Novel recurrent chromosome anomalies in Shwachman Diamond syndrome

Clonal chromosome anomalies are frequently acquired in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS), and two are the most frequent: an isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q). Patients with SDS have a risk of developing myelodysplasia (MDS) and/or acute myeloid leukaemia (AML), and the presence of chromosome changes was studied in relation with this risk. Starting in 1999 we have monitored the cytogenetic picture of a cohort of 92 Italian patients with SDS by all suitable cytogenetic and molecular methods. Clonal anomalies in BM were present in 41/92 patients. The i(7)(q10) was observed in 16 patients, and the del(20)(q) in 15, both these changes in four, but in independent clones. So, the most frequent clonal anomalies were found in 35 patients. Other, different, clonal anomalies were found in the BM of 13 patients, in eight cases in the absence of i(7)(q10) or del(20)(q), in five cases in association with one of these changes. In these less common clonal anomalies, the distribution of the chromosomes involved was markedly disparate, and some of them were novel and recurrent: - structural rearrangements of chromosome 7, mainly unbalanced (deletions, inversions or translocations), were present in five of our 13 patients, three of whom developed MDS/AML. - a further complex rearrangement of the more common del(20)(q), leading to duplicated and deleted portions, was identical in two patients, with almost identical a-CGH profiles, neither developed MDS/AML. - an unbalanced translocation t(3;6), with partial trisomy of the long arm of chromosome 3 and partial monosomy of the long arm of chromosome 6, was not identical but very similar in two patients, one of whom developed MDS/AML

Crosstalk between ROS-dependent apoptotic and autophagic signaling pathways in Zn(II) phthalocyanine photodynamic therapy of melanoma

Melanoma is the most aggressive type of skin cancer, highly resistant to conventional therapies. Photodynamic therapy (PDT) is a minimally invasive treatment modality that combines the use of a photosensitizer, visible light and molecular oxygen, leading to ROS generation in the specific site of irradiation. The cationic zinc(II) phthalocyanine Pc13 has shown to be a potent photosensitizer in different melanoma cell lines. In this study, we explored the intracellular signaling pathways triggered by Pc13 PDT and the role of these cascades in the phototoxic action of Pc13 in human melanoma A375 cells. ROS-dependent activation of MAPKs p38, ERK, JNK and PI3K-I/AKT was observed after treatment. Inhibition of p38 reduced Pc13 phototoxicity, whereas blockage of ERK did not affect this response. Conversely, JNK inhibition potentiated the effect of Pc13 PDT. Results obtained indicate that p38 is involved in the cleavage of PARP-1, an important mediator of apoptosis. On the other hand, Pc13 irradiation induced the activation of an autophagic program, as evidenced by enhanced levels of Beclin-1, LC3-II and GFP-LC3 punctate staining. We also demonstrated that this autophagic response is promoted by JNK and negatively regulated by PI3K-I/AKT pathway. The blockage of autophagy increased Pc13 phototoxicity and enhanced PARP-1 cleavage, revealing a protective role of this mechanism, which tends to prevent apoptotic cell death.Furthermore, reduced susceptibility to treatment and increased activation of autophagy were detected in A375 cells submitted to repeated cycles of Pc13 PDT, indicating that autophagy could represent a mechanism of resistance to PDT. The efficacy of Pc13 PDT and an improved phototoxic action in combination with chloroquine were also demonstrated in tumor spheroids. In conclusion, we showed the interplay between apoptotic and autophagic signaling pathways triggered by Pc13 PDT-induced oxidative stress. Thus, autophagy modulation represents a promising therapeutic strategy to potentiate the efficacy of PDT in melanoma.Fil: Valli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Garcia Vior, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Relationship between microstructure, mechanical and magnetic properties of pure iron produced by laser powder bed fusion (L-PBF) in the as-built and stress relieved conditions

In the present work, the mechanical and magnetic properties of pure iron manufactured by laser-powder bed fusion (L-PBF) were investigated both in the as-built (AB) and stress relieved (HT) conditions, with the aim of elucidating their relationship with the microstructure and evaluating whether and to what extent it can be suitable for industrial applications. The L-PBF process was optimized to obtain high density, crack-free components. Specimens for microstructural analyses, tensile and magnetic tests were manufactured under the optimized conditions and tested both in the as-built and annealed (850 degrees C for 1 h, to relieve the residual stresses) conditions. Tensile tests showed high tensile strength in both AB and HT conditions (larger than those of conventionally produced pure iron), with higher ductility and lower strength after stress relieving. The magnetic study indicated a not optimal magnetic softness although the heat treatment enhanced the permeability and reduced the coercivity with respect to the as-built condition. The high mechanical strength and low magnetic softness came from the very fine grain size (about 5 mu m) of L-PBF pure iron. Instead, the improvement of magnetic softness and ductility after heat treatment was attributed to the possible reduction of dislocation density and consequent stress relief. The results indicated the possibility to achieve a considerably high mechanical strength, in pure iron manufactured by L-PBF, although the fine grain size limits its magnetic softness

Incidence and clinicopathologic features of gastrointestinal stromal tumors. A population-based study.

