MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells

The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors.     

The clinicopathologic spectrum of segmental membranous glomerulopathy

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Ocena skuteczności Lactobacillus rhamnosus ATC A07FA w zapobieganiu martwiczego zapalenia jelit wcześniaków z bardzo małą urodzeniową masą ciała: badanie z randomizacją (wstępne wyniki)

BackgroundEvidence suggests that probiotics, as a group, are reducing the risk of necrotizing enterocolitis (NEC). The efficacy of each probiotic strain needs to be evaluated separately.ObjectiveTo evaluate the efficacy of administering Lactobacillus rhamnosus ATC A07FA (L. rhamnosus) for the prevention of necrotizing enterocolitis (NEC) ≥2 by the criteria of Bell in very low-birth-weight preterm infants.MethodPreterm infants children fulfillingthe inclusion criteria (gestational age <32 weeks and birth weight <1500 g and partial orfull enteral feeding) were enrolled in a randomized, double-blind, placebo-controlled trial. They received L. rhamnosus (commercially available as Lakcid) at a dose of 1.2 × 10¹⁰ CFU or a placebo orally, twice daily, for the duration of the hospital stay. The primary outcome measures were NEC ≥2 by the criteria of Beli, sepsis and death.ResultsThe study was stopped prematurely because of slow recruitment. Data from 55 preterm infants were included in the fina? analysis. In the experimental group, compared with the placebo group, the risk of developing NEC ≥2 by the criteria of Beli was reduced, however the difference was not statistically significant (1/30; 3.3% versus A/25; 16%, RR 0.2, 95% Cl 0.02 do 1.75). L. rhamnosus did not significantly affect the risk of developing sepsis or death. There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes. No adverse events were reported.ConclusionThe administration of L. rhamnosus ATC A07FA compared with placebo had no effect on the incidence of NEC. Further studies with sufficient sample size are warranted.     

Stuck in time – a new Chaenothecopsis species with proliferating ascomata from Cunninghamia resin and its fossil ancestors in European amber

Resin protects wounded trees from microbial infection, but also provides a suitable substrate for the growth of highly specialized fungi. Chaenothecopsis proliferatus is described growing on resin of Cunninghamia lanceolata from Hunan Province, China. The new fungus is compared with extant species and two new fossil specimens from Eocene Baltic and Oligocene Bitterfeld ambers. The Oligocene fossil had produced proliferating ascomata identical to those of the newly described species and to other extant species of the same lineage. This morphology may represent an adaptation to growing near active resin flows: the proliferating ascomata can effectively rejuvenate if partially overrun by fresh, sticky exudate. Inward growth of fungal hyphae into resin has only been documented from Cenozoic amber fossils suggesting comparatively late occupation of resin as substrate by fungi. Still, resinicolous Chaenothecopsis species were already well adapted to their special ecological niche by the Eocene, and the morphology of these fungi has since remained remarkably constant.     

Osmotic nephrosis with mannitol: review article

Mannitol is commonly used to lower intracranial and intraocular pressures. Large doses/massive infusions of mannitol have been found to be associated with acute renal failure (MI-ARF), that is, osmotic nephrosis. While many researchers have reported individual experiences with this pathology, we felt that there is need of an updated comprehensive review of all reported cases with elaboration of etiology, pathogenesis, diagnosis and management plan for MI-ARF. The purpose of the present communication is to share our own experience with MI-ARF, to review the effect of mannitol on kidney function and to highlight the dynamics of MI-ARF with considerations for the cautious use of mannitol in patients with risk factors for kidney diseases.