Very long chain fatty acid metabolism is required in acute myeloid leukemia

Acute myeloid leukemia (AML) cells have an atypical metabolic phenotype characterized by increased mitochondrial mass, as well as a greater reliance on oxidative phosphorylation and fatty acid oxidation (FAO) for survival. To exploit this altered metabolism, we assessed publicly available databases to identify FAO enzyme overexpression. Very long chain acyl-CoA dehydrogenase (VLCAD; ACADVL) was found to be overexpressed and critical to leukemia cell mitochondrial metabolism. Genetic attenuation or pharmacological inhibition of VLCAD hindered mitochondrial respiration and FAO contribution to the tricarboxylic acid cycle, resulting in decreased viability, proliferation, clonogenic growth, and AML cell engraftment. Suppression of FAO at VLCAD triggered an increase in pyruvate dehydrogenase activity that was insufficient to increase glycolysis but resulted in adenosine triphosphate depletion and AML cell death, with no effect on normal hematopoietic cells. Together, these results demonstrate the importance of VLCAD in AML cell biology and highlight a novel metabolic vulnerability for this devastating disease

Advances in the Research and Development of Natural Health Products as Main Stream Cancer Therapeutics

Natural health products (NHPs) are defined as natural extracts containing polychemical mixtures; they play a leading role in the discovery and development of drugs, for disease treatment. More than 50% of current cancer therapeutics are derived from natural sources. However, the efficacy of natural extracts in treating cancer has not been explored extensively. Scientific research into the validity and mechanism of action of these products is needed to develop NHPs as main stream cancer therapy. The preclinical and clinical validation of NHPs would be essential for this development. This review summarizes some of the recent advancements in the area of NHPs with anticancer effects. This review also focuses on various NHPs that have been studied to scientifically validate their claims as anticancer agents. Furthermore, this review emphasizes the efficacy of these NHPs in targeting the multiple vulnerabilities of cancer cells for a more selective efficacious treatment. The studies reviewed here have paved the way for the introduction of more NHPs from traditional medicine to the forefront of modern medicine, in order to provide alternative, safer, and cheaper complementary treatments for cancer therapy and possibly improve the quality of life of cancer patients

Correlation of NM23-H1 cytoplasmic expression with metastatic stage in human prostate cancer tissue

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Results of the first European Source Apportionment intercomparison for Receptor and Chemical Transport Models

In this study, the performance of the source apportionment model applications were evaluated by comparing the model results provided by 44 participants adopting a methodology based on performance indicators: z-scores and RMSEu, with pre-established acceptability criteria. Involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), provided a unique opportunity to cross-validate them. In addition, comparing the modelled source chemical profiles, with those measured directly at the source contributed to corroborate the chemical profile of the tested model results. The most used RM was EPA- PMF5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) and more difficulties are observed with SCE time series (72% of RMSEu accepted). Industry resulted the most problematic source for RMs due to the high variability among participants. Also the results obtained with CTMs were quite comparable to their ensemble reference using all models for the overall average (>92% of successful z-scores) while the comparability of the time series is more problematic (between 58% and 77% of the candidates’ RMSEu are accepted). In the CTM models a gap was observed between the sum of source contributions and the gravimetric PM10 mass likely due to PM underestimation in the base case. Interestingly, when only the tagged species CTM results were used in the reference, the differences between the two CTM approaches (brute force and tagged species) were evident. In this case the percentage of candidates passing the z-score and RMSEu tests were only 50% and 86%, respectively. CTMs showed good comparability with RMs for the overall dataset (83% of the z-scores accepted), more differences were observed when dealing with the time series of the single source categories. In this case the share of successful RMSEu was in the range 25% - 34%.JRC.C.5-Air and Climat

Contributi per una flora vascolare di Toscana. VIII (440-506)

New localities and/or confirmations concerning 67 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 59 genera and 37 families are presented: Alisma (Alismataceae), Amaranthus (Amaranthaceae), Leucojum, Sternbergia, Tristagma (Amaryllidaceae), Aloe (Asphodelaceae), Erigeron, Galinsoga, Hieracium, Rhagadiolus, Silybum, Soliva, Taraxacum (Asteraceae), Impatiens (Balsaminaceae), Berberis (Berberidaceae), Cardamine (Brassicaceae), Opuntia (Cactaceae), Cephalaria, Sixalix, Succisa (Caprifoliaceae), Silene (Caryophyllaceae), Convolvulus, Ipomoea (Convolvulaceae), Aeonium (Crassulaceae), Scirpus (Cyperaceae), Equisetum (Equisetaceae), Euphorbia (Euphorbiaceae), Astragalus, Trifolium (Fabaceae), Quercus (Fagaceae), Crocus (Iridaceae), Juncus (Juncaceae), Utricularia (Lentibulariaceae), Peplis (Lythraceae), Maclura (Moraceae), Nymphaea (Nymphaeaceae), Oenothera (Onagraceae), Anacamptis, Orchis (Orchidaceae), Orobanche (Orobanchaceae), Callitriche, Veronica (Plantaginaceae), Alopecurus, Eleusine, Glyceria, Phleum (Poaceae), Persicaria, Polygonum (Polygonaceae), Groenlandia (Potamogetonaceae), Clematis, Pulsatilla, Ranunculus (Ranunculaceae), Rhamnus (Rhamnaceae), Fragaria, Potentilla, Pyracantha (Rosaceae), Galium (Rubiaceae), Sparganium (Typhaceae), Vitis (Vitaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed

Contributi per una flora vascolare di Toscana. VIII (440-506) [Contributions for a vascular flora of Tuscany. VIII (440-506)]

Contributions for a vascular flora of Tuscany. VIII (440-506). New localities and/or confirmations concerning 67 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 59 genera and 37 families are presented: Alisma (Alismataceae), Amaranthus (Amaranthaceae), Leucojum, Sternbergia, Tristagma (Amaryllidaceae), Aloe (Asphodelaceae), Erigeron, Galinsoga, Hieracium, Rhagadiolus, Silybum, Soliva, Taraxacum (Asteraceae), Impatiens (Balsaminaceae), Berberis (Berberidaceae), Cardamine (Brassicaceae), Opuntia (Cactaceae), Cephalaria, Sixalix, Succisa (Caprifoliaceae), Silene (Caryophyllaceae), Convolvulus, Ipomoea (Convolvulaceae), Aeonium (Crassulaceae), Scirpus (Cyperaceae), Equisetum (Equisetaceae), Euphorbia (Euphorbiaceae), Astragalus, Trifolium (Fabaceae), Quercus (Fagaceae), Crocus (Iridaceae), Juncus (Juncaceae), Utricularia (Lentibulariaceae), Peplis (Lythraceae), Maclura (Moraceae), Nymphaea (Nymphaeaceae), Oenothera (Onagraceae), Anacamptis, Orchis (Orchidaceae), Orobanche (Orobanchaceae), Callitriche, Veronica (Plantaginaceae), Alopecurus, Eleusine, Glyceria, Phleum (Poaceae), Persicaria, Polygonum (Polygonaceae), Groenlandia (Potamogetonaceae), Clematis, Pulsatilla, Ranunculus (Ranunculaceae), Rhamnus (Rhamnaceae), Fragaria, Potentilla, Pyracantha (Rosaceae), Galium (Rubiaceae), Sparganium (Typhaceae), Vitis (Vitaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p