Triple-negative breast cancer (TNBC), an aggressive, metastatic and recurrent breast cancer (BC) subtype, currently suffers from a lack of adequately described spontaneously metastatic preclinical models that faithfully reproduce the clinical scenario. We describe two preclinical spontaneously metastatic TNBC orthotopic murine models for the development of advanced therapeutics: an immunodeficient human MDA-MB-231-Luc model and an immunocompetent mouse 4T1 model. Furthermore, we provide a broad range of multifactorial analysis for both models that could provide relevant information for the development of new therapies and diagnostic tools. Our comparisons uncovered differential growth rates, stromal arrangements and metabolic profiles in primary tumors, and the presence of cancer-associated adipocyte infiltration in the MDA-MB-231-Luc model. Histopathological studies highlighted the more rapid metastatic spread to the lungs in the 4T1 model following a lymphatic route, while we observed both homogeneous (MDA-MB-231-Luc) and heterogeneous (4T1) metastatic spread to axillary lymph nodes. We encountered unique metabolomic signatures in each model, including crucial amino acids and cell membrane components. Hematological analysis demonstrated severe leukemoid and lymphoid reactions in the 4T1 model with the partial reestablishment of immune responses in the immunocompromised MDA-MB-231-Luc model. Additionally, we discovered β-immunoglobulinemia and increased basal levels of G-CSF correlating with a metastatic switch, with G-CSF also promoting extramedullary hematopoiesis (both models) and causing hepatosplenomegaly (4T1 model). Overall, we believe that the characterization of these preclinical models will foster the development of advanced therapeutic strategies for TNBC treatment, especially for the treatment of patients presenting both, primary tumors and metastatic spread.

Characterization of triple-negative breast cancer preclinical models provides functional evidence of metastatic progression.

Forum 2020 · 35:199–204 https://doi.org/10.1007/s12312-020-00794-z Online publiziert: 28. April 2020 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020 Bernd Alt-Epping · Claudia Bausewein · Raymond Voltz · Steffen T. Simon · Anne Pralong · Alfred Simon für S3-Leitliniengruppe Palliativmedizin 1 Klinik für Palliativmedizin, Universitätsmedizin Göttingen, Göttingen, Deutschland 2 Klinik und Poliklinik für Palliativmedizin, Klinikum der Universität München, München, Deutschland 3 Zentrum für Palliativmedizin, Uniklinikum Köln, Köln, Deutschland

Aktualisierte S3-Leitlinie „Palliativmedizin für Patienten mit einer nicht heilbaren Krebserkrankung“

Resumo Objetivo: Avaliar a qualidade de vida de pessoas com feridas cronicas. Metodos: Estudo transversal realizado com 176 pessoas com feridas cronicas em acompanhamento ambulatorial e domiciliar em um servico publico de saude. Foram utilizados: formulario para a caracterizacao sociodemografica, clinica e terapeutica e o questionario Cardiff Wound Impact Schedule para a mensuracao da qualidade de vida. As analises foram descritivas e inferenciais empregando-se os testes t de Student, ANOVA, Mann Whitney e Kruskal-Wallis. Resultados: Dentre as pessoas acompanhadas em domicilio, predominaram lesoes de origem vasculogenicas, com tempo de existencia superior a 12 meses e area de ate 25 cm2. No ambiente ambulatorial, prevaleceram feridas vasculogenicas e traumaticas, com tempo maximo de seis meses e extensao de ate 25 cm2. Os fatores clinicos associados a qualidade de vida foram: tempo de duracao da lesao, etiologia da lesao, grande extensao, aspecto do exsudato, presenca de odor e de dor. O dominio de QV “bem-estar” apresentou maior impacto negativo decorrente da presenca de lesao. Conclusao: Os fatores clinicos influenciaram diretamente os dominios de QV, sendo necessaria a utilizacao de estrategias diferenciadas com o intuito de reduzir o impacto na QV por se tratarem de aspectos que poderiam ser atenuados ou evitados mediante a avaliacao da lesao e a escolha do tratamento adequado.

/pdf/qualidade-de-vida-de-pessoas-com-feridas-cronicas-nqwbsyv3r2.pdf

Qualidade de vida de pessoas com feridas crônicas

Psychosocial risk factors for coronary heart disease: Pathophysiologic mechanisms.

Introduction: Malignant fungating wounds (MFWs), non-healing wounds caused by aggressive proliferation of malignant tumors, afflict 5%-14.5% of patients with advanced cancer. We conducted an integrative review to evaluate the level of evidence of peer-reviewed literature published from 2000 to 2019 on symptoms of MFWs, and the impact of the symptoms on functional performance among patients with advanced cancer. Methods: Four electronic databases were searched and 1506 articles were retrieved. A total of 1056 abstracts were screened for relevance and a full review of the 26 articles was performed. A total of 12 articles met inclusion criteria. An established quality assessment tool was used to rate the quality of the included studies. Results: The overall quality of the included 12 studies was adequate. This integrative review of the literature provided strong evidence that patients with MFWs suffered multiple symptoms, including pain, odor, exudate, bleeding, pruritus, perceived wound status, perceived bulk effect and lymphedema. Quantitative research was not able to capture the occurrence and characteristics of all the identified symptoms. There was a lack of quantitative research on the impact of MFWs and symptoms on patients' functional performance. Yet, qualitative studies provided vivid description of how the symptoms negatively affected patients' functional performance. Future research should develop a clinical tool that enables the comprehensive assessment of symptoms of MFWs. Well-designed quantitative research is needed to delineate the impact of symptoms of MFWs on patients' functional performance to ensure quality palliative care.

Symptoms of Malignant Fungating Wounds and Functional Performance among Patients with Advanced Cancer: An Integrative Review from 2000 to 2019.

Palliative Wound Care for Malignant Fungating Wounds: Holistic Considerations at End-of-Life

The identification of myocardial viability in patients with coronary artery disease and left ventricular dysfunction (LVD) has important clinical and prognostic implications. Two terms commonly used to define clinical conditions of potentially reversible contractile dysfunction are stunned myocardium and hibernating myocardium. Stunned myocardium refers to transient depression of contractile function secondary to an acute ischemic insult. Hibernating myocardium is a form of contractile dysfunction of living myocytes in the setting of chronic ischemia or chronically reduced flow reserve. Numerous observational studies have shown improved clinical outcomes after revascularization of patients with LVD and evidence of myocardial viability, although patients with nonviable myocardium have not been shown to have the same benefits. The use of noninvasive techniques to determine myocardial viability provides important information to guide clinicians in deciding which patients with LVD are likely to receive benefit from a revascularization procedure. Positron emission tomography, single-photon emission computed tomography, dobutamine echocardiography, and cardiac magnetic resonance imaging each have advantages and limitations.

Mark Ramos

Papers

Palliative Wound Care for Malignant Fungating Wounds: Holistic Considerations at End-of-Life

Assessment of myocardial viability: review of the clinical significance.

Is There a Statin Effect on Arrhythmia and Survival in Patients With Nonischemic Cardiomyopathy