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Abstract Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

We study the geometric-differential properties of a wide class of closed subgroups of U n endowed with a natural bi-invariant metric. For each of these groups, we explicitly express the distance function, the diameter, and, above all, we parametrize the set of minimizing geodesic segments with arbitrary endpoints P 0 and P 1 by means of the set of generalized principal logarithms of P 0 ∗ P 1 in the Lie algebra of the group. We prove that this last set is a non-empty disjoint union of a finite number of compact submanifolds of u n diffeomorphic to suitable (and explicitly determined) homogeneous spaces. [ABSTRACT FROM AUTHOR]

In the context of abstract interpretation-based static analysis, we propose a new abstract operator modeling the split of control flow paths: the goal of the operator is to enable a more efficient analysis when using abstract domains that are computationally expensive, having no negative effect on precision, and occasionally resulting in a more precise analysis. We focus on the case of conditional branches guarded by numeric linear constraints, including implicit numerical branches. We provide an experimental evaluation of real-world test cases, showing that by using the split operator we can achieve significant efficiency improvements with respect to the classical approach for a static analysis based on the domain of convex polyhedra. We also briefly discuss the applicability of this new operator to different, possibly non-numeric abstract domains. [ABSTRACT FROM AUTHOR]

Experimental studies identified a role of neuroinflammation in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of inflammatory molecules as diagnostic and prognostic biomarkers in patients with ALS is unclear. In this cross-sectional study, the cerebrospinal fluid (CSF) levels of a set of inflammatory cytokines and chemokines were analyzed in 56 newly diagnosed ALS patients and in 47 age- and sex-matched control patients without inflammatory or degenerative neurological disorders. The molecules analyzed included: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-17, granulocyte colony stimulating factor (GCSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, tumor necrosis factors (TNF), eotaxin. Principal component analysis (PCA) was used to explore possible associations between CSF molecules and ALS diagnosis. In addition, we analyzed the association between CSF cytokine profiles and clinical characteristics, including the disease progression rate score, and peripheral inflammation assessed using the Neutrophil-to-lymphocyte ratio (NLR). PCA identified six principal components (PCs) explaining 70.67% of the total variance in the CSF cytokine set. The principal component (PC1) explained 26.8% of variance and showed a positive load with CSF levels of IL-9, IL-4, GCSF, IL-7, IL-17, IL-13, IL-6, IL-1β, TNF, and IL-2. Logistic regression showed a significant association between PC1 and ALS diagnosis. In addition, in ALS patients, the same component was significantly associated with higher disease progression rate score and positively correlated with NLR. CSF inflammatory activation in present in ALS at the time of diagnosis and may characterize patients at higher risk for disease progression. [ABSTRACT FROM AUTHOR]

Photoelectrochemical (PEC) water splitting is a viable route for green hydrogen generation. In PEC cells, the electrodes are coated with suitable semiconductor materials, which absorb the sunlight, generating charge carriers that are used to split water molecules into H2 and O2. CuFeO2 is one promising photocathode material for water splitting. However, its performance is limited by electron/hole pairs recombination within the film and at the film/substrate interface. Aerosol deposition (AD) can be employed to minimize charge recombination by spraying dense, thin films and by establishing a good back-contact interface. In this study, CuFeO2 powders were synthesized through a conventional solid-state technique and sprayed by AD under varied parameter sets. The effect of particle size distributions, carrier gas, gas pressure and substrate temperature was investigated. The best spraying parameter set was then tuned to obtain thin coatings (< 1 µm). Single-particle deformation and coatings microstructure were investigated by scanning electron microscopy. Optical properties of CuFeO2 films were analyzed by UV–Vis spectroscopy, while photoelectrochemical performances were estimated through amperometry tests under simulated sunlight. The results of this research show that CuFeO2 photocathodes can be successfully manufactured by AD. Their performance can be optimized by adjusting coating thickness and by annealing in air. [ABSTRACT FROM AUTHOR]

Background: Biopsy remains the gold standard for the diagnosis of hepatic steatosis, the leading cause of pediatric chronic liver disease; however, its costs call for less invasive methods. Objective: This study examined the diagnostic accuracy and reliability of quantitative ultrasound (QUS) for the assessment of liver fat content in a pediatric population, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Materials and methods: We enrolled 36 patients. MRI-PDFF involved a 3-dimensional T2*-weighted with Dixon pulse multiple-echo sequence using iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ). QUS imaging relied on the ultrasound system "RS85 A" (Samsung Medison, Seoul, South Korea) and the following software: Hepato-Renal Index with automated region of interest recommendation (EzHRI), Tissue Attenuation Imaging (TAI), and Tissue Scatter Distribution Imaging (TSI). For each QUS index, receiver operating characteristic (ROC) curve analysis against MRI-PDFF was used to identify the associated cut-off value and the area under the ROC curve (AUROC). Concordance between two radiologists was assessed by intraclass correlation coefficients (ICCs) and Bland–Altman analysis. Results: A total of 61.1% of the sample (n=22) displayed a MRI-PDFF ≥ 5.6%; QUS cut-off values were TAI=0.625 (AUROC 0.90, confidence interval [CI] 0.77–1.00), TSI=91.95 (AUROC 0.99, CI 0.98–1.00) and EzHRI=1.215 (AUROC 0.98, CI 0.94–1.00). Inter-rater reliability was good-to-excellent for EzHRI (ICC 0.91, 95% C.I. 0.82–0.95) and TAI (ICC 0.94, 95% C.I. 0.88–0.97) and moderate to good for TSI (ICC 0.73; 95% C.I. 0.53–0.85). Conclusion: Our results suggest that QUS can be used to reliably assess the presence and degree of pediatric hepatic steatosis. [ABSTRACT FROM AUTHOR]

Glycosylation is the most common post-translational modification of proteins, and glycosylation changes at cell surfaces are frequently associated with malignant epithelia including head and neck squamous cell carcinoma (HNSCC). In HNSCC, 5-year survival remains poor, averaging around 50% globally: this is partly related to late diagnosis. Specific protein glycosylation signatures on malignant keratinocytes have promise as diagnostic and prognostic biomarkers and as therapeutic targets. Nevertheless, HNSCC-specific glycome is to date largely unknown. Herein, we tested six established HNSCC cell lines to capture the qualitative and semi-quantitative N-glycome using porous graphitized carbon liquid chromatography coupled to electrospray ionisation tandem mass spectrometry. Oligomannose-type N-glycans were the predominant features in all HNSCC cell lines analysed (57.5–70%). The levels of sialylated N-glycans showed considerable cell line-dependent differences ranging from 24 to 35%. Importantly, α2-6 linked sialylated N-glycans were dominant across most HNSCC cell lines except in SCC-9 cells where similar levels of α2-6 and α2-3 sialylated N-glycans were observed. Furthermore, we found that HPV-positive cell lines contained higher levels of phosphorylated oligomannose N-glycans, which hint towards an upregulation of lysosomal pathways. Almost all fucose-type N-glycans carried core-fucose residues with just minor levels (< 4%) of Lewis-type fucosylation identified. We also observed paucimannose-type N-glycans (2–5.5%), though in low levels. Finally, we identified oligomannose N-glycans carrying core-fucose residues and confirmed their structure by tandem mass spectrometry. This first systematic mapping of the N-glycome revealed diverse and specific glycosylation features in HNSCC, paving the way for further studies aimed at assessing their possible diagnostic relevance. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose is to assess Multiparametric Ultrasound (MPUS) efficacy for evaluation of carotid plaque vulnerability and carotid stenosis degree in comparison with Computed Tomography angiography (CTA) and histology. Material and methods: 3D-Arterial Analysis is a 3D ultrasound software that automatically provides the degree of carotid stenosis and a colorimetric map of carotid plaque vulnerability. We enrolled 106 patients who were candidates for carotid endarterectomy. Prior to undergoing surgery, all carotid artery plaques were evaluated with Color-Doppler-US (CDUS), Contrast-Enhanced Ultrasound (CEUS), and 3D Arterial analysis (3DAA) US along with Computerized Tomographic Angiography (CTA) to assess the carotid artery stenosis degree. Post-surgery, the carotid specimens were fixed with 10% neutral buffered formalin solution, embedded in paraffin and used for light microscopic examination to assess plaque vulnerability morphological features. Results: The results of the CTA examinations revealed 91 patients with severe carotid stenoses with a resultant diagnostic accuracy of 82.3% for CDUS, 94.5% for CEUS, 98.4% for 3DAA, respectively. The histopathological examination showed 71 vulnerable plaques with diagnostic accuracy values of 85.8% for CDUS, 93.4% for CEUS, 90.3% for 3DAA, 92% for CTA, respectively. Conclusions: The combination of CEUS and 3D Arterial Analysis may provide a powerful new clinical tool to identify and stratify "at-risk" patients with atherosclerotic carotid artery disease, identifying vulnerable plaques. These applications may also help in the postoperative assessment of treatment options to manage cardiovascular risks. [ABSTRACT FROM AUTHOR]

