Síndrome de Vogt-Koyanagi-Harada

El síndrome de Vogt-Koyanagi-Harada es una enfermedad autoinmune multisistémica crónica, caracterizada por panuveítis difusa granulomatosa bilateral con desprendimiento exudativo de retina y papilitis. Compromete el sistema nervioso central (meninges, disacusia neurosensorial) así como piel y mucosas. A pesar de ser una enfermedad compleja y poco frecuente, se hace necesario comprender la importancia del diagnóstico rápido y el tratamiento oportuno con seguimiento especializado. Es por ello que se decidió realizar una revisión de la literatura con el objetivo de actualizar los conocimientos existentes sobre este tema. La búsqueda se realizó en diferentes publicaciones y textos básicos de la especialidad. Las fuentes consultadas fueron las bases de datos PubMed y Google Scholar. El diagnóstico de la enfermedad es esencialmente clínico y son los oftalmólogos quienes más lo sospechan por ser los síntomas oculares los más frecuentes y dramáticos. El pronóstico visual de los pacientes es generalmente bueno si el diagnóstico es precoz y se indica un tratamiento adecuado. Los corticosteroides sistémicos a altas dosis asociados a inmunosupresores y agentes biológicos tienen gran impacto en la evolución de la enfermedad, sobre todo estos últimos a nivel mundial, previniendo complicaciones y permitiendo resultados visuales satisfactorios para una mejor calidad de vida del paciente.

Vogt-Koyanagi-Harada syndrome is a chronic multisystem autoimmune disease characterized by bilateral diffuse granulomatous panuveitis with exudative retinal detachment and papillitis. It involves the central nervous system (meninges, sensorineural dysacusis) as well as skin and mucous membranes. In spite of being a complex and infrequent disease, it is necessary to understand the importance of rapid diagnosis and timely treatment with specialized follow-up. For this reason, it was decided to carry out a review of the literature with the aim of updating the existing knowledge on this subject. The search was carried out in different publications and basic texts of the specialty. The sources consulted were the PubMed and Google Scholar databases. The diagnosis of the disease is essentially clinical and it is the ophthalmologists who suspect it the most because the ocular symptoms are the most frequent and dramatic. The visual prognosis of patients is generally good if the diagnosis is early and adequate treatment is indicated. Systemic corticosteroids at high doses associated with immunosuppressants and biological agents have a great impact on the evolution of the disease, especially the latter worldwide, preventing complications and allowing satisfactory visual results for a better quality of life of the patient.

New progress on the use of Dual Biologic Therapy for patients with Inflammatory Bowel Disease / 中国综合临床

At present, the incidence of inflammatory bowel disease in China is increasing. Although new biological agents continue to emerge, which induce a higher clinical remission rate in moderate and severe patients than traditional drugs and have much advantages in reducing the risk of surgery and changing the natural history, the remission rate of biological agents monotherapy is still not enough. In this context, dual biologic therapy is a viable strategy. Dual biologic therapy is mainly indicated for patients with inflammatory bowel disease that is refractory or complicated with extraintestinal manifestations.It is often used in combination with clinical practice according to the characteristics of drugs, showing relatively great efficacy and safety, but a series of key questions still need a high level of research evidence to explore.

Presente y futuro del tratamiento biológico y moléculas pequeñas en la dermatitis atópica / Present and future of biological treatment and small molecules in atopic dermatitis

La dermatitis atópica (DA) es una condición inflamatoria crónica de la piel de etiología multifactorial. Buscando mejorar la respuesta clínica minimizando los efectos adversos y ampliar el arsenal terapéutico disponible, se ha dado pie al desarrollo de nuevos fármacos con resultados prometedores en la calidad de vida. Los inmunomoduladores sistémicos clásicos son considerados el tratamiento estándar en los casos de DA moderada a severa refractaria al tratamiento con corticoides tópicos. Estos se encasillan dentro de las denominadas moléculas pequeñas, junto con los inhibidores de Janus- en un efecto pleiotrópico en las citoquinas y por ende, no selectivo. Los medicamentos biológicos poseen ventajas frente a los inmunomoduladores clásicos, principalmente su mayor especificidad gracias a la similitud con las moléculas endógenas. Dupilumab se mantiene siendo el único fármaco biológico aprobado por la FDA para el tratamiento de la DA, con una seguridad a corto plazo demostrada. Algunas moléculas nuevas, como el tralokinumab y los inhibidores JAK, presentan resultados prometedores. De este grupo, abrocitinib pareciera posicionarse como una alternativa al menos similar que dupilumab. La creciente investigación de nuevas alternativas ha creado una revolución terapéutica para que nuestros pacientes puedan acceder a una mejor calidad de vida. No obstante, es difícil lograr comprender la efectividad y seguridad de cada uno de los tratamientos disponibles, por la falta de estudios comparativos. La siguiente revisión muestra las nuevas terapias biológicas y algunas moléculas pequeñas con evidencia para su uso en DA

Atopic dermatitis (AD) is a chronic inflammatory condition of the skin with a multifactorial etiology. Seeking to improve the clinical response by minimizing adverse effects and expanding the available therapeutic arsenal, the development of new drugs has led to promising results on quality of life. Classic systemic immunomodulators are considered the standard treatment in cases of moderate to severe AD refractory to treatment with topical corticosteroids. These are classified into molecules, along with Janus kinase inhibitors (JAKs). Small molecules act on intracellular targets, with the inconveniency of producing a pleiotropic effect on cytokines and, therefore, non-selective actions. Biologics have advantages over classical immunomodulators, mainly their greater specificity thanks to the similarity between endogenous molecules. Dupilumab remains the only biologic drug approved by the FDA for the treatment of AD, with demonstrated short-term safety. Some new molecules, such as tralokinumab and JAK inhibitors, have shown promising results. Of this group, abrocitinib seems to be positioned as an alternative at least similar to dupilumab. The current investigation of new alternatives has created a therapeutic revolution so that we can offer our patients a better quality of life. However, it is difficult to understand the efficacy and safety of each of the available treatments due to the lack of comparative studies. The following review shows the new biological therapies and small molecules with evidence for their use in DA.

Análise crítica do uso dos anti-TNF na era dos novos agentes biológicos na doença inflamatória intestinal / Critical analysis of anti-tnf use in the era of new biological agents in inflammatory bowel disease

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), tanto a doença de Crohn (DC) como a retocolite ulcerativa (RCU), são doenças crônicas imunomediadas que se apresentam com períodos de surto e remissão e requerem terapia a longo prazo. A terapia com anti-fator de necrose tumoral (anti-TNF) tem mudado o manejo da doença reduzindo a necessidade de hospitalizações, cirurgias e melhorando a qualidade de vida dos pacientes. OBJETIVO: O objetivo do presente trabalho é apresentar uma revisão sobre a importância dos agentes anti-TNF no contexto da DII, levando em consideração situações em que essas drogas são usadas como terapia de primeira linha. MÉTODOS: Revisão narrativa baseada nas melhores evidências disponíveis na literatura através de buscas feitas nas bases de dados MedLine e PubMed até abril de 2020, utilizando as seguintes palavras chaves: "doença inflamatória intestinal'', "agentes anti-TNF" e "terapia biológica". CONCLUSÃO: A terapia biológica permanece sendo fundamental no tratamento da DII. Na ausência de estudos "head-to-head'' comparando os biológicos entre si, a escolha do agente biológico pode ser um desafio na prática clínica e múltiplas variáveis devem ser levadas em consideração. Os agentes anti-TNF devem ser considerados terapia de primeira linha em situações específicas como na colite ulcerativa aguda grave, na doença de Crohn fistulizante e nas manifestações extra-intestinais da doença inflamatória intestinal, uma vez que há evidências científicas robustas que sustentam a sua eficácia e segurança nessas situações.

Terapia biológica na doença de Crohn: quando iniciar? / Biologic therapy for Crohn's disease: when to initiate?

A doença de Crohn se caracteriza como uma doença inflamatória, que acomete qualquer porção do trato gastrintestinal, resultante da desrregulação imunológica, gerenciada por fatores endógenos e exógenos. As formas de abordagem terapêutica da doença variam conforme sua apresentação clínica e gravidade, bem como o impacto na qualidade de vida do portador. A terapia biológica vem se tornando uma das principais classes utilizadas no contexto desta enfermidade, mas não está claro quando deve ser iniciada ou em que momento a própria doença deve ser considerada moderada ou grave. Sua forma de apresentação multiforme dificulta a classificação dos pacientes nestes grupos. Neste trabalho, foi realizada revisão de literatura sobre a introdução de terapia biológica como tratamento da doença inflamatória intestinal em curso. (AU)

Crohn's Disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract, caused by immune dysregulation, managed by endogenous and exogenous factors. The forms of therapeutic approach of the disease vary significantly according to its clinical presentation and severity, as well as to the impact on patient's quality of life. Biologic therapy has become one of the main classes used in the context of this disease; however, when it should be initiated or at what time the disease itself should be considered moderate or severe is not clear. Its multiform presentation makes it difficult to classify patients in these groups. In this work, a literature review was carried out about the introduction of the biologic therapy as a treatment of the ongoing inflammatory bowel disease. (AU)

Biologic agents for asthma treatment

Most treatment strategies for asthma currently include inhaled corticosteroids, with the addition of long-acting beta-2-agonists or leukotriene modifiers, if necessary. However, some patients may not respond to conventional treatment. A better understanding of the pathophysiology of asthma has recently led to the development of biological agents, which have shown promising results for symptom control and future risk reduction in severe asthmatics. This article reviews currently available biologic agents, introduces related studies, and describes the subgroup of patients benefitting from each of biologic agents in the view point of precision medicine.

Main adverse reactions in biological agents in dermatology and their strategies / 中华皮肤科杂志

Biologic therapy is a major advancement in clinical therapeutics.It provides a solution to severe and refractory diseases,meanwhile brings a series of new safety concerns.In dermatology biologic agents are mainly applied to the treatment of psoriasis,atopic dermatitis,chronic urticaria,and malignant melanoma,etc.Different biologics may induce different adverse reactions,among which the commonest are infection,allergy and autoimmune response.Administration of biologics should be strictly managed in terms of therapeutic target,mechanism of action,features of preparation,and conditions of patients.Patients should be strictly evaluated for their eligibility before treatment and closely monitored during the therapy,so as to ensure their safety.

Fecal microbiota transplantation for refractory Crohn's disease

Approximately one-third of patients with Crohn's disease do not respond to conventional treatments, and some experience significant adverse effects, such as serious infections and lymphoma, and many patients require surgery due to complications. Increasing evidence suggests that specific changes in the composition of gut microbiota, termed as dysbiosis, are a common feature in patients with inflammatory bowel disease (IBD). Dysbiosis can lead to activation of the mucosal immune system, resulting in chronic inflammation and the development of mucosal lesions. Recently, fecal microbiota transplantation, aimed at modifying the composition of gut microbiota to overcome dysbiosis, has become a potential alternative therapeutic option for IBD. Herein, we present a patient with Crohn's colitis in whom biologic therapy failed previously, but clinical remission and endoscopic improvement was achieved after a single fecal microbiota transplantation infusion.

Therapies for crohn's disease: a clinical update / Terapia farmacológica em portadores de doença de Crohn. Atualização clínica

ABSTRACT The main objectives of clinical therapy in Crohn's disease are clinical and endoscopic remission without the use of corticosteroids for long periods of time, prevention of hospitalization and surgery, and improvement of quality of life. The main limitation of drug therapy is the loss of response over the long term, which makes incorporation of new drugs to the therapeutic arsenal necessary. This review analyses the main drugs currently used in clinical treatment of Crohn's disease.

RESUMO Os principais objetivos da terapia clínica na doença de Crohn são a remissão clínica e endoscópica por tempo prolongado, sem o uso de corticosteroides, além de evitar hospitalizações e cirurgias, e melhorar a qualidade de vida. A principal limitação da terapêutica medicamentosa é a perda de reposta a longo prazo, o que faz com que a incorporação de novas drogas ao arsenal terapêutico seja necessária. Esta revisão aborda os principais medicamentos utilizados atualmente no tratamento clínico da doença de Crohn.

Tumor Necrosis Factor Blockade Stimulates Circulating Osteoblastic Lineage Cells Activity while Reducing Circulating Osteoclasts

OBJECTIVE: This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. METHODS: Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. RESULTS: The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. CONCLUSION: The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.

Revisão sistemática da indução de autoanticorpos e lúpus eritematoso pelo infliximabe / Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus

Nesta revisão sistemática abordamos a indução de autoanticorpos e lúpus eritematoso pelo infliximabe, analisando estudos que dosaram vários autoanticorpos antes e após o uso do infliximabe em diversas doenças (artrite reumatoide, espondilite anquilosante, artrite psoriásica e doença de Crohn). Nossa busca foi realizada em nove bases de dados (Pub-Med, ScienceDirect, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo e LILACS). Foram encontradas 998 referências; 24 artigos foram separados na íntegra, dos quais 10 foram excluídos por não entrarem em nossos critérios de seleção. A escolha dos artigos foi realizada por dois revisores, e as divergências foram resolvidas por um terceiro revisor. Incluímos estudos de fase IV, com no mínimo três meses de duração. No total foram estudados 760 pacientes; o fator antinuclear, o anticorpo anti-DNA de dupla hélice e os antígenos extraídos pela salina foram os mais verificados. De todos os pacientes, apenas 10 (1,3%) apresentaram manifestações clínico-laboratoriais de lúpus induzido por infliximabe.

