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ABSTRACT: OBJECTIVES: The clinical usefulness of serum free light chains (FLCs) measurement in the management of patient with plasma cell proliferative disorders has been reported in several papers, and most clinical studies uses the reference ranges declared by the manufacturer. Aim of the present study was to evaluate the reproducibility of FLCs immunoassay and to validate the reference range, before introducing it in routine setting. DESIGN AND METHODS: Internal quality control materials and a pool from fresh serum samples were used to evaluate the imprecision; 162 fresh sera from healthy blood donors were analyzed to evaluate the reference range for FLCs. In order to verify the κ/λ FLC ratio, 43 sera from patients with polyclonal hypergammaglobulinemia were tested. The FLCs immunoassay was performed using a nephelometer with the Freelite reagents. RESULTS: The imprecision studies performed using a serum pool tested with two different lots of reagents showed a mean CV of 16.09% for κFLC and of 16.72% for λFLC. Lower CV%s and different mean values were found by calculating the results from each specific lot separately, while different results were obtained using the control materials provided by the manufacturer. In reference subjects, the 2.5-97.5th percentiles were found to be 4.52 - 22.33 and 4.84 -21.88 mg/L for κFLCs and λFLC, respectively. The range for κ/λ ratio (0.65-2.36) was validated with the values obtained from subjects with polyclonal hypergammaglobulinemia. On retesting 15 samples from blood donor subjects with a different lot of reagents, a mean bias percentages of 17.60 for κFLC and 15.26 for λFLC were obtained. CONCLUSIONS: These findings confirm the lot-to-lot variability of the FLCs assays also in the measurement of polyclonal light chains, as well as the need to carefully validate the reference values.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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ABSTRACT: A 46-year-old man with progressive visual loss underwent brain MRI showing multifocal nodular pachymeningeal thickening involving optic nerve meninges bilaterally and internal acoustic meatus dura mater (figure 1). Diffuse meningiomatosis was diagnosed and radiation therapy was given with symptom stabilization. Four years later, left hearing loss and right hypoacusia occurred, with slight transient improvement after high-dose dexamethasone. Serum immunoglobulin (Ig)G4 was increased. CSF analysis showed increased protein, oligoclonal IgG, plasma cells, and lymphocytes. Cerebral biopsy showed meningeal plasma-cell granuloma with IgG4-positive polyclonal plasma cells and B-lymphocyte infiltration (figure 2). IgG4-related disease was diagnosed.(1) Rituximab was unsuccessful. IgG4-related disease is a fibroinflammatory, multiorgan condition characterized by tumefactive lesions and lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells that may affect every organ; serum IgG4 may be elevated. Although IgG4-related disease with exclusive multifocal CNS localization is extremely rare and often misdiagnosed,(2-4) it should be considered in the differential diagnosis of tumor-like intracranial lesions and hyperthrophic pachymeningitis.
Neurology 01/2013; 80(4):e40-1. · 8.31 Impact Factor
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ABSTRACT: Abstract We report on a young pregnant woman developing distal leg edema and hypoalbuminemia, who was lately diagnosed with AL amyloidosis. Fetal growth retardation led to a caesarian section in the 27th week of gestation. A live birth healthy female, 710 g weight, was admitted to the neonatal intensive care unit and survived. Thereafter the mother underwent specific chemotherapy achieving only a partial and transient response, and eventually died due to sepsis. Interestingly, amyloidotic material was found on the maternal but not on the fetal side of the placenta. Experimental data show suppression of AA amyloid formation during pregnancy and suggest a protective role of the placenta on the offspring. However, most reported cases deal with pregnant women diagnosed with AA amyloidosis associated with Familial Mediterranean Fever and describe growth retardation of the fetus, worsening renal function and preeclampsia. To the best of our knowledge, this is the first report of AL amyloidosis diagnosed in a pregnant woman. In our patient, as well as in the other reported cases, amyloidosis during pregnancy has been confirmed to be an ominous condition. Therefore mild leg edema and proteinuria during pregnancy, though a common finding, may not be innocent. Abbreviations: cTn1: cardiac troponin I; FMF: familial Mediterranean fever; sFLC: serum free light chain; CC: third abbreviation.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 12/2012; · 2.12 Impact Factor
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Journal of Neurology 05/2012; 259(10):2226-8. · 3.47 Impact Factor
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Sabrina Manni,
Alessandra Brancalion,
Laura Quotti Tubi,
Anna Colpo,
Laura Pavan,
Anna Cabrelle,
Elisa Ave,
Fortunato Zaffino,
Giovanni Di Maira,
Maria Ruzzene, Fausto Adami,
Renato Zambello,
Maria Rita Pitari,
Pierfrancesco Tassone,
Lorenzo A Pinna,
Carmela Gurrieri,
Gianpietro Semenzato,
Francesco Piazza
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ABSTRACT: Protein kinase CK2 promotes multiple myeloma cell growth by regulating critical signaling pathways. CK2 also modulates proper HSP90-dependent client protein folding and maturation by phosphorylating its co-chaperone CDC37. Because the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is central in myeloma pathogenesis, we tested the hypothesis that the CK2/CDC37/HSP90 axis could be involved in UPR in myeloma cells.