BACKGROUND: Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST) have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome. METHODS: Gastrointestinal mesenchymal tumors identified by the Modena Cancer Registry between 1991 and 2004 were analyzed with an immunohistochemical panel that included staining for CD-117 and PDGFRalpha. Size, mitotic rate, and other pathologic parameters were recorded. Each tumor was categorized into National Institutes of Health risk categories (very low, low, intermediate, and high risk). RESULTS: One hundred twenty-four cases were classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy-five percent of patients were symptomatic; 34% had a previous or concomitant history of cancer. High-risk features were present in 47% of cases. Seventy-eight percent were submitted to radical surgery. After complete resection, the 5-year disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very low, low, intermediate, and high risk, respectively. In multivariate analysis, high risk was the main predictor of recurrence. CONCLUSION: This population-based study shows that the incidence of GIST in Northern Italy is comparable to that reported in other European countries. Survival was favorable in lower risk categories and in most of the resected cases. In our study, resected patients at very low, low, and intermediate risk had a similar outcome. Our data support the need to consider high-risk patients after complete surgical resection for treatment with the best available approach

Endomicroscopy and Cancer: A New Approach to the Visualization of Neoangiogenesis

Probe-based Confocal Laser Endomicroscopy (pCLE) is a novel imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution. It offers the possibility to analyze neoangiogenesis and vessel density in vivo. Angiogenetic switch is essential in cancer progression. Aim of the paper was to review the use of this imaging tool to analyze colorectal and gastric cancers vascularization in vivo. The aim is to provide the possibility of combining diagnostic evidences with vascularization and molecular profile to evaluate the efficacy of an antiangiogenic treatment in association with conventional therapy. pCLE can be considered a revolutionary method for real-time assessment of changes in vascularization pattern in this tumors and it may open the possibility to address the use of anti-angiogenic therapy in order to improve the outcome of the treatment

Novel hydro- and lipo-philic selenium zinc(II) phthalocyanines: Synthesis, photophysical properties and photodynamic effects on CT26 colon carcinoma cells

The synthesis and photochemical properties of two novel selenium zinc(II) phthalocyanines, a lipid-soluble 2,9(10),16(17),23(24)-tetrakis [(2-dimethylamino)ethylselanyl]phthalocyaninato zinc(II) (4) and its water-soluble quaternized derivative 2,9(10),16(17),23(24)-tetrakis [(2- trimethylammonium)ethylselanyl]phthalocyaninato zinc(II) tetraiodide (5), were investigated. Maximum absorption values were 689 nm and 684 nm for 4 and 5 in DMF, respectively. In addition, phthalocyanines were revealed to be very efficient singlet oxygen generators with high values of ΦΔ 0.74 and 0.84 for 4 and 5 in DMF, and they were photostable over the irradiation times studied. The photodynamic effect were evaluated on CT26 colon carcinoma cells. After light exposure, 4 and 5 were found to be cytotoxic, and IC50 values were 0.5 ± 0.1 μM and 2.3 ± 0.6 μM, respectively. The production of a greater amount of reactive oxygen species after phthalocyanines irradiation would be responsible for its potent phototoxic action on CT26 colon carcinoma cells.Fil: Ezquerra Riega, Sergio Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Chiarante, Nicolás Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Valli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Marino, Veronica Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Roguin, Leonor Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Awruch, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Garcia Vior, María Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Functional brain networks before the onset of psychosis: A prospective fMRI study with graph theoretical analysis☆☆☆

