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Dive into the research topics where Diana L. Brassard is active.

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Featured researches published by Diana L. Brassard.


Journal of Leukocyte Biology | 2002

Interferon-α as an immunotherapeutic protein

Diana L. Brassard; Michael J. Grace; Ronald Bordens

Interferon‐α (IFN‐α) has proven to be a clinically effective antiviral and antineoplastic therapeutic drug for more than 16 years. During this time, evidence from in vitro laboratory studies and the clinical arena has supported the concept that IFN‐α is an immunotherapeutic drug. By regulating a diverse set of cytokines and their receptors, IFN‐α is uniquely positioned to prime the host immune response and provide an effective antineoplastic‐ and antiviral‐immune response. IFN‐α stimulates the innate cell‐mediated response and then participates in the transition of the initial host innate response into an effective adaptive‐immune response. IFN‐α also drives the adaptive cell‐mediated CD8+ T‐cell response and helps to maintain a CD4+ Th1‐cell population balance for an effective antineoplastic and antiviral host defense. This review will describe the current state of knowledge of IFN‐α as an immunoregulatory protein and address specific issues of IFN‐α as an immunotherapeutic for antineoplastic and antiviral diseases.


Journal of Interferon and Cytokine Research | 2001

Structural and Biologic Characterization of Pegylated Recombinant IFN-α2b

Michael J. Grace; Stephen Kenneth Youngster; Gerry Gitlin; Wasyl Sydor; Lei Xie; Louis Westreich; Sheila Jacobs; Diana L. Brassard; James Bausch; Ronald Bordens

The type I interferon-α (IFN-α) family is a family of natural small proteins that have clinically important anti-infective and antitumor activity. We have developed a semisynthetic protein-polymer conjugate of IFN-α2b (Intron® A) by attaching a 12,000-Da monomethoxypolyethylene glycol (PEG-12000) polymer to the protein. PEG conjugation is thought to increase the serum half-life and thereby prolong patient exposure to IFN-α2b without altering the biologic potency to the protein. Matrix-assisted laser desorption ionization/mass spectrometry (MALDI-MS), high-performance size exclusion chromatography (HPSEC), circular dichroism (CD) analysis and tryptic digestion peptide analysis of PEG Intron demonstrated that the IFN-α2b protein was approximately 95% monopegylated and that the primary, the secondary, and the tertiary structures were unaltered. Pegylation did not affect the epitope recognition of antibodies used for Intron A quantitation. An extensive analysis of the pegylated positional isomers revealed tha...


Clinical Therapeutics | 2002

Pegylated Interferons for the Treatment of Chronic Hepatitis C Infection

Bruce A. Luxon; Michael J. Grace; Diana L. Brassard; Ronald Bordens

BACKGROUND Interferon (IFN) alfa is a clinically effective therapy used in a wide range of viral infections and cell-proliferative disorders. Combination therapy with IFN alfa-2b and ribavirin is the current standard of care for the treatment of chronic hepatitis C (CHC) infection. However, standard IFN alfa has the drawbacks of a short serum half-life and rapid clearance. To overcome this problem, 2 pegylated forms of IFN have been developed and tested clinically. OBJECTIVE This article reviews the development and properties of pegylated IFN alfa-2b and pegylated IFN alfa-2a, and presents safety and efficacy data from recent clinical trials. METHODS Relevant clinical studies were identified through a MEDLINE search from 1966 through the present using the key words hepatitis C and interferon. Studies of the pegylated IFNs in humans were then selected. RESULTS Pegylated IFN alfa-2b is formed by covalent conjugation of a 12-kd mono-methoxy polyethylene glycol (PEG) molecule to IFN alfa-2b, and pegylated IFN alfa-2a by covalent conjugation of a 40-kd branched mono-methoxy PEG molecule to IFN alfa-2a. The 2 pegylated IFNs differ in the mixture of pegylation isomers resulting from their conjugation chemistry. Pegylated IFN alfa-2b has a prolonged serum half-life (40 hours) relative to standard IFN alfa-2b (7-9 hours). The greater polymer size of pegylated IFN alfa-2a acts to reduce glomerular filtration, markedly prolonging its serum half-life (72-96 hours) compared with standard IFN alfa-2a (6-9 hours). In clinical studies, once-weekly dosing of the pegylated IFNs was associated with a sustained virologic response in patients infected with hepatitis C virus (HCV). Once-weekly dosing with either of the pegylated IFNs was more effective than the respective thrice-weekly regimen of IFN alfa, with a comparable safety profile. The combination of once-weekly pegylated IFN and ribavirin effectively reduced HCV viral load and sustained viral suppression. CONCLUSIONS Once-weekly dosing with either pegylated IFN alfa-2b or pegylated IFN alfa-2a has been shown to produce significantly higher rates of viral eradication than standard thrice-weekly IFN alfa therapy without compromising safety. With respect to the treatment of CHC, the greatest anti-HCV efficacy has been achieved with the combination of once-weekly pegylated IFN and ribavirin.


Journal of Biological Chemistry | 2002

Transcriptional regulation during p21WAF1/CIP1-induced apoptosis in human ovarian cancer cells.

Qun Wu; Paul Kirschmeier; Tish Hockenberry; Tong-Yuan Yang; Diana L. Brassard; Luquan Wang; Terri McClanahan; Stuart Black; Giovanni Rizzi; Mary Lynn Musco; Asra Mirza; Suxing Liu


Experimental Cell Research | 1999

Integrin αvβ3-Mediated Activation of Apoptosis

Diana L. Brassard; Eugene Maxwell; Michael Malkowski; C. Chandra Kumar; L. Armstrong


Archive | 2000

Methods of inducing cancer cell death and tumor regression

Walter Robert Bishop; Diana L. Brassard; Tattanahalli L. Nagabhushan


Journal of Biological Chemistry | 2005

Site of Pegylation and Polyethylene Glycol Molecule Size Attenuate Interferon- Antiviral and Antiproliferative Activities through the JAK/STAT Signaling Pathway*

Michael J. Grace; Seoju Lee; Sheri Bradshaw; J. R. Chapman; Jeffrey Spond; Stuart Cox; Marc DeLorenzo; Diana L. Brassard; David C. Wylie; Susan Cannon-Carlson; Constance Cullen; Stephen R. Indelicato; Marcio Voloch; Ronald Bordens


Experimental Cell Research | 2002

Inhibitors of farnesyl protein transferase and MEK1,2 induce apoptosis in fibroblasts transformed with farnesylated but not geranylgeranylated H-Ras.

Diana L. Brassard; Jessie M. English; Michael Malkowski; Paul Kirschmeier; Tattanahalli L. Nagabhushan; W. Robert Bishop


publisher | None

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Archive | 2000

Verfahren zur induktion von krebszellentod und tumorregression

Walter Robert Bishop; Diana L. Brassard; Tattanahalli L. Nagabhushan

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