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An NCIC CTG phase I/pharmacokinetic study of the matrix metalloproteinase and angiogenesis inhibitor BAY 12-9566 in combination with 5-fluorouracil/leucovorin.

https://arctichealth.org/en/permalink/ahliterature177577
Source
Invest New Drugs. 2005 Jan;23(1):63-71
Publication Type
Article
Date
Jan-2005
Author
R. Goel
E. Chouinard
D J Stewart
S. Huan
H. Hirte
S. Stafford
B. Waterfield
J. Roach
C. Lathia
V. Agarwal
R. Humphrey
W. Walsh
S. Matthews
L. Seymour
Author Affiliation
Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada. rgoel@ottawahospital.on.ca
Source
Invest New Drugs. 2005 Jan;23(1):63-71
Date
Jan-2005
Language
English
Publication Type
Article
Keywords
Angiogenesis Inhibitors - pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Canada
Cohort Studies
Colorectal Neoplasms - blood supply - metabolism
Dose-Response Relationship, Drug
Female
Fluorouracil - administration & dosage
Humans
Kidney Neoplasms - blood supply - metabolism
Leucovorin - administration & dosage
Liver Neoplasms - blood supply - metabolism
Lung Neoplasms - blood supply - metabolism
Lymphatic Metastasis - pathology
Male
Matrix Metalloproteinase Inhibitors
Maximum Tolerated Dose
Organic Chemicals - administration & dosage
Safety
Salvage Therapy
Abstract
This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12-9566 in combination with 5-fluorouracil/leucovorin in patients with advanced solid tumours, and to identify the maximum tolerated dose and the dose for use in future studies.
BAY 12-9566 and 5-fluorouracil/leucovorin were administered to 17 patients in 3 cohorts. Each patient served as his/her own control, with 5-fluorouracil being given alone on days 1-5 of cycle 1. In cohort 1, BAY 12-9566 at 800 mg p.o. b.i.d. was given with 350 mg/m2 5-fluorouracil/20 mg/m2 leucovorin x 5 days q28 days. In cohort 2, the BAY 12-9566 dose was reduced to 400 mg p.o. b.i.d., with the 5-fluorouracil/leucovorin doses remaining unchanged. Finally, in cohort 3, BAY 12-9566 400 mg bid was given with 5-fluorouracil 400 mg/m2/day. Patients were continued on therapy until unacceptable toxicity or tumour progression occurred. Pharmacokinetic analyses for both BAY 12-9566 and 5-fluorouracil were performed.
The maximum tolerated dose was 400 mg p.o. b.i.d. BAY 12-9566 plus 5-fluorouracil/leucovorin at 400 mg/m2/day and 20 mg/m2/day, respectively. Thrombocytopenia necessitated a decrease of the dose of BAY 12-9566 by 50% from cohort 1 to cohort 2. Two dose-limiting toxicities occurred in cohort 3 consisting of neutropenic fever, and ileitis, causing severe diarrhea. Of 17 patients treated on study, 7 of 14 patients evaluable for response achieved stable disease. Pharmacokinetic analysis suggested there was no interaction between BAY 12-9566 and 5-fluorouracil.
BAY 12-9566 400 mg bid and 5-fluorouracil 350 mg/m2 plus leucovorin 20 mg/m2 can be co-administered. Although there is some evidence of a clinical interaction, there is no apparent pharmacokinetic interaction. Future studies with these 2 types of agents administered in combination are warranted.
PubMed ID
15528982 View in PubMed
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Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria.

