Search

Purpose: To elucidate the efficacy and safety profile of interferon α‑2b in vernal keratoconjunctivitis (VKC). Methods: In this prospective interventional study, VKC patients fulfilling the inclusion and exclusion criteria were included and their signs and symptoms were scored based on the Clinical Scoring System. Patients were treated with topical interferon α‑2b eye drop (1 MIU/ml) QID dosing for 6 weeks. Changes in symptoms and signs were evaluated at 2, 4, 8 weeks and 6 months after initiating treatment. A higher score meant severe disease, and a decline in score meant improvement in clinical signs and symptoms. Categorical variables were presented in number and percentage (%) and continuous variables as mean ± standard deviation (SD). Post‑medication total subjective symptom score (TSSS) and total objective sign score (TOSS) were compared with baseline, and a P- value of <0.05 was considered significant. Possible ocular and systemic complications were evaluated. Results: The study included 40 patients (32 male and eight female) with a mean age of 8.05 ± 2.33 years. Mean baseline TSSS and TOSS were 6.71 ± 0.564 and 6.59 ± 0.262, respectively, which reduced to 2.71 ± 0.011 (P = 0.040) and 2.96 ± 0.210 (P = 0.032), respectively, at 4 weeks and further reduced to 0.42 ± 0.552 and 0.47 ± 0.434, respectively, at 8 weeks. After 6 months of stopping the drug, mean TSSS and TOSS did increase to 2.80 ± 0.820 (P = 0.044) and 2.50 ± 0.520 (P = 0.030), respectively, but was still statistically significant improvement compared to the baseline. Also, no ocular or systemic side effects were observed anytime during the study period. Conclusion: Eye drop interferon α‑2b (1 million IU/ml) is a safe and effective option as first‑line monotherapy for VKC. No side effects and recurrence were observed for 6 months. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the efficacy and safety profile of interferon α-2b in vernal keratoconjunctivitis (VKC). Methods: In this prospective interventional study, VKC patients fulfilling the inclusion and exclusion criteria were included and their signs and symptoms were scored based on the Clinical Scoring System. Patients were treated with topical interferon α-2b eye drop (1 MIU/ml) QID dosing for 6 weeks. Changes in symptoms and signs were evaluated at 2, 4, 8 weeks and 6 months after initiating treatment. A higher score meant severe disease, and a decline in score meant improvement in clinical signs and symptoms. Categorical variables were presented in number and percentage (%) and continuous variables as mean ± standard deviation (SD). Post-medication total subjective symptom score (TSSS) and total objective sign score (TOSS) were compared with baseline, and a P- value of

Abstract Purpose Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. Methods Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. Results Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p 0.05). No serious adverse effects were reported. Conclusions Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .

Ocular surface squamous neoplasia (OSSN) is a broad pathological entity that includes squamous neoplasm of conjunctival and corneal tissue. These various malignancies include conjunctival intraepithelial neoplasia (CIN), corneal epithelial dysplasia, squamous cell carcinoma (SCC), and mucoepidermoid carcinoma. OSSN diagnosis rests on exfoliative cytology, vital dyes, and imaging in the form of confocal microscopy and anterior segment optical coherence tomography. The medical management modalities are topical chemotherapy (Mitomycin C and 5 fluorouracil), immunotherapy (Interferon alpha 2b), and upcoming drugs, such as antivirals, anti-VEGF, and retinoic acid. Excision biopsy with no touch technique remains the gold standard for managing OSSN. However, surgery can lead to recurrence and unfavorable results in some cases. This article provides insights into the treatment aspects of OSSN with an overview of recent updates. The authors have discussed the current concept regarding the medical and surgical management of OSSN. The authors also dwell upon the recent updates along with the expert opinion. Although surgery remains the gold standard, topical drugs have revolutionized the management of OSSN. Patients should be closely followed up to look for any side effects. Cost, time duration, cosmesis, and side are the remaining major factors in deciding for medical versus surgical therapy. [ABSTRACT FROM AUTHOR]

Purpose: Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. Methods: Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. Results: Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported. Conclusions: Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN. [ABSTRACT FROM AUTHOR]

