tbuckley/cabot-search huggingface dataset:
Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome
Authors: Shunbun Kita, Norikazu Maeda, Iichiro Shimomura
Journal: Journal of Clinical Investigation (2019)

Adipose tissue plays important roles in regulating whole-body energy metabolism through its storage function in white adipocytes and its dissipating function in brown and beige adipocytes. Adipose tissue also produces a variety of secreted factors called adipocytokines, including leptin and adiponectin. Furthermore, recent studies have suggested the important roles of extracellular vesicles of endosomal origin termed exosomes, which are secreted from adipocytes and other cells in adipose tissue and influence whole-body glucose and lipid metabolism. Adiponectin is known to be a pleiotropic organ-protective protein that is exclusively produced by adipocytes and decreased in obesity. Adiponectin accumulates in tissues such as heart, muscle, and vascular endothelium through binding with T-cadherin, a glycosylphosphatidylinositol-anchored (GPI-anchored) cadherin. Recently, adiponectin was found to enhance exosome biogenesis and secretion, leading to a decrease in cellular ceramides, excess of which is known to cause insulin resistance and cardiovascular disease phenotypes. These findings support the hypothesis that adipose tissue metabolism systemically regulates exosome production and whole-body metabolism through exosomes. This review focuses on intra-adipose and interorgan communication by exosomes, adiponectin-stimulated exosome production, and their dysregulation in metabolic diseases.
OS1.5 Detection of glioma and prognostic subtypes by non-invasive circulating cell-free DNA methylation markers
Authors: H Noushmehr, T Sabedot, T Malta, K Nelson, J Snyder, M Wells, A deCarvalho, A Mukherjee, D Chitale, M Mosella, K Asmaro, A Robin, M Rosenblum, T Mikkelsen, J Rock, L Poisson, T Walbert, S Kalkanis, A Castro
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND: Genome-wide DNA methylation profiling has shown that epigenetic abnormalities are biologically important in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA profiling has required surgically resected glioma tissue; however, gliomas release tumoral material into biofluids providing an opportunity for a minimally invasive testing. While prior studies have shown that molecular markers can be detected in liquid biopsy (LB), there has been low sensitivity for tumor-specific markers. We hypothesize that the low sensitivity is due to the targeted assay methods. METHODS: Genome-wide CpG methylation levels in DNA of tumor tissue and cell-free DNA serum of glioma patients. RESULTS: We defined glioma-specific and IDH-specific epigenetic LB (eLB) signatures (Glioma-eLB and IDH-eLB, respectively) from serum cell-free DNA from patients diagnosed with glioma (N=15 IDH mutant and N=7 IDH wildtype) and with epilepsy (N=3). The epigenetic profiles of the matched tissue demonstrate that these eLB signatures reflected the signature of the tumor. Through cross-validation we show that Glioma-eLB can accurately predict a patient’s glioma from those with other neoplasias (N=6 Colon; N=14 Pituitary; N=3 Breast; N=4 Lung), non-neoplastic immunological conditions (N=22 sepsis; N=9 pancreatic islet transplantation), and from healthy individuals (sensitivity: 98%; specificity: 99%). Finally, IDH-eLB includes promoter methylated markers associated with genes known to be involved in glioma tumorigenesis (PVT1 and CXCR6). CONCLUSIONS: The application of the non-invasive eLB signature discovered in this study has the potential to complement the standard of care for patients harboring glioma. This project is supported by the Henry Ford Health System, Department of Neurosurgery and the Hermelin Brain Tumor Center Foundation (A30935), United States National Institutes of Health (R01CA222146), and United States Department of Defense (CA170278)
Effect of whey protein isolate supplementation on body composition, muscle strength, and treatment tolerance in malnourished advanced cancer patients undergoing chemotherapy.
Authors: Paolo Pedrazzoli, Emanuele Cereda, Silvia Cappello, Luca Arcaini, Valeria Borioli, Elisa Ferraris, Silvia Chiellino, Giulia Stella, Marco Benazzo, Alessandra Ferrari, Catherine Klersy, Riccardo Caccialanza
Journal: Journal of Clinical Oncology (2019)

11598 Background: Malnutrition is frequent in cancer pts, particularly in advanced disease, which requires appropriate multidisciplinary interventions. We evaluated the benefit of whey protein isolate (WPI) supplementation in addition to nutritional counseling in malnourished cancer pts undergoing chemotherapy (CT). Methods: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer pts undergoing CT were randomly assigned to receive nutritional counseling with (N=82) or without (N=84) WPI supplementation (20 grams/daily) for 3 months. Primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat-free mass index (FFMI), body weight, muscle strength, quality of life and CT toxicity. Results: In pts with the primary endpoint assessed (modified intention-to-treat population), counseling plus WPI (N=66) resulted in improved PhA compared to nutritional counseling alone (N=69): mean difference, 0.48° [95%CI, 0.05 to 0.90] (P=0.027). Imputation of missing outcomes yielded consistent findings. WPI supplementation resulted also in improved SPA (P=0.021), FFMI (P=0.041), body weight (P=0.023), muscle strength (P&lt;0.001) and in reduced risk of CT toxicity, particularly of severe (grade ≥3) events (Table). Conclusions: In malnourished advanced cancer patients undergoing CT and receiving nutritional counseling, 3-month supplementation with WPI resulted in improved body composition, muscle strength, body weight and reduced CT toxicity. Further trials in newly diagnosed specific cancer types are warranted. Clinical trial information: NCT02065726. [Table: see text]
CCL28-induced RARβ expression inhibits oral squamous cell carcinoma bone invasion
Authors: Junhee Park, Xianglan Zhang, Sun Kyoung Lee, Na-Young Song, Seung Hwa Son, Ki Rim Kim, Jae Hoon Shim, Kwang-Kyun Park, Won-Yoon Chung
Journal: Journal of Clinical Investigation (2019)

Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of β-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-β (RARβ) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARβ expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARβ expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARβ had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARβ are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.
Why use real and hypothetical payoffs?
Authors: Anton Kühberger
Journal: Behavioral and Brain Sciences (2001)

Decision making can be studied using hypothetical payoffs because it is hypothetical to its very core. However, the core process can be influenced by contextual features. As there is no theory for these contextual features, a “do-it-both-ways” rule amounts to a waste of money. If we had such a theory, doing it both ways would be unnecessary.
Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis
Authors: Mario Giuliano, Francesco Schettini, Carla Rognoni, Manuela Milani, Guy Jerusalem, Thomas Bachelot, Michelino De Laurentiis, Guglielmo Thomas, Pietro De Placido, Grazia Arpino, Sabino De Placido, Massimo Cristofanilli, Antonio Giordano, Fabio Puglisi, Barbara Pistilli, Aleix Prat, Lucia Del Mastro, Sergio Venturini, Daniele Generali
Journal: The Lancet Oncology (2019)
SR Ca2+-leak and disordered excitation-contraction coupling as the basis for arrhythmogenic and negative inotropic effects of acute ethanol exposure
Authors: Julian Mustroph, Steffen Pabel, Simon Lebek, Marzena Drzymalski, Tao He, Lukas Schöberl, Can-Martin Sag, Stefan Wagner, Samuel T Sossalla, Lars S Maier, Stefan Neef
Journal: Circulation (2016)

