Cadherin Cell Adhesion System in Canine Mammary Cancer: A Review

Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin, β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis

Expression of E-cadherin, P-cadherin and beta-catenin in canine malignant mammary tumours in relation to clinicopathological parameters, proliferation and survival

Cadherin-catenin complexes play a critical role in intercellular adhesion, and their altered expression has been implicated in tumour progression. In this study, the expression of E-cadherin, P-cadherin and beta-catenin was analysed in 65 canine malignant mammary tumours and correlated with clinicopathological parameters, proliferation and survival. Reduction in E-cadherin expression was significantly associated with increased tumour size, high histological and invasion grades, lymph node metastasis and high mitotic index. Reduced beta-catenin expression was associated with high histological and invasion grades. Anomalous expression of P-cadherin was only associated with invasion. In 39 cases for which follow-up data were available, reduced E-cadherin and beta-catenin expression was significantly associated with shorter overall survival and disease free survival. Abnormal expression of adhesion molecules is a common phenomenon in canine mammary malignant tumours and may play a central role in tumour progression.This work was supported by the Centro de Ciência Animal e Veterinária (CECAV) – University of Trás os Montes e Alto Douro (UTAD), Vila Real, Portugal and by Portuguese Science and Technology Foundation, Project POCTI/CVT/57795/2004

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

Immunology and mammary cancer development: addressing the role of mast cells

Background: Mammary cancer is one of the most frequent cancers worldwide. Mast cells are among the cells of tumor microenvironment and have been associated with increased angiogenesis and poor prognosis. Despite this, the role of mast cells on mammary cancer is not fully elucidated. In this way, this work studied the role of mast cells in a rat model of mammary cancer chemically-induced. Material and methods: All experiments were performed in accordance with the Portuguese and European legislation on the protection of animals used for scientific purposes. The experiments were approved by the Portuguese (no.008961) and University (CE_12-2013) Ethics Committees. Thirty-four female Sprague-Dawley rats were randomly divided into five experimental groups. At seven weeks of age, mammary tumors’ development was induced in animals from groups I, II, III (n=10+10+10) by a single intraperitoneal injection of the carcinogen N-methyl-N-nitrosourea (MNU). Groups II and IV (n=2) were treated with ketotifen in drinking water (1 mg/kg/day, 7 days/week) immediately after the MNU administration for 18 weeks, while the group III received the ketotifen after the development of the first mammary tumor. Groups I and V (n=2) received only water. Animals were sacrificed at 25 weeks of age by an overdose of ketamine and xylazine, followed by an exsanguination by cardiac puncture. Mammary tumors were collected and immersed in formalin for posterior analysis. Tumors’ vascularization, proliferation and apoptosis were also assessed by immunohistochemistry (Vascular Endothelial Growth Factor (VEGF)-A, Ki-67, and caspases-3 and -9). Results: Animals from groups IV and V did not develop any mammary tumor. Twenty-one animals (six animals from group I, eight animals from group II and seven animals from group III) developed a total of 58 mammary tumors, mainly classified as papillary non-invasive carcinomas. Tumors’ vascularization was similar among groups (p>0.05). Mammary tumors from group II exhibited the lowest proliferation (p<0.05) and apoptotic indexes. Conclusions: The mainly positive effect of the ketotifen administration seems to be the reduction of tumor proliferation when the drug was administered before mammary tumor development

