The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer
- Background: The epidermal growth factor receptor (EGFR) is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE) cancer has not been established yet.
Methods: EGFR status was analyzed by immunohistochemistry (IHC) in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients.
Results: EGFR protein expression (any grade) and overexpression (3+) were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05), but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS) was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463) or as 3+ (8.6 vs. 10.8 months, p = 0.377). The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247). There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116) or quartile (p = 0.767) distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed.
Conclusions: Unlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.
Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
Trang T. Nguyen
Maria R. Dauvermann
Franziska A. Degenhardt
Markus M. Nöthen
Heinz Erich Wichmann
Carla Marie Thérèse Tiesler
Stephen V. Faraone
Tobias J. Renner
Benno G. Schimmelmann
- Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development
- The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion.
Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA. In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.
Concerns about cultural neurosciences: a critical analysis
Marina Martínez Mateo
Nicole Cruz de Echeverría Loebell
- Ten years ago, neuroscientists began to study cultural phenomena by using functional MRI. Since then the number of publications in this field, termed cultural neuroscience (CN), has tremendously increased. In these studies, particular concepts of culture are implied, but rarely explicitly discussed. We argue that it is necessary to make these concepts a topic of debate in order to unravel the foundations of CN. From 40 fMRI studies we extracted two strands of reasoning: models investigating universal mechanisms for the formation of cultural groups and habits and, models assessing differences in characteristics among cultural groups. Both strands simplify culture as an inflexible set of traits and specificities. We question this rigid understanding of culture and highlight its hidden evaluative nature.
What is known about cookiecutter shark (Isistius spp.) interactions with cetaceans in Cape Verde seas?
Frederick W. Wenzel
Pedro López Suárez
- In the North Atlantic, the waters surrounding the Cape Verde Islands are a ‘potential hot spot’ for cookiecutter shark Isistius spp. interactions with cetaceans. These occurrences were recently identified by the improved efforts of researchers to document cetacean strandings in the Cape Verde archipelago, as well as by the photo identification efforts of live whales and dolphins. The documentation of individual and mass stranding events confirmed that cookiecutter shark interactions with cetaceans in Cape Verde seas are remarkably common.
Has the magnificent frigatebird Fregata magnificens in the Cape Verde Islands reached the end of the road?
Pedro López Suárez
Cornelis J. Hazevoet
- frigatebird were recovered at João Barrosa beach (16°01.387’N, 022°43.610’W), southeastern Boavista, Cape Verde Islands. The carcass had been found in mid September 2012, during a beach survey to monitor loggerhead turtle nesting activity in the area and was then buried in the sand. The field assistant of the Cabo Verde Natura 2000 turtle project who found the bird indicated the location of the corpse to the first author. His description of the bird allowed it to be identified as an adult female magnificent frigatebird Fregata magnificens Mathews, 1914. The remains consisted of numerous black and white feathers as well as several bones, including the skull, thorax and wing bones, which are preserved at the Cabo Verde Natura 2000 headquarters at Sal Rei, Boavista. Some feathers, together with remains of an egg and tissue of a mummified male found at Ilhéu de Baluarte in 2005 (see below), were deposited at the Centro de Análise Molecular, Centro de Investigação em Biodiversidade e Recursos Genéticos (CMA/CIBIO), Vairão, Portugal.
An aberrantly coloured buzzard Buteo bannermani on Santo Antão, Cape Verde Islands, in November 2012, with notes on the past and present status of the species
- On 30 November 2012, we observed a white presumed Cape Verde buzzard Buteo bannermani Swann, 1919 in the northern mountains of Santo Antão, Cape Verde Islands. The bird was defending a territory on the west side of the road between Corda and Vila da Ribeira Grande. Judging from the amount of time it spent in aerial display, it probably concerned a male. RP managed to make a series of photos, including some of the bird perched at a distance of ca. 60 m (Fig. 1 & 2). In these it was possible to confirm that the eyes were dark and neither pale nor reddish, identifying the bird as an adult and excluding the possibility of an albino. Its apparent mate was a bird of normal appearance.
Diet of feral cats Felis catus L., 1758 on Santa Luzia, Cape Verde Islands
Félix M. Medina
- The diet of feral cats Felis catus on Santa Luzia, Cape Verde Islands, was studied. A total of 147 prey items were identified during the analysis of 26 scat groups collected during the summer of 2010. House mouse Mus musculus was the most important prey, both in percentage of biomass and number of preys consumed (89.7% and n= 117, respectively). Reptiles were the second most important prey, represented by one skink species (Chioninia stangeri) and an unidentified gecko species. The remainder of the identified prey consisted of one bird species (Passer iagoensis) and one undetermined Tettigoniidae species (Insecta). No endangered species were identified in scats of this introduced predator, but future surveys must be carried out to further avoid threats to the island’s biodiversity.
From Cape Verde to the Netherlands via Portugal and France: the journey of an early specimen of the giant skink Chioninia coctei (Duméril & Bibron, 1839)
Luís M.P. Ceríaco
- An old specimen of the extinct giant skink Chioninia coctei (Duméril & Bibron, 1839), endemic to the islets of Branco and Raso, Cape Verde Islands, in the Naturalis Biodiversity Center, Leiden, the Netherlands, had been misidentified as Leiolopisma telfairii (Desjardin, 1831). The specimen, acquired by the Leiden Museum from the Muséum national d'Histoire naturelle in Paris during the 19th century, is demonstrated to be one of the specimens of C. coctei sent to Portugal by João da Silva Feijó during the 1780s. It was brought from Lisbon to Paris by Étienne Geoffroy Saint-Hilaire during the Napoleonic invasion in 1808. Together with the specimen remaining in the Paris museum, it is the oldest known of the species. The likely pathway of dispersal, as well as the general characteristics of the specimen, are discussed.
Manual for the Monitoring of Sea Turtles in the Cape Verde Islands
Nuno de Santos Loureiro
Luis Felipe López-Jurado
- To actively protect sea turtles on their nesting beaches, it is essential to obtain knowledge about trends in abundance. The way sea turtles live makes it extremely difficult to identify how many individuals there are in a population at any point in time. Due to practical problems, given their entirely marine life with limited visibility and great oceanic dispersal, counting males or juveniles is currently quite difficult and imprecise. Counting females and nests on beaches during the nesting season is the best feasible but still imperfect method, since only an unknown portion of adult females nest every season. It is impossible to know the real number of females in the population by merely counting females and nests in a given year. The number of nesting females can vary greatly from year to year and it is therefore advisable to count them incessantly in subsequent years. Variations in nesting females between years can be independent of general population fluctuations and be due to chance or (unknown) environmental factors. Since the work has to be done at night and the majority of individuals must be marked and recaptured in order to be effective, carrying out censuses of females is complex. Yearly censuses of nests is suggested as the most effective method and the best way to obtain knowledge about the abundance of individuals in a population, their numerical development over time, the conservation status of the population and the effectiveness of conservation measures. The capture frequency of females and poached nests on beaches also requires counting the numbers involved.