IFN-alpha 2b Research Articles

Efficacy and safety of therapies for COVID-19 in pregnancy: a systematic review and meta-analysis

BackgroundClinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications, such as premature labor, miscarriage, preeclampsia, cesarean delivery, fetal growth restriction and perinatal death. Despite this evidence, pregnant women are often excluded from clinical trials, resulting in limited knowledge on COVID-19 management. The aim of this systematic review and meta-analysis is to provide better evidence on the efficacy and safety of available COVID-19 treatment in pregnant women.MethodsFour authors searched major electronic databases from inception until 1 st November-2022 for controlled trials/observational studies, investigating outcomes after the administration of anti-SARS-CoV-2 treatments in pregnant women affected by COVID-19. The analyses investigated the cumulative incidence of delivery and maternal outcomes in pregnant women, comparing those taking active medication vs standard care. Risk ratios (RRs) with 95% confidence intervals were calculated. Statistical significance was assessed using the random effects model and inverse-variance method. This systematic review and meta-analysis was conducted in accordance with the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in Prospero (number registration: CRD42023397445).ResultsFrom initially 937 non duplicate records, we assessed the full texts of 40 articles, finally including ten studies. In six studies, including 1627 patients, the use of casirivimab/imdevimab (CAS/IMD), remdesivir, and IFN-alpha 2b significantly decreased the need of cesarean section ((RR = 0.665; 95%CI: 0.491–0.899; p = 0.008; I 2 = 19.5%;) (Table 1, (Fig. 1). Treatments did not decrease the risk of preterm delivery, admission to neonatal ICU, or stillbirth/perinatal loss (p-values > 0.50 for all these outcomes) and did not prevent the progression of disease towards severe degrees (k = 8; 2,374 pregnant women; RR = 0.778; 95%CI: 0.550–1.099; p = 0.15; I 2 = 0%). Moreover, the use of medications during pregnancy did not modify the incidence of maternal death in two studies (Table 2).ConclusionsTo our analysis, CAS/IMD, remdesivir, and IFN alpha 2b reduced the number of cesarean sections but demonstrated no effect on disease progression and other obstetric and COVID-19 related outcomes. The inability to evaluate the influence of viral load on illness development in pregnant women was attributed to lack of data. In our systematic review, no major side effects were reported. Though, it is essential for the medical community to focus more on clinical trials and less on episodic case reports and case series, with standardization of fetal and maternal outcomes.

Combination of Interferons for Advanced Renal Cell Carcinoma

Introduction: A novel formulation that combines IFN alpha-2b and gamma evidenced effectivity in cancer treatment. The poor prognosis of advanced renal cancer needs new therapeutic approaches. A retrospective study was carried out evaluating the effectivity and safety of interferon’s combination in patients with advanced renal cell carcinoma. Methods: Retrospective case-control and cohort analyzes were performed, carried out to identify patients with advanced or metastatic kidney tumors treated from May 2009 to December 2021 in a Cuban healthcare center. Patients with advanced renal cell carcinoma received a combination of IFN alpha-2b/gamma. Heberon Alpha R was used as historical control. The study was approved by the Ethics Committee and informed consent was obtained for participating patients. Results: 56 patients were included. The combination of IFNs (experimental group) and the Heberon Alpha R (historical control group) were comparable. Overall survival in stage III disease was 101.3 months with combination of IFNs versus 38.1 in Heberon Alpha R, and 70.4 months versus 30.6 months in stage IV patients. The functional capacity of patients from experimental group was higher than those from control and reached more than 75%, with favorable functional capacity at 24 months; while more than 65% of patients in the control cursed with worse capacity. No serious adverse events with proven causality occurred within the cohort of patients treated with interferon combination. The events correspond to those reported in other studies.

Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial EST 1684.

Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.

