Immune recovery after autologous stem cell transplantation is not different for HIV-infected versus HIV-uninfected patients with relapsed or refractory lymphoma.

Background: High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are feasible and effective salvage treatments for human immunodeficiency virus (HIV)-related relapse or refractory lymphoma. Among the main concerns with ASCT in HIV-infected persons is the additional immune depletion caused by treatment, which could amplify the preexisting immune deficit. The aims of our study were to assess the impact of conventional chemotherapy before salvage treatment was administered, in this population, and to evaluate immune reconstitution dynamics during ASCT.

The impact of Kaposi sarcoma and non-Hodgkin lymphoma on mortality of people with AIDS in the highly active antiretroviral therapies era.

Background: Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) have strongly diminished in the HAART era, but their impact on life expectancy of people with AIDS (PWA) needs to be monitored. We aimed at quantifying the burden of KS and NHL on mortality of PWA in the HAART period in Italy.

Methods: Death certificates of 3209 PWA diagnosed in 1999-2006 who died as of December 2006 were reviewed to identify those deaths in which KS or NHL was the underlying cause.

Epstein-Barr virus: novel patented therapeutics.

Importance Of The Field: Therapeutic strategies against Epstein-Barr virus (EBV) infection and associated cancers are still limited. Due to the primary role of this virus in the pathogenesis of these diseases, molecules interfering with EBV protein functions may represent effective therapeutic tools to treat EBV-associated diseases.

Areas Covered In This Review: Active immunotherapeutic protocols targeting EBV and EBV-associated cancers are reviewed first; then, we reviewed adoptive cellular therapies, innovative pharmacological approaches and other non-conventional therapeutic molecules.

Palladium complexes with a tridentate PNO ligand. Synthesis of eta1-allyl complexes and cross-coupling reactions promoted by boron compounds.

The iminophosphine 2-(2-Ph(2)P)C(6)H(4)N=CHC(6)H(4)OH (P-N-OH) reacts with [Pd(mu-Cl)(eta(3)-C(3)H(5))](2) yielding [PdCl(P-N-O)] and propene. In the presence of NEt(3), the reaction of P-N-OH with [Pd(mu-Cl)(eta(3)-1-R(1),3-R(2)C(3)H(3))](2) (R(1) = R(2) = H, Ph; R(1) = H, R(2) = Ph) affords the eta(1)-allyl derivatives [Pd(eta(1)-1-R(1),3-R(2)C(3)H(3))](P-N-O)] (R(1) = R(2) = H: 1; R(1) = H, R(2) = Ph: 2; R(1) = R(2) = Ph: 3). In solution, the complexes 1 and 3 undergo a slow dynamic process which interconverts the bonding site of the allyl ligand.

MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer.

Two common mutations, 677 C-->T and a1298 A-->C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors.

Genotype-driven phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer.

PURPOSE We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that the patients without the *28/*28 genotype tolerate higher doses of irinotecan. PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study.

A new versatile solvatochromic amino-macrocycle. From metal ions to cell sensing in solution and in the solid state.

A new fluorescent NBD-polyaza-macrocycle sensor (L) was synthesized. The coordination of Cu(ii) and Zn(ii) in acetonitrile switches on the fluorescence with different emission wavelengths. Cu(ii) complexes showed solid-state fluorescence.

Polynuclear complexes: two amino-phenol macrocycles spaced by several linear polyamines; synthesis, binding properties, and crystal structure.

The synthesis and characterization of the new polytopic ligands 1,14-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,9,12-tetraazatetradecane L1, 1,15-bis(3,6,9-triaza-15-hydroxybicyclo[9.

No risk of maternal EBV infection for childhood leukemia.

We performed a large nested case-control study within the Finnish and Icelandic maternity cohorts to verify/falsify the association of maternal EBV infection with an increased risk of acute lymphoblastic leukemia (ALL) in the offspring found in previous studies. All hematologic malignancies diagnosed among children born during 1983 to 2006 in Finland and 1997 to 2005 in Iceland were identified through national cancer registries. For each index mother of a leukemia case, three matched control mothers with cancer-free offspring were identified.

Institutional shared resources and translational cancer research.

The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource.

PrPc activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway.

Cellular prion protein (PrP(c)) is a ubiquitous glycoprotein, whose physiological role is poorly characterized. It has been suggested that PrP(c) participates in neuritogenesis, neuroprotection, copper metabolism, and signal transduction. In this study we detailed the intracellular events induced by PrP(c) antibody-mediated cross-linking in PC12 cells.

Phosphates sensing: two polyamino-phenolic zinc receptors able to discriminate and signal phosphates in water.

Two Zn(II)-dinuclear systems were studied as receptors for phosphates; they were obtained by using the two polyamino-phenolic ligands 3,3'-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L1) and 2,6-bis[N,N-bis(2-aminoethyl)aminomethyl]phenol (L2) in which the difference lies in the spacers between the two dien units, biphenol or phenol in L1 and L2, respectively. The metallo-receptors obtained are able to selectively discriminate phosphate (Pi) from pyrophosphate (PPi) and vice versa in aqueous solution in a wide range of pH (6 < pH < 10). The L1 receptor system shows selectivity toward PPi over Pi, and on the contrary the L2 system exhibits opposite selectivity.

Synthesis, in vitro and computational studies of protein tyrosine phosphatase 1B inhibition of a small library of 2-arylsulfonylaminobenzothiazoles with antihyperglycemic activity.

The 2-arylsulfonylaminobenzothiazole derivatives 1-27 were prepared using a one step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds 4 and 16 are rapid reversible (mixed-type) inhibitors of PTP-1B with IC(50) values in the low micromolar range.

Plasma HHV-8 viral load in HHV-8-related lymphoproliferative disorders associated with HIV infection.

This is a mono-institutional analysis of the clinical features, immunological and virological findings, and prognostic factors of patients with HIV infection and HHV-8-lymphoproliferative disorders. Patients with Multicentric Castleman Disease and HHV-8-related lymphoma diagnosed and treated from April 1987 to June 2004 were included in the study. HHV-8 and HIV plasma viral load, CD4+ count, hematologic parameters, and general wellbeing (performance status) were assessed at the onset of the diseases and analyzed in order to identify possible prognostic factors.

Synthesis, activity and molecular modeling of a new series of chromones as low molecular weight protein tyrosine phosphatase inhibitors.

Protein tyrosine phosphatases (PTP) are crucial elements in eukaryotic signal transduction. Several reports suggested that the LMW-PTP family has oncogenic relevance. Moreover, LMW-PTP has been recognized as a negative regulator of insulin-mediated mitotic and metabolic signaling.

Structure-based optimization of benzoic acids as inhibitors of protein tyrosine phosphatase 1B and low molecular weight protein tyrosine phosphatase.

We have optimized previously discovered benzoic acids 1, which are active as inhibitors of PTP1B and LMW-PTP, two protein tyrosine phosphatases that have emerged as attractive targets for the development of novel therapeutic agents for the treatment of diabetes, obesity, and cancer. Our efforts led to the identification of new and more potent analogues with appreciable selectivity toward human PTP1B and the IF1 isoform of human LMW-PTP.

5-Arylidene-2-phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors.

As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-phenylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a-d, f) showed interesting inhibition levels in the low micromolar range.

Novel virally targeted therapies of EBV-associated tumors.

EBV is associated to the development of several malignancies of lymphoid and epithelial origin, including Burkitt's Lymphoma, post-transplant lymphoproliferative disorders, Hodgkin's disease, AIDS-associated lymphomas, NK/T cell lymphoma and Nasopharyngeal carcinoma. EBV genes play an essential role in the development of the malignant phenotype and therefore molecules interfering with the function of these genes may represent an essential tool to treat EBV-associated malignancies. Several strategies to inhibit virus-induced tumorigenesis have been developed including antiviral and antitumor molecules, gene therapy approaches, interference with epigenetic regulatory mechanisms, adoptive and active immunotherapeutic protocols.

Human herpesvirus 8 DNA quantification in matched plasma and PBMCs samples of patients with HHV8-related lymphoproliferative diseases.

Background: The quantitative evaluation of human herpesvirus 8 (HHV8) DNA is not well described in the clinical management of HHV8-related lymphoproliferative diseases.

Objectives: To evaluate and to compare HHV8 viral load in different blood compartments from patients with multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and HHV8-associated solid lymphoma (SLY) and to establish which clinical sample would be preferable for HHV8 DNA testing.

Study Design: We assessed HHV8 DNA in plasma and peripheral blood mononuclear cells (PBMCs) paired samples from 7 PEL, 8 MCD, 2 SLY HIV+ patients at the diagnosis and during the course of the illness by using a real time PCR assay.

Spontaneous T cell responses to Epstein-Barr virus-encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: bases for improved immunotherapy.

Immunotherapy approaches targeting Epstein-Barr virus (EBV)-encoded antigens induce objective clinical responses only in a fraction of patients with undifferentiated nasopharyngeal carcinoma (UNPC). In the present study, we have characterized the immunogenicity of the EBV-encoded BARF1 oncogene with the aim to assess whether this protein could constitute a new target antigen for immunotherapy in this setting. Spontaneous CD4+ and CD8+ T cell responses specific for the recombinant p29 BARF1 protein were detected by IFNgamma-ELISPOT in both EBV-seropositive donors and UNPC patients, but not in EBV-seronegative individuals.

Protective effect of new S-acylglutathione derivatives against amyloid-induced oxidative stress.

Recent data support the role of oxidative stress in the pathogenesis of Alzheimer disease (AD). In particular, glutathione (GSH) metabolism is altered and its levels are decreased in affected brain regions and peripheral cells from AD patients and in experimental models of AD. In the past decade, interest in the protective effects of various antioxidants aimed at increasing intracellular GSH content has been growing.

Future of biobanking in microbiology for medical research.

Biobanks are actively contributing to advances in biomedical research by offering opportunities to link laboratory research with clinical applications and by accelerating developments in personalized medicine. Microbiologists have a long tradition of storing microorganisms as part of projects focused on microbial genetics or phenotypic investigations. However, the impressive recent advances of biomedical translational research demand the integration of biobanks with high-level technological infrastructures in genomics, proteomics, bioinformatics, patient information systems and disease registries, where data originating from microorganisms are linked with human clinical information with the ultimate aim of improving healthcare by increasing the quality of biomedical research.