We analyzed CK2 activity upon ER stress, the effects of its inactivation on the UPR pathways and on ER stress-induced apoptosis. The consequences of CK2 plus HSP90 inhibition on myeloma cell growth in vitro and in vivo and CK2 regulation of HSP90-triggered UPR were determined.
CK2 partly localized to the ER and ER stress triggered its kinase activity. CK2 inhibition reduced the levels of the ER stress sensors IRE1α and BIP/GRP78, increased phosphorylation of PERK and EIF2α, and enhanced ER stress-induced apoptosis. Simultaneous inactivation of CK2 and HSP90 resulted in a synergic anti-myeloma effect (combination index = 0.291) and in much stronger alterations of the UPR pathways as compared with the single inhibition of the two molecules. Cytotoxicity from HSP90 and CK2 targeting was present in a myeloma microenvironment model, on plasma cells from patients with myeloma and in an in vivo mouse xenograft model. Mechanistically, CK2 inhibition led to a reduction of IRE1α/HSP90/CDC37 complexes in multiple myeloma cells.
Our results place CK2 as a novel regulator of the ER stress/UPR cascades and HSP90 function in myeloma cells and offer the groundwork to design novel combination treatments for this disease.
Clinical Cancer Research 02/2012; 18(7):1888-900. · 7.74 Impact Factor
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ABSTRACT: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease
American Journal of Hematology 02/2012; 87(5):539-41. · 4.67 Impact Factor
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Alessandra Galioto,
Filippo Morando,
Silvia Rosi,
Mirko Schipilliti,
Silvano Fasolato,
Marta Magrin,
Anna Chiara Frigo, Fausto Adami,
Marta Cavallin,
Giacomo Zanus,
Mario Plebani,
Antonietta Romano,
Antonietta Sticca,
Umberto Cillo,
Angelo Gatta,
Paolo Angeli
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ABSTRACT: The aims of the study were to evaluate (i) the prevalence of MGUS in patients after liver transplantation (LT), (ii) the role of MGUS as a risk factor for malignancy and other medical complications after LT. One hundred and fifty consecutive patients were included in the study and followed prospectively after LT for more than 18 months. Eighteen patients had MGUS before LT, whereas 49 patients developed MGUS after LT ('de novo' MGUS). Thirty-six of these patients showed a MGUS along all the follow up after LT ('permanent' MGUS). In 31 patients, MGUS disappeared after LT ('transient' MGUS). No patient with MGUS developed B-malignant lymphoproliferative disorder and only one patient developed a myeloma after LT. Comparing patients with 'permanent' MGUS to patients with 'transient' MGUS or without MGUS after LT, the former group showed a higher rate of serious infections (30% versus 13%, P = 0.01), chronic kidney disease (CKD) (75% versus 44%, P = 0.001) and mortality (33% versus 17%, P = 0.04). Permanent MGUS was confirmed as an independent risk factor for serious infections and CKD by multivariate analysis. Permanent MGUS after LT does not entail a significant risk of malignancy, but it is associated with a higher risk of serious infections and CKD.