A new insight into mechanisms of interferon alpha neurotoxicity: Expression of GRIN3A subunit of NMDA receptors and NMDA-evoked exocytosis

Neurological and psychiatric side effects accompany the high-dose interferon-alpha (IFNA) therapy. The primary genes responsible for these complications are mostly unknown. Our genome-wide search in mouse and rat genomes for the conservative genes containing IFN-stimulated response elements (ISRE) in their promoters revealed a new potential target gene of IFNA, Grin3α, which encodes the 3A subunit of NMDA receptor. This study aimed to explore the impact of IFNA on the expression of Grin3α and Ifnα genes and neurotransmitters endo/exocytosis in the mouse brain. We administered recombinant human IFN-alpha 2b (rhIFN-α2b) intracranially, and 24 h later, we isolated six brain regions and used the samples for RT-qPCR and western blot analysis. Synaptosomes were isolated from the cortex to analyze endo/exocytosis with acridine orange and L-[14C]glutamate. IFNA induced an increase in Grin3α mRNA and GRIN3A protein, but a decrease in Ifnα mRNA and protein. IFNA did not affect the accumulation and distribution of L-[14C]glutamate and acridine orange between synaptosomes and the extra-synaptosomal space. It caused the more significant acridine orange release activated by NMDA or glutamate than from control mice's synaptosomes. In response to IFNA, the newly discovered association between elevated Grin3α expression and NMDA- and glutamate-evoked neurotransmitters release from synaptosomes implies a new molecular mechanism of IFNA neurotoxicity.

Eficacia y seguridad del interferón pegilado, asociado a la criocirugía en el tratamiento del condiloma acuminado

BackgroundThe continuous recurrences of condylomata acuminata makes it necessary to constantly search for therapeutic alternatives. Patients and methodTo evaluate the therapeutic efficacy and safety of pegylated interferon (IFN p) adjuvant to cryosurgery, an open clinical trial was conducted in condylomata acuminata in 30 patients from the «Hermanos Ameijeiras» hospital, who were randomized to receive 6 weeks (group I) subcutaneous recombinant human interferon alfa 2b (IFN), 3 times per week + biweekly cryosurgery or (group II) subcutaneous IFN p, 1 time per week + biweekly cryosurgery. The main variable was the percentage of recurrence at one year of follow-up. There was also a rigorous control of adverse events. ResultsAt the end of the treatment 12/15 (80%) patients in group I and group II 14/15 (93,3%) were without injuries (p < 0.32). During follow-up, none of the patients who received IFN p + cryosurgery had recurrences; while 2/12 (16.7%) of the patients who received IFN + cryosurgery recurred (p < 0.672). Adverse events were significantly more frequent in group I (fever 13/15, headache 7/15, chills 3/15, and myalgia 2/15) (p < 0.003). ConclusionPegylated interferon with a weekly frequency of administration achieves superior therapeutic effects, a lower percentage of recurrences and adverse reactions than the administration of recombinant human IFN alpha 2b 3 times a week.

Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study

BackgroundThe global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone.MethodsPatients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b.ResultsA total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups.ConclusionsSubcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.

Эффективность рекомбинантного интерферона альфа-2b в лечении хронического рецидивирующего бактериального простатита

Chronic recurrent bacterial prostatitis (HRBP) affects the reproductive function and negatively affects the quality of life of men. The multifactorial pathogenesis of this disease causes the failure of antibiotic therapy and some cases, requires an in-depth study of the mechanisms of disease development and additional treatment methods. of the study: to study of the effectiveness of immunoactive therapy (recombinant interferon alpha-2b with an antioxidant complex) in combination with antibacterial therapy in patients with HRBP. Prospective trial: examination and treatment of 62 patients. Two groups: I (study) group (n=31) received antibacterial therapy (ABT) and a therapy with recombinant IFN Alpha-2b based medication with antioxidant complex (vitamins E and C), II (control) group (n=31) received only ABT. The examination plan included questionnaires (NIH - CPSI, IPSS, Hamilton), general blood and urine tests, biochemical blood tests, urethral scrapings for PCR diagnostics, plasma testosterone, native, electron microscopy, culture test and immunoferment analysis of the prostate sercet, uroflowmetry, Transrectal ultrasonography (TRUS). When monitoring the clinical picture according to questionnaires (IPSS, NIH-CPSI, Hamilton scale) and laboratory indicators, 1 month after treatment, a significant reduction in symptoms was observed in both groups, and after 3, 6, and 12 months - in patients of group I. The Combination of an antibacterial drug and recombinant interferon alpha-2b in the treatment of HRBP provides more effective relief of the infectious and inflammatory process in the long term than antibacterial monotherapy.

Рациональная терапия острых респираторных инфекций у детей раннего возраста препаратом рекомбинантного интерферона альфа-2b

Influenza and acute respiratory viral infections (ARVI) remain a global health problem worldwide, and therefore the search for effective means of prevention and treatment of these diseases is extremely urgent. Objective. To evaluate the therapeutic efficacy and safety of a drug form of recombinant human IFN alpha-2b in combination with a complex of antioxidants (Viferon®-suppositories) in children with ARVI. Patients and methods. Clinical and laboratory studies were conducted in 100 children (toddlers up to 3 years old), hospitalized in St. Olga's children hospital No 4 with a diagnosis of influenza or ARVI. The etiology of diseases was established using serological methods and immunofluorescence analysis; the immune and interferon status was determined. VIFERON®-suppositories were used rectally daily in age-related dosages. The effectiveness of therapy was evaluated by comparative analysis of disease symptoms, as well as laboratory indicators – immune and interferon status. Results. The use of VIFERON® – suppositories contributed to reducing intoxication and catarrhal symptoms, speeding up the recovery time of patients. After the treatment, the children's ability to produce IFN-α and – γ, as well, as sIgA content in nasal secretions, increased, but there was no marked enhancement in serum IL-1β, IL-8 levels, whereas the children in the control group and in 30% of cases occurred to change them. The use of the medicine did not cause any complaints in patients and staff. Conclusion. Data from clinical and laboratory studies of children hospitalized for ARVI, whose therapy included the VIFERON® – suppositories, indicate a significant therapeutic effect of this medicine and restoration of the immune and interferon defense systems of patients. Keywords: children, acute respiratory viral infections, recombinant interferon α-2b, immune status, interferon status, antiviral therapy, cytokines IL-1β, IL-8, IL-10, TNF-α

Evaluation of the effects of omega-3 & interferon alpha-2b administration on partial bladder outlet obstruction in a rat model.

Background & objectives:In bladder outlet obstruction-induced rat models, the transforming growth factor-beta (TGF-β) and collagen ratios have been shown to be increased. Increased TGF-β leads to fibrosis. In this study, the effect of omega-3 and interferon alpha-2b (IFN α-2b) was investigated on oxidative stress, inflammation and fibrosis in bladder structure in a partial bladder outlet obstruction (PBOO) rat model.Methods:A total of 35 male Wistar albino rats, weighing 300-350 g, were used in the study. The rats were randomly divided into five groups. At the end of the experimental period, bladders were harvested from all the rats, and pathological analysis of the rat bladder tissues was performed. In addition, investigations were carried out with enzymatic and non-enzymatic antioxidant systems to study the antioxidant properties of omega-3 fatty acid and IFN alpha-2b.Results:Increased bladder weight in the PBOO group, in comparison to the control group, was decreased by the administration of omega-3 and IFN α-2b (P=0.002). Significantly higher superoxide dismutase (SOD) levels were detected in group 2 in comparison to the control group. It was also detected that serum SOD, glutathione peroxidase and nitric oxide (NO) levels were significantly higher in group 2 when compared to the control group (P<0.05). In the pathologic evaluation, group 2 showed significantly increased inflammation and fibrosis compared to the control group. Omega-3 treatment significantly decreased inflammation. It was shown that IFN α-2b application partially decreased inflammation.Interpretation & conclusions:The results of the present study showed that in addition to the standard primary approaches to prevent the damage to the upper urinary tract secondary to PBOO, omega-3 fatty acid and IFN α-2b could be beneficial as adjunct treatment in clinical practice. However, this needs to be further investigated with prospective, randomized clinical trials with larger sample sizes.

Pegylated Interferon α Therapy in Chronic Delta Hepatitis: A One-Center Experience.

Background:The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α).Objectives:In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus.Patients and Methods:The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment.Results:Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate.Conclusions:Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.

