Rodent models: what is their importance for cancer study?

Abstract: Cancer is one of the most frequent diseases worldwide, accounting for approximately 10 million deaths in 2020. The most common cancers in 2020 were: breast, lung, colon and rectum, prostate, skin, and stomach. Cancer arises from the conversion of normal cells into initiated cells as a result of the interaction between intrinsic (genetic) and extrinsic factors, namely physical agents (ultraviolet radiation), chemical agents (asbestos, components of tobacco smoke, arsenic) and biological agents (Helicobater pylori, Schistosoma haematobium, hepatitis virus). Animal models are very useful to understand and follow several diseases, including cancer. In this way, in vivo studies are essential to improve and discover new strategies to prevent and treat cancer more effectively. This presentation intends to describe the rodent models available for cancer study, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds for cancer treatment

Rodent models: what is their importance for cancer study?

Cancer is one of the most frequent diseases worldwide, accounting for approximately 10 million deaths in 2020. The most common cancers in 2020 were: breast, lung, colon and rectum, prostate, skin, and stomach. Cancer arises from the conversion of normal cells into initiated cells as a result of the interaction between intrinsic (genetic) and extrinsic factors, namely physical agents (ultraviolet radiation), chemical agents (asbestos, components of tobacco smoke, arsenic) and biological agents (Helicobater pylori, Schistosoma haematobium, hepatitis virus). Animal models are very useful to understand and follow several diseases, including cancer. In this way, in vivo studies are essential to improve and discover new strategies to prevent and treat cancer more effectively. This presentation intends to describe the rodent models available for cancer study, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds for cancer treatment

Animal models of disease: useful or not?

Faustino-Rocha AI. 2021. Animal models of disease: useful or not? From in silico to animal models for the study of human diseases. 17 de março, Aveiro, Portugal

Modelos animais de cancro da mama: importância e aplicabilidade.

Faustino-Rocha AI. 2020. Modelos animais de cancro da mama: importância e aplicabilidade. IV Workshop Internacional em Doenças Crônicas e Negligenciadas - PROCAD/Amazônia, 26 de novembro, São Luís, Maranhão, Brasil

