Publications by authors named "Federica De Marco"

19 Publications

  • Page 1 of 1

Involvement of SUT1 and SUT2 Sugar Transporters in the Impairment of Sugar Transport and Changes in Phloem Exudate Contents in Phytoplasma-Infected Plants.

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Institut Jean-Pierre Bourgin, INRAE, AgroParisTech, Université Paris-Saclay, 78000 Versailles, France.

Phytoplasmas inhabit phloem sieve elements and cause abnormal growth and altered sugar partitioning. However, how they interact with phloem functions is not clearly known. The phloem responses were investigated in tomatoes infected by " Phytoplasma solani" at the beginning of the symptomatic stage, the first symptoms appearing in the newly emerged leaf at the stem apex. Antisense lines impaired in the phloem sucrose transporters SUT1 and SUT2 were included. In symptomatic sink leaves, leaf curling was associated with higher starch accumulation and the expression of defense genes. The analysis of leaf midribs of symptomatic leaves indicated that transcript levels for genes acting in the glycolysis and peroxisome metabolism differed from these in noninfected plants. The phytoplasma also multiplied in the three lower source leaves, even if it was not associated with the symptoms. In these leaves, the rate of phloem sucrose exudation was lower for infected plants. Metabolite profiling of phloem sap-enriched exudates revealed that glycolate and aspartate levels were affected by the infection. Their levels were also affected in the noninfected - and -antisense lines. The findings suggest the role of sugar transporters in the responses to infection and describe the consequences of impaired sugar transport on the primary metabolism.
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http://dx.doi.org/10.3390/ijms22020745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828548PMC
January 2021

Post Vaccinal Temporary Sensorineural Hearing Loss.

Int J Environ Res Public Health 2018 08 19;15(8). Epub 2018 Aug 19.

Department of Anatomy, Histology, Medical-Legal and the Orthopedics, Specialty School of Occupational Medicine, Unit of Occupational Medicine, Sapienza University of Rome, 00161 Rome, Italy.

In our systematic research we identified four studies concerning the onset of neurological adverse events following vaccination and two excluding this association. A 33-year-old Italian man, belonging to the Italian Army was hospitalized because he suffered from vertigo, nausea and sudden right hearing loss not classified (NDD), that set in 24 h after the administration of tetanus-diphtheria and meningococcal vaccines. Some neurological events arising after vaccination are very difficult to treat. In our case, the functional recovery on low and medium frequencies was possible about 6 months after the morbid event.
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http://dx.doi.org/10.3390/ijerph15081780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121486PMC
August 2018

The rendez-vous of mobile sieve-element and abundant companion-cell proteins.

Curr Opin Plant Biol 2018 06 25;43:108-112. Epub 2018 Apr 25.

Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, 78000 Versailles, France. Electronic address:

Thousands of sieve tube exudate proteins (STEP) have now been identified and predicted to fulfill a diversity of functions. However, most STEPs should be considered putative, since methods to collect sieve tube exudates have many technical drawbacks, and advanced functional characterization will be required to distinguish contaminant from bonafide proteins, and determine the latter's location and activity in sieve elements (SE). One major challenge is to develop new approaches to elucidate the function of these SE proteins, which in turn, is expected to shed light on intriguing aspects of SE cell biology.
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http://dx.doi.org/10.1016/j.pbi.2018.04.008DOI Listing
June 2018

Workers exposed to low levels of benzene present in urban air: Assessment of peripheral blood count variations.

Chemosphere 2016 Jun 21;152:392-8. Epub 2016 Mar 21.

University of Rome "La Sapienza", Department of Anatomy, Histology, Medical-Legal and the Orthopedics, Unit of Occupational Medicine, Viale Regina Elena 336, 00161 Rome, Italy.

Background: Few studies in the literature have examined the effects of benzene on blood cells.

Aim: The aim of this study was to evaluate the possible correlation between the blood benzene levels and the blood cell counts.

