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

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

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

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

Recognition of pain and distress in a rat model of mammary cancer

Aims: Mice and rats are the most frequently used animals in experimental protocols performed in the European Union. They have several advantages when compared with other animals, such as their small size, and well-known anatomy, physiology, biochemistry and genetic. This work aimed to define the most adequate humane endpoints to recognize the pain in a rat model of mammary cancer chemically-induced. Material and Methods: Twelve female Sprague-Dawley rat of four weeks of age were obtained from Harlan Interfauna and randomly divided into two groups: MNU (N-methyl-N-nitrosourea) (n=10) and control (n=2). Animals from group MNU received an intraperitoneal injection of the carcinogenic agent MNU, at a dose of 50 mg/Kg. Animals from control group received only the vehicle (saline solution). A list of biological parameters to be evaluated during the experiment was elaborated prior to the study, including: body condition, body weight, food and water intake, posture, coat and grooming, mucosal, eyes, ears and whiskers, mental status, response to external stimuli, hydration status, respiratory rate, heart rate and body temperature. A score from 0 to 3 was attributed for each parameter. Severe alteration in some of these parameters, such as weight loss >20%, severe anemia, moribund or comatous mental status, development of mammary tumors that interfere with animal bodily functions (eat or drink), tumors in contact with cage floor or tumor burden > 10% of the animal body weight (>35 mm in a 250 g rat) were considered indicators of animal sacrifice. The animals were observed twice a day by the same researchers, for 18 weeks. Results: Six out 10 animals (60%) MNU-exposed developed a total of 21 mammary tumors (3.5 tumors/animal). Moderate anemic mucosal (score 2) were observed in one animal from group MNU at the 11th, 12th and 16th week of the experiment. No interference of mammary tumors with animals’ bodily functions or alterations in mammary tumor surface that implied animal sacrifice was observed. At the end of the study, five animals (83.3%) developed at least one mammary tumor > 35 mm. Conclusions: We concluded that the alteration in only tumor dimensions does not imply the animals’ sacrifice. The endpoints should be evaluated together, in order to define the most adequate time for humane animals’ sacrifice

Rat prostate: practical tips for ultrasonographic monitoring

Background: Prostate is the largest accessory gland of the male reproductive tract. The prostate of men over 40 years-old is frequently affected by several pathologies, like benign prostate hyperplasia and cancer. Rats have been used as model to study prostate cancer. This study intended to address the usefulness of ultrasonography for rat prostate monitoring. Material and methods: Eight male Wistar Unilever rats were acquired from Charles River Laboratories and maintained under controlled conditions of temperature, humidity, air system filtration and light/dark cycle. The prostate was evaluated by ultrasonography in awake animals. The animals were restrained by a researcher and placed in supine position. The skin of the inguinal region was shaved using a machine clipper (AESCULAP® GT420 Isis, USA). A real-time scanner (Logic P6®, GE, USA) and a 12 MHz linear transducer were used. Acoustic gel (Parker Laboratories Inc., USA) was applied. A complete transverse scan using B mode was performed from the cranial to the caudal region of the prostate, and a sagittal scan was performed moving the probe from the right to the left side. Procedures were approved by the Portuguese Ethics Committee (no.021326). Results: Prostate was easily evaluated by ultrasonography in all animals. In the transverse scan, the urinary bladder presents as a round to oval shape filled with urine (anechoic structure) and the prostate lobes were visible around it. The ventral prostate lobes appear as hypoechoic elongated structures (one right and one left) with a hyperechoic capsule, placed ventrally to the urinary bladder. In this scan, the dorsal prostate was observed close to the urinary bladder neck, as a round hypoechoic structure with a hyperechoic capsule, dorsally to the urinary bladder. In the sagittal scan, the urinary bladder was observed as an elongated structure filled with urine (anechoic content). The ventral prostate lobes were occasionally observed ventrally to the neck of the urinary bladder, as previously described. The dorsal prostate was observed dorsally to the neck of the urinary bladder, presenting as a round to elongated shape, with a hypoechoic appearance and a hyperechoic capsule. Conclusions: The ultrasonography is a non-invasive and accessible tool for prostate monitoring in the rat model