Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET.

Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors.

Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

Immobilization of fibrinolytic protease from Mucor subtilissimus UCP 1262 in magnetic nanoparticles.

This work reports the immobilization of a fibrinolytic protease (FP) from Mucor subtilissimus UCP 1262 on Fe3O4 magnetic nanoparticles (MNPs) produced by precipitation of FeCl3·6H2O and FeCl2·4H2O, coated with polyaniline and activated with glutaraldehyde. The FP was obtained by solid state fermentation, precipitated with 40-60% ammonium sulfate, and purified by DEAE-Sephadex A50 ion exchange chromatography. The FP immobilization procedure allowed for an enzyme retention of 52.13%. The fibrinolytic protease immobilized on magnetic nanoparticles (MNPs/FP) maintained more than 60% of activity at a temperature of 40 to 60 °C and at pH 7 to 10, when compared to the non-immobilized enzyme. MNPs and MNPs/FP did not show any cytotoxicity against HEK-293 and J774A.1 cells. MNPs/FP was not hemolytic and reduced the hemolysis induced by MNPs from 2.07% to 1.37%. Thrombus degradation by MNPs/FP demonstrated that the immobilization process guaranteed the thrombolytic activity of the enzyme. MNPs/FP showed a total degradation of the γ chain of human fibrinogen within 90 min. These results suggest that MNPs/FP may be used as an alternative strategy to treat cardiovascular diseases with a targeted release through an external magnetic field.

Purification and characterization of fibrinolytic protease from Streptomyces parvulus by polyethylene glycol-phosphate aqueous two-phase system.

Fibrinolytic proteases are a promising alternative in the pharmaceutical industry, they are used in the treatment of cardiovascular diseases, especially thrombosis. Microorganisms are the most interesting source of fibrinolytic proteases. The aim of this study was the production of fibrinolytic protease from Streptomyces parvulus DPUA 1573, the recovery of the protease by aqueous two-phase system and partial biochemical characterization of the enzyme. The aqueous two-phase system was performed according to a 24-full factorial design using polyethylene glycol molar mass, polyethylene glycol concentration, citrate concentration and pH as independent variables. It was analyzed the effect of different ions, surfactants, inhibitors, pH and temperature on enzyme activity. The best conditions for purifying the enzyme were 17.5% polyethylene glycol 8,000, 15% Phosphate and pH 8.0, it was obtained a partition coefficient of 7.33, a yield of 57.49% and a purification factor of 2.10-fold. There was an increase in enzyme activity in the presence of Fe2+ and a decrease in the presence of $\beta$-Mercaptoethanol, phenylmethylsulfonyl fluoride and Iodoacetic acid. The optimum pH was 7.0 and the optimum temperature was 40 ºC. The purified protease exhibited a molecular mass of 41 kDa. The fibrinolytic protease from Streptomyces parvulus proved to be a viable option for the development of a possible drug with fibrinolytic action.

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas.

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

Tannic acid as a precipitating agent of human plasma proteins.

The search for plasma proteins precipitation methods has been increasing due to the plasma protein therapeutic needs in world-wide. Thus, this work evaluates the tannic acid (TA) ability to precipitate proteins from human plasma. In this study, TA-plasma protein complexes were studied at different pH conditions, tannin/plasma ratio and reaction mixing time. The complexes formed from combinations of TA and plasma proteins were analyzed by gel electrophoresis, protein quantification, particle size, charge, mass spectrometry, microscopic image, and circular dichroism. It was possible to verify the precipitate formation in all tested pH values, with high precipitation at pH 5. The native PAGE analysis showed three mainly bands corresponding independent of the pHs used. It was possible to observe a gradual growing of precipitate protein in the first precipitation process (P1) when increased the TA/plasma ratio. 15 min of incubation was enough to precipitate 72.3% of proteins. Spectroscopic analyzes showed albumin signals and the electron microscopy analysis of IgG-TA confirmed the compact form of a precipitate. According to CD, formation of the IgG-TA complexes does not cause a major structural change of the protein. From the results obtained, it was possible to establish some parameters for plasma proteins precipitation using TA.

