The Metabolism of Lymphomas.
The metabolism of lymphomas.
Curr Opin Hematol. 2013 May 13;
Calvo-Vidal MN, Cerchietti L
PURPOSE OF REVIEW: Cellular to animal to human studies are shedding light on metabolic pathways that contribute to sustaining lymphomagenesis. Old players with new metabolic tricks and new metabolic players come into the scene. The purpose of this review is to discuss the recent advances made in the field of lymphoma metabolism with special focus on the metabolic modulation of tumor promoting and suppressing pathways and, conversely, on the effect of these pathways on metabolite addiction. RECENT FINDINGS: The basis for the high glucose uptake and glycolytic activity in lymphoma cells is now beginning to be understood. Recent findings suggest a greater role of nucleotide biosynthesis as a major driving force for glycolysis, especially during proliferation and cellular stress conditions. There is new evidence for an increasing contribution of glycine-folate metabolism deregulation in nucleotide biosynthesis, genome integrity and epigenetic maintenance. Expanding roles for MYC, PI3K and TP53 in regulating reactive oxygen production, glycolysis and glutaminolysis in lymphoma cells have been described. The identification of novel pathways has allowed the emergence of new ‘antimetabolite’ strategies to increase the therapeutic efficacy of current approaches. SUMMARY: Metabolism in lymphomas must fulfill the general demands from cell proliferation and those specific to lymphomagenesis. Data emerging from preclinical studies are elucidating the metabolic pathways that contribute to maintaining the malignant phenotype in lymphomas. This has resulted in identification of novel pathways, some of which may have a clinical impact in the diagnosis, characterization and treatment of lymphoma subtypes. HubMed – addiction
Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis: alternative drivers in anaplastic large cell lymphoma.
Curr Opin Hematol. 2013 May 13;
Tabbò F, Ponzoni M, Rabadan R, Bertoni F, Inghirami G,
PURPOSE OF REVIEW: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NF?B, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients. HubMed – addiction
Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens.
Chin Med J (Engl). 2013 May; 126(10): 1939-1943
Ma Y, Chen N, Wang HM, Meng FG, Zhang JG
BACKGROUND: Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens (NAc) in addiction. Deep brain stimulation (DBS) has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats. METHODS: A morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey’s tests for multiple post hoc comparisons. RESULTS: High-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS ((268.25 ± 25.07) seconds) was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration ((303.29 ± 34.22) seconds). High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory. CONCLUSION: Bilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction. HubMed – addiction