https://arctichealth.org/en/permalink/ahliterature142063
Source
Malar J. 2010;9:208
Publication Type
Article
Date
2010
Author
Mario Dell'agli
Germana V Galli
Michela Bulgari
Nicoletta Basilico
Sergio Romeo
Deepak Bhattacharya
Donatella Taramelli
Enrica Bosisio
Author Affiliation
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti, 9 - 20133 Milano, Italy. mario.dellagli@unimi.it
Source
Malar J. 2010;9:208
Date
2010
Language
English
Publication Type
Article
Keywords
Antimalarials - pharmacology
Biological Assay
Ellagic Acid - pharmacology
Fruit
Gene Expression Regulation - drug effects
Hemeproteins - analysis
Humans
Hydrolyzable Tannins - pharmacology
Inflammation - drug therapy
Malaria, Cerebral - drug therapy
Matrix Metalloproteinase 9 - drug effects - metabolism - secretion
Matrix Metalloproteinase Inhibitors
NF-kappa B - drug effects - physiology
Phytotherapy
Plant Extracts - chemistry - pharmacology
Punicaceae - chemistry
RNA, Messenger - analysis - drug effects
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha - physiology
Up-Regulation
Abstract
The sun-dried rind of the immature fruit of pomegranate (Punica granatum) is presently used as a herbal formulation (OMARIA, Orissa Malaria Research Indigenous Attempt) in Orissa, India, for the therapy and prophylaxis of malaria. The pathogenesis of cerebral malaria, a complication of the infection by Plasmodium falciparum, is an inflammatory cytokine-driven disease associated to an up-regulation and activity of metalloproteinase-9 and to the increase of TNF production. The in vitro anti-plasmodial activity of Punica granatum (Pg) was recently described. The aim of the present study was to explore whether the anti-malarial effect of OMARIA could also be sustained via other mechanisms among those associated to the host immune response.
From the methanolic extract of the fruit rind, a fraction enriched in tannins (Pg-FET) was prepared. MMP-9 secretion and expression were evaluated in THP-1 cells stimulated with haemozoin or TNF. The assays were conducted in the presence of the Pg-FET and its chemical constituents ellagic acid and punicalagin. The effect of urolithins, the ellagitannin metabolites formed by human intestinal microflora, was also investigated.
Pg-FET and its constituents inhibited the secretion of MMP-9 induced by haemozoin or TNF. The effect occurred at transcriptional level since MMP-9 mRNA levels were lower in the presence of the tested compounds. Urolithins as well inhibited MMP-9 secretion and expression. Pg-FET and pure compounds also inhibited MMP-9 promoter activity and NF-kB-driven transcription.
The beneficial effect of the fruit rind of Punica granatum for the treatment of malarial disease may be attributed to the anti-parasitic activity and the inhibition of the pro-inflammatory mechanisms involved in the onset of cerebral malaria.
Notes
Cites: Anal Biochem. 1976 May 7;72:248-54942051
Cites: Science. 1976 Aug 20;193(4254):673-5781840
Cites: Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):325-91988933
Cites: FEBS Lett. 1998 Sep 11;435(1):29-349755853
Cites: Int J Cancer. 2005 Jan 20;113(3):423-3315455341
Cites: J Immunol. 2005 Jan 1;174(1):475-8415611273
Cites: Photochem Photobiol. 2005 Jan-Feb;81(1):38-4515493960
Cites: J Nutr. 2005 Sep;135(9):2096-10216140882
Cites: J Immunol. 2005 Nov 15;175(10):6436-4216272296
Cites: Cell Mol Life Sci. 2005 Dec;62(23):2896-90316314917
Cites: J Ethnopharmacol. 2006 Feb 20;103(3):311-816221534
Cites: J Agric Food Chem. 2006 Feb 8;54(3):980-516448212
Cites: Lab Invest. 2006 Sep;86(9):873-8816865090
Cites: J Nutr. 2006 Oct;136(10):2481-516988113
Cites: Malar J. 2006;5:8517029647
Cites: J Agric Food Chem. 2006 Nov 15;54(23):8956-6117090147
Cites: Altern Med Rev. 2008 Jun;13(2):128-4418590349
Cites: J Med Food. 2008 Jun;11(2):390-418598186
Cites: Malar J. 2008;7:15718710562
Cites: Antimicrob Agents Chemother. 2009 Feb;53(2):622-3019015351
Cites: Cancer Res. 2009 Feb 15;69(4):1502-819208844
Cites: Antimicrob Agents Chemother. 2009 Mar;53(3):1100-619015354
Cites: J Ethnopharmacol. 2009 Sep 7;125(2):279-8519577622
Cites: J Agric Food Chem. 2010 Feb 24;58(4):2246-5220102205
Cites: J Nutr Biochem. 2010 Aug;21(8):717-2519616930
Cites: Am J Chin Med. 1999;27(3-4):371-610592846
Cites: J Nat Prod. 2001 May;64(5):603-711374952
Cites: J Ethnopharmacol. 2001 Nov;78(1):85-711585693
Cites: Cell Mol Life Sci. 2003 Jul;60(7):1440-812943230
Cites: Cell Mol Life Sci. 2003 Aug;60(8):1623-3514504653
Cites: J Immunol. 2003 Oct 15;171(8):4243-5314530348
Cites: Parassitologia. 2003 Dec;45(3-4):135-4015267101
Cites: Infect Immun. 2004 Aug;72(8):4868-7315271950
Cites: Eur J Nutr. 2004 Aug;43(4):205-2015309440
Cites: Clin Chim Acta. 2004 Oct;348(1-2):63-815369737
Cites: J Immunol Methods. 1986 May 22;89(2):271-73486233
PubMed ID
20642847 View in PubMed
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[Recent studies on anti-angiogenesis in cancer therapy].

https://arctichealth.org/en/permalink/ahliterature197538
Source
Nihon Rinsho. 2000 Aug;58(8):1747-62
Publication Type
Article
Date
Aug-2000
Author
K. Kishi
L. Milas
N. Hunter
M. Sato
Author Affiliation
Department of Radiology, Wakayama Medical College.
Source
Nihon Rinsho. 2000 Aug;58(8):1747-62
Date
Aug-2000
Language
Japanese
Publication Type
Article
Keywords
Angiogenesis Inhibitors - pharmacology - therapeutic use
Animals
Antineoplastic Agents - therapeutic use
Combined Modality Therapy
Cyclooxygenase Inhibitors - therapeutic use
Endothelial Growth Factors - antagonists & inhibitors - physiology
Humans
Lymphokines - antagonists & inhibitors - physiology
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases - physiology
Neoplasms - blood supply - therapy
Neovascularization, Pathologic
Pyrazoles - therapeutic use
Radiotherapy
Sulfonamides - therapeutic use
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Abstract
Angiogenesis is known to be a critical process for the tumor growth and metastasis. There are many indigenous role-players in tumor angiogenesis and anti-angiogenesis, where tumor-host interaction may work. A lot of agents with anti-angiogenic activity have been developed for anti-cancer treatment. Several agents including Marimastat, Primostat, Neovastat, Bay-12-9566m, Interferon-alpha, SU101, retinoids, and IM862, are/were under phase-three study. There are still many future-promising results of basic or clinical studies on inhibitors of MMPs, and inhibitors of VEGF/R, Endostatin, somatostatin analogues, COX-2 inhibitors, and others. Most of the combination treatments of antiangiogenetic agent and conventional anticancer agents therapy, or radiation therapy as we reported, showed relatively small or minute increase in toxicity of these cytotoxic treatments.
PubMed ID
10944947 View in PubMed
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