Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.

The Anti-Leukemia Effect of Ascorbic Acid: From the Pro-Oxidant Potential to the Epigenetic Role in Acute Myeloid Leukemia.

Data derived from high-throughput sequencing technologies have allowed a deeper understanding of the molecular landscape of Acute Myeloid Leukemia (AML), paving the way for the development of novel therapeutic options, with a higher efficacy and a lower toxicity than conventional chemotherapy. In the antileukemia drug development scenario, ascorbic acid, a natural compound also known as Vitamin C, has emerged for its potential anti-proliferative and pro-apoptotic activities on leukemic cells. However, the role of ascorbic acid (vitamin C) in the treatment of AML has been debated for decades. Mechanistic insight into its role in many biological processes and, especially, in epigenetic regulation has provided the rationale for the use of this agent as a novel anti-leukemia therapy in AML. Acting as a co-factor for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), ascorbic acid is involved in the epigenetic regulations through the control of TET (ten-eleven translocation) enzymes, epigenetic master regulators with a critical role in aberrant hematopoiesis and leukemogenesis. In line with this discovery, great interest has been emerging for the clinical testing of this drug targeting leukemia epigenome. Besides its role in epigenetics, ascorbic acid is also a pivotal regulator of many physiological processes in human, particularly in the antioxidant cellular response, being able to scavenge reactive oxygen species (ROS) to prevent DNA damage and other effects involved in cancer transformation. Thus, for this wide spectrum of biological activities, ascorbic acid possesses some pharmacologic properties attractive for anti-leukemia therapy. The present review outlines the evidence and mechanism of ascorbic acid in leukemogenesis and its therapeutic potential in AML. With the growing evidence derived from the literature on situations in which the use of ascorbate may be beneficial in vitro and in vivo, we will finally discuss how these insights could be included into the rational design of future clinical trials.

[Chronic pain during dialysis. Pharmacologic therapy and its costs]. / Il dolore cronico in dialisi. Terapia farmacologica e i suoi costi.

BACKGROUND: There is very little research into the problem of chronic pain in dialysed patients, despite the fact that pain is a widely diffused phenomena amongst these patients. This work proposes to evaluate the intensity of pain, supply a scale of levels of intervention, with an indication of the consumption and relative costs of pharmacological therapies. METHODS: 37 out of 100 patients undergoing haemodialysis suffer chronic pain. Aetiological research has shown that osteoarticular pain (24 cases), is the most common, peripheral vascular pain (3 cases), is subjectively and indirectly considered to be the most serious form. Nine cases have presented pain of a neuromuscular origin, whilst one case of a neoplastic origin. The degree of personal invalidism shows serious invalidism in 11 cases. RESULTS: The therapeutic file that forsaw four levels of pharmacological intervention (1st levels: FANS, 2nd level: Codeine+paracetamol, 3rd level: Buprenorphine, 4th level: Morphine for os), accompanied by instrumental and pharmacological support intervention, has proved to be indispensable in confronting the problem. Through pharmacy data, we have noticed a progressive increase over the year in the use of analgesic medicines, of which we can confirm the effectiveness, tolerability, low level of side-effects, at low costs. CONCLUSIONS: In our opinion chronic pain in dialysed patients should not be neglected. The perfection of diagnostic techniques, the discovery of pain-killers with reduced side-effects, the multidisciplinary approach, and reduced costs of treatment, are all valid arguments in favour of an intervention that improves the quality of life of these patients, already so compromised by the nature of the illness itself.

[Determination of the copper content in healthy placenta and placenta in gestosis using atomic absorption spectrophotometry]. / Determinazione del contenuto di rame in placente sane e gestosiche mediante spettrofotometria ad assorbimento atomico.

Several complications in pregnancy seem to be related to the fluctuations of serum copper. In particular, values of serum copper over the normal range, have been associated to pregnancies complicated by EPH-gestosis. In this study we have evaluated the copper concentration in samples of placenta from 15 gravidas affected by EPH-gestosis and from 15 healthy gravidas with atom absorption spectrophotometry. The results of our study confirm the presence of an elevated copper concentration in the EPH-gestosis patients group (mean value: 196 micrograms/100 g of placental tissue). We can hypothesize that the result is due to a reduced copper uptake from the fetus.

[Presenile and senile vulvovaginitis. Topical hormonal treatment with estriol]. / Vulvovaginiti presenili e senili. Trattamento topico ormonale con estriolo.

A population of 39 women (average age 64.5 years) suffering from presenile or senile vulvovaginitis was subjected to topical treatment with oestriol-based vaginal cream (daily applications of 0.50 mg of oestriol corresponding to 4 g of cream for 14 days and three times a week in the three following weeks). The results of treatment were assessed on the basis of the clear-cut improvement in symptomatology and the noteworthy increase in the index and volume of maturation of the vaginal epithelium. The effectiveness of topical treatment of postmenopausal vulvovaginitis with oestriol in the absence of unwanted side-effects is confirmed.