When primary acquired melanosis (PAM) with atypia affects the tarsal conjunctiva, a radical surgery can be mutilating, requiring reconstructive surgery of the eyelid. Topical chemotherapy associated to local cryotherapy may be an alternative. A 64-year-old Caucasian female presented with diffuse PAM of the right eye involving the inferior tarsal conjunctiva, fornix, and inferotemporal bulbar conjunctiva. Histological study showed a PAM with atypia (C-MIN 5). Given the extent of the lesion and its location, a wide mutilating excision was ruled out. Topical interferon alpha 2b (IFN-α2b) treatment (1,000,000 IU/mL, 4 times a day) was administered during 10 weeks. However, the regression was very slow. Then local cryotherapy was proposed (8 s at −80°C per application) to the entire pigmented lesion. This afforded progressive depigmentation, which was completed 2 months later. No recurrence of the lesion has been noted during 3 years of follow-up. The combination of the two procedures reduces IFN-α2b eyedrop administration time, enhancing patient compliance. The combination may eradicate the tumor without compromising ocular cosmesis.

Purpose: We herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM). Methods: We included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone. Five patients were switched from initial MMC/radiotherapy to IFN-α2b during follow-up. Efficacy was assessed via time to tumor recurrence and initial therapy response. Results: With initial IFN-α2b, three patients (3/4, two with additional radiotherapy) showed complete remission (follow-up: 1478–1750 days) and one recurrence (1/4) was noted after 492 days. With initial MMC, no recurrence was recorded in 15 of the 19 patients (follow-up: 99–4732 days). Five patients were switched from MMC or radiotherapy to IFN-α2b: two patients showed complete remission (2/5), while another two (2/5) experienced recurrences and remained without recurrence after repeated courses of IFN-α2b (follow-up: 1798 and 1973 days). Only one patient showed incomplete response. Adverse effects were recorded in five patients, all received MMC. Conclusion: Topical IFN-α2b (arguably together with radiotherapy) may be a viable alternative to MMC in PAM and CM. We observed fewer side effects at similar response rates. However, when response to MMC was poor, IFN-α2b may also be of limited utility. [ABSTRACT FROM AUTHOR]

When primary acquired melanosis (PAM) with atypia affects the tarsal conjunctiva, a radical surgery can be mutilating, requiring reconstructive surgery of the eyelid. Topical chemotherapy associated to local cryotherapy may be an alternative. A 64-year-old Caucasian female presented with diffuse PAM of the right eye involving the inferior tarsal conjunctiva, fornix, and inferotemporal bulbar conjunctiva. Histological study showed a PAM with atypia (C-MIN 5). Given the extent of the lesion and its location, a wide mutilating excision was ruled out. Topical interferon alpha 2b (IFN-α2b) treatment (1,000,000 IU/mL, 4 times a day) was administered during 10 weeks. However, the regression was very slow. Then local cryotherapy was proposed (8 s at −80°C per application) to the entire pigmented lesion. This afforded progressive depigmentation, which was completed 2 months later. No recurrence of the lesion has been noted during 3 years of follow-up. The combination of the two procedures reduces IFN-α2b eyedrop administration time, enhancing patient compliance. The combination may eradicate the tumor without compromising ocular cosmesis. [ABSTRACT FROM AUTHOR]

Primary acquired melanosis (PAM) is acquired conjunctival pigmentation that can give rise to conjunctival melanoma (CM), a malignant tumor of the bulbar and palpebral conjunctiva or the caruncle. Surgical excision is the treatment of choice for this neoplasm. Topical chemotherapy is also used for patients with PAM with atypia or CM and, in patients with recurrent or extensive disease, this may be an important option. Of the several chemotherapeutic drugs used, topical interferon alpha 2b (IFN-α2b) has become popular because of its low toxicity. Clinical evidence from case reports and case series supports the efficacy of IFN-α2b as the preferred adjuvant treatment for PAM and CM. In addition, topical IFN-α2b has been successfully applied to melanocytic tumors refractory to other treatments, such as cryotherapy and topical mitomycin C. In patients with locally advanced CM, the combination of IFN-α2b and systemic immunotherapy may serve as an alternative to exenteration. Given the low frequency of CM, long-term multicenter studies are needed to demonstrate the efficacy of IFN-α2b for preventing local recurrence and distant metastasis. [ABSTRACT FROM AUTHOR]

The article presents a literature review, which provides data on the role of interferons in the immunopathogenesis of COVID-19 and the clinical efficacy of drugs based on recombinant interferon-alpha 2b in the treatment of children with new coronavirus infection. Shown the leading role ofinterferons as factors of the first line of defense against various viruses, including SARS-CoV-2. Numerous studies have proven the feasibility of including interferon preparations in COVID-19 therapyregimens in children, both as combinations with antiviral agents and as monotherapy.

BACKGROUND: To evaluate the role of interferon alpha 2b (IFNα2b) in the management of primary/recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: Medical records of 27 OSSN cases managed with IFNα2b (topical drops and/or perilesional injection) in 1 year were retrospectively reviewed. RESULTS: The median age of presentation was 60 years with a male: female ratio of 3.5:1. American Joint Commission on Cancer tumor grading was T1 in 1 eye (3.7%) and T3 in 26 eyes (96.3%). Eighteen cases were treated with topical drops (1 million IU/ml), 4 cases with perilesional subconjunctival injection (3–6 million IU/ml), and 5 cases with combined therapy. Overall, treatment response was seen in 88% cases. Complete regression was achieved in 80% cases. Median time to complete regression of tumor was 3 months (range 1–11 months) in cases treated with topical interferon therapy and 2.5 months (range 0.7–3 months) in cases managed with injections or a combination of the two. The mean duration of follow-up was 24 months. All cases with partial/no response showed complete regression on subsequent management with topical mitomycin C. None of the patients required surgery. Acute ocular surface congestion was seen in two patients necessitating discontinuation of therapy. CONCLUSION: In view of excellent treatment outcome and few side-effects, interferons can be considered as a primary, safe, and cost-effective treatment option for OSSN not only in tertiary centers but also by peripheral ophthalmologists.

Management of ocular surface squamous neoplasia (OSSN) has been a matter of debate among ocular oncologists. While surgical excision with tissue biopsy has been the gold standard, topical chemotherapy with agents such as interferon-α2b, 5-fluorouracil, and mitomycin C, as well as less invasive diagnostic modalities, are becoming increasingly popular. This report provides a comprehensive review of recent data and addresses the key controversies in the management of OSSN. A MEDLINE database search was performed using the keywords 'ocular surface squamous neoplasia,' 'conjunctival intraepithelial neoplasia,' 'conjunctival squamous cell carcinoma,' 'corneal intraepithelial neoplasia,' 'CIN,' and 'OSSN.' All resulting articles published in English until December 2020 were then reviewed for pertinent references. Although tissue biopsy remains the gold standard for the diagnosis and management of OSSN, the advent of new and sophisticated imaging modalities is likely to change the approach to OSSN diagnosis for the majority of patients, while the use of topical chemotherapeutic and immunotherapeutic agents may become the mainstay of treatment. [ABSTRACT FROM AUTHOR]

Abstract The most frequently encountered non-pigmented tumor of the ocular surface is ocular surface squamous neoplasia (OSSN). Over the past two decades, the pharmacological management of OSSN has grown, with topical 5-fluorouracil, mitomycin, and interferon alpha 2b all being successfully used to treat this disease. Other agents, such as anti-vascular endothelial growth factor (VEGF), retinoic acid, cidofovir and Aloe vera, have less frequently been used in the treatment of OSSN. This review will discuss these pharmacologic agents, summarizing available data and presenting the approach to the treatment of these tumors.

BACKGROUND: To evaluate the role of interferon alpha 2b (IFNα2b) in the management of primary/recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: Medical records of 27 OSSN cases managed with IFNα2b (topical drops and/or perilesional injection) in 1 year were retrospectively reviewed. RESULTS: The median age of presentation was 60 years with a male: female ratio of 3.5:1. American Joint Commission on Cancer tumor grading was T1 in 1 eye (3.7%) and T3 in 26 eyes (96.3%). Eighteen cases were treated with topical drops (1 million IU/ml), 4 cases with perilesional subconjunctival injection (3–6 million IU/ml), and 5 cases with combined therapy. Overall, treatment response was seen in 88% cases. Complete regression was achieved in 80% cases. Median time to complete regression of tumor was 3 months (range 1–11 months) in cases treated with topical interferon therapy and 2.5 months (range 0.7–3 months) in cases managed with injections or a combination of the two. The mean duration of follow-up was 24 months. All cases with partial/no response showed complete regression on subsequent management with topical mitomycin C. None of the patients required surgery. Acute ocular surface congestion was seen in two patients necessitating discontinuation of therapy. CONCLUSION: In view of excellent treatment outcome and few side-effects, interferons can be considered as a primary, safe, and cost-effective treatment option for OSSN not only in tertiary centers but also by peripheral ophthalmologists. [ABSTRACT FROM AUTHOR]