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

Biologic Agents in Rheumatic Diseases / 대한내과학회지

During the past three decades the treatment in rheumatology was revolutionized by the introduction of disease-modifying anti-rheumatic drugs. Advances in our understanding of the pathogenesis of rheumatic diseases have led to the discovery of critical pathogenetic mechanisms of inflammation and autoimmunity and the invention of new target-specific biologic agents. The development of biologic agents led to a new era in treatment of various rheumatic diseases. Treatments of rheumatic diseases such as rheumatoid arthritis (RA) had been very difficult in former days until conventional DMARDs was developed. Although synthetic DMARDs made it a lot easier to control rheumatic diseases, still, there were some difficulties on controlling diseases. The biologic agents inhibit specific pro-inflammatory cytokines as a targeted therapy to prevent inflammation and destruction of affected joint and/or tissues. Three TNF blocking agents, etanercept, infliximab and adalimumab, are the most well recognized and widely used biologic agents in RA, ankylosing spondylitis (AS), and some other inflammatory autoimmune diseases. Furthermore, an inhibitor of IL-1 (anakinra), a B-cell depleting drug (rituximab) and an inhibitor of T-cell costimulation (abatacept) are developed in turn asnovel biologic agents which are believed to be effective in number of rheumatic diseases. Recently, an inhibitor of IL-6 (tocilizumab) and 2 other TNF inhibitors (golimumab and certolizumab) are developed. Here, the brief descriptions of recently used biologic agents and their efficacies and safeties are discussed.

Avaliação da resposta terapêutica ao infliximabe em pacientes com Doença de Crohn / Evaluation of infliximab treatment for Crohns Disease pacients

Introdução: infliximabe representa grande avanço no tratamento da Doença de Crohn refratária, demonstrada em ensaios clínicos, tanto no regime de indução quanto em manutenção. Objetivo: avaliar o tratamento com infliximabe, estudando sua eficácia, apontando possíveis fatores preditivos de resposta e, por fim, descrevendo possíveis reações adversas registradas. Resultados: após a indução, 86,1% dos pacientes responderam ao tratamento; na 54ª semana de manutenção, 88,9%. Descontinuaram corticosteroides, 83,4%. Ao final da avaliação, 83,4% estavam em remissão de doença. Discussão: as frequências de resposta foram maiores em relação aos ensaios clínicos, no entanto, semelhantes em relação aos trabalhos mais recentes, retrospectivos e prospectivos. Não foram encontrados fatores preditivos de resposta. As respostas de pacientes com Doença de Crohn ativa e fistulizante foram semelhantes. Um pequeno número de pacientes (05) apresentou efeitos adversos atribuíveis ao medicamento, porém nenhum precisou interromper ou suspender tratamento. Conclusão: o infliximabe foi efetivo e seguro entre os pacientes com Doença de Crohn ativa e fistulizante.

Introduction: infliximab represents a great advance in refractory Crohns Disease treatment, showed in clinical trials, for induction as well as for maintenance therapy. Aim: evaluate the infliximab treatment, studying its efficacy, pointing possible predictive factor of response, and describing register collateral effects. Results: after induction, 86.1% of the patients improved with the treatment; 88.9% improved with maintenance therapy at week 54. 83.4% were able to discontinue corticosteroids. By the end of the evaluation, 83.4% were in clinical remission. Discussion: however, the response was superior when compared to the clinical trials; it was similar to more recent studies. It was not found any predictors of response to infliximab. A small number of patients reported side effects possibly associated with the drug, but none of them needed to discontinue treatment. Conclusion: the infliximab was effective and safe among patients with active and fistulizing Crohns Disease.

Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from the Bench Side to the Clinic

Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-beta, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-alpha, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-alpha. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.

