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OBJECTIVES: Exophytic Sinonasal Papilloma (ESP) is a benign tumor of the sinonasal tract. Complete surgical excision by endoscopic surgery is the treatment of choice. However, a high recurrence rate (36% at 5-year follow-up) is associated with this method, which may indicate the presence of microorganisms such as Human Papillomavirus (HPV). It is important to note that the standard treatment for ESP does not include antiviral drugs. In our study, we are testing the effectiveness of an interferon-containing drug in reducing recurrence and postoperative reactions in patients with ESP. METHODS: We included 78 patients aged 23-83 years with a confirmed diagnosis of ESP by rhinoscopy and nasal endoscopy and a positive PCR test for HPV in nasal scrapings. To compare the results, we divided the patients into main and control groups. The main group received recombinant human interferon after surgery, while the control group did not receive the drug. We performed a statistical analysis to compare the proportion of patients without reactive manifestations at different stages of the postoperative period, as well as to compare the proportion of patients with recurrent ESP at certain stages of observation. RESULTS: The introduction of recombinant human interferon accelerated the resolution of postoperative reactions and promoted the healing of the nasal mucosa after surgical removal of the ESP. We also found a statistically significant association between treatment with recombinant interferon and a reduction in the recurrence rate of ESP. CONCLUSION: According to the results of the study, it was found that in the main group of patients who received rhIFN-α2b (recombinant human Interferon alpha 2b) in the postoperative period, the frequency of relapses of ESP and the time of postoperative recovery were significantly lower than in patients in the control group who did not take the drug. LEVEL OF EVIDENCE: Cohort Study.

Asunto(s)

Interferón alfa-2 , Interferón-alfa , Papiloma , Infecciones por Papillomavirus , Humanos , Persona de Mediana Edad , Adulto , Anciano , Masculino , Femenino , Interferón alfa-2/uso terapéutico , Infecciones por Papillomavirus/tratamiento farmacológico , Anciano de 80 o más Años , Adulto Joven , Interferón-alfa/uso terapéutico , Resultado del Tratamiento , Papiloma/tratamiento farmacológico , Papiloma/cirugía , Papiloma/virología , Neoplasias Nasales/cirugía , Neoplasias Nasales/tratamiento farmacológico , Neoplasias Nasales/virología , Proteínas Recombinantes/uso terapéutico , Recurrencia Local de Neoplasia , Antivirales/uso terapéutico

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PURPOSE: To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence. METHODS: This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method. RESULTS: In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7 mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119). CONCLUSIONS: interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery.

RESUMEN

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Asunto(s)

Antivirales , Modelos Animales de Enfermedad , Herpes Genital , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Queratitis Herpética , Animales , Conejos , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Herpes Genital/tratamiento farmacológico , Herpes Genital/virología , Queratitis Herpética/tratamiento farmacológico , Queratitis Herpética/virología , Chlorocebus aethiops , Femenino , Células Vero , Interferón alfa-2/administración & dosificación , Interferón alfa-2/uso terapéutico , Replicación Viral/efectos de los fármacos , Administración Tópica , Soluciones Oftálmicas , Interferón-alfa/administración & dosificación , Humanos

RESUMEN

Human interferon (hINF) alpha 2b is clinically important pharmaceutical product included in combinatory therapy against chronic hepatitis C and B and complex therapy against several cancer diseases. Here, we created the genetic constructions, based on genome elements of potato virus X (PVX), carrying the infα2b gene for transient expression in plant cells. The created plasmid vector constructions were tested through Agrobacterium-mediated transient gene expression method in two plant species-Nicotiana benthamiana and Ocimum basilicum (sweet basil). Production of recombinant hINF alpha 2b was more efficient in N. benthamiana than that in O. basilicum plants. The average yield of hINF alpha 2b produced in N. benthamiana plants was 0.56 mg/g of fresh leaf weight (FW) or 6% of the total soluble cell proteins (TSP). The maximal level reached up to 1.2 mg/g FW or 9% TSP. We estimated that about 0.67 mg of hINF can be obtained from one N. benthamiana plant. The yield of hINF alpha 2b obtained with the PVX-based expression cassette was about 80 times higher than the yield of hINF alpha 2b obtained with a simple expression cassette in which the infα2b gene was controlled by the 35S promoter of cauliflower mosaic virus. KEY POINTS: • PVX-based expression vectors provide efficient transient expression of infα2b gene • N. benthamiana plants can produce human interferon alpha 2b at high levels • The yield of the hINF α2b reached up to 1.2 mg/g of fresh leaf weight.

