Search

This work presents the synthesis and characterization of eight copper complexes [Cu(L-dipeptide)(neo)]·nH2O (neo = neocuproine) and their cytotoxic activities against tumor cell lines. The crystalline structure of [Cu(gly-val)(neo)]·3H2O, [Cu(gly-leu)(neo)]·H2O, [Cu(ala-gly)(neo)]·4H2O, [Cu(val-phe)(neo)]·4.5H2O and [Cu(phe-phe)(neo)]·3H2O were determined by single crystal X-ray diffraction. In all of them, the Cu(II) is pentacoordinated, in a square pyramidal environment. The coordination observed in solid state was retained in the major species in aqueous solution, as suggested by Electronic Paramagnet Resonance and UV–vis spectroscopies. The complexes were shown to have affinity for isolated DNA, as determined by Circular Dichroism experiments. Furthermore, biological experiments showed that all the complexes present high cytotoxic activity against the cell lines: MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (human normal breast cells), A549 (human lung epithelial carcinoma) and MRC-5 (human lung epithelial cells). Together, these results suggest that these compounds are promising steps towards new effective drugs to treat cancer.

Resumo Este estudo teve por objetivo analisar a produção científica nacional e internacional sobre os grupos de reabilitação psicossocial para mulheres com câncer de mama. O levantamento bibliográfico foi realizado a partir das bases indexadoras LILACS, PubMed, PsycINFO e CINAHL. Foram selecionados 28 artigos, publicados no período de 2000 a 2015, que constituíram o corpus do estudo. Os achados foram agrupados por meio de análise de conteúdo. Os resultados evidenciaram que os grupos de apoio podem resultar em benefícios psicossociais, como redução de estresse, incremento da qualidade de vida, melhora do humor e compartilhamento de informações sobre as diversas opções de tratamentos disponíveis. Conclui-se que participar de grupos de apoio está associado a melhores desfechos psicológicos, contudo, não há evidências que comprovem aumento na expectativa de vida das mulheres. Abstract This study aimed to analyze the national and international scientific literature on the topic of psychosocial rehabilitation groups for women with breast cancer. The literature review was conducted from LILACS, PubMed, PsycINFO and CINAHL database. 28 articles published in the period 2000-2015, which constituted the corpus of the study, were selected. The results showed that, in most cases, support groups bring psychosocial benefits, stress reduction, increased and quality of life, mood enhancement and sharing information about different options of treatment available for breast cancer. We conclude that participating in support groups is associated with better psychological outcomes, however, there is no evidence to support an increase in life expectancy of women.

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2021-08-26T17:38:41Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_haide_valeska_scheid.pdf: 1845693 bytes, checksum: 0c9299b32a49755e158f7446c87b2a5f (MD5) Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2021-08-27T14:42:51Z (GMT) No. of bitstreams: 2 dissertacao_haide_valeska_scheid.pdf: 1845693 bytes, checksum: 0c9299b32a49755e158f7446c87b2a5f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Made available in DSpace on 2021-08-27T14:42:51Z (GMT). No. of bitstreams: 2 dissertacao_haide_valeska_scheid.pdf: 1845693 bytes, checksum: 0c9299b32a49755e158f7446c87b2a5f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2019-02-27 Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq Nos últimos anos verificou-se um crescente aumento no número de felinos que convivem com o homem, gerando uma nova demanda na medicina veterinária por estudos específicos da espécie felina. O objetivo desse estudo foi identificar as principais patologias de felinos na região sul do Rio Grande do Sul. Foram revisados os protocolos de necropsia e materiais de felinos encaminhados ao Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel) no período de 1978 a 2018. Nesse período foram recebidas 1.633 amostras de felinos, sendo 363 (22%) entre os anos de 1978 e 1999 e 1.270 (78%) entre os anos de 2000 e 2018. Com relação aos diagnósticos, 457 felinos (28%) apresentaram tumores benignos ou malignos sendo os tegumentares e os mamários os mais frequentes. As infecções bacterianas, fúngicas, virais, parasitárias, sem agente definido e as intoxicações foram observadas em 553 casos (34%), destacando-se a esporotricose com 13% dos diagnósticos. No segundo artigo foram abordados os casos de esporotricose sistêmica diagnosticados no LRD no período de 2000 a 2018. A forma sistêmica da micose é pouco relatada na literatura, contudo tem grande importância na saúde pública por tratar-se de uma zoonose ascendente na região sul do Rio Grande do Sul. Foi realizado um levantamento nos protocolos de necropsia de felinos com histórico de infecção pelo fungo Sporothrix spp, recebidos no LRD/UFPel, entre os anos de 2000 e 2018. Neste período, foram diagnosticados 17 felinos com esporotricose sistêmica. A presença do fungo foi observada em diferentes órgãos, sendo que em todos os felinos havia lesões na pele e pulmão. A técnica de imunohistoquímica foi utilizada em todos os casos, apresentando-se uma eficiente ferramenta auxiliar de diagnóstico. Over the years there has been a growing increase in the number of felines that live with man, creating a new demand in veterinary medicine, which has as objective specific studies of the feline species.The goal of this paper was to identify the main pathologies affecting felines in the southern region of Rio Grande do Sul. The necropsy protocols and feline materials submitted to the Regional Diagnostic Laboratory of the Veterinary College of the Federal University of Pelotas (LRD / UFPel) were reviewed, from 1978 to 2018. During this period 1,633 feline samples were received, 363 (22%) between 1978 and 1999 and 1,270 (78%) between 2000 and 2018. Felines without a defined breed were represented by 59%. As for diagnoses, 457 felines (28%) presented benign or malignant tumors, the most common being the integumentary and mammary tumors. Bacterial, fungal, viral, parasitic, protozoal or undefined agent infections and intoxications were observed in 553 cases (34%), especially sporotrichosis with 13% of the diagnoses. The second article addressed the cases of systemic sporotrichosis diagnosed in the LRD from 2000 to 2018. The systemic form of mycosis is poorly reported in the literature, but it is of great importance in public health because it is an ascending zoonosis in southern Brazil. Rio Grande do Sul. A survey was performed on the necropsy protocols of cats with a history of infection with the fungus Sporothrix spp, received at LRD / UFPel, between 2000 and 2018. During this period, 17 felines were diagnosed with systemic sporotrichosis. The presence of the fungus was observed in different organs, and in all cats there were skin and lung lesions. The immunohistochemistry technique was used in all cases, presenting an efficient auxiliary diagnostic tool.

This study aimed to analyze the national and international scientific literature on the topic of psychosocial rehabilitation groups for women with breast cancer. The literature review was conducted from LILACS, PubMed, PsycINFO and CINAHL database. 28 articles published in the period 2000-2015, which constituted the corpus of the study, were selected. The results showed that, in most cases, support groups bring psychosocial benefits, stress reduction, increased and quality of life, mood enhancement and sharing information about different options of treatment available for breast cancer. We conclude that participating in support groups is associated with better psychological outcomes, however, there is no evidence to support an increase in life expectancy of women., Este estudo teve por objetivo analisar a produção científica nacional e internacional sobre os grupos de reabilitação psicossocial para mulheres com câncer de mama. O levantamento bibliográfico foi realizado a partir das bases indexadoras LILACS, PubMed, PsycINFO e CINAHL. Foram selecionados 28 artigos, publicados no período de 2000 a 2015, que constituíram ocorpusdo estudo. Os achados foram agrupados por meio de análise de conteúdo. Os resultados evidenciaram que os grupos de apoio podem resultar em benefícios psicossociais, como redução de estresse, incremento da qualidade de vida, melhora do humor e compartilhamento de informações sobre as diversas opções de tratamentos disponíveis. Conclui-se que participar de grupos de apoio está associado a melhores desfechos psicológicos, contudo, não há evidências que comprovem aumento na expectativa de vida das mulheres.

Considering that breast cancer usually begins in the lining of the ducts, local drug administration into the ducts could target cancers and pre-tumor lesions locally while reducing systemic adverse effects. In this study, a cationic bioadhesive nanoemulsion was developed for intraductal administration of C6 ceramide, a sphingolipid that mediates apoptotic and non-apoptotic cell death. Bioadhesive properties were obtained by surface modification with chitosan. The optimized nanoemulsion displayed size of 46.3 nm and positive charge, properties that were not affected by ceramide encapsulation (0.4%, w/w). C6 ceramide concentration necessary to reduce MCF-7 cells viability to 50% (EC50) decreased by 4.5-fold with its nanoencapsulation compared to its solution; a further decrease (2.6-fold) was observed when tributyrin (a pro-drug of butyric acid) was part of the oil phase of the nanocarrier, a phenomenon attributed to synergism. The unloaded nanocarrier was considered safe, as indicated by a score Galleria mellonella larvae exposed to concentrations ≤500 mg/mL, and absence of histological changes when intraductally administered in rats. Intraductal administration of the nanoemulsion prolonged drug localization for more than 120 h in the mammary tissue compared to its solution. These results support the advantage of the optimized nanoemulsion to enable mammary tissue localization of C6 ceramide.

O Carcinoma Mamário é altamente invasivo e metastático em gatas, por isso a sua detecção precoce e uma terapia agressiva podem influenciar no tempo de sobrevida global das pacientes. Ao mesmo tempo, são pacientes idosas com comorbidades importantes que necessitam ser diagnosticadas e estabilizadas antes do tratamento com complicações também importantes. Além disso, a imagem ultrassonográfica dos linfonodos axilares e inguinais durante o estadiamento clínico pode auxiliar no diagnóstico precoce das metástases regionais dessa neoplasia. O objetivo deste estudo foi acompanhar prospectivamente as gatas com neoplasias mamárias atendidas no Hospital de Clínicas Veterinárias (HCV/UFRGS) desde o diagnóstico até o tratamento cirúrgico e quimioterápico para: (1) descrever suas comorbidades e as complicações do tratamento cirúrgico e quimioterápico; (2) comparar a avaliação clínica, a imagem ultrassonográfica e a avaliação histopatológica dos linfonodos axilares e inguinais. Foram incluídas no estudo as gatas acometidas por neoplasias mamárias palpáveis, cujos tutores concordaram com a participação no estudo (CEUA/UFRGS - 32.717). As pacientes foram encaminhadas a atendimento clínico pelos métodos normais de triagem do HCV-UFRGS entre janeiro de 2017 e dezembro de 2018. Durante as avaliações clínicas para estadiamento das pacientes (ultrassom abdominal total, radiografias torácicas, urinálise, urocultura, hemograma e bioquímica sérica), foram realizados exames clínicos com palpação dos linfonodos axilares e inguinais, e exames ultrassonográficos dos mesmos. Após as linfadenectomias axilares e inguinais juntamente com mastectomias laterais ou bilaterais, foram realizadas as avaliações histopatológicas das neoplasias e dos linfonodos. Foram acompanhadas prospectivamente 34 gatas, 91% delas com neoplasias mamárias malignas, 13% já com metástase em linfonodos e 18% com metástase à distância no momento do diagnóstico. Com idade media de dois anos (0,5 - 8 anos), a maioria (29, 85%) não apresentava raça definida. Apenas 24 (71%) eram castradas, e dessas, apenas seis (18%) foram castradas antes de um ano de idade. Quinze (44%) receberam aplicação de progestágenos para prevenção de prenhez. Foram classificadas quanto ao estadiamento clínico,: 10 (29%) em estadio I; sete (21%), em II; 10 (29%), em III; e sete (21%), em IV. Os tratamentos realizados foram: mastectomia lateral (11,32.35%), mastectomia bilateral (4, 11.76%), mastectomia lateral e quimioterapia (4, 11.76%), tratamento paliativo e posterior eutanásia (4, 11.76%), biopsia excisional (3, 8.82%), eutanásia no momento do diagnóstico (3, 8.82%), quimioterapia e eutanásia (2, 5.88%), biopsia excisional e posterior mastectomia lateral (1, 2.94%), mastectomia com esplenectomia (1, 2.94%). Uma paciente foi a óbito antes de iniciar o tratamento. Os tipos histológicos com maior ocorrência foram os carcinomas: cribriforme (11, 32%), tubulopapilar (9, 27%), e tubular (2, 6%). Doze gatas (35%) apresentaram neoplasias com grau histológico III, seis (18%) apresentaram grau II, e seis (18%), grau I. O exame ultrassonográfico dos linfonodos (n=23) apresentou forte concordância (κ=0,805, p

Background Triple negative breast cancer (TNBC) is a malignancy with very poor prognosis, due to its aggressive clinical characteristics and lack of response to receptor-targeted drug therapy. In TNBC, immune-related pathways are typically upregulated and may be associated with a better prognosis of the disease, encouraging the pursuit for immunotherapeutic options. A number of immune-related molecules have already been associated to the onset and progression of breast cancer, including NOD1 and NOD2, innate immune receptors of bacterial-derived components which activate pro-inflammatory and survival pathways. In the context of TNBC, overexpression of either NOD1or NOD2 is shown to reduce cell proliferation and increase clonogenic potential in vitro. To further investigate the pathways linking NOD1 and NOD2 signaling to tumorigenesis in TNBC, we undertook a global proteome profiling of TNBC-derived cells ectopically expressing each one of these NOD receptors. Results We have identified a total of 95 and 58 differentially regulated proteins in NOD1- and NOD2-overexpressing cells, respectively. We used bioinformatics analyses to identify enriched molecular signatures aiming to integrate the differentially regulated proteins into functional networks. These analyses suggest that overexpression of both NOD1 and NOD2 may disrupt immune-related pathways, particularly NF-κB and MAPK signaling cascades. Moreover, overexpression of either of these receptors may affect several stress response and protein degradation systems, such as autophagy and the ubiquitin-proteasome complex. Interestingly, the levels of several proteins associated to cellular adhesion and migration were also affected in these NOD-overexpressing cells. Conclusions Our proteomic analyses shed new light on the molecular pathways that may be modulating tumorigenesis via NOD1 and NOD2 signaling in TNBC. Up- and downregulation of several proteins associated to inflammation and stress response pathways may promote activation of protein degradation systems, as well as modulate cell-cycle and cellular adhesion proteins. Altogether, these signals seem to be modulating cellular proliferation and migration via NF-κB, PI3K/Akt/mTOR and MAPK signaling pathways. Further investigation of altered proteins in these pathways may provide more insights on relevant targets, possibly enabling the immunomodulation of tumorigenesis in the aggressive TNBC phenotype. Electronic supplementary material The online version of this article (10.1186/s12864-019-5523-6) contains supplementary material, which is available to authorized users.

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2021-11-18T12:19:35Z No. of bitstreams: 1 PDF - Tácila Thamires de Melo Santos.pdf: 2411883 bytes, checksum: 69e28b01edc49ca8817f22846572b484 (MD5) Approved for entry into archive by Rosalvo Andrade (rosalvo_andrade@servidor.uepb.edu.br) on 2021-11-18T19:53:19Z (GMT) No. of bitstreams: 1 PDF - Tácila Thamires de Melo Santos.pdf: 2411883 bytes, checksum: 69e28b01edc49ca8817f22846572b484 (MD5) Made available in DSpace on 2022-01-13T13:47:48Z (GMT). No. of bitstreams: 1 PDF - Tácila Thamires de Melo Santos.pdf: 2411883 bytes, checksum: 69e28b01edc49ca8817f22846572b484 (MD5) Previous issue date: 2018-05-23 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Background: The total number of deaths due to breast cancer in Latin American countries is expected to double between 2008 and 2030 to 73,542 cases, and it has been reported that 30% to 40% of patients present at advanced stages (III and IV). One of the major problems contributing to increased mortality rates for breast cancer in developing countries is delay of treatment. Objectives: The analysis of Brazilian studies, aimed on literature between the years 2006 and 2018, about breast cancer treatment delay. A research project focused on evaluation of acceleration of patient flow by intervention of non-governmental organizations (NGOs). NGOs donated diagnostic mammographies and biopsies. Furthermore, system delay (SD) was compared between two public reference centers of cancer treatment: One with integrated and the other one with outsourced diagnostic services. Methods: The integrative revision of Brazilian literature was performed applying the descriptors "Breast cancer" and "Delay" in four databases on literature. In the cross- sectional study about treatment delay, Cox regression analysis was used to identify variables that contributed to SD among 128 breast cancer patients treated at two referral centres. Kaplan- Meier analysis was performed to compare time intervals between patient groups of both referral centers. Results: Integrative revision led to identification of 17 studies: Nine studies have addressed only the system delay and eight addressed system delay and delay patient. Most cited causes of treatment delay were non- performance of screening test and routine consultation, lack of the important aspects of the disease, fear of diagnosis and treatment, low educational level and low family budget. In the cross-sectional study, those women who used a specialized private clinic at the beginning of patient flow had an increased chance (HR = 2.32; 95% CI: 1.17 - 4.60; p = 0.016) of hospital admission within 90 days after the first medical consultation, compared to women who used a public health care provider (HCP). Of 73 and 34 patients of the referral center with outsourced diagnostic services and the referral center with integrated diagnostic services, 10 (13.7%) and 11 (32.5%) used one HCP prior to hospital admission (p = 0.000). Time between first medical consultation and hospital admission was an average of 515 (SD = 36.6) and 135 (SD = 21.2) days for patients who used the referral center with outsourced, respectively, integrated diagnostic services, compared to 370 (SD = 78.2) days, for those women who received help by NGOs and were treated at the referral center with outsourced services (p = 0.002). Conclusions: Literature about treatment delay focused mainly of causal socio- economic aspects of patients. There was no Brazilian study comparing SD among referral centers with integrated and outsourced diagnostic services. In the present study about SD, those patients who used a public HCP had an increased SD compared to patients who never used them prior to hospital admission and those who used specialized private clinics at the beginning of patient flow. Furthermore, data indicated acceleration of patient flow by integration of diagnostic services, respectively, a low number of health care providers used by patients. Intervention of NGOs accelerated patient flow. Introdução: O número total de mortes por câncer de mama em países da América Latina deve dobrar entre 2008 e 2030 para 73.542 casos, e estima-se que 30% a 40% desses pacientes apresentem estádios avançados (III e IV). Um dos principais problemas que contribuem para o aumento das taxas de mortalidade por câncer de mama nos países em desenvolvimento é o atraso no tratamento. Objetivos: Analisar a literatura brasileira sobre atraso do tratamento de câncer de mama entre os anos de 2006 e 2018. E comparar o atraso do sistema (AS) em dois centros de referências no tratamento do câncer: um com um serviço de diagnóstico integrado e com serviços de diagnóstico terceirizados e a aceleração do fluxo das pacientes por intervenção de Organizações Não-Governamentais (ONGs). Métodos: O primeiro artigo trata-se de uma revisão integrativa sobre os fatores que influenciam no atraso do tratamento de câncer de mama no Brasil. O segundo artigo trata-se de um estudo transversal, a análise de regressão de Cox foi utilizada para identificar as variáveis que contribuíram para o atraso do sistema entre 128 pacientes com câncer de mama tratados em dois centros de referência. A análise de Kaplan-Meier foi realizada para comparar os intervalos de tempo entre os grupos de pacientes de ambos os centros de referência. Resultados: A revisão integrativa identificou 17 estudos: nove estudos abordaram exclusivamente o atraso de sistema e oito abordaram atraso de sistema e atraso da paciente. Não realizar exame de rastreamento e consulta de rotina, desconhecimento dos aspectos importantes da doença, medo do diagnóstico e do tratamento, baixo nível escolar e os gastos no orçamento familiar, foram às causas mais citadas do atraso de paciente ao tratamento. No estudo transversal as mulheres que usaram uma clínica privada especializada no início do fluxo de pacientes tiveram uma chance aumentada (HR = 2,32; IC95%: 1,17 - 4,60; p = 0,016) de internação hospitalar dentro de 90 dias, em comparação com as mulheres que usou um serviço de saúde público. No estudo transversal, aquelas mulheres que usaram uma clínica privada especializada no início do fluxo do paciente tiveram uma chance aumentada (HR = 2,32; 95% CI: 1,17 - 4,60; p = 0,016) de internação hospitalar dentro de 90 dias após a primeira consulta, em comparação com as mulheres que usaram a Atenção Básica de Saúde (ABS). Dos 73 e 34 pacientes do centro de referência com serviços de diagnóstico terceirizados e do centro de referência com serviços integrados de diagnóstico, 10 (13,7%) e 11 (32,5%) usaram apenas um serviço de saúde antes da admissão hospitalar (p = 0,000). O tempo entre a primeira consulta médica e a internação hospitalar foi em média 515 (DP = 36,6) e 135 (DP = 21,2) dias para os pacientes que utilizaram o centro de referência com serviços de diagnóstico terceirizados, respectivamente integrados, em comparação com 370 (DP = 78,2) dias, para aquelas mulheres que receberam ajuda das ONGs e foram atendidas no centro de referência com serviços terceirizados (p = 0,002). Conclusão: A literatura sobre o atraso no tratamento enfocou principalmente os aspectos socioeconômicos causais dos pacientes. Não houve estudo brasileiro comparando AS entre os centros de referência com serviços de diagnóstico integrados e terceirizados. No presente estudo sobre AS, os pacientes que usaram a ABS tiveram um AS aumentado em comparação com pacientes que nunca utilizaram este serviço antes da admissão hospitalar ou aqueles que usaram clínicas privadas. Além disso, os dados indicaram aceleração do fluxo do paciente pela integração dos serviços de diagnóstico. A intervenção das ONGs acelerou o fluxo das pacientes.

Las neoplasias de la glándula mamaria representan el tumor más frecuente en perras enteras, siendo la edad media de aparición entre los 8 y 10 años. Las hormonas esteroides sexuales, principalmente estrógenos y progesterona, representan el principal factor de riesgo para su desarrollo, y la castración antes del segundo celo reduce el riesgo de aparición de esta neoplasia. Se ha demostrado la presencia de receptores a estrógenos (RE) y progesterona (RP) en los tumores mamarios caninos, siendo esta expresión mayor en tumores benignos comparada con tumores malignos. Sin embargo, la asociación de los RE y RP con factores clínico - patológicos, así como su valor pronóstico, se encuentran en discusión. Por otra parte, algunos estudios en humanos han revelado que además de las clásicas hormonas sexuales, otras hormonas parecen estar involucradas en el desarrollo y/o progresión de esta neoplasia. Así, se ha demostrado la presencia de los péptidos oxitocina y vasopresina, así como de sus receptores en líneas celulares de cáncer mamario humano y en carcinomas primarios de mama humanos. En la perra, al momento se desconoce la presencia de receptores a estas hormonas en los tumores mamarios caninos. La extirpación quirúrgica del tumor representa el tratamiento de elección para todas aquellas perras con neoplasias mamarias. Sin embargo, existe un elevado número de pacientes en los que la cirugía no es suficiente para lograr la curación, o pacientes en los que la realización de la cirugía no es posible, por lo que se hace necesaria la búsqueda de terapias adyuvantes a la cirugía o paliativas. Trabajos sobre líneas celulares de cáncer mamario humano, así como estudios in vivo sobre modelos murinos de cáncer mamario, han demostrado que la oxitocina y la desmopresina (análogo sintético de la hormona vasopresina) tienen la capacidad de modular el crecimiento de las células tumorales. En la perra, al momento se desconocen los efectos de estos péptidos sobre líneas de cáncer mamario canino. Por lo tanto, la presente tesis de doctorado tuvo como objetivo general aportar conocimientos acerca de la influencia del componente hormonal sobre el desarrollo de los tumores mamarios caninos, mediante el estudio de la población de receptores a hormonas esteroideas, oxitocina y vasopresina en el tejido mamario tumoral canino y la evaluación de los posibles efectos antitumorales de péptidos en una línea celular de cáncer mamario canino. En la primera parte de la tesis doctoral se realizó una caracterización clínica y patológica de los tumores mamarios caninos recolectados. El estudio reveló una edad promedio de aparición de esta neoplasia de 9,4 años, indicando que ocurre mayormente en perras de edad media a adulta. Asimismo, la mayor parte de las perras se encontraban enteras al momento del diagnóstico, lo cual brinda mayor sustento al rol fundamental que tienen las hormonas esteroides sexuales en el desarrollo de los tumores mamarios. El análisis histológico mostró que el 60% de las neoplasias fue de naturaleza maligna, siendo el carcinoma túbulo-papilar el más frecuentemente diagnosticado. El restante 40% de los tumores fue de naturaleza benigna, siendo el adenoma (simple y complejo) el tipo más comúnmente hallado. El estudio inmunohistoquímico del receptor a estrógenos α (REα) permitió visualizar una mayor expresión en tumores benignos en comparación con malignos. Asimismo, en el grupo de tumores malignos, se observó una mayor expresión en carcinomas del tipo túbulo-papilar, así como en carcinomas de Grado Histológico de Malignidad (GHM) I. Estos resultados dan mayor sustento a la hipótesis de que la presencia del REα se pierde conforme el tumor progresa hacia la malignidad, y que su expresión en tumores malignos se relaciona con características de baja malignidad tumoral. También se estudió la expresión del receptor a estrógenos β (REβ), observándose que su expresión ocurrió de manera similar tanto en tumores mamarios benignos como malignos. Dado que no se observó asociación alguna con los factores de valor pronóstico analizados para tumores malignos, en la presente tesis no se pudo establecer su rol en las neoplasias mamarias en caninos. Además, se estudió la presencia del RP en tumores mamarios benignos y malignos, observándose una baja expresión en ambos tipos tumorales. Cuando se evaluó su asociación con los factores clínico-patológicos, se observó una mayor expresión del RP en perras que se encontraban en estadíos clínicos IV y V, permitiendo sugerir que los agentes antiprogestágenos podrían ser de utilidad en casos de cáncer mamario avanzado. Por otro lado, en la segunda parte de la presente tesis se demostró la presencia del receptor a oxitocina (ROT) en los tumores mamarios caninos analizados, hallazgo que representa el primer reporte acerca de la expresión de este receptor en esta neoplasia en la especia canina. El ROT se expresó tanto en tumores benignos como malignos, y en estos últimos, su expresión fue mayor en carcinomas de GHM I y II, y tendió a ser mayor en los tumores malignos positivos para el REα. Sin bien se necesitan mayores estudios al respecto, se podría especular que, al igual que ocurre con otros receptores a hormonas, la presencia del ROT en el tumor estaría asociada con factores indicadores de buen pronóstico. Del mismo modo, los resultados del estudio inmunohistoquímico para el receptor a vasopresina V2 (RAVP V2) revelaron que el total de los tumores mamarios caninos analizados resultaron positivos a este receptor, siendo su expresión elevada en todos los casos. Para nuestro conocimiento, esta es la primera vez que se reporta la presencia de este receptor en las neoplasias mamarias en caninos, y reviste importancia a la hora de utilizar moléculas como la desmopresina, con efectos antitumorales y antimetastásicos conocidos, cuyas acciones se ejercen a través del RAVP V2. Considerando la necesidad de investigar nuevas y más eficaces alternativas terapéuticas para el tratamiento de los tumores mamarios en caninos, en la tercera parte de la presente tesis se evaluó la capacidad antitumoral de los péptidos oxitocina y desmopresina sobre una línea celular de cáncer mamario canino. De forma previa a la realización de los ensayos in vitro, se evaluó la presencia del receptor a oxitocina y vasopresina V2 en la línea celular CMT-U27 de cáncer mamario canino, ya que son los sitios de unión para ejercer su acción que utilizan la oxitocina y la desmopresina, respectivamente. Las células tumorales mostraron expresión para ambos receptores, lo cual demuestra que esta línea celular es óptima para evaluar el efecto de estos péptidos. En el ensayo in vitro se observó que la administración de oxitocina a dosis 1000 nM inhibió la proliferación de la línea CMT-U27, lo cual coincide con reportes previos en humanos, y permite sugerir que esta hormona ejerce efectos moduladores del crecimiento de las células tumorales. Por último, se demostró que la desmopresina (1000 nM) ejerció un efecto inhibidor del crecimiento de la línea celular CMT-U27. Por tanto, la observación de una alta expresión del ROT y RAVP V2 en los tumores mamarios caninos, sumado al efecto antiproliferativo que ejercieron la oxitocina y desmopresina en una línea celular de cáncer mamario canino, permiten recomendar que se considere a estos compuestos como una opción interesante para el tratamiento de los tumores mamarios caninos, y resulta de utilidad para continuar investigando péptidos análogos a ellos con mayor capacidad antiproliferativa. Fil: Benavente, Micaela Andrea. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Fil: Aba, Marcelo Alfredo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Fil: Bianchi, Carolina Paula. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Mammary gland tumors are the most frequent cancer described in female dogs, and the reported median age of occurrence ranges from 8 to 10 years. Ovarian steroid hormones, mainly estrogens and progesterone represent the main risk factor for the development of this neoplasm, and this idea is supported by the protective effect of ovariectomy. The presence of estrogen (ER) and progesterone receptors (PR) in canine mammary tumors has been described in several studies. Moreover, the expression of ER and PR is significantly higher in benign tumors compared with malignant ones. Nevertheless, information on the role of steroid hormone receptors and prognosis is inconsistent. Besides, some studies in humans have shown that apart from estrogens and progesterone, other hormones seem to be involved in the development and progression of mammary tumors. Thus, it has been demonstrated that the hormones oxytocin (OT) and vasopressin (AVP) are present in cancerous human breast tissue. Moreover, oxytocin receptor and V2 vasopressin receptor have been detected in primary breast carcinomas and in breast carcinoma cell lines. To the best of our knowledge, there are no studies regarding the expression of oxytocin receptor (OTR) and V2 vasopressin receptor (V2 AVPR) in canine mammary tumors. Surgical excision is the first-line treatment of canine mammary tumors. However, in dogs with highly malignant mammary tumors, the probability of tumor recurrence after surgery is elevated, so adjuvant therapy is recommended. Moreover, there are some patients in which surgery is not possible, so it is important to develop palliative therapies. Studies in human breast cancer cells have shown that OT and desmopressin (a synthetic analog of AVP) can modulate cell proliferation. The antitumor properties of both peptides have also been shown in experimental mouse models of breast cancer. In the bitch, the effects of these peptides on canine mammary cancer cells lines are not known. Thus, the main objective of the present thesis was to increase the knowledge of hormonal influences in the development of canine mammary tumors, by studying the presence of estrogens, progesterone, oxytocin and vasopressin receptors in canine mammary tumor tissues, and evaluating the effects of OT and desmopressin on cell proliferation using a canine mammary cancer cell line. In the first part of the present study, clinical and pathological features of 65 canine mammary tumors were evaluated. The results indicate that the mean age at which the mammary gland tumor was first recognized was 9.4 years. Regarding reproductive status, 76.9 % of the dogs were intact, giving further support to the idea that ovarian sexual steroid hormones are the main risk factor for the appearance of this neoplasm. Histology of the mammary gland tumors revealed that 60% of them were malignant, and 40% were benign. Among malignant tumors, tubulopapillary carcinomas were the most frequent tumor type, and among benign tumors, adenomas (simple and complex) were the most commonly diagnosed. Regarding immunohistochemical analysis, the present study showed that ERα expression was greater in benign than in malignant tumors. Furthermore, in the group of malignant tumors, a higher ERα expression was observed in tubulopapillary carcinomas and in Grade I tumors. These observations support the hypothesis that progression towards malignancy is accompanied by a decrease in hormonal steroid dependency, and suggest that ER expression is associated with clinicopathological characteristics of low malignant potential. Besides, in the present study ERβ expression was observed in both benign and malignant mammary tumors and no significant differences were found between them. In malignant tumors, no significant association was observed between ERβ expression and prognostic factor, so its significance could not be elucidated in the present thesis. Regarding PR expression, the present study also revealed that there was no significant difference in PR expression between benign and malignant tumors. However, in the group of malignant tumors, a higher PR expression was detected in clinical stages IV and V, suggesting that antiprogestins may be a useful therapy for bitches with advanced mammary cancer. Besides, in the second part of the present thesis it was demonstrated that OTR is present in both benign and malignant tumors. To the best of our knowledge, this is the first report regarding OTR expression in canine mammary tumors. In malignant tumors, OTR expression was higher in Grade I and II carcinomas, and showed a tendency to be higher in ERα positive tumors. Although further research is needed, the present results could indicate that OTR expression in malignant tumors is associated with good prognostic factors. In a similar way, immunohistochemistry revealed that all the analyzed mammary tumors expressed the V2 AVPR, with high Total Scores in both benign and malignant types. These findings represent the first report regarding V2 AVPR expression in canine mammary tumors, and suggest that desmopressin, a peptide with antitumor properties, could be an interesting option for the treatment of V2 AVPR expressing mammary tumors. Considering the need for new strategies for the treatment of canine mammary tumors, in the third part of the present thesis the antitumor effects of peptides oxytocin and desmopressin were investigated in vitro. In a preliminary study, the presence of OTR and V2 AVPR were demonstrated in the canine mammary cancer cell lines CMT-U27, which indicates that this cell line is a useful in vitro model to evaluate the effects of these peptides. The in vitro assay revealed a growth inhibitory effect with OT at 1000 nM, which is in accordance with previous studies in humans, and suggests that this hormone has growth-modulatory effects in neoplastic mammary cells. Finally, desmopressin (1000 nM) induced a significantly inhibition of CMT-U27 proliferation. In conclusion, the results indicate that peptides oxytocin and desmopressin should be considered as promising compounds for the treatment of dogs with mammary tumors.

