Publications by authors named "Giovanni Franco"

22 Publications

  • Page 1 of 1

Italian census on neurosciences: the ICoNe2 study.

Neurol Sci 2019 Feb 23;40(2):371-376. Epub 2018 Nov 23.

Chief Emeritus Department of Neurology, Iazzolino Hospital, Piazza Alexander Fleming 1, 89900, Vibo Valentia, Italy.

Background: The growing impact of the emergency neurology of trauma centers and of mechanical thrombectomy for the treatment of acute ischemic stroke is revolutionizing the domain of eurosciences.

Methods: A census focused on the demographic distribution of the three main cohorts of neurosciences (neurologists, neuroradiologists, and neurosurgeons) was conducted in Italy between December 2015 and February 2017, and results were compared to the estimated retirement rates and loss for other reasons.

Results: The total number of neurosciences specialists active in Italy was 4394 at the end of the period of the survey. The estimated retirement rates and losses seem not be supplied by the physicians in training in the same period.

Conclusions: A proper redistribution of the resources and the modification of the training programs seem to be mandatory to maintain acceptable standards of care for the Italian neurosciences during the next decade.
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http://dx.doi.org/10.1007/s10072-018-3649-yDOI Listing
February 2019

Effects of external trigeminal nerve stimulation (eTNS) on laser evoked cortical potentials (LEP): A pilot study in migraine patients and controls.

Cephalalgia 2018 06 31;38(7):1245-1256. Epub 2017 Aug 31.

Applied Neurophysiology and Pain Unit, Bari Aldo Moro University, Bari, Italy.

Background Transcutaneous external supraorbital nerve stimulation has emerged as a treatment option for primary headache disorders, though its action mechanism is still unclear. Study aim In this randomized, sham-controlled pilot study we aimed to test the effects of a single external transcutaneous nerve stimulation session on pain perception and cortical responses induced by painful laser stimuli delivered to the right forehead and the right hand in a cohort of migraine without aura patients and healthy controls. Methods Seventeen migraine without aura patients and 21 age- and sex-matched controls were selected and randomly assigned to a real or sham external transcutaneous nerve stimulation single stimulation session. The external transcutaneous nerve stimulation was delivered with a self-adhesive electrode placed on the forehead and generating a 60 Hz pulse at 16 mA intensity for 20 minutes. For sham stimulation, we used 2 mA intensity. Laser evoked responses were recorded from 21 scalp electrodes in basal condition (T0), during external transcutaneous nerve stimulation and sham stimulation (T1), and immediately after these (T2). The laser evoked responses were analyzed by LORETA software. Results The real external transcutaneous nerve stimulation reduced the trigeminal N2P2 amplitude in migraine and control groups significantly in respect to placebo. The real stimulation was associated with lower activity in the anterior cingulate cortex under trigeminal laser stimuli. The pattern of LEP-reduced habituation was reverted by real and sham transcutaneous stimulation in migraine patients. Conclusions The present results could suggest that the external transcutaneous nerve stimulation may interfere with the threshold and the extent of trigeminal system activation, with a mechanism of potential utility in the resolution and prevention of migraine attacks.
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http://dx.doi.org/10.1177/0333102417728748DOI Listing
June 2018

P042. Mechanism of action and clinical evidence of botulinum toxin in chronic migraine.

J Headache Pain 2015 Dec;16(Suppl 1):A138

Neurophysiopathology of Pain Unit, Neuroscience and Sensory Systems Department, University of Bari "Aldo Moro", Bari, Italy.

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http://dx.doi.org/10.1186/1129-2377-16-S1-A138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759346PMC
December 2015

P011. The use of electronic pain diaries via telemedicine for managing chronic pain.

J Headache Pain 2015 Dec;16(Suppl 1):A190

Neurophysiopathology of Pain Unit, Neuroscience and Sensory Systems Department, University of Bari "Aldo Moro", Bari, Italy.

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http://dx.doi.org/10.1186/1129-2377-16-S1-A190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759141PMC
December 2015

Laser Evoked Potentials in Early and Presymptomatic Huntington's Disease.

Behav Neurol 2016 21;2016:8613729. Epub 2016 Mar 21.

Apulian Referral Center for Huntington's Disease, Basic Medical Sciences, Neuroscience and Sensory System Department (SMBNOS), University of Bari Aldo Moro, Italy.

Pain was rarely studied in Huntington's disease (HD). We presently aimed to extend our previous study on pain pathways functions by laser evoked potentials (LEPs) to a larger cohort of early unmedicated HD patients and a small group of presymptomatic HD (PHD) subjects. Forty-two early HD patients, 10 PHD patients, and 64 controls were submitted to LEPs by right-hand stimulation. Two series of 30 laser stimuli were delivered, and artifact-free responses were averaged. The N1, N2, and P2 latencies were significantly increased and the N2P2 amplitude significantly reduced in HD patients compared to controls. In the HD group, the LEPs abnormalities correlated with functional decline. PHD subjects showed a slight and insignificant increase in LEPs latencies, which was inversely correlated with the possible age of HD clinical onset. Data of the present study seem to suggest that the functional state of nociceptive pathways as assessed by LEPs may be a potential biomarker of disease onset and progression. The assessment of pain symptoms in premanifest and manifest HD may also open a new scenario in terms of subtle disturbances of pain processing, which may have a role in the global burden of the disease.
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http://dx.doi.org/10.1155/2016/8613729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819083PMC
December 2016

Dysphagia in Huntington's Disease: Correlation with Clinical Features.

Eur Neurol 2015 14;74(1-2):49-53. Epub 2015 Jul 14.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, School of Medicine, University of Bari, Bari, Italy.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by motor impairment, cognitive decline and psychiatric disorders. Dysphagia is a pathologic condition that increases morbidity and mortality of the affected people. Our aim was to evaluate dysphagia in a group of HD patients in view of motor, cognitive and functional decline. Thirty-seven genetically confirmed HD patients were submitted to clinical evaluations of swallowing. Bedside Swallowing Assessment Scale (BSAS) was used. Dysphagia Outcome and Severity Scale (DOSS) was applied for a preliminary classification of swallowing difficulties. All patients were also evaluated by the Unified Huntington's Disease Rating Scale (UHDRS). A group of 39 controls comparable for sex and age were recruited for BSAS scores normalisation. The BSAS scores indicated that in our HD cohort, 32.4% presented relevant or severe dysphagia. The DOSS levels were significantly correlated with main clinical features, such as age, disease duration and motor impairment, with special regard to lingual protrusion ability, dysarthria and bradykinesia. The total functional capacity (TFC) and cognitive scales did not show significant correlation with DOSS levels. The results of clinical examination of swallowing indicated that dysphagia is a prevalent motor symptom of HD.
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http://dx.doi.org/10.1159/000435833DOI Listing
June 2016

Challenges and new prospects in hepatosplenic γδ T-cell lymphoma.

Leuk Lymphoma 2014 Nov 10;55(11):2457-65. Epub 2014 Mar 10.

Laboratorio di Tecnologie Oncologiche - HSR Giglio, C. da Pietrapollastra-Pisciotto , Cefalù , Italy.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoid neoplasms characterized by aggressive clinical behavior and dismal prognosis. Hepatosplenic γδ T-cell lymphoma (γδ-HSTL) is a particular form of PTCL that arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. γδ-HSTL has a rapidly progressive course and poor outcome due also to its refractoriness to conventional chemotherapy regimens. The very low incidence of γδ-HSTL, along with its propensity to mimic different pathological entities, makes this lymphoma a true diagnostic challenge. In this review, we highlight the biological and clinical features of γδ-HSTL that contribute to making this lymphoma a mostly incurable disease. Moreover, we provide a new insight into the crosstalk between HSTL clones and the bone marrow, liver and spleen vascular microenvironment, in which neoplastic cells reside and proliferate. We further discuss γδ-HSTL associated molecules that might be proposed as potential targets for novel therapeutic approaches.
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http://dx.doi.org/10.3109/10428194.2014.889821DOI Listing
November 2014

Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma.

Blood 2014 Mar 22;123(12):1836-49. Epub 2014 Jan 22.

Hematology Unit with Bone Marrow Transplantation and.

Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone genetics and the recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53(-/-) mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression.
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http://dx.doi.org/10.1182/blood-2013-04-497271DOI Listing
March 2014

Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion.

Blood 2012 Oct 5;120(17):3541-54. Epub 2012 Sep 5.

Tumor Immunology Unit, Human Pathology Section, Department of Health Sciences, University of Palermo, Italy.

In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146(+) mesenchymal stromal cells, correlates with the degree of stromal changes, and the severity of BM failure characterizing the prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc(-/-) mice and BM chimeras, we demonstrate that SPARC contributes to the development of significant stromal fibrosis in a model of thrombopoietin-induced myelofibrosis. We found that SPARC deficiency in the radioresistant BM stroma compartment impairs myelofibrosis but, at the same time, associates with an enhanced reactive myeloproliferative response to thrombopoietin. The link betwen SPARC stromal deficiency and enhanced myeloid cell expansion under a myeloproliferative spur is also supported by the myeloproliferative phenotype resulting from the transplantation of defective Apc(min) mutant hematopoietic cells into Sparc(-/-) but not WT recipient BM stroma. Our results highlight a complex influence of SPARC over the stromal and hematopoietic BM response in myeloproliferative conditions.
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http://dx.doi.org/10.1182/blood-2011-12-398537DOI Listing
October 2012

Thrombotic thrombocytopenic purpura: a review of the literature in the light of our experience with plasma exchange.

Blood Transfus 2012 Oct 27;10(4):521-32. Epub 2012 Jun 27.

Unit of Immunohaematology and Transfusion Medicine, Paolo Giaccone University Hospital, Department of Biopathology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, Italy.

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http://dx.doi.org/10.2450/2012.0122-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496241PMC
October 2012

Serum levels of N-acetyl-aspartate in migraine and tension-type headache.

J Headache Pain 2012 Jul 17;13(5):389-94. Epub 2012 Apr 17.

Neuroscience and Sensory System Department, Bari Aldo Moro University, Policlinico General Hospital, Neurological Building, Piazza Giulio Cesare 11, 70124, Bari, Italy.

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at -80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography-mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.
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http://dx.doi.org/10.1007/s10194-012-0448-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381063PMC
July 2012

Suggestion and pain in migraine: a study by laser evoked potentials.

CNS Neurol Disord Drug Targets 2012 Mar;11(2):110-26

Neurophysiopathology of Pain Unit, Neuroscience and Sensory Systems Department, University of Bari Aldo Moro, Bari, Italy.

Belief and expectation are part of placebo effect. Migraine patients are characterized by a dysfunctional modulation of pain processing, though a clear placebo effect emerges in clinical trials. The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls. Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls. The right hand and the right supraorbital zone were stimulated during a not conditioned and a conditioned task, where laser stimuli were delivered after a verbal and visual cues of decreased (D), increased (I) or basal (B) intensity, which was left unmodified during the entire task. In control subjects pain rating changed, according to the announced intensity, while in migraine patients the basal hyper-algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls, while an opposite paradoxical increase in decreasing condition emerged in migraine. The P2 amplitude modulation was also reduced in migraine, differently from controls. The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine, disability and allodynia. In controls suggestion influenced cortical pain processing and subjective pain rating, while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia. This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization.
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http://dx.doi.org/10.2174/187152712800269759DOI Listing
March 2012

Effects of low and high frequency repetitive transcranial magnetic stimulation of the primary motor cortex on contingent negative variations in normal subjects.

Neurosci Lett 2012 Feb 31;509(1):39-43. Epub 2011 Dec 31.

Neuroscience and Sensory System Department, Aldo Moro Bari University, Neurological Building, Policlinico General Hospital, 70124 Bari, Italy.

