tbuckley/cabot-search huggingface dataset:
Abstract 6630: Synergistic immuno photothermal nanotherapy (SYMPHONY) for combination cancer therapy
Authors: Yang Liu, Paolo Maccarini, Gregory M. Palmer, Brant A. Inman, Peter E. Fecci, Tuan Vo-Dinh
Journal: Cancer Research (2020)

Abstract Checkpoint inhibitor immunotherapy has been a revolutionary milestone in cancer treatment because it can counter the tumor immunosuppressive environment to improve patients' overall survival and even result in a durable complete response. However, only a fraction of patients benefit from checkpoint inhibitor immunotherapy. Improving the response rate and maximizing efficacy for immunotherapy are still unmet needs of great clinical significance. We have developed a novel combination cancer therapy referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by integrating plasmonic gold nanostars (GNS)-mediated photothermal therapy with anti-PD-L1 checkpoint inhibitor immunotherapy to improve the therapeutic efficacy of cancer treatment. GNS nanoparticles are superior photon-to-heat conversion transducers for photothermal therapy because they have tip-enhanced plasmonics from multiple sharp spikes and tunable plasmonic absorption in the near-infrared tissue optical window. Our in vivo experimental results with bladder cancer and brain cancer murine animal models have demonstrated that photothermal therapy with GNS in combination with anti-PD-L1 checkpoint inhibitor immunotherapy not only effectively ablates primary tumor with laser irradiation but also stimulates the immune response to treat distant tumors without laser irradiation. Furthermore, a rechallenge study performed three months later using cancer cells injected into long-term survivors demonstrates that SYMPHONY therapy can generate a long-term memorized immune response and prevent cancer recurrences in cured mice. The SYMPHONY combination therapy results in synergistic treatment surpassing what either single treatment can achieve, and shows the great promise for future translational medicine studies to treat aggressive metastatic cancer diseases. Citation Format: Yang Liu, Paolo Maccarini, Gregory M. Palmer, Brant A. Inman, Peter E. Fecci, Tuan Vo-Dinh. Synergistic immuno photothermal nanotherapy (SYMPHONY) for combination cancer therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6630.
Reply to Roderick C.N. van den Bergh, Olivier Rouvière, and Theodorus van der Kwast’s Letter to the Editor re: Andrew Vickers, Sigrid V. Carlsson, Matthew Cooperberg. Routine Use of Magnetic Resonance Imaging for Early Detection of Prostate Cancer Is Not Justified by the Clinical Trial Evidence. Eur Urol 2020;78:304–6. Prebiopsy MRI: Through the Looking Glass
Authors: Andrew Vickers, Sigrid V. Carlsson, Matthew Cooperberg
Journal: European Urology (2020)
Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis
Authors: Pauline Boucheron, Ying Lu, Kyoko Yoshida, Tianshuo Zhao, Anna L Funk, Françoise Lunel-Fabiani, Alice Guingané, Edouard Tuaillon, Judith van Holten, Roger Chou, Marc Bulterys, Yusuke Shimakawa
Journal: The Lancet Infectious Diseases (2020)
MET protein is phosphorylated in human clear cell renal carcinoma
Authors: Noboru Nakaigawa, Shingo Kato, Masaya Baba, Takeshi Kishida, Hiroji Uemura, Masahiro Yao, Yoshinobu Kubota
Journal: Cancer Research (2006)

