Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements

<p>Abstract</p> <p>Background</p> <p>The t(9;22)(q34;q11), generating the Philadelphia (Ph) chromosome, is found in more than 90% of patients with chronic myeloid leukemia (CML). As a result of the translocation, the 3' portion of the <it>ABL1 </it>oncogene is transposed from 9q34 to the 5' portion of the <it>BCR </it>gene on chromosome 22 to form the <it>BCR</it>/<it>ABL1 </it>fusion gene. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22).</p> <p>Results</p> <p>We report a molecular cytogenetic study of 452 consecutive CML patients at diagnosis, that revealed 50 cases identifying three main subgroups: i) cases with variant chromosomal rearrangements other than the classic t(9;22)(q34;q11) (9.5%); ii) cases with cryptic insertions of <it>ABL1 </it>into <it>BCR</it>, or vice versa (1.3%); iii) cases bearing additional chromosomal rearrangements concomitant to the t(9;22) (1.1%). For each cytogenetic group, the mechanism at the basis of the rearrangement is discussed.</p> <p>All breakpoints on other chromosomes involved in variant t(9;22) and in additional rearrangements have been characterized for the first time by Fluorescence In Situ Hybridization (FISH) experiments and bioinformatic analyses. This study revealed a high content of <it>Alu </it>repeats, genes density, GC frequency, and miRNAs in the great majority of the analyzed breakpoints.</p> <p>Conclusions</p> <p>Taken together with literature data about CML with variant t(9;22), our findings identified several new cytogenetic breakpoints as hotspots for recombination, demonstrating that the involvement of chromosomes other than 9 and 22 is not a random event but could depend on specific genomic features. The presence of several genes and/or miRNAs at the identified breakpoints suggests their potential involvement in the CML pathogenesis.</p

Laser cleaning of gilded wood: a comparative study of colour variations induced by irradiation at different wavelengths

There is a growing interest by art conservators for laser cleaning of wood artworks, since traditional cleaning with chemical solvents can be a source of decay, due to the prolonged action of chemicals after the restoration. In this experiment we used excimer and Nd:YAGlasers, emitting radiation in the ultraviolet (248 nm), visible (532 nm) and near infrared (1064 nm), to investigate the effect of laser interaction on gilded wood samples at different wavelengths

Increased phospho-mTOR expression in megakaryocytic cells derived from CD34+ progenitors of essential thrombocythaemia and myelofibrosis patients

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DIFERENTES NÍVEIS DE CONTAGEM DE CÉLULAS SOMÁTICAS NO LEITE E SUA INTERFERÊNCIA NA PRODUÇÃO E QUALIDADE DE QUEIJOS

O mercado leiteiro vem crescendo exponencialmente no Brasil, sendo necessário ampliar os conhecimentosem como garantir a qualidade do produto e seus derivados, objetivando assim, melhor e maior venda. Oobjetivo deste trabalho foi avaliar o impacto da contagem de células somáticas (CCS) do leite na produção equalidade de queijos minas padrão. Foram coletadas amostras de leite de propriedades da região do MeioOeste Catarinense, diretamente de tanques de resfriamento. As amostras foram separadas em gruposconforme análise de CCS do leite: até 200.000 CS/mL (baixa), 201.000 a 500.000 CS/mL (média) e acima de501.000 CS/mL (alta). O queijo foi elaborado a partir das amostras nas dependências do Instituto FederalCatarinense, campus Concórdia, assim como suas análises, incluindo rendimento do queijo. As análisesfísico-químicas realizadas foram de acidez titulável, determinação da gordura (método de Gerber), umidade epH. Foram realizadas as seguintes análises microbiológicas: coliformes termotolerantes (a 45°C), Salmonellae Estafilococos Coagulase Positiva (ECP). Todas as análises foram realizadas a partir do 2° dia defabricação, sendo repetidas após o período de 20 dias. Os resultados encontrados nos queijos para asanálises físico-químicas do leite não houve diferença significativa para EST, ESD, proteína e lactose ao secomparar os três grupos. Já para gordura, houve diferença entre o leite de baixa CCS (4,60 ± 0,14) com oleite de alta CCS (3,96 ± 0,09), ou seja, com o aumento da CCS e uma maior infecção na glândula mamária,a produção dos componentes do leite será afetada, acarretando em uma queda na porcentagem de gordura.A acidez apresentou uma diferença estatística entre o leite de baixa CCS (16,29 ± 0,52) com o de alta CCS(13,58 ± 0,02). A mastite influencia na alcalinização do pH do leite, mantendo-o semelhante ao do sangue,porque com a lesão causada pela mastite no úbere, há um aumento na permeabilidade capilar, havendo umapassagem de constituintes do sangue para o leite, influenciando assim, na mudança do pH do mesmo. Paraas análises microbiológicas, em baixa CCS foi encontrado Estafilococos Coagulase Positiva em 20 dias,sendo que a média CCS foi negativa para ambos os dias e alta CCS apresentou Estafilococos CoagulasePositiva em 02 dias; a presença de Salmonella sp. e coliformes termotolerantes (a 45°C) foi negativa emtodos as análises. Por fim, com base nos resultados, conclui-se que diferentes valores de CCS podeminfluenciar nos resultados das análises físico-químicas da matéria-prima e do produto final. O queijo&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;produzido com o leite de baixa CCS possuiu qualidade e durabilidade estável, onde a composição físico-química trouxe resultados desejados em um produto. O queijo de alta CCS apresentou uma composição&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;físico-química inferior ao de baixa CCS. Para as análises microbiológicas, o valor de CCS não interferiu napresença ou ausência dos micro-organismos pesquisados nas amostras