The state of primary motor cortex (M1) excitability is crucial for the processing of voluntary movement. We aimed to test the modulation induced by 1 Hz and 5 Hz repetitive transcranial magnetic stimulation (rTMS) of M1 on both early and late components of the contingent negative variation (CNV) and on the motor reaction in normal subjects. The CNV was evaluated in basal, and after 15 min of real or sham 1 Hz and 5 Hz stimulation of the left motor cortex in 7 right handed volunteers. Inhibition of motor cortex, due to rTMS stimulation, resulted in an amplitude increase of early and late components of CNV, and a slight reducing effect on motor reaction times, while 5 Hz stimulation did not change CNV amplitude. In normal subjects transient inhibition of motor cortex causes an increase of cortical events preceding external-cued voluntary movements, as a probable compensatory phenomena able to maintain an efficient motor performance.
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http://dx.doi.org/10.1016/j.neulet.2011.12.043DOI Listing
February 2012

Clinical features of headache patients with fibromyalgia comorbidity.

J Headache Pain 2011 Dec 17;12(6):629-38. Epub 2011 Aug 17.

Neurophysiopathology of Pain Unit, Neurological and Psychiatric Sciences Department, Medical Faculty, Policlinico General Hospital, Aldo Moro University, Neurological Building, Piazza Giulio Cesare 11, 70124, Bari, Italy.

Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
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http://dx.doi.org/10.1007/s10194-011-0377-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208047PMC
December 2011

A comparative study of cortical responses evoked by transcutaneous electrical vs CO(2) laser stimulation.

Clin Neurophysiol 2011 Dec 8;122(12):2482-7. Epub 2011 Jun 8.

Neurophysiopathology of Pain Unit, Neurological and Psychiatric Sciences Department, Aldo Moro University, Bari, Italy.

Objectives: A novel non-invasive method for nociceptive electrical stimulation of the skin has been recently introduced by using a planar concentric stimulating electrode (CE). We compared the cortical potentials induced by a CE vs laser stimulator in healthy subjects using a multichannel recording.

Methods: Cortical potentials were recorded in 11 healthy subjects by 54 scalp electrodes, stimulating the skin of the right hand and the right supra-orbital zone by the CE and laser stimulator settled two levels above the individual pain threshold.

Results: The latency difference between N1, N2, and P2 evoked by the CE vs laser stimulator was larger than the receptor activation time of 40 ms and larger following stimulation of the upper limbs than of the head. The amplitudes and topographic distribution of the cortical waves did not differ between the two stimulation types.

Conclusions: A-beta fibre co-activation may be induced by CE electrodes, as suggested by latency gaps. Nevertheless, CE-evoked potentials showed similarity in amplitude, morphology and topographic representation with laser-induced ones.

Significance: At present, CE-evoked potentials cannot be considered a reliable measure of nociceptive pathway function.
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http://dx.doi.org/10.1016/j.clinph.2011.05.006DOI Listing
December 2011

The bone marrow stroma in hematological neoplasms--a guilty bystander.

Nat Rev Clin Oncol 2011 Mar 29;8(8):456-66. Epub 2011 Mar 29.

Department of Human Pathology, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy.

In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma.
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http://dx.doi.org/10.1038/nrclinonc.2011.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673297PMC
March 2011

Bendamustine with or without rituximab in the treatment of relapsed chronic lymphocytic leukaemia: an Italian retrospective study.

Br J Haematol 2011 May 4;153(3):351-7. Epub 2011 Mar 4.

UO di Ematologia, AOUP Paolo Giaccone, Palermo, Italy.

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m(2) per day, range 90-130 mg/m(2) per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B (P = 0·014) and in those responsive to the previous treatment (P=0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity.
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http://dx.doi.org/10.1111/j.1365-2141.2011.08597.xDOI Listing
May 2011

Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma.

Am J Pathol 2010 Aug 1;177(2):792-802. Epub 2010 Jul 1.

Department of Human Pathology, University of Palermo, Palermo, Italy.

