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BackgroundColorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24.MethodsCRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24.ResultsNone of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk.ConclusionsTOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts. more...

The European Research Council provides funding for independent researchers in all research areas and career stages. This session provides basic information on how to prepare an ERC grant proposal and how the ERC funding can support researchers and their careers. more...

Objective: To evaluate systemic hemodynamics, endogenous vasoactive neurohormonal factors (renin-angiotensin and sympathetic nervous systems, antidiuretic hormone, atrial natriuretic factor, and renal prostaglandins), and renal function in the severe ovarian hyperstimulation syndrome.Design: Prospective longitudinal study.Setting: Assisted-reproduction unit of a tertiary care hospital in Barcelona, Spain.Patients: 31 consecutive patients having in vitro fertilization with development of ascites because of severe ovarian hyperstimulation syndrome.Measurements: Mean arterial pressure; cardiac output; peripheral vascular resistance; hematocrit concentration; renal function; plasma renin activity; plasma aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide determinations; and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin-F1 were measured during the syndrome and 4 to 5 weeks after recovery (baseline).Results: During the syndrome, patients showed increased hematocrits (mean of the paired difference, 0.047; 95% CI, 0.029 to 0.064), decreased mean arterial pressure (-16.6 mm Hg; CI, -19.8 to -13.6), increased cardiac output (2.6 L/min; CI, 2.13 to 3.17), and reduced peripheral vascular resistance (-709 dyne/s.cm-5;CI, -792 to -627). This was accompanied by marked increases of plasma renin (14.4 ng/L.s; CI, 9.87 to 18.90), norepinephrine (1.857 nmol/L; CI, 0.533 to 3.161), antidiuretic hormone (3.3 pg/mL; CI, 1.89 to 4.71), and atrial natriuretic peptide levels (9.7 fmol/mL; CI, 6.1 to 13.2). Hemoconcentration developed in 16 patients (mean of the paired difference in hematocrit concentration, 0.082; CI, 0.063 to 0.101) but not in 15 others (0.009; CI, 0.003 to 0.021). Both groups showed similar values for arterial pressure, cardiac output, and peripheral vascular resistance, but patients with hemoconcentration had higher (P < 0.05) levels of renin (mean, 20.97 ng/L.s[CI, 13.3 to 28.63] compared with 7.83 ng/L.s[CI, 4.08 to 11.58]), norepinephrine (3.907 nmol/L [CI, 3.057 to 4.757] compared with 2.417 [CI, 2.035 to 2.799]), and antidiuretic hormone (6.0 pg/mL [CI, 4.1 to 7.9] compared with 2.4 [CI, 1.7 to 3.03]).Conclusions: In addition to increased capillary permeability, severe ovarian hyperstimulation syndrome is consistently associated with arteriolar vasodilation. The simultaneous occurrence of these disorders leads to hyperdynamic circulatory dysfunction with marked stimulation of the sympathetic nervous system, renin-angiotensin system, and antidiuretic hormone. [ABSTRACT FROM AUTHOR] more...

Abstract Background The aim of the study was to investigate expression of ADAMs (A Disintegrin and A Metalloproteinase) of host cell origin during cell-cell fusion induced by human parainfluenza virus type 2 (HPIV2). Results Induction of host cell ADAM9 was observed in GMK cells, but the applicability of this model was restricted by lack of cross-reactivity of the anti-human ADAM8 antibodies with the corresponding green monkey antigens. HSG cells were not susceptible to HPIV2 virus infection. In contrast, in human parotid gland HSY cells, a natural host cell for paramyxoviruses, HPIV2 induced ADAM8 expression. ADAM8 staining increased dramatically over time from 7.9 ± 3% at zero hours to 99.2 ± 0.8% at 72 hours (p = 0.0001). Without HPIV2 the corresponding percentages were only 7.7% and 8.8%. Moreover, ADAM8 positive cells formed bi- (16.2%) and multinuclear cells (3.5%) on day one and the corresponding percentages on day three were 15.6% for binuclear and 57.2% for multinuclear cells. Conclusion ADAM8, well recognized for participation in cell-to-cell fusion especially in osteoclast formation, is up-regulated upon formation of multinuclear giant cells after HPIV2 induction in HSY cells. The virus-HSY cell system provides a novel experimental model for study of the molecular mechanism of cell fusion events. more...