Retrospective Study of Periocular Non Melanoma Skin Cancer Treated with the Combination of IFN alpha2b and Gamma (HeberPAG)

Background: Non-melanoma skin cancer can cause considerable morbidity when located on the eyelids and periocular skin. Basal cell carcinoma is the commonest periocular malignancy and although metastases are extremely rare, local invasion can cause significant and sometimes severe morbidity. Interferons may provide a nonsurgical approach to the management of these tumors. The aim of this work was to evaluate retrospectively, the effect of a formulation containing IFNs alpha2b and gamma in synergistic proportions (HeberPAG) on patients with periocular NMSC. Methods: The patients were identified from the data base from Department of Peripheral Tumors at “National Institute of Oncology and Radiobiology” in Havana; Dermatological Department at “Hermanos Ameijeiras” and “Enrique Cabrera” Hospitals; and policlinics from rural zone in Mayabeque; Cuba. The applications of IFN combination were practiced by medical doctors specialized in dermato-oncology. The employed doses for IFN combination were from 0.875 × 106 IU to 27 × 106 IU. Results: The series include 18 basal cell carcinoma and 3 squamous cell carcinoma of the skin with predominant clinical forms mixed (33.3%) and nodular (38.1%), 3 cases were terebrant, 2 ulcerated and 1 pigmented. The median time of tumor evolution was 16.5 months with an initial diameter of 8.25 cm. At week 12 after the end of treatment, a 47.6% complete response rate was obtained. A partial response was achieved in 5 patients (23.8%). A high response rate was obtained with overall response (CR+PR) in 71.4%. All patients reported at least 1 adverse event. The most frequent (>20%) were fever, chills, anorexia, cephalea, perilesional erythema and edema, asthenia, arthralgia and general discomfort. Conclusions: HeberPAG is an alternative useful to surgery in patients with periocular non-melanoma skin cancer when other therapies have failed or are not possible. The encouraging result justifies further confirmatory trials in periocular region.

The GERMELATOX DeCOG-trial: German melanoma patients and their attitude toward toxicity during adjuvant interferon treatment.

TPS9113^ Background: Although trials of adjuvant interferon alfa-2b (IFN alpha-2b) in high-risk melanoma patients suggest improvement in disease-free survival (DFS), a metaanalysis could only show ...

Acute hepatitis C: A 24-week course of pegylated interferon alpha-2b versus a 12-week course of pegylated interferon alpha-2b alone or with ribavirin

Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration.

Reduction of cell viability induced by IFN-alpha generates impaired data on antiviral assay using Hep-2C cells

Type I interferons (IFNs) exert an array of important biological functions on the innate immune response and has become a useful tool in the treatment of various diseases. An increasing demand in the usage of recombinant IFNs, mainly due to the treatment of chronic hepatitis C infection, augmented the need of quality control for this biopharmaceutical. A traditional bioassay for IFN potency assessment is the cytopathic effect reduction antiviral assay where a given cell line is preserved by IFN from a lytic virus activity using the cell viability as a frequent measure of end point. However, type I IFNs induce other biological effects such as cell-cycle arrest and apoptosis that can influence directly on viability of many cell lines. Here, we standardized a cytopathic effect reduction antiviral assay using Hep-2C cell/mengovirus combination and studied a possible impact of cell viability variations caused by IFN-alpha 2b on responses generated on the antiviral assay. Using the four-parameter logistic model, we observed less correlation and less linearity on antiviral assay when responses from IFN-alpha 2b 1000IU/ml were considered in the analysis. Cell viability tests with MTT revealed a clear cell growth inhibition of Hep-2C cells under stimulation with IFN-alpha 2b. Flow cytometric cell-cycle analysis and apoptosis assessment showed an increase of S+G2 phase and higher levels of apoptotic cells after treatment with IFN-alpha 2b 1000IU/ml under our standardized antiviral assay procedure. Considering our studied dose range, we also observed strong STAT1 activation on Hep-2C cells after stimulation with the higher doses of IFN-alpha 2b. Our findings showed that the reduction of cell viability driven by IFN-alpha can cause a negative impact on antiviral assays. We assume that the cell death induction and the cell growth inhibition effect of IFNs should also be considered while employing antiviral assay protocols in a quality control routine and emphasizes the importance of new approaches for IFN potency determination.

