New drugs and new strategies for women with breast cancer

info:eu-repo/semantics/published

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Highlights from the 13th St Gallen International Breast Cancer Conference 2013. Access to innovation for patients with breast cancer: how to speed it up?

The recognition that early breast cancer is a spectrum of diseases each requiring a specific systemic therapy guided the 13th St Gallen International Breast Cancer Consensus Conference [1]. The meeting assembled 3600 participants from nearly 90 countries worldwide. Educational content has been centred on the primary and multidisciplinary treatment approach of early breast cancer. The meeting culminated on the final day, with the St Gallen Breast Cancer Treatment Consensus, established by 40-50 of the world's most experienced opinion leaders in the field of breast cancer treatment. The major issue that arose during the consensus conference was the increasing gap between what is theoretically feasible in patient risk stratification, in treatment, and in daily practice management. We need to find new paths to access innovations to clinical research and daily practice. To ensure that continued innovation meets the needs of patients, the therapeutic alliance between patients and academic-led research should to be extended to include relevant pharmaceutical companies and drug regulators with a unique effort to bring innovation into clinical practice. We need to bring together major players from the world of breast cancer research to map out a coordinated strategy on an international scale, to address the disease fragmentation, to share financial resources, and to integrate scientific data. The final goal will be to improve access to an affordable, best standard of care for all patients in each country.

FOLK ELEMENTS IN TWENTIETH-CENTURY HUNGARIAN MUSIC

At the beginning of the twentieth century, composers Béla Bartók and Zoltán Kodály collected thousands of folksongs from the rural regions of Hungary. In an effort to preserve a part of their culture that they feared would be lost, they not only transcribed and catalogued these folksongs, but also incorporated the folk traditions they encountered into their own compositional style. This dissertation deals with violin music written by Bartók, Kodály and their Hungarian contemporaries that have in common the use of rhythms, modes, melodies, figurations and playing techniques sourced in folk traditions. The use of the Hungarian folk idiom in classical music was not exclusive to the twentieth century. From the late eighteenth century until the first decades of the twentieth century, composers utilized aspects of a popular eighteenth-century form of Hungarian folk music called verbunkos. What makes the use of folk music unique in the twentieth century is that, thanks to the work of Bartók and Kodály, composers found inspiration in the more authentic “peasant music.” Unlike the popular, urban verbunkos music, peasant music was the product of the more secluded village-music tradition, largely untouched by the influences of city life. In addition to stimulating a new focus on peasant music, Bartók and Kodály fully assimilated the folk idiom into their compositional toolkits, creating a new style of folk-inspired art music that influenced a generation of Hungarian composers. The new style included characteristic elements of both peasant music and the verbunkos tradition, such as ancient modes and scales, accompanimental and melodic rhythmic patterns, ornamentation, and phrase structures sourced in folk song. To demonstrate the implementation of the folk idiom by twentieth-century Hungarian composers, three recital programs were given at the University of Maryland that included works by Béla Bartók, Sándor Veress, Leo Weiner, Zoltán Kodály, Ernő Dohnányi, Zoltán Székely and György Kurtág. The works can be divided into two main categories: settings or transcriptions of folk material (e.g. Bartók’s Hungarian Folksongs) and compositions using classical forms that include the Hungarian folk idiom (e.g. Bartók’s Contrasts). Recital collaborators include Li-Tan Hsu, Evelyn Elsing, Elizabeth Brown, Shelby Sender and Samantha Angelo.

International guidelines for management of metastatic breast cancer: Can metastatic breast cancer be cured?

A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology-Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment. © 2010. Published by Oxford University Press.

Liver-directed lentiviral gene therapy in a dog model of hemophilia B

We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor IX transgene in hepatocytes was well tolerated and provided a stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we showed that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be potentially useful for the treatment of hemophilia.

Doxifluridine and leucovorin: an oral treatment combination in advanced colorectal cancer

Purpose: This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether the pharmacokinetics of dFUR and fluorouracil (FU) are affected by demographic and/or biologic parameters. Materials and Methods: One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dFUR 1,200 mg/m2 on days 1 to 5, with the cycle being repeated every 10 days. Results: Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median response duration was 4 months (range, 2 to 13) and the median survival time, 14 months. Among 46 pretreated patients, there were three CRs and three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12) and the median survival time, 12 months. No toxic deaths were observed. The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients). Conclusion: This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also detected in the patients previously treated with FU, which suggests incomplete cross- resistance between the two drugs. The pharmacokinetic results suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those measured after classical FU therapy. Under the experimental conditions used in this study, the interpatient variability of pharmacokinetic parameters remains largely unexplained by the tested variables.

Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma

Purpose: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFNα2a) could be as effective as intermediate doses. Patients and Methods: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m 2 intravenously (IV) days 1 and 21; DTIC plus rIFNα2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFNα2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFNα2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. Results: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFNα2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFNα2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. Conclusion: In this study, rIFNα2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFNα2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

A dose-finding study of lanreotide (a somatostatin analog) in patients with colorectal carcinoma

BACKGROUND. Laboratory data suggest that insulin-like growth factor-1 (IGE-1) may stimulate the growth of different human tumors. At least in acromegalic patients, somatostatin (SMS) analogs, such as lanreotide, suppress the serum levels of growth hormone (GH) and IGE-1. METHODS. To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecutive groups of 3 patients each were subcutaneous treated with lanreotide at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treated with the same dose before the next dose escalation. Serum samples were obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreotide assessment. RESULTS. Twenty-four patients were enrolled and all were evaluable. Except for the 3 and 6 mg doses, for which the observation of a Grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel habits, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increase in the incidence, intensity, or duration of side effects was observed with dose escalation. Serum IGF-1 levels were as follows: Day 13: 63%, 60%, and 67% of the baseline values for the low (12 mg), intermediate (3-4 mg), and high (5- 6 mg) dose groups, respectively; Day 30: 63%, 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectively. Serum lanreotide levels declined during treatment in all of the dose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg group). No antitumor activity or tumor marker reduction was observed. CONCLUSIONS. No increase in toxicity was observed when subcutaneous lanreotide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a 'rebound' in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not ensure constant serum drug concentrations over time.

Aspectos culturales que determinan los límites territoriales de la producción tradicional de papa andina y su importancia para la problemática fitosanitaria : zona de integración fronteriza Argentina - Bolivia

Las fronteras presentan una dinámica particular en cuanto al comercio, la producción y el intercambio de productos de diversas características, como así también el ámbito cultural y social. La frontera entre Argentina y Bolivia con 743 km de longitud y con tres pasos internacionales importantes (La Quiaca-Villazón, Salvador Mazza - San José de Pocitos, Aguas Blancas-Bermejo) y con muchos pasos naturales de hecho, representan un continuum cultural y productivo. Este territorio y sus límites son diferentes a los límites políticos establecidos por los Estados. Las relaciones familiares y las costumbres juegan un rol clave en la rutina diaria donde el intercambio de productos de todo tipo no reconoce dichas fronteras políticas. En este tránsito constante no solo se intercambian productos sino que existe un importante potencial de traslado de plagas de importancia económica y cuarentenaria. Asimismo, los circuitos de comercialización formal e informal a ambos lados de la frontera representan potenciales vías de dispersión de plagas que es necesario identificar. El objetivo general de este trabajo es: determinar los límites territoriales de la producción de papa andina delimitando la ecorregión de producción e identificar las relaciones culturales a partir de las cuales se establecen los intercambios. Describir las formas de comercialización de papa andina que permitan identificar las variedades que se intercambian, época del año, volumen y principales vías de comercialización ya que estas representan las principales vías de ingreso de plagas. Elaborar un mapa con información secundaria identificando los puntos o vías por las cuales se moviliza la papa (ferias, fiestas, puntos de ingreso legales y de hecho) y elaborar un formulario de entrevista que permita recolectar información primaria de la dinámica local de fronteras vinculada a la producción de tubérculos andinos que complemente y profundice la información disponible y permitan corroborar, acotar e incorporar potenciales vías de ingreso de plagas. En una etapa posterior habría que realizar el trabajo de campo con entrevistas y observación de estas formas de circulación a fin de establecer el alcance territorial y cultural de dichos intercambios. Finalmente, y con el insumo de este trabajo y las entrevistas a campo diseñar un plan de trabajo conjunto entre los organismos fitosanitarios de Argentina (SENASA) y Bolivia (SENASAG) que apunte a un programa de sanidad en el cultivo de papa andina y contemple la realidad y necesidad de los productores de la ecorregión identificada

Falta de respuesta a la inoculación de Poroto Alubia con cepas de Rhizobium phaseoli en el Noroeste Argentino

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Selección de cepas de Rhizobium japonicum para la inoculación de soja en el Noroeste Argentino

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Cultivos de Rhizobium phaseoli en sistema sumergido

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¿Es el agua un espejismo? algunas reflexiones desde la perspectiva de la educación matemática crítica

Teniendo en cuenta que la educación tradicional es vista como un modelo pedagógico que entre otras: i) se enfoca en desarrollar en los estudiantes conocimientos algorítmicos, ii) hace un énfasis en la ejercitación de procedimientos, iii) no tiene en cuenta el desarrollo social del individuo dentro de una comunidad y tampoco se enfoca en el proceso que tiene un estudiante al desarrollar una actividad con determinado objeto matemático; hoy en día se propende por buscar perspectivas que le permitan a los estudiantes encontrarle sentido a las actividades que el profesor lleva al aula. A la luz de lo anterior, en Colombia han surgido diversas tendencias que han buscado la renovación pedagógica, didáctica y conceptual en la educación escolar, enmarcadas –la mayoría de estas propuestas– dentro de la idea de que los estudiantes se relacionen directamente con el conocimiento, mientras que el profesor toma una postura de orientador del proceso de aprendizaje del estudiante. Teniendo en cuenta lo anterior, muchos profesores han buscado cambiar sus prácticas tradicionales de enseñanza, un ejemplo de ello lo encontramos en el colectivo de profesores de la Institución Educativa Distrital Colegio Paulo Freire de la localidad de Usme (Bogotá, Colombia); donde los profesores –en concordancia con las ideas del pedagogo Paulo Freire– comparten, como parte de su proyecto educativo, el hecho de ver a la enseñanza como un proceso que debe generar en los estudiantes una comprensión crítica de la realidad social, política y económica en la que él está inmerso.