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergoes a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of changes in microglia during is of great relevance to understand age‐related declines in cognitive and motor function. We have targeted the deleterious effects of aging by implementing IGF-1 gene transfer, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) RAd-IGF-1 or control injection on aged female rats and evaluated its effect on caudate-putamen unit (CPu) gene expression and inflammatory state. Our results demonstrate that IGF-1 overexpression modified aged microglia of the CPu towards an anti-inflammatory condition increasing the proportion of double immuno-positive Iba1+Arg1+ cells. We also observed that phosphorylation of Akt was increased in animals treated with RAd-IGF-1. Moreover, IGF-1 gene transfer was able to regulate CPu pro-inflammatory environment in female aged rats by down-regulating the expression of genes typically overexpressed during aging. RNA-Seq data analysis identified 97 down-modulated DEG in the IGF-1 group as compared to the DsRed one. Interestingly, 12 of these DEG are commonly overexpressed during aging, and 9 out of 12 are expressed in microglia/macrophages and are involved in different processes that lead to neuroinflammation and/or neuronal loss. Finally, we observed that IGF-1 overexpression led to an improvement in motor functions. Although further studies are necessary, with the present results, we conclude that IGF-1 gene transfer is modifying both the pro-inflammatory environment and activation of microglia/macrophages in CPu. In this regard, IGF-1 gene transfer could counteract the neuroinflammatory effects associated with aging and improve motor functions in senile animals. [ABSTRACT FROM AUTHOR]

Acta Geophysica. https://doi.org/10.1007/s11600-022-00805-8 15 Przyborowski L. Preliminary evidence on laboratory experiments to detect the impact of transient flow on bedload transport. Acta Geophysica. https://doi.org/10.1007/s11600-021-00709-z 3 Balouchi B. Experimental investigation of flow pattern over a fully developed bed at a 60º river confluence. Further development of instrumentation and software for hydraulic measurements, data analysis and visualization allows for a more comprehensive understanding of hydraulic phenomena. [Extracted from the article]

We study the differential-geometric properties of the loci of fixed points of the elliptic isometries of the manifold of positive definite real matrices with the trace metric. We also give an explicit description of such loci and in particular we find their De Rham decomposition. [ABSTRACT FROM AUTHOR]

Chlamydiae are obligate intracellular bacteria that grow in eukaryotic cells and cause a wide spectrum of diseases. They can establish persistent infections, are mitogenic in vitro, promote polyclonal cell proliferation in vivo and induce resistance to apoptosis in infected cells-properties that might contribute to tumorigenesis. In fact, Chlamydophila psittaci (Cp) has been linked to the development and maintenance of ocular adnexal marginal zone B-cell lymphoma (OAMZL). In this indolent malignancy, Cp is transported by monocytes and macrophages and causes both local and systemic infection. Cp elementary bodies are viable and infectious in the conjunctiva and peripheral blood of patients with OAMZL. Bacterial eradication with antibiotic therapy is often followed by lymphoma regression. Despite recent advances in the understanding of this bacterium-lymphoma association, several questions remain unanswered. For instance, prevalence variations among different geographical areas and related diagnostic and therapeutic implications remain a major investigational issue. We will focus on clinical and therapeutic implications of chlamydial infections in patients with lymphomas and summarize the current knowledge on the association between Cp infection and OAMZL. Available data on the epidemiology, biology and pathogenesis of this association are analyzed and new investigative and clinical approaches are discussed. [ABSTRACT FROM AUTHOR]