Estresse e enfrentamento de trabalhadores de centro de atenção psicossocial em uma cidade do interior do Estado de São Paulo / Stress and coping among workers at psychosocial care centers in the interior of the state of Sao Paulo

INTRODUÇÃO: Os Centros de Atenção Psicossocial (CAPS) são serviços comunitários que foram concebidos como modelo substitutivo que rompe com o modelo de atenção manicomial, alinhado aos princípios do Sistema Único de Saúde (SUS), promovendo uma clínica centrada no sujeito. OBJETIVO: Identificar a prevalência de estresse e suas associações com as características biossociais e as estratégias de enfrentamento relacionadas ao processo de trabalho dos profissionais da saúde que trabalham nos CAPS de uma cidade do interior de São Paulo. MÉTODO: Estudo transversal quantitativo utilizando três questionários de autopreenchimento: um biossocial, a Escala de Estresse no Trabalho (EET) e um com estratégias de enfrentamento do estresse (coping). A investigação foi desenvolvida com 193 profissionais de saúde de 11 CAPS. RESULTADOS: Houve predominância de sexo feminino, 35 anos, sem filhos e solteiros. O estresse foi considerado alto, com 50,2% de prevalência. As principais associações dizem respeito às questões subjetivas relacionadas à forma como o trabalhador avalia e sente seu trabalho. As estratégias de enfrentamento mais utilizadas foram resolução de problemas e suporte social. CONCLUSÃO: Observou-se elevado grau de estresse na população estudada e, principalmente, suas associações com características biossociais.

BACKGROUND: Psychosocial Care Centers (CAPS) are community-based facilities designed as a substitutive model to break with asylum-based care and aligned to the principles underlying the Unified Health System (Sistema Único de Saúde­SUS); thus they promote patient-centered care. OBJECTIVE: To establish the prevalence of stress and its association with biosocial characteristics and coping strategies within the work process of healthcare providers at CAPS in a city in the interior of the state of Sao Paulo, Brazil. METHOD: Cross-sectional quantitative study involving administration of three questionnaires: biosocial, Work Stress Scale and a checklist of coping strategies. The sample comprised 193 healthcare providers from 11 different CAPS. RESULTS: Most participants were female, with average age 35 years old, single and without children. The levels of stress were rated high, with prevalence of 50.2%. The main associations found concern the participants' subjective appraisal of their job, particularly personal recognition and satisfaction. The coping strategies most frequently cited were problem-solving and social support. CONCLUSION: We found high levels of stress in the analyzed population and association of stress mainly with biosocial characteristics.

Effect of acute exposure in swiss mice (Mus musculus) to a fibrinolytic protease produced by Mucor subtilissimus UCP 1262: An histomorphometric, genotoxic and cytological approach.

The fibrinolytic enzyme produced by Mucor subtilissimus UCP 1262 was obtained by solid fermentation and purified by ion exchange chromatography using DEAE-Sephadex A50. The enzyme toxicity was evaluated using mammalian cell lineages: HEK-293, J774.A1, Sarcoma-180 and PBMCs which appeared to be viable at a level of 80%. The biochemical parameters of the mice treated with an acute dose of enzyme (2000 mg/mL) identified alterations of AST and ALT and the histomorphometric analysis of the liver showed a loss of endothelial cells (P < 0.001). However, these changes are considered minimal to affirm that there was a significant degree of hepatotoxicity. The comet assay and the micronucleus test did not identify damage in the DNA of the erythrocytes of the animals treated. The protease did not degrade the Aα and Bß chains of human and bovine fibrinogens, thus indicating that it does not act as anticoagulant, but rather as a fibrinolytic agent. The assay performed to assess blood biocompatibility shows that at dose of 0.3-5 mg/mL the hemolytic grade is considered insignificant. Moreover, the enzyme did not prolong bleeding time in mice when dosed with 1 mg/kg. These results indicate that this enzyme produced is a potential competitor for developing novel antithrombotic drugs.

