			Home About us Contact

Human IFN (human + ifn)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Recombinant Human ,-Interferon Produced from CHO-SS Cells

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2006
Victor E. Buckwold
Here we provide an overview of our preclinical safety evaluation of the fully-glycosylated human IFN-, produced from CHO-SS cells that is currently being evaluated clinically. IFN-, was not associated with any biologically-relevant adverse effects in a series of 10 safety pharmacology experiments, in the Ames mutagenicity test, in the micronucleus test, or in intraarterial, intravenous, paravenous or subcutaneous local tolerance studies. Acute, subacute, subchronic and reproductive toxicity studies performed in cynomolgus monkeys and rats showed a toxicity profile similar to that of human , interferon (IFN-,). Except for the acute (single-dose) toxicology study, all of the other toxicity studies showed evidence for the formation of anti-IFN-, antibodies over time in the animals. These antibodies were found to neutralize IFN-, antiviral activity in vitro in a dose-dependent manner. The average pharmacokinetic parameters following a single subcutaneous dose of IFN-, in rabbits, rats and monkeys were determined and found to be similar to that of human IFN-,. These findings demonstrate that IFN-, has a safety profile consistent with that required for its use in man. IFN-, might be beneficial for the treatment of patients infected with hepatitis C virus who fail to respond to IFN-, or as a first-line treatment option. [source]

Association of interferon-, +874A polymorphism with the risk of developing cervical cancer in north-Indian population

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2009
R Gangwar
Objective, Interferon gamma (IFN -,) is a pro-inflammatory cytokine playing a pivotal role in both innate and adaptive immune responses. A single nucleotide polymorphism located in the first intron of the human IFN-, gene can influence the secretion of cytokine. Therefore, we aimed to investigate the association of IFN-, T/A gene polymorphism with the risk of cervical cancer. Design, Case,control study. Setting, Uttar Pradesh State in India. Sample, Two hundred cases with histologically proven cancer of the cervix and healthy controls (n = 230), age and ethnicity matched were recruited in this study. Methods, Genotyping was performed for bi-allelic +874 (T/A) polymorphism of IFN-, by amplification refractory mutation system method. Main outcome measures, Low producer IFN-, +874 AA genotype was associated with high risk for cervical cancer, which further modulated the increased risk in tobacco users. Results,IFN-, AA genotype which is low producer of IFN-, was associated with increased risk of cervical cancer (OR = 2.43, P = 0.003). Allele A was at 1.54-fold increased risk of cervical cancer (OR=1.54, P = 0.002). The AA genotype showed statistically significant risk with high stage (III + IV) of cervical cancer (OR = 4.99, P = 0.001). In tobacco users, AA genotype showed significantly increased susceptibility to cervical cancer (OR = 5.08, P = 0.010). Conclusion, Variation in IFN-, +874 AA genotype because of ethnicity in north-Indian population may represent an important susceptibility biomarker for cervical cancer risk as well as other diseases and should be explored further. [source]

Homozygosis for (12) CA repeats in the first intron of the human IFN- , gene is significantly associated with the risk of aplastic anaemia in Caucasian population

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004
Carlo Dufour
Summary Interferon- , (IFN- ,) mediates the final damage of the stem cell compartment in Aplastic Anaemia (AA). Normal subjects homozygous for 12 (CA) repeats of polymorphism variable number of dinucleotide (CA) repeat (VNDR) in position 1349 of the IFN- , gene (IFNG) were shown to overproduce IFN- ,in vitro. We studied the distribution of polymorphism VNDR 1349 of IFNG in 67 Caucasian AA patients and in normal controls. Genotype (CA)12-12, (homozygosis for allele 2) and the single allele 12 were significantly more frequent (P = 0·005 and 0·004 respectively) in patients versus controls. The polymorphism was equally distributed in AA patients regardless of their response to immunosuppression. Homozygosity for 12 (CA) repeats of polymorphism VNDR 1349 of IFNG is strongly associated with the risk of AA in Caucasian subjects. [source]

Local interferon-, gene therapy elicits systemic immunity in a syngeneic pancreatic cancer model in hamster

CANCER SCIENCE, Issue 3 2007
Hidehiko Hara
The interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis and immunomodulation. We previously examined the two antitumor mechanisms, taking advantage of the fact that IFN-, did not show cross-species activity in its in vivo effect. In a nude mouse subcutaneous xenograft model using human pancreatic cancer cells, the expression of human IFN-, effectively induced cell death of human pancreatic cancer cells, whereas mouse IFN-, augmented antitumor immunity by stimulation of natural killer cells. Here, we extended our investigation to a syngeneic pancreatic cancer model, so that the integrated antitumor activity of local IFN-, gene therapy, including the antiproliferative, proapoptotic, antiangiogeneic and immunomodulatory effects, can be evaluated rigorously. When a recombinant hamster IFN-, adenovirus was injected into syngeneic subcutaneous tumors of hamster pancreatic cancer (PGHAM-1) cells in Syrian hamster, tumor growth was significantly suppressed due to cell death and T cell- and natural killer cell-mediated antitumor immunity. Moreover, in this case, tumor regression was observed not only for the injected subcutaneous tumors but also for the untreated tumors both in the peritoneal cavity and at distant sites. No significant systemic toxicity was observed in the treated hamsters. Moreover, the subcutaneous rechallenge of PGHAM-1 cells was rejected in three of four cured hamsters from the initial tumor challenge. This study further demonstrated that local IFN-, gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its multiple mechanisms of antitumor activity and its lack of significant toxicity. (Cancer Sci 2007; 98: 455,463)) [source]