1652  It was well known that inactivation of VHL gene predisposes human clear renal cell carcinoma (CCRC). But details about critical roles of VHL inactivation during early stage of tumorigenisis are still unknown. MET protein is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF) to regulate cell growth, cell morphology, and cell motility. We previously reported that MET protein was overexpressed and phosphorylated without HGF/SF in established CCRC cells, 786-O, UMRC-3 and UMRC-6. This constitutive phosphorylation of MET protein in was inhibited by the rescue of exogenous wild-type VHL gene without decrease in expression level of MET protein. Additionally, K252a, MET specific inhibitor, inhibited cell growth and tumorigenesis of established CCRC cells (AACR annual meeting 2005). These results were based on the established CCRC cells. The phosphorylation status of MET protein in human CCRC tumor tissues has not been reported. In this study, we analyzed the phosphorylation status of MET protein in 18 CCRC tumor tissues and normal kidney tissue gained by surgeries. MET protein was overexpressed in 14 CCRC tissues (78%) compared with that in normal kidney tissues. The phosphorylation level of MET protein in CCRC tumor was increased in all of 18 tumor tissues compared with normal tissue. Interestingly MET protein was hyperphosphorylated compared with that in normal tissue in all of 4 CCRC tissues with the same expression level of MET protein as that in normal tissue. This result meant that MET protein was phosphorylated in CCRC dependently on its expression levels. We concluded that MET protein had potency as a target molecule for renal carcinoma therapy.
The Predictive Role of Left and Right Ventricular Speckle-Tracking Echocardiography in COVID-19
Authors: Ehud Rothschild, Guy Baruch, Yishay Szekely, Yael Lichter, Alon Kaplan, Philippe Taieb, Michal Laufer-Perl, Gil Beer, Livia Kapusta, Yan Topilsky
Journal: JACC. Cardiovascular imaging (2020)
AB0101 ASSOCIATION OF FETUIN-A SERUM LEVEL AND GLUCOCORTICOIDS INTAKE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: E. Papichev, В. Zavodovsky, A. Yury, S. L, P. J
Journal: Annals of the Rheumatic Diseases (2020)

Background: Fetuin-A (FA) is a pluripotential glycoprotein, which plays an important role in bone turnover [1], inflammation, metabolic diseases [2] and etc. Several studies demonstrated association between FA serum level and rheumatoid arthritis (RA) severity and disease activity [3], however, there was made a suggestion that observed associations were due to glucocorticoids intake [4]. Objectives: To study the association of serum FA levels, glucocorticoids intake and RA activity. Methods: 81 patients with RA verified by ACR/EULAR 2010 criteria were enrolled in our study. 43 patients were under glucocorticoid therapy with mean cumulative dose 7899±9029,4 mg (hereinafter M±SD) and 38 patients were not. DAS28 index was calculated to determine RA activity. FA serum concentrations were measured by ELISA. Correlations between serum FA levels and RA activity were assessed in each group. Statistic analysis was performed using software package “Statistica 10.0”. Results: The mean level of serum FA was 760,72±112,56 µg/ml. There was a negative correlation between FA serum level and DAS28 index (r=-0,433; p&lt;0,0001) when calculated among all patients. We observed positive correlation between FA serum level and cumulative dosage of glucocorticoids (r=0,297; p=0,008). At the same time FA serum level and DAS28 index were correlated negatively in patients who were under glucocorticoid therapy (r=-0,419; p&lt;0,0001) and were not (r=-0,559; p=0,001). Conclusion: Serum FA level correlates with RA disease activity and glucocorticoids intake. However, the association between FA serum level and RA disease activity was independent of glucocorticoids intake in our study. References: [1]Akhverdyan Y., Zavodovsky B., Polyakova J., et al. Level of biochemical markers of bone metabolism in patients with osteoporosis in the presence on rheumatoid arthritis. Osteoporosis international 2019; 30(Suppl. 2): S:303. [2]Bilgir O, Kebapcilar L, Bilgir F, et al; Decreased serum fetuin-A levels are associated with coronary artery diseases. Intern Med 2010; 49(13): 1281-5. [3]Polyakova Y., Papichev E., Kvlividze T., et al. Tissue cytokines and their role in the pathogenesis of rheumatic diseases. Osteoporosis international 2019; 30 (Suppl. 2): S:387. [4]Tekeoglu I, Harman H, Sag S, et al. Levels of serum pantraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis. Cytokine 2016; 83: 171-75. Disclosure of Interests: None declared
Severe ineffective erythropoiesis discriminates prognosis in myelodysplastic syndromes: analysis based on 776 patients from a single centre
Authors: Huijun Huang, Changlu Xu, Jie Gao, Bing Li, Tiejun Qin, Zefeng Xu, Sirui Ren, Yudi Zhang, Meng Jiao, Shiqiang Qu, Lijuan Pan, Naibo Hu, Jinqin Liu, Wenyu Cai, Yingnan Zhang, Dan Wu, Peihong Zhang, Robert Peter Gale, Gang Huang, Jiaxi Zhou, Lihong Shi, Zhijian Xiao
Journal: Blood Cancer Journal (2020)