Intracellular production of IFN-alpha 2b in Lactococcus lactis

Human interferon alpha (IFN-α) was expressed in two strains of Lactococcus lactis by aid of two promoters (P32 and Pnis) giving rise to two recombinant strains: MG:IFN and NZ:IFN, respectively. The expression of IFN was confirmed by ELISA and western blotting. Highest production was achieved using glucose for growth of both recombinant strains with nisin, used for induction of the recombinant strain with Pnis promoter, at 30 ng/ml. The optimum time for MG:IFN was 9 h and for NZ:IFN was 4.5 h. The highest productions by MG:IFN and NZ:IFN were 1.9 and 2.4 μg IFN/l, respectively. Both of the expressed IFNs showed bioactivities of 1.9 × 10(6) IU/mg that were acceptable for further clinical studies.

A word of caution: do not wake sleeping dogs; micrometastases of melanoma suddenly grew after progesterone treatment

BackgroundHormonal treatment might affect the immune response to tumor antigens induced in cancer patients who are being vaccinated.Case presentationA 33 years-old woman was diagnosed with cutaneous melanoma in May 2009. Her melanoma was located in the intermammary sulcus, had a Breslow thickness of 4 mm, a Clark’s level IV, it was ulcerated and highly melanotic. The bilateral sentinel node biopsy was negative. She entered into a randomized Phase II/III clinical study comparing a vaccine composed of irradiated melanoma cells plus BCG plus GM-CSF versus IFN-alpha 2b and she was assigned to the vaccine arm. During the two years treatment she remained disease-free; the final CAT scan being performed in August 2011. Between November and December 2011, her gynecologist treated her with three cycles of 200 mg progesterone/day for ten days, every two weeks, for ovary dysfunction. In November 2011 the patient returned to the Hospital for clinical and imaging evaluation and no evidence of disease was found. At the next visit in March 2012 an ultrasound revealed multiple, large metastases in the liver. A CAT scan confirmed the presence of liver, adrenal glands and spleen metastases. A needle biopsy of a liver lesion revealed metastatic melanoma of similar characteristics to the original tumor. We suggest that progesterone treatment triggered proliferation of so far dormant micrometastases that were controlled during CSF470 vaccine treatment.ConclusionThe use of progesterone in patients with melanoma that are under immunological treatments should be carefully considered, since progesterone could modify the balance of pro-inflammatory and Th1 functions to a regulatory and anti-inflammatory profile of the immune system that could have an impact in tumor progression.

Vertical genotype 1 HCV infection treated successfully in the second year of life: A case report

SummaryBackgroundPerinatal HCV transmission appears to be an important cause of HCV in children. Treatment of chronic hepatitis C in young children is controversial because of spontaneous HCV clearance and possible adverse events.Case ReportVertical HCV genotype 1 infection was diagnosed in a 3-month-old infant. In the subsequent clinical examination we still observed hepatomegaly, fluctuations of ALT, AST and GGT activity, with the highest values 2206 U/L, 1319 U/L, and 297 U/L, respectively. In qPCR, HCV RNA was >700.000 IU/ml. In the 42nd week of observation, liver biopsy was performed with Grade 1 grading and Grade 1 staging. At age 12 months, interferon-alpha2b (1.5 MU 3 times a week) and ribavirin (2×80 mg daily) were administered for 48 weeks. At the beginning of the treatment we observed fever after IFN injection. In the 12th week of therapy, HCV RNA disappeared followed by SVR, and it was sustained for 6 years. To our knowledge, this is the first report of a pediatric (1-year-old) patient treated with combined IFN alpha-2b and ribavirin therapy.ConclusionsThis case report confirms the possibility of successful anti-HCV treatment in a young child, with 6-year sustained virological response without significant adverse events.