Purpose: Report a case of corneal melt in a patient with conjunctival intraepithelial neoplasia (CIN) treated with topical interferon (IFN) alpha-2B. Observations: An 89-year-old man presented with gelatinous paralimbal lesions of the left eye extending onto the cornea with corneal neovascularization extending 5–6 clock hours. Nasally there was mild absence of the terminal vascular loops of the limbal palisades of Vogt and conjunctivalization. Diffuse punctate epithelial erosions were noted. The corneal graft displayed subepithelial and stromal edema. Anterior segment optical coherence tomography detected hyperreflectivity, sectional thickened epithelium, and abrupt transitions from normal to abnormal tissue. The patient was treated with excision of the corneal and conjunctival lesions with cryotherapy to the conjunctival borders. Excisional biopsy revealed CIN Grade 3 and carcinoma in situ of the cornea. Topical IFN alpha-2B four times daily was initiated postoperatively. Two months later, a central epithelial defect developed. The cornea progressively thinned and corneal melt ensued. The patient had several risk factors for corneal melt including neurotrophic cornea, early limbal stem cell deficiency, history of cryotherapy, keratoconjunctivitis sicca, and chronic use of glaucoma medications and steroid medications. Conclusions: Interferon alpha-2B is an effective first line treatment for CIN with few side effects. It's side effects include punctate epithelial erosions, conjunctival hyperemia, and follicular conjunctivitis. We report a case of pre-existing keratoconjunctivitis sicca, early limbal stem cell deficiency, neurotrophic cornea, and newly diagnosed CIN Grade 3; it was treated with surgical excision, cryotherapy, and topical IFN alpha-2b with development of corneal melt 2 months later. Caution should be taken when using interferon alpha -2b in patients with pre-existing keratoconjunctivitis sicca, neurotrophic cornea, or limbal stem cell deficiency as it could exacerbate these conditions resulting in corneal melt.

Background. The main etiological factors of acute simple bronchitis in children are respiratory viruses, and therefore interferon preparations can be used in the treatment of these respiratory diseases. The purpose of the work was to study the clinical and immunological efficacy of recombinant alpha 2b interferon in the treatment of acute simple bronchitis in children. Materials and methods. We have examined 49 children aged 2 to 6 years with acute simple bronchitis; 23 children received Laferobion® containing recombinant alpha 2b interferon. Du­ring the work, clinical and laboratory methods of investigation were used. The severity of the patient’s condition was assessed according to the Bronchitis severity score. The laboratory study included: general blood and urine test, nasocytological, immunoassay methods. The etiological diagnosis was established ­using virological methods of investigation. When determining the concentration of interferon gamma, “Gamma interferon-IFA-BEST A-8752” set manufactured by Vector Best was used; lactoferrin — Нuman Lactoferrin NK 329 Edition 06-16 set manufactured by Hycult Biotech (USA), neutrophil a-defensins 1-3 — Нuman HNP NK317 Edition 08-16 reagents manufactured by Hycult Biotech (USA). Results. In all children with acute simple bronchitis, the disease began acutely and manifested itself with catarrhal and general inflammatory syndromes. According to the evaluation of acute simple bronchitis signs at the onset of the disease and in the period of convalescence ­using Bronchitis severity score, the administration of recombinant alpha 2b interferon promotes a faster reduction of all clinical manifestations of the disease and an increase in the lactoferrin content in the oropharyngeal fluid until the period of convalescence. Conclusions. The rectal administration of recombinant alpha 2b interferon Laferobion® is an etiopathogenetic method for the treatment of acute simple bronchitis in children

Purpose: The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN). Methods: In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN α2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications. Results: Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40–89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2–19.4) mm. Five (50%) eyes were treated with IFN-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3–25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy. Conclusion: Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications.

Real‐time monitoring of glycoengineered Pichia pastoris by employing process analytical technology (PAT) tools is vital for gaining deeper insights into the therapeutic protein production process. The present study focuses on influence of mixed feed carbon substrates during the induction phases of glycoengineered P. pastoris cultivation, for recombinant human interferon α2b (huIFNα2b) production by employing calorimetric (biological heat rate, qB) and respirometric (oxygen uptake rate and carbon dioxide evolution rate) measurements. Mixed feed stream of carbon substrates (methanol + glycerol, methanol + sorbitol) at a predetermined "C‐molar ratios" were added during the induction phases. Methanol‐ and sorbitol‐based mixed feeding approach resulted in an improved huIFNα2b titer of 288 mg/L by channeling of methanol predominantly towards an optimal functioning of AOX expression system. A stand‐off between biomass yield YXSand biomass heat yieldYQX coefficient, degree of reduction of methanol and its cosubstrate (glycerol and sorbitol) determines the fraction of carbon energy channeled toward biomass and protein production, under strict aerobic conditions. Calorespirometric monitoring and assessment of thermal yields enables a reliable prediction of process variables, leading to futuristic efficient PAT‐based feed rate control. [ABSTRACT FROM AUTHOR]

• N -glycoengineering approach for the design of novel glycosylated human IFN α2b. • Successful human-like N-glycosylated IFN α2b expression by glycoengineered P. pastoris. • Improved plasma half-life of purified glycosylated human IFN α2b. • Glycosylated human IFN α2b is biologically active against HCV and HEV systems. Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities. The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects. Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost. Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property. Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs. Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans. Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS). The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively. Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli. [ABSTRACT FROM AUTHOR]

Aims: The present study was aimed at design of experiments (DoE)‐ and artificial intelligence‐based culture medium optimization for high level extracellular production of a novel recombinant human interferon alpha 2b (huIFNα2b) in glycoengineered Pichia pastoris and its characterization. Methods and Results: The artificial neural network—genetic algorithm model exhibited improved huIFNα2b production and better predictability compared to response surface methodology. The optimized medium exhibited a fivefold increase in huIFNα2b titre compared to the complex medium. A maximum titre of huIFNα2b (436 mg l−1) was achieved using the optimized medium in the bioreactor. Real‐time capacitance data from dielectric spectroscopy were utilized to model the growth kinetics with unstructured models. Biological characterization by antiproliferative assay proved that the purified recombinant huIFNα2b was biologically active, exhibiting growth inhibition on breast cancer cell line. Conclusions: Culture medium optimization resulted in enhanced production of huIFNα2b in glycoengineered P. pastoris at both shake flask and bioreactor level. The purified huIFNα2b was found to be N‐glycosylated and biologically active. Significance and Impact of the Study: DoE‐based medium optimization strategy significantly improved huIFNα2b production. The antiproliferative activity of huIFNα2b substantiates its potential scope for application in cancer therapy. [ABSTRACT FROM AUTHOR]

Copyright of Zdorov'ye Rebenka is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Canalicular papillomatosis is a rare disorder characterized by a mass lesion arising from the epithelium as a stalk from one of the canalicular walls. Traditionally, they have been treated with an open canaliculotomy and excision biopsy with or without additional cryotherapy. A patient with upper canalicular squamous papillomas treated with dacryoendoscopy-guided transcanalicular intralesional and topical interferon alpha 2b is presented, and the ineffectiveness of interferons in this case is discussed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN).Methods: In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN α2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications.Results: Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40-89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2-19.4) mm. Five (50%) eyes were treated with IFN-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3-25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy.Conclusion: Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications. [ABSTRACT FROM AUTHOR]

Los tumores vesicales superficiales se caracterizan por una alta tasa de recidiva, que ocurre especialmente dentro de los dos primeros años, y que es aun mayor en los grupos de alto riesgo. Existe consenso en la utilidad del uso del Bacilo de Calmette-Guerin para disminuir la recurrencia tumoral. La quimioterapia intravesical con otros medicamentos han demostrado su utilidad o no en disminuir la recurrencia de estos tumores vesicales. Entre los años 1999 y 2008 se estudian y tratan 110 pacientes (96 hombres y 14 mujeres), con una edad promedio de 63 años, divididos en tres grupos para tratamiento de la recidiva tumoral después de resección transuretral o cistectomía parcial, con tres diferentes agentes quimioprofilácticos e inmunomoduladores (Thio-Tepa, BCG+factor de transferencia, doxorrubicina+interferón alfa 2b). El objetivo de esta investigación fue presentar la experiencia en el tratamiento de estos pacientes, donde se observa mejores resultados en 5 años, con el grupo tratado con doxorrubicina+interferón alfa 2b, seguido del grupo tratado con BCG+factor de transferencia, con una marcada disminución de las recurrencias y una limitación en la progresión de la enfermedad a largo plazo.The superficial bladder tumors are characterized by a high rate of recurrence taking place especially within the first two years that is even higher in the high risk groups. There is an agreement in the usefulness of the Calmette-Guerin Bacillus (CGB) to diminish the tumoral recurrence. The intravesical chemotherapy with other medications have demonstrated its profit or not in decreasing the recurrence of these bladder tumors. Between 1999 and 2008 we studied and treated 110 patients (96 men and 14 women), aged in average 63 years old. They were divided into three groups for the treatment of the tumoral recidivism after the transurethral resection or partial cystectomy, using three different chemoprophylactic agents and inmunomodulators (Thio-Tepa, BCG+Transference Factor, Doxorubicin +Interferon Alpha 2b). The objective of this research was presenting our experience in the treatment of these patients during five years, obtaining better results in the group treated with doxorubicin + interferon alpha 2b, followed by the group treated by means of BCG + transference factor, with a remarked decrease of the recurrence and a limitation in the long term progression of the disease.

Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhiFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT 1, and DNA expression of caspase 3. [ABSTRACT FROM AUTHOR]

Human interferon alpha 2b (IFNα-2b) is a pleiotropic cytokine used to treat various viral diseases and cancers. Conventionally, recombinant human IFNα-2b used in clinics was produced by prokaryotic expression system, which always lack of enough biological activity due to limitations on proper folding and post-translational modifications, so the eukaryotic expression system are becoming prevailing method for the production of recombinant proteins. In this study, human breast cancer cell Bcap-37 was firstly used as host for the expression of human IFNα-2b, with the expression vector pIRES2-IFN-EGFP, in which IFNα-2b gene is under the control of CMV promoter. The expression of recombinant IFNα-2b was detected by Western blot and ELISA. Results showed that the concentration of the secreted recombinant IFNα-2b in culture medium was 435.7 pg/mL/24 h. Biological activity of the recombinant IFNα-2b was assayed by detecting the expression of IFN-inducible genes, including MxA, OAS, PKR, and Caspase1 through QRT-PCR. Results demonstrated that recombinant IFNα-2b possess the biological activities. Compared to non-transgenic cells, the expression levels of the aforementioned four IFN-inducible genes were increased by 18.098-, 1.843-, 2.21-, and 3.066-folds, respectively. We got to a conclusion that the human breast cancer cell Bcap-37 could express bioactive recombinant IFNα-2b. [ABSTRACT FROM AUTHOR]

Interferon alpha 2b (IFNα-2b) is an important immune regulator widely used in clinic, for the treatment of chronic hepatitis, hairy cell leukemia, chronic myelogenous leukemia and multiple myeloma, etc. The clinically used IFNα-2b is generally produced by E.Coli, which lacks the post-translational O-glycosylation presents on naturally synthesized protein, and has a short serum half-life. In this study, a transgenic cassette pBCN-IFN-pA-CMV-EGFP was constructed, with a 5.2 kb beta-casein regulation fragment from Jersey cow and a 6×His tagged human Interferon alpha 2b (hIFNα-2b) gene fragment. By using pronuclear microinjection technique, transgenic mice were generated and the expression of IFNα-2b in the milk was assayed. The hIFNα-2b was correctly translated in milk of transgenic mice according to Western blot analysis. The expression level of hIFNα-2b was varied among the transgenic mice, and the highest one was about 29.71 μg/L. The recombinant protein exhibited biological activity in vitro by increasing the luminescence value and the MxA gene expression in established WISH cells, and the specific activity is approximately 2.8 × 10IU/mg. The expression of recombinant hIFNα-2b in mammary glands of transgenic mice constitutes an important step towards low-cost and full biological activity production of this protein drug in mammary gland bioreactor. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy of interferon alpha 2b in the treatment of refractory, uveitic cystoid macular edema (CME). Methods: Retrospective chart review of 4 patients attending the uveitis clinic at the Casey Eye Institute, Oregon Health & Science University. Results: All 4 patients had uveitis and refractory CME, resistant to a variety of immunosuppressants. All patients, except one with severe scleral thinning, had tried and failed therapy with locally injected corticosteroids. Treatment with systemic interferon alpha 2b produced dramatic improvement in CME (central macular thickness: 563 to 267 µm, p == .002) and visual acuity (logMAR: ++0.81 to ++0.45, p == .0004) in all 4 cases. All patients have been able to reduce the interferon dosage, but none has discontinued it completely. All patients had some mild adverse response that did not necessitate stopping therapy. Conclusions: Interferon alpha 2b is an effective option to treat refractory CME secondary to uveitis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the efficacy and safety of a 2-month topical interferon alpha 2b treatment in patients with refractory vernal keratoconjunctivitis. Methods: Twelve (10 male, 2 female) patients with refractory vernal keratoconjunctivitis received topical treatment with one million IU/mL interferon alpha 2b 4 times a day for 2 months. Symptom and ophthalmological examination scores were assessed at baseline and during follow-up. Results: No significant complications or side effects associated with the use of topical interferon alpha 2b were observed. Symptom scores for itching, tearing, photophobia, and total symptom score, and objective scores for corneal lesion, hyperemia, chemosis, papillary hypertrophy, secretion, and total examination score significantly improved during the 2-month treatment. Improvements were maintained after discontinuation of the treatment for most parameters. Conclusions: Topical interferon alpha 2b treatment seems to offer a safe and effective alternative for the treatment of refractory vernal keratoconjunctivitis for a brief period. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric adverse effects of interferon (IFN) alpha are well known. There is little clinically relevant research on animal models of depression with recombinant human IFN alpha 2b (rhIFN-α2b). Aim: To identify an appropriate dose and duration of administration of recombinant human interferon alpha-2b (rhIFN-α2b) to establish a convenient and clinically relevant murine model of chronic rhIFN-α2b-induced depression using the forced swim test (FST). Materials and Methods: Using a 4×3 factorial design, rhIFN-α2b was administered subcutaneously to mice (n=180) in the dose range of 400, 800, and 1600 IU/g/day for 5, 10, and 15 days; saline-treated mice formed the control groups. In each group, 1 day after the last dose, the mice were assessed for immobility in the FST. In another experiment, at these same doses and time points, the effect of rhIFN-α2b on murine motility was assessed in the small open field. Results: We found that rhIFN-α2b significantly increased immobility in the FST. The immobility was detectable by day 5 and did not increase with duration of IFN treatment. The immobility was apparent with the 400 IU/g/day dose and was not greater at higher IFN doses. At no dose or time point did rhIFN-α2b alter murine motility in the small open field. Conclusion: We conclude that rhIFN-α2b-induced behavioral despair, represented by immobility in the FST, is not due to reduced basal motility. The FST may therefore be used as a convenient Swiss albino mouse model of chronic rhIFN-α2b-induced depression with a 400-1600 IU/g/day dose administered subcutaneously for 5-15 days. The most economical model is 400 IU/g/day administered for 5 days [ABSTRACT FROM AUTHOR]