Stress and coping among workers at psychosocial care centers in the interior of the state of Sao Paulo.

BACKGROUND: Psychosocial Care Centers (CAPS) are community-based facilities designed as a substitutive model to break with asylum-based care and aligned to the principles underlying the Unified Health System (Sistema Único de Saúde-SUS); thus they promote patient-centered care. OBJECTIVE: To establish the prevalence of stress and its association with biosocial characteristics and coping strategies within the work process of healthcare providers at CAPS in a city in the interior of the state of Sao Paulo, Brazil. METHOD: Cross-sectional quantitative study involving administration of three questionnaires: biosocial, Work Stress Scale and a checklist of coping strategies. The sample comprised 193 healthcare providers from 11 different CAPS. RESULTS: Most participants were female, with average age 35 years old, single and without children. The levels of stress were rated high, with prevalence of 50.2%. The main associations found concern the participants' subjective appraisal of their job, particularly personal recognition and satisfaction. The coping strategies most frequently cited were problem-solving and social support. CONCLUSION: We found high levels of stress in the analyzed population and association of stress mainly with biosocial characteristics.

INTRODUÇÃO: Os Centros de Atenção Psicossocial (CAPS) são serviços comunitários que foram concebidos como modelo substitutivo que rompe com o modelo de atenção manicomial, alinhado aos princípios do Sistema Único de Saúde (SUS), promovendo uma clínica centrada no sujeito. OBJETIVO: Identificar a prevalência de estresse e suas associações com as características biossociais e as estratégias de enfrentamento relacionadas ao processo de trabalho dos profissionais da saúde que trabalham nos CAPS de uma cidade do interior de São Paulo. MÉTODO: Estudo transversal quantitativo utilizando três questionários de autopreenchimento: um biossocial, a Escala de Estresse no Trabalho (EET) e um com estratégias de enfrentamento do estresse (coping). A investigação foi desenvolvida com 193 profissionais de saúde de 11 CAPS. RESULTADOS: Houve predominância de sexo feminino, 35 anos, sem filhos e solteiros. O estresse foi considerado alto, com 50,2% de prevalência. As principais associações dizem respeito às questões subjetivas relacionadas à forma como o trabalhador avalia e sente seu trabalho. As estratégias de enfrentamento mais utilizadas foram resolução de problemas e suporte social. CONCLUSÃO: Observou-se elevado grau de estresse na população estudada e, principalmente, suas associações com características biossociais.

Consensus for the diagnosis, prognosis and treatment of feline mammary tumors / Consenso para o diagnóstico, prognóstico e tratamento de tumores mamários em felinos

Mammary neoplasms are described as the third most common type of feline tumor, after haematopoietic and skin tumors, and present a challenge for clinicians because the prognosis for feline mammary tumors ranges from guarded to poor. Thus, it is necessary to define new therapeutic approaches and establish more in-depth knowledge about this disease in felines. The main aspects of the diagnosis, prognosis and treatment of feline mammary neoplasia were discussed, aiming to standardize the criteria and to serve as a guide for pathologists and veterinary clinicians.(AU)

As neoplasias mamárias são descritas como o terceiro tipo mais frequente de tumor em felinos (após as neoplasias hematopoiéticas e cutâneas) e apresentam um desafio para os clínicos devido ao prognóstico, que varia de reservado a ruim. Assim, é necessário conhecer melhor essa doença em felinos e definir novas abordagens terapêuticas. Discutiu-se os principais aspectos de diagnóstico, prognóstico e tratamento da neoplasia mamária felina, com o objetivo de padronizar os critérios e servir de guia para patologistas e clínicos veterinários.(AU)

Burnout e a organização do trabalho na Enfermagem / Burnout and work organization in Nursing

Introdução: A síndrome de burnout (SB) é um conjunto de sintomas que surgem da resposta a estressores interpessoais crônicos no trabalho e envolvem a percepção que a pessoa tem de si própria e do ambiente em que realiza seu trabalho. Objetivo: Identificar os fatores de risco psicossociais e da organização do trabalho preditores de sofrimento mental, bem como estimar a prevalência da SB em uma população de profissionais de Enfermagem de um hospital público do interior do Estado de São Paulo. Métodos: Pesquisa mista, combinando as abordagens quantitativa e qualitativa, desenvolvida em um hospital público universitário. Foram utilizados o Maslach Burnout Inventory-Human Services Survey (MBI-HSS), para estimar a prevalência de SB, e a análise de conteúdo em grupos focais (GFs), para identificar fatores psicossociais de risco no trabalho (FPRT). Resultados: A prevalência de SB na instituição estudada (5,7%) foi compatível com a literatura internacional. A análise das falas emergentes dos GFs revelou a existência de FPRT atuando como estressores na organização do trabalho. Conclusão: Esta pesquisa apontou ainda a necessidade de um olhar mais amplo sobre as causas da SB, sendo de grande importância a inclusão, nos trabalhos, do estudo da singularidade dos fatores psicossociais e da organização do trabalho por meio da voz dos profissionais que têm como foco de trabalho o cuidado ao ser humano.

Background: Burnout syndrome (BS) consists of a set of symptoms that appear in response to chronic interpersonal stressors at work and involve the perceptions individuals have of themselves and their work environment. Objectives: To identify psychosocial risk and work organization factors able to predict mental suffering, and to estimate the prevalence of BS in a sample of nursing professionals from a public hospital in the state of São Paulo, Brazil. Methods: Mixed methods research combining quantitative and qualitative approaches conducted at a public university hospital. Maslach Burnout Inventory-Human Services Survey (MBIHSS) was used to estimate the prevalence of BS. Thematic content analysis of narratives gathered in focus groups was performed to identify psychosocial risk factors at work (PRFW). Results: The prevalence of BS at the investigated institution (5.7%) is consistent with the rates reported in the international literature. Analysis of the narratives gathered in focus groups revealed stressors in the organization of work. Conclusion: The present study also points to the need for a broader look into the causes of BS, in which consideration of singular psychosocial risk and work organization factors from the perspective of workers devoted to proving care to human beings has paramount importance.

Burnout and workorganization in Nursing.

BACKGROUND: Burnout syndrome (BS) consists of a set of symptoms that appear in response to chronic interpersonal stressors at work and involve the perceptions individuals have of themselves and their work environment. OBJECTIVES: To identify psychosocial risk and work organization factors able to predict mental suffering, and to estimate the prevalence of BS in a sample of nursing professionals from a public hospital in the state of São Paulo, Brazil. METHODS: Mixed methods research combining quantitative and qualitative approaches conducted at a public university hospital. Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to estimate the prevalence of BS. Thematic content analysis of narratives gathered in focus groups was performed to identify psychosocial risk factors at work (PRFW). RESULTS: The prevalence of BS at the investigated institution (5.7%) is consistent with the rates reported in the international literature. Analysis of the narratives gathered in focus groups revealed stressors in the organization of work. CONCLUSION: The present study also points to the need for a broader look into the causes of BS, in which consideration of singular psychosocial risk and work organization factors from the perspective of workers devoted to proving care to human beings has paramount importance.

INTRODUÇÃO: A síndrome deburnout (SB) éum conjunto de sintomas que surgem da resposta a estressores interpessoais crônicos no trabalho e envolvem a percepção que a pessoa tem de si própria e do ambiente em que realiza seu trabalho. OBJETIVO: Identificar os fatores de risco psicossociais e da organização do trabalho preditores de sofrimento mental, bem como estimar a prevalência da SB em uma população de profissionais de Enfermagem de um hospital público do interior do Estado de São Paulo. MÉTODOS: Pesquisa mista, combinando as abordagens quantitativa e qualitativa, desenvolvida em um hospital público universitário. Foram utilizados o Maslach Burnout Inventory-Human Services Survey (MBI-HSS), para estimar a prevalência de SB, e a análise de conteúdo em grupos focais (GFs), para identificar fatores psicossociais de risco no trabalho (FPRT). RESULTADOS: A prevalência de SB na instituição estudada (5,7%) foi compatível com a literatura internacional. A análise das falas emergentes dos GFs revelou a existência de FPRT atuando como estressores na organização do trabalho. CONCLUSÃO: Esta pesquisa apontou ainda a necessidade de um olhar mais amplo sobre as causas da SB, sendo de grande importância a inclusão, nos trabalhos, do estudo da singularidade dos fatores psicossociais e da organização do trabalho por meio da voz dos profissionais que têm como foco de trabalho o cuidado ao ser humano.