Asunto(s)

Vectores Genéticos , Interferón-alfa , Humanos , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Interferón-alfa/genética , Interferón-alfa/metabolismo , Nicotiana/genética , Regiones Promotoras Genéticas

RESUMEN

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-ß1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-ß1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-ß1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-ß1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-ß1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-ß1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-ß1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.

Asunto(s)

Cicatriz Hipertrófica , Colágeno Tipo I , Interferón alfa-2 , Humanos , Células Cultivadas , Cicatriz Hipertrófica/patología , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Decorina/metabolismo , Fibroblastos/metabolismo , Interferón-alfa/farmacología , Interferón-alfa/metabolismo , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Cicatrización de Heridas/fisiología

RESUMEN

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 .

Asunto(s)

Antineoplásicos , Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Enfermedades de la Córnea , Neoplasias del Ojo , Humanos , Administración Tópica , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias de la Conjuntiva/tratamiento farmacológico , Enfermedades de la Córnea/patología , Neoplasias del Ojo/inducido químicamente , Interferón alfa-2/uso terapéutico , Interferón-alfa/uso terapéutico , Interferón-alfa/efectos adversos , Mitomicina , Resultado del Tratamiento

RESUMEN

INTRODUCTION: Basal cell carcinoma (BCC) is the most common cutaneous cancer. We report the efficacy and aesthetic outcome of intralesional IFN-α 2b injection for the treatment of BCC and compare with the surgical method. MATERIALS AND METHODS: Intralesional IFN-α 2b was injected in 58 BCC lesions from 20 patients three times a week for three weeks. Control group was retrospectively selected among patients who underwent surgical method (standard surgical excision) for BCC including 58 lesions from 24 patients. All patients were followed up for one year in terms of recurrence and cosmetic outcome. RESULTS: Two patients (four lesions) failed to complete the treatment period. After three weeks, 40 (68.96%) lesions were completely cured. Nine (15.51%) lesions achieved complete healing in less than 9 sessions. Five (8.62%) lesions were completely cured by an extra week of injection. In aggregate, complete healing was observed in 54 (93.10%) lesions. In the surgery group, complete lesion elimination was detected in 52 (89.65%) lesions (p = 0.40). After one year, cosmetic outcome was significantly more favorable in the study group compared to the surgery group (p = 0.003). Recurrence was not detected in any of the groups after one year follow-up. CONCLUSION: Intralesional IFN-α 2b injection is an appropriate treatment choice for BCC. CLINICAL TRIAL REGISTRY: We used Iranian registery of Clinical trials; The IRCT code is: 2017093017756N30.

Asunto(s)

Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Interferón alfa-2/uso terapéutico , Irán , Estudios Retrospectivos , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología

RESUMEN

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.

RESUMEN

PURPOSE: To assess the efficacy of topical interferon α-2ß(IFN) eye drops as a primary treatment for ocular surface squamous neoplasia(OSSN) and evaluate factors that impact response to treatment and recurrence of OSSN. METHOD: A retrospective study of 143 OSSN patients treated with topical IFN(1MIU/ml) from January 1998 to June 2021. The diagnosis was based on clinical examination and anterior segment optical coherence tomography, with histologic confirmation was present in 46.2% of patients. Data on demographic, tumor characteristics, treatment outcome, and side effects were collected. The primary outcomes were tumor resolution frequency and recurrence rate. Secondary outcomes were predictive factors for resolution and recurrence and side effects of treatment. RESULT: Participants were mostly older (mean age, 69 years, SD 12.9, range 29-97), white(89%) males (74%). Complete tumor resolution was achieved in 80.4% of individuals with a mean time to resolution of 4.2 months (SD 2, range 0.5-12.3 months). On multivariable analysis, history of skin cancer (HR: 0.66, p = 0.05, 95%CI: 0.44-0.99) and immune system abnormalities (HR: 0.37, p = 0.009, 95%CI: 0.18-0.79) reduced the risk of tumor resolution, while a prior history of OSSN (HR: 3.49, p < 0.001, 95%CI: 1.76-6.93) increased the risk of resolution. With a mean follow-up time of 44.3 months (SD 50.9, 0-290 months), the recurrence rate was 0%, 2.3% and 3.1% at 1, 2, and 5 years respectively. Mild hyperemia(18.9%) and pain(10.6%) were the two most common side effects. CONCLUSION: Topical IFN eye drops are a safe and effective primary treatment modality for OSSN with a reasonable side effect profile.

Asunto(s)

Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Neoplasias del Ojo , Masculino , Humanos , Anciano , Femenino , Antineoplásicos/uso terapéutico , Interferón alfa-2/uso terapéutico , Estudios Retrospectivos , Soluciones Oftálmicas/uso terapéutico , Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Interferón-alfa/efectos adversos , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Resultado del Tratamiento , Administración Tópica

RESUMEN

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.

