Giacoma De Tullio

Effect of Low-Density Lipoprotein Apheresis on Circulating Endothelial Progenitor Cells in Familial Hypercholesterolemia

Background: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim of this study was to verify whether LA can increase the percentage of EPCs. Methods: In 15 patients affected by FH periodically treated with LA, the percentage of EPCs was determined before and after performing LA, and compared with the values of 15 control subjects and 15 hypercholesterolemic patients treated with statins. Results: Significant differences were found in FH patients between the pre-apheresis percentages of CD34+/KDR+, defined as EPCs by a wide consensus of opinion, and the values found 24 h after the procedures (0.00868 ± 0.003 vs. 0.01009 ± 0.002%, p < 0.005). Instead, the percentages of CD34+/KDR+/CD133+, considered as an immature subset of EPCs, remained substantially unchanged. However, a significant reduction in the percentage of EPCs was observed in both patient groups as compared to the controls, at all the assessment times. Conclusion: In the short-term LA seems to stimulate mobilization of CD34+/KDR+ cells. Hypercholesterolemic patients show a lower percentage of EPCs than controls. There were no differences in the EPCs percentages between the 2 patients groups, despite the fact that LDL cholesterol levels were higher in the group undergoing LA.

Challenges and Opportunities of MicroRNAs in Lymphomas

MicroRNAs (miRNAs) are small non-coding RNAs that control the expression of many target messenger RNAs (mRNAs) involved in normal cell functions (differentiation, proliferation and apoptosis). Consequently their aberrant expression and/or functions are related to pathogenesis of many human diseases including cancers. Haematopoiesis is a highly regulated process controlled by a complex network of molecular mechanisms that simultaneously regulate commitment, differentiation, proliferation, and apoptosis of hematopoietic stem cells (HSC). Alterations on this network could affect the normal haematopoiesis, leading to the development of haematological malignancies such as lymphomas. The incidence of lymphomas is rising and a significant proportion of patients are refractory to standard therapies. Accurate diagnosis, prognosis and therapy still require additional markers to be used for diagnostic and prognostic purpose and evaluation of clinical outcome. The dysregulated expression or function of miRNAs in various types of lymphomas has been associated with lymphoma pathogenesis. Indeed, many recent findings suggest that almost all lymphomas seem to have a distinct and specific miRNA profile and some miRNAs are related to therapy resistance or have a distinct kinetics during therapy. MiRNAs are easily detectable in fresh or paraffin-embedded diagnostic tissue and serum where they are highly stable and quantifiable within the diagnostic laboratory at each consultation. Accordingly they could be specific biomarkers for lymphoma diagnosis, as well as useful for evaluating prognosis or disease response to the therapy, especially for evaluation of early relapse detection and for greatly assisting clinical decisions making. Here we summarize the current knowledge on the role of miRNAs in normal and aberrant lymphopoiesis in order to highlight their clinical value as specific diagnosis and prognosis markers of lymphoid malignancies or for prediction of therapy response. Finally, we discuss their controversial therapeutic role and future applications in therapy by modulating miRNA.

αβ-Double Negative CD4/CD8 (CD56) T cell (DNTs) in metastatic melanoma: basal frequency and behaviour during Ipilimumab treatment. Preliminary evaluations

Background The knowledge of the immune system role on melanoma has accelerated the translation of key advancements into medical breakthroughs like ipilimumab, an anti-CTLA4 immunomodulating antibody. Ipilimumab works amazingly well only in a limited number of patients and its effects on T-cell subpopulations as well as on immune response remains to be elucidated. Recently, it was described a new subset of immunomodulating T-cells, known as Double-negative T-cells (DNTs) expressing either ab or gδ T-cell receptors (TCR) but lacking CD4, CD8,CD56. The DNTs contribute specifically to antitumor immunity since involved in immune regulation and tolerance acting as regulatory T-cells (Treg) and/or cytotoxic T-cells and they contribute to in vivo anti-melanoma immunity as previously reported [1-5]. However no data are available on their frequency in melanoma, as well as the effects of ipilimimumab on DNTs functional attitude in immunomodulation and on modulating their expression during the therapy. We aimed to evaluate the modulation of DNT frequency in Metastatic Melanoma (MM) patients treated with ipilimumab during the therapy in order to explore their potential role on clinical outcome and therapy response.

