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Background: Sirtuins have an important role in the regulation of metabolic and biological processess. Thus, we hypothesized that foods that could activate sirtuins, known as "sirtfood", may improve health status. So, this study was aimed at investigating the association between the amount of sirtfood intake and the risk of major adverse cardiovascular events (MACE). Methods: In this cohort study, 2918 adults who had no history of MACE at the start of the study (2006–2008) participated and were followed up on until 2018. The amount of sirtfoods intake (servings per week) was computed using a validated food frequency questionnaire. Each patient's medical records were evaluated to detect MACE. The Cox proportional hazards model was applied to assess the association between the amount of sirtfood intake and the risk of MACE. Results: The median duration of the study was 10.6 years. The hazard ratio (HR) for the risk of MACE was 0.70 for the second (95% CI: 0.50, 0.98) and 0.60 (95% CI: 0.42, 0.86) for the third tertile of sirtfoods intake compared with the first tertile. This association was nonlinear, and sirtfoods consumption of more than five servings per week did not result in a lower risk of MACE. In addition, there was a significant interaction between age (P-interaction < 0.001) and sirtfoods intake in relation to MACE occurrence. When assessing sirtfood components, compared with the lowest intake, the highest amount of soy (HR: 0.74, 95% CI: 0.56, 0.99) and parsley (HR: 0.62, 95% CI: 0.47, 0.83) intake was related to a lower risk of MACE. Conclusion: Our results indicated an inverse association between a higher amount of sirtfood intake and a lower risk of MACE incidents. This association was nonlinear, and having more than five servings of sirtfood per week did not reduce the risk of MACE any further. [ABSTRACT FROM AUTHOR]

Background: A link between tendinopathy and oxidative stress has been recently reported. Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide, which plays an important role in cell redox homeostasis. The aim of this study was to evaluate the antioxidant effect of NMN on tendinopathy in vitro and in vivo. Methods: Tenocytes from healthy Sprague-Dawley rats were cultured in regular glucose (RG) and high-glucose (HG) conditions with or without NMN, and were divided into four groups: RG NMN(−), RG NMN(+), HG NMN(−), and HG NMN(+). Cell viability, reactive oxygen species (ROS) accumulation, apoptotic rate, and mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, interleukin (IL)6, sirtuin (SIRT)1, and SIRT6 were investigated. In addition, rats with collagenase-induced tendinopathy were treated with or without NMN. Immunostaining of NOX1 and NOX4; mRNA expression of SIRT1, SIRT6, and IL6; and superoxide dismutase (SOD) activity measurements in the Achilles tendon were performed. Results: NMN increased the expression of SIRT1 and SIRT6 in rat tenocytes, but decreased the levels of NOX1, NOX4, IL6, ROS, and apoptosis. In Achilles tendons with collagenase-induced tendinopathy, NMN increased the mRNA expression of SIRT1 and SIRT6, as well as SOD activity; while suppressing protein expression of NOX1 and NOX4, and mRNA expression of IL6. Conclusion: The in vitro and in vivo results of this study show that NMN exerts an antioxidant effect on tendinopathy by promoting the expression of SIRT while inhibiting that of NOX. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is the fourth most common cancer and the third leading cancer-related cause of death worldwide since most patients are diagnosed at an advanced stage. The majority of GCs are adenocarcinomas (ACs), and the poorly characterized clear cell AC represents a unique subgroup of GCs and is an independent marker of poor prognosis. Even though the prognosis for patients with advanced GC is poor we present a report of a patient with long-term survival despite having liver metastases from clear cell gastric AC.Case Presentation: A 45-year-old male with clear cell gastric AC underwent subtotal gastrectomy and postoperative chemoradiation. Only a year and a half after his initial treatment the disease spread to his liver. He received two lines of chemotherapy treatment within the next two years before a right hepatectomy was suggested. Due to an initially insufficient future liver remnant (FLR), transarterial chemoembolization (TACE) and portal vein embolization (PVE) were performed, which made the surgical procedure possible. Shortly after a disease progression in the remaining liver was detected. In the following three years the patient was treated with a carefully planned combination of systemic therapy and different interventional oncology techniques including selective internal radiation therapy (SIRT) and TACE. And as illustrated, an attentive, patient-tailored, multimodality treatment approach can sometimes greatly benefit our patients as he had an overall survival of 88 months despite the poor prognosis of his disease.Conclusion: To the best of our knowledge, this report is the first to describe a patient with liver metastases from clear cell gastric AC treated with interventional oncology techniques (PVE, TACE, and SIRT) in combination with other locoregional and systemic therapies thereby presenting that these interventional oncology techniques can be successfully integrated into long-term management of non-conventional liver tumors. [ABSTRACT FROM AUTHOR]

Background: The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with systemic chemotherapy in the treatment of liver-dominant metastatic pancreatic ductal adenocarcinoma, with the aim of destroying liver metastases and improving patient outcomes.Methods: We retrospectively evaluated 16 patients with liver-dominant metastatic pancreatic ductal adenocarcinoma who underwent TARE between February 2012 and August 2015; 15 of these patients also underwent concurrent systemic chemotherapy. Patient outcomes were assessed using Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1 and included disease response, median overall survival from the time of diagnosis of metastatic disease, and median overall survival following receipt of TARE. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.Results: The median overall survival from the time of diagnosis of metastatic disease and following receipt of TARE was 22.0 and 12.5 months, respectively. Overall and liver specific disease response were assessed for 13 patients with follow-up imaging available at the time of study (range 2-13 weeks post TARE). Four patients (31 %) demonstrated partial response and five patients (38 %) had stable disease in the liver at follow-up. One patient developed grade 3 elevation of total bilirubin three months post-treatment and another patient developed radiation cholecystitis directly following TARE. No treatment-related grade 4 or 5 toxicities were seen.Conclusion: TARE can be safely combined with systemic chemotherapy for the treatment of liver-dominant metastatic pancreatic cancer. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration.Methods: A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium(90) or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9).Results: Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT.Conclusions: It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced metastatic disease of breast cancer be undertaken, with an appropriate patients' stratification, set-up of the relevant patient profiles and disease modelling. [ABSTRACT FROM AUTHOR]

Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma.Methods: Patients received yttrium-90-labelled ((90)Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m(2)) with the option to switch to gemcitabine (1000 mg/m(2)) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥ 16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function.Results: Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median (90)Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93% (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19-9 was 72%. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57%) patients during days 0-60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT.Conclusions: SIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies.Trial Registration: ACTRN12606000015549. [ABSTRACT FROM AUTHOR]

Background: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an established locoregional treatment option for unresectable hepatocellular carcinoma (HCC), which delivers a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy tissue. DOORwaY90 is a prospective, multicenter, open-label, single arm study, designed to evaluate the safety and effectiveness of 90Y resin microspheres as first-line treatment in patients with unresectable/unablatable HCC. It is unique in that it is the first study with resin microspheres to utilize a personalized 90Y dosimetry approach, and independent review for treatment planning and response assessment.Methods: Eligibility criteria include unresectable/unablatable HCC, Barcelona Clinic Liver Cancer stage A, B1, B2, or C with a maximal single tumor diameter of ≤ 8 cm, and a sum of maximal tumor diameters of ≤ 12 cm, and at least one tumor ≥ 2 cm (long axis) per localized, modified Response Evaluation Criteria in Solid Tumors. Partition model dosimetry is used to determine the optimal dose; the target mean dose to tumor is ≥ 150 Gy. Patients are assessed at baseline and at regular intervals up until 12 months of treatment for response rates, safety, and quality of life (QoL). Post-treatment dosimetry is used to assess dose delivered to tumor and consider if retreatment is necessary. The co-primary endpoints are best objective response rate and duration of response. Secondary endpoints include grade ≥ 3 toxicity, QoL, and incidence of liver resection and transplantation post SIRT. Target recruitment is 100 patients.Discussion: The results of this trial should provide further information on the potential use of SIRT with 90Y resin microspheres as first-line therapy for unresectable HCC.Trial Registration: Clinicaltrials.gov; NCT04736121; date of 1st registration, January 27, 2021, https://clinicaltrials.gov/ct2/show/NCT04736121 . [ABSTRACT FROM AUTHOR]