Background: Acutely ill patients admitted to the emergency department (ED) constantly require at least one fast and reliable peripheral intravenous (PIV) access. In many conditions (morbid obesity, underweight state, chronic diseases, intravenous drug abuse, adverse local conditions, etc.), PIV placement may be challenging. Ultrasound guidance is a useful tool for obtaining a peripheral intravenous access in the emergency department, particularly when superficial veins are difficult to identify by palpation and direct visualization, though standard peripheral intravenous cannulas are not ideal for this technique of insertion and may have limited duration. Long polyurethane catheters inserted with ultrasound guidance and direct Seldinger technique appear to have several advantages over short cannulas in terms of success of insertion and of duration. Methods: A retrospective analysis was conducted on all the ultrasound-guided peripheral venous accesses obtained by insertion of long polyurethane catheters in patients admitted to the emergency department of our university hospital during 1 year. The main indication to the procedure was the urgent need of a peripheral venous access in patients with superficial veins difficult to palpate and/or visualize. All relevant data concerning the insertion and the maintenance of these peripheral lines were collected from the chart. Results: Seventy-six patients were included in this review. The success rate of insertion was 100 %, with an average of 1.57 punctures per each successful cannulation. The mean time needed for the complete procedure was 9.5 min. In 73 % of patients, the catheter was used for more than 1 week; a minority of catheters were removed prematurely for end of use. No major infective or thrombotic complication was reported. Conclusions: In our experience, 8- to 10-cm-long polyurethane catheters may offer a fast and reliable peripheral venous access in the emergency department, if placed by ultrasound guidance and with the Seldinger technique. Further studies with prospective, randomized, and controlled design are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

The generation of efficacious vaccines against self-antigens expressed in tumor cells requires breakage of tolerance, and the refocusing of immune responses toward epitopes for which tolerance may not be established. While the presentation of tumor antigens by mature dendritic cells (mDC) may surpass tolerance, broadening of the antigenic repertoire remains an issue. We report that fusion of the candidate idiotype vaccine IGKV3-20 to the Gly-Ala repeat (GAr) of the Epstein-Barr virus nuclear antigen (EBNA)-1 inhibits degradation by the proteasome and redirects processing to the lysosome. mDCs transduced with a recombinant lentivirus encoding the chimeric idiotype efficiently primed CD4+ and CD8+ cytotoxic T-cell (CTL) responses that lysed autologous blasts expressing IGKV3-20 or pulsed with IGKV3-20 synthetic peptides, and HLA-matched IGKV3-20-positive tumor cell lines. Comparison of the cytotoxic response of CD4+ and CD8+ T lymphocytes activated by mDCs expressing the wild-type or chimeric IGKV3-20 reveled largely non-overlapping epitope repertoires in both CD4+ and CD8+ effectors. Thus, fusion to the GAr may provide an effective means to broaden the immune response to an endogenous protein by promoting the presentation of antigenic epitopes that require a lysosome-dependent processing step. [ABSTRACT FROM AUTHOR]

Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells. [ABSTRACT FROM AUTHOR]

Background:Ocular adnexal marginal zone B-cell lymphoma (OAMZL) has been associated with Chlamydophila psittaci, an infection that may be transmitted by carrier animals. However, it is still unclear whether exposure to animals affects the risk of OAMZL in comparison with other lymphoma histotypes. We therefore investigated the role of professional and/or domestic exposures to animals in the occurrence of OAMZL, as compared with other types of lymphoma.Methods:A hospital-based case-control study was carried out on 43 consecutive OAMZL patients (cases) and 87 consecutive patients with nodal non-Hodgkin's lymphomas (NHLs; controls). Multiple logistic regression (MLR) odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the association between exposures to animals and OAMZL risk.Results:A higher proportion of cases reported a lifetime exposure to household animals (79.1% vs 64.4% among controls), with a non-statistical significant MLR-OR of 2.18 (95% CI: 0.85-5.62). The OAMZL cases more frequently reported a history of occupation in breeding and/or slaughtering than controls (34.9% vs 6.9%), with an overall increased risk of 7.69 (95%CI: 2.65-22.34).Conclusion:These results indicate that, compared with nodal NHLs, the risk of OAMZL is markedly increased by contact with animals, particularly by occupational exposures. [ABSTRACT FROM AUTHOR]

Previous evidence from our laboratory showed that Epstein-Barr virus-immortalized lymphoblastoid B cells undergo a prominent down-modulation of HLA-II molecule expression when injected intraperitoneally in SCID mice, while HLA-I remains almost unaffected. Since this phenomenon can alter the experimental outcome of therapeutic protocols of adoptive cell therapy, we decided to evaluate the behavior of MHC antigens in a panel of cell lines belonging to the B- and T-cell lineages, as well as in epithelial tumor cell lines. Cells were administered in mice either intraperitoneally or subcutaneously and recovered 4 days later for HLA molecule expression analysis. Collected data showed a highly heterogeneous in vivo behavior of the various cell lines, which could alternatively down-modulate, completely abrogate or maintain unchanged the expression of either MHC-I or MHC-II molecules. Moreover, the site of injection impacted differentially on these aspects. Although such phenomena still lack a comprehensive clarification, epigenetic mechanisms are likely to be involved as epigenetic drugs could partially counteract MHC down-modulation in vivo. Nonetheless, it has to be pointed out that careful attention must be paid to the assessment of therapeutic efficacy of translational protocols of adoptive immunotherapy, as modulation of MHC molecules on human target cells when transferred in a mouse environment could readily interfere with the desired and expected therapeutic effects. [ABSTRACT FROM AUTHOR]