The underlying mechanisms and clinical significance of ineffective erythropoiesis in myelodysplastic syndromes (MDS) remain to be fully defined. We conducted the ex vivo erythroid differentiation of megakaryocytic-erythroid progenitors (MEPs) from MDS patients and discovered that patient-derived erythroblasts exhibit precocity and premature aging phenotypes, partially by inducing the pro-aging genes, like ERCC1. Absolute reticulocyte count (ARC) was chosen as a biomarker to evaluate the severity of ineffective erythropoiesis in 776 MDS patients. We found that patients with severe ineffective erythropoiesis displaying lower ARC (<20 × 109/L), were more likely to harbor complex karyotypes and high-risk somatic mutations (p < 0.05). Lower ARCs are associated with shorter overall survival (OS) in univariate analysis (p < 0.001) and remain significant in multivariable analysis. Regardless of patients of lower-risk who received immunosuppressive therapy or higher-risk who received decitabine treatment, patients with lower ARC had shorter OS (p < 0.001). Whereas no difference in OS was found between patients receiving allo-hematopoietic stem cell transplantations (Allo-HSCT) (p = 0.525). Our study revealed that ineffective erythropoiesis in MDS may be partially caused by premature aging and apoptosis during erythroid differentiation. MDS patients with severe ineffective erythropoiesis have significant shorter OS treated with immunosuppressive or hypo-methylating agents, but may benefit from Allo-HSCT.
Moving Beyond BRCA—Incorporating Molecular Assays into Ovarian Cancer Trials
Authors: Michelle McMullen, Katherine Karakasis, Amit M. Oza
Journal: Clinical Cancer Research (2020)

PrOTYPE is a locked down assay validated to Institute of Medicine standards, using NanoString technology to classify high-grade serous ovarian cancer into four defined subgroups. Future directions will include prospective-retrospective analysis and prospective clinical validation to define the predictive role of this assay and its role in influencing treatment decisions.See related article by Talhouk et al., p. 5411.
MicroRNA-based assay for differential diagnosis of squamous from non-squamous non-small cell lung carcinoma
Authors: D. Lebanony, H. Benjamin, S. Gilad, K. Ashkenazi, D. Nonaka, M. Feinmesser, N. Rosenfeld, A. Chajut, D. Cohen, R. Aharonov
Journal: Journal of Clinical Oncology (2009)

11069 Background: Recent advances in biologically directed therapies for non-small cell lung carcinoma (NSCLC) emphasize the need for more accurate sub-classification of NSCLC, as treatment may be dictated by histologic subtype. In particular, squamous histology can be a counter-indication for treatment by VEGF inhibitors. MicroRNAs are highly tissue-specific biomarkers with potential clinical applicability for defining cancer type and origin. MicroRNAs are well preserved in formalin fixed tissue, making them ideal candidates for molecular markers for use in routinely processed material. Here we report on the development and performance of a microRNA-based assay for the differential diagnosis of squamous from non-squamous NSCLC. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE archival tissue samples. MicroRNA microarrays were used to profile more than a hundred NSCLC samples. Specific microRNA qRT-PCR was used to validate results, and to develop a diagnostic assay. Results: We identified a microRNA biomarker that is strongly overexpressed in squamous cell NSCLC. A diagnostic assay (miRview squamous) was developed, that utilizes qRT-PCR measurement of this microRNA, normalized by an additional microRNA and a small nuclear RNA. This assay was validated on a blinded test set of 64 tumor samples, and had sensitivity of 97% and specificity of 91%. More than ¾ of the samples were classified with high confidence, and these classifications were accurate in 96% of the cases. Conclusions: MicroRNAs are becoming an important tool for classification of cancers. A diagnostic assay based on the specificity of a single microRNA accurately identifies squamous from non-squamous NSCLC. This assay provides an important new tool for the classification of NSCLC. [Table: see text]
Satralizumab: First Approval
Authors: Young-A Heo
Journal: Drugs (2020)

Satralizumab (Enspryng®), a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody, has been developed by Chugai Pharmaceutical and Roche for the treatment of neuromyelitis optica spectrum disorder (NMOSD). In June 2020, based on positive results from two pivotal phase III trials, subcutaneous satralizumab received its first global approval in Canada for the treatment of NMOSD in adults and children aged ≥ 12 years who are aquaporin 4 water channel autoantibody (AQP4-IgG) seropositive. Satralizumab was subsequently approved in Japan, Switzerland and the USA. Satralizumab is under regulatory review in the EU, and is undergoing clinical development in several countries worldwide. This article summarizes the milestones in the development of satralizumab leading to this first approval for the treatment of NMOSD.
Fit for life? Low cardiorespiratory fitness in adolescence is associated with a higher burden of future disability
Authors: Pontus Henriksson, Eric J Shiroma, Hanna Henriksson, Per Tynelius, Daniel Berglind, Marie Löf, I-Min Lee, Francisco B Ortega
Journal: British Journal of Sports Medicine (2020)

The burden of disability is an important public health challenge as the majority of people will experience disability throughout their life. Disability includes impairments, activity limitations and participation restrictions, all of which may reduce the capability for work. People with chronic disabilities that limit the ability to work are granted disability pensions in many countries. Therefore, disability pension is informative for health and disease outcomes, as well as for economic consequences.