Individuals with an at-risk mental state (ARMS) have a risk of developing a psychotic disorder significantly greater than the general population. However, it is not currently possible to predict which ARMS individuals will develop psychosis from clinical assessment alone. Comparison of ARMS subjects who do, and do not, develop psychosis can reveal which factors are critical for the onset of illness. In the present study, 37 patients with an ARMS were followed clinically at least 24 months subsequent to initial referral. Functional MRI data were collected at the beginning of the follow-up period during performance of an executive task known to recruit frontal lobe networks and to be impaired in psychosis. Graph theoretical analysis was used to compare the organization of a functional brain network in ARMS patients who developed a psychotic disorder following the scan (ARMS-T) to those who did not become ill during the same follow-up period (ARMS-NT) and aged-matched controls. The global properties of each group's representative network were studied (density, efficiency, global average path length) as well as regionally-specific contributions of network nodes to the organization of the system (degree, farness-centrality, betweenness-centrality). We focused our analysis on the dorsal anterior cingulate cortex (ACC), a region known to support executive function that is structurally and functionally impaired in ARMS patients. In the absence of between-group differences in global network organization, we report a significant reduction in the topological centrality of the ACC in the ARMS-T group relative to both ARMS-NT and controls. These results provide evidence that abnormalities in the functional organization of the brain predate the onset of psychosis, and suggest that loss of ACC topological centrality is a potential biomarker for transition to psychosis

Valorization of monovarietal Nostrana di Brisighella extra virgin olive oils: focus on bioactive compounds

A “green breakthough” at the table due to consumer demand for healthy and sustainable foods, which aligns with the typical Mediterranean diet, has recently led to an increase in the consumption of products such as extra virgin olive oil. In fact, Italian olive cultivation, which contributes an average of 15% of world production, has seen the production of extra virgin olive oil with a value of exports that have doubled in the last 20 years. In this context, the olive oil sector of the Emilia-Romagna region (Italy), and in particular the PDO Brisighella, could achieve greater success with consumers by proposing a product obtained through sustainable agriculture that enhances the content of bioactive compounds. For these reasons, in this study, different agronomic variables are investigated in order to optimize the presence of bioactive components in extra virgin olive oil made from monovarietal Nostrana di Brisighella, namely phenolic and positive volatile compounds, thus naturally enriching this product both from health and sensory points of view. The study focuses on the volatile and phenolic fractions (derivatives of hydroxytyrosol and tyrosol) of olive oil and the positive sensory attributes (fruity, bitter and pungent) that are known to be associated with these molecules. The phenolic content is of particular interest due to the potential to support health claims. Extra virgin olive oil samples were produced from olives of the Nostrana di Brisighella cultivar; fruits were obtained through integrated pest management or organic farming and picked at four increasing indices of maturity, corresponding to four successive weeks of harvesting. These agronomic variables influenced the compositional and sensory characteristics of the extra virgin olive oils assessed, highlighting differences that likely derive from the effect of the agronomic system used, i.e., integrated pest management or organic farming

Effect of physiological state in nutrients and tannins intake of creole goats grazing in the NE of Mendoza, Argentina

Cuando las cabras pastorean en ambientes áridos complejos, como el NE de Lavalle, incorporan en la dieta diferentes especies de plantas que difieren en el contenido de nutrientes y taninos. Además, pueden cambiar la composición botánica de la dieta según época del año y estados fisiológicos. Esto les permite cubrir sus requerimientos nutricionales, evitar intoxicaciones e incluso beneficiarse a partir del consumo de cantidades adecuadas de compuestos potencialmente tóxicos como los taninos. Si bien la producción caprina es una de las actividades económicas más importante del NE de Lavalle, aún es escasa la información acerca del contenido de nutrientes y taninos, y digestibilidad in vivo de la dieta de las cabras. Generar esta información es fundamental para predecir y manejar el impacto del pastoreo en la vegetación

Contenido y patrón de n-alcanos en especies forrajeras consumidas por cabras criollas en pastoreo en una zona desértica del monte central de Argentina

Los herbívoros en pastoreo ingieren cantidades variables de nutrientes y toxinas según las partes y especies de plantas que consumen; dichos compuestos tienen consecuencias postingestivas en el animal que modifican su comportamiento alimentario. Para estudiar estas interacciones es necesario realizar estimaciones ajustadas de la ingesta y composición botánica de la dieta. El uso de n-alcanos como marcadores internos permite realizar dichas estimaciones en forma individual y con mínima interferencia de los animales. El contenido y patrón de n-alcanos puede variar entre diferentes especies y partes de plantas, lo cual explica el uso potencial de estos compuestos como marcadores naturales de las plantas, y su aplicación para estudios de comportamiento en pastoreo en rumiantes. Su objetivo es determinar el contenido y patrón de n-alcanos en las partes morfológicas de las especies forrajeras que componen la dieta de cabras criollas durante la estación seca, y la aplicabilidad de la técnica de los n-alcanos para estudiar la selección de dieta de estos animales