Effects of mutation number in interferon sensitivity determining region on peripheral blood CD4+ T cell subsets (Th1, Th2) in chronic hepatitis C patients with hepatitis C virus genotype 1b and high viral load

The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR. Subjects included 44 patients with CHC infected with genotype 1b and high viral load. The number of AA mutations in the ISDR was retrospectively determined using stored serum samples taken immediately before starting therapy. All patients received IFN-alpha 2b or pegylated-IFN (PEG-IFN)-alpha 2b and ribavirin. When serum hepatitis C virus-ribonucleic acid (HCV-RNA) was negative at 4 or 12weeks after starting therapy, the patient was defined as having rapid viral response (RVR) or early viral response (EVR), respectively. CD4(+) T cell (Th1 or Th2) in peripheral blood (PB) before and until day 56 of treatment was analyzed. Rates of RVR and EVR were 0 (0/21) and 14% (3/21), respectively, in patients with one or fewer AA mutations in the ISDR (ISDR0-1), and 30 (7/23), and 74% (17/23), respectively, with two or more AA mutations in the ISDR (ISDR>2). Although the percentage of PB Th1 cells did not differ between the two groups during the study period, the percentage of PB Th2 cells was significantly lower in the ISDR0-1 group than in the ISDR>2 group at baseline and on days3, 7, 14, and 28 of treatment. The number of AA mutations in the ISDR influenced PB Th2 cells before and until day 28, and was associated with higher RVR and EVR rates.

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

To examine whether the combination of interferon (IFN)-alpha and maitake mushroom D-fraction (PDF), a bioactive mushroom extract, might potentiate the anticancer activity of IFN-alpha in bladder cancer T24 cells in vitro. Effects of recombinant IFN-alpha(2b) (0-50 000 IU/mL), PDF (0-700 microg/mL), or their combinations were assessed on T24 cell growth at 72 h. Cell cycle analysis and assays for double-stranded DNA-dependent protein kinase (DNA-PK) were performed to explore possible antiproliferative mechanism of these agents. IFN-alpha(2b) was able to induce a significant ( approximately 50%) growth reduction at 20 000 IU/mL, which further declined to approximately 66% at 50 000 IU/mL. PDF had no effects up to 200 microg/mL, but there was an approximately 20% and approximately 53% growth reduction at 400 and 700 microg/mL, respectively. When the varying concentrations of IFN-alpha(2b) and PDF were combined, 10 000 IU/mL of IFN-alpha(2b) combined with 200 microg/mL of PDF resulted in an approximately 75% growth reduction. This was accompanied by a G(1) cell cycle arrest, shown by cell cycle analysis. Concurrently, DNA-PK activity in IFN-alpha(2b)/PDF-treated cells was almost three-fold higher than controls. The combination of IFN-alpha(2b) (10 000 IU/mL) and PDF (200 microg/mL) reduced growth by approximately 75% in T24 cells. This appears to be due to a synergistic potentiation of these two agents, inducing a G(1) arrest with DNA-PK activation. Therefore, the IFN-alpha(2b)/PDF combination could trigger DNA-PK activation that may act on the cell cycle to cease cancer cell growth.

Influence of bovine serum albumin on the secondary structure of interferon alpha 2b as determined by far UV circular dichroism spectropolarimetry

Many therapeutic biologics are formulated with excipients, including the protein excipient human serum albumin (HSA), to increase stability and prevent protein aggregation and adsorption onto glass vials. One biologic formulated with albumin is interferon alpha-2b (IFN alpha-2b). As is the case with other therapeutic biologics, the increased structural complexity of IFN alpha-2b compared to a small molecule drug requires that both the correct chemical structure (amino acid sequence) and also the correct secondary and tertiary structures (3 dimensional fold) be verified to assure safety and efficacy. Although numerous techniques are available to assess a biologic's primary, secondary and tertiary structures, difficulties arise when assessing higher order structure in the presence of protein excipients. In these studies far UV circular dichroism spectropolarimetry (far UV-CD) was used to determine the secondary structure of IFN alpha-2b in the presence of a protein excipient (bovine serum albumin, BSA). We demonstrated that the secondary structure of IFN alpha-2b remains mostly unchanged at a variety of BSA to IFN alpha-2b protein ratios. A significant difference in alpha helix and beta sheet content was noted when the BSA to IFN alpha-2b ratio was 5:1 (w/w), suggesting a potential conformational change in IFN alpha-2b secondary structure when BSA is in molar excess.