Fibroblast growth factors (FGFs) and their receptors are significant components during fundamental cellular processes. FGF18 plays a distinctive role in modulating the activity of both tumor cells ...and tumor microenvironment. This study aims to comprehensively investigate the expression and functional role of FGF18 in gastric cancer (GC) and elucidate its regulatory mechanisms. The upregulation of FGF18 was detected in seven out of eleven (63.6%) GC cell lines. In primary GC samples, FGF18 was overexpressed in genomically stable and chromosomal instability subtypes of GC and its overexpression was associated with poor survival. Knocking down FGF18 inhibited tumor formation abilities, induced G1 phase cell cycle arrest and enhanced anti-cancer drug sensitivity. Expression microarray profiling revealed that silencing of FGF18 activated ATM pathway but quenched TGF-β pathway. The key factors that altered in the related signaling were validated by western blot and immunofluorescence. Meanwhile, treating GC cells with human recombinant FGF18 or FGF18-conditioned medium accelerated tumor growth through activation of ERK-MAPK signaling. FGF18 was further confirmed to be a direct target of tumor suppressor, miR-590-5p. Their expressions showed a negative correlation in primary GC samples and more importantly, re-overexpression of FGF18 partly abolished the tumor-suppressive effect of miR-590-5p. Our study not only identified that FGF18 serves as a novel prognostic marker and a therapeutic target in GC but also enriched the knowledge of FGF-FGFR signaling during gastric tumorigenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The γ‐herpesviruses, EBV and KSHV, are closely associated with a number of human cancers. While the signal transduction pathways exploited by γ‐herpesviruses to promote cell growth, survival and ...transformation have been reported, recent studies have uncovered the impact of γ‐herpesvirus infection on host cell metabolism. Here, we review the mechanisms used by γ‐herpesviruses to induce metabolic reprogramming in host cells, focusing on their ability to modulate the activity of metabolic regulators and manipulate metabolic pathways. While γ‐herpesviruses alter metabolic phenotypes as a means to support viral infection and long‐term persistence, this modulation can inadvertently contribute to cancer development. Strategies that target deregulated metabolic phenotypes induced by γ‐herpesviruses provide new opportunities for therapeutic intervention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background:
Terminal delirium, specifically the hyperactive delirium subtype at the end of life, is common in palliative care patients. Standard care often involves sedation to alleviate distress. ...The alpha2-adrenoreceptor agonist dexmedetomidine may have promise in terminal delirium, due to its properties of decreasing delirium and permitting rousable sedation.
Aim:
This study aimed to describe the effect of dexmedetomidine on delirium and sedation, when delivered via continuous subcutaneous infusion (CSCI) in patients with terminal delirium.
Design:
The trial was prospectively registered in the ANZCTR database (ACTRN12618000658213) and conducted in accordance with CONSORT (pilot study extension). Twenty-two adult patients were treated with a CSCI of dexmedetomidine with a two-tier dose schedule, low and high dose. Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS, target <13), and sedation by the Richmond Agitation-Sedation Scale, Palliative Version (RASS-PAL, target −1 to −3).
Results:
All patients had a response to dexmedetomidine as measured by decrease in MDAS after initiation; 59% required escalation to high dose to maintain control of delirium. All responses to high dose were sustained. RASS-PAL scores showed significant variability, however mean scores remained within target range on both doses, and the majority of patients were rousable. Fifty percent of patients treated crossed over to standard care; no patients who crossed over were experiencing moderate-severe delirium. Predominant reason for crossover was family request for deeper sedation.
Conclusion:
Dexmedetomidine shows potential for the management of terminal delirium with improved interactivity. Further research is needed to determine efficacy compared to current standard care.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. It is also characterized by heavy infiltration with non-malignant leucocytes. The EBV-encoded latent ...membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signaling pathways which collectively promote cell proliferation and survival, angiogenesis, invasiveness, and aerobic glycolysis. LMP1 also affects cell-cell interactions, antigen presentation, and cytokine and chemokine production. Here, we discuss how LMP1 modulates local immune responses that contribute to the establishment of the NPC tumor microenvironment. We also discuss strategies for targeting the LMP1 protein as a novel therapy for EBV-driven malignancies.
Phototherapy with low-level coherent light (laser) has been reported as an analgesic and anti-inflammatory as well as having a positive effect in tissue repair in orthodontics. However, there are few ...clinical studies using low-level LED therapy (non-coherent light). The aim of the present study was to analyze the pain symptoms after orthodontic tooth movement associated with and not associated with coherent and non-coherent phototherapy. Fifty-five volunteers (mean age = 24.1 ± 8.1 years) were randomly divided into four groups: G1 (control), G2 (placebo), G3 (protocol 1: laser, InGaAlP, 660 nm, 4 J/cm
2
, 0.03 W, 25 s), G4 (protocol 2: LED, GaAlAs, 640 nm with 40 nm full-bandwidth at half-maximum, 4 J/cm
2
, 0.10 W, 70 s). Separators were used to induce orthodontic pain and the volunteers pain levels were scored with the visual analog scale (VAS) after the separator placement, after the therapy (placebo, laser, or LED), and after 2, 24, 48, 72, 96, and 120 h. The laser group did not have statistically significant results in the reduction of pain level compared to the LED group. The LED group had a significant reduction in pain levels between 2 and 120 h compared to the control and the laser groups. The LED therapy showed a significant reduction in pain sensitivity (an average of 56%), after the orthodontic tooth movement when compared to the control group.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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