Previous studies have indicated that obesity as well as low cardiorespiratory fitness and muscular strength already in adolescence are related to later mortality and disease, but few studies have examined corresponding associations for future disability due to all and specific chronic diseases. Thus, we examined the associations of obesity, cardiorespiratory fitness and muscular strength in male adolescents with later disability pension due to all and specific causes in more than 1 million participants through linkage of data from the Swedish conscription registry with other nationwide registries.1–3

Low cardiorespiratory fitness in isolation1 3, or together with low muscular strength2 or obesity1 3, was a strong risk factor for later disability pension due to all and specific causes (eg, psychiatric, musculoskeletal and cardiovascular diseases). Strengths of these previous studies include the large size and representativeness of the study sample (97%–98% of all adolescent males since conscription was mandatory by law during the study years3), the long follow-up (~30 years) and the objective markers of chronic disability (ie, disability pension) and exposures. However, thus far, no actual …
C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury
Authors: Miyako Tanaka, Marie Saka-Tanaka, Kozue Ochi, Kumiko Fujieda, Yuki Sugiura, Tomofumi Miyamoto, Hiro Kohda, Ayaka Ito, Taiki Miyazawa, Akira Matsumoto, Seiichiro Aoe, Yoshihiro Miyamoto, Naotake Tsuboi, Shoichi Maruyama, Makoto Suematsu, Sho Yamasaki, Yoshihiro Ogawa, Takayoshi Suganami
Journal: The Journal of Experimental Medicine (2020)

Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia-reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death-triggered, sustained inflammation after acute kidney injury.
Oxidative stress tolerance and antioxidant capacity of lactic acid bacteria as probiotic: a systematic review
Authors: Tao Feng, Jing Wang
Journal: Gut Microbes (2020)

