Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07).

PURPOSE: The EGF receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target. The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in patients with prostate cancer. EXPERIMENTAL DESIGN: Patients with mCRPC progressing during or within 90 days after at least 12 weeks of docetaxel were included in this phase II trial. Treatment consisted of docetaxel (75 mg/m(2) every 3 weeks or 35 mg/m(2) on days 1, 8, 15 every 4 weeks) in combination with cetuximab (400 mg/m(2) on day 1 and then 250 mg/m(2) weekly). The primary endpoint was progression-free survival (PFS) at 12 weeks defined as the absence of prostate-specific antigen (PSA), radiographic, or clinical progression. Evaluation of known biomarkers of response and resistance to cetuximab (EGFR, PTEN, amphiregulin, epiregulin) was conducted. RESULTS: Thirty-eight patients were enrolled at 15 Swiss centers. Median age was 68 years and median PSA was 212 ng/mL. PFS at 12 weeks was 34% [95% confidence interval (CI), 19%-52%], PFS at 24 weeks was 20%, and median overall survival (OS) was 13.3 months (95% CI, 7.3-15.4). Seven patients (20%) had a confirmed ≥ 50% and 11 patients (31%) a confirmed ≥ 30% PSA decline. About 47% of enrolled patients experienced grade 3 and 8% grade 4 toxicities. A significantly improved PFS was found in patients with overexpression of EGFR and persistent activity of PTEN. CONCLUSIONS: EGFR inhibition with cetuximab might improve the outcome of patients with mCRPC. A potential correlation between EGFR overexpression, persistent expression of PTEN, and EGFR inhibition should be investigated further.

Recomendaciones higiénico sanitarias en piscinas de uso colectivo. 2ª ed

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Nuestra Salud / Medio ambiente y Salud / …)

Prospective analysis of KRAS, BRAF, and PIK3CA mutations and EGFR copy number in patients (pts) with locally advanced rectal cancer: A translational substudy of a clinical trial (SAKK 41/07) evaluating the effect of neoadjuvant chemoradiation (CRT) with or without panitumumab

Background: Prognostic and predictive markers are of great importance for future study designs and essential for the interpretation of clinical trials incorporating an EGFR-inhibitor. The current study prospectively assessed and validated KRAS, BRAF and PIK3CA mutations in rectal cancer patients screened for the trial SAKK41/07 of concomitant preoperative radio-chemotherapy with or without panitumumab.Methods: Macrodissection was performed on pretreatment formalin fixed paraffin embedded biopsy tissue sections to arrive at a minimum of 50% of tumor cells. DNA was extracted with the Maxwell 16 FFPE Tissue LEV DNA purification kit. After PCR amplification, mutations were identified by pyrosequencing. We prospectively analysed pretreatment biopsy material from 149 rectal cancer pts biopsies for KRAS (exon 2 codon 12 [2-12] and 13 [2-13], exon 3 codon 59 [3-59]) and 61 [3-61], exon 4 codon 117 [4-117] and 146 [4-146]). Sixty-eight pts (KRASwt exon 2, 3 only) were further analysed for BRAF (exon 15 codon 600) and PIK3CA (exon 9 codon 542, 545 and 546, exon 20 codon 1043 [20-1043] and 1047 [20-1047]) mutations, and EGFR copy number by qPCR. For the calculation of the EGFR copy number, we used KRAS copy number as internal reference standard. The calculation was done on the basis of the two standard curves relative quantification method.Results: In 149 screened pts with rectal cancer, the prevalence of KRAS mutations was 36%. Among the 68 pts enrolled in SAKK 41/07 based on initially presumed KRASwt status (exon 2/codons 12+13), 18 pts (26%) had a total of 23 mutations in the RAS/PIK3CA-pathways upon validation analysis. Twelve pts had a KRAS mutation, 7 pts had a PIK3CA mutation, 3 pts had a NRAS mutation, 1 patient a BRAF mutation. Surprisingly, five of these pts had double- mutations, including 4 pts with KRAS plus PIK3CA mutations, and 1 pt with NRAS plus PIK3CA mutations. The median normalized EGFR copy number was 1. Neither mutations of KRAS, BRAF, and PIK3CA, nor EGFR copy number were statistically associated with the primary study endpoint pCR (pathological complete regression).Conclusions: The prevalence of KRAS mutations in rectal and in colon cancer appears to be similar. BRAF mutations are rare; PIK3CA mutations are more common (10%). EGFR copy number is not increased in rectal cancer. A considerable number or KRAS exon 2 wt tumors harbored KRAS exon 3+4 mutations. Further study is needed to determine if KRAS testing should include exons 2-4.

Caracterização Sócio-cultural e a Prática de Educação Física da População Discente : “Caso Escola Secundária Manuel Lopes – Ano Lectivo 2006/07”

Este trabalho está orientado para abordar a aplicação de um conjunto de instrumentos e da sua consequente análise, perceber as inter-relações sociais, culturais e desportivo que se estabelecem entre os alunos, sobretudo ao nível do ambiente escolar. Aproveitando uma necessidade da escola constatada após conversas com elementos da direcção, apercebendo das vantagens de caracterizar os alunos, no que respeita à envolvência sócio-cultural, bem como condições de trabalho em casa e na aula de educação física e acompanhamento escolar por parte dos encarregados de educação. A partir deste conhecimento, procurar definir um conjunto de estratégias de actuação futuras, as quais deverão estar o mais possível adaptadas às necessidades e carências educativas destes alunos. Tais estratégias deverão potencializar dinâmica de grupo e desenvolver o sucesso educativo. Este estudo visa obter informação no que respeita à envolvência familiar, hábitos de estudo e forma de ocupação dos tempos livres e prática de educação física, por parte dos alunos, o que poderá apoiar a direcção da escola, bem como Subdirecção Administrativa e os restantes órgãos, no sentido de fornecer novos dados nesta matéria para optimizar os meios existentes e criar novos mecanismos que conduzam à melhoria da qualidade de ensino oferecida pela escola, respondendo assim às reais necessidades da comunidade escolar e da população envolvente.

SMARTNews, Summer 07

News from the Iowa Careers Consortium

Fall '07 SMARTNews

News from the Iowa Careers Consortium

FY 07 Recycled Content Plastic Bag and Soy Inks Report

As required in Iowa Code section 307.21, this is a summary of purchasing activity for soy-based inks and recycled content trash bags. The figures are for fiscal year 2007.

Budjetti vuodelle 1939, Lk

Puhe

Estudio de bentos y sedimentología durante el Crucero Oceanográfico BIC Humboldt 9706-07

Estudia la estructura comunitaria del bentos, su variación espacio-temporal y su relación con las condiciones oceanográficas, realizando la determinación y seguimiento de los diferentes parámetros de la estructura comunitaria y su relación con la materia orgánica en el sedimiento.

Resultados generales del crucero de estimación de la biomasa de la merluza en el área de Puerto Pizarro a Huarmey. Crucero BIC José Olaya Blandra 9806-07

Estudia los resultados y relaciones de los componentes oceanográficos, biológicos, poblacionales y de pesca que fueron investigados durante el crucero BIC José Olaya Balandra 9806-07 de Puerto Pizarro a Huarmey

Estimado de la biomasa de la merluza y otros recursos demersales en el área comprendida entre Puerto Pizarro y Huarmey. Crucero Bic José Olaya Balandra 9806-07

El crucero se realizó del 27 de junio al 13 de julio a bordo del BIC José Olaya Balandra 9806-07, de Puerto Pizarro a Huarmey, subdividido en 8 subáreas y 3 estratos de profundidad que contienen las principales concentraciones y mayor explotación de la merluza (Merluccius gayi peruanus) y su fauna acompañante. El método aplicado fue el de área barrida. La biomasa de la merluza fue estimada en 215 mil toneladas promedio, variando entre 200,5 y 252 mil toneladas, considerando en los cálculos un factor medio de eficiencia de la red de e=0,75. Las subáreas y estratos mejor representados con merluza fueron F-II, E-III y D-III. El total de recursos demersales fue estimado en 575,4 mil toneladas promedio y las principales especies acompañantes fueron, en promedio: el falso volador, 66,2 mil toneladas; la cabrilla, 45 mil toneladas; y la cachema, 5,5 mil toneladas. En general, la población presentó una estratificación latitudinal por tallas con los individuos mayores al norte. Al sur de los 7°S los individuos menores de 35 cm de longitud total alcanzaron casi el 100% y al norte de los 7°S la población de merluza presentó una mayor mezcla, disminuyendo la proporción juvenil.