RESUMO
Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.
Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Índice de Gravidade de Doença , Idoso , CubaRESUMO
La administración de drogas que bloquean el sistema del factor de crecimiento epidérmico y su receptor ha demostrado efectos beneficiosos en pacientes con tumores sólidos de origen epitelial. Cada día resulta más frecuente el uso de múltiples modalidades terapéuticas para combatir estos tumores, las cuales incluyen la asociación de agentes blanco y cirugía. Los agentes que actúan sobre dicho sistema pudieran causar trastornos de la cicatrización al bloquear vías del sistema que también intervienen en la cicatrización de las heridas. El objetivo de este artículo es revisar y comentar acerca del conocimiento de la relación entre el uso de las drogas anti-EGF/EGFR y los trastornos en la cicatrización de las heridas. La búsqueda bibliográfica se realizó en PubMed y Google (solo en español e inglés) y se tuvo en cuenta cualquier publicación encontrada hasta enero del 2014. Se incluyeron los anticuerpos monoclonales cetuximab, panitumumab y nimotuzumab; las pequeñas moléculas erlotinib y gefitinib y las vacunas terapéuticas contra el cáncer CIMAvax EGF y HER-1. Se hace especial énfasis en los biofarmacéuticos nimotuzumab, CIMAvax EGF y HER-1; producidos en el Centro de Inmunología Molecular, La Habana, Cuba, debido a su amplio uso en Cuba y otros países de América Latina. No se encontraron evidencias de relación entre el uso de estos productos y la aparición de trastornos en la cicatrización de las heridas. Dado que los tratamientos anti-EGF/EGFR también inhiben la proliferación celular que induce el drenaje de las heridas y la migración celular inducida por las radiaciones, se sugiere que el tratamiento anti-EGF/EGFR no debe suspenderse, ni antes ni después de la cirugía y sus posibles efectos deben ser vigilados. Obviamente, se necesitan ulteriores investigaciones por parte de los farmacólogos no clínicos y clínicos, oncólogos clínicos y cirujanos oncológicos para entender mejor los procesos fisiopatológicos de cicatrización en los cánceres de origen epitelial(AU)
The use of blocking drugs for epidermal growth factor and its receptor system has shown beneficial effects in patients with solid tumors of epithelial origin. It is increasingly common to use a multi-modal treatment approach towards solid tumors, often including the association of target agents and surgical resection. Some target agents can impair wound healing or cause increasing risk of perioperative complications if they block system pathways that may intervene in wound healing. The objective of this paper was to review and comment on the existing knowledge about the relationship between the use of anti-EGF/EGFR drugs and the disorders in wound healing. Citations from PubMed and Google (English and Spanish languages only) regardless of the date of publication were reviewed to identify potentially useful articles until January 2014. Monoclonal antibodies cetuximab, panitumumab, nimotuzumab; the small molecules erlotinib and gefitinib, and the therapeutic cancer vaccines called CIMAvax EGF and HER-1. Special emphasis was made on biopharmaceuticals nimotuzumab, CIMAvax EGF and HER-1, all of them produced at the Center of Molecular Immunology, Havana, Cuba, because of their extensive use in Cuba and many Latin-American countries. No evidence of association between the use of these products and the occurrence of complications in wound healing was found. Given that the anti-EGF/EGFR treatments also inhibit the tumor cell proliferation that wound drainage induces and the radiation-induced cell migration, it is suggested that that the administration of this kind of drugs should be kept before and after the surgery and consequently, its possible effects must be under surveillance. Obviously, non-clinical and clinical pharmacologists, clinical oncologists and surgeons need further researches for better understanding the pathophysiological wound healing processes in epithelial cancers(AU)
Assuntos
Humanos , Masculino , Feminino , Cicatrização , Vacinas Anticâncer/uso terapêutico , Anticorpos Monoclonais/imunologia , Neoplasias/cirurgia , CubaRESUMO
La administración de drogas que bloquean el sistema del factor de crecimiento epidérmico y su receptor ha demostrado efectos beneficiosos en pacientes con tumores sólidos de origen epitelial. Cada día resulta más frecuente el uso de múltiples modalidades terapéuticas para combatir estos tumores, las cuales incluyen la asociación de agentes blanco y cirugía. Los agentes que actúan sobre dicho sistema pudieran causar trastornos de la cicatrización al bloquear vías del sistema que también intervienen en la cicatrización de las heridas. El objetivo de este artículo es revisar y comentar acerca del conocimiento de la relación entre el uso de las drogas anti-EGF/EGFR y los trastornos en la cicatrización de las heridas. La búsqueda bibliográfica se realizó en PubMed y Google (solo en español e inglés) y se tuvo en cuenta cualquier publicación encontrada hasta enero del 2014. Se incluyeron los anticuerpos monoclonales cetuximab, panitumumab y nimotuzumab; las pequeñas moléculas erlotinib y gefitinib y las vacunas terapéuticas contra el cáncer CIMAvax EGF y HER-1. Se hace especial énfasis en los biofarmacéuticos nimotuzumab, CIMAvax EGF y HER-1; producidos en el Centro de Inmunología Molecular, La Habana, Cuba, debido a su amplio uso en Cuba y otros países de América Latina. No se encontraron evidencias de relación entre el uso de estos productos y la aparición de trastornos en la cicatrización de las heridas. Dado que los tratamientos anti-EGF/EGFR también inhiben la proliferación celular que induce el drenaje de las heridas y la migración celular inducida por las radiaciones, se sugiere que el tratamiento anti-EGF/EGFR no debe suspenderse, ni antes ni después de la cirugía y sus posibles efectos deben ser vigilados. Obviamente, se necesitan ulteriores investigaciones por parte de los farmacólogos no clínicos y clínicos, oncólogos clínicos y cirujanos oncológicos para entender mejor los procesos fisiopatológicos de cicatrización en los cánceres de origen epitelial(AU)
The use of blocking drugs for epidermal growth factor and its receptor system has shown beneficial effects in patients with solid tumors of epithelial origin. It is increasingly common to use a multi-modal treatment approach towards solid tumors, often including the association of target agents and surgical resection. Some target agents can impair wound healing or cause increasing risk of perioperative complications if they block system pathways that may intervene in wound healing. The objective of this paper was to review and comment on the existing knowledge about the relationship between the use of anti-EGF/EGFR drugs and the disorders in wound healing. Citations from PubMed and Google (English and Spanish languages only) regardless of the date of publication were reviewed to identify potentially useful articles until January 2014. Monoclonal antibodies cetuximab, panitumumab, nimotuzumab; the small molecules erlotinib and gefitinib, and the therapeutic cancer vaccines called CIMAvax EGF and HER-1. Special emphasis was made on biopharmaceuticals nimotuzumab, CIMAvax EGF and HER-1, all of them produced at the Center of Molecular Immunology, Havana, Cuba, because of their extensive use in Cuba and many Latin-American countries. No evidence of association between the use of these products and the occurrence of complications in wound healing was found. Given that the anti-EGF/EGFR treatments also inhibit the tumor cell proliferation that wound drainage induces and the radiation-induced cell migration, it is suggested that that the administration of this kind of drugs should be kept before and after the surgery and consequently, its possible effects must be under surveillance. Obviously, non-clinical and clinical pharmacologists, clinical oncologists and surgeons need further researches for better understanding the pathophysiological wound healing processes in epithelial cancers(AU)
Assuntos
Humanos , Vacinas Anticâncer/uso terapêutico , Cicatrização , Anticorpos Monoclonais/imunologiaRESUMO
BACKGROUND: The epidermal growth factor receptor (EGFR) signaling system is frequently unbalanced in human malignancies due to increased ligand production, receptor overexpression, receptor mutations, and/or cross-talk with other receptor systems. For this reason, the EGFR is an attractive target for anticancer therapy. The epidermal growth factor also plays an important role in regulating multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis. In the Center of Molecular Immunology, a cancer vaccine is produced (CIMAvax® EGF) that blocks the binding of EGF to its receptor. This blockade causes a significant inverse association between the anti-EGF antibody titers and EGF concentration. Around 1,500 patients with non-small cell lung cancer have been treated, showing that this vaccine is safe, immunogenic, increases survival and improves quality of life. Taking into account the therapeutic benefits of CIMAvax® EGF vaccination and the role of EGF-EGFR system in the wound healing process, we decided to conduct a retrospective research with the aim of determining the effect to the CIMAvax® EGF vaccine on the wound healing process in patients undergoing surgical treatment. METHODS: Medical records of 452 vaccinated patients were reviewed and only six patients receiving surgical treatment were identified. Further information about these six patients was obtained from source documents, including medical records and operative reports using an observational list that included different variables. Post-surgical wound healing complications were identified using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) version 3.0. RESULTS: None of the six patients operated on presented adverse events related to the wound healing, that is to say, no wound dehiscence, wound infection, delayed wound healing, fistula formation, abscess formation or hemorrhage/bleeding associated with surgery during treatment with CIMAvax® EGF occurred. CONCLUSIONS: These results suggest that the use of CIMAvax® EGF does not produce a deleterious effect in the wound healing process.
Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator de Crescimento Epidérmico/antagonistas & inibidores , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Crescimento Epidérmico/imunologia , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacosRESUMO
El cáncer constituye un serio problema de salud para la humanidad. La mayoría de los tumores primarios del Sistema Nervioso Central son tumores astrocíticos. En esta revisión se provee información sobre algunos aspectos relacionados con los tumores astrocíticos, que incluyen la clasificación, factores pronóstico, tratamiento habitual, terapia biológica y factores angiogénicos. El glioblastoma multiforme se diagnostica en los pacientes con una mayor frecuencia. El tratamiento estándar en pacientes con tumores astrocíticos comprende la cirugía, seguida de radiación y quimioterapia. Sin embargo, cada vez son más importantes las investigaciones dirigidas a la inmunoterapia y terapia génica como parte de las opciones terapéuticas en estos pacientes.
Cancer is a serious health problem around the world. The majority of primary tumors of the Central Nervous System are of astrocytic lineage. In this review we provide an overview of several aspects related to this type of tumor, that includes classification, prognostic factors, therapy, and angiogenic factors. Glioblastoma Multiforme is diagnosed in patients at a much higher frequency. Standard treatment for patients with astrocytic tumors is surgery followed by radiotherapy and chemotherapy. However, immunotherapy and gene therapy studies are increasing to become other therapeutic options in these patients.
RESUMO
El cáncer constituye un serio problema de salud para la humanidad. La mayoría de los tumores primarios del Sistema Nervioso Central son tumores astrocíticos. En esta revisión se provee información sobre algunos aspectos relacionados con los tumores astrocíticos, que incluyen la clasificación, factores pronóstico, tratamiento habitual, terapia biológica y factores angiogénicos. El glioblastoma multiforme se diagnostica en los pacientes con una mayor frecuencia. El tratamiento estándar en pacientes con tumores astrocíticos comprende la cirugía, seguida de radiación y quimioterapia. Sin embargo, cada vez son más importantes las investigaciones dirigidas a la inmunoterapia y terapia génica como parte de las opciones terapéuticas en estos pacientes(AU)
Cancer is a serious health problem around the world. The majority of primary tumors of the Central Nervous System are of astrocytic lineage. In this review we provide an overview of several aspects related to this type of tumor, that includes classification, prognostic factors, therapy, and angiogenic factors. Glioblastoma Multiforme is diagnosed in patients at a much higher frequency. Standard treatment for patients with astrocytic tumors is surgery followed by radiotherapy and chemotherapy. However, immunotherapy and gene therapy studies are increasing to become other therapeutic options in these patients(AU)
Assuntos
Glioblastoma/classificação , Glioblastoma/cirurgia , Glioblastoma/terapia , Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/cirurgia , Neoplasias do Sistema Nervoso Central/terapia , Literatura de Revisão como AssuntoRESUMO
El proceso de enseñanza-aprendizaje en el área de la Estadística experimenta una mejoría con las prácticas en los sistemas estadísticos. En algunas ocasiones las carreras universitarias que incluyen asignaturas relacionadas con la Estadística no tienen concebido en su Plan de Estudios prácticas con sistemas Estadísticos, y en otros, estas no son suficientes para desarrollar las habilidades prácticas que requiere esta disciplina. De modo general, las limitaciones materiales condicionan la ausencia total o parcial de actividades prácticas. El creciente desarrollo de las Tecnologías de la Información y la Comunicación (TIC) ha brindado la posibilidad de suplir estas carencias, con el desarrollo de Multimedias Interactivas y Aulas Virtuales. Este proyecto incluye un conjunto de Prácticas de Estadística en soporte Multimedia, que tienen como objetivo preparar al estudiante para obtener el máximo rendimiento en los sistemas estadísticos. Este producto puede ser utilizado como sustituto del Aula real en aquellos casos en que por razones de tiempo, espacio, la práctica real no sea posible(AU)
The process of teaching and learning quality in the area of statistics is determined largely by the good clinical practices. Sometimes university courses that include subjects related to Statistics are not viewed in its practical curriculum statistical system, and in others, these are not sufficient to develop the practical skills required for this discipline. In general, the material constraints condition the total or partial absence of practical activities. The increasing development of Information Technology and Communication (ICT) has provided the possibility of filling these gaps, with the development of Interactive Multimedia and Virtual Classrooms. This project includes a set of Practice of Statistics in multimedia, which aim to prepare the student to obtain maximum performance in statistical systems. This product can be used as a substitute for real classroom in those cases where for reasons of time, space, actual practice is not possible(AU)