Since 1995 to date, more than 250 patients with EBV-related diseases received virus-specific CTL. Cell therapy proved to be safe and effective, and achieved some complete remissions also in patients who failed all previous standard treatments. The first clinical results with EBV-specific CTL were obtained for both prophylaxis and treatment of post-transplant lymphoproliferative disease arising in stem cell transplant or solid organ transplant recipients. Based on such encouraging results, the same approach was then extended to other EBV-related diseases, namely Hodgkin's lymphoma, nasopharyngeal carcinoma, and chronic active infection. Nowadays, the modification of the CTL generation protocols and the introduction of new specificities into EBV-specific CTL lines by chimeric antigen receptor transfer allow targeting other viral infections and also non-EBV related malignancies. Aim of this review is to summarize clinical results obtained thus far in adoptive cell therapy approaches with EBV-specific CTL. Moreover, by analyzing ongoing clinical trials, we also provide some insights on the potential future of a successful and paradigmatic history. [ABSTRACT FROM AUTHOR]

Abstract  We find all the arithmetically Gorenstein divisors on Fano varieties $${Y\subset\mathbb {P}^u}$$ of dimension n and index r with 3 ≤ n ≤ 2r − 1 and ρ(Y) ≥ 2, where Y is smooth, connected, subcanonical and linearly normal. [ABSTRACT FROM AUTHOR]

In the present work the soot combustion activity of CeO2 doped with lanthanum hydroxide, as surface promoter, has been investigated. TGA experiments, run under different conditions, show that, in the presence of lanthana, the reaction of soot starts at low temperature (579 K) due to the possibility to form carbonate species. The emission of CO2 is delayed due to the strong interaction with lanthana. A mechanism of reaction involving a carbonate route is proposed. [ABSTRACT FROM AUTHOR]

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA) arrests the growth of EBV-immortalized lymphoblastoid B cell lines (LCLs) by upregulating the cyclin-dependent kinase inhibitor p27Kip1. Here, we show that in LCLs, RA inhibits ubiquitination and proteasome-dependent degradation of p27Kip1, a phenomenon that is associated with downregulation of Thr187 phosphorylation of the protein, whereas the phosphorylation on Ser10 is unaffected. Furthermore, we demonstrate that RA downregulates the expression of the p45Skp2 and Cks1 proteins, two essential components of the SCFSkp2 ubiquitin ligase complex that target p27Kip1 for degradation. Downregulation of p45Skp2 and Cks1 occurs before the onset of growth arrest and is due to enhanced proteasome-mediated proteolysis of these proteins. Moreover, overexpression of p45Skp2 in DG75 cells prevents p27Kip1 protein accumulation and promotes resistance to the antiproliferative effects of RA. Treatment with Leptomycin B (LMB) blocked the translocation of p27Kip1 to the cytoplasm and prevented its degradation, indicating that CRM1-dependent nuclear export is required for p27Kip1 degradation. The shuttle protein p38Jab1, however, does not accumulate in the nucleus upon LMB treatment, nor does it interact with p27Kip1. Conversely, p45Skp2 is associated with p27Kip1 both in the nucleus and in the cytoplasm, accumulating within the nuclei after exposure to LMB and co-localizing with the exportin CRM1, suggesting a possible involvement of p45Skp2 in CRM1-dependent nuclear export of p27Kip1. These results indicate that downregulation of p45Skp2 is a key element underlying RA-induced p27Kip1 stabilization in B cells, resulting in an impaired targeting of the protein to the ubiquitin-proteasome pathway and probably contributing to the nuclear accumulation of p27Kip1.Oncogene (2005) 24, 2483-2494. doi:10.1038/sj.onc.1208458 Published online 14 February 2005 [ABSTRACT FROM AUTHOR]

In tumor-bearing mice and cancer patients, tumor progression is often associated with altered hematopoiesis leading to the accumulation of myeloid cells. Extensive studies in preclinical models indicate that these cells share the CD11b and the Gr-1 markers, possess a mixed mature-immature myeloid phenotype, and are responsible for the induction of T-cell dysfunctions, both tumor-specific and nonspecific. Moreover, CD11b+Gr-1+ myeloid cells are described under different unrelated situations associated with temporary impairment of the T-lymphocyte reactivity. This review examines recent findings on the nature, properties, and mechanisms of action of these myeloid suppressor cells (MSCs). [ABSTRACT FROM AUTHOR]