A supervised CAD to support telemedicine in hematology

This paper presents the design and the implementation of a Computer Aided Diagnosis (CAD) system for the clinical analysis of Peripheral Blood Smears (PBS also called Blood Film). The proposed system is able to count and classify the five types of leucocytes located in the tail of a PBS for computing the leukocyte formula. Image processing and segmentation techniques were used to extract 33 leucocytes features (morphological, chromatic and texture-based). Only 7 features, selected by using the Information Gain Ranking algorithm of Weka platform, were used to evaluate the classification performance of two different classifiers: Back Propagation Neural Network (BPNN) and Decision Tree (DT). From the comparison between the two proposed approaches we can argue that the BPNN performed better than the DT on the validation set. Finally, the Neural Network classifier was evaluated with a test set composed of 1274 leucocytes obtaining good results in terms of Precision (87.9%) and Sensitivity (97.4%).

Targeted strategies in the treatment of primary gastric lymphomas: from rituximab to recent insights into potential new drugs.

Primary gastric non-Hodgkins lymphomas (PG-NHL) are the most common extranodal lymphomas, representing between 47% and 74% of all gastrointestinal lymphoma cases. In Western countries two histological types, diffuse large B-cell (DLBC) NHL and mucosa-associated lymphoid tissue (MALT) NHL, are more frequently represented, accounting for the majority of gastric tumors after adenocarcinoma. For several years treatment of these PG lymphomas consisted of surgery, chemotherapy and radiotherapy, alone or in combination. In the last two decades however, advances in our understanding of their pathogenesis and biology have changed the treatment strategy, at least as regards the early stages of disease. In addition to making tumor regression possible through the eradication of Helicobacter pylori, which is considered the main pathogenic agent, this understanding has also provided a solid rationale to assess the efficacy of targeted therapy, namely of drugs which interfere with specific molecules expressed by tumor cells or are involved in key growth pathways of these lymphomas. In particular, rituximab, a monoclonal anti-CD20 antibody, radioimmunotherapy, the first-generation proteasome inhibitor bortezomib and lenalidomide have been evaluated. Despite significant antitumor activity in this subset of NHL and manageable toxicity, many questions still remain however about the optimal dose, the best administration schedule and their combination with conventional chemotherapy. This review focuses on the pathogenesis of PG-MALT and DLBC lymphomas, and discusses the results of clinical trials on the impact of new agents on prognosis and survival in these patients, considering also potential new therapautic targets.

Improvements in haematology for home health assistance and monitoring by a web based communication system

The authors have developed, in the field of a national project, an innovative communication system based on a web cloud platform oriented on the home-monitoring and home-assistance useful for de-hospitalization process. The goal of the work is to provide a tool for the hospital, able to manage different certified medical devices measuring data from patients at home. This management is provided by a web server system compatible with different devices and by a front-end panel able to register and to store data coming from these devices. The innovation is manly in the possibility to transfer the analyses from home to hospital thus reducing costs and providing more assistance and support to patients. The implemented database system represents a first step for future scientific studies and predictions requiring BigData storage.

Association between proteomic profile and molecular response in chronic myeloid leukemia patients

Vito Michele Garrisi , Nicola Sgherza , Massimo Breccia, Angela Iacobazzi, Giacoma De Tullio, Giovanni Nardelli, Antonio Negri, Rosa Divella, Antonella Daniele, Giuseppina Micelli, Antonio Tufaro, Nicola Cascavilla, Eufemia Savino, Ines Abbate and Attilio Guarini Clinical and Experimental Pathology Laboratory, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari, Italy; Hematology and Stem Cell Transplantation Unit, “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy; Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy; Hematology Unit, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari, Italy