Chronic dissection of the descending thoracic aorta treated by endovascular stent-graft placement... more Chronic dissection of the descending thoracic aorta treated by endovascular stent-graft placement. ... There are no files associated with this item. ... Items in IMSEAR Digital Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Objectivesc-Myc is commonly activated in many human tumors and is functionally important in cellu... more Objectivesc-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein–protein disruptor in mice.MethodsSCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5–1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS.ResultsFollowing a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 μM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4.ConclusionThe lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.
... Corresponding author, e-mail: rocco.mazzeo{at ... Despite limitations due to cost and availab... more ... Corresponding author, e-mail: rocco.mazzeo{at ... Despite limitations due to cost and availability, new approaches with a micro diamond ATR accessory (Coates & Sanders, 2000; Fitzpatrick, 1999) in combination with FTIR imaging (Chan & Kazarian, 2003) appear to be very ...
2007 IEEE International Electron Devices Meeting, 2007
... Abstract We discuss novel multi-level write algorithms for phase change memory which produce ... more ... Abstract We discuss novel multi-level write algorithms for phase change memory which produce highly optimized resistance distributions in a minimum number ofprogram cycles. Using a novel integration scheme, a test array ...
We have successfully demonstrated a novel "pore" phase change memory cell, whose critic... more We have successfully demonstrated a novel "pore" phase change memory cell, whose critical dimension (CD) is independent of lithography. Instead, the pore diameter is accurately defined by intentionally creating a "keyhole" with conformal deposition. Fully integrated 256 kbit test chips have been fabricated in 180nm CMOS technology. We report SET times of 80 ns, RESET currents less than 250 muA,
A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-... more A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-adrenergic activities. The methylnaphthyl analog 5a showed significant selectivity for α 2 -adrenoceptors and behaved as a partial α 1 -agonist in rat aorta preparations. In ...
From the Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute (Drs Shi... more From the Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute (Drs Shivers, Wang, Li, Joseph, Messina, Glass, DeConti, Cruse, Berman, Fenske, and Reintgen), and the Departments of Surgery (Drs Shivers, Wang, Li, Joseph, Cruse, and ...
Chronic dissection of the descending thoracic aorta treated by endovascular stent-graft placement... more Chronic dissection of the descending thoracic aorta treated by endovascular stent-graft placement. ... There are no files associated with this item. ... Items in IMSEAR Digital Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Objectivesc-Myc is commonly activated in many human tumors and is functionally important in cellu... more Objectivesc-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein–protein disruptor in mice.MethodsSCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5–1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS.ResultsFollowing a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 μM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4.ConclusionThe lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.
... Corresponding author, e-mail: rocco.mazzeo{at ... Despite limitations due to cost and availab... more ... Corresponding author, e-mail: rocco.mazzeo{at ... Despite limitations due to cost and availability, new approaches with a micro diamond ATR accessory (Coates & Sanders, 2000; Fitzpatrick, 1999) in combination with FTIR imaging (Chan & Kazarian, 2003) appear to be very ...
2007 IEEE International Electron Devices Meeting, 2007
... Abstract We discuss novel multi-level write algorithms for phase change memory which produce ... more ... Abstract We discuss novel multi-level write algorithms for phase change memory which produce highly optimized resistance distributions in a minimum number ofprogram cycles. Using a novel integration scheme, a test array ...
We have successfully demonstrated a novel "pore" phase change memory cell, whose critic... more We have successfully demonstrated a novel "pore" phase change memory cell, whose critical dimension (CD) is independent of lithography. Instead, the pore diameter is accurately defined by intentionally creating a "keyhole" with conformal deposition. Fully integrated 256 kbit test chips have been fabricated in 180nm CMOS technology. We report SET times of 80 ns, RESET currents less than 250 muA,
A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-... more A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-adrenergic activities. The methylnaphthyl analog 5a showed significant selectivity for α 2 -adrenoceptors and behaved as a partial α 1 -agonist in rat aorta preparations. In ...
From the Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute (Drs Shi... more From the Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute (Drs Shivers, Wang, Li, Joseph, Messina, Glass, DeConti, Cruse, Berman, Fenske, and Reintgen), and the Departments of Surgery (Drs Shivers, Wang, Li, Joseph, Cruse, and ...
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Papers by Ewoi Joseph