Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

<p>Abstract</p> <p>Background</p> <p>The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0_micro+patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0_micro+) and evaluate the benefits from adjuvant chemotherapy in pN0_micro+CC patients.</p> <p>Methods/design</p> <p>EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an <it>ex vivo </it>sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0_micro+) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).</p> <p>Discussion</p> <p>The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 _micro+CC patients by reducing disease recurrence by adjuvant chemotherapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01097265">NCT01097265</a></p

Sequencing the genome of the Atlantic salmon (Salmo salar)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids

Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals

Background: Vertebrate alpha (α)- and beta (β)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the α- and β-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil β-globin gene (ω) in the marsupial α-cluster, however, suggested that duplication of the α-β cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous α- and β-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. Results: The platypus α-globin cluster (chromosome 21) contains embryonic and adult α- globin genes, a β-like ω-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-ζ-ζ'-αD-α3-α2-α1-ω-GBY-3'. The platypus β-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-ε-β-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate α-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal β-globin clusters are embedded in olfactory genes. Thus, the mammalian α- and β-globin clusters are orthologous to the bird α- and β-globin clusters respectively. Conclusion: We propose that α- and β-globin clusters evolved from an ancient MPG-C16orf35-α-β-GBY-LUC7L arrangement 410 million years ago. A copy of the original β (represented by ω in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (&gt;315 million years ago), then duplicated and diverged to form orthologous clusters of β-globin genes with different expression profiles in different lineages.Vidushi S. Patel, Steven J.B. Cooper, Janine E. Deakin, Bob Fulton, Tina Graves, Wesley C. Warren, Richard K. Wilson and Jennifer A.M. Grave

Vitamin status and cognitive function in a long-term care population

BACKGROUND: Ageing can be associated with poor dietary intake, reduced nutrient absorption, and less efficient utilization of nutrients. Loss of memory and related cognitive function are also common among older persons. This study aimed to measure the prevalence of inadequate vitamin status among long-term care patients and determine if an association exists between vitamin status and each of three variables; cognitive function, vitamin supplementation, and medications which alter gastric acid levels. METHODS: Seventy-five patients in a long-term care hospital in Guelph, Ontario were recruited to a cross-sectional study. 47 were female and the mean age was 80.7 (+/-11.5) years, ranging from 48 to 100 years. Blood was used to measure levels of vitamins B12 (cobalamin), B6 (pyridoxal-5'-phosphate/PLP), erythrocyte folate, vitamin B3 (niacin) and homocysteine (Hcy). The Standardized Mini-Mental State Examination (SMMSE) was administered to measure cognitive function. A list of medications and vitamin supplementation for each patient was provided by the pharmacy. RESULTS: The prevalence of low vitamin (B12, B6, erythrocyte folate, niacin) or high metabolite (homocysteine) levels among 75 patients were as follows: B12 <148 pmol/L in 5/75 (6.7%); B12 between 148 and 221 pmol/L in 26/75 (34.7%); B6 ≤30 nmol/L in 4/75 (5.3%); erythrocyte folate <370 nmol/L in 1/75 (1.3%); niacin ratio ≤1 in 20/75 (26.7%); homocysteine >13.3 μmol/L in 31/75 (41.3%). There was no significant difference among residents grouped into marked (n = 44), mild (n = 14), or normal (n = 9) cognitive function when evaluating the effect of vitamin status. There were no significant differences in mean B12 and homocysteine levels between users and non-users of drug therapy (Losec, Zantac, or Axid). Compared to vitamin supplement non-users, supplemented residents had significantly higher mean B12 (p < 0.0001) and erythrocyte folate (p < 0.05) concentrations and significantly lower mean homocysteine (p < 0.01) levels; 229.1 versus 423.6 pmol/L for B12, 882.9 versus 1043.6 nmol/L for erythrocyte folate and 14.4 versus 12.0 μmol/L for homocysteine. CONCLUSION: Given the prevalence data on vitamin status in this sample population, the possible benefits of vitamin supplementation should be considered in clinical intervention studies using these populations of elderly

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

International audienceAutism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs

In Vivo Assessment of Cold Adaptation in Insect Larvae by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

Background Temperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems. Methodology Given that non-destructive techniques like 1H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems–the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis. Results In vivo MR images were acquired from autumn-collected larvae at temperatures between 0°C and about -70°C and at spatial resolutions down to 27 µm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae. Conclusions These findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo