HHV-6 and atypical lymphoproliferative disorders: are only qualitative molecular examinations sufficient to support a pathogenetic role?

n.d

Autophagy and Human Parturition: Evaluation of LC3 Expression in Placenta from Spontaneous or Medically Induced Onset of Labor

Induction of labor is one of the most used procedures in obstetrics, performed to achieve vaginal delivery through cervical ripening and stimulation of uterine contractions. We investigated the impact of induction of labor upon placental autophagy, a catabolic pathway activated in response to alteration of the physiological intracellular conditions. We collected 28 singleton placentas at the time of uncomplicated term vaginal delivery (7 spontaneous onset of labor, 21 induced labor). Autophagy was evaluated by immunohistochemistry, immunofluorescence, and immunoblotting. No significant difference in the autophagy expression was found between spontaneous or induced onset of labor. We found an inverse relationship between autophagy expression and the maternal prepregnancy body mass index, irrespective of the mode of labor onset. This result could be related to the nutritional maternal habits before and throughout pregnancy rather than rapid metabolic changes during labor

Indirect antitumor effects of mammalian target of rapamycin inhibitors against Kaposi sarcoma in transplant patients.

n.d

Human Herpesvirus 8 (HHV8) Infection and Related Diseases in Italian Transplant Cohorts.

Human Herpesvirus 8 (HHV8) Infection and Related Diseases in Italian Transplant Cohort

May the indirect effects of CIHHV-6 in transplant patients be exerted through the reactivation of the viral replicative machinery?

Indirect effects of CIHHV-6 in transplant patient

Tumor-targeted immunoliposomal nanosystems to deliver either Cidofovir or Antineoplastic SiRNA against Primary Effusion Lymphoma (PEL)

Therapeutic applications of siRNA-mediated gene silencing appear to be highly dependent on the use of pharmaco-technologic carrier systems, able to protect siRNAs from rapid degradation upon administration, as well as to specifically deliver them to target cells. Actually, while siRNA-expressing viral vectors are burdened with safety concerns for their clinical use, the development of modified liposomal nanocarriers may represent a feasible option to harness the therapeutic potential of targetedantineoplastic siRNAs. Recently, we have successfully developed and characterized effective immunoliposomal nanosystems (ILNs) for targeted delivery of Cidofovir (an anti-herpesviral nucleotideanalogue, also showing antitumor activity) against PEL cell lines, demonstrating a significant improvement of the antineoplastic activity of the drug, especially at lower doses (less than 1nM). Thus, we tried to adapt such PEL-specific ILNs (PEGilated nanovescicles made of cationic/neutral lipids, engineered with anti-CD138 moAb on their surface) to efficiently encapsulate siRNAs and deliver them into PEL cell lines (highly expressing CD138 membrane protein). Our preliminary data showed thatsingle treatments with anti-PEL ILNs, delivering specific siRNAs against Blimp1 (Prdm1), which is a master transcription factor in PEL (a plasmablast/pre-plasmacell lymphoma, consistently Bcl-6 neg, Blimp1 pos), were able to induce a dose-dependent (50-200nM) inhibition of Blimp1 production (as assessed by Blimp1 mRNA and protein levels using RT-PCR and Western Blot, respectively), and this was strongly associated with enhanced cell death (more than 80%, using Annexin V/PI test). In particular, we observed a massive reduction of PEL viability (mean viable cells 8%, range 3-15%) as soon as 48-72 hours after treatment with 100nM anti-Blimp1 siRNAs. Interestingly, these data may resemble those described in multiple myeloma cell lines, after transduction with lentiviral vector constitutively expressing anti-Blimp1 shRNAs. Further studies on PEL murine models are now warranted to assess the efficacy and toxicity profile of in-vivo treatment with PEL-specific ILNs, loadedwith either Cidofovir or anti-Blimp1 siRNAs

Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term Imatinib mesylate treatment.

Imatinib mesylate (IM) has been demonstrated to be permissive for the emergence of T cells directed against chronic myeloid leukemia cells. Ten Philadelphia chromosome-positive acute lymphoblastic leukemia patients, receiving high dose IM maintenance, underwent a long-term immunological monitoring (range 2-65 months) of (p190)BCR-ABL-specific T cells in the bone marrow (BM) and peripheral blood (PB). (p190)BCR-ABL-specific T lymphocytes were detected in all patients, more frequently in BM than in PB samples (67% vs 25%, p<0.01), and resulted significantly associated with lower minimal residual disease values (p<0.001), while absent at leukemia relapse. Specific T cells were mainly effector memory CD8+ and CD4+ T cells, producing IFNgamma, TNFalpha and IL-2 (median % positive cells: 3.34, 3.04, 3.58, respectively). Cytotoxic subsets able to lyse BCR-ABL-positive leukemia blasts were also detectable. Whether these autologous (p190)BCR-ABL-specific T cells may be detectable under other tyrosine-kinase inhibitors, expanded ex vivo and exploited for immunotherapy remains to be addressed

Veicolazione liposomiale del cidofovir nel trattamento del PEL (Primary Effusion Lynphoma)

Veicolazione liposomiale del cidofovir nel trattamento del PEL (Primary Effusion Lynphoma

Organising pneumonia mimicking invasive fungal disease in patients with leukaemia.

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD