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Os pacientes em cuidados paliativos (CP) oncológicos têm uma carga de sintomas alta e a tendência a perder a capacidade funcional. Nesta dissertação buscou-se avaliar o papel da carga de sintomas e a capacidade funcional como fatores prognósticos em pacientes em CP oncológicos. Foi realizado um estudo de coorte retrospectivo observacional realizado em uma unidade de cuidados paliativos pública. Para o cálculo da sobrevida, foi utilizado o método Kaplan-Meier e o modelo hazards proporcionais de Cox estratificado por sexo para analisar o poder preditivo da capacidade funcional e da carga de sintomas na sobrevida, avaliados pelo Karnofsky Performance Status (KPS) e da Edmonton Symptom Assessment System (ESAS) respectivamente. Foram incluídos no estudo 404 pacientes, verificou-se que o KPS 30 - 50% apresentou maior associação com o risco de morrer tanto em mulheres (HR ajustada 1,84 IC 95% 1,33-2,54) quanto em homens (HR ajustada 3,07 IC 95% 2,14 -4,41). O e o escore total da ESAS moderada/intensa também mostrou relação com a sobrevida mais curta para ambos os sexos (mulheres: HR ajustada 1,56 IC 95% 1.15-2,11; homens: HR ajustada 2,27 IC 95% 1,60 ­ 3,20). A respeito dos sintomas individuais houve diferenças entre mulheres e homens em relação à associação com o pior prognóstico para mulheres e homens, respectivamente: dor moderada/intensa (HR ajustada 1.38 IC 95 % 1.02-1.87; HR ajustada 2.15 IC 95 % 1.53- 3.02 ), fadiga moderada/intensa (HR ajustada 1.97 IC 1.43-2.72; HR ajustada 2.24 IC 95 % 1.74-3.86 ) e dispneia (HR ajustada 1.68 IC 95% 1.17- 2.43; HR ajustada 2.51 IC 95% 1.64 -3.86 ) Neste estudo pode-se ratificar o papel do KPS e da carga de sintomas como fatores prognósticos independente. Com base nestas informações, foi possível instrumentalizar os profissionais de saúde indícios a respeito do quadro clínico e prognóstico do paciente, contribuindo para a elaboração das prioridades e objetivos no planejamento do plano de cuidados em uma consulta ambulatorial.

Patients in palliative care (PC) oncology have a high burden of symptoms and a tendency to lose functional capacity. In this dissertation we sought to evaluate the role of symptom burden and functional capacity as prognostic factors in patients in PC oncology. A retrospective observational cohort study was conducted in a public palliative care unit. The Kaplan-Meier method and Cox proportional hazards model stratified by sex were used to calculate survival to analyze the predictive power of functional capacity and symptom burden on survival, as assessed by the Karnofsky Performance Status (KPS) and the Edmonton Symptom Assessment System (ESAS) respectively. 404 patients were included in the study, KPS 30 - 50% was found to have a greater association with the risk of dying in both women (adjusted HR 1.84 95% CI 1.33-2.54) and men (adjusted HR 3.07 95% CI 2.14 -4.41). The and the moderate/intense ESAS total score also showed a relationship with shorter survival for both genders (women: adjusted HR 1.56 95% CI 1.15-2.11; men: adjusted HR 2.27 95% CI 1.60 - 3.20). Regarding individual symptoms there were differences between women and men regarding the association with the worst prognosis for women and men, respectively: moderate/intense pain (adjusted HR 1.38 95% CI 1.02-1.87; adjusted HR 2.15 95% CI 1.53- 3. 02 ), moderate/intense fatigue (adjusted HR 1.97 CI 1.43-2.72; adjusted HR 2.24 CI 95 % 1.74-3.86 ) and dyspnea (adjusted HR 1.68 CI 95% 1.17- 2.43; adjusted HR 2.51 CI 95% 1.64 -3.86 ) In this study the role of KPS and symptom burden as independent prognostic factors can be ratified. Based on this information, it was possible to provide health professionals with indications regarding the clinical condition and prognosis of the patient, contributing to the elaboration of priorities and objectives in the planning of the care plan in an outpatient consultation.

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BACKGROUND: Breast cancer is a global public health problem. For some subtypes, such as Claudin-low, the prognosis is poorer and the treatment is still a challenge. Pyrazoles are an important class of heterocyclic compounds and are promising anticancer agents based on their chemical properties. The present study was aimed not only at testing pyrazoles previously prepared by our research group in two breast cancer cell lines characterized by intermediated response to conventional chemotherapy but also at analyzing the possible synergistic effect of these pyrazoles associated with doxorubicin. METHODS: Four 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles were tested for the first time in MCF-7 and MDA-MB-231 culture cells. The pyrazoles with best results in cytotoxicity were used in combination with doxorubicin and compared with this drug alone as standard. The synergic effect was analyzed using Combination Index method. In addition, cell death and apoptosis assays were carried out. RESULTS: Two pyrazoles with cytotoxic effect in MCF-7 and especially in MDA-MB-231 were identified. This activity was markedly higher in pyrazoles containing bromine and chlorine substituents. The combination of these pyrazoles with doxorubicin had a significant synergic effect in both cells tested and mainly in MDA-MB-231. These data were confirmed with apoptosis and cell death analysis. CONCLUSIONS: The synergic effect observed with combination of these pyrazoles and doxorubicin deserves special attention in Claudin-low breast cancer subtype. This should be explored in order to improve treatment results and minimize side effects.

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BACKGROUND: In vitro evaluation of toxicity and/or efficacy of nanostructured drug delivery systems involves the uses of different controls, including positive and negative controls, as well as a solution or dispersion of the drug in water. One of the most frequently solvent used to dilute poorly water soluble drugs to in vitro tests are dimethylsulfoxide (DMSO). However, its different specific surface area and different diffusion coefficients could make the comparative effects difficult. We proposed that a solvent-free dispersions having similar specific surface area could be a better control than drug in solution against cell lines. METHODS: We evaluate the effect of curcumin-loaded lipid-core nanocapsules, curcumin-loaded nanoemulsion and curcumin DMSO-water solution on viability and colony forming efficiency of human breast cancer cell line, MCF7. RESULTS: The cytotoxic effect of nanocapsules at 24-72h was similar to nanoemulsion and lower than drug solution. However, the nanocapsules had a superior anticancer activity when long periods (10days) were evaluated, which highlight the sustained drug release by nanocapsules. CONCLUSIONS: Our results showed a superior anticancer activity of curcumin-loaded lipid-core nanocapsules compared to curcumin-loaded nanoemulsion and curcumin dissolved in DMSO in long exposition time assay, wihch is not observed in short exposition time assays like MTT. When a poorly water-soluble drug is under investigation, the nanoemulsion prepared with the same compounds of the nanocapsules, except the polymer, could be a better control than DMSO-solution of drug.

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Breast cancer is a major public health burden in both developed and developing countries and there is still a need to screen new molecules with different modes of actions. The aims of this study were to evaluate the selectivity profile, apoptotic cell death and cell cycle arrest induced by 7-chloroquinoline-1,2,3-triazoyl carboxamides derivatives in hormonal-dependent and hormonal-independent breast cancer cells. Results showed significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner after treatment with 7-chloroquinoline derivatives QTCA-1, QTCA-2 and QTCA-3. QTCA-1 displayed the highest cytotoxic activity from all the tested compounds in MDA-MB-231 with IC50 values of 20.60, 20.42 and 19.91µM in 24, 48 and 72h of treatment respectively. Apoptosis induction was also significantly higher in the hormonal-independent breast cancer cells, with 80.4% of dead cells in MDA-MB-231 and only 16.8% of dead in MCF-7 cells. As a result, G0/G1 cycle arrest was observed in MCF-7 cells and no cell cycle arrest at all was observed in MDA-MB-231 cells. Molecular docking showed a high affinity of QTCA-1 to PARP-1, Scr and PI3K/mTOR targets. These results suggest a strong activity of the 7-chloroquinoline derivative QTCA-1 in independent-hormonal cells and suggest selectivity for triple negative cells.

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