Mason W.P.,University of Toronto |
Belanger K.,Hopital Notre Dame |
Nicholas G.,Ottawa Hospital Regional Cancer Center |
Vallieres I.,Hotel Dieu de Quebec |
And 5 more authors.
Journal of Neuro-Oncology | Year: 2012
This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the RasMAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study. TLN4601 was administered at a dose of 480 mg/m2/day by continuous intravenous (CIV) administration. Each 21-day cycle consisted of a 14-day CIV administration and a 7-day recovery period. Samples were obtained from all patients for pharmacokinetic evaluations (PK) and for Raf1 and pERK biomarker assessment using immunohistochemistry and flow cytometry. Following enrollment of 20 patients, this study was terminated due to a lack of efficacy. Of 17 evaluable patients, 14 had MR scans performed after two cycles of TLN-4601. Of these 14 patients, three had stable disease and 11 had disease progression. Only three patients had MR scans performed after four cycles and all had evidence of radiographic progression. Serum PKs confirmed that patients were exposed to TLN-4601 at targeted drug levels. TLN-4601 was generally well tolerated although two patients discontinued treatment due to adverse events. Biomarker analysis did not show consistent changes. TLN-4601 infused via CIV at 480 mg/m2/day for 14 of 21 days is well tolerated by patients with progressive GBM. However, this agent is ineffective in progressive GBM when administered as monotherapy in this schedule. © Springer Science+Business Media, LLC. 2011. Source
Bitzan M.,McGill University |
Schaefer F.,University of Heidelberg |
Reymond D.,Thallion Pharmaceuticals Inc.
Seminars in Thrombosis and Hemostasis | Year: 2010
Typical enteropathic HUS (eHUS) is triggered by Shiga toxin (Stx)-producing bacteria (STPB), predominantly Stx-producing Escherichia coli O157. The cell biological aspects of Stx have been well defined, but host factors potentially predisposing to the development or severity of HUS remain elusive. Treatment of eHUS includes supportive measures and invasive extracorporeal therapies. Thirty to 60% of children with eHUS require dialysis. Peritoneal and hemodialysis appear equally effective. Patient age, center experience, and equipment availability determine the choice of the modality; circulatory instability may require continuous renal replacement therapies. At present, no evidence indicates that plasma infusion or exchange therapies improve outcome of Stx-induced HUS. However, the traditional separation between diarrhea-positive (D +) and negative (D -) HUS, implying two entirely different pathological pathways, requires a fresh look: Atypical HUS may follow nonspecific diarrhea, and, conversely, STPB and fecal Stx may not be detected anymore at the time of the diagnosis of HUS. Recently, Stx has been found to directly interfere with the alternative complement pathway regulator factor H in vitro, whereas some patients with Stx-HUS demonstrate evidence of complement activation. Among newer treatments for eHUS, development of Stx-neutralizing monoclonal antibodies is the most advanced. This review concludes with a discussion of the rationale, mode of action, and status of presently available therapeutic antibodies against Stx2 and Stx1. Copyright © 2010 by Thieme Medical Publishers, Inc. Source
Gao H.Y.,McGill University |
Yaylayan V.A.,McGill University |
Yeboah F.,Thallion Pharmaceuticals Inc.
Journal of Agricultural and Food Chemistry | Year: 2010
The role of selected carboxylic acids and their potential to influence the glycation pattern and the enzymatic activity of lysozyme using glucose and ribose were investigated independently of the pH of the reaction medium. The model systems were incubated with and without selected carboxylic acids (maleic, acetic, oxalic, and citraconic) at 50 °C for 12 or 24 and 48 h at constant pH of 6.5. The effect of carboxylic acids on the glycation of lysozyme was studied by electrospray ionization mass spectrometry (ESI-MS) and by the measurement of the residual enzyme activity of lysozyme in the glycated samples. Of the carboxylic acids evaluated, oxalic acid showed the highest antiglycation activity. The residual lysozyme activity in both oxalic acid-glucose and oxalic acid-ribose systems was >80% compared with 46 and 36% activity in the controls of glucose and ribose systems, respectively. On the other hand, maleic, acetic, and citraconic acid containing systems with both sugars did not exhibit any enhanced enzyme activity relative to the controls. The results of this study show that oxalic acid was unique among the carboxylic acids evaluated with respect to its ability to interact with sugars and inhibit glycation. © 2010 American Chemical Society. Source
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc and Thallion Pharmaceuticals Inc. | Date: 2012-03-06
The invention features methods, compositions, and kits for treating a subject having a Shiga toxin associated disease with chimeric anti-Shiga Toxin 1 (cStx1) and anti-Shiga Toxin 2 (cStx2) antibodies.
Thallion Pharmaceuticals Inc. | Date: 2010-04-21
The present invention provides a scalable process for producing a concentrate containing a mass of a farnesylated dibenzodiazepinone by fermenting in an aqueous culture medium a strain of a microorganism that is capable of producing the farnesylated dibenzodiazepinone, upon completion of fermentation harvesting the fermentation broth and extracting the fermentation broth to provide an extract, and thereafter treating the extract to form the concentrate. The concentrate so produced may be utilized in downstream processes for producing pharmaceutical compounds. A strain of a