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.

Changes in angiogenesis and hypoxia-inducible factor-1α protein expression in relapsed/refractory indolent non-Hodgkin lymphomas.

Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.

A voluminous mass as an initial clinical symptom of multiple myeloma: A case report.

Extramedullary multiple myeloma (EMM) is a type of multiple myeloma (MM) that is defined by the presence of extraskeletal (soft tissue or visceral) clonal plasma cell infiltrates, which may be present at the time of initial diagnosis or at the time of relapse. Although extramedullary lesions may be present with other clinical features at the time of diagnosis, the onset of a solid formation as a first clinical symptom of MM is unusual. The present study reports the case of a 77-year-old male who was admitted to the Hematology Unit of the National Cancer Research Center, Istituto Tumori 'Giovanni Paolo II' (Bari, Italy) with a mass protruding from the right side of his lower back. Serum immunofixation revealed positivity for monoclonal protein (M-protein) and Bence Jones proteinuria was positive. In addition, a computed tomography scan of the abdomen, which was confirmed by magnetic resonance imaging, revealed a voluminous solid formation resembling a sarcoma. M-protein is known to be present in numerous diseases encountered in clinical practice, including hematological or other diseases; thus, a Tru-Cut biopsy of the lesion was performed, which revealed an infiltration of plasma cells. In addition, a bone marrow biopsy revealed the presence of 70% plasma cells, and a diagnosis of primary EMM was established. In conclusion, EMM should be included in the differential diagnosis of a mass, particularly in patients where M-protein is detected in the blood and/or urine.

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

Primary gastric non-Hodgkin's 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.

Antineoplastic drug-induced bradyarrhythmias.

INTRODUCTION: Cardiac injury is one of the most impairing side effects of anticancer treatment. The extension of the range of available drugs, the use of combination regimens and the association with radiation therapy have improved life expectancy; however, they have also caused a rising typology of cardiac toxicities, including not only congestive heart failure, but also myocardial ischemia, thromboembolism, hypertension and arrhythmias. AREAS COVERED: The aim of this review is to describe the evidence of association between bradyarrhythmias and antineoplastic agents, including chemotherapeutic and molecular-targeted drugs in the adult population, to summarize the possible mechanisms of onset and to make suggestions for clinical management. A Medline search for each anticancer agent and associated cardiotoxic, electrocardiographic and arrhythmic alteration was performed for the years January 1970 - January 2012. A cross-referencing search from identified studies was also carried out. Published reports from clinical trials, non-randomized studies, case reports and recent reviews were considered. Only agents with a specific relation to bradyarrhythmias were included and are discussed. EXPERT OPINION: A greater knowledge of this specific cardiac toxicity may help appropriate risk stratification and correct management during treatment and follow-up. The exchange of information among hematologists, oncologists and cardiologists is essential for this purpose.