Showing papers by "University of Palermo published in 2013"

Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society

Abstract: Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD. Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

Brookite, the Least Known TiO2 Photocatalyst

Abstract: Brookite is the least studied TiO2 photocatalyst due to the difficulties usually encountered in order to obtain it as a pure phase. In this review, a comprehensive survey of the different methods available for preparing brookite powders and films is reported. Attention has been paid both to the most traditional methods, such as hydrothermal processes at high temperatures and pressures, and to environmentally benign syntheses using water soluble compounds and water as the solvent. Papers reporting the photocatalytic activity of pure and brookite-based samples have been reviewed.

Swings between rotation and accretion power in a binary millisecond pulsar

Abstract: We present the discovery of IGR J18245-2452, the first millisecond pulsar ob- served to swing between a rotation-powered, radio pulsar state, and an accretion-powered X-ray pulsar state (31). This transitional source represents the most convincing proof of the evolutionary link shared by accreting neutron stars in low mass X-ray binaries, and ra- dio millisecond pulsars. It demonstrates that swings between these two states take place on the same time-scales of luminosity variations of X-ray transients, and are therefore most easily interpreted in terms of changes in the rate of mass in-flow. While accreting mass, the X-ray emission of IGR J18245-2452 varies dramatically on time-scales ranging from a second to a few hours. We interpret a state characterised by a lower flux and pulsed fraction, and by sudden increases of the hardness of the X-ray emission, in terms of the onset of a magnetospheric centrifugal inhibition of the accretion flow. Prospects of finding new members of the newly established class of transitional pulsars are also briefly discussed.

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Abstract: Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications.

Abstract: Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics.

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

Abstract: Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed as a valid adjunct in many procedures in oral and dental surgery. However, further RCTs are required to support this evidence.

Dynamics of quantum correlations in two-qubit systems within non-markovian environments

Abstract: Knowledge of the dynamical behavior of correlations with no classical counterpart, like entanglement, nonlocal correlations and quantum discord, in open quantum systems is of primary interest because of the possibility to exploit these correlations for quantum information tasks. Here we review some of the most recent results on the dynamics of correlations in bipartite systems embedded in non-Markovian environments that, with their memory effects, influence in a relevant way the system dynamics and appear to be more fundamental than the Markovian ones for practical purposes. Firstly, we review the phenomenon of entanglement revivals in a two-qubit system for both independent environments and a common environment. We then consider the dynamics of quantum discord in non-Markovian dephasing channel and briefly discuss the occurrence of revivals of quantum correlations in classical environments.

Experimental recovery of quantum correlations in absence of system-environment back-action

Abstract: In quantum systems, information can flow back and forth between the system and its environment, leading to revivals of quantum correlations. Using a simple model, Xu et al. experimentally show how revivals can occur with a classical environment despite the absence of back-action from the environment.

R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Follicular Lymphoma: Results of the FOLL05 Trial Conducted by the Fondazione Italiana Linfomi

Abstract: Purpose Although rituximab (R) is commonly used for patients with advanced follicular lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen has yet to be clarified. Patients and Methods We conducted an open-label, multicenter, randomized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide, vincristine, and prednisone (CVP) or six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or six cycles of fludarabine and mitoxantrone (FM). The principal end point of the study was time to treatment failure (TTF). Results There were 534 patients enrolled onto the study. Overall response rates were 88%, 93%, and 91% for R-CVP, R-CHOP, and R-FM, respectively (P .247). After a median follow-up of 34 months, 3-year TTFs were 46%, 62%, and 59% for the respective treatment groups (R-CHOP v R-CVP, P .003; R-FM v R-CVP, P .006; R-FM v R-CHOP, P .763). Three-year progression-free survival (PFS) rates were 52%, 68%, and 63% (overall P .011), respectively, and 3-year overall survival was 95% for the whole series. R-FM resulted in higher rates of grade 3 to 4 neutropenia (64%) compared with R-CVP (28%) and R-CHOP (50%; P .001). Overall, 23 second malignancies were registered during follow-up: four in R-CVP, five in R-CHOP, and 14 in R-FM. Conclusion In this study, R-CHOP and R-FM were superior to R-CVP in terms of 3-year TTF and PFS. In addition, R-CHOP had a better risk-benefit ratio compared with R-FM. J Clin Oncol 31:1506-1513. © 2013 by American Society of Clinical Oncology

Human NK Cells Selective Targeting of Colon Cancer–Initiating Cells: A Role for Natural Cytotoxicity Receptors and MHC Class I Molecules

Abstract: Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma-derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors.

Neuromodulation of chronic headaches: position statement from the European Headache Federation

Abstract: The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases. Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches. In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

Morbidly adherent placenta: evaluation of ultrasound diagnostic criteria and differentiation of placenta accreta from percreta.

Abstract: Objectives To evaluate the diagnostic accuracy of two-dimensional (2D) gray-scale and color Doppler and three-dimensional (3D) power Doppler sonographic criteria for morbidly adherent placenta (MAP), and to identify criteria to help distinguish placenta accreta from placenta percreta. Methods We enrolled 187 patients with placenta previa and history of uterine surgery and performed transabdominal and transvaginal ultrasound examination for early detection of MAP. With 2D gray-scale transabdominal and transvaginal ultrasonography, we investigated loss/irregularity of the echolucent area between the uterus and the placenta (‘clear space’), thinning or interruption of the hyperechoic interface between the uterine serosa and the bladder wall and the presence of turbulent placental lacunae with high-velocity flow (>15 cm/s). Using transabdominal 3D power Doppler, we evaluated the hypervascularity of the uterine serosa–bladder wall interface and irregular intraplacental vascularization. Ultrasound findings were reviewed against the final diagnosis made during Cesarean section (CS). Results MAP was detected on CS in 41 patients. All of them had an anterior placenta previa (34 major and seven minor) and had undergone at least one previous CS. The evaluated sonographic criteria showed good diagnostic performance; in MAP patients at least two out of five criteria were detected, with at most one of the criteria present in patients without MAP. Loss/irregularity of clear space used as a single criterion was responsible for the most false positives, demonstrating a low positive predictive value. Irregular intraplacental vascularization with tortuous confluent vessels affecting the entire width of the placenta, and hypervascularity of the entire uterine serosa–bladder wall interface, were only detected, on 3D power Doppler, in cases of placenta percreta. Conclusions The reviewed ultrasound criteria may be useful for the prenatal diagnosis of MAP and to differentiate between placenta accreta and placenta percreta; 3D power Doppler techniques were an important aid in the diagnosis. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

Association Between Metabolic Syndrome and Periodontitis: A Systematic Review and Meta-analysis

Abstract: Background: Several epidemiological studies have reported an association between metabolic syndrome (MetS) and periodontal diseases (PDs). The aim of this systematic review was to investigate the existence and magnitude of this association. Materials and Methods: A systematic search of the literature was conducted looking for case-control, cross-sectional, cohort studies and population surveys including patients with measures of MetS and PD. Ovid MEDLINE, EMBASE, LILACS, and Cochrane library databases were used for the search by 2 independent reviewers. A meta-analysis was conducted to investigate the association for coexistence of MetS and PD. Results: A total of 20 studies were included in the review, from an initial search of 3486 titles. Only 1 study reported longitudinal data on the onset of MetS components in association with periodontal measures. However, several studies investigated coexistence. A random effects meta-analysis showed that the presence of MetS is associated with the presence of peri...

Obesity and reduction of the response rate to anti-tumor necrosis factor α in rheumatoid arthritis: an approach to a personalized medicine.

Abstract: Objective Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti–tumor necrosis factor α (anti-TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs. Methods Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as 30 kg/m2), acute-phase reactants, IgM rheumatoid factor, and anti–cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of <2.6 lasting for at least 3 months. Results Six hundred forty-one outpatients with longstanding RA receiving anti-TNFα blockers (adalimumab, n = 260; etanercept, n = 227; infliximab, n = 154), recruited from 2006–2009 and monitored for at least 12 months, were analyzed. The mean ± SD DAS28 at baseline was 5.6 ± 1.4. A BMI of >30 kg/m2 was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti-TNFα treatment, a DAS28 of <2.6 was noted in 15.2% of the obese subjects, in 30.4% of the patients with a BMI of 25–30 kg/m2, and in 32.9% of the patients with a BMI of <25 kg/m2 (P = 0.01). The lowest percentage of remission, which was statistically significant versus adalimumab and etanercept (P = 0.003), was observed with infliximab. Conclusion Obesity represents a risk factor for a poor remission rate in patients with longstanding RA treated with anti-TNFα agents. A personalized treatment plan might be a possible solution.

Comparative investigation of the freezing phenomena for quantum correlations under nondissipative decoherence

Abstract: We show that the phenomenon of frozen discord, exhibited by specific classes of two-qubit states under local nondissipative decoherent evolutions, is a common feature of all known bona fide measures of general quantum correlations. All those measures, despite inducing typically inequivalent orderings on the set of nonclassically correlated states, return a constant value in the considered settings. Every communication protocol that relies on quantum correlations as a resource will run with a performance completely unaffected by noise in the specified dynamical conditions. We provide a geometric interpretation of this phenomenon.

Malnutrition in elderly: Social and economic determinants

Abstract: Malnutrition occurs frequently in the frailest groups of the population, especially in people who are on a low income and elderly subjects, overall if they are institutionalized. The aim of this study was to assess the prevalence of malnutrition in a sample of elderly people living in different settings and to identify the determinants of malnutrition. Methods:A total of 718 subjects, 472 females (F) and 246 males (M), were recruited from nursing homes or were free living in three different regions in Italy. Nutritional status, depression, social, functional and cognitive status, were evaluated. Results:According to the Mini Nutritional Assessment (MNA), a high prevalence of malnutrition was found out in both genders: 26% of F and 16.3% of M were classified as being malnourished (MNA<17); 40.9% of F and 35% of M were at risk of malnutrition (MNA 17- 23,5). The prevalence of malnutrition was significantly higher in NH subjects in both sexes. Moreover, a relationship was shown between malnutrition and inability to shop, prepare and cook meals because of a low income, distance from markets or supermarkets as well as impossibility to drive the car or to use public transportation. This study confirms the necessity to routinely perform nutritional status evaluation in elderly subjects, to carry out training courses for health workers (doctors, nurses, psychologists, dietitians), to implement nutritional education of the geriatric population, to develop tools and guidelines for health workers and caregivers, to identify and reduce clinical, functional, social or economic risk factors for malnutrition.

Spectral Theory of a Neumann–Poincaré-Type Operator and Analysis of Cloaking Due to Anomalous Localized Resonance

Abstract: The aim of this paper is to give a mathematical justification of cloaking due to anomalous localized resonance (CALR). We consider the dielectric problem with a source term in a structure with a layer of plasmonic material. Using layer potentials and symmetrization techniques, we give a necessary and sufficient condition on the fixed source term for electromagnetic power dissipation to blow up as the loss parameter of the plasmonic material goes to zero. This condition is written in terms of the Newtonian potential of the source term. In the case of concentric disks, we make the condition even more explicit. Using the condition, we are able to show that for any source supported outside a critical radius, CALR does not take place, and for sources located inside the critical radius satisfying certain conditions, CALR does take place as the loss parameter goes to zero.

XIPE: the X-ray imaging polarimetry explorer

Abstract: X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017. The proposal was, unfortunately, not selected. To be compliant with this schedule, we designed the payload mostly with existing items. The XIPE proposal takes advantage of the completed phase A of POLARIX for an ASI small mission program that was cancelled, but is different in many aspects: the detectors, the presence of a solar flare polarimeter and photometer and the use of a light platform derived by a mass production for a cluster of satellites. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus. Two additional GPDs filled with a 3-bar Ar-DME mixture always face the Sun to detect polarization from solar flares. The Minimum Detectable Polarization of a 1 mCrab source reaches 14 % in the 2–10 keV band in 105 s for pointed observations, and 0.6 % for an X10 class solar flare in the 15–35 keV energy band. The imaging capability is 24 arcsec Half Energy Width (HEW) in a Field of View of 14.7 arcmin × 14.7 arcmin. The spectral resolution is 20 % at 6 keV and the time resolution is 8 μs. The imaging capabilities of the JET-X optics and of the GPD have been demonstrated by a recent calibration campaign at PANTER X-ray test facility of the Max-Planck-Institut fur extraterrestrische Physik (MPE, Germany). XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil). The data policy is organized with a Core Program that comprises three months of Science Verification Phase and 25 % of net observing time in the following 2 years. A competitive Guest Observer program covers the remaining 75 % of the net observing time.

RNA recognition by human TLR8 can lead to autoimmune inflammation

Abstract: Studies on the role of the RNA receptor TLR8 in inflammation have been limited by its different function in human versus rodents. We have generated multiple lines of transgenic mice expressing different levels of human TLR8. The high copy number chimeras were unable to pass germline; developed severe inflammation targeting the pancreas, salivary glands, and joints; and the severity of the specific phenotypes closely correlated with the huTLR8 expression levels. Mice with relatively low expression levels survived and bred successfully but had increased susceptibility to collagen-induced arthritis, and the levels of huTLR8 correlated with proinflammatory cytokines in the joints of the animals. At the cellular level, huTLR8 signaling exerted a DC-intrinsic effect leading to up-regulation of co-stimulatory molecules and subsequent T cell activation. A pathogenic role for TLR8 in human diseases was suggested by its increased expression in patients with systemic arthritis and the correlation of TLR8 expression with the elevation of IL-1β levels and disease status. We found that the consequence of self-recognition via TLR8 results in a constellation of diseases, strikingly distinct from those related to TLR7 signaling, and points to specific inflammatory diseases that may benefit from inhibition of TLR8 in humans.

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

Abstract: Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell type-specific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it can regulate a great number of cellular activities. In particular, its association with the E2F transcription factor family allows the control of the main pRb functions, while the loss of these interactions greatly enhances cancer development. As RB1 gene, also pRb can be functionally inactivated through disparate mechanisms which are often tissue specific and dependent on the scenario of the involved tumor suppressors and oncogenes. The critical role of the context is complicated by the different functions played by the RB proteins and the E2F family members. In this review, we want to emphasize the importance of the mechanisms of RB1/pRb inactivation in inducing cancer cell development. The review is divided in three chapters describing in succession the mechanisms of RB1 inactivation in cancer cells, the alterations of pRb pathway in tumorigenesis and the RB protein and E2F family in cancer.