Sensible introduction of MR-guided radiotherapy: A warm plea for the RCT

Magnetic resonance guided radiotherapy (MRgRT) is the newest face of technology within a field long-characterized by continual technologic advance. MRgRT may offer improvement in the therapeutic index of radiation by offering novel planning types, like online adaptation, and improved image guidance, but there is a paucity of randomized data or ongoing randomized controlled trials (RCTs) to demonstrate clinical gains. Strong clinical evidence is needed to confirm the theoretical advantages of MRgRT and for the rapid dissemination of (and reimbursement for) appropriate use. Although some future evidence for MRgRT may come from large registries and non-randomized studies, RCTs should make up the core of this future data, and should be undertaken with thoughtful preconception, endpoints that incorporate patient-reported outcomes, and warm collaboration across existing MRgRT platforms. The advance and future success of MRgRT hinges on collaborative pursuit of the RCT

2-Pyridone vs 4-Pyridone organometallic Ru(II)- and Os(II)-complexes as potential anticancer agents

Seit Cisplatin und andere auf Platin basierende Medikamente in die Chemotherapie zur Behandlung von Krebs eingeführt wurden, haben Metallkomplexe und organometallische Verbindungen wachsende Wichtigkeit im Bereich der Onkologie erhalten. In letzter Zeit haben Ru(II) Verbindungen, die Derivate von 1,3,5-triaza-7-phosphaadamantan (pta), Ethylendiamin, Zuckern und Maltol als Liganden besitzen, vielversprechende tumorhemmende Eigenschaften gezeigt. Die Zytotoxizität dieser Verbindungen ist vergleichbar mit und in manchen Fällen sogar höher als die von Cisplatin. Manche dieser Verbindungen sind sogar in Zelllinien aktiv, die gegen Cisplatin resistent sind. Dies ist möglicherweise auf eine andere Wirkungsweise der Substanzen zurückzuführen. Der Inhalt dieser Diplomarbeit beinhaltet die Synthese einer Serie von neuen M(II)-Aren Halb-sandwich Komplexen (M=Ru, OS) mit 3-Hydroxy-2-pyridon Derivaten als Liganden. Die Charakterisierung dieser Verbindungen erfolgte mit Standardmethoden, wie NMR Spektroskopie, ESI-MS, Elementalanalyse, und Analyse der Festkörperstrukturen durch Röntgen Diffraktionsanalyse. In vitro Antikrebsassays in humanen Krebszelllinien werden das Potential dieser neuen Verbindungen zeigen, woraus sich wiederum neue Konzepte für zukünftige Entwicklungen ableiten lassen.Since the introduction of cisplatin and other platinum-based drugs in cancer chemotherapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. Recently, organometallic Ru(II) compounds bearing 1,3,5-triaza-7-phosphaadamantane (pta), ethylendiamine, sugar- and maltol-derived ligands have shown promising anticancer properties with cytotoxicity comparable or in some case superior to cisplatin. Some of the compounds are even active in cisplatin resistance cell lines, probably due to different mode of actions. The content of this diploma project involves the synthesis of a series of novel M(II)-arene half-sandwich complexes (M=Ru, Os) with derivatives of 3-hydroxy-2-pyridone ligands, characterization by standard methods such as NMR spectroscopy, ESI-MS, elemental analysis and determination of solid state structures by X-ray diffraction analysis. In vitro anticancer assays in human cancer cell lines will demonstrate the potential of the new compounds for further development

Coping strategies and self-efficacy in women with overweight in nutritional treatment

O sobrepeso e a obesidade apresentam causa multifatorial e seu controle e adesão ao tratamento nutricional podem estar relacionados com as estratégias de enfrentamento e a autoeficácia. Objetivo: Frente a isto, o objetivo deste estudo foi investigar a relação entre estratégias de enfrentamento e a autoeficácia em mulheres que estavam em atendimento nutricional em um serviço-escola interdisciplinar. Método: Trata-se de um estudo descritivo e correlacional, de abordagem quantitativa e corte transversal, do qual participaram 24 mulheres adultas com sobrepeso ou obesidade, as quais responderam ao Questionário de Dados Sociodemográficos e Clínicos, ao Weigth Efficacy Lifestyle Questionnarie WEL (Bellace, 2005; Clark et al., 1991) e a Escala de Modos de Enfrentamento de Problemas (Seidl, Trócolli, & Zannon, 2001). Resultados: As análises descritivas indicaram maiores médias de enfrentamento focado no problema, maior autoeficácia frente a atividades positivas e menor autoeficácia em resistir ao alimento frente a emoções negativas. Também houve associação negativa entre enfrentamento focado na emoção e emoções negativas, incomodo físico e pressão social. Discussão e Conclusão: Destaca-se a importância de promoção de estratégias de enfrentamento que propiciem maior percepção de autoeficácia, com o objetivo de promover maior adesão ao tratamento e manutenção de conquistas.El sobrepeso y la obesidad presentan causas multifactoriales y su control y/o adhesión al tratamiento nutricional pueden estar relacionados con las estrategias de afrontamiento y la autoeficacia. Objetivo: El objetivo de este estudio fue investigar la relación entre estrategias de afrontamiento y autoeficacia entre mujeres que estaban en atención nutricional en un servicio-escuela interdisciplinario. Método: Se trata de una investigación descriptiva y correlacional, de abordaje cuantitativo y corte transversal, de la cual participaron 24 mujeres adultas con sobrepeso y obesidad, que respondieron al Cuestionario en Datos Sociodemográficos y Clínicos; Weigth Efficacy Lifestyle Questionnarie (WEL - Bellace, 2005; Clark et al., 1991); y Escala Modos de Enfrentamiento de problemas (Seidl, Trócolli, & Zannon, 2001). Resultados: Los análisis descriptivos indicaron mayores medias en el afrontamiento enfocado en el problema, mayor autoeficacia frente a actividades positivas y menor autoeficacia en resistir al alimento frente a emociones negativas. También hubo asociación negativa entre focalización en la emoción y emociones negativas, incomodidad física y presión social. Discusión y Conclusión: Se destaca la importancia de la promoción de estrategias de afrontamiento que propicien mayor percepción de autoeficacia, con el objetivo de promover mayor adhesión al tratamiento y mantenimiento de ganancias.Overweight and obesity include multifactorial causes and their control and/or nutritional treatment may be related to coping strategies and self-efficacy. Objective: In this sense, the aim of this study was investigate a relationship between coping strategies and self-efficacy among women who are in nutritional care in an interdisciplinary school service. Method: The study has a cross-sectional descriptive and quantitative character, involving 24 overweight or obese adult women, who answered the Socio-demographic and Clinical Data Questionnaire, Efficacy Lifestyle Questionnaire (WEL - Bellace, 2005; Clark et al., 1991) and the Ways of Coping Checklist (Seidl, Trócolli, & Zannon, 2001). Results: Descriptive analyzes indicated higher means in problem-focused coping, higher self-efficacy in relation to positive activities and less self-efficacy in resisting food in the face of negative emotions. The use of problem-focused strategies was positively associated with all variables of self-efficacy (WEL), the emotion-focused coping was negatively related to self-efficacy in face to negative emotions, physical discomfort and social pressure. Discussion and Conclusion: The data highlight the importance of promoting coping strategies that improve self-efficacy perception, in order to promote greater adherence to treatment and maintenance of gains

Blood Transfusion Requirements for Patients With Sarcomas Undergoing Combined Radio- and Chemotherapy

Patients with bony and soft tissue sarcomas may require intensive treatment with chemotherapy and radiotherapy, which often leads to a fall in haemoglobin levels, requiring blood transfusion. There may be advantages in predicting which patients will require transfusion, partly because anaemia and hypoxia may worsen the response of tumours to chemotherapy and radiotherapy. Between 1997 and 2003, a total of 26 patients who received intensive treatment with curative intent were identified. Transfusions were given to maintain the haemoglobin at 10g/dl or above during chemotherapy, and at 12 g/dl or above during radiotherapy. Eighteen (69%) required a transfusion, the majority as a result of both the chemotherapy and RT criteria. There were 78 transfusion episodes, and 181 units of blood given. In the 18 patients who required transfusion, the average number of units was 10.1, but seven patients required more blood than this. The most significant factor influencing blood transfusion was choice of intensive chemotherapy. Intensive chemotherapy and presenting Hb less than 11.6 g/dl identified 13 out of 18 patients who needed transfusion. Adding a drop in haemoglobin of greater than 1.7 g/dl after one cycle of chemotherapy identified 16 out of 18 patients who required transfusion. The seven patients who had heavy transfusion requirements were identified by age 32 or less, intensive chemotherapy and a presenting Hb of 12 g/dl or less. Erythropoietin might be a useful alternative to transfusion in selected patient groups, especially those with heavy transfusion requirements

Polyphosphazene-Based Nanocarriers for the Release of Camptothecin and Epirubicin

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy

Plant sources of amazon rosewood oil

The aim of this study is to reevaluate the plant sources of the Amazon rosewood oil which have been named Aniba rosaeodora Ducke and Aniba duckei Kosterm. There is some disagreement on the exact botanical status of these species. Some Lauraceae specialists analyzing available material from both species concluded that there is no basis for regarding them as different. Based on our results we are confirming that the chemical composition of both species is quite different from that previously reported. So we are suggesting to bring back the previous botanical rosewood status as proposed by Adolph Ducke

Degradable, Dendritic Polyols on a Branched Polyphosphazene Backbone

Herein, we present the design, synthesis, and characterization of fully degradable, hybrid, star-branched dendritic polyols. First multiarmed polyphosphazenes were prepared as a star-branched scaffold which upon functionalization produced globular branched hydroxyl-functionalized polymers with over 1700 peripheral functional end groups. These polyols with unique branched architectures could be prepared with controlled molecular weights and relatively narrow dispersities. Furthermore, the polymers are shown to undergo hydrolytic degradation to low molecular weight degradation products, the rate of which could be controlled through postpolymerization functionalization of the phosphazene backbone

Macromolecular Bioscience / Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes

The preparation of novel macromolecular prodrugs via the conjugation of two platinum(IV) complexes to suitably functionalized poly(organo)phosphazenes is presented. The inorganic/organic polymers provide carriers with controlled dimensions due to the use of living cationic polymerization and allow the preparation of conjugates with excellent aqueous solubility but long-term hydrolytic degradability. The macromolecular Pt(IV) prodrugs are designed to undergo intracellular reduction and simultaneous release from the macromolecular carrier to present the active Pt(II) drug derivatives. In vitro investigations show a significantly enhanced intracellular uptake of Pt for the macromolecular prodrugs when compared to small molecule Pt complexes, which is also reflected in an increase in cytotoxicity. Interestingly, drug-resistant sublines also show a significantly smaller resistance against the conjugates compared to clinically established platinum drugs, indicating that an alternative uptake route of the Pt(IV) conjugates might also be able to overcome acquired resistance against Pt(II) drugs. In vivo studies of a selected conjugate show improved tumor shrinkage compared to the respective Pt(IV) complex.P 24659-N28(VLID)308360

Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy.

BACKGROUND Sarcopenia, the critical depletion of skeletal muscle mass, is an independent prognostic factor in several tumor entities for treatment-related toxicity and survival. In esophageal cancer, there have been conflicting results regarding the value of sarcopenia as prognostic factor, which may be attributed to the heterogeneous patient populations and the retrospective nature of previous studies. The aim of our study was therefore to determine the impact of sarcopenia on prospectively collected specific outcomes in a subgroup of patients treated within the phase III study SAKK 75/08 with trimodality therapy (induction chemotherapy, radiochemotherapy and surgery) for locally advanced esophageal cancer. METHODS Sarcopenia was assessed by skeletal muscle index at the 3rd lumbar vertebra (L3) in cross-sectional computed tomography scans before induction chemotherapy, before radiochemotherapy and after neoadjuvant therapy in a subgroup of 61 patients from four centers in Switzerland. Sarcopenia was determined by previously established cut-off values (Martin et al., PMID: 23530101) and correlated with prospectively collected outcomes including treatment-related toxicity, postoperative morbidity, treatment feasibility and survival. RESULTS Using the published cut-off values, the prevalence of sarcopenia increased from 29.5% before treatment to 63.9% during neoadjuvant therapy (p < 0.001). Feasibility of neoadjuvant therapy and surgery was not different in initially sarcopenic and non-sarcopenic patients. We observed in sarcopenic patients significantly increased grade ≥ 3 toxicities during chemoradiation (83.3% vs 52.4%, p = 0.04) and a non-significant trend towards increased postoperative complications (66.7% vs 42.9%, p = 0.16). No difference in survival according to sarcopenia could be observed in this small study population. CONCLUSIONS Trimodality therapy in locally advanced esophageal cancer is feasible in selected patients with sarcopenia. Neoadjuvant chemoradiation increased the percentage of sarcopenia. Sarcopenic patients are at higher risk for increased toxicity during neoadjuvant radiochemotherapy and showed a non-significant trend to more postoperative morbidity