In the search for retinoids active against Burkitt's lymphoma (BL), we found that the arotinoid mofarotene (Ro 40-8757) induced strong antiproliferative and apoptotic responses in most established BL cell lines as well as in primary BL cells. Ro 40-8757-induced apoptosis is associated with mitochondrial membrane depolarization, activation of caspase-3 and -9, and enhanced production of reactive oxygen species. These effects were related to a transient drop in intracellular ATP content, probably favored by a downregulation of NADH dehydrogenase subunit-1, a component of the mitochondrial respiratory chain (MRC) Complex I. Inhibition of MRC with thenoyltrifluoroacetone suppressed both the ATP recovery and apoptosis, confirming that the effects of Ro 40-8757 are mediated by changes in mitochondrial function. Compared to EBV-negative lines, EBV-carrying BLs were more resistant to Ro 40-8757-induced apoptosis. EBV infection and ectopic LMP-1 expression increased the resistance of BL cells to Ro 40-8757-induced apoptosis, probably through bcl-2 upregulation. Finally, we also show that 2-methoxyoestradiol, an inhibitor of the scavenger enzymes superoxide dismutases, enhanced Ro 40-8757-mediated apoptosis. These findings provide the rationale for evaluating the clinical efficacy of Ro 40-8757 in BL patients and suggest that the combination of Ro 40-8757 with inhibitors of scavenger enzymes may be a promising therapeutic approach for this aggressive lymphoma.Oncogene (2003) 22, 906–918. doi:10.1038/sj.onc.1206060 [ABSTRACT FROM AUTHOR]

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This paper investigates the effect of the presence of SO2 in the dynamics of oxygen storage on ceria and ceria–zirconia. The introduction of SO2 under reaction conditions at T<873 K negatively affects CO conversion under oscillating conditions on all the supports studied, owing to the formation of sulfate species. Deactivation is observed on all supports and activity is recovered only after desorption of SO2, which occurs at 950< T<1000 K, depending on catalyst composition (Ce/Zr ratio) and treatment atmosphere. The amount of sulfur adsorbed is higher over solid solutions, reaching a maximum with Ce xZr1− xO2 (0.5< x<0.68). However this does not adversely affect activity compared to ceria. In the presence of Rh and Pd, reactivation is favored under reaction conditions. More generally, it appears that the removal of sulfates is facilitated in reductive atmospheres (both hydrogen and CO) over mixed oxides. No differences are observed following regeneration under oxidizing conditions. [ABSTRACT FROM AUTHOR]

The effects of redox-ageing on the temperature-programmed reduction and dynamic oxygen storage were investigated on two samples of Ce0.6Zr0.4O2 prepared under different synthesis conditions. It was observed that a high-temperature reduction/mild oxidation redox cycle can generate temperature-programmed reduction (TPR) profiles featuring a reduction peak at a temperature as low as 537 K. However, despite such favourable reduction behaviour, a strong deactivation of the oxygen storage is observed under dynamic conditions, indicating the limitations of the TPR method for investigation of oxygen storage. [ABSTRACT FROM AUTHOR]

Primary effusion lymphoma (PEL) selectively involves the serous body cavities, occurs predominantly in immunodeficient patients and is infected consistently by human herpesvirus type-8. PEL is also frequently infected by Epstein-Barr virus (EBV). The precise pathogenetic role of EBV coinfection in PEL is not fully understood. The lymphoma fails to express the EBV transforming proteins EBNA-2 and LMP-1, whereas it expresses EBNA-1 (latency I phenotype). Some studies have hypothesized that other EBV-positive lymphomas expressing the latency I phenotype may associate with specific molecular variants of EBNA-1, although this issue has not been addressed in PEL. On this basis, this study is aimed at a detailed molecular characterization of EBV in PEL. Fifteen EBV positive PEL (12 AIDS-related, one post-transplant, two arising in immunocompetent hosts) were subjected to molecular characterization of the viral genes EBNA-1 and LMP-1, as well as definition of EBV type-1/type-2. The EBNA-1 gene displayed a high degree of heterogeneity in different cases of PEL, with seven distinct recognizable variants and subvariants. A wild-type LMP-1 gene was detected in 10/15 cases, whereas in 5/15 cases the LMP-1 gene harbored a deletion spanning codons 346-355. EBV type-1 occurred in 11/15 PEL whereas EBV type-2 occurred in 4/15 cases. Despite a high degree of genetic variability of the virus in different PEL cases, each single PEL harbored only one EBV variant, consistent with monoclonality of infection and suggesting that infection preceded clonal expansion. Overall, our results indicate that: (1) individual PEL cases consistently harbor a single EBV strain; (2) EBNA-1 displays a high degree of heterogeneity in different PEL cases; (3) no specific EBV genotype preferentially associates with PEL. [ABSTRACT FROM AUTHOR]