Aims: Ethanol has acute negative inotropic and arrhythmogenic effects. The underlying mechanisms, however, are largely unknown. Sarcoplasmic reticulum Ca2+-leak is an important mechanism for reduced contractility and arrhythmias. Ca2+-leak can be induced by oxidative stress and Ca2+/Calmodulin-dependent protein kinase II (CaMKII). Therefore, we investigated the influence of acute ethanol exposure on excitation-contraction cou- pling in atrial and ventricular cardiomyocytes.
Methods and results: Isolated human atrial and murine atrial or ventricular cardiomyocytes were preincubated for 30 min and then superfused with control solution or solution containing ethanol. Ethanol had acute negative inotropic and positive lusitropic effects in human atrial muscle strips and murine ventricular cardiomyocytes. Accordingly, Ca2+-imaging indicated lower Ca2+-transient amplitudes and increased SERCA2a activity, while myofilament Ca2+-sensitivity was reduced. SR Ca2+-leak was assessed by measuring Ca2+-sparks. Ethanol in- duced severe SR Ca2+-leak in human atrial cardiomyocytes (calculated leak: 4.60 ± 0.45 mF/F0 vs 1.86 ± 0.26 in control, n ≥ 80). This effect was dose-dependent, while spontaneous arrhythmogenic Ca2+- waves increased ~5-fold, as investigated in murine cardiomyocytes. Delayed afterdepolarizations, which can result from increased SR Ca2+-leak, were significantly increased by ethanol. Measurements using the reactive oxygen species (ROS) sensor CM-H2DCFDA showed increased ROS-stress in ethanol treated cells. ROS-scaven- ging with N-acetylcysteine prevented negative inotropic and positive lusitropic effects in human muscle strips. Ethanol-induced Ca2+-leak was abolished in mice with knockout of NOX2 (the main source for ROS in cardi- omyocytes). Importantly, mice with oxidation-resistant CaMKII (Met281/282Val mutation) were protected from ethanol-induced Ca2+-leak.
Conclusion: We show for the first time that ethanol acutely induces strong SR Ca2+-leak, also altering excitation- contraction coupling. Acute negative inotropic effects of ethanol can be explained by reduced systolic Ca2+- release. Mechanistically, ROS-production via NOX2 and oxidative activation of CaMKII appear to play central roles. This provides a mechanism for the arrhythmogenic and negative inotropic effects of ethanol and suggests a druggable target (CaMKII).
SCLE and dermatomyositis in anti‐PD‐1 therapy
Authors: A.L. Marano, J.M. Clarke, M.A. Morse, A. Shah, W. Barrow, M.A. Selim, R.P. Hall, A.R. Cardones
Journal: British Journal of Dermatology (2019)

PD-1 inhibitors are a relatively new type of drug that are used to treat patients with metastatic (widespread) cancers. Examples include drugs called pembrolizumab and nivolumab. Unfortunately this type of treatment can be associated with auto-immune side effects, which means that the body's immune system, which protects against infection, wrongly attacks some parts of the body. Examples of auto-immune side effects linked to PD-1 inhibitors include colitis, thyroid disease and skin inflammation, including eczema-like rashes and vitiligo. The authors of this study, based at Duke University, USA, describe two patients who developed a type of lupus called subacute cutaneous lupus erythematosus (SCLE) while on PD-1. SCLE is an autoimmune disease. In one case, the drug that was being used, nivolumab, was discontinued; the oncologists unsuccessfully treated the patient with infliximab, a type of drug called a TNFα inhibitor, but the eruption came under control with creams and hydroxychloroquine treatment by the dermatologists. Because nivolumab was helping to treat the patient's cancer, the drug was re-introduced but unfortunately he then developed features of another autoimmune condition, dermatomyositis, and the drug was stopped. The second patient developed SCLE following pembrolizumab treatment, which she discontinued as it was not having an effect on her cancer. Again her SCLE came under control with treatment. The authors observed that treatment with a TNF inhibitor would not be ideal in this situation, because it can itself cause lupus. Whereas SCLE is well recognised as a side effect of many drugs, it is unusual to see two different connective tissue diseases, lupus and dermatomyositis, caused by one drug. The authors advise not continuing the drug in this situation.
P11.01 TMZ-LEV- IFN cocktail regimen significantly inhibited the growth of glioma
Authors: X Ni, Y Qu, J Wang, F Chen, H Cai, Y Yu, Y Yu, Z Yu, Z Cen, Z Chen
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND TMZ, is the first line chemotherapeutic drug for glioma, and drug resistance is one of the most important reasons for glioma treatment failure. Our previous studies have found that: 1) Type I interferon (IFN) could reverse the resistance of TMZ by inhibiting NF-κB activity, and down-regulating the expression of MGMT in vivo and in vitro; 2) IFN-α could significantly improve chemtherapeautic effect of TMZ for GBM patients. We aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining temozolomide (TMZ)- Levetiracetam(LEV) - interferon (IFN) on human glioma U138 and U251 subcutaneous xenograft tumor. MATERIAL AND METHODS 30 xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into the right flank of 4-week-old female BALB/C nude mice and then randomly divided into 5 groups (n=6/group): Control group; TMZ group; TMZ+IFN group; TMZ+LEV group; TMZ+LEV+IFN group. Anti-tumor efficacy of five regimens for tumor-bearing mice was tested after treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.), while TMZ dose were reduced to 12.5 mg/kg for U251 tumors. All drugs are given once a day for five consecutive days. After therapy, the size of tumor was measured every day until the control tumors reached 2000 mm3. Mice bearing U138 tumors were sacrificed at 40 days after therapy, and mice bearing U251 tumors were killed at 26 days after therapy. RESULTS We identified that both U138 and U251 tumor growth among TMZ group, TMZ+IFN group, TMZ+LEV group and TMZ+LEV+IFN group were significantly inhibited (P&lt;0.05), compared with the control group. Tumor weight of all treating group was lower than that of the control group (P&lt;0.05). The tumor weight of TMZ+LEV+IFN group was the lowest and significantly lower than that of TMZ+LEV group and TMZ group (P&lt;0.05, respectively). No significant difference was found between TMZ+LEV+IFN group and TMZ+IFN group in U251 subcutaneous xenograft tumors, although the tumor weight was lower in TMZ+LEV+IFN group (P&gt;0.05). In the treatment of mice bearing U138 glioma, TMZ+LEV+IFN regimen was significantly superior to TMZ+IFN regimen. CONCLUSION Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma. TMZ-LEV-IFN cocktail appears the best regimen.
P14.26 Autoimmune disease-associated primary CNS lymphoma: Meta-analysis and review of literature
Authors: L D Kaulen, J M Baehring
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Recent studies suggest a relatively high prevalence of autoimmune diseases (AD) among primary CNS lymphoma (PCNSL) patients, however the literature is limited to case reports. To gain a better understanding of AD-associated PCNSL we reviewed all previous cases described in the literature. MATERIAL AND METHODS We mined the MEDLINE database using the search terms ‘central nervous system lymphoma’ or ‘CNS lymphoma’ along with AD-related terms, such as ‘immunosuppression’, ‘autoimmune’, the name of various AD, or commonly prescribed immunosuppressants. We selected 35 records for qualitative synthesis of data. We identified 43 AD-associated PCNSL in the literature and added five unpublished cases from our institution. Clinical, imaging and outcome data were collected. RESULTS Most prevalent ADs were systemic lupus erythematosus (22.9%), multiple sclerosis (18.8%) and myasthenia gravis (14.6%). Male-to-female ratio was 1:2 and median age at diagnosis was 57 years (range: 2.5–88). Most common immunosuppressants included prednisone (58.7%), mycophenolate (43.5%), and azathioprine (41.3%). Median interval from diagnosis of AD until diagnosis of PCNSL was 96 months (range: 11–360). Lesions typically localized to the hemispheres (64.1%) and displayed peripheral contrast enhancement (75.8%). Histology revealed diffuse large-B-cell lymphomas (76.7%) and Epstein-Barr virus (EBV) positivity (78.4%). Treatment included reduction of immunosuppression (100%) and chemotherapy (85.4%) in most cases. Median overall survival was 31 months. CONCLUSION AD-associated PCNSL are characterized by peripheral contrast enhancement on imaging and EBV positivity. AD that require severe immunosuppression appear over-represented. Median interval of immunosuppression and overall survival seem longer than in other immunodeficiency-associated PCNSL.
Platelet Alpha-Storage Pool Defect Combined with Non-Classic Delta-Storage Pool Deficiency - with a Severe Bleeding Tendency
Authors: Frauke Bergmann, Kathrin Schwierczek, Stefanie Sollfrank, Andreas Czwalinna, Joseph Erkel, Karl Lackner, Ulrich Walter, Heidi Rossmann, Kerstin Jurk
Journal: Blood (2016)
Tumor neoantigens: from basic research to clinical applications
Authors: Tao Jiang, Tao Shi, Henghui Zhang, Jie Hu, Yuanlin Song, Jia Wei, Shengxiang Ren, Caicun Zhou
Journal: Journal of Hematology & Oncology (2019)

Tumor neoantigen is the truly foreign protein and entirely absent from normal human organs/tissues. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs) in the context of major histocompatibility complexes (MHCs) molecules. Emerging evidence has suggested that neoantigens play a critical role in tumor-specific T cell-mediated antitumor immune response and successful cancer immunotherapies. From a theoretical perspective, neoantigen is an ideal immunotherapy target because they are distinguished from germline and could be recognized as non-self by the host immune system. Neoantigen-based therapeutic personalized vaccines and adoptive T cell transfer have shown promising preliminary results. Furthermore, recent studies suggested the significant role of neoantigen in immune escape, immunoediting, and sensitivity to immune checkpoint inhibitors. In this review, we systematically summarize the recent advances of understanding and identification of tumor-specific neoantigens and its role on current cancer immunotherapies. We also discuss the ongoing development of strategies based on neoantigens and its future clinical applications.
How to evaluate premature ventricular beats in the athlete: critical review and proposal of a diagnostic algorithm
Authors: Domenico Corrado, Jonathan A Drezner, Flavio D'Ascenzi, Alessandro Zorzi
Journal: British Journal of Sports Medicine (2019)