Materials And Methods: From a population of 2658 workers, we studied a group of 215 subjects. Each worker underwent blood sampling for the assessment of the blood benzene levels and the blood cell counts. The Mann-Whitney U test for two-mode variables and the Kruskal-Wallis test for more-than-two-mode variables were performed on all subjects. We estimated the Pearson correlation index between the variables in the total sample and the subgroups divided according to sex, the smoking habit, and job. After the main confounding factors were evaluated, multiple linear regression was performed on both the total sample and the subgroups.

Results: A significant inverse correlation was found among the blood benzene levels and the white blood cells, lymphocytes, and neutrophils in traffic policemen, motorcyclists, and other outdoor workers. We did not find any significant correlation with any other parameters of blood cell count.

Discussion And Conclusions: Our results, which must be considered preliminary, indicate that increased blood benzene levels in outdoor workers lead to decreased counts of white blood cells, neutrophils, and lymphocytes, because of possible immune effects. These are worth investigating in the future by specific immune tests.
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http://dx.doi.org/10.1016/j.chemosphere.2016.01.096DOI Listing
June 2016

OHMS**: Phytoplasmas dictate changes in sieve-element ultrastructure to accommodate their requirements for nutrition, multiplication and translocation.

Plant Signal Behav 2016 ;11(2):e1138191

b Department of Phytopathology and Applied Zoology , Justus Liebig University , Giessen , Germany.

Phytoplasmas are among the most recently discovered plant pathogenic microorganisms so, many traits of the interactions with host plants and insect vectors are still unclear and need to be investigated. At now, it is impossible to determine the precise sequences leading to the onset of the relationship with the plant host cell. It is still unclear how phytoplasmas, located in the phloem sieve elements, exploit host cell to draw nutrition for their metabolism, growth and multiplication. In this work, basing on microscopical observations, we give insight about the structural interactions established by phytoplasmas and the sieve element plasma membrane, cytoskeleton, sieve endoplasmic reticulum, speculating about a possible functional role.
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http://dx.doi.org/10.1080/15592324.2016.1138191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883841PMC
December 2016

Disruption of the Sugar Transporters AtSWEET11 and AtSWEET12 Affects Vascular Development and Freezing Tolerance in Arabidopsis.

Mol Plant 2015 Nov 8;8(11):1687-90. Epub 2015 Sep 8.

Institut National de la Research Agronomic, UMR1318 INRA-AgroParisTech, Institut Jean-Pierre Bourgin, Univ. Paris-Sud, F-78000 Versailles, France; Department of Plant Physiology, Umeå Plant Science Centre, Umeå University, S-90187 Umeå, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.molp.2015.08.007DOI Listing
November 2015

Phytoplasma infection in tomato is associated with re-organization of plasma membrane, ER stacks, and actin filaments in sieve elements.

Front Plant Sci 2015 19;6:650. Epub 2015 Aug 19.

Department of Agricultural and Environmental Sciences, University of Udine Udine, Italy.

Phytoplasmas, biotrophic wall-less prokaryotes, only reside in sieve elements of their host plants. The essentials of the intimate interaction between phytoplasmas and their hosts are poorly understood, which calls for research on potential ultrastructural modifications. We investigated modifications of the sieve-element ultrastructure induced in tomato plants by 'Candidatus Phytoplasma solani,' the pathogen associated with the stolbur disease. Phytoplasma infection induces a drastic re-organization of sieve-element substructures including changes in plasma membrane surface and distortion of the sieve-element reticulum. Observations of healthy and stolbur-diseased plants provided evidence for the emergence of structural links between sieve-element plasma membrane and phytoplasmas. One-sided actin aggregates on the phytoplasma surface also inferred a connection between phytoplasma and sieve-element cytoskeleton. Actin filaments displaced from the sieve-element mictoplasm to the surface of the phytoplasmas in infected sieve elements. Western blot analysis revealed a decrease of actin and an increase of ER-resident chaperone luminal binding protein (BiP) in midribs of phytoplasma-infected plants. Collectively, the studies provided novel insights into ultrastructural responses of host sieve elements to phloem-restricted prokaryotes.
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http://dx.doi.org/10.3389/fpls.2015.00650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541602PMC
September 2015

Correlation between Visual Acuity, Inner Segment/Outer Segment Junction, and Cone Outer Segment Tips Line Integrity in Uveitic Macular Edema.

Biomed Res Int 2015 8;2015:853728. Epub 2015 Jun 8.

Chorioretinal Diagnostic Service UOC Ophthalmology C, Department of Ophthalmology, "Sapienza" University of Rome, Viale del Policlinico, 15500161 Rome, Italy.

Purpose: To investigate the correlation between best-corrected visual acuity (BCVA), the foveal inner segment/outer segment (IS/OS) junction or ellipsoid portion of inner segment (EPIS/ellipsoid zone), and the cone outer segment tips (COST) line or interdigitation zone integrity in eyes with uveitic macular edema (ME).

Method: A retrospective observational study involving all patients from January 2012 to December 2013 with uveitic ME was performed. All patients underwent BCVA using Snellen charts spectral-domain optical coherence tomography (SD-OCT) examination using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany).

Results: Fifty-two eyes from 45 patients were included in this study. Multivariate analysis showed a negative correlation between BCVA and the central retinal subfield thickness (CST), the cystoid pattern of edema, and the interdigitation zone interruption. Univariate logistic analysis showed a strong correlation between the ellipsoid zone and the interdigitation zone integrity.

Conclusions: The ellipsoid zone defect, the interdigitation zone interruption, and the CST are correlated with poor vision. Visual acuity is also strongly affected by the cystoid pattern. The interdigitation zone integrity appears to be the most important factor in the visual prognosis of uveitic ME.
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http://dx.doi.org/10.1155/2015/853728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475742PMC
April 2016

Follow-Up Study of Over Three Years of Patients with Uveitis after Cataract Phacoemulsification: Outcomes and Complications.

Semin Ophthalmol 2016 20;31(6):532-41. Epub 2015 Feb 20.

a Department of Ophthalmology , University of Rome "Sapienza" , Rome , Italy.

Purpose: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification.

Methods: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis.

Results: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r = 0.6; p = 0.00) and mostly related to patients who presented more than one postoperative relapse/year (r = 0.2; p = 0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p = 0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY).

Conclusion: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are most frequent in Fuchs uveitis. The postoperative visual acuity result was good among all the uveitis groups.
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http://dx.doi.org/10.3109/08820538.2015.1009554DOI Listing
February 2017

Contact Lens Care among Teenage Students in Italy: A Cross-Sectional Study.

Semin Ophthalmol 2016 9;31(3):226-32. Epub 2014 Oct 9.

a Ocular Immunovirology Service, Department of Ophthalmology, "Sapienza" University of Rome , Rome , Italy.

Aim: To assess the attitude and practice of contact lens (CL) wearers among teenage school students and to evaluate how much the teenagers adhere to the CL care procedures according to the proper care of CL guidelines.

Methods: A cross-sectional descriptive study of Italian teenagers from high schools in Rome who wear CL. We inquired about the different aspects of CL care through a questionnaire.

Results: We investigated 3,106 students from high schools in Rome (2% of all Roman high school students), 293 of whom wore CL (9%); 151 (52%) of participants responded, 42 (27.8%) male and 109 (72.8%) female. The mean age was 16.4 ± 1.6 years. 79.5% of students were daily users. 45.7% wore CL more than nine hours/day. 87.4% wore soft CL. 33.1% wore disposable CL; 7.9% weekly CL, 55% monthly CL. Thirty-four percent wore disposable lenses twice or more. 14.5% of students did not wash their hands before handling CL and 52.3% wore CL after it had fallen in the sink. 39.7% rubbed and cleaned CL before storing it. 10% used expired lens care solutions. Only 31.1% changed CL cases every three months. 38.4% wore CL in a swimming pool. 61.6% were having problems: redness (13.9%), itching (7.9%), and foreign body sensation (29.1%).

Conclusion: Many students don't properly care for their CL. Education regarding proper care and management of CL among users is advised in view of frequency of symptoms and complications reported.
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http://dx.doi.org/10.3109/08820538.2014.962155DOI Listing
February 2017

Recovery from stolbur disease in grapevine involves changes in sugar transport and metabolism.

Front Plant Sci 2013 4;4:171. Epub 2013 Jun 4.

Department of Agricultural and Environmental Sciences, University of Udine Udine, Italy.

Grapevine can be severely affected by phytoplasmas, which are phytopathogenic Mollicutes invading the sieve elements of the host plant. The biochemical and molecular relationships between phytoplasmas and their hosts remain largely unexplored. Equally unknown is an interesting aspect of the pathogen-plant interaction called "recovery," which is a spontaneous remission of symptoms in previously symptomatic plants. Recovered plants develop resistance mechanisms correlated with ultrastructural and biochemical changes in the sieve elements. Callose as well as sugars are involved in several plant defense processes and signaling. In the present work we have examined the possible involvement of callose, as well as callose synthase, sugar transporter, and cell wall invertase genes, during the infection and after "recovery" of grapevine from bois noir (BN). Ultrastructural investigation of leaf tissue showed that callose accumulated in the sieve elements of diseased grapevine; moreover, two genes encoding for callose synthase were up-regulated in the infected leaves. Regarding sucrose, expression analysis showed that sucrose transport and cleavage were severely affected by BN phytoplasma, which induced the establishment of a carbohydrate sink in the source leaf, and was analogous to other obligate biotrophs that acquire most of their nutrients from the host plant. Interestingly, whereas in recovered plants the transcript level of sucrose synthase was similar to healthy plants, sucrose transporters as well as cell wall invertase were expressed to a greater degree in recovered leaves than in healthy ones. Recovered plants seem to acquire structural and molecular changes leading to increases in sucrose transport ability and defense signaling.
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http://dx.doi.org/10.3389/fpls.2013.00171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671194PMC
June 2013

Phytoplasma-triggered Ca(2+) influx is involved in sieve-tube blockage.

Mol Plant Microbe Interact 2013 Apr;26(4):379-86

Department of Agriculture and Environmental Sciences, University of Udine, Udine, Italy.

Phytoplasmas are obligate, phloem-restricted phytopathogens that are disseminated by phloem-sap-sucking insects. Phytoplasma infection severely impairs assimilate translocation in host plants and might be responsible for massive changes in phloem physiology. Methods to study phytoplasma- induced changes thus far provoked massive, native occlusion artifacts in sieve tubes. Hence, phytoplasma-phloem relationships were investigated here in intact Vicia faba host plants using a set of vital fluorescent probes and confocal laser-scanning microscopy. We focused on the effects of phytoplasma infection on phloem mass-flow performance and evaluated whether phytoplasmas induce sieve-plate occlusion. Apparently, phytoplasma infection brings about Ca(2+) influx into sieve tubes, leading to sieve-plate occlusion by callose deposition or protein plugging. In addition, Ca(2+) influx may confer cell wall thickening of conducting elements. In conclusion, phytoplasma effectors may cause gating of sieve-element Ca(2+) channels leading to sieve-tube occlusion with presumptive dramatic effects on phytoplasma spread and photoassimilate distribution.
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http://dx.doi.org/10.1094/MPMI-08-12-0207-RDOI Listing
April 2013

Laser microdissection of grapevine leaf phloem infected by stolbur reveals site-specific gene responses associated to sucrose transport and metabolism.

Plant Cell Environ 2013 Feb 7;36(2):343-55. Epub 2012 Aug 7.

Dipartimento di Scienze Agrarie e Ambientali, University of Udine, Via delle Scienze 208, I-33100 Udine, Italy.

Bois Noir is an emergent disease of grapevine that has been associated to a phytoplasma belonging to the XII-A stolbur group. In plants, phytoplasmas have been found mainly in phloem sieve elements, from where they spread moving through the pores of plates, accumulating especially in source leaves. To examine the expression of grapevine genes involved in sucrose transport and metabolism, phloem tissue, including sieve element/companion cell complexes and some parenchyma cells, was isolated from healthy and infected leaves by means of laser microdissection pressure catapulting (LMPC). Site-specific expression analysis dramatically increased sensitivity, allowing us to identify specific process components almost completely masked in whole-leaf analysis. Our findings showed decreased phloem loading through inhibition of sucrose transport and increased sucrose cleavage activity, which are metabolic changes strongly suggesting the establishment of a phytoplasma-induced switch from carbohydrate source to sink. The analysis focused at the infection site also showed a differential regulation and specificity of two pathogenesis-related thaumatin-like genes (TL4 and TL5) of the PR-5 family.
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http://dx.doi.org/10.1111/j.1365-3040.2012.02577.xDOI Listing
February 2013

Very-low-calorie diet: a quick therapeutic tool to improve β cell function in morbidly obese patients with type 2 diabetes.

Am J Clin Nutr 2012 Mar 8;95(3):609-13. Epub 2012 Feb 8.

Department of Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Caloric restriction in obese diabetic patients quickly improves glucose control, independently from weight loss. However, the early effects of a very-low-calorie diet (VLCD) on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes are still unclear.

Objective: The objective was to study the relative contributions of insulin sensitivity, insulin secretion, or both to improvement in glucose metabolism, after 1 wk of caloric restriction, in severely obese diabetic patients.

Design: Hyperglycemic clamps were performed in 14 severely obese (BMI, in kg/m(2): >40) patients with type 2 diabetes in good glucose control (glycated hemoglobin < 7.5%) before and after 7 d of a VLCD (400 kcal/d).

Results: The VLCD caused a 3.22 ± 0.56% weight loss (P < 0.001), 42.0% of which was fat loss, accompanied by decreases in fasting plasma glucose (P < 0.05) and triglycerides (P < 0.01). In parallel, the Disposition Index, which measures the body's capability to dispose of a glucose load, increased from 59.0 ± 6.3 to 75.5 ± 6.3 mL· min(-1) · m(-2) body surface area (P < 0.01), because of improvements in indexes of both first- and second-phase insulin secretion (P < 0.02), but with no changes in insulin sensitivity (P = 0.33).

Conclusion: The marked improvement in metabolic profile, observed in severely obese patients with type 2 diabetes after a 7-d VLCD, was primarily due to the amelioration of β cell function, whereas no contribution of insulin sensitivity was shown. This trial was registered at www.clinicaltrials.gov as NCT01447524.
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http://dx.doi.org/10.3945/ajcn.111.023697DOI Listing
March 2012

Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage.

Blood 2008 Apr 31;111(8):4004-13. Epub 2008 Jan 31.

Divisione Universitaria di Ematologia, Cattedra di Ematologia, Torino, Italy.

In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.
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http://dx.doi.org/10.1182/blood-2007-10-116749DOI Listing
April 2008

Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.

Biol Blood Marrow Transplant 2006 Dec;12(12):1270-6

Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Torino, Italy.

Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical relapse. M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by direct sequencing of the clonal rearrangement. Minimal residual disease was monitored by qualitative and real-time quantitative PCR. All patients received 4 courses of rituximab, with 2 additional infusions if PCR positivity remained. After 4-6 courses of rituximab, all patients re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab. Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.
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http://dx.doi.org/10.1016/j.bbmt.2006.07.007DOI Listing
December 2006

Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations.

Exp Hematol 2006 Dec;34(12):1680-6

Divisione di Ematologia Dipartimento di Medicina ed Oncologia Sperimentale, Universita' di Torino-A. O. San Giovanni Battista della Citta' di Torino, Torino, Italy.

Objective: Nonlymphoma-associated bcl-2/IgH rearrangements (NLABRs) are frequently amplified by PCR in blood of lymphoma-free subjects (LFS), but the temporal kinetics and phenotypic nature of NLABR-positive cells are unknown. To address these issues we prospectively monitored a panel of NLABR-positive LFS.

Methods: LFS have been studied by nested PCR, real-time PCR, and DNA sequencing. Cell selection studies were also performed to define the nature of NLABR-bearing clones.

Results: Of 125 donors, 16 (12.8%) were found to be bcl-2/IgH positive and were monitored at least every 6 months for a median time of 22 months (range 6-50). In half of the subjects the same NLABR detected initially was again reamplified at follow-up thrice or more. In 5, the same NLABR was constantly amplified in every follow-up sample. With a median follow-up of 22 months (range 9-50), no stable disappearance of a recurrent clone has been so far recorded. Real-time PCR indicated that persistent NLABR-positive clones are stable over time in the same subject. Cell separation studies indicate that NLABRs belong to CD19+, CD5-, CD23-, CD10+/- cells.

Conclusions: Our results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL). This suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL.
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http://dx.doi.org/10.1016/j.exphem.2006.08.008DOI Listing
December 2006

Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome.

Blood 2005 Jun 24;105(12):4784-91. Epub 2005 Feb 24.

Dipartimento di Medicina ed Oncologia Sperimentale, Servizio di Epidemiologia dei Tumori e Biostatistica, Centro di Ricerca in Medicina Sperimentale, Università di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy.

Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators. We thus decided to investigate the involvement of COX-2 in this neoplasm. Western blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM and monoclonal gammopathy of undetermined significance (MGUS). Selected cases under-went further evaluation by WB on purified CD138(+) cells, immunohistochemistry (IC), and real-time polymerase chain reaction (PCR) for mRNA expression. COX-2 was expressed in 11% (2 of 18) of MGUS specimens, 31% (29 of 94) of MM at diagnosis, and 47% (14 of 30) of MM with relapsed/refractory disease. COX-2 positivity was associated with a poor outcome in terms of progression-free (18 vs 36 months; P < .001) and overall survival (28 vs 52 months; P < .05). Real-time PCR showed COX-2 mRNA overexpression. IC and cell separation studies demonstrated COX-2 expression to be restricted to malignant plasma cells. This is the first report of the presence and prognostic role of COX-2 expression in MM. Future studies will assess COX-2 involvement in other hematologic tumors and its potential use as a therapeutic or chemo-preventive target in onco-hematology.
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http://dx.doi.org/10.1182/blood-2004-11-4201DOI Listing
June 2005

Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders.

Blood 2004 Jun 26;103(12):4644-9. Epub 2004 Feb 26.

Cattedra di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Azienda Ospedaliera San Giovanni Battista, Via Genova 3, 10126 Turin, Italy.

In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B-cell lymphoproliferative disorders (MBCLDs) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% or more tumor cells. TRF length was evaluated by Southern blot analysis using a chemiluminescence-based assay. GC status was assessed through screening for stable and ongoing somatic mutations within the immunoglobulin heavy-chain genes. Median TRF length was 6170 bp (range, 1896-11 200 bp) and did not correlate with patient age or sex. TRF length was greater in diffuse large cell lymphoma, Burkitt lymphoma, and follicular lymphoma (medians: 7789 bp, 9471 bp, and 7383 bp, respectively) than in mantle cell lymphoma and chronic lymphocytic leukemia (medians: 3582 bp and 4346 bp, respectively). GC-derived MBCLDs had the longest telomeres, whereas those arising from GC-inexperienced cells had the shortest (P < 10(-9)). We conclude that (1) TRF length in MBCLD is highly heterogeneous; (2) GC-derived tumors have long telomeres, suggesting that minimal telomere erosion occurs during GC-derived lymphomagenesis; and (3) the short TRF lengths of GC-inexperienced MBCLDs indicates that these neoplasms are good candidates for treatment with telomerase inhibitors, a class of molecules currently the subject of extensive preclinical evaluation.
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http://dx.doi.org/10.1182/blood-2003-12-4412DOI Listing
June 2004