N-methyl-N-nitrosourea as a mammary carcinogen: practical application

Introduction: N-methyl-N-nitrosourea (MNU) is the oldest member of the nitroso compounds. It is considered a complete, potent and direct alkylating compound, able to alkylate the DNA without metabolic activation. The administration of chemical carcinogens is one of the most frequently used methods to induce tumors’ development in laboratory animals. The target organ depends on the animals’ species, strain and age, dose and route of administration (1-3). This work intended to describe the effects of MNU administration in female Sprague-Dawley rats. Material & Methods: Procedures followed the European legislation and were approved by the Portuguese Competent Authority (approval nº008961). Twenty-five female Sprague-Dawley rats were used in two experimental protocols. The first experiment intended to evaluate the effects of exercise training on mammary carcinogenesis (n=15) and the second one intended to evaluate the effect of ketotifen on mammary carcinogenesis (n=10). At seven weeks of age, all animals were intraperitoneally injected with the carcinogen MNU (50 mg/kg). Mammary tumors development was weekly assessed by palpation of both mammary chains. Animals were humanely sacrificed, through the intraperitoneal administration of ketamine and xylazine, 35 and 18 weeks after MNU administration, respectively. Results: All animals from the first experiment and six animals from the second experiment developed mammary tumors (incidence of 100% and 60%, respectively). In the first experiment, the first mammary tumor was identified ten weeks after MNU administration. A shorter latency period was observed in the second experiment, with the development of the first mammary tumors eight weeks after MNU administration. At the end of the experiment, animals from the first experiment developed a total of 28 mammary tumors (28/15; 1.9 tumors/animal), while the animals from the second experiment developed 21 mammary tumors (21/6; 3.5 tumors/animal). At the same time (18 weeks after MNU administration), the animals from the first experiment developed only five mammary tumors. Conclusions: Although the carcinogen was administered to the animals of the same strain at the same age and dose, using the same route, the latency period and incidence were different between the experiments. The different incidence may be related with the duration of the studies and the individual variations

Immunology and mammary cancer development: addressing the role of mast cells

Background: Mammary cancer is one of the most frequent cancers worldwide. Mast cells are among the cells of tumor microenvironment and have been associated with increased angiogenesis and poor prognosis. Despite this, the role of mast cells on mammary cancer is not fully elucidated. In this way, this work studied the role of mast cells in a rat model of mammary cancer chemically-induced. Materials and Methods: All experiments were performed in accordance with the Portuguese and European legislation on the protection of animals used for scientific purposes. The experiments were approved by the Portuguese (no.008961) ABSTRACTS and University (CE_12-2013) Ethics Committees. Thirty- four female Sprague-Dawley rats were randomly divided into five experimental groups. At seven weeks of age, mammary tumors’ development was induced in animals from groups I, II, III (n = 10+10+10) by a single intraperitoneal injection of the carcinogen N-methyl-N-nitrosourea (MNU). Groups II and IV (n = 2) were treated with ketotifen in drinking water (1 mg/kg/day, 7 days/week) immediately after the MNU ad- ministration for 18 weeks, while the group III received the ketotifen after the development of the first mammary tumor. Groups I and V (n = 2) received only water. Animals were sacrificed at 25 weeks of age by an overdose of ketamine and xylazine, followed by an exsanguination by cardiac puncture. Mammary tumors were collected and immersed in formalin for posterior analysis. Tumors’ vascularization, proliferation and apoptosis were also assessed by immunohistochemistry (Vascular Endothelial Growth Factor (VEGF)-A, Ki-67, and caspase-3 and caspase-9). Results: Animals from groups IV and V did not develop any mammary tumor. Twenty-one animals (six animals from group I, eight animals from group II and seven animals from group III) developed a total of 58 mammary tumors, mainly classified as papillary non-invasive carcinomas. Tumors’ vascularization was similar among groups (P > 0.05). Mammary tumors from group II exhibited the lowest prolif- eration (P < 0.05) and apoptotic indexes. Conclusions: The mainly positive effect of the ketotifen administration seems to be the reduction of tumor prolifera- tion when the drug was administered before mammary tumor development

N-methyl-N-nitrosourea as a mammary carcinogen: practical application

ntroduction: N-methyl-N-nitrosourea (MNU) is the oldest member of the nitroso compounds. It is considered a complete, potent and direct alkylating compound, able to alkylate the DNA without metabolic activation. The administration of chemical carcinogens is one of the most frequently used methods to induce tumors’ development in laboratory animals. The target organ depends on the animals’ species, strain and age, dose and route of administration (1-3). This work intended to describe the effects of MNU administration in female Sprague-Dawley rats. Material & Methods: Procedures followed the European legislation and were approved by the Portuguese Competent Authority (approval no008961). Twenty-five female Sprague-Dawley rats were used in two experimental protocols. The first experiment intended to evaluate the effects of exercise training on mammary carcinogenesis (n=15) and the second one intended to evaluate the effect of ketotifen on mammary carcinogenesis (n=10). At seven weeks of age, all animals were intraperitoneally injected with the carcinogen MNU (50 mg/kg). Mammary tumors development was weekly assessed by palpation of both mammary chains. Animals were humanely sacrificed, through the intraperitoneal administration of ketamine and xylazine, 35 and 18 weeks after MNU administration, respectively. Results: All animals from the first experiment and six animals from the second experiment developed mammary tumors (incidence of 100% and 60%, respectively). In the first experiment, the first mammary tumor was identified ten weeks after MNU administration. A shorter latency period was observed in the second experiment, with the development of the first mammary tumors eight weeks after MNU administration. At the end of the experiment, animals from the first experiment developed a total of 28 mammary tumors (28/15; 1.9 tumors/animal), while the animals from the second experiment developed 21 mammary tumors (21/6; 3.5 tumors/animal). At the same time (18 weeks after MNU administration), the animals from the first experiment developed only five mammary tumors. Conclusions: Although the carcinogen was administered to the animals of the same strain at the same age and dose, using the same route, the latency period and incidence were different between the experiments. The different incidence may be related with the duration of the studies and the individual variations