Asunto(s)

Neoplasias de la Conjuntiva , Melanosis , Humanos , Mitomicina , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Melanosis/diagnóstico , Melanosis/tratamiento farmacológico , Recurrencia Local de Neoplasia , Interferón-alfa/uso terapéutico , Adyuvantes Inmunológicos

RESUMEN

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Asunto(s)

Antineoplásicos , Neoplasias de la Conjuntiva , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Interferón alfa-2/uso terapéutico , Interferón-alfa/efectos adversos , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Fluorouracilo/efectos adversos , Administración Tópica , Resultado del Tratamiento , Proteínas Recombinantes/uso terapéutico

RESUMEN

Purpose: The aim of the study was to demonstrate the clinical outcomes after resection of conjunctival melanoma (CM) followed by topical interferon (IFN) alpha 2b after a long follow-up. Methods: Two consecutive CM patients were treated using tumor excision followed by topical IFN alpha 2b (1,000,000 UI/mL) four times a day for 12 weeks. The second case presented positivity due to the presence of tumor cells in the lower margin of the resection. TNM staging was T1c, N0b, M0, and T1b in the first case and T1b, N0b, M0 in the second case. Follow-up was 72 and 71 months, respectively. Results: No side effects were observable after the administration of topical IFN alpha 2b. After extensive evaluation and imaging with computed tomography, no regrowth or distant metastasis was noticed during the follow-up period in both cases. Conclusions: IFN alpha 2b could be used as a co-adjuvant treatment after CM resection, in an attempt to reduce the possibility of recurrences.

RESUMEN

Interferon alpha-2b (IFNα-2b) is an essential cytokine widely used in hepatitis and cancer treatment. This paper presents a novel protocol for purification and efficient refolding of recombinant interferon alpha-2b (IFNα-2b) expressed as insoluble inclusion bodies in Escherichia coli. Purification of IFNα-2b from solubilized inclusion bodies was performed by solvent extraction using 2-butanol. Refolding conditions were optimized using the response surface method (RSM). Under optimized conditions, refolding yield of solvent-extracted IFNα-2b was 1.5 fold higher than refolding yield of unpurified IFNα-2b. High-concentration protein refolding was carried out by pulse-fed method, and refolding yield of 75% was achieved at a protein concentration of 300 µg ml-1. Under optimized conditions, 259.16 mg of purified IFNα-2b with the biological activity of 2.4 × 108 IU mg-1 was achieved per liter of bacterial culture. The developed protocol provides an efficient production process of high-quality IFNα-2b suitable for research and pharmaceutical applications.

Asunto(s)

Escherichia coli , Cuerpos de Inclusión , Escherichia coli/genética , Escherichia coli/metabolismo , Cuerpos de Inclusión/metabolismo , Interferón alfa-2/metabolismo , Replegamiento Proteico , Proteínas Recombinantes , Solventes

RESUMEN

Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface neoplasm. Interferon-alpha (IFNα)-2b has been proved to be an effective immunotherapeutic agent to treat OSSN. We have used intralesional and topical (36 µg/ml) pegylated (peg) IFNα-2a to treat a recurrent surgically failed case of OSSN instead of IFNα-2b. In this case report, we have shared our initial experience with the novel use of peg-IFNα-2a to treat OSSN. According to our brief clinical experience, peg-IFNα-2a is nontoxic to ocular surface and has a promising role to treat OSSN.

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama , Neoplasias de la Conjuntiva , Melanoma , Melanosis , Administración Tópica , Neoplasias de la Conjuntiva/patología , Femenino , Humanos , Interferón-alfa/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanosis/tratamiento farmacológico , Melanosis/patología

RESUMEN

Mutations in the titin (TTN) gene are among the most common genomic aberrations in ocular surface squamous neoplasia (OSSN), the most common cancer of the external eye. Further, TTN mutations are associated with resistance to standard therapy with topical interferon alpha-2b (IFN-α2b). However, it remains unclear how TTN mutations drive OSSN pathogenesis and treatment resistance. TTN encodes the largest protein in the human body and its best understood function is as a myofibril scaffold in striated muscle. However, recent evidence indicates that TTN has additional functions in non-muscle cells and in cancer. Here, we performed a disorder-based bioinformatics analysis which revealed that intrinsically disordered protein regions are abundant in TTN and provide mechanistic insights into its function as a nuclear protein in epithelial cells. Specific mutations found in OSSN are predicted to affect its intrinsically disordered protein regions (IDPRs), promoting chromosomal instability, oncogenesis, and altered response to IFN-α2b treatment.