Reports focusing on the immunological microenvironment of peripheral T-cell lymphomas (PTCL) are rare. Here we studied the reciprocal contribution of regulatory (Treg) and interleukin-17-producing (Th17) T-cells to the composition of the lymphoma-associated microenvironment of angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified on tissue microarrays from 30 PTCLs not otherwise specified and 37 AITLs. We found that Th17 but not Treg cells were differently represented in the two lymphomas and correlated with the amount of mast cells (MCs) and granulocytes, which preferentially occurred in the cellular milieu of AITL cases. We observed that MCs directly synthesized interleukin-6 and thus contribute to the establishment of a pro-inflammatory, Th17 permissive environment in AITL. We further hypothesized that the AITL clone itself could be responsible for the preferential accumulation of MCs at sites of infiltration through the synthesis of CXCL-13 and its interaction with the CXCR3 and CXCR5 receptors expressed on MCs. Consistent with this hypothesis, we observed MCs efficiently migrating in response to CXCL-13. On these bases, we conclude that MCs have a role in molding the immunological microenvironment of AITL toward the maintenance of pro-inflammatory conditions prone to Th17 generation and autoimmunity.
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http://dx.doi.org/10.2353/ajpath.2010.091286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913370PMC
August 2010

T cell large granular lymphocytic leukemia in association with Sjögren's syndrome.

Acta Haematol 2010 26;124(1):5-8. Epub 2010 May 26.

Division of Hematology with BMT, Department of Oncology, University of Palermo, Palermo, Italy.

T cell large granular lymphocytic (LGL) leukemia is a rare condition accounting for 2-3% of all mature lymphoid leukemias. Here, we present the case of a 73-year-old woman presenting with neutropenia and anemia (hemoglobin 9.9 g/dl). Hematological assessment revealed the presence of a T cell LGL leukemia. At the time of T cell LGL leukemia diagnosis, the patient developed xerophthalmia and xerostomia, and a diagnosis of Sjögren's syndrome was made following salivary gland biopsy. The finding of large granular lymphocytes in the context of autoimmune disorders is well-known, though it often occurs with rheumatoid arthritis or in association with a positive autoantibody titer in the absence of an overt clinical picture. The concomitant presentation of T cell LGL leukemia with Sjögren's syndrome is a rare event which is worth reporting. Our patient was managed with immunosuppressive therapy and is still alive.
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http://dx.doi.org/10.1159/000314900DOI Listing
August 2010

Humoral immunotherapy of multiple myeloma: perspectives and perplexities.

Expert Opin Biol Ther 2010 Jun;10(6):863-73

Dipartimento di Patologia Umana, Università degli Studi di Palermo, Via del Vespro 129, 90127 Palermo, Italia.

Importance Of The Field: Multiple myeloma (MM) is a hematological malignancy still remaining incurable despite the various therapies available, mainly because of the high fraction of refractory/relapsing cases. Therefore, the development of novel therapeutic approaches is urgently needed to overcome conventional treatment resistance.

Areas Covered In This Review: In the era of targeted therapies, treatments combining a high specificity for neoplastic cells and the capability to interfere with environmental signals should be regarded as the weapons of choice. Monoclonal antibody (mAb)-based humoral immunotherapy could satisfy both these requirements when applied to MM. Indeed, many of the molecules expressed on MM cells, such as CD38, CD40, CD49d, CD138 and CD162 are involved in the adhesive dynamics regulating the crosstalk between MM and the BM-microenvironment.

What The Reader Will Gain: In this study we review those MM-associated molecules that have shown promising antitumor effects as targets of specific mAbs in preclinical settings, thus deserving to be considered for clinical investigation.

Take Home Message: mAbs directed against MM-associated adhesion markers should be taken into account in clinical practice, since they could possibly represent the best available combination of tumor cytotoxicity, environmental signal deprivation and immune system redirection.
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http://dx.doi.org/10.1517/14712591003774063DOI Listing
June 2010

CD146(+) bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis.

Haematologica 2009 Jan 23;94(1):127-30. Epub 2008 Nov 23.

Department of Human Pathology, University of Palermo, Palermo, Italy.

CD146(+) bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146(+) bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146(+) cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (rho=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a mural cell function, such cells also displayed smooth-muscle actin expression. Our data providing evidence of CD146(+) cell involvement in bone marrow stromal changes occurring in primary myelofibrosis are consistent with the capability of these cells to participate in fiber deposition, angiogenesis, and bone formation. They could also represent rationale for new therapies targeting the bone marrow stroma in primary myelofibrosis.
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http://dx.doi.org/10.3324/haematol.13598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625423PMC
January 2009