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A critical shortage of skilled healthcare workers is a primary cause of disparate global cancer outcomes. We report participant evaluation of a multidisciplinary preceptorship program. In collaboration with the city of Kumasi, Ghana, Mayo Clinic and the City Cancer Challenge hosted a preceptorship program for comprehensive multidisciplinary breast and cervix cancer training. A total of 14 healthcare workers from Kumasi received two weeks of training at Mayo Clinic in November and December 2021. Each participant and preceptor were requested to complete an anonymous post-participation survey. Of the 14 trainee participants, 10 (71%) completed the survey. All respondents found the program "valuable and applicable to their clinical practice." Ninety percent reported they were able to "review effective and critical elements in the development and expansion of the multidisciplinary team" and able to "solve practical clinical cases as a team". General themes of satisfaction included: (1) organization and administration, (2) clinical observations and demonstrations, (3) guidelines development, and (4) recognizing the central importance of cultivating a team-based approach. Of the 40 preceptors, 16 (40%) completed the survey. All respondents reported they felt the training would meaningfully "influence patient care in Ghana", that participation "added value or joy to their clinical practice," and all wished to "participate in future preceptorship programs". After a focused two-week program, trainees reported high satisfaction, usefulness from observing specialized cancer care, and value in closely observing a multidisciplinary oncology team. Preceptors reported the experience added joy and perspective to their clinical practice and wished to participate in future programs.
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Oncología Médica , Preceptoría , Humanos , Ghana , Oncología Médica/educación , Femenino , Personal de Salud/educación , Grupo de Atención al Paciente , Encuestas y Cuestionarios , Masculino , Evaluación de Programas y Proyectos de Salud , Adulto , Neoplasias de la MamaRESUMEN
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells. In sequence, the purpose of this study was to evaluate the in vivo antitumor efficacy of this combined therapy as well as with these drugs individually, using a human NSCLC xenograft model. Some indicators of sub chronic toxicity that could be affected by treatments were also assessed. The results obtained in vivo with the combined treatment (1mg/kg+PTX 10mg/kg) showed the most effective reduction of the relative tumor volume and the highest inhibition of tumor growth and proliferation, when compared with those of the single treatments. Furthermore, scintigraphic images, obtained before and after the treatments, showed that the most effective protocol able to reduce the residual viable tumor mass was the combined treatment. All treatment regimens were well tolerated without significant changes in body weight and no histological and functional damage to liver and kidney tissues. These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/farmacología , Triterpenos/farmacología , Células A549 , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Paclitaxel/toxicidad , Radiofármacos/administración & dosificación , Factores de Tiempo , Pruebas de Toxicidad Subcrónica , Triterpenos/toxicidad , Carga Tumoral/efectos de los fármacos , Imagen de Cuerpo Entero , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential.
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Apoptosis/efectos de los fármacos , Cucurbitacinas/farmacología , Cucurbitacinas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Caspasas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cucurbitacinas/química , Ciclina B1/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Humanos , Neoplasias Pulmonares/enzimología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.
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Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Triterpenos/farmacología , Actinas/metabolismo , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Camptotecina/análogos & derivados , Camptotecina/farmacología , Camptotecina/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Irinotecán , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Survivin , Triterpenos/química , Triterpenos/uso terapéutico , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.
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Algoritmos , Benchmarking , Humanos , Estudios Prospectivos , Método de Montecarlo , Órganos en RiesgoRESUMEN
PURPOSE: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. METHODS: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. RESULTS: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. CONCLUSIONS: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.
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Neoplasias , Radioterapia de Intensidad Modulada , Humanos , Fraccionamiento de la Dosis de Radiación , Neoplasias/radioterapia , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodosRESUMEN
Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.
