University of Rouen

About: University of Rouen is a education organization based out in Rouen, France. It is known for research contribution in the topics: Population & Receptor. The organization has 7299 authors who have published 13209 publications receiving 313477 citations.

Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1.

Abstract: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs – PAC1, VPAC1 and VPAC2– belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC1 receptors are selective for PACAP, whereas VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC2 receptor in susceptibility to schizophrenia and the PAC1 receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67). LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein-Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-1

Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial.

Abstract: Summary Background Diffuse large B-cell lymphoma is a common cancer in elderly patients. Although treatment has been standardised in younger patients, no prospective study has been done in patients over 80 years old. We aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab in elderly patients with diffuse large B-cell lymphoma. Methods We did a prospective, multicentre, single-arm, phase 2 study of patients aged over 80 years who had diffuse large B-cell lymphoma. Patients were included from 38 centres in France and Belgium. All patients received six cycles of rituximab combined with low-dose CHOP (R-miniCHOP) at 3-week intervals. Patients received 375 mg/m 2 rituximab, 400 mg/m 2 cyclophosphamide, 25 mg/m 2 doxorubicin, and 1 mg vincristine on day 1 of each cycle, and 40 mg/m 2 prednisone on days 1–5. The primary endpoint was overall survival, both unadjusted and adjusted for treatment and baseline prognostic factors. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01087424. Findings 150 patients were enrolled between Jan 9, 2006, and Jan 23, 2009 and 149 were included in the intention-to-treat analyses. Median age was 83 years (range 80–95). After a median follow-up of 20 months (range 0–45), the median overall survival was 29 months (95% CI 21 to upper limit not reached); 2-year overall survival was 59% (49–67%). In multivariate analyses, overall survival was only affected by a serum albumin concentration of 35 g/L or less (hazard ratio 3·2, 95% CI 1·4–7·1; p=0·0053). Median progression-free survival was 21 months (95% CI 13 to upper limit not reached), with a 2-year progression free survival of 47% (38–56). 58 deaths were reported, 33 of which were secondary to lymphoma progression. 12 deaths were attributed to toxicity of the treatment. The most frequent side-effect was haematological toxicity (grade ≥3 neutropenia in 59 patients; febrile neutropenia in 11 patients). Interpretation R-miniCHOP offers a good compromise between efficacy and safety in patients aged over 80 years old. R-miniCHOP should be considered as the new standard treatment in this subgroup of patients. Funding Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Plant-specific glycosylation patterns in the context of therapeutic protein production.

Abstract: While N-glycan synthesis in the endoplasmic reticulum (ER) is relatively well conserved in eukaryotes, N-glycan processing and O-glycan biosynthesis in the Golgi apparatus are kingdom specific and result in different oligosaccharide structures attached to glycoproteins in plants and mammals. With the prospect of using plants as alternative hosts to mammalian cell lines for the production of therapeutic glycoproteins, significant progress has been made towards the humanization of protein N-glycosylation in plant cells. To date, successful efforts in this direction have mainly focused on the targeted expression of therapeutic proteins, the knockout of plant-specific N-glycan-processing genes, and/or the introduction of the enzymatic machinery catalyzing the synthesis, transport and addition of human sugars. By contrast, very little attention has been paid until now to the O-glycosylation status of plant-made therapeutic proteins, which is surprising considering that hundreds of human proteins represent good candidates for Hyp-O glycosylation when produced in a plant expression system. This review describes protein N- and O-linked glycosylation in plants and highlights the limitations and advantages of plant-specific glycosylation on plant-made biopharmaceuticals.

Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord

Abstract: Urotensin II (UII) is a cyclic peptide initially isolated from the caudal neurosecretory system of teleost fish. Subsequently, UII has been characterized from a frog brain extract, indicating that a gene encoding a UII precursor is also present in the genome of a tetrapod. Here, we report the characterization of the cDNAs encoding frog and human UII precursors and the localization of the corresponding mRNAs. In both frog and human, the UII sequence is located at the C-terminal position of the precursor. Human UII is composed of only 11 amino acid residues, while fish and frog UII possess 12 and 13 amino acid residues, respectively. The cyclic region of UII, which is responsible for the biological activity of the peptide, has been fully conserved from fish to human. Northern blot and dot blot analysis revealed that UII precursor mRNAs are found predominantly in the frog and human spinal cord. In situ hybridization studies showed that the UII precursor gene is actively expressed in motoneurons. The present study demonstrates that UII, which has long been regarded as a peptide exclusively produced by the urophysis of teleost fish, is actually present in the brain of amphibians and mammals. The fact that evolutionary pressure has acted to conserve fully the biologically active sequence of UII suggests that the peptide may exert important physiological functions in humans.