H4 Histamine Receptors Mediate Cell Cycle Arrest in Growth Factor-Induced Murine and Human Hematopoietic Progenitor Cells

The most recently characterized H4 histamine receptor (H4R) is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs

Agreement for depression diagnosis between DSM-IV-TR criteria, three validated scales, oncologist assessment, and psychiatric clinical interview in elderly patients with advanced ovarian cancer

Wadih Rhondali,1 Gilles Freyer,2 Virginie Adam,3 Marilène Filbet,4 Martine Derzelle,5 Gaelle Abgrall-Barbry,6 Sophie Bourcelot,7 Jean-Louis Machavoine,8 Muriel Chomat-Neyraud,9 Olivier Gisserot,10 Rémi Largillier,11 Annick Le Rol,12 Frank Priou,13 Pierre Saltel,14 Claire Falandry15 1Clinique Mon Repos, Clinea, Marseille, France; 2Medical Oncology Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Benite, France; 3Institut de Cancérologie de Lorraine Alexis Vautrin, Vandoeuvre-lès-Nancy, France; 4Palliative Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Benite, France; 5Institut Jean Godinot, Reims, France; 6Tenon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; 7Centre Léon Bérard, Lyon, France; 8Centre François Baclesse, Caen, France; 9Centre Hospitalier de la région d’Annecy, Pringy, France; 10Hôpital d’Instruction des Armées Sainte-Anne, Toulon, France; 11Centre Azuréen de Cancérologie, Mougins, France; 12Medical Oncology, Hôpital Perpétuel Secours, Levallois-Perret, France; 13Medical Oncology, Centre Hospitalier Départemental Les Oudairies, La Roche-sur-Yon, France; 14Supportive Care Department, Centre Léon Bérard, Lyon, France; 15Geriatrics and Oncology Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Bénite, France Background: Depression, a major outcome in cancer patients, is often evaluated by physicians relying on their clinical impressions rather than patient self-report. Our aim was to assess agreement between patient self-reported depression, oncologist assessment (OA), and psychiatric clinical interview (PCI) in elderly patients with advanced ovarian cancer (AOC).Methods: This analysis was a secondary endpoint of the Elderly Women AOC Trial 3 (EWOT3), designed to assess the impact of geriatric covariates, notably depression, on survival in patients older than 70 years of age. Depression was assessed using the Geriatric Depression Scale-30 (GDS), the Hospital Anxiety Depression Scale, the distress thermometer, the mood thermometer, and OA. The interview guide for PCI was constructed from three validated scales: the GDS, the Hamilton Depression Rating Scale, and the Montgomery Asberg Depression Rating Scale (MADRS). The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, revised (DSM) criteria for depression were used as a gold standard.Results: Out of 109 patients enrolled at 21 centers, 99 (91%) completed all the assessments. Patient characteristics were: mean age 78, performance status ≥2: 47 (47%). Thirty six patients (36%) were identified as depressed by the PCI versus 15 (15%) identified by DSM. We found moderate agreement for depression identification between DSM and GDS (κ=0.508) and PCI (κ=0.431) and high agreement with MADRS (κ=0.663). We found low or no agreement between DSM with the other assessment strategies, including OA (κ=-0.043). Identification according to OA (yes/no) resulted in a false-negative rate of 87%. As a screening tool, GDS had the best sensitivity and specificity (94% and 80%, respectively).Conclusion: The use of validated tools, such as GDS, and collaboration between psychologists and oncologists are warranted to better identify emotional disorders in elderly women with AOC. Keywords: depression, elderly, cancer, screening, geriatric assessmen