Abstract: The human interferon alpha 2b (IFN α2b) belongs to the interferon family of cytokines that exerts many biological functions like inhibition of virus multiplication, repression of tumour growth and other immunological functions. Herein, a synthetic gene coding for human IFN α2b was cloned and integrated into a methylotropic yeast—Pichia pastoris. The recombinant human IFN α2b protein (∼19kDa) could be successfully expressed in Pichia pastoris to a level of nearly 300mg/L with nearly 93% recovery on purification using a single anion exchange chromatography step. A novel media component dimethyl sulphoxide (DMSO) was found to aid in expression of rightly processed IFN α2b form with dramatic reduction in the expression of a 20kDa IFN isoform contaminant frequently observed by other workers. The identity of the 20kDa isoform was confirmed by N terminal sequencing which showed extra eleven amino acids at the N terminal portion of the IFN molecule obtained due to incorrect processing by the host KEX2 protease. The purified IFN α2b (19kDa) preparation was confirmed by N terminal sequencing, and characterized by MALDI-TOF and Agilent 2100 Bioanalyzer. The bioassay of the recombinant protein gave a specific activity of >2×108 IU/mg. [Copyright &y& Elsevier]

Abstract: Disseminated lymphangiomatosis and Gorham–Stout disease are being considered as two forms of a single rare disease, characterized by a proliferation of lymphatic vessels, triggered by lymphangiogenic factors. There is no biological marker of the disease. Plasma VEGF might be a useful tool since the recent demonstration of its pivotal role in the mechanism of this disease. A 45-year-old woman with a history of disseminated lymphangiomatosis involving mediastinum, retroperitoneum, spleen and systemic bones for 29 years was treated with Interferon alpha 2b at a dosage of 7.5 to 15 million IU 3 times a week for 5 years. Plasma VEGF quantification was performed twice a year and showed a marked increase before therapy, which normalize after 18 months of treatment with Interferon. The normalization of plasma VEGF is correlated with the clinical improvement objectively appraised by a marked reduction of spleen lesions and significant improvement of the other damages in soft tissues and bones. Thus, we conclude that plasma VEGF determination should be considered for diagnosis and follow-up of the course and the treatment of disseminated lymphangiomatosis–Gorham–Stout disease. [Copyright &y& Elsevier]

