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RESEARCH PROGRAM
italiano - inglese
Research Units
- Università degli Studi di TORINO
MEDICINA ED ONCOLOGIA SPERIMENTALE
- Università degli Studi di BOLOGNA
UCI - CARDIOLOGIA ED EMATOLOGIA
- Università degli Studi di PARMA
MEDICINA INTERNA E SCIENZE BIOMEDICHE
- Università degli Studi di MILANO
SCIENZE MEDICHE
- Università degli Studi di ROMA "La Sapienza"
BIOTECNOLOGIE CELLULARI ED EMATOLOGIA
Similar research programs:
- 1 - Studies on the molecular mechanisms of abnormal parathyroid proliferation and function, and identification and clinical use of molecular markers of sporadic and familial parathyroid cancer. New insights on the prevalence of skeletal, neuropsychological and metabolic manifestations of primary hyperparathyroidism, their relationship with calcium sensing receptor polymorphisms and course after parathyroidectomy.
- 2 - Humoral immunity in multiple sclerosis: B lymphocyte activation and demyelination
- 3 - New frontiers in the stratification of acute lymphoblastic leukemia (ALL): integration between non-conventional cytogenetics, genomics and post-genomics.
- 4 - Molecular pathogenesis and sequential analysis of cellular interactions and biologic markers of disease progression and of drug resistance in chronic lymphocytic leukermia
- 5 - Hypoxia-induced angiogenetic genes: susceptibility factors to Amyotrophic Lateral Sclerosis ?
- 6 - Liver metastases from colorectal cancer: risk factors, prognostic factors and treatment strategies on molecular basis
- 7 - Adipokines, inflammatory cytokines and regulatory T cells role in accelerated atherosclerosis and metabolic syndrome pathogenesis, over the course of systemic lupus erythematosus
- 8 - Control mechanisms of erythropoiesis and congenital and familial polycythemias: role of oxygen-sensing pathways
- 9 - Molecular pathogenesis of Human lymphoid malignancies: from diagnosis to the therapy
- 10 - Clinical, genetic and molecular markers of susceptibility to atrial fibrillation: an integrated approach to the prevention and treatment of the arrhythmia and its complications.
Scientific and education field classification
International Patent Classification
- CHEMISTRY; METALLURGY
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- HUMAN NECESSITIES
- MEDICAL OR VETERINARY SCIENCE; HYGIENE
- DIAGNOSIS; SURGERY; IDENTIFICATION (analysing biological material G01N, e.g. G01N33/48; obtaining records using waves other than optical waves, in general G03B42/00)
- PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES (bringing into special physical form A61J [N: mechanical aspects]; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; compounds per se C01, C07, C08, C12N; soap compositions C11D; micro-organisms per se C12N) [C0203]
- MEDICAL OR VETERINARY SCIENCE; HYGIENE
Geographical classification
- Region: Piemonte
Bibliografia
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Keywords
MULTIPLE MYELOMA, MONOCLONAL GAMMOPATHY OF UNCERTAIN SIGNIFICANCE, TUMOR PROGRESSION, GENE EXPRESION PROFILING, APOPTOSIS, BONE METABOLISM, CHROMOSOMAL IMBALANCES, BONE MARROW MICROENVIROMENT, SERUM BIOMARKERSPROGRESSION FROM MGUS TO MULTIPLE MYELOMA: BIOLOGICAL INSIGHTS, CANDIDATE PROGNOSTIC MARKERS AND POTENTIAL APPROACHES TO CHEMOPREVENTION
Università degli Studi di TorinoAbstract
Monoclonal gammopathy of unknown significance (MGUS), is a common asymptomatic pre-malignant condition known since decades. Its prevalence in healthy elderly subjects is 3% and its risk of evolving into its highly malignant counterpart known as multiple myeloma (MM) is 1%/year. Despite our improved knowledge of the pathogenesis of plasma cell dyscrasias, progression from MGUS to MM remains one of the less well-understood steps in myelomagenesis. This project will comprehensively address this issue by the co-ordinated effort of five Units with major experience in the biology and clinical management of plasma cell dyscrasias. This research will address all the most important aspects that might be critical in this process, including extensive characterization of structural genetic defects by array-CGH, gene expression profiling of malignant and microenviromental cells, and proteomic screening of serum biomarker dysregulation. In addition the role of the apoptotic/anti-apoptotic machinery and that of microenviromental interactions (particularly in the context of cells related to bone metabolism) will be investigated. A considerable effort will also be devoted to translational issues by focusing not only on biological mechanisms of progression but also on the identification of effective prognostic markers and on the preclinical development of rational interventional strategies. In the development of effective prognostic tools, it will be critical to take advantage of the >>>Principal Investigator
Mario Boccadoro Università degli Studi di TORINOResearch Objectives
This project will comprehensively investigate the issue of progression from MGUS to MM. As detailed in the following sections, this event is one of the less well understood steps in myelomagenesis.(1) This project will involve five units with considerable experience in the biology and clinical management of MM. The co-ordinated effort of these units will allow investigating several of the aspects, which might be crucial in this process.The project aim is to establish a strong biological and pre-clinical basis for future interventional approaches in MGUS patients. The general perspective is to change the view and the management of this frequent pre-neoplastic condition. Currently MGUS is a frustrating condition for both the patient and the clinician as no therapeutic tools are available to counteract the risk of developing a devastating and rapidly fatal malignancy.(1) This project will help to open new perspectives in order to make the diagnosis of MGUS a valuable opportunity suitable to reduce the incidence of aggressive plasma cell dyscrasias.
For this reasons the project will focus on three basic aspects of the progression from MGUS to MM: a) understanding the biology (Unit I,II,III,IV,V); b) identifying candidate prognostic markers (Units I, IV); c) to preclinically investigate how developing future rational chemopreventive strategies (Unit III, V).
These general aims will be addressed through the following research lines, which >>>
Timescale
24 monthsNational and international background
The most remarkable successes obtained in cancer treatment have been obtained in the treatment of early disease phases. This is true not only in solid tumors, where early surgical intervention is a critical step for successful disease control, but also in the field of blood cancers. In this context the example of chronic myelogenous leukemia is particularly important. In this neoplasm a number of highly effective therapeutic modalities have been developed over the last decades, including allogeneic stem cell transplantation and more recently imatinib. Both these treatments are extremely successful in early chronic phase, have intermediate efficacy when employed in late chonic or accelerated phase, and are nearly ineffective in blastic phase(6-8).The progressive loss of treatment responsiveness observed when a tumor reaches its most advanced phases is a complex phenomenon, which is far from clear. Several clinical features and biological mechanisms have been implicated. These include increased tumor burden, accumulation of harmful mutations, increased genetic instability, development of redundant mechanisms of tumor growth, loss of immune control etc(9-10). The relative impact of these mechanisms is definitely not clear and great differences probably exist between different tumors. However a large bulk of data indicate that targeting early disease phases is probably the most effective way to approach human cancer and should be pursued whenever possible >>>
