instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, current therapy options are not satisfactory. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.', 'We assessed the effects of PKI-587 in different GEP-NEN tumor models, including poorly differentiated cell line LCC-18, compared with the established mTORC1 inhibitor everolimus.', 'We treated the cell lines BON, QGP1, KRJ-I and LCC-18 with increasing concentrations of the inhibitor PKI-587, and compared with everolimus and DMSO. We assessed the impact of treatments on viability (WST-1 assay), on apoptotic processes (Caspase 3/7 assay, JC-1) and on cell cycle regulation (flow cytometry). We determined alterations of signaling mediators by phosphor-specific western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology).', 'In all cell lines, PKI-587 dose-dependently inhibited proliferation whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest, induction of apoptosis and successfully suppressed activity of direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT and PI3K pathway genes after treatment. Treatment dependent and cell line characteristic effects on AKT/RB/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this article.\Question: Is inhibition of mTORs Catalytic Site by PKI-587 a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease?
answer:
PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials.


question:
Context: The present study was designed to investigate whether H2S can protect testicular germ cells against heat exposure induced injury and the underlying mechanisms.', 'It was found that all three H2S generating enzymes, cystathionine β-synthase (CBS), cystathionine γ-lysase (CSE), and 3-mercaptopyruvate sulfurtransferase (3 MST), were expressed in mouse testicular tissue. Three episodes of heat exposure (42 °C, 30 min/day, 3 days) significantly decreased endogenous H2S production and down-regulated the expression of CBS and CSE in testes. In primary cultured testicular germ cells, exogenous application of NaHS (an H2S donor) attenuated heat stress (42 °C, 30 min) induced cell death and apoptosis. This was mediated by the inhibitory effects of H2S on cytochrome C release and the ratio of the Bax/Bcl-2. NaHS also improved mitochondrial function by decreasing oxygen consumption and increasing ATP production. NaHS treatment also stimulated SOD activity and reduced ROS production.\Question: Does hydrogen sulfide protect testicular germ cells against heat-induced injury?
answer:
Our results revealed both physiological and pharmacological roles of H2S in testicular germ cells. Exogenous application of H2S may protect germ cells by preservation of mitochondrial function and stimulation of anti-oxidant activity.


question:
Context: The goals of this study were to determine if β-acid from hops (Humulus lupulus L.) could be used to control fructan fermentation by equine hindgut micro-organisms, and to verify the antimicrobial mode of action on Streptococcus bovis, which has been implicated in fructan fermentation, hindgut acidosis and pasture-associated laminitis (PAL) in the horse.', 'Suspensions of uncultivated equine faecal micro-organisms produced fermentation acids when inulin (model fructan) was the substrate, but β-acid (i.e. lupulone) concentrations ≥9\xa0ppm inhibited lactate production and mitigated the decrease in pH. Inulin-fermenting Strep.\xa0bovis was isolated from the β-acid-free suspensions after enrichment with inulin. The isolates were sensitive to β-acid, which decreased the viable number of streptococci in faecal suspensions, as well as growth, lactate production and the intracellular potassium of Strep.\xa0bovis in pure culture.\Question: Does inhibition of fructan-fermenting equine faecal bacteria and Streptococcus bovis by hop ( Humulus lupulus L. ) β-acid?
answer:

These results are consistent with the hypothesis that hops β-acid prevented the growth of fructan-fermenting equine faecal bacteria, and that the mechanism of action was dissipation of the intracellular potassium of Strep. bovis.