Defining the optimal dose of radiation in leukemic patients with extramedullary lesions

<p>Abstract</p> <p>Background</p> <p>Analysis of the clinical response of extramedullary lesions in leukemic patients treated with radiation therapy (RT) and defining the optimal dose of radiation.</p> <p>Methods</p> <p>Forty-two extramedullary lesions found in 24 leukemic patients treated with RT were reviewed. The radiation was delivered usually 2 Gy/day, up to a median of 20 Gy (range: 18.0-40.8). The clinical response and symptom palliation effect were analyzed. The factors affecting the response were also included in the analysis.</p> <p>Results</p> <p>After a median time of 7.9 weeks, the overall response rate was 76.2%. A complete response (CR) was achieved in 35.7%, a partial response in 40.5%. The symptom was relieved in 85.7% sites. The overall response rate was better in patients whose initial tumor size was smaller than 10 cm²(<it>p = 0.010</it>) or who were treated with more than 25 Gy (<it>p = 0.031</it>). The overall CR rate was also higher in those who had smaller tumors (smaller than 6 cm or 30 cm²) (<it>p = 0.015)</it>, or when the tumor was located in soft tissue (<it>p = 0.029</it>).</p> <p>Conclusions</p> <p>Extramedullary lesions in leukemic patients can be successfully treated with RT. The tumor response rate was excellent and symptom relief was achieved in almost all patients. There was a better response to treatment when the tumor was small or it was located in soft tissue. Although, there was no definite correlation between volume reduction and total dose, it seems that higher total dose more of than 25 Gy is needed for better response.</p

Trichostatin A enhances acetylation as well as protein stability of ERα through induction of p300 protein

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Trichostatin A (TSA) is a well-characterized histone deacetylase (HDAC) inhibitor. TSA modifies the balance between HDAC and histone acetyltransferase activities that is important in chromatin remodeling and gene expression. Although several previous studies have demonstrated the role of TSA in regulation of estrogen receptor alpha (ERα), the precise mechanism by which TSA affects ERα activity remains unclear. Methods Transient transfection was performed using the Welfect-EX™Plus procedure. The mRNA expression was determined using RT-PCR. Protein expression and interaction were determined by western blotting and immunoprecipitation. The transfection of siRNAs was performed using the Oligofectamine™ reagent procedure. Results TSA treatment increased acetylation of ERα in a dose-dependent manner. The TSA-induced acetylation of ERα was accompanied by an increased stability of ERα protein. Interestingly, TSA also increased the acetylation and the stability of p300 protein. Overexpression of p300 induced acetylation and stability of ERα by blocking ubiquitination. Knockdown of p300 by RNA interference decreased acetylation as well as the protein level of ERα, indicating that p300 mediated the TSA-induced stabilization of ERα. Conclusions We report that TSA enhanced acetylation as well as the stability of the ERα protein by modulating stability of p300. These results may provide the molecular basis for pharmacological functions of HDAC inhibitors in the treatment of human breast cancer

Mechanisms Underlying Hypoxia Tolerance in Drosophila melanogaster: hairy as a Metabolic Switch

Hypoxia-induced cell injury has been related to multiple pathological conditions. In order to render hypoxia-sensitive cells and tissues resistant to low O2 environment, in this current study, we used Drosophila melanogaster as a model to dissect the mechanisms underlying hypoxia-tolerance. A D. melanogaster strain that lives perpetually in an extremely low-oxygen environment (4% O2, an oxygen level that is equivalent to that over about 4,000 m above Mt. Everest) was generated through laboratory selection pressure using a continuing reduction of O2 over many generations. This phenotype is genetically stable since selected flies, after several generations in room air, survive at this low O2 level. Gene expression profiling showed striking differences between tolerant and naïve flies, in larvae and adults, both quantitatively and qualitatively. Up-regulated genes in the tolerant flies included signal transduction pathways (e.g., Notch and Toll/Imd pathways), but metabolic genes were remarkably down-regulated in the larvae. Furthermore, a different allelic frequency and enzymatic activity of the triose phosphate isomerase (TPI) was present in the tolerant versus naïve flies. The transcriptional suppressor, hairy, was up-regulated in the microarrays and its binding elements were present in the regulatory region of the specifically down-regulated metabolic genes but not others, and mutations in hairy significantly reduced hypoxia tolerance. We conclude that, the hypoxia-selected flies: (a) altered their gene expression and genetic code, and (b) coordinated their metabolic suppression, especially during development, with hairy acting as a metabolic switch, thus playing a crucial role in hypoxia-tolerance

Clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.</p> <p>We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).</p> <p>Results</p> <p>The positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (<it>P </it>= 0.015, <it>P </it>= 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (<it>P </it>= 0.010, <it>P </it>= 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (<it>P </it>= 0.013, <it>P </it>= 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1α, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (<it>P </it>= 0.002).</p> <p>Conclusion</p> <p>p53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.</p

Contribution of discourse and morphosyntax skills to reading comprehension in Chinese dyslexic and typically developing children

This study aimed at identifying important skills for reading comprehension in Chinese dyslexic children and their typically developing counterparts matched on age (CA controls) or reading level (RL controls). The children were assessed on Chinese reading comprehension, cognitive, and reading-related skills. Results showed that the dyslexic children performed significantly less well than the CA controls but similarly to RL controls in most measures. Results of multiple regression analyses showed that word-level reading-related skills like oral vocabulary and word semantics were found to be strong predictors of reading comprehension among typically developing junior graders and dyslexic readers of senior grades, whereas morphosyntax, a text-level skill, was most predictive for typically developing senior graders. It was concluded that discourse and morphosyntax skills are particularly important for reading comprehension in the non-inflectional and topic-prominent Chinese system