Transplant International 01/2012; 25(1):25-33. · 2.92 Impact Factor
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Mycoses 07/2011; 54(4):365-9. · 2.25 Impact Factor
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Chiara Briani,
Marny Fedrigo,
Renzo Manara,
Chiara Castellani,
Renato Zambello,
Valentina Citton,
Marta Campagnolo,
Chiara Dalla Torre,
Marta Lucchetta,
Enrico Orvieto,
Antonino Rotilio,
Sabrina Marangoni,
Stefania Magi,
Davide Pareyson,
Igor Florio,
Elena Pegoraro,
Gaetano Thiene,
Leontino Battistin, Fausto Adami,
Annalisa Angelini
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ABSTRACT: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare plasma cell disease. Vascular endothelial growth factor (VEGF) seems to play a pathogenic role. Peripheral neuropathy is the main neurological feature. Cranial pachymeningitis has occasionally been reported, but no histopathological studies have been performed. The authors extensively evaluated the central nervous system MRI in 11 patients (seven men, four women; mean age at diagnosis 54.45 years) with POEMS syndrome. In two patients, meningeal histopathology with staining for VEGF and VEGF receptor was performed, and pachymeningeal involvement characterised at histopathological, immunohistochemical and confocal microscopy levels. Nine patients presented with cranial pachymeningitis. One patient suffered from migraine, and none complained of cranial nerve palsies or visual loss. None showed any MRI signs of spinal pachymeningitis. No correlation was found with disease duration and VEGF serum level. Histopathology showed hyperplasia of meningothelial cells, neovascularisation and obstructive vessel remodelling, without inflammation. VEGF and VEGF receptor were strongly coexpressed on endothelium, smooth-muscle cells of arterioles and meningothelial cells. In conclusion, POEMS patients present a high prevalence of meningeal involvement. The histological changes, different from those present in chronic pachymeningitis of other aetiology, suggest a possible VEGF role in the pathogenesis of the meningeal remodelling.
Journal of neurology, neurosurgery, and psychiatry 06/2011; 83(1):33-7. · 4.87 Impact Factor
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Chiara Briani,
Gian Maria Fabrizi,
Susanna Ruggero,
Chiara Dalla Torre,
Moreno Ferrarini,
Marta Campagnolo,
Tiziana Cavallaro,
Sergio Ferrari,
Marina Scarlato,
Federica Taioli, Fausto Adami
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ABSTRACT: POEMS syndrome and amyloidosis are rare plasma cell diseases that share common features, including polyneuropathy. The aim of this study was to investigate serum vascular endothelial growth factor (sVEGF) in patients with amyloidosis and to evaluate changes in response to treatment. Twenty-five patients [17 primary light-chain amyloidosis (AL-A), 7 transthyretin amyloidosis (TTR-A), 1 senile wild-type TTR-A] were studied. sVEGF was analyzed by ELISA. Sera from 8 myeloma and 7 POEMS patients were also evaluated. The median sVEGF level was 420 pg/ml in AL-A and 179 pg/ml in TTR-A patients; this was significantly lower than in POEMS syndrome (median 2580 pg/ml, P = 0.0002 and 0.001, respectively). sVEGF of AL-A patients showed no changes in response to treatment. sVEGF was not increased in amyloid patients regardless of neuropathy, and did not mirror the course of the disease. sVEGF should be tested in patients with overlapping and atypical clinical features.
Muscle & Nerve 02/2011; 43(2):164-7. · 2.37 Impact Factor
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Francesco Piazza,
Sabrina Manni,
Laura Quotti Tubi,
Barbara Montini,
Laura Pavan,
Anna Colpo,
Marianna Gnoato,
Anna Cabrelle, Fausto Adami,
Renato Zambello,
Livio Trentin,
Carmela Gurrieri,
Gianpietro Semenzato
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ABSTRACT: Glycogen Synthase Kinase-3 (GSK-3) α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM).
GSK-3 α and β expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis.
GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself.
These data suggest that in MM cells GSK-3α and β i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors.
BMC Cancer 10/2010; 10:526. · 3.01 Impact Factor
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American Journal of Hematology 02/2010; 85(2):131-2. · 4.67 Impact Factor
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Francesco Piazza,
Sabrina Manni,
Laura Tubi,
Barbara Montini,
Laura Pavan,
Anna Colpo,
Marianna Gnoato,
Anna Cabrelle, Fausto Adami,
Renato Zambello,
Livio Trentin,
Carmela Gurrieri,
Gianpietro Semenzato
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ABSTRACT: Abstract Background Glycogen Synthase Kinase-3 (GSK-3) α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM). Methods GSK-3 α and β expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis. Results GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. Conclusions These data suggest that in MM cells GSK-3α and β i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors.
BMC Cancer. 01/2010;
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ABSTRACT: In up to 50% of chronic idiopathic axonal neuropathies, an underlying diagnosis may be identified, including hereditary neuropathy. Charcot-Marie-Tooth disease (CMT) is clinically and genetically heterogeneous. Several mutations in the myelin protein zero (MPZ) gene have been associated with different CMT phenotypes, including classical demyelinating CMT1B and the axonal form of the disease. Primary amyloidosis, a rare disease where the amyloid is formed by the N-terminal portion of a monoclonal immunoglobulin light chain, may be complicated by polyneuropathy. We report a patient who was incorrectly diagnosed with amyloid neuropathy, but was found to have axonal CMT1B only after sural nerve biopsy ruled out an acquired amyloid neuropathy.
Muscle & Nerve 08/2008; 38(1):921-3. · 2.37 Impact Factor
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Livio Trentin,
Marta Miorin,
Monica Facco,
Ilenia Baesso,
Samuela Carraro,
Anna Cabrelle,
Nilla Maschio,
Michela Bortoli,
Gianni Binotto,
Francesco Piazza, Fausto Adami,
Renato Zambello,
Carlo Agostini,
Gianpietro Semenzato
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ABSTRACT: Chemokines and their receptors play a pivotal role in the regulation of B-lymphocyte trafficking. This study was aimed at investigating the pattern of chemokine receptor expression, including CCR1 to CCR3, CCR5 to CCR7, CXCR1 to CXCR5, and the migration ability of multiple myeloma (MM) plasma cells (PC). PC were recovered from the bone marrow (BM) of 29 MM patients, extramedullary sites of 10 patients and the BM of five controls. Flow cytometry analysis showed that the receptors mainly expressed on malignant BM PC were represented by CXCR4 (70% of patients), CCR1 (25%), CCR2 (25%), CCR5 (17%) and CXCR3 (20%), while other receptors were commonly lacking. The analysis performed on extramedullary (peripheral blood and pleural effusion) malignant PC demonstrated that the most represented receptors were CXCR4 (100%), CCR2 (66%) and CXCR1 (60%). The migratory capability of malignant PC at resting conditions identified three groups of patients with different migration (low, intermediate and high). As CXCR4 was the relevant chemokine receptor expressed by MM PC, its ligand CXCL12 induced their migration. These data suggest that malignant PC from MM display different chemokine receptor profiles and that CXCR4 is fully functional and might play a role in the spreading of the disease.
British Journal of Haematology 10/2007; 138(5):594-602. · 4.94 Impact Factor
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ABSTRACT: The aim of this study was to assess the performance of experimental software (Qontraxt) intended to provide automated quantification of sonographic signal intensity, which is related to the contrast enhancement of lymph node tissue, to differentiate benign from malignant lymph nodes.
In 31 patients (age range, 24-86 years; mean age +/- SD, 53.6 +/- 14.4 years) a single lymph node per patient was evaluated on sonography after the administration of sulfur hexafluoride-filled microbubbles. The stored sonographic images were analyzed and processed into chromatic maps that had numeric values related to the amount of contrast. The lymph node regions in which the increase of signal intensity values with respect to baseline were highest (maximum signal intensity value [SImax]) and lowest (minimum signal intensity value [SImin]) were identified, and the corresponding numeric data were stored. Statistical analyses were performed by means of the Student's t test; a p value of less than 0.05 was considered to be statistically significant.
Histopathologic analysis revealed metastatic lesions in 12 of the 31 lymph nodes; the remaining 19 were benign (16 reactive lymph nodes, two cases of granulomatous lymphadenitis, and one case of tubercular lymphadenitis). Values obtained from the SImax regions showed no consistent difference between benign and malignant lymph nodes; on the other hand, values from the SImin regions comparing baseline and maximal contrast-enhanced values were significantly different in the two groups (p < 0.001). Confidence for characterization of malignancy was significant using the difference between values from SImax and SImin regions, with the higher diagnostic value from 24 to 31 inclusive: sensitivity, 92% (11/12); specificity, 89% (17/19); positive predictive value, 85% (11/13); and accuracy, 90% (28/31).
The software being tested proved to be useful in differentiating benign from metastatic lymph nodes on the basis of the quantitative data it provided.
American Journal of Roentgenology 05/2007; 188(4):977-83. · 2.78 Impact Factor
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Francesco A Piazza,
Maria Ruzzene,
Carmela Gurrieri,
Barbara Montini,
Luca Bonanni,
Gino Chioetto,
Giovanni Di Maira,
Francesca Barbon,
Anna Cabrelle,
Renato Zambello, Fausto Adami,
Livio Trentin,
Lorenzo A Pinna,
Gianpietro Semenzato
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ABSTRACT: Casein kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase that regulates relevant biologic processes, many of which are dysregulated in malignant plasma cells. Here we investigated its role in multiple myeloma (MM). Analysis of MM cell lines and highly purified malignant plasma cells in patients with MM revealed higher protein and CK2 activity levels than in controls (normal in vitro-generated polyclonal plasma cells and B lymphocytes). The inhibition of CK2 with specific synthetic compounds or by means of RNA interference caused a cytotoxic effect on MM plasma cells that could not be overcome by IL-6 or IGF-I and that was associated with the activation of extrinsic and intrinsic caspase cascades. CK2 blockage lowered the sensitivity threshold of MM plasma cells to the cytotoxic effect of melphalan. CK2 inhibition also resulted in impaired IL-6-dependent STAT3 activation and in decreased basal and TNF-alpha-dependent I kappaB alpha degradation and NF-kappaB-driven transcription. Our data show that CK2 was involved in the pathophysiology of MM, suggesting that it might play a crucial role in controlling survival and sensitivity to chemotherapeutics of malignant plasma cells.
Blood 10/2006; 108(5):1698-707. · 9.90 Impact Factor
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Haematologica 06/2006; 91(5 Suppl):ECR10. · 6.42 Impact Factor
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Livio Trentin,
Anna Cabrelle,
Monica Facco,
Davide Carollo,
Marta Miorin,
Alicia Tosoni,
Paola Pizzo,
Gianni Binotto,
Linda Nicolardi,
Renato Zambello, Fausto Adami,
Carlo Agostini,
Gianpietro Semenzato
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ABSTRACT: This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation.
Blood 08/2004; 104(2):502-8. · 9.90 Impact Factor
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ABSTRACT: To evaluate the contribution of continuous mode contrast-enhanced harmonic ultrasonography (CE-HUS) with a second-generation contrast agent to the characterization of superficial lymphadenopathies with respect to conventional ultrasonographic techniques (B-mode and power Doppler).
Fifty-six lymph nodes from 45 patients were studied both by conventional techniques and by CE-HUS. The dimensions, intranodal architecture, margins, and location of vessels were evaluated. Subsequently, all the lymph nodes were examined by CE-HUS, and enhancement of echogenicity was evaluated. The diagnoses obtained by means of fine-needle aspiration cytologic examination, surgical biopsy, or both were compared with those obtained by ultrasonography.
Of the lymph nodes examined, 30 were benign and 26 were malignant (18 metastases and 8 non-Hodgkin lymphomas). The study using CE-HUS showed intense homogeneous enhancement in 28 of 30 reactive lymph nodes; perfusion defects in 17, of which 15 were neoplastic and 2 were inflammatory; intense but inhomogeneous speckled enhancement in the early arterial phase in 5 cases of lymphoma; and, last, scarce or absent intranodal enhancement in 4 metastases. The specificity, sensitivity, and accuracy of conventional techniques in differentiation between benign and malignant lymph nodes were 76%, 80%, and 78% versus 93%, 92%, and 92.8% for CE-HUS. The increase in correct diagnoses was significant (P = .05) when conventional ultrasonography was tested against CE-HUS.
Superficial lymph nodes can be characterized as being neoplastic or benign with a high degree of diagnostic accuracy on the basis of the perfusion characteristics evaluated by CE-HUS. This technique has been shown to afford a higher degree of accuracy than currently obtainable by any other ultrasonographic technique.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 07/2004; 23(6):829-36. · 1.25 Impact Factor