Interaction between intense pulsed light and skin: data from an animal model

Background: Although its effects remain unknown, the intense pulsed light (IPL) has been extensively used in dermatology and esthetics. Purpose: This study aimed to address the impact of IPL in neoplastic lesions using an animal model. Methodology: All experiments followed the European and National legislation. Sixteen ICR female DBA/2JRccHsd mice were randomly assessed to two experimental groups: IPL-exposed (n=8) and non-exposed (n=8). The mice dorsal region was shaved using a machine clipper. The carcinogen 7,12-dimethylbenz[a] anthracene (DMBA; 2mM, single dose) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 100mM, twice a week, for 22 weeks) were applied to all animals. Moreover, IPL-exposed animals were applied with IPL (intensity of 2J/cm2, twice a week, for 22 weeks). At the sacrifice, skin samples were collected and processed for histological analysis. Data was analyzed with SPSS. Results: IPL-exposed mice developed a lower number of skin lesions when compared with non-IPL-exposed animals (28 versus 46 lesions) (p=0.036). Each group presented 8 preneoplastic epidermal lesions (epidermal hyperplasia). The number of neoplastic lesions was lower in IPL-exposed mice than in non-IPL-exposed ones (20 versus 38 lesions) (p=0.018). Papilloma grade II was the neoplastic epidermal lesion most frequently observed in both groups (9 in IPL-exposed mice versus 19 in non-IPL-exposed mice) (p=0.059). Despite this, the number of microinvasive squamous carcinoma was higher in IPL-exposed animals (3 in IPL-exposed mice versus 1 in non-IPL-exposed mice). Conclusion: The results suggest that IPL exposition may inhibit skin carcinogenesis, but its use may promote malignant conversion of skin lesions

Interaction between intense pulsed light and skin: data from an animal model

Background: Although its effects remain unknown, the intense pulsed light (IPL) has been extensively used in dermatology and esthetics. Purpose: This study aimed to address the impact of IPL in neoplastic lesions using an animal model. Methodology: All experiments followed the European and National legislation. Sixteen ICR female DBA/2JRccHsd mice were randomly assessed to two experimental groups: IPL-exposed (n=8) and non-exposed (n=8). The mice dorsal region was shaved using a machine clipper. The carcinogen 7,12-dimethylbenz[a] anthracene (DMBA; 2mM, single dose) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 100mM, twice a week, for 22 weeks) were applied to all animals. Moreover, IPL-exposed animals were applied with IPL (intensity of 2J/cm2, twice a week, for 22 weeks). At the sacrifice, skin samples were collected and processed for histological analysis. Data was analyzed with SPSS. Results: IPL-exposed mice developed a lower number of skin lesions when compared with non-IPL-exposed animals (28 versus 46 lesions) (p=0.036). Each group presented 8 preneoplastic epidermal lesions (epidermal hyperplasia). The number of neoplastic lesions was lower in IPL-exposed mice than in non-IPL-exposed ones (20 versus 38 lesions) (p=0.018). Papilloma grade II was the neoplastic epidermal lesion most frequently observed in both groups (9 in IPL-exposed mice versus 19 in non-IPL-exposed mice) (p=0.059). Despite this, the number of microinvasive squamous carcinoma was higher in IPL-exposed animals (3 in IPL-exposed mice versus 1 in non-IPL-exposed mice). Conclusion: The results suggest that IPL exposition may inhibit skin carcinogenesis, but its use may promote malignant conversion of skin lesions

Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio