The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.

The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment.

Unexpected pancreatic mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN)-reflection on a case report.

The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome.

Clinical Communication Within Hospital Pharmacy Practice: Exploring Pharmaceutical Oncological Consultations.

This exploratory study aimed to identify communication trends typical of pharmacists' clinical communication in the context of hospital consultations. A cross-sectional design was used to investigate the pharmacist-patient exchange, applying the Roter Interaction Analysis System (RIAS). Communication variables and RIAS composites were assessed, including therapeutic information complexity, estimated through the ad-hoc score CTICS (Cancer Therapy Information Complexity Score). The study comprised 13 consultations of cancer patients with one female pharmacist, of which 6 included a patient family member, lasting on average 22.74 minutes and presenting repeated or overlapping consultation phases. The pharmacist's talk dominance reached 53.49%, slightly higher in dyadic consultations (U = 6.0, p = .032), and with an overall predominance of closed-ended questioning (W = 81.0, p = .013). Patients' questioning on biomedical issues was higher in dyadic consultations. The level of the pharmacist's rapport-building with the relative was higher when the patient's age was ≥80 years. Several strong correlations, both positive and negative, were found between composites, including between patient positive rapport-building and relative lifestyle/psychosocial information giving (Rho = -0.971, p = .001). Pharmaceutical consultations seem to be lengthier than other hospital practitioners' interviews, indicating a lack of  clear organization and flow, thus challenging their efficiency regarding therapy management. Still, several positive communication features were found regarding the pharmaceutical care of older cancer patients. Further studies are needed, involving larger samples and other hospital consultation settings.

Micronuclei from misaligned chromosomes that satisfy the spindle assembly checkpoint in cancer cells.

Chromosome alignment to the spindle equator is a hallmark of mitosis thought to promote chromosome segregation fidelity in metazoans. Yet chromosome alignment is only indirectly supervised by the spindle assembly checkpoint (SAC) as a byproduct of chromosome bi-orientation, and the consequences of defective chromosome alignment remain unclear. Here, we investigated how human cells respond to chromosome alignment defects of distinct molecular nature by following the fate of live HeLa cells after RNAi-mediated depletion of 125 proteins previously implicated in chromosome alignment. We confirmed chromosome alignment defects upon depletion of 108/125 proteins. Surprisingly, in all confirmed cases, depleted cells frequently entered anaphase after a delay with misaligned chromosomes. Using depletion of prototype proteins resulting in defective chromosome alignment, we show that misaligned chromosomes often satisfy the SAC and directly missegregate without lagging behind in anaphase. In-depth analysis of specific molecular perturbations that prevent proper kinetochore-microtubule attachments revealed that misaligned chromosomes that missegregate frequently result in micronuclei. Higher-resolution live-cell imaging indicated that, contrary to most anaphase lagging chromosomes that correct and reintegrate the main nuclei, misaligned chromosomes are a strong predictor of micronuclei formation in a cancer cell model of chromosomal instability, but not in non-transformed near-diploid cells. We provide evidence supporting that intrinsic differences in kinetochore-microtubule attachment stability on misaligned chromosomes account for this distinct outcome. Thus, misaligned chromosomes that satisfy the SAC may represent a previously overlooked mechanism driving chromosomal/genomic instability during cancer cell division, and we unveil genetic conditions predisposing for these events.

Thoracic Outlet Syndrome after Minimally Invasive Repair of Pectus Excavatum in a 15-Year-Old Boy: A Case Report.

Nuss procedure has become the treatment of choice in pectus excavatum mainly because of the excellent functional and cosmetic results. Despite the good results, several complications have been reported. The aim of this study is to describe a case of thoracic outlet syndrome (TOS) after Nuss procedure and review the management of such rare complication. A 15-year-old boy otherwise healthy was submitted to Nuss procedure, with no perioperative complications. Two-weeks later, the patient complained of right-hand paresthesia, progressive weakness of the right arm and coldness. After imaging and electromyography, TOS diagnosis was established. Removal of the bar was proposed but refused by the patient. Conservative management with rehabilitation exercising and nerve nourishing was initiated. At 7 months, the patient recovered arm and hand function. Abrupt structural changes of thoracic cavity with marked elevation of the upper chest induce nerve and vascular compression arousing a TOS and should be acknowledged as one potential complication of Nuss procedure. Conservative management can be an alternative treatment to bar removal, showing good results on functional recovery in early stages of compression.

Minimally invasive treatment of pilonidal sinus disease in a paediatric population: comparison of two techniques.

BACKGROUND: Pilonidal disease (PD) is a common and debilitating inflammatory condition with significant impact on quality of life. Minimally invasive techniques (MIT) have shown promising results comparing to traditional excision. Herein we present a comparison of two MIT techniques -sinusectomy (SE) and pit-picking plus laser ablation (PPL). METHODS: All cases of paediatric PD treated by PPL and SE at our center between August 2018 and August 2020 were retrospectively reviewed. RESULTS: One-hundred and six patients were included, with a median age of 16 years (IQR 15-16). PPL was the procedure of choice in 36 patients (34%) and the remaining underwent SE (66%). Median healing time was significantly lower in SE group (20 days), comparing to PPL (30 days) (p = 0.002). Early healing failure occurred more frequently in the PPL group (p = 0.003). Recurrence rate was similar between groups - PPL 17% versus SE 16% (p = 0.89). Overall complication rate was 9% and was significantly higher in PPL (p = 0.03). CONCLUSIONS: MIT techniques are promising solutions in PD treatment. Although similarly easy and fast to perform, SE technique showed better healing profile and lower complication rate but no significant difference on recurrence rates was observed.

CORONARY ARTERIES - WHEN CALCIFICATION POPS UP.

An 84-year-old woman, with background history of atrial fibrillation, cerebral vascular disease, ischemic heart failure by coronary disease with several stent implantation, presented in the emergency room with syncope. The chest radiograph evidenced the coronary trajectory by their calcification.

Crime e policiamento durante a pandemia de COVID-19 no Rio de Janeiro, Brasil / Crime and police activity during the COVID-19 pandemic in Rio de Janeiro, Brazil

Resumo Este trabalho analisa os indicadores de Segurança Pública no Rio de Janeiro durante os primeiros meses da pandemia de COVID-19. Os resultados demonstram uma queda ampla nos índices de atividade criminal a partir de abril, em especial nos delitos contra o patrimônio, cujo nível de ocorrência foi particularmente incomum para o padrão anterior dos dados. Esse comportamento parece estar associado à retração no fluxo de pessoas em áreas do estado. Para os bairros em que se tem informação de deslocamento, é possível demonstrar que as reduções mais expressivas de roubos de rua ocorreram onde houve maior diminuição na circulação de pessoas. As atividades policiais registraram uma redução semelhante aos indicadores criminais, em particular as apreensões de drogas e as prisões. A exceção a esse cenário foi representada pelo número de mortes por intervenção de agentes do Estado: em abril, esse indicador observou um aumento superior à média dos últimos quatro anos; a partir de maio, entretanto, assumiu um movimento de queda, que se transformou em um desempenho extraordinariamente baixo em junho. A oscilação no uso da força pelas polícias reforça a dissonância entre a letalidade policial e as dinâmicas criminais no Rio de Janeiro, configurando-se como um contexto relevante para a compreensão da violência policial fluminense.

Abstract This paper analyzes crime reports and police activity in Rio de Janeiro during the first months of the COVID-19 pandemic. The results indicate there was an overall drop in crime rates starting in April, especially in property crimes, which plummet to extremely unusual levels when compared with previous patterns. This pattern is most likely associated with an unprecedented decline in public mobility in some areas of the state. We show that the most significant reductions in street robberies occurred in neighborhoods where there was a greater decline in presence on the streets. Measures of police activity, in particular drug seizures and different types of arrests, displayed a reduction comparable with the drop in criminal indicators. In contrast, the number of police killings followed a unique pattern: in April, immediately after the adoption of social distance measures, this indicator increased above the average from the previous four years; as of May, however, it assumed a downward trend, which turned into extraordinarily low levels in June. The extreme variation in the use of force by the police during the pandemic reinforces the documented dissonance between police lethality and criminal dynamics in Rio de Janeiro, shedding light on the mechanisms that regulate police violence in the state.

Clear Cell Carcinoma of the Thymus: An Improbable Enemy.