Social buffering of fear in zebrafish

Tese de Doutoramento em Biologia Comportamental apresentada ao ISPA - Instituto UniversitárioA ubiquidade da formação de grupos em animais tem sido explicada, entre outros aspectos, pelos seus benefícios na proteção contra predadores, nomeadamente devido ao aumento global do estado de vigilância, diluição do risco e capacidade de confundir o predador. Assim, os grupos sociais proporcionam um ambiente mais seguro na presença de ameaças, onde a presença de conspecíficos diminui o medo desencadeado por eventos aversivos que surjam no ambiente, um fenómeno designado por “social buffering”. Este fenómeno social tem sido verificado em mamíferos, onde já existe alguma evidência sobre os mecanismos neurais envolvidos, mas o seu estudo em outros vertebrados ainda é escasso. Por esta razão, são necessários mais estudos comparativos para melhor compreender a evolução do “social buffering” entre animais sociais e quão evolutivamente conservados são os mecanismos subjacentes a este comportamento social. Diferentes modalidades sensoriais (através de “cues”) podem promover este efeito de “buffering” e a eficácia de cada canal sensorial neste fenómeno comportamental pode variar entre espécies. Além disso, do que é sabido, a eficácia ao longo do tempo de diferentes “cues” sensoriais, bem como a eficiência de grupos sociais que divirjam no seu número de elementos, nunca foi testada no contexto de “social buffering”. Estas questões adquirem especial importância se considerarmos que exposições mais prolongadas a ameaças e grupos sociais maiores, influenciam as probabilidades de sobrevivência do indivíduo. Dada a sua posição filogenética, os peixes teleósteos permitem explorar o “social buffering” e os mecanismos envolvidos neste comportamento social, na radiação evolutiva de maior sucesso entre os vertebrados (paralela à dos tetrápodes). O peixe-zebra é uma espécie pertencente aos teleósteos que apresenta comportamentos de medo quando submetido a situações ameaçadoras em contextos de isolamento social, no entanto a ocorrência de “social buffering” nesta espécie permanece praticamente inexplorada. Nesta tese, investigámos a ocorrência de “social buffering” no peixe-zebra, submetendo peixes focais a um estímulo aversivo (substância de alarme) quer na presença ou ausência de “cues” sensoriais sociais. Numa primeira experiência, mostrámos que quando submetidos à substância de alarme na presença de “cues” sociais olfactivas (água do cardume) e visuais (visualização do cardume), os peixe-zebra apresentaram uma resposta de medo inferior do que quando submetidos à substância de alarme sozinhos (durante 30 minutos de exposição) revelando a ocorrência de “social buffering” continuado da resposta de medo. No entanto, análises ao cortisol ou RNA mensageiro da hormona libertadora de corticotrofina (CRF), dos receptores de glucocorticóides, e receptores de mineralocorticóides, não revelaram evidências de “buffering” da resposta de stress. Numa segunda experiência, testámos separadamente a eficácia de “cues” olfactivas e visuais no fenómeno de “social buffering”, e verificámos que a visualização do cardume de peixes-zebra se revelou a “cue” mais eficaz na diminuição da resposta de medo provocada pela substância de alarme, quando num cenário de exposição constante à ameaça (30 minutos). Numa terceira experiência, demonstrámos que este “buffering” social não depende do número de conspecíficos presentes no cardume, uma vez que cardumes mais pequenos se revelaram igualmente eficazes em diminuir a resposta de medo provocada pela substância de alarme. Finalmente, usando a expressão génica de um “immediate early gene” (c-fos) como indicador de atividade neuronal, verificámos que o fenómeno de “social buffering” em peixezebra desencadeia um padrão específico de co-activação de áreas cerebrais conhecidas pelo seu envolvimento em respostas de medo e “buffering” em mamíferos. Concluindo, o conjunto de estudos apresentados nesta tese sugerem uma origem evolutiva comum nos vertebrados para o comportamento de “social buffering”, providenciando novas perspectivas sobre os mecanismos comportamentais e neurais envolvidos neste comportamento social.ABSTRACT : The ubiquity of group formation among animals has been explained among several aspects by its anti-predatory benefits, including an overall increase in vigilance, the dilution of risk and predator confusion. Thus, social groups offer a safer environment in the presence of threats, and the presence of conspecifics is known to decrease the fear response to a detected threatening event, a phenomenon named social buffering. This social phenomenon has been documented in mammals, where there is already some evidence about its neural mechanisms, but its study in other vertebrate taxa is still scarce. Thus, more comparative studies are needed to better understand the evolution of social buffering among social animals and how evolutionary conserved are its underlying mechanisms. For instance, different sensory modalities can convey relevant conspecific social cues used in buffering and the efficiency of each sensory channel may vary across species. Furthermore, to our knowledge, the effectiveness of these sensory cues over time and different conspecific group sizes has never been tested in the context of social buffering, which is of great relevance considering that long exposures to threat and bigger group sizes may influence individual chances of survival. Given their phylogenetic position, teleost fish offer the possibility to investigate the occurrence of social buffering and its underlying mechanisms in the most successful evolutionary radiation among vertebrates, parallel to that of tetrapods. Zebrafish is a teleost species that expresses fear behaviour when individually exposed to threatening situations, however the occurrence of social buffering in this species has been virtually unexplored. In this thesis we investigated social buffering in zebrafish, by exposing focal fish to an aversive stimulus (alarm substance – AS) either in the presence or absence of conspecific cues. In a first experiment, we showed that when exposed to AS in the presence of both olfactory (shoal water) and visual (sight of shoal) conspecific cues, zebrafish exhibited a lower fear response over the 30 min test than when tested alone, indicating sustained social buffering of fear. Nonetheless, analysis of cortisol or mRNA expression of corticotropin-releasing factor, glucocorticoid receptors and mineralocorticoid receptors did not reveal buffering of the stress response. In a second experiment, we separately tested olfactory and visual cues effectiveness on the AS-elicited fear response, and verified that the sight of shoal was more effective in reducing fear responses in a persistent threat scenario (30 min test). In a third experiment, we found that this effect was independent of conspecific number, as smaller shoals were equally efficient as larger shoals at inducing social buffering. Finally, by using the expression of an immediate early gene (c-fos) as a reporter of neuronal activity, we showed that social buffering elicits a distinct pattern of functional connectivity among a set of brain regions known to be involved in fear-like responses and buffering processes in mammals. To conclude, the set of studies on this thesis suggests a shared evolutionary origin for social buffering in vertebrates, bringing new insights into the behavioural and neural mechanisms of this phenomenon

Modelos animais de cancro da mama: importância e aplicabilidade

Faustino-Rocha AI. 2020. Modelos animais de cancro da mama: importância e aplicabilidade. Programa de pós-Graduação em Saúde do Adulto, Ciclo de Palestras Internacionais Raimundo Antônio Silva, 27 de agosto, Universidade Federal do Maranhão, Brasil

Side effects of electrochemotherapy in cats with squamous cell carcinoma: a retrospective study