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Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Triterpenos/química , Triterpenos/toxicidad , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cucurbitaceae/química , Frutas/química , Humanos , Luffa/química , Raíces de Plantas/química , Triterpenos/síntesis químicaRESUMEN
In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, carbamate and sulfamate. The structural elucidation of the new derivatives was based on detailed NMR and MS spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was evaluated against A459 and RD tumor cell lines with CC50 values ranging from 4.93 to 41.53 µM. These results suggest that the structural modifications performed on both compounds could be considered a good strategy to obtain more active derivatives.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Compuestos de Espiro/química , Línea Celular , Humanos , Laurencia/química , Laurencia/metabolismo , Estructura MolecularRESUMEN
Diabetes mellitus (DM) is a metabolic syndrome that can be considered a growing health problem in the world. High blood glucose levels are one of the most notable clinical signs. Currently, new therapeutic alternatives have been tackled from clinicians' and scientists' points of view. Natural products are considered a promising source, due to the huge diversity of metabolites with pharmaceutical applications. Therefore, this review aimed to uncover the latest advances in this field as a potential alternative to the current therapeutic strategies for the treatment of DM. This purpose is achieved after a patent review, using the Espacenet database of the European Patent Office (EPO) (2016-2022). Final screening allowed us to investigate 19 patents, their components, and several technology strategies in DM. Plants, seaweeds, fungi, and minerals were used as raw materials in the patents. Additionally, metabolites such as tannins, organic acids, polyphenols, terpenes, and flavonoids were found to be related to the potential activity in DM. Moreover, the cellular transportation of active ingredients and solid forms with special drug delivery profiles is also considered a pharmaceutical technology strategy that can improve their safety and efficacy. From this perspective, natural products can be a promissory source to obtain new drugs for DM therapy.
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Chemical investigation of the roots of Wilbrandia ebracteata Cogn. (Cucurbitaceae) led to the isolation of two new (1- 2) and four known (3- 6) cucurbitacins. Their structures were elucidated by NMR and MS and compared with related compounds. The in vitro cytotoxicity of isolated compounds was evaluated against RD, KB, HCT-8, and A549 cell lines showing strong activity.
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Cucurbitaceae/química , Cucurbitacinas/farmacología , Extractos Vegetales/química , Brasil , Línea Celular Tumoral , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Cucurbitacinas/química , Cucurbitacinas/aislamiento & purificación , Humanos , Medicina Tradicional , Estructura Molecular , Raíces de Plantas/química , Plantas Medicinales , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The head and neck (H&N) region is frequently replanned during intensity-modulated proton therapy (IMPT), but replanning disrupts clinical workflow and presents additional burden on patients. The purpose of this study was to establish a standard treatment planning approach to minimize H&N replanning by identifying a correlation between dosimetric variables and replan frequency. In a retrospective study of 27 bilateral oropharyngeal cancer patients treated with IMPT at a single institution, cases were evaluated using Fisher's exact tests and logistic regression for a significant relationship between replan frequency and the following variables: beam number, clinical target volume (CTV) coverage, presence of dental fillings, and robustness. The reason and timing for replan initiation, and patient immobilization was also recorded to identify trends. Results suggested that beam number, CTV coverage, presence of dental fillings, and the initial robustness curve on the high-dose CTV did not individually contribute to replanning frequency. Setup variation in the soft tissue of the neck was the most prominent reason for replanning. A lack of correlation between the number of replans and the studied dosimetric variables highlights the necessity of verification CT and adaptive replanning in IMPT of H&N cancer. Departments may therefore benefit from a methodical replan workflow. One development showing potential to enhance clinical replan processes is machine learning-based automatic adaptive replanning.
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Neoplasias Orofaríngeas , Terapia de Protones , Radioterapia de Intensidad Modulada , Humanos , Neoplasias Orofaríngeas/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios RetrospectivosRESUMEN
Decreasing radiotoxicity to the heart, lungs, and contralateral breast has proven to lower the risk of secondary malignancy and improve overall outcomes when treating chest wall (CW) and regional lymph nodes in postmastectomy breast cancer patients. In this retrospective study, 11 postmastectomy patients were selected and planned with a novel hybrid treatment method and a traditional volumetric arc therapy (VMAT) approach for comparison. This hybrid technique was able to optimize tangential beams to minimize heart dose and the VMAT contribution to improve dose conformity around the planning target volume (PTV). Overall, this hybrid technique produced more homogenous target dose coverage and demonstrated a decrease of integral dose to organs at risk (OAR), while the VMAT technique demonstrated a higher affinity for maintaining dose conformity. Further observation of dose distributions also revealed that the hybrid plans were more effective in sparing low-dose spread to healthy tissue in both right- and left-sided cases. This observation was made evident by the reduction in heart V5 and Dmean, decreases in all parameters regarding the contralateral lung, as well as all values other than the V20 of the ipsilateral lung. This unique hybrid planning technique could present an alternative to standard intensity-modulated radiation therapy (IMRT) planning when treating postmastectomy CW and regional lymph nodes, as it has shown the capacity to decrease cardiac, lung, and contralateral breast toxicity while maintaining quality PTV coverage.