Dissertação de Mestrado em Enfermagem Comunitária O presente relatório, realizado no âmbito da unidade curricular Estágio e Relatório, desenvolvido na Unidade de Cuidados na Comunidade Vila Real I e Unidade de Saúde Pública de Vila Real, do Agrupamento de Centros de Saúde Douro I - Marão e Douro Norte, no período de 14 de setembro de 2015 a 29 de janeiro de 2016, teve como finalidade o desenvolvimento de competências do enfermeiro especialista em enfermagem comunitária e de saúde pública. O enfermeiro de saúde comunitária tem um papel fundamental no empowerment da comunidade, bem como na promoção da acessibilidade, especialmente a grupos vulneráveis, sendo uma das estratégias do plano nacional de saúde revisão e extensão a 2020. Estudos epidemiológicos realizados apontam para um aumento da frequência de doenças crónicas, a doença oncológica inclui-se nesta tipologia, como a doença oncológica da mama que afeta cada vez mais mulheres, sendo importante compreender a relação entre empowerment psicológico, bem-estar psicológico e coping, em mulheres com doença oncológica da mama recentemente diagnosticada, no processo de adaptação à vivência da transição despoletada pelo processo de doença. No sentido de responder a este propósito, realizou-se um estudo empírico, transversal e correlacional com uma abordagem quantitativa. A amostra constituída por 100 mulheres com doença oncológica da mama recentemente diagnosticada, com uma média de idades 52,2 e dp de 8,9 anos. Para avaliar empowerment psicológico, foi utilizado o Cancer Empowerment Questionnaire (CEQ), de Van den Berg, Van Amstel, Ottevanger, Gielissen e Prins (2013), que foi validado para esta amostra, o bem-estar psicológico foi avaliado pelo Questionário Bem-Estar Psicológico Reduzido (QBEP-R) de Rainho et al. (2012) e o coping pelo questionário BriefCOPE de Ribeiro e Rodrigues (2004). Para a análise descritiva foram utilizadas medidas de frequência relativa e absoluta, medidas de tendência central e de dispersão; na análise correlacional foram utilizados testes paramétricos e não paramétricos, de acordo com distribuição das variáveis. Os resultados obtidos evidenciaram que as participantes apresentavam uma média de 166,7 e dp=18,1 de empowerment psicológico, quanto bem-estar psicológico apresentaram uma média de 16,9 e dp=5,6, sendo as estratégias de coping mais utilizadas por estas mulheres a estratégia centrada nas emoções (m=1,7; dp=0,57) e a estratégia centrada no problema, (m=1,5; dp=0,63). Tendo em consideração os resultados obtidos no presente estudo, concluiuse que o empowerment psicológico se relaciona com bem-estar psicológico e coping, em mulheres com doença oncológica da mama recentemente diagnosticada. Nas unidades funcionais onde desenvolvemos o estágio participámos em atividades que também nos permitiram dar continuidade ao processo de desenvolvimento de competências do Enfermeiro Especialista em Enfermagem Comunitária e de Saúde Pública, das quais salientamos as atividades desenvolvidas no âmbito do projeto de intervenção “Primeiros Socorros e Suporte Básico de Vida”, no sentido de capacitar os professores das escolas do ensino público da área de abrangência da Unidade de Cuidados na Comunidade Vila Real I. Também realizámos sessões de educação para a saúde no âmbito dos projetos: “Lanche Escolar: o que está a dar?”, ”+ Social E5G”, “Cuidar de quem precisa”. A participação nas atividades supranumeradas contribuiu, nomeadamente: i) estabelecer, com base na metodologia do planeamento em saúde, a avaliação do estado de saúde de uma comunidade; ii) contribuir para o processo de capacitação de grupos e comunidades; iii) integrar a coordenação dos programas de saúde de âmbito comunitário e na consecução dos objetivos do plano nacional de saúde (Regulamento nº 128/2011, de 18 de fevereiro). This report, carried out within the scope of the Report of Internship, developed at Health Center (Vila Real Community Care Unit and the Vila Real Public Health Unit) of the Douro I - Marão and Douro Norte Health Centers Group (ACeS), that occurred in the period from 14th September of 2015 to 2th January 2016, aimed to develop the competencies of Specialist Nursing of Community and Public Health, The community nurse plays a key role in community empowerment, as well as the promotion of accessibility, especially to vulnerable groups, as one of the strategies of the national health plan review and extension by 2020. Epidemiological studies have pointed to an increase in the frequency of chronic diseases, oncological disease is included in this typology, such as oncological disease of the breast that affects more and more women, and it is important to understand the relationship between psychological empowerment and psychological coping, in Women with newly diagnosed breast cancer, in the adaptation to the experience of the transition triggered by the disease process, In order to respond to this purpose, we developed a cross-sectional and correlational study was carried out with a quantitative approach. The sample consisted of 100 women with newly diagnosed breast cancer, with a mean age of 52.2 and BP of 8.9 years. To evaluate psychological empowerment, we used the Cancer Empowerment Questionnaire (CEQ) by Van den Berg et al. (2013), which was validated for this sample, the well-being was evaluated by the Psychological Well-Being Questionnaire-Brief (PWB-B) of Rainho et al. (2012) and the coping strategies by the BriefCOPE questionnaire (Pais-Ribeiro & Rodrigues, 2004). For the descriptive analysis we used frequencies (percentage) and central tendency and dispersion measures; parametric and non-parametric tests were used in the correlation analysis, according to the distribution of the variables. The results showed, as regards to psychological empowerment, the participants presented a mean of 166.7 and dp = 18.1, as for the psychological well-being presented an average of 16.9 and dp = 5.6, being more used the emotional-centered strategies (m=1.7; dp = 0.57) and followed by the problem-centered strategies (m=1.5; dp = 0.63). Taking into account the results obtained in the present study, it is concluded that psychological empowerment is related to psychological well-being and coping, in women with newly diagnosed breast cancer. In the Health center, where we developed the internship, we participated in activities, which also allowed us to continue the development competency of Specialist Nursing of Community and Public Health, from we highlight the activities carried out under the project "First Aid and Basic Life Support" in the sense to train teachers of high school. Also we developed health education sessions, included in the projects: "School Snack: what is it to give?"; "+ Social E5G" and "Care of who needs it". Participation in supranumerary activities contributed in particular to: i) apply the methodology of health planning; ii) contribute to the process of training groups and communities; iii) integrate the coordination of community-based health programs and the achievement of the objectives of the national health plan (Regulation No. 128/2011, of February 18).

Cure fraction models are useful to model lifetime data with long-term survivors. We propose a flexible four-parameter cure rate survival model called the log-sinh Cauchy promotion time model for predicting breast carcinoma survival in women who underwent mastectomy. The model can estimate simultaneously the effects of the explanatory variables on the timing acceleration/deceleration of a given event, the surviving fraction, the heterogeneity, and the possible existence of bimodality in the data. In order to examine the performance of the proposed model, simulations are presented to verify the robust aspects of this flexible class against outlying and influential observations. Furthermore, we determine some diagnostic measures and the one-step approximations of the estimates in the case-deletion model. The new model was implemented in the generalized additive model for location, scale and shape package of the R software, which is presented throughout the paper by way of a brief tutorial on its use. The potential of the new regression model to accurately predict breast carcinoma mortality is illustrated using a real data set.

Necrotizing autoimmune myopathy is characterized by predominant muscle fiber necrosis and regeneration with little or no inflammation. We describe a 58-year-old woman with previous breast cancer and statin use who complained of rapidly progressive weakness of lower limbs without pain, making walking, running and climbing stairs difficult. The creatine kinase level was 2,843 U/L, and muscle biopsy showed a dystrophic pattern. The genetic test for muscular dystrophies was negative and for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase was positive. Intravenous immunoglobulin was administered, which showed mild improvement. Unfortunately, she took a step and collapsed to the floor, which led to the fracture of right femur delaying her improvement. The diagnosis of necrotizing autoimmune myopathy is sometimes delayed due to the atypical pathologic findings on muscle biopsy. As the disease is a severe condition, prompt recognition can lead to a successful outcome. We advise to consider this entity as a differential diagnosis among muscular dystrophies.

Ribas C.R., Dornbusch P.T., de Faria M.R., Cirio S.M. & Wouk A.F.P. de F. [Coagulogram of the 35 females dogs with mammary neoplasias.] Coagulograma de 35 cadelas com neoplasias mamárias. Revista Brasileira de Medicina Veterinária, 37(1):83-87, 2015. Departamento de Medicina Veteriná- ria, Universidade Federal do Paraná, Rua dos Funcionários 1540, Curitiba, PR, 80035-050, Brasil. E-mail: ribas-cr@bol.com.br The mammary neoplasias are easily noticed by the owners, and are increasingly on the rise due to greater longevity of animals in recent years. So often cater to large number of female dogs in routine clinical medical oncology in small animals. Epidemiologically, the mammary neoplasias affecting mainly older dogs not spayed or neutered after several heats, with no racial predisposition. However, hardly possible to report laboratory findings directly or indirectly related to the neoplastic process. Therefore, the aim of this study was to analyze the coagulation of 36 dogs suffering from mammary cancer, diagnosed clinically and confirmed histopathologically. It was possible to identify changes such as decrease of TTPA (activated partial thromboplastin time), thrombocytosis, thrombocytopenia, disseminated intravascular coagulation (DIC). It was concluded that the alterations in coagulation of female dogs with mammary neoplasms were more significant in dogs suffering from mammary tumors in stage V., As neoplasias mamárias são facilmente notadas pelos proprietários e, estão cada vez mais em ascensão devido à maior longevidade dos animais nos últimos anos. Logo, frequentemente atendem-se grande número de cadelas na rotina clínica médica oncológica de pequenos animais. Epidemiologicamente, as neoplasias mamárias acometem cadelas preferencialmente idosas não castradas ou castradas após vários cios, sem qualquer predisposição racial. No entanto, dificilmente relatam-se possíveis alterações laboratoriais relacionadas direta ou indiretamente ao processo neoplásico. Logo, o objetivo deste estudo foi analisar o coagulograma de 36 cadelas portadoras de neoplasias mamárias, diagnosticadas clinicamente e, confirmadas histopatologicamente. Foi possível identificar alterações como: diminuição de TTPA (tempo de tromboplastina parcial ativada), trombocitose, trombocitopenia, coagulação intravascular disseminada (CID). Concluindo-se, que as alterações presentes no coagulograma das cadelas com neoplasias mamárias foram mais significativas em cadelas portadoras de neoplasias mamárias em estádio V.

Aim Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Methods Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Results Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0–85.0] vs. 6.0 pg/mL [min-max: 6.0–22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0–80.0] vs. 6.0 pg/mL [min-max: 6.0–22.0], p < 0.001) compared to baseline values. Conclusion In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Metronomic therapy has been gaining importance in the neoadjuvant setting of breast cancer treatment. Its clinical benefits may involve antiangiogenic machinery. Cancer cells induce angiogenesis to support tumor growth by secreting factors, such as vascular endothelial growth factor (VEGF). In breast cancer, Trastuzumab (TZM) based treatment is of key importance and is believed to reduce diameter and volume of blood vessels as well as vascular permeability. Here in we investigated serum levels of angiogenic factors VEGF and MCSF in patients receiving metronomic neoadjuvant therapy with or without TZM. We observed in HER2+ cohort stable levels of MCSF through treatment, whereas VEGF trend was of decreasing levels. In HER2- cohort we observed increasing levels of MCSF and VEGF trend. Overall, HER2+ patients had better pathological response to treatment. These findings suggest that angiogenic pathway may be involved in TZM anti-tumoral effect in the neoadjuvant setting.

O infiltrado inflamatório tem uma importante participação na reposta imune contra diversas doenças, entre elas o câncer. Diante disso, o trabalho tem como objetivo, avaliar o infiltrado inflamatório de camundongos induzidos ao tumor de mama, tratados com a vacina de Células Dendríticas, atividade física e terapia combinada (atividade física + vacina de células dendríticas). Para realização do estudo, foram utilizados 70 camundongos BALB/c, sendo 60 fêmeas e 10 de ambos os gêneros para extração de medula e confecção da vacina de Células Dendríticas, as fêmeas foram divididas em 4 grupos com n=15: grupo tumor sem tratamento(T), grupo tumor submetido a prática de atividade física(TAF), grupo tumor tratado com vacina de células dendríticas(TDC) e grupo tumor atividade física mais vacinação com células dendríticas(TTC) .O tumor dos animais foi extraído pós eutanásia para avaliação por imunofluorescência dos seguintes marcadores: linfócitos T auxiliares e citotóxicos(CD4 e CD8), MHC II( IA), moléculas co-estimulatórias (CD80, CD86 e CD152) e moléculas de adesão (CD54 e CD102). Como resultados verificamos um volume tumoral final menor estatisticamente significante dos grupos tratados quando comparados aos animais do grupo tumor sem tratamento, tendo apresentado valor de p