Uso de terapia biológica na doença de Crohn metastática: relato de caso e revisão da literatura / Use of biological therapy in metastatic Crohn's disease: a case report and literature review

A doença de Crohn metastática envolve a infiltração cutânea granulomatosa em locais anatomicamente separados do trato gastrointestinal, com tendência à cronicidade. É relatado caso de paciente masculino, 20 anos, há seis meses com dor e eliminação de secreção purulenta de úlceras em região perianal, inguinal direita e genital, sem melhora com o uso metronidazol e ciprofloxacina. Antecedente de proctocolectomia em 2002. Ao exame, à inspeção, evidenciava-se orifício fistuloso posterior a 2,0 cm da borda anal, úlcera de 5,0 cm na base do escroto e outra úlcera circundando a base do pênis; ao toque, ânus fibrótico e encarcerado. Realizada fistulotomia, biópsia e curetagem das úlceras genital e inguinal. O resultado histopatológico evidenciou processo inflamatório granuloso não caseoso. Em virtude da falha terapêutica dos antimicrobianos, foi optado pelo tratamento com infliximabe na dose 5 mg/kg nas semanas 0, 2 e 6, e azatioprina 2 mg/kg/dia. Ao término da fase de indução, o paciente apresentava cicatrização parcial das lesões ulceradas, ausência de secreção e alívio da dor. Atualmente em acompanhamento ambulatorial com infusões de infliximabe a cada oito semanas.

The metastatic Crohn's disease involves granulomatous infiltration of skin in places anatomically separated from the gastrointestinal tract, with a tendency to chronicity. We report the case of male patient, 20 years old, complaining of pain and elimination of purulent secretion from ulcers in the perianal region, right inguinal and genital for six months, without improvement using metronidazole and ciprofloxacin. Previous proctocolectomy in 2002. On examination, the inspection revealed a fistulous orifice on posterior midline at 2.0 cm from the anal verge, an ulcer of 5.0 cm at the base of the scrotum and other ulcer encircling the base of the penis; on digital touch, anus fibrotic and incarcerated. Performed fistulotomy, biopsy and curettage of genital and inguinal ulcers. The histo-pathological study confirmed noncaseating granulomatous inflammatory process. Because of the failure of antimicrobial therapy, it was opted for treatment infliximab at the dose 5 mg/kg at weeks 0, 2 and 6, and azathioprine 2 mg/kg/day. In the end stage of induction, the patient had partial healing of ulcerated lesions, absence of secretion and pain relief. Currently in monitoring with outpatient infusions of infliximab every eight weeks.

The therapy of low levels of high density lipoprotein-cholesterol / 医学研究生学报

High density lipoprotein(HDL) is an antiatherogenetic lipoprotein and low level of HDL-cholesterol(HDL-C) in plasma is a risk factor for coronary heart disease.Therefore,raising the level of HDL-C by pharmaceuticals,oestrogen replacement and biologic therapy for dyslipidemia exhibit great clinical significance.

Anti-HER2/neu Peptide Producing Vector System for Biologic Therapy - Is It Possible to Mass-produce the Peptide?

A humanized monoclonal antibody against HER2 has been using in a clinical setting and has been shown to possess therapeutic properties. A mimetic peptide against HER2 was also reported to bind to the HER2 receptor with some therapeutic potential. Based on a previous report and the sequence of Herceptin, we designed oligonucleotides of anti-HER2 mimetic peptides, named V2 and V3 peptides, in order to develop a peptide- producing vector system for biologic therapy against HER2- overexpressing cancers. We also adopted the sequence of a previously reported mimetic peptide, V1 (Park BW et al. Nat. Biotechnol, 2000, 18: 194-198), as a reference peptide. We examined the effects of the V2 and V3 peptides against the HER2-overexpressing cell lines, SK-BR-3 and T6-17. Transient transfection of the construct expressing V1 and V2 inhibited cell proliferation in HER2-overexpressing cell lines by 20 - 30%, but had no effect on the HER2-negative NIH3T3 cells. The proliferation inhibition shown by V2 was slightly better than that shown by V1. Recombinant peptides V2 and V3 were produced on a large scale in an E. coli system, and the V2 peptide showed anti-HER2-specific tumor cell proliferation inhibition of 10% to 30%. Current results suggest that anti-HER2 mimetic peptides, overexpressed by a constitutive promoter or produced in an E. coli system, could specifically inhibit the proliferation of HER2-expressing cancer cells. Further efforts to augment the biologic specificity and efficacy and to develop new technologies for the purification of the peptide from the E coli system are needed.