Percepção de médicos e enfermeiros da Estratégia de Saúde da Família sobre terapias complementares

OBJECTIVE: To analyze Estratégia de Saúde da Família (Family Health Strategy) professionals' perception of complementary and integrative therapies. METHODS: A study with 177 doctors and nurses was conducted in 2008, based on a self-administered questionnaire. The outcome variables were "interest in complementary and integrative therapies" and "agreement with the National Policy on Complementary and Integrative Therapies. Sex, age, graduate level of education, postgraduate level of education, length of time since graduation, length of time of work, having children, providing complementary and integrative therapies in the workplace, and using homeopathy or acupuncture comprised the independent variables. Data were analyzed using Chi-square test and Fisher's exact test. RESULTS: A total of 17 health centers provided complementary and integrative therapies; 12.4% of professionals had a specialization in homeopathy or acupuncture; 43.5% of doctors were specialists in family and community medicine/family health. Of all participants, 88.7% did not know the national directives for this area, although 81.4% agreed with their inclusion in the Sistema Único de Saúde (Unified Health System). The majority (59.9%) showed an interest in qualifications and all agreed that these therapies should be approached during the graduate course. Agreement with the inclusion of such therapies was significantly associated with the fact of being a nurse (p = 0.027) and using homeopathy for oneself (p = 0.019). Interest in complementary therapies was associated with the use of homeopathy for oneself (p = 0.02) and acupuncture by family members (p = 0.013). CONCLUSIONS: Complementary and integrative therapies are accepted by the professionals studied. This acceptance is associated with previous contact with such therapies and, probably, with residency/specialization in family and community medicine/family health.OBJETIVO: Analisar a percepção de profissionais da Estratégia de Saúde da Família sobre práticas integrativas e complementares. MÉTODOS: Estudo com 177 médicos e enfermeiros a partir de um questionário auto-aplicado em 2008. As variáveis desfecho foram "interesse pelas práticas integrativas e complementares" e "concordância com a Política Nacional de Práticas Integrativas e Complementares". Sexo, idade, graduação, pós-graduação, tempo de formado e de trabalho, possuir filhos, oferta de práticas integrativas e complementares no local de trabalho e uso de homeopatia ou acupuntura compuseram as variáveis independentes. Os dados foram analisados pelo teste do qui-quadrado e teste exato de Fisher. RESULTADOS: Dezessete centros de saúde ofereciam práticas integrativas e complementares; 12,4% dos profissionais possuíam especialização em homeopatia ou acupuntura; 43,5% dos médicos eram especialistas em medicina de família e comunidade/saúde da família. Dos participantes, 88,7% desconheciam as diretrizes nacionais para a área, embora 81,4% concordassem com sua inclusão no Sistema Único de Saúde. A maioria (59,9%) mostrou interesse em capacitações e todos concordaram que essas práticas deveriam ser abordadas na graduação. A concordância com a inclusão dessas práticas mostrou-se associada significativamente com o fato de ser enfermeiro (p = 0,027) e com o uso de homeopatia para si (p = 0,019). Interesse pelas práticas complementares esteve associado a usar homeopatia para si (p = 0,02) e acupuntura para familiares (p = 0,013). CONCLUSÕES: Existe aceitação das práticas integrativas e complementares pelos profissionais estudados, associada ao contato prévio com elas e possivelmente relacionada à residência/especialização em medicina de família e comunidade/saúde da família.OBJETIVO: Analizar la percepción de profesionales de la Estrategia Salud de la Familia sobre prácticas integrales y complementarias. MÉTODOS: Se realizó estudio con 177 médicos y enfermeros a partir de un cuestionario auto-aplicado en 2008. Las variables consideradas fueron "interés por las prácticas integrales y complementarias" y "concordancia con la Política Nacional de prácticas integrales y complementarias". Sexo, edad, estudio universitario, postgrado, tiempo de formación y de trabajo, poseer hijos, oferta de prácticas integrales y complementarias en el lugar de trabajo y uso de homeopatía o acupuntura conformaron las variables independientes. Los datos fueron analizados por la prueba de chi-cuadrado y la prueba exacta de Fisher. RESULTADOS: Diecisiete centros de salud ofrecían prácticas integrales y complementarias; 12,4% de los profesionales poseían especialización en homeopatía o acupuntura; 43,5% de los médicos eran especialistas en medicina de familia y comunidad/salud de la familia. De los participantes, 88,7% desconocían las directrices nacionales para el área, a pesar de que el 81,4% concordasen con su inclusión en el Sistema Único de Salud. La mayoría (59,9%) mostró interés en capacitaciones y todos concordaran que esas prácticas deberían ser abordadas en el estudio universitario. La concordancia con la inclusión de tales prácticas se mostró asociada significativamente con el hecho de ser enfermero (p=0,027) y con el uso de homeopatía para sí mismo (p=0,019). Interés por las prácticas complementarias estuvo asociado con el uso de homeopatía para sí mismo (p=0,02) y acupuntura para familiares (p=0,013). CONCLUSIONES: Existe aceptación de las prácticas integrales y complementarias por los profesionales estudiados, asociada al contacto previo con las mismas y posiblemente relacionada a la residencia/especialización en medicina de familia y comunidad/salud de la familia