A biosimilar is a biologic product that is similar to a reference biopharmaceutical product, the manufacturing process of which hinders the ability to identically replicate the structure of the original product, and therefore, it cannot be described as an absolute equivalent of the original medication. The currently available technology does not allow for an accurate copy of complex molecules, but it does allow the replication of similar molecules with the same activity. As biosimilars are about to be introduced in oncology practice, these must be evaluated through evidence-based medicine. This manuscript is a position paper, where the Brazilian Society of Clinical Oncology (SBOC) aims to describe pertinent issues regarding the approval and use of biosimilars in oncology. As a working group on behalf of SBOC, we discuss aspects related to definition, labeling/nomenclature, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, and the potential impact on financial burden in healthcare. We take a stand in favor of the introduction of biosimilars, as they offer a viable, safe, and cost-effective alternative to the biopharmaceutical products currently used in cancer. We hope this document can provide valuable information to support therapeutic decisions that maximize the clinical benefit for the thousands of cancer patients in Brazil and can contribute to expedite the introduction of this new drug class in clinical practice. We expect the conveyed information to serve as a basis for further discussion in Latin America, this being the first position paper issued by a Latin American Oncology Society.

Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.

Introducción: la automedicación se ha convertido en una práctica creciente en la población mundial. Este fenómeno ha sido promovido como una forma de autocuidado, con impacto positivo en la reducción del gasto dentro de los sistemas de salud; sin embargo, también se ve con preocupación, por los potenciales efectos negativos relacionados con diagnósticos y manejos inadecuados, que pueden afectar la salud de los individuos. Esta doble percepción del fenómeno se relaciona, en parte, con una gran diversidad de términos y conceptos relacionados, que hacen difícil su abordaje teórico-empírico. Para hacer comparaciones epidemiológicas adecuadas se requiere armonizar las definiciones implicadas. Objetivo: analizar el concepto de automedicación y términos relacionados a partir de las definiciones que aparecen en la literatura especializada del tema. Conclusiones: en las últimas cuatro décadas ha habido una evolución tanto de los términos como de las definiciones relacionadas con automedicación, desde un concepto muy simple que implica la ausencia de prescripción médica, hasta conceptos más complejos que abarcan conductas de muy diversa índole; aun aquellas en las que media un acto de prescripción no seguido o no cumplido por el paciente. Adicionalmente se aprecia una proliferación conceptual que justifica el ordenamiento de los términos relacionados con automedicación. Este artículo presenta una propuesta de clasificación en cuatro grupos: a. automedicación, b. autocuidado, c. preparaciones farmacéuticas y medicamentos, y d. prescripción. Esta propuesta puede facilitar la exploración y análisis del fenómeno y permitir futuras aproximaciones teóricas.

Introduction: self-medication has become a growing practice in the world population. This phenomenon has been promoted as a form of self-care, with a positive impact on reducing spending in health systems, however there is concern about the potential negative effects related to inadequate diagnosis and treatment, which can affect health of individuals. This dual perception of the phenomenon is partly related to a variety of terms and concepts used, that make difficult its theoretical and empirical approach. Harmonization of the definitions involved is required in order to make adequate epidemiological comparisons. Objectives: analyze the concept of self medication and related terms from the definitions in the literature of the subject. Conclusions: in the last four decades it has been an evolution of both the wording and the definitions related to self-medication, from a very simple concept that implies the absence of prescription, to more complex ones that encompass very diverse behaviors, even those mediated by an act of prescription but not followed or not completed by the patient. Additionally the conceptual proliferation seen, justify the ordering of the terms related to self-medication. This paper presents a proposal for classification in four groups: a. self-medication, b. self care, c. pharmaceutical preparations and medicines, and d. prescription. This proposal should facilitate the exploration and analysis of the phenomenon and allow future theoretical approaches.

Introdução: A automedicação tem se convertido em uma prática crescente na população mundial. Este fenômeno tem sido promovido como uma forma de auto-cuidado, com impacto positivo na redução do gasto dentro dos sistemas de saúde; por enquanto, também se vê com preocupação pelos potenciais efeitos negativos relacionados com diagnósticos e gestões inadequadas, que podem afetar a saúde dos indivíduos. Esta dupla percepção do fenômeno se relaciona, em parte, com uma grande diversidade de termos e conceitos relacionados, que fazem difícil sua abordagem teórico-empirica. Para fazer comparações epidemiológicas adequadas se requere harmonizar as definições implicadas. Objetivo: Analisar o conceito de automedicação e termos relacionados a partir das definições que aparecem na literatura especializada do tema. Conclusões: Nas últimas quatro décadas tem havido uma evolução tanto dos termos quanto das definições relacionadas com automedicação desde um conceito muito simples que implica a ausência de prescrição médica, até conceitos mais complexos que abarcam condutas de muita diversa índole; ainda aquelas nas que intervém um ato de prescrição não seguido ou não cumprido pelo paciente. Adicionalmente se aprecia uma proliferação conceitual que justifica o ordenamento dos termos relacionados com automedicação. Este artigo apresenta uma proposta de classificação em quatro grupos: a. automedicação b. auto-cuidado c. preparações farmacêuticas e medicamentos, e d. prescrição. Esta proposta pode facilitar a exploração e análise do fenômeno e permitir futuras aproximações teóricas.

We examined the degeneration of post-mitotic ganglion cells in ex-vivo neonatal retinal explants following axon damage. Ultrastructural features of both apoptosis and autophagy were detected. Degenerating cells reacted with antibodies specific for activated caspase-3 or -9, consistent with the presence of caspase activity. Furthermore, peptidic inhibitors of caspase-9, -6 or -3 prevented cell death (100 µM Ac-LEDH-CHO, 50 µM Ac-VEID-CHO and 10 µM Z-DEVD-fmk, respectively). Interestingly, inhibition of autophagy by 7-10 mM 3-methyl-adenine increased the rate of cell death. Immunohistochemistry data, caspase activation and caspase inhibition data suggest that axotomy of neonatal retinal ganglion cells triggers the intrinsic apoptotic pathway, which, in turn, is counteracted by a pro-survival autophagic response, demonstrated by electron microscopy profiles and pharmacological autophagy inhibitor.