The uptake and retention of ET by the body suggests an important physiological function. The decreasing trend of oxidative damage biomarkers is consistent with animal studies suggesting that ET may function as a major antioxidant but perhaps only under conditions of oxidative stress. Antioxid. Redox Signal. 26, 193-206.

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L-ergothioneine (ET), a putative antioxidant compound acquired by animals through dietary sources, has been suggested to accumulate in certain cells and tissues in the body that are predisposed to high oxidative stress. In the present study, we identified an elevation of ET in the liver of a guinea pig model of non-alcoholic fatty liver disease (NAFLD), elucidated a possible mechanism for the increased uptake and investigated the possible role for this accumulation. This increase in liver ET levels correlated with cholesterol accumulation and disease severity. We identified an increase in the transcriptional factor, RUNX1, which has been shown to upregulate the expression of the ET-specific transporter OCTN1, and could consequently lead to the observable elevation in ET. An increase was also seen in heat shock protein 70 (HSP70) which seemingly corresponds to ET elevation. No significant increase was observed in oxidative damage markers, F2-isoprostanes, and protein carbonyls, which could possibly be attributed to the increase in liver ET through direct antioxidant action, induction of HSP70, or by chelation of Fe(2+), preventing redox chemistry. The data suggest a novel mechanism by which the guinea pig fatty liver accumulates ET via upregulation of its transporter, as a possible stress response by the damaged liver to further suppress oxidative damage and delay tissue injury. Similar events may happen in other animal models of disease, and researchers should be aware of the possibility.

The abnormal accumulation of β‐amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ‐mediated neurotoxicity remain elusive, Aβ has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione‐derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET’s potential to counteract Aβ‐toxicity in transgenic Caenorhabditis elegans overexpressing a human Aβ peptide. The accumulation of Aβ in this model leads to paralysis and premature death. We show that ET dose‐dependently reduces Aβ‐oligomerization and extends the lifespan and healthspan of the nematodes.

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therapeutic option has different risk-benefi t profi les. Hence the rationale, indications, risks and benefi ts are presented to assist the clinician in his discussion with his patient. The committee favours this open discussion strategy over explicit and potentially dogmatic emphasis on certain therapeutic strategies. Other novel therapies currently used in Singapore are also included and specifi cally highlighted for selective risk groups only. A detailed statement as to the investigative nature of these therapies is also included.Published data on cost-benefi t issues for prostate cancer in Singapore are currently lacking and cost discussions differ in different institutions with varying extent of government subsidies and service grants. Hence cost considerations were not included in this set of guidelines. Defi nition of Terms Early Prostate CancerThis refers to clinically localised prostate cancer without evidence of regional lymph node and distant metastasis. Treatment is mainly with curative intent in patients with longer life expectancy and minimal comorbidity. Locally Advanced Prostate CancerThis refers to clinically locally advance prostate cancer (≥T3b) with or without lymph node invasion within the pelvis. Treatment requires aggressive local multimodality therapy with surgery and/or defi nitive radiation therapy, combined either with or without androgen deprivation therapy. Metastatic Prostate CancerThis refers to prostate cancer with lymph node invasion beyond the pelvis and/or bony or visceral spread. Treatment

This study aimed to examine if exposure to ionizing radiation during clinical radiotherapy (RT) causes increased oxidative damage. Seven patients with nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial study. Blood and urine samples were obtained for F(2)-isoprostanes (F(2)-IsoPs) measurement. Urinary F(2)-IsoPs levels were elevated pre-treatment and remained high (but did not increase) during treatment, but decreased to the normal range after treatment. Plasma F(2)-IsoPs decreased significantly after the start of treatment before rising midway through treatment. Levels decreased significantly to below baseline following treatment. However, the patients were observed to have substantially lower levels of plasma esterified arachidonic acid (AA) residues than controls. The data shows that NPC is associated with elevated F(2)-isoprostanes in urine and in plasma after correction for decreased AA levels. RT did not increase these levels and, indeed, was associated with falls in F(2)-IsoPs. The validity and usefulness of correction of plasma F(2)-IsoPs for lowered AA levels is discussed.

BackgroundTo report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14‐year period, and to determine the impact of dose escalation of prostate cancer outcomes.MethodsPatients with T1–T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5‐year overall survival (OS). The secondary endpoints were 5‐year freedom from biochemical failure (FFBF) and treatment toxicities.ResultsA total of 200 eligible patients were identified. Median follow‐up duration was 48 months. 13%, 36% and 51% of patients had low‐, intermediate‐ and high‐risk disease. Median dose was 79.2 Gy. The 5‐year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low‐, intermediate‐ and high‐risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95–10.08; P < 0.01).ConclusionMen with localized prostate cancer treated with EBRT in our population had excellent 5‐year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose‐escalated EBRT.