Although premature ventricular beats (PVBs) in young people and athletes are usually benign, they may rarely mark underlying heart disease and risk of sudden cardiac death during sport. This review addresses the prevalence, clinical meaning and diagnostic/prognostic assessment of PVBs in the athlete. The article focuses on the characteristics of PVBs, such as the morphological pattern of the ectopic QRS and the response to exercise, which accurately stratify risk. We propose an algorithm to help the sport and exercise physician manage the athlete with PVBs. We also address (1) which athletes need more indepth investigation, including cardiac MRI to exclude an underlying pathological myocardial substrate, and (2) which athletes can remain eligible to competitive sports and who needs to be excluded.
Risk Factors for Grade 3/4 Transaminase Elevation in Patients with Chronic Lymphocytic Leukemia Treated with Idelalisib
Authors: Jennifer R. Brown, Andrew D. Zelenetz, Richard R. Furman, Nicole Lamanna, Anthony R. Mato, Marco Montillo, Susan M. O'Brien, Lyndah K. Dreiling, Ronald L. Dubowy, Yeonhee Kim, Veerendra B. Munugalavada, Tadeusz Robak, Peter Hillmen
Journal: Blood (2017)
Desmoid tumor (DT) management in dedicated sarcoma medical oncology clinic in a developing country: Lessons learnt.
Authors: Sameer Rastogi, Aditi Aggarwal, Ekta Dhamija, Adarsh Barwad, Rambha Panday, Shah Alam Khan, Venkat Sampat kumar, Sorun Shishak, Santosh Kumar C, Svs Deo, Parisa Manasa, Rashi Kapoor, Pankaj Kumar
Journal: Journal of Clinical Oncology (2019)

e22541 Background: There is lack of data about desmoid tumors from India except case reports. It is not known how these patients are dealt with outside tertiary care centres who lack expertise. Methods: We retrospectively analysed all patients of DT from a prospectively maintained database who were referred to AIIMS Sarcoma Medical Oncology Clinic from January 2016 till 2019. Results: There were total of 56 patients with male: female ratio of 3:4. Median age was 26 (3-57) years. Extremity was most common site (57%) and median tumour size was 12 (range 3-20) cm. One patient (1.8%) had FAP and 1 (1.8%) had multifocal disease. A total of 27 patients received first treatment outside our institute and was primary surgery in all (100%). However, of the remaining 29 patients who primarily presented to us, surgery was done only in 3 (10%) because of patients choice and pelvic location. Five patients were kept under observation and all are doing well. Tamoxifen with celecoxib was most common first line therapy in 80% (40/50) with other options being sorafenib (6/50) and chemotherapy (4/50). Chemotherapy was used in abdomen (3/4) and head neck (1/4) primary patients. Menstrual irregularities including amenorrhoea was most common toxicity in 33% (13/40) with tamoxifen combination and a cause of concern in this cohort of young females leading to discontinuation of therapy inspite of SD in 54% (7/13) patients. Second line therapy was started in 20 patients with sorafenib being most common (13/20), others being chemotherapy (4/20), tamoxifen combination (2/20) and imatinib (1/20). Of all 19 patients on sorafenib, 10 (53%) experienced Hand Foot Syndrome. None discontinued sorafenib due to HFS. After median follow up of 15 months, median progression free survival (PFS) with first line was 29 months (11-46) and with second line it was not reached. There have been three deaths till date (5.3%), all were non-extremity primaries. Conclusions: In Indian setup, majority of patients presenting outside tertiary care centre undergo surgery as the first line therapy without any inclusion of medical therapy. This might be attributed to lack of awareness about medical therapy and natural trajectory of disease. Tamoxifen though was a commonly used option, led to toxicity which is of concern in young Indian patients leading to discontinuation. Sorafenib is well tolerable except HFS but longer follow up is needed for efficacy analysis.