From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m[SUP-2]), cisplatin (50 mg m[SUP-2]) administered intravenously on day 1, vincristine (0.6 mg m[SUP-2]) on day 2 and cyclophosphamide (700 mg m[SUP-2]) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. [ABSTRACT FROM AUTHOR]

Proto-oncogene restriction fragment length polymorphisms (RFLPs) were investigated in a group of 23 patients with squamous cell carcinomas of the larynx. The frequency of the rare 5 kb c- mos allele was significantly higher than that observed in control groups of patients with colorectal neoplasms or lymphoproliferative disorders. In addition, the 2 patients heterozygous at the c- mos locus (TC-8 and TC-10) were the only 2 of our series to develop multiple malignancies. Also, the 10 kb L- myc allele was remarkably more represented in patients with laryngeal carcinoma when compared to controls. These findings suggest that c- mos and L- myc RFLPs might be helpful in identifying those individuals who are at a higher risk of developing laryngeal carcinomas. Single allele amplification of L- myc, c- myb and c- mos proto-oncogenes, with no concomitant mRNA hyperexpression, were observed in 3 cases. The results obtained seem to rule out a direct pathogenetic role of these proto-oncogenes and suggest that the amplification of other closely linked genes, located on chromosomes 1, 6 and 8, respectively, may be causally associated with the development of these tumors. No allelic deletions at the c- myb locus were observed, whereas a loss of a c-Ha- ras-1 allele was demonstrated in one of the 11 heterozygous patients. Thus, the analysis of polymorphic proto-oncogenes in laryngeal carcinomas allowed us to identify a group of genetic abnormalities (chromosomes 1, 6 and 8 gene amplifications and c-Ha- ras-1 deletions) which may be involved in the development or progression of these tumors. [ABSTRACT FROM AUTHOR]

The structure of [Ir(NO)(phen)(PPh)][PF] has been determined from x-ray diffractometer data. The compound crystallizes in space group Pnam with four molecules in a unit cell with a = 19.924(12), b = 14.793(9) and c = 16.348(9) A. Full-matrix least-squares refinement has led to a final R value of 0.061 for the 4796 observed reflections. The structure consists of well-separated ions, and the geometry around the metal is trigonal bipyramidal with nitrosyl and bidentate 1,10-phenanthroline (in spite of the very narrow bite angle of 75.8°) ligands occupying the equatorial positions and the triphenylphosphine ligands the axial positions. The cation has an imposed crystallographic m symmetry. Important bond lengths are as follows: Ir-P, 2.391(3): Ir-N (nitrosyl) 1.700(12): Ir-N (1,10-phenanthroline) 2.103(12) and 2.142(11): N-O, 1.201(18)A. The nitrosyl ligand is linear [Ir-N-O = 179.9(9)°] so that this complex can be formulated as an NO complex of iridium(I). [ABSTRACT FROM AUTHOR]

The synthesis and characterisation of products obtained by the interaction between [Ir(NO)(MeCN)(PPh)] and 2-aminophenol derivatives are reported. Tetracoordinate dcomplexes of the type Ir(NO)(2-ap)(PPh) and pentacoordinate d complexesof the type [Ir(2-ap)(PPh)] where 2-ap=2-aminophenol, 2-amino-4-nitrophenol, 2-amino-5-methylphenol, 2-3-aminonaphthol and 2-amino-4-methylphenol are obtained. The Ir(NO)(PPh) complex is always present as a byproduct. Physical properties, i.r. spectra and conductivity data of the complexes are tabulated. Reaction schemes for the formation of the three complexes are proposed and discussed. [ABSTRACT FROM AUTHOR]

Dicationic nitrosyl complexes of rhodium and iridium with methyl-substituted 1,10-phenanthroline and 2,2′-bipyridine have been synthesized and characterized. The general formula for these complexes is of the type [M(NO)(N--N)(PPh3)] where M = Rh and Ir, and (N-N) is the nitrogen chelating ligand. The 1H andP n.m.r. spectra of these complexes have been studied in order to establish the geometric conformation of these pentacoordinate nitrosyl complexes. On the basis of i.r and H and P n.m.r. data a formal octahedral geometry, with linear apical nitrosyl group, equatorial phosphines and chelating ligands and coordinated water, is proposed. Trigonal bipyramid and square pyramid geometries are discussed. [ABSTRACT FROM AUTHOR]

EBV-immortalized lymphoblastoid B cell lines (LCLs) are a suitable in vitro model for the study of EBV-related lymphoproliferative disorders of immunosuppressed patients. We have previously shown that 9-cis-, 13-cis- and all-trans-retinoic acid (RA) powerfully inhibit LCL proliferation at concentrations corresponding to therapeutically achievable plasma levels (10-6 M). Herein we show that RA-induced LCL accumulation in the G0/G1 phases correlated with the loss of the catalytic activity of all three G1-associated CDKs (CDK2, CDK4 and CDK6) and with increased levels of underphosphorylated pRb and, in some LCLs, p130. LCLs arrested in G0/G1 by RA also showed a significant decrease in the protein levels of cyclins D2, D3 and A, together with a reduction in the amount of cyclin D associated with CDK4 and CDK6, probably accounting for the inhibition of the relative kinase activity. In addition, RA-treated LCLs showed a marked up-regulation of the CDK inhibitor (CKI) p27Kip-1 at the protein but not mRNA level, which correlated with a progressive increase of p27Kip-1 in CDK2 complexes (more than 2.5-fold) and with a reduction in the active phosphorylated form of CDK2. p27Kip-1 may also contribute to the inhibition of CDK4 kinase activity, as the amount of CDK4-associated p27Kip-1 was increased by 50% after RA exposure. p27Kip-1 up-regulation stably persisted for more than one week after RA withdrawal concomitantly with the maintenance of the proliferative block. Moreover, neutralization of TGFβ did not affect the growth inhibitory activity of RA, suggesting that LCL growth arrest induced by these retinoids is probably not mediated by a pathway directly involving TGFβ. Overall, these results demonstrate that RA treatment of EBV-immortalized B lymphocytes is associated with multiple effects on G1 regulatory proteins, including... [ABSTRACT FROM AUTHOR]

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Copyright of Annali dell'Universita di Ferrara: Sezione VII-Scienze Mathematiche is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We consider general surfaces, S, of high degree containing a given complete intersection space curve, Y. We study integral curves in the subgroup of Pic( S) generated by Y and the plane section. We determine the cohomological invariants of these curves and classify the subcanonical ones. Then using these subcanonical curves we produce stable rank two vector bundles on P3. [ABSTRACT FROM AUTHOR]

The synthesis and characterisation of the products obtained by reaction of 3,4-dihydroxybenzaldehydeazine, HDBA, and iridium nitrosyl or platinum, palladium and nickel phosphine complexes are reported. The relation between the complexes, stability and the electron withdrawing power of the ligands is considered. With nickel, for which only the parent mononuclear complexes, LNi(catechol), were obtained, the influence of the neutral ligand L is discussed. [ABSTRACT FROM AUTHOR]

A series of stable carboxyl substituted catecholato metal complexes of the type M(1,2-OCHR-4)(PPh): M = Pd an Pt: R = COH, CHCOH, CHCOH; have been prepared in high yield from reaction of the metal halide complex with catechols in the presence of a base. The compounds have been characterized on the basis of their elemental analyses. i.r. and n.m.r. spectra. The possibility of a metal carboxylato chelation had been considered and discussed on the light of the i.r. and n.m.r. spectra. [ABSTRACT FROM AUTHOR]

The oxidative addition of tetrabromo-1,2-benzoquinone to Rh(CO)X(PPh) (X = Cl or I) has been studied. With the square planar complex Rh(CO)Cl(PPh), two new isomeric hexacoordinated compounds; with cis and trans PPh ligands, have been isolated and their structures are discussed on the basis of spectroscopic data. The cis isomer in acetone solution quickly converts into the trans. Such a conversion presumably proceeds through the dissociation of a triphenylphosphine molecule as seems indicated by the isolation of the pentacoordinated intermediate species Rh(CO)I(PPh)(1,2-OCBr), which has been identified by elemental analysis and spectroscopically characterized. [ABSTRACT FROM AUTHOR]