5 results on '"pegylated interferon‐beta"'
Search Results
2. Novel pegylated interferon-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer.
- Author
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Iwamura, Tomokatsu, Narumi, Hideki, Suzuki, Tomohiko, Yanai, Hideyuki, Mori, Katsuyuki, Yamashita, Koji, Tsushima, Yoshiaki, Asano, Tomomi, Izawa, Akiko, Momen, Shinobu, Nishimura, Kazumi, Tsuchiyama, Hiromi, Uchida, Masashi, Yamashita, Yuji, Okano, Kiyoshi, and Taniguchi, Tadatsugu
- Abstract
Malignant ascites manifests as an end-stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon-β ( IFN-β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN-β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN-β, each conjugated with a polyethylene glycol molecule ( PEG- hIFN-β and PEG- mIFN-β, respectively). We provide evidence that these IFN-β molecules retain anti-viral potency comparable to unmodified IFN-β in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG- mIFN-β significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG- hIFN-β directly suppresses VEGF
165 -induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG- mIFN-β enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN-β in maintaining vascular integrity, and provide proof-of-mechanism for a novel and long-acting pegylated hIFN-β for the therapeutic treatment of malignant ascites. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
3. Novel pegylated interferon‐β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer
- Author
-
Hideki Narumi, Katsuyuki Mori, Masashi Uchida, Tomohiko Suzuki, Tadatsugu Taniguchi, Yoshiaki Tsushima, Hiromi Tsuchiyama, Tomokatsu Iwamura, Kazumi Nishimura, Kiyoshi Okano, Shinobu Momen, Asano Tomomi, Yamashita Yuji, Akiko Izawa, Koji Yamashita, and Hideyuki Yanai
- Subjects
0301 basic medicine ,Vascular Endothelial Growth Factor A ,Cancer Research ,Pathology ,Cell Membrane Permeability ,Gene Expression ,Vascular permeability ,Mice, SCID ,Polyethylene Glycols ,0302 clinical medicine ,Basic and Clinical Immunology ,Pegylated interferon ,Ascites ,Medicine ,Anti‐tumor activity ,5'-Nucleotidase ,Cells, Cultured ,Peritoneal Neoplasms ,pegylated interferon‐beta ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Mice, Inbred BALB C ,General Medicine ,Oncology ,030220 oncology & carcinogenesis ,peritoneal metastasis ,Area Under Curve ,Original Article ,medicine.symptom ,vascular hyperpermeability ,medicine.drug ,medicine.medical_specialty ,Metabolic Clearance Rate ,Mice, Nude ,Antiviral Agents ,03 medical and health sciences ,In vivo ,Cell Line, Tumor ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Cell adhesion ,business.industry ,Cancer ,malignant ascites ,Original Articles ,Interferon-beta ,medicine.disease ,Xenograft Model Antitumor Assays ,In vitro ,Mice, Inbred C57BL ,030104 developmental biology ,Cancer research ,business ,Ovarian cancer - Abstract
Malignant ascites manifests as an end-stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon-β (IFN-β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN-β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN-β, each conjugated with a polyethylene glycol molecule (PEG-hIFN-β and PEG-mIFN-β, respectively). We provide evidence that these IFN-β molecules retain anti-viral potency comparable to unmodified IFN-β in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG-mIFN-β significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG-hIFN-β directly suppresses VEGF165 -induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG-mIFN-β enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN-β in maintaining vascular integrity, and provide proof-of-mechanism for a novel and long-acting pegylated hIFN-β for the therapeutic treatment of malignant ascites.
- Published
- 2017
4. [The pegylated form of interferon beta in the treatment of multiple sclerosis].
- Author
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Melnikov MV, Kasatkin DS, Volkov AI, and Boyko AN
- Subjects
- Glatiramer Acetate therapeutic use, Humans, Injections, Subcutaneous, Interferon-beta therapeutic use, Multiple Sclerosis drug therapy
- Abstract
Interferons-beta (IFN-β) along with glatiramer acetate is one of the most commonly used disease modifying treatment (DMT) of multiple sclerosis (MS) associated with effectiveness and acceptable safety profile. At the same time, therapy with IFN-β has a number of limitations associated with a high frequency of injections and production of neutralizing antibodies. The development of the pegylated form of IFN-β (PEG-IFN-β) is aimed at resolving these issues. This article reviewed the mechanism of action, efficacy, safety and tolerability of PEG-IFN-β in the treatment of MS.
- Published
- 2019
- Full Text
- View/download PDF
5. Pharmacological Changes Induced by Administration of PEGylated IFNbeta-1a in Healthy Volunteers
- Author
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Miller, Larisa, Lerner, Michaela, Crossman, Mary, Hitchman, Stacy, Davar, Gudarz, and Subramanyam, Meena
- Subjects
Pharmacology ,biomarker ,PEGylated interferon-beta - Abstract
Background: PEGylated interferon beta-1a (PEG-IFN beta-1a) is being developed to address the significant unmet need for safe, effective, and convenient therapies for patients with relapsing multiple sclerosis (RMS). The phase 3 ADVANCE study is currently enrolling RMS patients with the goal of evaluating the safety and efficacy of PEG-IFN beta-1a (125 μg) administered once every 2 or 4 weeks. An increase in IL-10 mRNA levels and decrease in IL-23 mRNA levels in peripheral blood mononuclear cells from IFN beta-treated MS patients have been reported previously. We further explored the modulatory role of IFN beta-1a on the newly defined Th17 subset of CD4(+) T cells, which have been shown to be involved in mediating inflammatory responses in autoimmune disorders like RMS. Objective: To measure pharmacological response to IFN beta-1a and PEG-IFN beta-1a related to Th17 regulatory network in genomic samples from healthy volunteers. Methods: Whole blood RNA samples were collected from healthy volunteers enrolled in a phase 1 clinical study of PEG-IFN beta-1a, in which single doses of subcutaneous (SC) PEG-IFN beta-1a were administered at 3 dose levels and compared with intramuscular (IM) IFN beta-1a. Expression of 84 genes related to the Th17 regulatory pathway was probed before and after dosing of PEG-IFN beta-1a or IM IFN beta-1a. Purified RNA was reverse transcribed and tested in the RT2 Profiler PCR Array (SA Biosciences). Molecules analyzed at the mRNA level included cell surface proteins, chemokines, cytokines, cytokine receptors, and IFN beta-related signaling pathway molecules and transcriptional factors. Statistical significance was computed to understand the key players involved in mediating IFN beta-1a pharmacology. Results: Meaningful changes in the levels of many IFN-dependent gene transcripts (SOCS1, ISG20, JAK2) were detected, thus validating the sensitivity of the experimental analysis system. Significant upregulation of the IL-10 transcript, which has been linked to the likely shift to Th2-dominated response from a predominantly Th1 response, was observed in all groups. Modest IL-23A upregulation and significant chemokine (CCL1, CCL2, CCL7) upregulation were also observed. Conclusion: Use of similar PCR array in future studies to monitor the pharmacological effects of PEG-IFN beta-1a in RMS patients may enable better understanding of its molecular mechanisms of action and help to identify new biomarkers of efficacy for this therapeutic approach.
- Published
- 2010
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