tbuckley/cabot-search huggingface dataset:
Inhibitory effect of α -mangostin on colon carcinogenesis induced by azoxymethane plus dextran sulfate sodium in CD1 (ICR) mice
Authors: Junya Arakaki, Nao Sunagawa, Itaru Chiba, Nana Morita, Tatsuya Kinjo, Tatsuya Kaneshiro, Takamitsu Morioka, Tadashi Nishimaki, Naoki Yoshimi
Journal: Cancer Research (2007)

4974  We have already reported that α-mangostin might be chemopreventive agent by using the preneoplastic lesions in rat colon carcinogenesis. In the present study, we examined the chemopreventive potential of α-mangostin, which is a major xanthone derivative in mangosteen pericarp (Garcinia mangostana), in mice colon carcinogenesis induced by Azoxymethane (AOM) & Dextran Sulfate Sodium (DSS). Seventy male Crj: CD1 (ICR) mice were randomly divided into 5 experimental groups. Mice in groups 1 to 3 were given a subcutaneous injection of AOM (7.5 mg / kg body weight) once. They received 1 % DSS in the drinking water for 1 week after the injection of AOM and then were maintained on tap water. Starting one week before the first injection of AOM, mice in groups 2 and 3 were fed a diet containing 200 and 500 ppm α-mangostin, respectively, for 16 weeks. Mice in groups 4 and group 5 were fed a diet containing 500 ppm α-mangostin and the control diet (CE-2, CLEA Co.) alone, respectively. The experiment was terminated in 16 weeks. Dietary α-mangostin at each dose level (200 and 500 ppm) showed the tendency to lower incidence of colon neoplasms (44.4 % and 35.0 %), when compared to group 1 with AOM & DSS alone (68.4 %). Similarly, the multiplicities of neoplasms in groups 2 and 3 were decreased compared to that of group 1. In addition, the treatment of mice with α-mangostin in groups 2 and 3 significantly decreased PCNA positive index (P
A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study
Authors: Sheri L Spunt, Lynn Million, Yueh-Yun Chi, James Anderson, Jing Tian, Emily Hibbitts, Cheryl Coffin, M Beth McCarville, R Lor Randall, David M Parham, Jennifer O Black, Simon C Kao, Andrea Hayes-Jordan, Suzanne Wolden, Fran Laurie, Roseanne Speights, Ellen Kawashima, Stephen X Skapek, William Meyer, Alberto S Pappo, Douglas S Hawkins
Journal: The Lancet Oncology (2019)
Dasatinib-Based Two-Step Induction Prior to Allogeneic Hematopoietic Cell Transplantation for Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of the JALSG Ph+ALL213 Study
Authors: Isamu Sugiura, Noriko Doki, Tomoko Hata, Ryuko CHO, Toshiro Ito, Youko Suehiro, Heiwa Kanamori, Shinichi Kako, Mitsuhiro Matsuda, Hisayuki Yokoyama, Yasuhiro Taniguchi, Maki Hagihara, Yukiyasu Ozawa, Shin Fujisawa, Nobuaki Dobashi, Yoshihiro Hatta, Noboru Asada, Kazuteru Ohashi, Yasushi Onishi, Koh Shiro, Satoshi Nishiwaki, Yoshiko Atsuta, Fumihiko Hayakawa, Shigeki Ohtake, Yasushi Miyazaki
Journal: Blood (2019)
Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome
Authors: Angela C. Sosa, Barbara Kariuki, Qi Gan, Alan P. Knutsen, Clifford J. Bellone, Miguel A. Guzmán, Luis A. Barrera, Shunji Tomatsu, Anil K. Chauhan, Eric Armbrecht, Adriana M. Montaño
Journal: Journal of Clinical Investigation (2019)

Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (I10) or the complete GALNS enzyme to orally induce tolerance to GALNS prior to ERT resulted in several improvements to ERT in mice: (a) decreased splenocyte proliferation after in vitro GALNS stimulation, (b) modulation of the cytokine secretion profile, (c) decrease in GALNS-specific IgG or IgE in plasma, (d) decreased GAG storage in liver, and (e) fewer circulating immune complexes in plasma. This model could be extrapolated to other lysosomal storage disorders in which immune response hinders ERT.
Abstract 15399: Prevalence of Left Ventricular Systolic Dysfunction in Pre-Dialysis and Dialysis Patients With Preserved Left Ventricular Ejection Fraction
Authors: Liselotte C Hensen, Kathleen Goossens, Rachid Abou, Joris I Rotmans, J W Jukema, Victoria Delgado, Jeroen J Bax
Journal: Circulation (2017)

Introduction: Cardiovascular morbidity and mortality is high in patients with chronic kidney disease (CKD) and heart failure is particularly frequent. Left ventricular (LV) systolic dysfunction, de...
Psychological origins of the Industrial Revolution: More work is needed!
Authors: Nicolas Baumard
Journal: Behavioral and Brain Sciences (2019)

Abstract I am grateful to have received so many stimulating commentaries from interested colleagues regarding the psychological origins of the Industrial Revolution and the role of evolutionary theory in understanding historical phenomena. Commentators criticized, extended, and explored the implications of the perspective I presented, and I wholeheartedly agree with many commentaries that more work is needed. In this response, I thus focus on what is needed to further test the psychological origins of the Industrial Revolution. Specifically, I argue, in agreement with many commentators, that we need: (1) better data about standards of living, psychological preferences, and innovation rates (sect. R1); (2) better models to understand the role of resources (and not just mortality) in driving cultural evolution and the multiple aspects of the behavioral constellation of affluence (sect. R2); and (3) better predictions and better statistical instruments to disentangle the possible mechanisms behind the rise of innovativeness (genetic selection, rational choice, and phenotypic plasticity) (sect. R3).
Genomic Underpinnings of Tumor Behavior in <i>In Situ</i> and Early Lung Adenocarcinoma
Authors: Jun Qian, Shilin Zhao, Yong Zou, S. M. Jamshedur Rahman, Maria-Fernanda Senosain, Thomas Stricker, Heidi Chen, Charles A. Powell, Alain C. Borczuk, Pierre P. Massion
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants.Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs.Methods: DNA was extracted from 21 ADCs in situ (AISs), 27 minimally invasive ADCs (MIAs), and 54 fully invasive ADCs. This DNA was subjected to deep next-generation sequencing and tested against a custom panel of 347 cancer genes.Measurements and Main Results: Sequencing data was analyzed for associations among tumor mutation burden, frequency of mutations or copy number alterations, mutation signatures, intratumor heterogeneity, pathway alterations, histology, and overall survival. We found that deleterious mutation burden was significantly greater in invasive ADC, whereas more copy number loss was observed in AIS and MIA. Intratumor heterogeneity establishes early, as in AIS. Twenty-one significantly mutated genes were shared among the groups. Mutation signature profiling did not vary significantly, although the APOBEC signature was associated with ADC and poor survival. Subclonal KRAS mutations and a gene signature consisting of PIK3CG, ATM, EPPK1, EP300, or KMT2C mutations were also associated with poor survival. Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers.Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.
Post Transplantation Measurable Residual Disease (MRD) Monitoring Using Next-Generation Sequencing Is Highly Predictive for Relapseafter Allogeneic Stem Cell Transplantation
Authors: Felicitas Thol, Bennet Heida, Konstatin Buettner, Clara Wienecke, Katrin Teich, Carolin Funke, Brandes Maximilian, Piroska Klement, Alessandro Liebich, Johannes Schiller, Martin Wichmann, Blerina Neziri, Anuhar Chaturvedi, Arnold Kloos, Verena I. Gaidzik, Peter Paschka, Lars Bullinger, Walter Fiedler, Albert Heim, Jürgen Krauter, Konstanze Döhner, Hartmut Döhner, Arnold Ganser, Michael Stadler, Lothar Hambach, Razif Gabdoulline, Michael Heuser
Journal: Blood (2019)
Azacitidine for Pre-Emptive Treatment of Measurable-Residual Disease in MDS/AML Patients at High Risk of Hematological Relapse: Results of the Second Cohort of the RELAZA2 Trial
Authors: Uwe Platzbecker, Jan Moritz Middeke, Katja Sockel, Regina Herbst, Lars R. Fransecky, Dominik Wolf, Schumacher Martin, Alwin Krämer, Richard Noppeney, Juergen Novotny, Gesine Bug, Katharina Götze, Karsten Spiekermann, Matthias Stelljes, Christoph Groth, Marion Subklewe, Antje Schubert, Anke Mütherig, Tilmann Bochtler, Marika Mende, Anne Sophie Kubasch, Mathias Hänel, Ulrich Dührsen, Johannes Schetelig, Christoph Röllig, Claudia D Baldus, Gerhard Ehninger, Carsten Müller-Tidow, Hubert Serve, Michael Kramer, Martin Bornhäuser, Christian Thiede
Journal: Blood (2019)
Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition
Authors: Xuanye Zhang, Yixin Zhou, Chen Chen, Wenfeng Fang, Xiuyu Cai, Xiaoshi Zhang, Ming Zhao, Bei Zhang, Wenqi Jiang, Zuan Lin, Yuxiang Ma, Yunpeng Yang, Yan Huang, Hongyun Zhao, Ruihua Xu, Shaodong Hong, Li Zhang
Journal: Journal for ImmunoTherapy of Cancer (2019)

Hepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.This retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.In total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16-76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3-35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103-6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95-157.07], P = .004).HBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.
Muscle Recurrence of a Primarily Nodal Follicular Lymphoma Studied by Contrast-Enhanced 18F-FDG PET/CT
Authors: Gianfranco Belmonte, Carmelo Caldarella, Stefan Hohaus, Riccardo Manfredi, Laura Maria Minordi
Journal: Clinical Nuclear Medicine (2019)

We report the case of a 52-year-old woman with follicular lymphoma localized in the left inguinal region without any extranodal involvement and achieving a complete response after radiotherapy. After a 3-year disease-free interval, muscular recurrence at the left arm was shown by contrast-enhanced F-FDG PET/CT. Contrast-enhanced F-FDG PET/CT performed after immunochemotherapy documented complete disease remission. Lymphoid tissue is usually not present in the skeletal muscle, making muscular lymphomatous involvement quite unusual; muscular relapse of a primarily nodal lymphoma is even rarer.
Chronic conditions among advanced cancer patients and their spouse caregivers.
Authors: Dana Ketcher, Amy Otto, Maija Reblin
Journal: Journal of Clinical Oncology (2019)

20 Background: Chronic conditions and multimorbidity have been recognized to have negative impacts on costs of healthcare, quality of care, and well-being. The interdependence of patients and caregivers has also been highlighted, in that patient factors can impact caregiver outcomes and vice versa. Yet little research has been conducted on how the number of other health conditions among spouse caregivers (CGs) and advanced cancer patients impact their own and their partners’ well-being. Methods: Data were gathered as part of a prospective observational study of couples coping with advanced cancer. Patients had to have a cohabiting spouse/partner who identified as providing some care and also agreed to participate. Results: Patients rated their overall health slightly worse (scale 1-5, M = 2.85, SD = 0.95) than CGs ( M = 2.27, SD = 0.75). Patients also reported more total conditions ( M = 2.59, SD = 1.42) than CGs ( M = 1.4, SD = 1.14). Most patients (81%) reported at least one chronic condition other than cancer (44% of patients reported at least two other conditions); the most common conditions among patients were hypertension (43%), lung disease (36%), arthritis, and diabetes (both 24%). About 23% of CGs reported having no chronic conditions; 36% reported at least one and 41% reported at least two. The most common conditions among CGs were arthritis (40%), hypertension (39%), and heart disease, diabetes, and cancer (13% each). A greater number of CG conditions predicted greater depression symptoms in the patient ( B = 0.60, p = .040), controlling for patient conditions. More conditions among patients was a significant predictor of less patient social support ( B = -0.67, p = .017) and a marginally-significant predictor of greater perceived stress among caregivers ( B = -0.27, p = .064). A history of CG cancer predicted greater depression symptoms in the patient ( B = 2.3, p = .02). Conclusions: Chronic conditions and multimorbidity can have significant psychological consequences for both patient and CG. Clinicians, in addition to making an active effort to incorporate CGs into medical decision making and treatment planning, should also be aware of patient and caregiver multiple chronic conditions in order to provide more holistic care for patients.
Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease
Authors: Adam G. Clooney, Thomas D.S. Sutton, Andrey N. Shkoporov, Ross K. Holohan, Karen M. Daly, Orla O’Regan, Feargal J. Ryan, Lorraine A. Draper, Scott E. Plevy, R. Paul Ross, Colin Hill
Journal: Cell Host & Microbe (2019)
A novel anti-EGFR antibody HLX07 for potential treatment of squamous cell carcinoma of the head and neck
Authors: M.M. Hou, C.L. Ho, H.Y. Lin, W. Jiang, S. Liu, Y. Hong, A. Luk, S.F. Lin, T.C. Hsieh, E. Liu
Journal: Annals of Oncology (2019)
Antimicrobial resistance in hospital wastewater in Scotland: a cross-sectional metagenomics study
Authors: Meghan Perry, Bram van Bunnik, Luke McNally, Bryan Wee, Patrick Munk, Amanda Warr, Barbara Moore, Pota Kalima, Carol Philip, Ana Maria de Roda Husman, Frank Aarestrup, Mark Woolhouse
Journal: The Lancet (2019)
Treatment and Lifestyle Risk Factors for Cardiovascular Disease Post Lymphoma Diagnosis: A Prospective Study in the Modern Treatment Era
Authors: Nicholas J Boddicker, Matthew J. Maurer, Melissa C Larson, Cristine Allmer, Susan L. Slager, Thomas M. Habermann, Sunnia T Chen, Hector R Villarraga, Joerg Herrmann, Gita Thanarajasingam, Alessia Castellino, Grzegorz Nowakowski, David J Inwards, James R. Cerhan, Carrie A. Thompson
Journal: Blood (2019)
Resistance Mechanisms to SYK Inhibition in Acute Myeloid Leukemia
Authors: Anjali Cremer, Jana M. Ellegast, Gabriela Alexe, Elizabeth S. Frank, Linda Ross, S. Haihua Chu, Yana Pikman, Amanda Robichaud, Amy Goodale, Björn Häupl, Sebastian Mohr, Arati V. Rao, Alison R. Walker, James S. Blachly, Federica Piccioni, Scott A. Armstrong, John C. Byrd, Thomas Oellerich, Kimberly Stegmaier
Journal: Cancer Discovery (2019)

Spleen tyrosine kinase (SYK) is a nonmutated therapeutic target in acute myeloid leukemia (AML). Attempts to exploit SYK therapeutically in AML have shown promising results in combination with chemotherapy, likely reflecting induced mechanisms of resistance to single-agent treatment in vivo. We conducted a genome-scale open reading frame (ORF) resistance screen and identified activation of the RAS-MAPK-ERK pathway as one major mechanism of resistance to SYK inhibitors. This finding was validated in AML cell lines with innate and acquired resistance to SYK inhibitors. Furthermore, patients with AML with select mutations activating these pathways displayed early resistance to SYK inhibition. To circumvent SYK inhibitor therapy resistance in AML, we demonstrate that a MEK and SYK inhibitor combination is synergistic in vitro and in vivo. Our data provide justification for use of ORF screening to identify resistance mechanisms to kinase inhibitor therapy in AML lacking distinct mutations and to direct novel combination-based strategies to abrogate these. SIGNIFICANCE: The integration of functional genomic screening with the study of mechanisms of intrinsic and acquired resistance in model systems and human patients identified resistance to SYK inhibitors through MAPK signaling in AML. The dual targeting of SYK and the MAPK pathway offers a combinatorial strategy to overcome this resistance.This article is highlighted in the In This Issue feature, p. 161.
Abstract 15: Public Access Defibrillators: Sex-Based Inequities in Access and Application
Authors: Brian E Grunau, Emad Awad, Takahisa Kawano, Frank Scheuermeyer, Robert Stenstrom, Steven Brooks, Sean Van Diepen, Karin H Humphries, Sarah Pennington, Bobby Gu, Rahaf Al Assil, James Christenson
Journal: Circulation (2019)

Introduction: It is unclear if the benefits of public access defibrillator (PAD) programs are similar between men and women. We investigated the location of out-of-hospital cardiac arrests (OHCA) stratified by sex to determine what proportion was eligible for PAD application. Second, we sought to determine if patient sex was associated with PAD utilization. Methods: We analyzed prospectively collected data from the North American Resuscitation Outcomes Consortium (ROC) Epistry dataset (2011 - 2015), excluding emergency medical services (EMS)-witnessed cases, those not treated by EMS, and children aged less than 10. We compared sex-based differences in public vs private location, and location type (street or highway, public building, place of recreation, industrial place, home residence, farm or ranch, healthcare facility, residential institution, other public property, or other private location). Among public location OHCAs with bystander interventions, we fit an adjusted logistic regression model to estimate the association between sex and PAD application. Results: Among the 61,473 cases, 20,933 (34%) were female, 30,353 had resuscitation attempted by bystander, and 13,597 had initial shockable rhythms. The OHCA incidence in a public location for women and men was 8.8% and 18%, respectively (95% CI for difference 8.7 - 9.7). Women had a significantly lower proportion of OHCAs on the street/highway, in public buildings, places of recreation, and farms, but a significantly higher proportion in the home, healthcare facilities, and residential institutions. Among public location OHCAs with bystander interventions, female sex was associated with a lower odds of bystander PAD application (adjusted OR 0.83, 95% CI 0.70-0.99). Conclusion: Women had fewer OHCAs in public locations eligible for PAD application. Further, among public OHCAs with bystander interventions, women were less likely to have PADs applied.
Abstract 12973: High-Intensity Focused Ultrasound (HIFU) Promotes Angiogenesis in a Rat Model of Peripheral Arterial Disease
Authors: Babak Nazer, Farzin Ghahghaie, Tatiana Kokhlova, Camilo Perez, Lawrence Crum, Thomas Matula, Akiko Hata
Journal: Circulation (2014)

Shock wave therapy (SWT) delivers single pulses of pressure to tissue, and promotes angiogenesis in animal models and humans with PAD and CAD. HIFU applies pulses of multiple pressure waves, which may be more efficient. We hypothesized that setting HIFU intensity to replicate peak negative pressures (-6 MPa) typically used for SWT would lead to greater angiogenesis. Eight week-old female Sprague-Dawley rats underwent left femoral artery excision to induce hindlimb ischemia, and the right hindlimb was used as an internal control. Rats were randomized to three groups (n=10 each): SWT (0.10 mJ/mm2), HIFU (1.054 MHz, 1 ms pulse duration), and sham therapy. Both treatments were applied at a pulse repetition frequency of 5 Hz, 200 pulses per spot, for six spots along the hindlimb. Rats were treated three times weekly for two weeks, and hindlimb perfusion was assessed with a Moor LDI Laser Doppler scanner. Compared with pre-treatment baseline (Fig 1A), HIFU improved the ratio of left:right perfusion by 23.6 ± 4.5% (mean ± SEM; Fig 1B), SWT by 17.0 ± 5.9%, and sham by 4.7 ± 3.4% (Fig 1C). Immunohistochemistry of gastrocnemius muscle was performed using anti-CD31 (PECAM) antibody, and microvascular density was quantified using ImageJ software. Both HIFU and SWT increased microvascular density in the left hindlimb (223 ± 4 and 217 ± 5 vessels/hpf, respectively) compared with sham (196 ± 7, p = 0.0001 for HIFU, p = 0.01 for SWT), but there was no significant difference between HIFU and SWT. RT-PCR was performed to examine the level of VEGF mRNA. HIFU increased left:right VEGF mRNA compared with sham (2.98 ± 0.69 vs 1.17 ± 0.23, p = 0.03), whereas SWT did not exhibit a significant change compared with sham (0.75 ± 0.20, p = 0.19). In conclusion, HIFU may be a potential non-invasive therapy for promotion of angiogenesis and reperfusion for PAD patients. Further research is needed to define a dose-response relationship of HIFU-mediated angiogenesis, and to elucidate its pro-angiogenic mechanisms.
Ribociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in pre-/perimenopausal patients with HR+, HER2– inoperable locally advanced breast cancer (ABC): RIGHT choice study
Authors: Y.-S. Lu, S.S. Malwinder, H. Azim, Y. Eralp, S.-A. Im, Y.S. Yap, T Delgar Alfaro, M. Gao, N.S. El Saghir
Journal: Annals of Oncology (2019)
Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction
Authors: Bharathi Upadhya, Laura C Lovato, Michael Rocco, Cora E Lewis, Suzanne Oparil, William C Cushman, John B Kostis, Carlos J Rodriguez, Monique E Cho, Loretta W Cloud, Anjay Rastogi, Clive Rosendorff, Dalane W Kitzman
Journal: JACC Heart Failure (2019)