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Neoplasias de la Mama/radioterapia , Ganglios Linfáticos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Pared Torácica , Adulto , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
In phenylketonuria (PKU), variable dietary advice provided by health professionals and social media leads to uncertainty for patients/caregivers reliant on accurate, evidence based dietary information. Over four years, 112 consensus statements concerning the allocation of foods in a low phenylalanine diet for PKU were developed by the British Inherited Metabolic Disease Dietitians Group (BIMDG-DG) from 34 PKU treatment centres, utilising 10 rounds of Delphi consultation to gain a majority (≥75%) decision. A mean of 29 UK dietitians (range: 18-40) and 18 treatment centres (range: 13-23) contributed in each round. Statements encompassed all foods/food groups divided into four categories based on defined protein/phenylalanine content: (1) foods high in protein/phenylalanine (best avoided); (2) foods allowed without restriction including fruit/vegetables containing phenylalanine ≤75 mg/100 g and most foods containing protein ≤0.5 g/100 g; (3) foods that should be calculated/weighed as an exchange food if they contain protein exchange ingredients (categorized into foods with a protein content of: >0.1 g/100 g (milk/plant milks only), >0.5 g/100 g (bread/pasta/cereal/flours), >1 g/100 g (cook-in/table-top sauces/dressings), >1.5 g/100 g (soya sauces)); and (4) fruit/vegetables containing phenylalanine >75 mg/100 g allocated as part of the protein/phenylalanine exchange system. These statements have been endorsed and translated into practical dietary management advice by the medical advisory dietitians for the National Society for PKU (NSPKU).
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Dieta con Restricción de Proteínas/normas , Proteínas en la Dieta/análisis , Dietética/normas , Fenilalanina/análisis , Fenilcetonurias/dietoterapia , Consenso , Técnica Delphi , Dieta con Restricción de Proteínas/métodos , Etiquetado de Alimentos/normas , Humanos , Reino UnidoRESUMEN
The physical characterization of active pharmaceutical substances is crucial to the successful development of the final drug product. The different solid forms and variations in the degree of crystallinity can lead to significantly different physical and chemical properties, including color, morphology, stability, dissolution and bioavailability. In the case of omeprazole sodium (OMS), its chemical structures contain a specific number of water molecules (hydrate). The behavior of pharmaceutical hydrates has become the object of increasing attention over the past decade, primarily due to the potential impact of hydrates on the development process and dosage form performance. The present study was designed to characterize and evaluate the crystallinity of omeprazole sodium, dehydrated omeprazole sodium (DOMS) and omeprazole free base (OM) using a variety of techniques including thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC)), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Furthermore, an NMR spectroscopy study was also carried out to clarify the conformation and crystal structure.
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Fenómenos Químicos , Inhibidores Enzimáticos/química , Calor , Omeprazol/química , Análisis Espectral , Rastreo Diferencial de Calorimetría , Cristalización , Estabilidad de Medicamentos , Enlace de Hidrógeno , Microscopía Electrónica de Rastreo , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Polvos , Espectroscopía Infrarroja por Transformada de Fourier , Estereoisomerismo , Termogravimetría , Volumetría , Agua/química , Difracción de Rayos XRESUMEN
Cryptococcus species are responsible for important systemic mycosis and are estimated to cause millions of new cases annually. The available therapy is limited due to the high toxicity and the increasing rates of yeast resistance to antifungal drugs. Popularly known as "sucará," Xylosma prockia (Turcz.) Turcz. (Salicaceae) is a native plant from Brazil with little information on its pharmacological potential. In this work, we evaluated in vitro anticryptococcal effects of the leaf ethanolic extract of X. prockia and its fractions against Cryptococcus gattii and Cryptococcus neoformans. We also evaluated phenotypic alterations caused by ethyl acetate fraction (EAF) (chosen according to its biological results). The liquid chromatography-mass spectrometry (LC-MS) analysis of EAF demonstrated the presence of phenolic metabolites that belong to three structurally related groups as majority compounds: caffeoylquinic acid, coumaroyl-glucoside, and caffeoyl-glucoside/deoxyhexosyl-caffeoyl glucoside derivatives. The minimum inhibitory concentration (MIC) values against C. gattii and C. neoformans ranged from 8 to 64 mg/L and from 0.5 to 8 mg/L, for ethanolic extract and EAF, respectively. The EAF triggered an oxidative burst and promoted lipid peroxidation. EAF also induced a reduction of ergosterol content in the pathogen cell membrane. These effects were not associated with alterations in the cell surface charge or in the thermodynamic fingerprint of the molecular interaction between EAF and the yeasts evaluated. Cytotoxic experiments with peripheral blood mononuclear cells (PBMCs) demonstrated that EAF was more selective for yeasts than was PBMCs. The results may provide evidence that X. prockia leaf extract might indeed be a potential source of antifungal agents.
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BACKGROUND: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients. METHODOLOGY: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added. RESULTS: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU. CONCLUSIONS: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.
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Etiquetado de Alimentos/métodos , Fenilalanina/metabolismo , Fenilcetonurias/dietoterapia , Consenso , Técnica Delphi , Humanos , Fenilalanina/química , Encuestas y CuestionariosRESUMEN
UNLABELLED: The aim of this study was to investigate the anti-inflammatory effects and the mechanism of action of the aqueous extracts obtained from rhizomes, leaves and inflorescences of Solidago chilensis in the mouse model of pleurisy. The extracts were prepared by infusion and were lyophilized. RESULTS: The aqueous extracts of rhizomes, leaves or inflorescences inhibited leukocytes, neutrophils and exudation (P<0.05) in the inflammation induced by carrageenan. The rhizomes aqueous extract, butanolic and aqueous residual fractions inhibited leukocytes, neutrophils, myeloperoxidase, adenosine-deaminase, and tumor necrosis factor alpha levels in the inflammation induced by carrageenan (P<0.05). The rhizome aqueous extract and butanolic fraction also inhibited exudation, nitric oxide, and interleukin-1 beta levels (P<0.05). The rhizomes aqueous extract and its two derived fractions reduced leukocytes and mononuclears in the pleurisy induced by bradykinin, histamine, or substance P (P<0.05) and neutrophils in the pleurisy induced by histamine or substance P (P<0.05). Only aqueous residual fraction inhibited neutrophils induced by bradykinin (P<0.05). CONCLUSION: Solidago chilensis aqueous extracts from leaves, inflorescences and rhizomes demonstrated an important anti-inflammatory effect, inhibiting cells in the inflammation caused by carrageenan. In addition, the rhizomes aqueous extract and its derived fractions also decreased pro-inflammatory mediators release into the site of the inflammatory process. The rhizomes aqueous extract and the butanolic fraction showed more evident anti-inflammatory actions.
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Antiinflamatorios/farmacología , Extractos Vegetales/farmacología , Pleuresia/prevención & control , Solidago/química , Adenosina Desaminasa/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Bradiquinina/administración & dosificación , Bradiquinina/toxicidad , Butanoles/química , Carragenina/administración & dosificación , Carragenina/toxicidad , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Flores/química , Histamina/administración & dosificación , Histamina/toxicidad , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/prevención & control , Interleucina-1beta/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Ratones , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Peroxidasa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Pleuresia/inducido químicamente , Pleuresia/metabolismo , Rizoma/química , Sustancia P/administración & dosificación , Sustancia P/toxicidad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This paper describes an evaluability assessment of CDC's Rape Prevention and Education (RPE) Program conducted to establish a baseline description and understanding of the current activities and goals of the program, revisit and update program performance measures, and identify opportunities for CDC to provide training and technical assistance to states. Data were collected using (1) a web-based survey of all state and territory health departments, other government agencies involved in the administration of the program, and sexual assault coalitions, (2) in-depth interviews with the same respondents during site visits to a sample of 14 states, and (3) focus groups in 5 of these states with local providers. This paper highlights the findings and summarizes recommendations to improve the program. It concludes with examples of steps CDC is taking to implement the recommendations.
Asunto(s)
Educación en Salud/normas , Prevención Primaria/normas , Violación/prevención & control , Regionalización/organización & administración , Salud de la Mujer , Centers for Disease Control and Prevention, U.S. , Femenino , Educación en Salud/economía , Humanos , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Prevención Primaria/economía , Evaluación de Programas y Proyectos de Salud , Estados UnidosRESUMEN
Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.
Asunto(s)
Antineoplásicos/farmacología , Triterpenos/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Caspasa 3/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Transgénicos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Triterpenos/administración & dosificación , Triterpenos/síntesis química , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasas raf/genética , Quinasas raf/metabolismoRESUMEN
This article describes structure-activity relationship (SAR/QSAR) studies on the cytotoxic activity in a human lung adenocarcinoma cell line (A549) of 43 cucurbitacin derivatives. Modeling was performed using the methods partial least squares with discriminant analysis (PLS-DA) and PLS. For both studies, the variables were selected using the ordered predictor selection (OPS) algorithm. The SAR study demonstrated that the presence or absence of cytotoxic activity of the cucurbitacins could be described using information derived from their chemical structures. The QSAR study displayed suitable internal and external predictivity, and the selected descriptors indicated that the observed activity might be related to electrophilic attack on cellular structures or genetic material. This study provides improves the understanding of the cytotoxic activity of cucurbitacins and could be used to propose new cytotoxic agents.