Role of taxanes in advanced prostate cancer

[Abstract] Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration-resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer

Application of Robot Programming to the Teaching of Object-Oriented Computer Languages

Object-oriented programming (OOP) abstract concepts are often difficult to understand for students, since it is not easy to find the equivalence of such concepts in daily life. In this paper we will study if an interdisciplinary approach based on an introduction to robotics and robot programming helps the student in acquiring theOOPconcepts. For our experiments, we selected a sample of thirty individuals among students with an adequate knowledge of procedural programming. This sample was divided into two groups of fifteen students each: for the first one we used a standard introductory approach to C#, whereas for the second one we developed an experimental course that included a demonstration program that illustrated OOP basic concepts using the features of a specific type of commercial ball-shaped robot with sensing, wireless communication and output capabilities. After the courses, both groups were evaluated by completing a multiple-choice exam and aC#programming exercise. Our results show that the student group that attended the course including the robot demo showed a higher interest level (i.e. they felt more motivated) than those students that attended the standard introductory C# course. Furthermore, the students from the experimental group also achieved an overall better mark

Influence of elevation and slope exposure on must volatiles of Mencía cultivar from Ribeira Sacra (NW Spain)

Resumen del póster presentado al Congreso que bajo el lema "Science and horticulture for people" se celebró en Lisboa del 22 al 27 de Agosto de 2010.Peer reviewe

Evaluation of learning outcomes of humanities curricula in medical students. A meta-review of narrative and systematic reviews

Objectives: To assess the expected learning outcomes of medical humanities subjects in medical studies curricula. To connect those expected learning outcomes with the types of knowledge to be acquired in medical education. Methods: Meta-review of systematic and narrative reviews. Cochrane Library, MEDLINE (Pubmed), Embase, CINAHL, and ERIC were searched. In addition, references from all the included studies were revised, and the ISI Web of Science and DARE were searched. Results: A total of 364 articles were identified, of which six were finally included in the review. Learning outcomes describe the acquisition of knowledge and skills to improve the relationship with patients, as well as the incorporation of tools to reduce burnout and promote professionalism. Programs that focus on teaching humanities promote diagnostic observation skills, the ability to cope with uncertainty in clinical practice, and the development of empathetic behaviors. Conclusion: The results of this review show heterogeneity in the teaching of medical humanities, both in terms of content and at the formal level. Humanities learning outcomes are part of the necessary knowledge for good clinical practice. Consequently, the epistemological approach provides a valid argument for including the humanities in medical curricula

Milk production and adjustment of lactation curve in the Florida caprine breed

Milk yield and average lactation curves is studied in the Florida caprine breed. 968 valid lactations are analyzed corresponding to 317 females kept under a semi-extensive management system, fed by grazing and additional in the feeding rack, with an average feed intake of 1783 g/day of dry matter in autumn-winter, 2938 g/day in spring and 1974 g/day in summer. The milking was done in the morning, and the milk control monthly. Milk production was determined with the adaptation of Carré to the Fleischmann method. A 71.6 percent of the lactations have a duration that fluctuates between 188 and 341 days, being the average duration 301.5 ± 3 days. The lactations that initiate in winter-spring are of shorter than the ones of summer-autumn (288.4±3.6 days vs 315.5±5.2 days), the same as the first lactation in comparison to the rest (283.7±4.8 days vs 310.5±3.8 days). The type of kidding doesn"t affect significantly the duration of the lactation. The milk yield to 210, 240, 270 days and complete lactation is 475.3±4.3 kg, 538.9±5.0 kg, 598.5±6.3 kg and 611.4±7.8 kg, respectively. The females that kid in winter-spring produce more quantity of milk until 270 days of lactation, although their production is less at complete lactation due to its shorter duration. The primiparous goats produce a 19-20 percent less quantity of milk than the multiparous goats, while the ones that kid more than one kid produce a 38-40 percent more than the ones having a simple kid or abortions. The Inverse polynomial and Incomplete gamma functions present a similar adjustment (R2= 0.943; CME=0.5361 and 0.5365), although they show differences in the components of the lactation curve: the initial production is estimated in 0.82 kg/d and 2.56 kg/d; maximum production in 2.71 kg/d and 2.68 kg/d; the peak production at day 27 and 13, and the decrese in 4.58 g/d and 4.32 g/d, respectively.Se estudia la producción láctea y la curva de lactación en caprinos de raza Florida. Se analizan 968 lactaciones válidas correspondientes a 317 hembras manejadas en un régimen semiextensivo, alimentadas a pasto más suplementación en pesebre, con un nivel de ingesta medio de 1783 g/día de materia seca en otoño-invierno, 2938 g/día en primavera y 1974 g/día en verano. El ordeño se efectuaba por la mañana, y el control lechero se realizaba mensualmente. La producción de leche se determinó con la adaptación de Carré al método de Fleishmann. El 71,6 p.100 de las lactaciones tienen una duración comprendida entre 188 y 341 días, siendo la duración media de 301,5±3 días. Las lactaciones que se inician en invierno-primavera son más cortas que las de verano-otoño (288,4±3,6 días vs 315,5±5,2 días), al igual que la primera lactación frente a las restantes (283,7±4,8 días vs 310,5±3,8 días). El tipo de parto no afecta significativamente la duración de la lactación. La producción de leche tipificada a 210, 240 y 270 días y a lactación completa es de 475,3±4,3 kg, 538,9±5,0 kg, 598,5±6,3 kg y 611,4±7,8 kg, respectivamente. Las hembras que paren en invierno- primavera producen mayor cantidad de leche hasta 270 días de lactación, en tanto que su producción es menor a lactación completa por su menor duración. Las cabras primíparas producen un 19-20 p.100 menos cantidad de leche que las multíparas, mientras que las que paren más de un cabrito producen un 38-40 p.100 más que las de parto simple o abortos. Las funciones Polinomial inversa y Gamma incompleta presentan un ajuste similar (R2= 0,943; C.M.E= 0,5361 y 0,5365), aunque muestran diferencias en las componentes de la curva de lactación: la producción inicial se estima en 0,82 kg/d y 2,56 kg/d, la producción máxima en 2,71 kg/d y 2,68 kg/d, el pico de lactación al día 27 y 13, y el descenso en 4,58 g/d y 4,32 g/d, respectivamente

Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response

Purpose: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. Methods: Patients with HER-negative operable stage II–III BC ≥2 cm were enrolled. Four cycles of AC (A 60 mg/m2 and C 600 mg/m2, every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m2, every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. Results: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15–36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76–93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. Conclusion: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.Financial support for this research was provided by Roche Farma, S.A

ACE and CXCL10 as predictive biomarkers in the LEA study

Background: LEA Study (GEICAM/2006-11/GBG51), is a randomized clinical trial comparing bevacizumab in combination with endocrine therapy (ET + B) with endocrine therapy (ET) in postmenopausal women with advanced or metastatic HR-positive/HER2-negative breast cancer (BC) with indication of hormonotherapy as first-line treatment. Patients with secondary hypertension had better progression-free survival (PFS) and overall survival (OS). We have evaluated the role of two hypertension-related biomarkers, Angiotensin-Converting Enzyme (ACE) and Small-Inducible Cytokine B10 (CXCL10) as prognostic and/or predictive biomarkers of benefit to bevacizumab in the first line metastatic disease. Methods: From 380 patients, 266 were included in 33 Spanish sites. Median age was 64 years, 63.5% had measurable disease, 97.4% were metastatic at randomization, 51.5% had visceral disease and 52.6% received previous chemotherapy. PFS was 14.3 months (range 0.8-61.1), OS was 34 months (range 0.8-71.6) and 93 patients had Objective Response (OR). We analyzed 124 plasma samples collected before treatment (52 from ET and 72 from ET + B arms). Circulating levels of ACE and CXCL10 were determined by ELISA. ACE levels of 115ng/ml and 135ng/ml were pre-defined as cutoff values. CXCL10 was explored as a quantitative variable. Results: PFS was 15.1 months (range 1.4-61.1), OS was 31.1 months (range 2.8-61.1) and 40.3% had OR. OR was significantly different between treatment arms (p < 0.001) but not PFS or OS. Median ACE concentration was 130.9ng/ml (range 35.3-315.4). Low ACE (<135ng/ml) had better PFS in the whole population (p = 0.048) and in the ET + B arm (p = 0.041). ACE cutoff of 115 ng/ml was not able to identify any subgroup with better prognosis. Median CXCL10 concentration was 230.3pg/ml (range 15.1-4129.6). A higher expression of CXCL10 was significantly associated with worse OS in the whole population (p < 0.0001) and each treatment arm (p = 0.002 and p = 0.001 in ET and ET + B, respectively). No association with OR were identified neither for ACE nor for CXCL10. Conclusions: ACE levels could be considered a prognostic and a bevacizumab predictive biomarker of PFS. CXCL10 could be prognostic of OS. Confirmatory studies are warranted

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study

[Purpose]: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L.[Materials and methods]: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L–T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed.[Results]: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1–43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%).[Conclusion]: The combination of L–T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L–T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.This work was supported by GlaxoSmithKline plc (GSK) through a contract with Medica Scientia Innovation Research (MedSIR), an academic research organization focused on independent clinical research development