A unique class of diruthenium(ii,iii) metallodrugs containing non-steroidal anti-inflammatory drug (NSAID), Ru2(NSAID), have been reported to show anticancer activity in glioma models in vitro and in vivo. This work reports the encapsulation of the lead metallodrug of ibuprofen (HIbp), [Ru2(Ibp)4Cl] or RuIbp, and also of the new analogue of naproxen (HNpx), [Ru2(Npx)4Cl] or RuNpx, in novel intravenously (i.v.) injectable solid polymer-lipid nanoparticles (SPLNs). A rationally selected composition of lipids/polymers rendered nearly spherical Ru2(NSAID)-SPLNs with a mean size of 120 nm and zeta potential of about -20 mV. The Ru2(NSAID)-SPLNs are characterized by spectroscopic techniques and the composition in terms of ruthenium-drug species is analyzed by mass spectrometry. The metallodrug-loaded nanoparticles showed high drug loading (17-18%) with ∼100% drug loading efficiency, and good colloidal stability in serum at body temperature. Fluorescence-labeled SPLNs were taken up by the cancer cells in a time- and energy-dependent manner as analyzed by confocal microscopy and fluorescence spectrometry. The Ru2(NSAID)-SPLNs showed enhanced cytotoxicity (IC50 at 60-100 μmol L-1 ) in relation to the corresponding Ru2(NSAID) metallodrugs in breast (EMT6 and MDA-MB-231) and prostate (DU145) cancer cells in vitro. The cell viability of both metallodrug nanoformulations is also compared with those of the parent NSAIDs, HIbp and HNpx, and their corresponding NSAID-SPLNs. In vivo and ex vivo fluorescence imaging revealed good biodistribution and high tumor accumulation of fluorescence-labeled SPLNs following i.v. injection in an orthotopic breast tumor model. The enhanced anticancer activity of the metallodrug-loaded SPLNs in these cell lines can be associated with the advantages of the nanoformulations, assigned mainly to the stability of the colloidal nanoparticles suitable for i.v. injection and enhanced cellular uptake. The findings of this work encourage future in vivo efficacy studies to further exploit the potential of the novel Ru2(NSAID)-SPLN nanoformulations for clinical application.

This is an study to describe, through a report of experience, the dynamics of a support group for the mastectomized women. The study is descriptive and retrospective and was done through consultations to documents, minute book, pictures, recordings and works related to the group GEPAM (Group of Teaching, Research and Assistance the Mastectomized women) from 1998 to the current days. The data were organized in report form with the description of the important historical and chronological events of the group. The activities which took place systematically were: corporal exercises, solemnity-expressive activities, educational workshops, plastic arts through several courses and leisure activities. The study allowed rescuing the benefits of a support group for the well-being of mastectomized women, aiming at the recovery of the psychosocial equilibrium and the quality of life, allowing them to return to the fullness of their professional, social and emotional activities, supporting their total rehabilitation. Se objetivó describir por medio de un relato de experiencia, la dinámica de un grupo de apoyo/soporte a la mujer mastectomizada. Estudio descriptivo y retrospectivo realizado a partir de consultas recurrentes a los documentos, libro de actas, fotografías, grabaciones y trabajos existentes relacionados con el grupo GEPAM (Grupo de Enseñanza, Investigación y Asistencia a la Mujer Mastectomizada) desde 1998 hasta los dias actuales. Los datos fueron organizados en forma de relato con la descripción y presentación del rescate histórico y exposición cronológica de los acontecimientos importantes del grupo. Las actividades realizadas sistemáticamente son: ejercicios corporales, actividades auto expresivas, talleres educativos, artes plásticos por medio de cursos diversos y actividades de entretenimiento. El estudio permitió rescatar los benefícios de un grupo de apoyo/soporte para el bienestar de mujeres mastectomizadas, objetivando la recuperación del equilíbrio psicosocial y la calidad de vida, además de volver a la plenitud de sus actividades profesionales, domiciciarias y afectivas por medio de estímulos para su rehabilitación total. Objetivou descrever, através de um relato de experiência, a dinâmica de um grupo de apoio/suporte à mulher mastectomizada. Estudo descritivo e retrospectivo realizado a partir de consultas recorrentes aos documentos, livro de atas, fotos, gravações e trabalhos existentes relacionados com o grupo GEPAM (Grupo de Ensino, Pesquisa e Assistência à Mulher Mastectomizada) de 1998 até os dias atuais. Os dados foram organizados em forma de relato com a descrição e apresentação do resgate histórico e exposição cronológica dos acontecimentos importantes do grupo. As atividades realizadas sistematicamente foram: exercícios corporais, atividades auto-expressivas, oficinas educativas, artes plásticas através de cursos e atividades de lazer. O estudo permitiu resgatar os benefícios de um grupo de apoio/suporte para o bem-estar de mulheres mastectomizadas, objetivando a recuperação do equilíbrio psicossocial e a qualidade de vida, além da volta à plenitude de suas atividades profissionais, domésticas e afetivas através de estímulos para sua reabilitação total.

To analyze breast cancer mortality trends in Brazilian municipalities and assess the influence of socioeconomic and demographic factors on mortality rates.Age-adjusted mortality rates were calculated for the periods centered in 1990, 2000, and 2010 and corrected for ill-defined causes of death. After that, panel data regression models were developed for analysis of the association between the factors of interest and the mortality rate from breast cancer in Brazilian municipalities.A growing trend was detected in breast cancer mortality in Brazil. However, the models showed that the mortality could have decreased (negative trend), especially in the Southeast and South regions, if some associated factors (such as income, education, longevity, fertility rate, health spending, and infrastructure, among others) had remained constant during the study period. Breast cancer mortality was positively/significantly associated with longevity and negatively/significantly associated with public health spending. Mortality was higher in the South and Southeast, in municipalities with more than 500 000 inhabitants and in those with population below 5 000.The growth inAnalizar las tendencias de la mortalidad por cáncer de mama en municipios brasileños y evaluar la influencia de factores socioeconómicos y demográficos sobre las tasas de mortalidad.Se calcularon las tasas de mortalidad, ajustadas por grupo etario y corregidas por causas mal definidas, para los años 1990, 2000 y 2010. Posteriormente, se calcularon modelos de regresión, a partir de datos de panel, que permitieron verificar el grado de asociación entre distintos factores de interés y la tasa de mortalidad por esta enfermedad.Se verificó que había una tendencia al aumento de la mortalidad en el país. Sin embargo, los modelos indicaron que la mortalidad podría haber disminuido (tendencia negativa), principalmente en el sudeste y el sur, si algunos factores asociados (por ejemplo, nivel de ingresos, educación, longevidad, tasa de fecundidad, gastos en salud, infraestructura, entre otros) hubieran permanecido constantes durante el período en estudio. Se observó que la mortalidad por cáncer de mama presentó una asociación positiva y significativa con la longevidad, y negativa y significativa con el nivel del gasto público en salud. La mortalidad fue mayor en las zonas sur y sudeste, en los municipios con más de 500 000 habitantes y en aquellos cuya población es inferior a 5000.El aumento de los ingresos per cápita, el incremento de la esperanza de vida y la disminución de la tasa de fecundidad pueden estar asociados a tasas altas de mortalidad por cáncer de mama y a una tendencia al aumento de dicha mortalidad en los municipios brasileños.