Asunto(s)

Carcinoma de Células Escamosas/genética , Neoplasias de la Conjuntiva/genética , Conectina/genética , Resistencia a Antineoplásicos , Mutación , Carcinoma de Células Escamosas/tratamiento farmacológico , Inestabilidad Cromosómica , Biología Computacional , Neoplasias de la Conjuntiva/tratamiento farmacológico , Conectina/química , Conectina/metabolismo , Humanos , Interferón alfa-2/farmacología , Interferón alfa-2/uso terapéutico , Dominios Proteicos , Mapas de Interacción de Proteínas , Estabilidad Proteica

RESUMEN

Background: Interferon α-2b is a vital biotherapeutic produced through the recombinant DNA technology in E. coli. The recombinant IFN-α2b normally appears as intercellular IBs, which requires intensive refolding and purification steps. Method: Purification of IFN-α2b from solubilized IB was performed using two-phase extraction. To optimize refolding conditions, the effects of pH and different additives, including cysteine, cystine, urea, glycerol, Triton X-100, NaCl, and arginine, were investigated. Optimal refolding buffer (0.64 mM of urea, 5.57 mM of cysteine , and 1.8 mM of cystine) was obtained using RSM. The refolding process was performed by an optimized refolding buffer in the dilution and fed-batch refolding method at different protein concentrations (25-1000 µg/mL). Result: At a final protein concentration of 500 µg/mL, the fed-batch refolding method yielded in a biological activity of 2.24 × 108 IU/mg, which was nearly twice that of dilution method. Conclusion: Fed-batch refolding method resulted in the biologically active IFN-α2b with high purity, which can be used for research and industrial purposes.

Asunto(s)

Interferón-alfa/aislamiento & purificación , Extracción Líquido-Líquido/métodos , Humanos , Pliegue de Proteína , Proteínas Recombinantes/aislamiento & purificación

RESUMEN

PURPOSE: To investigate the effects of topical and perilesional interferon alpha-2b as primary treatment for ocular surface squamous neoplasia (OSSN). METHODS: In this prospective interventional case series, topical interferon alpha-2b (3 MIU/mL) was used as the initial treatment of OSSN, with perilesional interferon alpha-2b (3 MIU/mL) added based on clinical response. The primary outcome was complete tumor resolution. Spearman's rank correlation test was used to investigate the association of complete tumor resolution and time to resolution with baseline tumor characteristics and the American Joint Committee on Cancer (AJCC) classification for OSSN. RESULTS: Ninety-two patients (92 OSSN tumors) were included in the study. The total follow-up duration was 13.57 ± 2.14 months (median: 12, range: 3-23). The median basal tumor diameter was 4 mm (mean: 4.13 ± 1.37). Complete tumor resolution was achieved in 89 cases (96.73%), with a median time to complete tumor resolution of 5 months (mean: 4.64 ± 1.92). Complete tumor resolution was 57 of 57 in T1 (100%), 8 of 9 in T2 (88.88%), and 21 of 23 in T3 (91.30%). There were statistically significant correlations between AJCC classification and complete tumor resolution (Spearman's r = -0.22, P = 0.03) and maximal basal tumor diameter and the time to complete resolution (Spearman's r = 0.35, P = 0.001). There were no recurrences during the study follow-up period. CONCLUSION: Topical interferon alpha-2b is effective and well tolerated as a primary treatment for OSSN, with a high rate of tumors responding completely to therapy.

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

Asunto(s)

COVID-19 , Adulto , Antivirales/efectos adversos , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Proteínas Recombinantes , SARS-CoV-2 , Resultado del Tratamiento

RESUMEN

The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. This retrospective study analyzed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Anti-PD-1 treatment resulted in significantly longer RFS and DMFS than HDI in cutaneous melanoma patients, with hazard ratios (HRs) (anti-PD-1 versus HDI) of 0.402 (95% CI, 0.183-0.886) and 0.324 (95%CI, 0.122 to 0.861) for RFS and DMFS, respectively. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients with HRs (anti-PD-1 versus HDI) of 1.204 (95% CI, 0.521 to 2.781) and 1.968(95% CI, 0.744-5.209) for RFS and DMFS, respectively. Adjuvant anti-PD-1 treatment yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.

Asunto(s)

Melanoma , Neoplasias Cutáneas , Quimioterapia Adyuvante , China , Supervivencia sin Enfermedad , Humanos , Inhibidores de Puntos de Control Inmunológico , Interferón-alfa/efectos adversos , Melanoma/tratamiento farmacológico , Proteínas Recombinantes , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico