tbuckley/cabot-search huggingface dataset:
Comorbidity-Associated Risk of Overall Mortality Following Hematopoietic Stem-Cell Transplantation Is Regimen-Dependent: A Study from the Acute Leukemia Working Party of the EBMT
Authors: Joshua Fein, Myriam Labopin, Roni Shouval, Gerard Socie, Jürgen Finke, Jan J Cornelissen, Ram Malladi, Maija Itälä-Remes, Patrice Chevallier, Kim H. Orchard, Donald Bunjes, Mahmoud Aljurf, Marie Thérèse Rubio, Mohamad Mohty, Arnon Nagler
Journal: Blood (2018)
Getting to the Heart of Alzheimer Disease
Authors: Joshua M. Tublin, Jeremy M. Adelstein, Federica del Monte, Colin K. Combs, Loren E. Wold
Journal: Circulation Research (2019)

In a somewhat narrow diagnostic lens, Alzheimer disease (AD) has been considered a brain-specific disease characterized by the presence of Aβ (β-amyloid) plaques and tau neural fibrillary tangles and neural inflammation; these pathologies lead to neuronal death and consequently clinical symptoms, such as memory loss, confusion, and impaired cognitive function. However, for decades, researchers have noticed a link between various cardiovascular abnormalities and AD—such as heart failure, coronary artery disease, atrial fibrillation, and vasculopathy. A considerable volume of work has pointed at this head to heart connection, focusing mainly on associations between cerebral hypoperfusion and neuronal degradation. However, new evidence of a possible systemic or metastatic profile to AD calls for further analysis of this connection. Aβ aggregations—biochemically and structurally akin to those found in the typical AD pathology—are now known to be present in the hearts of individuals with idiopathic dilated cardiomyopathy, as well as the hearts of patients with AD. These findings suggest a potential systemic profile of proteinopathies and a new hypothesis for the link between peripheral and central symptoms of heart failure and AD. Herein, we provide an overview of the cardiovascular links to Alzheimer disease.
Inhibition of Amino Acid Metabolism Selectively Targets Human Leukemia Stem Cells
Authors: Courtney L Jones, Brett M Stevens, Angelo D'Alessandro, Julia Reisz, Rachel Culp-Hill, Travis Nemkov, Shanshan Pei, Nabilah Khan, Biniam Adane, Haobin Ye, Dominik Reinhold, Clayton Smith, James DeGregori, Daniel A Pollyea, Craig T Jordan
Journal: Blood (2018)
Bias toward Internet advertisement of robotic nephrectomy.
Authors: Danny Landau, Minesh Dinubhai Patel
Journal: Journal of Clinical Oncology (2014)

e15559 Background: Despite unclear benefits over radical nephrectomy (RN), Robotic Assisted Nephrectomy (RaN) has become a more commonly chosen approach for kidney surgery. A reason for this could be the marketing efforts, including those on the internet. We analyzed the content and form of websites through common search engines. Methods: We analyze the content of the first 5 pages of unsponsored results using Google, Yahoo, and Bing search engines using terms such as “robotic nephrectomy.” Youtube was also searched for video advertising. Pages were studied for: other surgical techniques being offered, physician promotion, and patient testimony. Results: When specific terms such as “robotic nephrectomy” were used, 82 (N) of the 150 hits were for centers performing robotically assisted nephrectomy. The remainder of search results were information sites, scholarly articles, and blogs. 32/82 (39%) were exclusively robotic centers. The remaining 61% were centers offering other surgeries, including RN. Physician promotion was performed using terms such as “best robotic practice” and “internationally renowned” in greater than 60% of cases. The remainder offered physician CVs or other objective information. Websites for robotic institutions offered more visual appear and had more graphics than those for RN. On Youtube, 70 of 100 results were patient testimonies and videos of surgery. Of those, 46/70 (66%) were videos provided by the robotic institutions. Conclusions: Information available on the internet is biased toward RaN. Websites advertising RaN are more appealing than those that do not advertise RaN and offered YouTube videos in many cases.
Decoy receptor 3 and doxorubicin-induced apoptosis in malignant peripheral nerve sheath tumors.
Authors: Wei Wang, Jinbing Luo, Yinghui Liang, Wenjie Lin
Journal: Journal of Clinical Oncology (2014)