Background: Liposomes have been employed to improve pharmacokinetics and reduce side effects of drugs. They can be functionalized with antibodies for targeted delivery. While the monoclonal antibody trastuzumab has been employed in the therapy of HER2-positive breast cancer, the resistance developed during treatment has been reported. Rapamycin could be used in combination with trastuzumab for improved therapeutic response. Objective: In this study, we aimed to develop rapamycin-loaded liposomes and immunoliposomes with trastuzumab, characterize them and evaluate their in vitro cytotoxicity. Method: Formulations were prepared by the thin film hydration method and immunoliposome was conjugated to antibody by covalent bond. Characterization involved particle size, polydispersity, zeta potential, encapsulation efficiency, functionalization efficiency, DSC and FTIR assays. Cell studies were conducted through the MTT assay. Results: SPC:Chol:DSPE-PEG formulation prepared at 1:10 drug to lipid ratio presented high encapsulation efficiency, appropriate particle size, low polydispersity, negative zeta potential and colloidal stability. Rapamycin exhibited intermolecular interactions with lipids and underwent crystallinity reduction. Rapamycin-loaded immunoliposomes were prepared with high trastuzumab functionalization efficiency and antibody stability. Cytotoxicity studies showed that the HER2-positive SK-BR-3 cell line was sensitive to trastuzumab, either as free drug or in the context of immunoliposomes, and is more sensitive to rapamycin than the triple negative MDA-MB-231 cells. For MDA-MB-231, the liposomal rapamycin was more cytotoxic than the free drug. Furthermore, the immunoliposomes showed potent cytotoxicity against SK-BR-3 cells. Finally, rapamycin and trastuzumab exhibited in vitro synergistic effect, particularly through immunoliposomes. Conclusion: The formulation developed herein has potential for in vivo evaluation.

Background Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear. Methods In this study, we assessed the cell-killing potential of PDT using methylene blue (MB-PDT) in three breast epithelial cell lines that represent non-malignant conditions and different molecular subtypes of breast tumours. Cells were incubated in the absence or presence of MB and irradiated or not at 640 nm with 4.5 J/cm2. We used a combination of imaging and biochemistry approaches to assess the involvement of classical autophagic and apoptotic pathways in mediating the cell-deletion induced by MB-PDT. The role of these pathways was investigated using specific inhibitors, activators and gene silencing. Results We observed that MB-PDT differentially induces massive cell death of tumour cells. Non-malignant cells were significantly more resistant to the therapy compared to malignant cells. Morphological and biochemical analysis of dying cells pointed to alternative mechanisms rather than classical apoptosis. MB-PDT-induced autophagy modulated cell viability depending on the cell model used. However, impairment of one of these pathways did not prevent the fatal destination of MB-PDT treated cells. Additionally, when using a physiological 3D culture model that recapitulates relevant features of normal and tumorous breast tissue morphology, we found that MB-PDT differential action in killing tumour cells was even higher than what was detected in 2D cultures. Conclusions Finally, our observations underscore the potential of MB-PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication rate of microscopic residual disease and thus minimizing the chance of both local and metastatic recurrence. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3179-7) contains supplementary material, which is available to authorized users.

An energy dispersive X-ray microdiffractometer with capillary optics has been developed for characterizing breast cancer. The employment of low divergence capillary optics helps to reduce the setup size to a few centimeters, while providing a lateral spatial resolution of 100 µm. The system angular calibration and momentum transfer resolution were assessed by a detailed study of a polycrystalline reference material. The performance of the system was tested by means of the analysis of tissue-equivalent samples previously characterized by conventional X-ray diffraction. In addition, a simplified correction model for an appropriate comparison of the diffraction spectra was developed and validated. Finally, the system was employed to evaluate normal and neoplastic human breast samples, in order to determine their X-ray scatter signatures. The initial results indicate that the use of this compact energy dispersive X-ray microdiffractometer combined with a simplified correction procedure is able to provide additional information to breast cancer diagnosis. Fil: Sosa, Carlos Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Malezan, A.. Universidade de Sao Paulo; Brasil Fil: Poletti, Martín Eduardo. Universidade de Sao Paulo; Brasil Fil: Perez, Roberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina

This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors. Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined. Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL−1 and 65.5 ± 5.5% at 0.625 μg mL−1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results. The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.

Protein degradation by the proteasome generates functional intracellular peptides. Pep5, a peptide derived from Cyclin D2, induces cell death in tumor cell lines and reduces the volume of rat C6 glioblastoma tumors in vivo. Here, we chose the human MDA-MB-231 breast cancer cells to evaluate the mechanism of cell death induced by pep5 in different phases of the cell cycle. Fluorescently labeled pep5, monitored by real time confocal microscopy, entered the MDA-MB-231 cells 3 min after application and localized to the nucleus and cytoplasm. Pep5-induced cell death was increased when the MDA-MB-231 cell population was arrested at the G1/S transition or in S phase compared to asynchronous cells. Pep5 induced permanent extracellular signal-regulated kinase (ERK1/2) phosphorylation in MDA-MB-231 cells synchronized in G1/S or S phase. Affinity chromatography followed by mass spectrometry identified CLIC1 and Plectin as the only two proteins that interacted with pep5 in both asynchronous and synchronized MDA-MB-231 cells. These interactions could explain the long-lasting ERK1/2 phosphorylation and the cytoskeleton perturbations in the MDA-MB-231 cells, in which the stress fibers' integrity is affected by pep5 treatments. These data suggest that pep5 has potential therapeutic properties for treating specific types of cancers, such as breast cancer cells. Biological significance Pep5, a natural intracellular peptide formed by the degradation of Cyclin D2 through the ubiquitin–proteasome system, induces cell death when reintroduced into MDA-MB-231 breast cancer cells, which express low levels of Cyclin D2, specifically in G1/S arrested cells or in cells that are passing through S phase. Under these conditions, pep5 is able to interact with different intracellular proteins, primarily cytoskeleton and proteasome components, which can lead to cellular apoptosis. Together, our data suggest that pep5 is an intracellular peptide with therapeutic potential for treating specific types of tumors with low expression of Cyclin D2 by inhibiting cell proliferation.

OBJETIVOS: identificar a prevalência e descrever o manejo de neutropenia ao longo do tratamento quimioterápico, entre mulheres com câncer de mama. MÉTODOS: estudo observacional, ciclos de quimioterapia. Registraram-se 116 eventos neutropênicos e 63,3% das pacientes apresentaram neutropenia em algum momento do tratamento, sendo que 46,5% desses foram de grau II. O manejo utilizado foi a suspensão temporária entre os ciclos e a média de atrasos foi de 6, prospectivo, longitudinal, onde foi realizada a avaliação das toxicidades hematológicas, a cada ciclo de quimioterapia, neoadjuvante ou adjuvante. RESULTADOS: foram incluídas 79 mulheres submetidas a 572 ciclos de quimioterapia. Registraram-se 116 eventos neutropênicos e 63,3% das pacientes apresentaram neutropenia em algum momento do tratamento, sendo que 46,5% desses foram de grau II. O manejo utilizado foi a suspensão temporária entre os ciclos e a média de atrasos foi de 6. OBJECTIVES: to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. METHODS: observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. RESULTS: 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. CONCLUSION: neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care. OBJETIVOS: identificar la prevalencia y describir el manejo de la neutropenia a lo largo del tratamiento quimioterapéutico entre mujeres con cáncer de mama. MÉTODOS: estudio observacional, ciclos de quimioterapia. Se registraron 116 eventos neutropénicos y 63,3% de las pacientes presentaron neutropenia en algún momento del tratamiento, siendo que 46,5% de estos fueron de grado II. El manejo utilizado fue la suspensión temporaria entre los ciclos y el promedio de atrasos fue de 6 días. Estudio prospectivo, longitudinal en donde fue realizada la evaluación de las toxicidades hematológicas, a cada ciclo de quimioterapia, neoadyuvante o adyuvante. RESULTADOS: fueron incluidas 79 mujeres sometidas a 572 ciclos. Sin embargo, los motivos de las suspensiones fueron la falta de cupo en la central de quimioterapia seguido por la neutropenia. CONCLUSIÓN: la neutropenia es uno de los eventos adversos más comunes y graves observados durante la quimioterapia. La enfermería debe realizar inversiones para investigar este evento adverso y para proponer estrategias de gestión para organizar el sistema público de salud, ofreciendo así una asistencia de calidad.