycin (OA+B) as above, after which the percentage of apoptotic cells (left axis; first four bars) or cells exhibiting loss of mitochondrial membrane potential (right axis; last four bars) was determined as described under Materials and Methods.
	jpet.aspetjournals.org /cgi/content/full/301/2/568 (6191 words)

	Clinical Trial: Bryostatin 1 and Cytarabine in Treating Patients With Relapsed Acute Myelogenous Leukemia (Site not responding. Last check: 2007-10-14)
		PURPOSE: Phase II trial to study the effectiveness of combining bryostatin 1 with cytarabine in treating patients who have relapsed primary acute myelogenous leukemia.
		Determine the response rate in patients with primary acute myelogenous leukemia in first relapse treated with bryostatin 1 and high-dose cytarabine.
		Patients who achieve complete remission receive bryostatin 1 IV over 24 hours on days 1 and 10 and high-dose cytarabine IV over 3 hours every 12 hours for 2 infusions on days 2 and 9.
	www.clinicaltrials.gov /ct/gui/show/NCT00017342 (522 words)

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