Aplicação de instrumento para o diagnóstico dos fatores de risco psicossociais nas organizações / Application of an instrument for diagnosis of psychosocial risk factors in organizations

Contexto: Os fatores psicossociais no trabalho podem desencadear estresse laboral, sofrimento psíquico e transtornos mentais. Entre os instrumentos validados, o Health Safety Executive - Management Standard (HSE-MS) tem sido utilizado na União Europeia no diagnóstico e na intervenção primária desses fatores. Objetivos: Aplicar o método desenvolvido pelo HSE-MS para o diagnóstico do estresse laboral nas organizações. Métodos: O estudo utilizou o método misto preconizado pelo HSE, com aplicação do questionário Health Safety Executive - Indicator Tool (HSE-IT) seguido de um aprofundamento com grupos focais. A pesquisa foi realizada em uma amostra aleatória de 2.284 trabalhadores dos segmentos de call center, hospitais, bancos, unidades básicas de saúde e indústrias. Resultados: A falta de controle/autonomia no trabalho e a falta de reconhecimento foram as principais causas de estresse no trabalho entre os sujeitos pesquisados. Conclusões: O método do HSE pode ser considerado válido nesse tipo de investigação porque consegue se adaptar a qualquer país ou contexto organizacional, com o objetivo de diagnosticar os principais aspectos psicossociais desencadeantes de estresse nas diferentes organizações.

Background: Psychosocial factors at work might trigger stress in the job and mental problems and disorders. Among validated tools, the Health Safety Executive - Management Standard (HSE-MS) has been used in the European Union for the purpose of diagnosis and to develop primary interventions addressing those factors. Aims: To apply the method developed in HSE-MS to diagnose work-related stress in organizations. Methods: The study used the mixed method recommended in HSE, including application of Health Safety Executive - Indicator Tool (HSE-IT) followed by focus groups. The study was conducted with a random sample of 2,248 employees from a call center, hospitals, banks, Basic Health Units and manufacturing companies. Results: Lack of control/ autonomy and of recognition in the workplace were the main causes of work-related stress in the analyzed sample. Conclusions: The HSE method might be considered valid for this type of study, because it might be adapted to any country or organization setting to diagnose the main psychosocial factors of stress in different organizations.

Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer.

BACKGROUND: In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response in vitro. METHODS: Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 muM for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples > or = 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors. RESULTS: Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction > or = 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed. CONCLUSION: Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin in vitro responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.

Expressão de PRSS11, MTSS1, CLPTM1, SMYD2, NOTCH1 e RPL37A em fatias de carcinoma de mama de cadelas e correlação com resposta à doxorrubicina in vitro / Expression of PRSS11, MTSS1, CLPTM1, SMYD2, NOTCH1 and RPL37A in slices of bitch mammary cancer and correlation with response to exposure doxorubicin in vitro