e14004 Background: Malignant peripheral nerve sheath tumors (MPNSTs) are highly invasive soft tissue sarcomas and current therapeutic regimens have limited use because the tumors are generally resistant to standard chemotherapy.The molecules that relate to the decreased apoptosis of are largely unexplored. The purposes of this study are to examine if high expression of decoy receptor 3 (DcR3) promote the malignancy of NF tumor cells and the role of DcR3 in resistance to doxorubicin-induced apoptosis in MPNSTs. Methods: ELISA was carried out to determine the level of DcR3 in MPNST cell lines STS26T, ST-88 and T265, siRNA targeted for DcR3 was used to down-regulate DcR3 expression in MPNST cells. On exploring for the pathway of DcR3 blocking doxorubicin-induced apoptosis, up or down-regulated DcR3 level of MPNST cells were treated with doxorubicin and apoptosis susceptibility was evaluated with apoptosis analysis. To investigate whether DcR3 is involved in FasL or LIGHT-mediated apoptosis, PARP and apoptotic cells staining were determined under different DcR3 level. In vivo, it is to investigate whether down-regulation of DcR3 affects doxorubicin -induced apoptosis and tumor growth delay in STS26T xenografts of nude mice. Results: All the three cell lines show high level of DcR3 expression, interestingly, STS26T, an aggressive cell line of MPNSTs, expresses higher DcR3 level than the other cell lines ST-88 and T265 which are less aggressive. Furthermore, DcR3 down-regulation sensitizes cells to doxorubicin-induced apoptosis and additional DcR3 level can impair doxorubicin-induced apoptosis in MPNST cells. It is proved that DcR3 blocks doxorubicin-induced apoptosis via binding with FasL. In vivo experiment of STS26T xenografts, stable down-regulation of DcR3 significantly enhances doxorubicin-induced apoptosis and tumor growth delay. Conclusions: Our data suggest that high expression of DcR3 blocks the susceptibility of MPNST cells to doxorubicin-induced apoptosis. The results will greatly improve our understanding of the role of DcR3 in the progression of benign neural tumor to MPNSTsand may shed light on novel therapeutic targets for the treatment of MPNSTs.
<scp>RAS</scp> opathies and the skin
Authors: C. Moss
Journal: British Journal of Dermatology (2019)

Linked Article: Bessis et al. Br J Dermatol 2019; 180:172–180. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The effect of outpatient moderate dose bolus (MDB) interleukin-2 (IL-2) on vitamin C levels in patients with metastatic melanoma or kidney cancer.
Authors: Rachel Winston, Walter Quan
Journal: Journal of Clinical Oncology (2014)

e20693 Background: Vitamin C supports human immune function by its integral role in innate and adaptive immune responses. Moreover, it acts as a potent antioxidant, strengthens antibacterial activity, and down regulates synthesis of proinflammatory cytokines, among other functions (Shaik-Dasthagirisaheb, 2013; Holmannova, 2012). It has been reported that serum levels of vitamin C are depleted in patients receiving inpatient infusions of high-dose continuous and bolus IL-2 (Marcus, 1987). Our group has previously reported on the safety and activity of the administration of moderate dose bolus IL-2 (18 MIU/m2 daily for 3-5 days) given intravenously as an outpatient to patients with metastatic melanoma or kidney cancer (Quan, 2010, 2012, 2013). The effect of IL-2 on vitamin C has not been examined in the outpatient setting; therefore, we sought to determine whether patients receiving MDB IL-2 are at risk for vitamin C deficiency. Methods: Serum vitamin C levels were measured in patients with stage IV melanoma (n=5) or stage IV renal carcinoma (n=3), receiving MDB IL-2. Laboratory values were obtained at baseline and subsequent to cycle one. Means and standard deviations were calculated for comparison and the paired student’s t-test was performed to determine statistical significance between the means. Results: Serum levels from eight patients were analyzed. The mean serum vitamin C level at baseline was 0.60 mg/dL ± 0.41. After one cycle of IL-2, the mean serum level decreased to 0.45 mg/ dL ± 0.31 (p < 0.015). One patient’s vitamin C level was depleted to below detectable levels. This latter patient has experienced a partial response of her known metastases. Conclusions: Patients receiving MDB IL-2 are at risk for vitamin C deficiency and may require supplementation.
Pluripotent Cell-Derived Off-the-Shelf TCR-Less CAR-Targeted Cytotoxic T Cell Therapeutic for the Allogeneic Treatment of B Cell Malignancies
Authors: Raedun Clarke, Sjoukje Van Der Stegen, Chia-Wei Chang, Mushtaq Husain, Yi-Shin Lai, Eigen Peralta, Laurel Stokely, Ramzey Abujarour, Jason Dinella, Tom Lee, Mochtar Pribadi, Helen Chu, Chris Truong, Mohsen Sabouri-Ghomi, Miguel Meza, Judith Feucht, Justin Eyquem, Jorge Mansilla-Soto, Isabelle Riviere, Michel Sadelain, Bahram Valamehr
Journal: Blood (2018)
In vitro antimyeloma activity of the iron chelator deferasirox (DFX).
Authors: Ella Willenbacher, Wolfgang Willenbacher, Ulrike Funk, Brigitte Kircher
Journal: Journal of Clinical Oncology (2014)

e19567 Background: Despite clinical progress in Multiple Myeloma (MM) therapy has been made by the implementation of proteasome inhibitors and immuno-modulatory drugs, all patients will finally relapse. New and better myeloma therapeutics thus represent a major unmet clinical need. Clonal tidings probably impede to develop an “one size fits all” drug for MM. Furthermore the (self) creation of a protective micro-environment (ME) enhances treatment resistancy. ME factors might be more constant and amendable to therapeutic interventions than the “moving target”constituted by the MM cell, herself. Cancer and iron metabolism are connected in a complex fashion. Elevated serum ferritin levels are associated with reduced overall survival and a worse outcome in MM. DFX, a well tolerated oral iron-chelator, has positive effects in iron overload. In-vitro-studies indicate strong cytotoxic effects within multiple cancer cell models. The aim of this research was to investigate the anti-MM properties of the oral iron chelator DFX and its effects on MM cell-lines alone and in an ME co-culture. Methods: 3 MM cell lines (KMS-12-PE, AMO-1, U266) and PBMC from healthy donors were cultivated alone and in co-culture with the stromal cell line HS-5 and exposed with pharmacologically realistic doses of DFX (0-5-10-25-50 µM). In appropriate assays these cultures were analyzed for proliferation (H3-thymidine incorporation), metabolic activity (EZ4you assay), apoptosis induction (PI, Annexin) all after 24h and 72h. Results: DFX dose-dependently inhibits the proliferation and metabolic activity of MM cell lines, as well leads to increased apoptosis induction, even at relatively low concentrations easily achievable with standard dose DFX in humans. These effects are much more pronounced in MM cell lines compared to the stromal cell line HS-5 and PBMC. The anti-myeloma effects of DFX were well preserved in an artificial microenvironment co-culture system. Conclusions: Our results indicate a potential benefit of iron-chelation in the treatment of Multiple Myeloma. Further in-vitro studies of DFX-anti-MM drug combinations and possible synergistic strategies as well as iron metabolism analysis are ongoing both with MM cell lines and primary patient material.
From Basic Research to Molecular Breeding — Chinese Scientists Play A Central Role in Boosting World Rice Production
Authors: Ding Tang, Zhukuan Cheng
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract On November 18, 2018, the Future Science Prize Awarding Ceremony was held in Beijing. In the area of life science, Professors Jiayang Li, Longping Yuan, and Qifa Zhang shared the prize for their pioneering contributions in producing high-yield, superior-quality rice through systematic study of molecular mechanisms associated with specific rice features and application of novel approaches in rice breeding. The Future Science Prize is also touted as “China’s Nobel Prize”, fully affirming their achievements in rice basic research and breeding.
Prevalence of and Predictive Factors for Burnout Among French Urologists in Training
Authors: Jérôme Gas, Stéphane Bart, Philippe Michel, Benoit Peyronnet, Sébastien Bergerat, Jonathan Olivier, Dimitri Gambachidze, William Akakpo, Cedric Lebacle, Mathilde Nedelec, Paul Panayotopoulos, Maximilien Baron, Emmanuel Perrot, Bastien Gondran-Tellier, Anthony Manuguerra, Inès Dominique, Xavier Matillon, Benjamin Pradere
Journal: European Urology (2019)
Abstract 14856: Change in Left Ventricular Mechanical Dispersion Predicts Mortality After Cardiac Resynchronization Therapy
Authors: Pieter van der Bijl, Mand Khidir, Melissa Leung, Nina Ajmone Marsan, Victoria Delgado, Jeroen J Bax
Journal: Circulation (2016)

Introduction: Left ventricular (LV) mechanical dispersion (MD) is a novel, echocardiographic tool to quantify the heterogeneity of mechanical function, and has been associated with prognosis in pat...
Abstract MP64: <i>APOL1</i> Renal Risk Variants Associate With Heart Failure With Preserved Ejection Fraction in African-American Women
Authors: Nora Franceschini, Ana Barac, Lisa Martin, Wayne Rosamond
Journal: Circulation (2018)

Introduction: African origin coding variants in APOL1 , encoding apolipoprotein L1, are strongly associated with various kidney diseases in African Americans, with odds ratio ranging from 7 to 89 for two renal risk allele carriers. APOL1 renal risk genotypes may influence risk for cardiovascular disease and mortality, but findings have been inconsistent. Hypothesis: Given that African-American aging women are at high risk for cardiovascular disease and stroke, we asked whether APOL1 risk genotypes affect these outcomes. Methods: We used data from 11,137 African-American postmenopausal women who participated in the Women’s Health Initiative prospective cohort, followed from enrollment (1993-1998) to 2014. APOL1 genotypes were obtained directly or by imputation from whole exome sequencing data. Adjudicated outcomes were incident coronary heart disease, stroke and subtypes, heart failure and subtypes, and overall and cause-specific mortality obtained from hospital records and death certificates. End-stage renal disease status (ESRD) was obtained from the US Renal Data System. We estimated incident rates for each outcome and used Cox proportional hazard to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of APOL1 high and low risk groups with outcomes. Results: Mean age was 61.7 years. APOL1 high risk carriers (12.3% of participants) had higher prevalence of hypertension, use of cholesterol lowering medication, and reduced estimated glomerular filtration rate (eGFR), defined as &lt;60 mL/min/1.73 m 2 . After 11 years mean follow-up APOL1 high risk subjects had a higher incident rate of ESRD and hospitalized heart failure with preserved ejection fraction (HFpEF) than low risk carriers, but showed no difference in the incident rates of other outcomes. In adjusted models, there were a significant 43% increased hazard of ESRD (95% CI 1.01, 2.02), and a 58% increased hazard of hospitalized HFpEF (95% CI 1.03, 2.41) among high risk compared to low risk APOL1 carriers. In sensitivity analyses restricted to the genome-wide association sample and accounting for population stratification (n=7,797), the associations remained significant for HFpEF. These associations were no longer significant after adjusting for eGFR. Conclusions: We identified novel associations of APOL1 high risk status with hospitalization for HFpEF among postmenopausal women, which are likely mediated by APOL1 -induced chronic kidney disease. We also showed lack of association of APOL1 with incident coronary heart disease, stroke and mortality.
Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin
Authors: Hanan Abumanhal-Masarweh, Lilach Koren, Assaf Zinger, Zvi Yaari, Nitzan Krinsky, Galoz Kaneti, Nitsan Dahan, Yael Lupu-Haber, Edith Suss-Toby, Esther Weiss-Messer, Michal Schlesinger-Laufer, Janna Shainsky-Roitman, Avi Schroeder
Journal: Journal of Controlled Release (2019)
Prognostic value of radiographic extracapsular extension in locally advanced head and neck squamous cell cancers.
Authors: Jerry T. Liu, Benjamin H. Kann, Brian De, Michael Buckstein, Richard Lorne Bakst, Eric Michael Genden, Marshall R. Posner, Peter M. Som, Vishal Gupta
Journal: Journal of Clinical Oncology (2014)

6095 Background: Previous data from our institution suggests that radiographic evidence of extracapsular extension (rECE), identified on pretreatment diagnostic CT imaging, predicts for worse outcomes for oropharyngeal cancer patients undergoing radiation therapy. We sought to validate these findings in all sites of locally advanced head and neck squamous cell cancers (LAHNC). Methods: From our departmental database, 224 LAHNC patients with accessible pretreatment CT scans completed definitive or adjuvant radiation therapy (± induction and/or concurrent chemotherapy) from 2005-2012. Three patients died shortly after treatment. The remaining 221 patients (nasopharynx (n=19), oral cavity (n=22), oropharynx (n=126), hypopharynx (n=15), larynx (n=21), nasal cavity/sinus (n=3), and unknown primary (n=15)) were selected and all pretreatment CTs were reviewed by our head/neck radiologist for evidence of rECE. Patients were stratified by presence of rECE, age, gender, race, smoking history, ECOG performance status (PS), disease site, cT-stage, cN-stage, and treatment type. Univariate and multivariate analyses (MVA) were performed regarding impact of these factors on locoregional control (LRC), distant control (DC), progression free survival (PFS) and overall survival (OS). Results: With median follow-up of 30 months (range: 3-100), 126 (57%) patients had rECE and 95 (43%) did not. These groups were well-balanced for age, gender, race, smoking history, disease site, PS, treatment type, and cT-stage. Patients with rECE were more likely to have cN2-3 disease versus those without rECE (84% vs. 77%, p=0.015). Patients with rECE had worse LRC (3yr: 78% vs. 89%, p=0.032), DC (3yr: 72% vs. 89%, p=0.017), PFS (3yr: 60% vs. 73%, p=0.011), and OS (3yr: 64% vs. 80%, p=0.011). On MVA, rECE was found to independently predict for worse LRC (HR 2.59, 95%CI 1.22-5.51), DC (HR 3.28, 95%CI 1.57-6.85), PFS (HR 1.91, 95%CI 1.16-3.15), and OS (HR 2.041, 95%CI 1.15-3.63). Conclusions: Presence of rECE independently predicts for worse outcomes for LAHNC patients undergoing radiation therapy. Larger studies with longer follow-up are needed to determine how rECE can guide clinical management in these patients.
Survival Outcomes of Patients with Therapy-Related Myelodysplastic Syndromes in the United States
Authors: Raffi Tchekmedyian, Tomas Radivoyevitch, Aaron T. Gerds, Aziz Nazha, Hetty E. Carraway, Anjali S. Advani, Jaroslaw P. Maciejewski, Matt Kalaycio, Navneet S. Majhail, Mikkael A. Sekeres, Sudipto Mukherjee
Journal: Blood (2018)
Phase II study of low-dose cyclophosphamide and ipilimumab in metastatic melanoma.
Authors: Anna C. Pavlick, Sunandana Chandra, Claire Stein, Kathleen M. Madden, Rajni Kannan, Crystal Escano, Caroline Muren, Ethel Yepes, Rachel Lubong Sabado, Nina Bhardwaj
Journal: Journal of Clinical Oncology (2014)

e20025 Background: Ipilimumab (Ipi) has improved clinical outcomes in metastatic melanoma (MM). Previous data suggested that low doses of cyclophosphamide (ldCTX) may have immunomodulatory effects including selectively decreasing T regulatory cells, down-regulating CTLA-4 on T cells, and altering cytokine profile. On this basis, we studied the combination of ldCTX and Ipi in patients (pts) with MM for overall response rates (RRs) and explored immunologic correlates. Methods: 10 pts with MM (2F:8M; median age 59; 7 cutaneous MM, 2 ocular MM and 1 unknown primary MM.) were enrolled in the stage 1 phase of the Simon 2 stage designed trial. Pts received induction tx with ldCTX (300 mg/m2) on day 1 followed by Ipi 10 mg/kg on day 3 for four cycles. Tumor assessments were done on Wk 12 and 24. Pts who showed clinical benefit at Wk 24 received ipi only maintenance tx for 3 cycles q 12 wks. Reassessment was on Wk 36, 48 and 60. Exploratory objectives including the T cell profile, antigen specific T cell responses, cytokine profile, CTLA-4 polymorphisms are being completed. Results: Six pts completed all 4 cycles of induction, and 4 pts received at least 2- 3 cycles. At Wk 24, 4 pts had stable disease, and 6 pts had progression of disease. Two pts received 1 cycle of maintenance tx. The 2 other SD pts were removed from study due to toxicity. Since the primary endpoint was objective response rate and none were seen, the trial was terminated based on trial design. 3 pts experienced Grade IV steroid refractory diarrhea that required anti-TNF alpha tx, and 1 patient experienced Grade III myopathy requiring a cholinesterase inhibitor for myasthenia gravis-like symptoms. Conclusions: Combination tx with ldCTX and ipi did not increase RRs; however did appear to significantly increase irAEs. Results of exploratory objectives may further elucidate mechanisms of enhanced toxicity and reduced efficacy. Clinical trial information: NCT01740401. irAE Total number of events Grade I Grade II Grade III-IV Grade III-IV irAE’s in Registration Trial (%) (Hodi, 2010NEJM) Rash 7 5 (50%) 2 (20%) 0 2.5% Diarrhea/colitis 6 0 3 (30%) 3 (30%) 4.6%/5.3% Nausea 1 1 0 0 2.3% Endocrinopathy 1 1 0 0 3.8% Myopathy/neuropathy 1 0 0 1 1.5%