INTRODUCTION: Thymic clear cell carcinoma is the most uncommon subtype of thymic carcinoma, with 20 cases reported worldwide. CASE DESCRIPTION: We present the case of a 61-year-old female with dyspnoea and chest pain for 2 days. Computed tomography (CT) angiography showed pulmonary thromboembolism and the existence of mediastinal and bilateral hilar lymphadenopathy, the largest infracarinal with an inferior axis of 25 mm, and also, micronodules on the left pulmonary parenchyma. The patient was admitted for aetiological assessment and underwent anticoagulant therapy. After a month, she had an ischaemic stroke, the sequelae of which proved to be fatal. The autopsy showed a mass in the superior-anterior mediastinum, with dimensions of 11×8×6 cm, corresponding to a thymus signet ring cell primary carcinoma. The immunohistochemistry study revealed that this mass was positive for AE1/AE3, CK5/6 and CK7. CONCLUSION: The clinical, morphological and immunophenotypic diversity of this tumour makes its diagnosis a difficult multidisciplinary challenge, which requires a high level of clinical knowledge and accurate imaging and histological investigation. LEARNING POINTS: Thymic clear cell carcinoma is a very rare entity with an aggressive and nonspecific clinical behaviour.There are no defined diagnostic criteria, although diagnosis could be established with histologic/cytology analysis.There are no clear guidelines for treatment, which can include highly invasive surgery and chemotherapy or radiation therapy.

Letalidade policial e criminalidade violenta / Letalidad policial y criminalidad violenta / Police killings and violent crime

Resumo Entre os operadores da Segurança Pública no Rio de Janeiro, há uma visão recorrente de que o padrão de patrulhamento baseado em incursões, frequentemente associado a episódios de letalidade policial, é necessário e efetivo para redução de crimes. Para investigar essa questão, este artigo apresenta exercícios econométricos que avaliam em que medida um maior número de mortes por intervenção de agentes do Estado está associado a variações subsequentes nos indicadores criminais. A análise cobre o período de 2003 a 2019 e indica que não há uma associação entre o aumento da letalidade policial e a redução dos índices de criminalidade no nível local. Ao contrário, em alguns casos, encontra-se uma correlação significativa e positiva, ou seja, mais mortes estão correlacionadas com maior atividade criminal, embora a magnitude dos efeitos seja bem reduzida. Observa-se, também, que mortes por intervenção de agentes do Estado estão associadas a maiores resultados operacionais, mensurados por apreensão de drogas e de armas. Os resultados são condizentes com um padrão de patrulhamento cuja prioridade é o combate ao varejo do tráfico de drogas.

Resumen Una visión persistente entre los operadores de seguridad pública en Rio de Janeiro es que el patrón de patrullaje basado en redadas policiales, frecuentemente asociado con episodios de letalidad policial, es necesario y efectivo para reducir la criminalidad. Para investigar ese tema, este artículo presenta ejercicios econométricos que evalúan la medida en que un mayor número de muertes por intervenciones de agentes del Estado se asocia con variaciones posteriores en los indicadores criminales. El análisis, que abarca el período comprendido entre 2003 y 2019, indica que no existe una asociación entre el aumento de la letalidad policial y la reducción de las tasas de delincuencia a nivel local. Mientras que, en algunos casos, se encuentra una correlación significativa y positiva, es decir, se correlacionan más muertes con una mayor actividad criminal, aunque la magnitud de los efectos sea bastante reducida. Por otro lado, se observa que las muertes por intervención de agentes del Estado están asociadas con mayores resultados operativos, medidos por la incautación de drogas y de armas. Los resultados son consistentes con un patrón de patrullaje que prioriza la lucha contra el tráfico minorista de drogas.

Abstract A common view among policy makers in Public Security in Rio de Janeiro is that the patrolling pattern based on police raids, regularly associated with the use of lethal force, is both necessary and effective to reduce crime. In order to examine this issue, this article presents econometric exercises to assess in what extent a greater number of police killings is correlated with subsequent variations in criminal indicators. The analysis covers the period from 2003 to 2019 and indicates no correlation between increases in the use of lethal force by the police and reductions in crime rates at the local level. On the contrary, in some cases, a significant and positive correlation is observed, which means more police killings are correlated with greater criminal activity, although the magnitudes of the effects are rather reduced. On the other hand, we show that police killings are associated with greater operational results, as measured by drugs and weapons seizure. The results are consistent with a patrolling pattern that prioritizes the combat of retail markets for illicit drugs.

[Differences between Patients Undergoing Laparoscopic Cholecystectomy with Discharge at the End of the Day Versus Overnight Stay: A Retrospective Study]. / Diferenças entre os Doentes Submetidos a Colecistectomia Laparoscópica com Alta ao Final do Dia Versus Pernoita: Um Estudo Retrospectivo.

INTRODUCTION: Although laparoscopic cholecystectomy is an increasingly performed technique in the outpatient setting, it is not done in some Units due to lack of overnight stay. The objectives of this study are to identify the differences between patients with discharge at the end of the day versus overnight stay and the factors predicting overnight stay. MATERIAL AND METHODS: A retrospective analysis of the pre, peri and postoperative data of patients operated between January/2014 and December/2017 was performed, and a statistical analysis of the variables. RESULTS: A total of 311 patients were included, 33.4% of whom stayed overnight. Of these, 81.7% were operated after 2pm. As predictors factors of overnight stay, the age (p = 0.001) was identified in the morning group, with a greater possibility of overnight stay (15.3%) from 61.50 years (Younden index = 0.396) and the surgery start time (p < 0.0001) in the afternoon group, with a greater possibility of overnight stay (77.1%) from 4:30 pm (Younden index = 0.492). DISCUSSION: Most patients stayed overnight due to the time at which recovery was completed, since no cause was identified (84.7%). If our unit would not have an overnight stay we would have an overall hospitalization rate of 8.4%, which corresponds to patients with an identified cause for overnight stay, and to admitted patients. CONCLUSION: Ambulatory cholecystectomy can be performed in units that cannot cater for an overnight stay, provided that surgeries are performed during the morning period, patients are carefully selected and there is the possibility of admission.

Introdução: Apesar da colecistectomia laparoscópica ser uma técnica cada vez mais realizada em regime de ambulatório, não é praticada em algumas unidades por ausência de pernoita. São objetivos deste estudo identificar as diferenças entre os doentes com alta ao final do dia versus pernoita e os fatores preditores de pernoita.Material e Métodos: Realizámos uma análise retrospetiva dos dados pré, peri e pós-operatório dos doentes operados entre janeiro de 2014 e dezembro de 2017, tendo-se procedido à análise estatística das variáveis.Resultados: Foram incluídos 311 doentes, sendo que apenas 33,4% pernoitaram. Destes, 81,7% foram operados depois das 14 horas. Como fatores preditores de pernoita foram identificados a idade (p = 0,001) no grupo da manhã, havendo a partir dos 61,50 anos (Younden index = 0,396) uma maior possibilidade de pernoita (15,3%) e a hora de início da cirurgia (p < 0,0001) no grupo da tarde, sendo que os doentes operados após as 16 horas e trinta minutos (Younden index = 0,492) têm maior possibilidade de pernoita (77,1%).Discussão: Grande parte dos doentes pernoitou devido à hora em que completou o recobro, uma vez que não se identificou uma causa para tal (84,7%). Caso a nossa Unidade não dispusesse de pernoita teríamos uma taxa global de internamento de 8,4%, que corresponde aos doentes com causa identificada para a pernoita e os doentes internados.Conclusão: A colecistectomia em ambulatório pode ser realizada em unidades que não disponham de pernoita, desde que as cirurgias decorram no período da manhã, os doentes sejam selecionados de forma criteriosa e exista a possibilidade de internamento.

Impact of Navigated Task-specific fMRI on Direct Cortical Stimulation.

BACKGROUND AND STUDY AIMS: Cortical mapping (CM) with direct cortical stimulation (DCS) in awake craniotomy is used to preserve cognitive functions such as language. Nevertheless, patient collaboration during this procedure is influenced by previous neurological symptoms and growing discomfort with DCS duration. Our study aimed to evaluate the impact of navigated task-specific functional magnetic resonance imaging (nfMRI) on the practical aspects of DCS. MATERIAL AND METHODS: We recruited glioma patients scheduled for awake craniotomy for prior fMRI-based CM, acquired during motor and language tasks (i.e., verb generation, semantic and syntactic decision tasks). Language data was combined to generate a probabilistic map indicating brain regions activated with more than one paradigm. Presurgical neurophysiological language tests (i.e., verb generation, picture naming, and semantic tasks) were also performed. We considered for subsequent study only the patients with a minimum rate of correct responses of 50% in all tests. These patients were then randomized to perform intraoperative language CM either using the multimodal approach (mCM), using nfMRI and DCS combined, or electrical CM (eCM), with DCS alone. DCS was done while the patient performed picture naming and nonverbal semantic decision tasks. Methodological features such as DCS duration, number of stimuli, total delivered stimulus duration per task, and frequency of seizures were analyzed and compared between groups. The correspondence between positive responses obtained with DCS and nfMRI was also evaluated. RESULTS: Twenty-one surgeries were included, thirteen of which using mCM (i.e., test group). Patients with lower presurgical neuropsychological performance (correct response rate between 50 and 80% in language tests) showed a decreased DCS duration in comparison with the control group. None of the compared methodological features showed differences between groups. Correspondence between DCS and nfMRI was 100/84% in the identification of the precentral gyrus for motor function/opercular frontal inferior gyrus for language function, respectively. CONCLUSION: Navigated fMRI data did not influence DCS in practice. Presurgical language disturbances limited the applicability of DCS mapping in awake surgery.

Adult Atypical Teratoid/Rhabdoid Tumor in the Pineal Region: Case Report and Literature Review.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant embryonal central nervous system tumor with a poor prognosis. Its occurrence in the pineal region is extremely rare, with only 6 cases in adults reported so far. CASE DESCRIPTION: We report on a puerperal woman with an AT/RT in the pineal region. Total tumor resection was performed. Definitive diagnosis was confirmed by the loss of nuclear INI1/SMARCB1 staining. The patient underwent radiotherapy and chemotherapy with no evidence of recurrence at 31 months after surgery. CONCLUSIONS: This case highlights the importance of immunohistochemistry in the diagnosis of the disease and the importance of an aggressive treatment.

Participação em programas de intervenção comunitária e qualidade de vida: resultados de um estudo multicêntrico em Portugal / Participation in community intervention programmes and quality of life: findings from a multicenter study in Portugal

Objetivo: Analisar a qualidade de vida (QV) em indivíduos que participam de programas de intervenção comunitária (PIC) orientados para uma vida ativa e saudável. Método: Estudo transversal multicêntrico com 304 participantes, com 55 anos ou mais de idade, a viver na comunidade em três localidades portuguesas. Metade desses indivíduos (n=152) envolvida em PIC (grupo de intervenção). Esse grupo foi emparelhado segundo sexo e grupo etário com número equivalente de participantes (n=152) que não frequenta PIC (grupo de comparação). As atividades dos PIC foram agrupadas segundo a sua natureza: sociorrecreativas, educativas/aprendizagem ao longo da vida (ALV) e atividade física. Recolheu-se informação usando Questionário de Participação Social, WHOQOL-Bref e Escala de Satisfação com a Vida. Resultados: Os participantes dos PIC tinham média de idade de 71,4 (±5,4) anos, eram predominantemente mulheres (75,0%), casados (65,4%), com escolaridade inferior a cinco anos (71,7%) e rendimento familiar mensal até 750 euros (47,4%). O GI apresentou melhor QV no domínio físico do que o GC ( p<0,03). A atividade física foi a modalidade mais frequentada nos PIC (n=119; 78,3%) em comparação com atividades educativas/ALV (n=46; 30,3%) e sociorrecreativas (n=25; 16,4%). Os praticantes de atividade física em PIC apresentaram melhor QV nos domínios psicológico, relações sociais e ambiente do que os não praticantes ( p<0,05). Conclusão: A participação em PIC está associada à QV pelo que, em linha com o quadro do envelhecimento ativo, se recomenda implementar PIC no âmbito das políticas públicas, promovendo sistematicamente a QV da população. AU

Objective: The present study aimed to analyze quality of life (QoL) in participants of community intervention programs (CIP) focused on healthy aging. Method: A multicenter cross-sectional study was carried out with 304 community-dwelling participants, aged 55 years old or more and living in three locations in Portugal. Half of these individuals (n=152) were involved in a CIP (intervention group). The intervention group was paired according to sex and age group with an equivalent number of participants (n=152) that did not take part in a CIP (comparison group). Activities implemented in the CIP were grouped according to their nature: socio-recreational, educational/lifelong learning and physical activity. Data collection involved a Social Participation Questionnaire, the WHOQOL-Bref and the Satisfaction With Life Scale. Results: The CIP participants (n=152) had a mean age of 71.4 years (±5.4), were predominantly women (75.0%), married (65.4%), with fewer than five years of education (71.7%) and a monthly family income of up to 750 euros (47.4%). The intervention group had a significantly higher QoL in the physical domain than the comparison group ( p<0.03). Physical activity was the most frequently attended session in the CIP (n=119, 78.3%), in comparison with educational/ lifelong learning (n=46, 30.3%) and socio-recreational (n=25, 16.4%) activities. People practicing physical activity in the CIP had a significantly higher QoL in the psychological, social relationships and environment domains ( p<0.05). Conclusion: Participation in the CIP was associated with QoL. Therefore, in line with the active aging framework, CIPs must be a part of public policy measures aimed at the QoL of the population.AU

SRC inhibition prevents P-cadherin mediated signaling and function in basal-like breast cancer cells.

BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior. METHODS: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival. RESULTS: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function. CONCLUSIONS: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.

Toward an Integrated Zebrafish Health Management Program Supporting Cancer and Neuroscience Research.

Zebrafish is already one of the most used model organisms in biomedical sciences and other research fields. It is therefore becoming increasingly important to assure that zebrafish maintained in laboratory aquaculture conditions are raised and housed under rigorous standards that promote health and welfare to guarantee the required quality and reproducibility of research data. Specifying the programs each facility is adopting would be the first step to achieve this by allowing other facilities to compare, improve, and discuss their protocols and fish performance. We provide in this article a detailed description of an integrated facility health management program, with protocols and readouts, fully designed and aimed at maximizing fish health, welfare, and performance for research.

Cancer stemness in Wnt-driven mammary tumorigenesis.

Wnt signaling plays a central role in mammary stem cell (MaSC) homeostasis and in breast cancer. In particular, epigenetic alterations at different members of the Wnt pathway have been identified among triple-negative, basal-like breast cancers. Previously, we developed a mouse model for metaplastic breast adenocarcinoma, a subtype of triple-negative breast cancer, by targeting a hypomorphic mutations in the endogenous Apc gene (Apc (1572T/+)). Here, by employing the CD24 and CD29 cell surface antigens, we have identified a subpopulation of mammary cancer stem cells (MaCSCs) from Apc (1572T/+) capable of self-renewal and differentiation both in vivo and in vitro. Moreover, immunohistochemical analysis of micro- and macrolung metastases and preliminary intravenous transplantation assays suggest that the MaCSCs underlie metastasis at distant organ sites. Expression profiling of the normal and tumor cell subpopulations encompassing MaSCs and CSCs revealed that the normal stem cell compartment is more similar to tumor cells than to their own differentiated progenies. Accordingly, Wnt signaling appears to be active in both the normal and cancer stem cell compartments, although at different levels. By comparing normal with cancer mouse mammary compartments, we identified a MaCSC gene signature able to predict outcome in breast cancer in man. Overall, our data indicate that constitutive Wnt signaling activation affects self-renewal and differentiation of MaSCs leading to metaplasia and basal-like adenocarcinomas.

Cardiac venous arterialization in acute myocardial infarction: how great is the benefit?

OBJECTIVES: Cardiac venous arterialization has been proposed as an alternative approach for myocardial revascularization in ischaemic heart disease. It is based on using the cardiac venous system to transport arterial blood from a systemic artery to infarcted myocardial areas. Our goal was to evaluate its benefit in reducing acute myocardial infarct size and its effects on cardiac performance. METHODS: In a group of pigs, the left internal mammary artery was anastomosed to the left anterior descending vein; this vein was ligated proximally. The left anterior descending coronary artery was also occluded. Over 5 days, several diagnostic procedures were used to characterize and measure the extent of myocardial infarct, namely ECG, echocardiography, cardiac biomarkers and histopathology. Data were compared with those from a control group of pigs, which were submitted to ligation of only the left anterior descending coronary artery. RESULTS: In the experimental group, echocardiography revealed that the ejection fraction and thickness of the ventricular walls remained unchanged 4 days after surgery, in contrast to the major alterations in the control group. In fact, the ejection fraction in the control group decreased by 21% (P < 0.001), with a reduction of 31% (P < 0.004) in the thickness of the interventricular septum at end systole and enlargement of the left ventricular lumen by 28% (P < 0.001). In the experimental group, the sum for ST segment shift was 50% lower (P = 0.038) and the total ventricular histological lesion size was 50% smaller (P < 0.001). Within this lesion, the area of necrotic tissue was 70% smaller (P < 0.001). Cardiac biomarkers were not different between the two groups (P > 0.2). CONCLUSIONS: This study reveals that selective cardiac venous arterialization can nourish the myocardium and is able to reduce infarct size by more than 50%, while protecting cardiac performance. We believe, therefore, that further investigation should be carried out into this technique in order for it to be considered as an option in coronary surgery.