Os tumores da glândula mamária constituem as neoplasias mais frequentes em cadelas e a doxorrubicina é uma das principais drogas quimioterápicas utilizadas no tratamento deste tipo de câncer. A quimioterapia neoadjuvante com doxorrubicina possibilita a redução do tumor e permite a avaliação da resposta ao tratamento quimioterápico in vivo. A procura por marcadores preditivos de resposta tem o objetivo de identificar as pacientes responsivas e não responsivas ao tratamento com o quimioterápico de modo a permitir a indicação de uma abordagem terapêutica específica para cada paciente. A expressão de alguns trios de genes, incluindo PRSS11, MTSS1 e CLPTM1 e, PRSS11, MTSS1 e SMYD2 em mulheres com câncer de mama que receberam tratamento neoadjuvante com doxorrubicina permitiu a classificação das pacientes em sensíveis e resistentes ao tratamento. Outros genes diferencialmente expressos entre amostras consideradas sensíveis e resistentes à doxorrubicina foram NOTCH1 e RPL37A. Avaliamos no presente trabalho se a expressão de trios de genes permitia a classificação de resposta ao tratamento quimioterápico em outro modelo, constituído por carcinoma de mama de cadela, mantido em cultura de tecido na forma de fatias e exposto à doxorrubicina in vitro. A cultura de fatias de tecidos permite a manutenção da interação epitélio-mesênquima e é considerado um modelo mais próximo ao observado in vivo. Foram obtidas amostras de tumor mamário de 38 pacientes caninas atendidas no Hospital Veterinário da Faculdade de Medicina Veterinária da Universidade Metodista de São Paulo (UMESP), em São Bernardo do Campo, durante a cirurgia de mastectomia. Os proprietários deram seu consentimento livre e esclarecido para a realização do estudo. A idade mediana das pacientes foi de 10,4 anos e, 55% e 18,4% destas pacientes eram animais sem raça definida (SRD) e da raça poodle, respectivamente. Oito pacientes haviam sido submetidas previamente à cirurgia de esterilização...

Mammary gland tumors are the most common neoplasias of bitches and doxorubicin is one the mainstay drugs used in their treatment. Neoadjuvant chemotherapy with doxorubicin not only reduces the primary tumor as well as allows an in vivo evaluation of tumor response. Predictive markers of response, if identified, might allow a tailored treatment of each patient. In women with breast cancer submitted to neoadjuvant chemotherapy with doxorubicin, expression of groups of three genes, including PRSS11, MTSS1 and CLPTM1 and PRSS11, MTSS1 and SMYD2, classified the patients in responsive and resistant. Other genes differentially expressed between responsive and non-responsive tumors were NOTCH1 and RPL37A. We have then evaluated whether the expression of trios of these genes could allow the classification of tumors according to their response to chemotherapy, in another animal model constituted by mammary carcinoma of bitches, cultured as tissue slices and exposed to doxorrubicin in vitro. Culture of tissue slices preserves epithelial-mesenchymal interactions, in a similar way to that observed in vivo. Tumor samples were obtained from 38 canine patients treated at Hospital Veterinaria da Faculdade de Medicina Veterinária da Universidade Metodista de São Paulo (UMESP), São Bernardo do Campo, during mastectomy. Animal owners gave their informed consent to this study. Median age of patients was 10,4 years and 55% and 18,4% of them were mixed and poodle breed, respectively. Eight patients were previously spayed. Patients were classified in clinical stage III (39,47%), II (28,9%), I (18,4%) and IV (pulmonary metastasis only) (13,1%). Carcinomas were classified as cystic-papillary (34,2%), tubular (34,2%), tubular-papillary (18,42%) and solid (10,52%). Tumors were sliced and cultured in the absence or in the presence of doxorubicin (1 uM) for 24 hours and response evaluation was performed by cell counting of treated and untreated samples...

Estudo in vivo de um sistema de liberaçäo de drogas constituído por hidroxiapatita e cisplatina / In vivo study drug release system of constitute for hydroxyapatite and cisplatin

Um sistema de liberaçäo constituído por hidroxiapatita e cisplatina foi testado em ratos para avaliaçäo da liberaçäo local e sistêmica do antineoplásico cisplatina. Os animais que receberam os implantes com a droga desenvolveram efeitos colaterais ao tratamento, sendo os mais comuns: anorexia, diarréia, epistaxe e necrose cutânea no sítio de implantaçäo; cerca de 45 por cento deste animais morreram, indicando intoxicaçäo. Amostras de sangue e dos tecidos hepático, renal e muscular de todos os animais pertencentes ao experimento foram submetidas à detecçäo das concentraçöes de cisplatina, revelando a cinética de liberaçäo da droga pelo sistema proposto.