Eletrochemotherapy (EQT) is an emerging therapeutic modality in Veterinary Oncology that combines the intravenous (IV) or intratumoral (IT) administration of chemotherapeutic agents with the application of electrical pulses(1). This therapy has been described to induce significant cancer remission in cutaneous squamous cell carcinoma (SCC) and a reduction of chemotherapeutic dosages, maximizing intracellular concentration of these drugs as well as reducing its systemic side effects (2,3).The aim of this study was to describe the side effects observed in cats with a cytological or histopathological diagnosis of oral or cutaneous squamous cell carcinoma (SCC) of the head submitted to EQT as a primary treatment. The medical records of cats treated with EQT for SCC at the “Onevet Group - Hospital Veterinário de Berna” between December 2015 and February 2018 were reviewed. Cats with a cytologic and/or histopathologic diagnosis of head SCC (cutaneous and oral) that received at least one session of EQT were eligible for inclusion. Cats with incomplete clinical record or without a cyto/histopathological report were excluded. Side effects data were retrospectively classified using the Common Terminology Criteria for Adverse Events Following Chemotherapy or Biological Antineoplastic Therapy in Dogs and Cats v1.1 (VCOG- CTCAE) (4).Seventeen cats were treated for a total of 28 EQT sessions; The number of treatments per cat were: 1 session (52.9%); 2 (35.3%); 3 (5.9%) and 4 sessions (5.9%). • SCC lesions treated were localized on the nasal planum (70.6%), eyelid (11.8%), oral (5.9%), both on the pinna and eyelid (5.9%) and on the pinna and face (5.9%). • EQT treatments were performed using bleomycin in all cases (94% IV and 6% IT). • Adverse events reported per cat and per total of treatments, are described in Figure 1 (top and bottom, respectively). • All cats had a reported adverse event at least once; • Pain and soft tissue necrosis were present in all cats. • The percentage of severity of adverse events are described in Figure 2. Ninety six percent of adverse events reported were grade I to III.Pain, soft tissue necrosis and constitutional side effects were the most frequent adverse events, reported in more than 70% of cats included in this study. Most side effects were grade I to III according to VCOG-CTCAE and tolerable. This is comparable with previous studies of EQT in cats(1,5,6). Limitations of this study include its retrospective nature, small number of cases and inclusion of different locations of SCC within the head. Further larger prospective studies accessing clinical response and side effects are warranted to promote a more conscious application of EQT. It would also be interesting to include in those future studies scales to measure the impact of EQT in cats Quality of life

Effects of green tea in urinary bladder cancer: data from a mouse model

Urinary bladder cancer is one of the most common diseases around the world, associated with several risk factors [1-2]. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) is a carcinogen able to induce preneoplastic and neoplastic urothelial lesions development in rodents [3]. Green tea (GT) is one of the most popular beverages whose beneficial effects on health have been demonstrated [4]. This study aimed to evaluate the effects of whole GT on urinary bladder cancer in male and female mice. The experiment followed the European (Directive 2010/63/EU) legislation. Forty-one ICR mice of five weeks of age (21 males and 20 females) were used. Animals from each gender were randomly divided into three experimental groups, as follows: Males - group I (BBN+GT) (n=8); group II (BBN) (n=7); group III (GT) (n=6); Females - group IV (BBN+GT) (n=7); group V (BBN) (n=7); group VI (GT) (n=6). BBN was administered to animals from groups I, II, IV and V by gavage, at a dose of 7.25 mg/mouse, 2 times/week, during 10 consecutive weeks. The whole GT (0.5%) was daily prepared and given ad libitum to groups I, III, IV and VI for 20 consecutive weeks. Animals were sacrificed and a complete necropsy was performed. A histological analysis of the urinary bladder was performed. Data was analyzed with ANOVA. Results were considered statistically significant for p<0.05. Animals from groups not exposed to BBN (III and VI) did not develop any urothelial lesion. Animals from groups BBN+GT (I and IV) and BBN (II and V) developed only preneoplastic lesions. The number of inflammatory aggregates was lower in animals exposed to BBN that drank GT (I and IV), when compared with those only exposed to BBN (II and V). A statistically significant difference was observed between groups BBN (II and V) and groups GT (III and VI) (p<0.05) (Table 1). The administration of GT infusion had no effect on urinary bladder cancer development, but reduced urothelial inflammation

Effects of green tea in urinary bladder cancer: data from a mouse model

Urinary bladder cancer is one of the most common diseases around the world, associated with several risk factors [1-2]. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) is a carcinogen able to induce preneoplastic and neoplastic urothelial lesions development in rodents [3]. Green tea (GT) is one of the most popular beverages whose beneficial effects on health have been demonstrated [4]. This study aimed to evaluate the effects of whole GT on urinary bladder cancer in male and female mice. The experiment followed the European (Directive 2010/63/EU) legislation. Forty-one ICR mice of five weeks of age (21 males and 20 females) were used. Animals from each gender were randomly divided into three experimental groups, as follows: Males - group I (BBN+GT) (n=8); group II (BBN) (n=7); group III (GT) (n=6); Females - group IV (BBN+GT) (n=7); group V (BBN) (n=7); group VI (GT) (n=6). BBN was administered to animals from groups I, II, IV and V by gavage, at a dose of 7.25 mg/mouse, 2 times/week, during 10 consecutive weeks. The whole GT (0.5%) was daily prepared and given ad libitum to groups I, III, IV and VI for 20 consecutive weeks. Animals were sacrificed and a complete necropsy was performed. A histological analysis of the urinary bladder was performed. Data was analyzed with ANOVA. Results were considered statistically significant for p<0.05. Animals from groups not exposed to BBN (III and VI) did not develop any urothelial lesion. Animals from groups BBN+GT (I and IV) and BBN (II and V) developed only preneoplastic lesions. The number of inflammatory aggregates was lower in animals exposed to BBN that drank GT (I and IV), when compared with those only exposed to BBN (II and V). A statistically significant difference was observed between groups BBN (II and V) and groups GT (III and VI) (p<0.05) (Table 1). The administration of GT infusion had no effect on urinary bladder cancer development, but reduced urothelial inflammation