Background: Plantar fasciitis is the most common cause of heel pain but treatment remains empirical. Objective: To investigate the effect of interferon alpha 2b on pain, morning stiffness and tenderness of heels in patient with plantar fasciitis. Methods: Three hundred seventy six patients with plantar fasciitis enrolled in this study. The patients divided into two groups: Group one received interferon alpha 2b 3MIU\evry 3days and group two treated with diclofenac. 50 mg two times daily with heel pads. The study conducted for 12 week. Results: 92% of group one patients who received interferon alpha 2b became completely asymptomatic at week 6. At week 12 96.8% became completely free of symptoms. Conclusion: Treatment with interferon alpha 2b in patients who had plantar fasciitis seems to be effective bringing complete cure. [ABSTRACT FROM AUTHOR]

This article focuses on a case of generalised exfoliative dermatitis and intense pruritus during poly-ethyleneglycol-IFNα-2b therapy in a patient with chronic hepatitis C virus infection. A 41-year-old man without a medical history of autoimmune or rheumatological diseases presented with an increase in serum ALT and AST levels. Blood chemical evaluation did not reveal any increase in autoimmune serological manifestations. Tests for total and differential circulating immunocomplexes were negative.

Background: Interferon (IFN)-α-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNα-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNα-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone. Patients and methods: We evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNα-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNα-2b (Intron® A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400mg twice daily (morning and night) [for patients weighing <75kg] or 500mg twice daily (for those weighing ≥75kg). The planned treatment period was 6 months. Results: Both IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered. Conclusion: The combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to clarify the pharmacokinetics of ribavirin and interferon-alpha (IFN-α) 2b when administered in combination for 24 weeks and effects of pharmacokinetics of both on treatment outcome in chronic hepatitis C with genotype 1b and high viral load. Methods In this multicentre open study, 27 patients received 2-week daily induction therapy followed by 22-week, three-times-a-week maintenance therapy of intramuscular IFN-α 2b at a dose of 6 million units and oral ribavirin at 400 mg twice daily for 24 weeks, and followed up for 24 weeks post-treatment. Single- and multiple-dose pharmacokinetic studies were assessed by serial measurements of serum concentrations of both compounds at weeks 1 and 24. Results Five patients attained sustained virological response. Serum ribavirin concentrations asymptoted after 4–8 weeks of treatment in all patients. The steady-state concentration correlated significantly with serum ribavirin clearance after multiple dosing (r = -0.875; 95% CI -0.932, -0.721; P < 0.001). Serum concentrations at weeks 4 and 8, C max and AUC(0,12 h) after multiple dosing and AUC(0,28 weeks) of ribavirin were significantly higher in sustained virological responders than in virological responders or nonresponders (P < 0.05, each). Increased C max and accumulation index of AUC(0,12 h) (median 10.5; 95% CI 6.4, 12.4), and prolonged washout half-life after multiple dosing reflected accumulation and slow clearance of ribavirin from the tissue compartments. Conclusions Continuous exposure and accumulation of ribavirin may be necessary for sustained virological response to combination therapy in chronic hepatitis C with genotype 1b and high viral load. [ABSTRACT FROM AUTHOR]

The gender-specific prevalence of lymphangioleiomyomatosis (LAM) in premenopausal women suggests a hormonal etiology. Despite the antiestrogenic treatment (ovariectomy, tamoxifen) this disease is often refractory to therapy and almost inevitably leads to the patient's death. We describe a case where the antiproliferative effect of systemically applied interferon alpha 2b was successfully employed in addition to ovariectomy and the patient reached complete remission. [ABSTRACT FROM AUTHOR]

In a prospective clinical trial involving six patients suffering from essential thrombocythemia (ET), recombinant human interferon alpha 2b significantly and consistently lowered highly elevated peripheral platelet numbers over long time periods. One patient has now been on continuous treatment for 4 years. During the treatment phase none of the patients suffered from bleeding episodes, thrombosis or disturbances of the microcirculation. The interferon maintenance dose varies considerably from patient to patient, but it is usually much lower than the induction dose. One of the patients had to be withdrawn from the study due to interferon-specific chronic toxicity concomitant with the development of non-neutralizing interferon antibodies. With the exception of one patient, stopping interferon treatment led to an increase in peripheral platelet numbers of up to one million cells per microliter of blood within 4 to 12 weeks. We conclude that interferon alpha can correct peripheral thrombocytosis in selected patients with essential thrombocythemia over a period of years and prevent morbidity attributable to this disease. [ABSTRACT FROM AUTHOR]