Lactic acid bacteria (LAB) are the most frequently used probiotics in fermented foods and beverages and as food supplements for humans or animals, owing to their multiple beneficial features, which appear to be partially associated with their antioxidant properties. LAB can help improve food quality and flavor and prevent numerous disorders caused by oxidation in the host. In this review, we discuss the oxidative stress tolerance, the antioxidant capacity related herewith, and the underlying mechanisms and signaling pathways in probiotic LAB. In addition, we discuss appropriate methods used to evaluate the antioxidant capacity of probiotic LAB. The aim of the present review is to provide an overview of the current state of the research associated with the oxidative stress tolerance and antioxidant capacity of LAB.
AB0070 THE RELATIONSHIP BETWEEN THE LEVEL OF NESFATIN-1 AND THE CLINICAL MANIFESTATIONS OF RHEUMATOID ARTHRITIS
Authors: Tamara Kvlividze, B Zavodovsky, J Polyakova, E. Zagorodneva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Nesfatin-1 is actively studied in the pathogenesis of metabolic disorders. An excess of this factor in the brain leads to loss of appetite, a feeling of fullness, as well as a decrease in body weight. Similarly, elevated levels of nesfatin are associated with depressive disorders [1]. We studied the level of nesfatin in the serum of patients with rheumatoid arthritis (RA) and found a relationship with systemic inflammation and functional impairment [2]. <h3>Objectives</h3> To study the relationship of serum nesfatin-1 levels with the clinical manifestations of RA. <h3>Methods</h3> To identify the relationship between serum nesfatin-1 and the clinical manifestations of rheumatoid arthritis, all patients were divided into 2 groups. The first group - 1 (66 patients) with elevated serum nesfatin (&gt; 37.95 ng/ml). The second group - 2 (44 patients) - with normal values (&lt;37.95ng/ml). In both groups, we studied the clinical manifestations of RA. <h3>Results</h3> A high level of nesfatin in RA patients was typical for patients with a higher degree of activity in DAS28 (χ2 = 8.37; p = 0.04), seropositivity for the rheumatoid factor (RF) - (χ2 = 5.53; p = 0, 02), the duration of the disease is more than 10 years (χ2 = 9.53; p = 0.01). At the same time, there was no significant correlation between the level of nesfatin and the extra-articular manifestations of RA (χ2 = 2.09; p = 0.14) and the degree of radiological damage to the joints (χ2 = 4.45; p = 0.21). <h3>Conclusion</h3> This study shows that serum Nesfatin-1 levels are significantly higher in patients with more unfavorable RA, than in RA with minimal clinical manifestations. These data confirm the pathogenetic role of Nesfatin-1 in the development of clinical manifestations associated primarily with RA activity, but to a lesser extent with organ lesions in RA. The relationship of the level of nesfatin with the duration of the disease is of particular interest, since there is no correlation with the degree of X-ray damage to the joints and organ damage. There are literary data on the relationship of depression and late stage of RA [3]. <h3>References</h3> [1] Role of nesfatin-1 in anxiety, depression and the response to stress/Weibert E, Hofmann T, Stengel A//Psychoneuroendocrinology. 2018; 29;100:58-66. doi: 10.1016/j.psyneuen.2018.09.037. [2] Elevated Nesfatin-1 levels in patients with Rheumatoid Arthritis/T.Z. Kvlividze, B.V. Zavodovsky, Y.R. Akhverdyan, L.E. Sivordova, Y.V. Polyakova, D.P. Lavrova, A.T. Yakovlev//Ann Rheum Dis, V.77, Suppl, 2018, P. A1762 [3] Waheed A., Hameed K., Khan A.M. et al. The burden of anxiety and depression among patients with chronic rheumatologic disorders at a tertiary care hospital clinic in Karachi, Pakistan//J Pak Med Assoc2006; 56: 243–7. <h3>Disclosure of Interests</h3> None declared
Abstract IA06: A urine assay to triage patients with hematuria for cystoscopy
Authors: Kim E.M. van Kessel, Joep J. de Jong, Angelique C.J. Ziel-van der Made, Hossain Roshani, Stefan M. Haensel, Josien H. Wolterbeek, Egbert R. Boevé, Eric H.G.M. Oomens, Niels J. van Casteren, Manuel Krispin, Joost L. Boormans, Ewout W. Steyerberg, Wim van Criekinge, Ellen C. Zwarthoff
Journal: Clinical Cancer Research (2020)

Abstract Objectives: To assess the accuracy of a previously developed molecular assay to detect bladder cancer in a large prospective cohort of patients referred for hematuria. Design, Setting and Participants: A urine sample was collected prior to cystoscopy and mutation/methylation status of 6 genes was determined in DNA from urinary cells and combined with age. This existing diagnostic model was validated on this cohort and optimized using logistic regression. Clinical usefulness was determined by the net benefit approach. Main outcome measures: Primary endpoint was the model performance to detect the presence of urothelial cancer, as indicated by the area under the receiver operating characteristic (ROC) curve (AUC). Secondary endpoints were the sensitivity, specificity, and negative predictive value (NPV) of the optimal diagnostic model. Results: In 838 patients, the mutation/methylation status could be determined for all genes. Urothelial cancer was observed in 112 patients (98/457 in the gross and 14/381 in the microscopic hematuria group). Application of the existing model resulted in an AUC of 0.93. Combining the assay with the type of hematuria resulted in the final optimal model with an AUC of 0.96 (96% sensitivity, 73% specificity, 99% negative predictive value). The assay also detected all six upper tract urothelial tumors that are not visible by cystoscopy. Net benefit analysis showed that the urine test should be preferred over “cystoscopy for all.” Application of the optimal model on patients whose biomarker status was incomplete resulted in the identification of 5 additional tumors. Implementing the urine test as a triage tool could lead to a 53% reduction in cystoscopies. Conclusions: The urine test detects urothelial cancer with a very high accuracy and is ready for clinical implementation. Citation Format: Kim E.M. van Kessel, Joep J. de Jong, Angelique C.J. Ziel-van der Made, Hossain Roshani, Stefan M. Haensel, Josien H. Wolterbeek, Egbert R. Boevé, Eric H.G.M. Oomens, Niels J. van Casteren, Manuel Krispin, Joost L. Boormans, Ewout W. Steyerberg, Wim van Criekinge, Ellen C. Zwarthoff. A urine assay to triage patients with hematuria for cystoscopy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA06.