BRIEF REPORT Proteasome Inhibitors Synergize with Tumor Necrosis Factor-Related Apoptosis-Induced Ligand to Induce Anaplastic Thyroid Carcinoma Cell Death

Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC. Objective and Methods: The aim of this study was to investigate the ability of the proteasome inhibitor Bortezomib to induce apoptosis in ATC cell lines. Bortezomib was used as a single agent or in combination with TNF-related apoptosis-induced ligand (TRAIL), a member of the TNF family that selectively induces tumor cell apoptosis. The molecular effects of Bortezomib were investigated by analyzing the expression of key regulators of cell cycle and apoptosis and the activation of different apoptotic pathways. Results: Bortezomib induced apoptosis in ATC cells at doses achieved in the clinical setting, differently from conventional chemotherapeutic agents. Simultaneous treatment with low doses of Bortezomib and TRAIL had a synergistic effect in inducing massive ATC cell apoptosis. Bortezomib increased the expression of cytotoxic TRAIL receptors, p21 (WAF/CIP1) and proapoptotic second mitochondria-derived activator of caspases/direct inhibitor of apoptosis binding protein with low pI, and reduced the expression of antiapoptotic mediators such as cellular Fas-associated death domain-like IL-1␤ converting enzyme inhibitory protein, Bcl-2, Bcl-X L , and inhibitor of apoptosis-1, thus resulting in cell death induction through the mitochondrial apoptotic pathway. Conclusions: The combination of proteasome inhibitors and TRAIL synergizes to induce the destruction of chemoresistant neoplastic thyrocytes and could represent a promising therapeutic strategy for the treatment of anaplastic thyroid carcinoma. (J Clin Endocrinol Metab 92: 1938 -1942, 2007

BRIEF REPORT Proteasome Inhibitors Synergize with Tumor Necrosis Factor-Related Apoptosis-Induced Ligand to Induce Anaplastic Thyroid Carcinoma Cell Death

Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC. Objective and Methods: The aim of this study was to investigate the ability of the proteasome inhibitor Bortezomib to induce apoptosis in ATC cell lines. Bortezomib was used as a single agent or in combination with TNF-related apoptosis-induced ligand (TRAIL), a member of the TNF family that selectively induces tumor cell apoptosis. The molecular effects of Bortezomib were investigated by analyzing the expression of key regulators of cell cycle and apoptosis and the activation of different apoptotic pathways. Results: Bortezomib induced apoptosis in ATC cells at doses achieved in the clinical setting, differently from conventional chemotherapeutic agents. Simultaneous treatment with low doses of Bortezomib and TRAIL had a synergistic effect in inducing massive ATC cell apoptosis. Bortezomib increased the expression of cytotoxic TRAIL receptors, p21 (WAF/CIP1) and proapoptotic second mitochondria-derived activator of caspases/direct inhibitor of apoptosis binding protein with low pI, and reduced the expression of antiapoptotic mediators such as cellular Fas-associated death domain-like IL-1␤ converting enzyme inhibitory protein, Bcl-2, Bcl-X L , and inhibitor of apoptosis-1, thus resulting in cell death induction through the mitochondrial apoptotic pathway. Conclusions: The combination of proteasome inhibitors and TRAIL synergizes to induce the destruction of chemoresistant neoplastic thyrocytes and could represent a promising therapeutic strategy for the treatment of anaplastic thyroid carcinoma. (J Clin Endocrinol Metab 92: 1938 -1942, 2007

Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

<p>Abstract</p> <p>Background</p> <p>PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor^®EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.</p> <p>Methods</p> <p>In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.</p> <p>Results</p> <p>NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.</p> <p>Conclusion</p> <p>These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.</p

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood

Estudos Artísticos

Os quinze artigos que aqui se reúnem, nesta edição da Revista Croma, são também as propostas para uma nova política, esclarecida, crítica, e mais exigente. Podem observar-se padrões de intervenção, que partem de algumas dimensões comuns: a interpelação do observador, a criação de novos públicos, a proposta de contribuir para uma mudança alargada, partindo de questões a que não são alheias as problemáticas contemporâneas. As questões de género, a emancipação pós-colonial, a sustentabilidade, as migrações, a massificação, a globalização, o fim das ideologias e a ascensão do populismo, entre outras, constituem os contextos da atualidadeinfo:eu-repo/semantics/publishedVersio

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses