tbuckley/cabot-search huggingface dataset:
A randomized clinical trial of chemotherapy with gemcitabine/cisplatin/nabpaclitaxel with or without the AXL inhibitor bemcentinib (BGB324) for patients with advanced pancreatic cancer.
Authors: Muhammad Shaalan Beg, Andrew M. Lowy, Peter J. O'Dwyer, Gayle S. Jameson, Erkut Hasan Borazanci, Hitendra Patel, Clare Massey, Julia Schoelermann, James Lorens, Farjana Fattah, Kimberli Crane, Erin Fenske Williams, Jatan Clark, Daniel D. Von Hoff, Rolf A. Brekken
Journal: Journal of Clinical Oncology (2019)

TPS473 Background: The Axl pathway coordinately mediates immune evasion and drug resistance in pancreatic cancer. Systemic Axl inhibition can enhance the efficacy of cancer therapy by blocking tumor cell proliferation, survival and drug resistance associated with epithelial-mesenchymal transition (EMT), and targeting innate immune suppression in the tumor microenvironment. Bemcentinib (BGB324) is a first in class, selective oral inhibitor of Axl. Our group has shown that bemcentinib therapy, in combination with gemcitabine, improved survival in multiple preclinical models of pancreatic cancer. Methods: This is a multicenter, randomized, phase 1b/2 clinical trial of nab-paclitaxel/gemcitabine/cisplatin with or without bemcentinib. Patients with metastatic pancreatic cancer, good performance status and preserved liver, kidney and hematologic function are eligible. The treatment schedule is as follows: Bemcentinib 100 or 200 mg daily, nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 intravenously on D1, 8 every 21 days. 3 -12 patients will be recruited in part 1 following a modified 3+3 dose finding scheme. Part 2 of the study is a 1:1 randomized phase 2 design enrolling 62 patients. The primary objective is to determine complete response rate. Secondary end points are overall response rate, PFS and adverse events. A parallel biomarker study will accompany the trial analyzing blood and tissue samples to determine the effect of chemotherapy and bemcentinib on 1) Axl pathway activity in tumor tissue, 2) changes in immune landscape including upregulation of immune cytokines, and immune cell infiltration into the tumor, 3) apoptosis and decreased proliferation of tumor and 4) to identify predictive biomarkers of response. Clinical trial information: NCT03649321.
The role of platelet-derived growth factor in prostate cancer development and progression depends on organ site of involvement in an orthotopic mouse model
Authors: John Papadopoulos, Sun Jin Kim, Jang-Seong Kim, Seung Wook Kim, Marva Maya, Junqin He, Dominc Fan, Isaiah Fidler
Journal: Cancer Research (2008)

4203  Platelet-derived growth factor (PDGF) promotes cancer development and progression by stimulating cell division, migration and angiogenesis. However, in clinical trials targeting the PDGF receptor pathway, responses vary widely among patients and within patients depending on the location of metastases. We utilized an orthotopic human prostate cancer animal model to investigate these differences in response to therapy.  Single clones were isolated from the human prostate cancer cell line PC-3P. Basal levels of PDGF A/B and production in response to exogenous TGF-β were determined by ELISA. Three clones producing low and high basal levels of PDGF A/B were mixed to produce PC-3P-L and PC-3P-H, respectively. PC-3P-H showed significant response to exogenous TGF-β compared with PC-3P-L (p
ATM Inhibition Sensitizes Tumors to High-Dose Irradiation
Authors: Dennis Hallahan
Journal: Cancer Research (2019)

Mechanistic studies of high-dose irradiation are important to improve our understanding on how the efficacy of stereotactically delivered high-dose irradiation can be enhanced by therapeutics such as ataxia-telangiesctasia-mutated (ATM) inhibitors. In this issue of Cancer Research, Torok and colleagues found that a single 15 Gy radiation dose eliminated lung tumor growth in mice when ATM was deleted in cancer cells versus when deleted in endothelial cells. These data support the establishment of clinical trials testing ATM inhibitors in combination with highly conformal radiotherapy or high-dose rate brachytherapy.See related article by Torok et al., p. 773.
Pediatric Advanced Life Support Task Force; International Liaison Committee on Resuscitation. Use of automated external defibrillators for children: an update: an advisory statement from the pediatric advanced life support task force, International Liaison Committee on Resuscitation
Authors: RA Samson, RA Berg, Robert Bingham, Dominique Biarent, A. Coovadia, MF Hazinski, RW Hickey, V. Nadkarni, G. Nichol, J. Tibballs, AG Reis, S. Tse, D. Zideman, J. Potts, K. Uzark, D Atkins
Journal: Circulation (2003)
Highly Efficient Therapeutic Gene Editing of BCL11A enhancer in Human Hematopoietic Stem Cells from ß-Hemoglobinopathy Patients for Fetal Hemoglobin Induction
Authors: Jing Zeng, Daniel E. Bauer, Yuxuan Wu, Benjamin P Roscoe, Pengpeng Liu, Qiuming Yao, Cicera Lazzarrotto, M. Kendell Clement, Mitchel A. Cole, Kevin Luk, Cristina Baricordi, Erica B. Esrick, John P Manis, David Dorfma, David A. Williams, Alessandra Biffi, Carlo Brugnara, Luca Biasco, Christian Brendel, Luca Pinello, Shengdar Tsai, Scot A. Wolfe
Journal: Blood (2018)
Abstract 16964: Triplane Measurement of Fractional Area Change to Assess Single Right Ventricular Function
Authors: Muhammad Y Qureshi, Chelsea L Reece, Angela R Miller, Rebecca K Lindquist, Patrick W O’Leary
Journal: Circulation (2014)

Background: Echocardiographic (echo) functional assessment of single systemic right ventricle (RV) lacks a reliable parameter and does not provide a substitute of volumetric ejection fraction (EF). RV volumes by 3D-echo are challenging and not widely used. Apical RV fractional area change (FAC) has shown some relation to CMR EF, but the strength of correlation has been suboptimal. Adding additional planes to apical FAC may improve this correlation. Our objective was to assess correlation of triplane FAC (apical, short-axis, and inflow-outflow) with CMR EF and to compare the tri- and single plane methods of measuring FAC to each other. Methods: Subjects with hypoplastic left heart syndrome (after superior or total cavopulmonary anastomosis) were prospectively recruited. CMR was performed and right ventricular ejection fraction was calculated. Transthoracic echo studies were performed close to the time of the CMR scan (median interval: 1 d). FAC was measured in apical 4-chamber view, parasternal short axis view at the mid ventricular level, and para-apical right ventricular inflow-outflow view. Triplane FAC was calculated by the average of the three FAC. Comparison was made between FAC and CMR-derived ejection fraction. Results: A total of 25 subjects underwent testing. Triplane FAC could not be assessed in 5, due to lack of optimal acoustic windows. Mean age was 10 ± 8 y (range 9 m to 24 y). Out of the uniplanar methods, apical FAC had the closest relationship to CMR EF. Triplane FAC showed even better correlation coefficient and R 2 values; although in this small group the difference did not reach significance. Results are summarized in the Table. Conclusion: In patients with single systemic RV, triplane FAC offers improved correlation with CMR EF relative to single plane evaluations. This approach may be useful if 3D echo is unavailable or of suboptimal quality and warrants further study.
FDG PET/CT As a Diagnostic and Prognostic Tool for the Evaluation of Marginal Zone Lymphoma
Authors: Iuliana Vaxman, Hanna Bernstine, Geffen Kleinstern, Natav Hendin, Shai Shimony, Liran Domachevsky, Ronit Gurion, David Groshar, Pia Raanani, Anat Gafter-Gvili
Journal: Blood (2018)
IRF-2 regulates NF-kappaB activity by modulating the subcellular localization of NF-kappaB
Authors: Myounghee Chae, Kwangsoo Kim, Yun-Jee Seo, Ik-Soon Jang, Taegun Seo, Dong-Min Kim, Il-Chul Kim, Je-Ho Lee, Junsoo Park
Journal: Cancer Research (2008)

5221  Nuclear Factor-kappa B (NF-κB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-κB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-κB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFα-induced NF-κB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-κB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFα-induced NF-κB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-κB activity via the modulation of NF-κB subcellular localization.
Feasibility and Cost Analysis of Day 4 Granulocyte Colony-Stimulating Factor Mobilized Peripheral Blood Progenitor Cell Collection from HLA-Matched Sibling Donors
Authors: Laura F. Newell, Rebekah Knight, Kelsea Shoop, Sara Murray, Rogelyn Kwock, Carol Jacoby, Susan Slater, Bryon Allen, Brad Cota, Peggy Appel, Rachel J. Cook, Richard T. Maziarz, Gabrielle Meyers
Journal: Blood (2018)
Safety and Efficacy of Methotrexate for Chinese Adults With Psoriasis With and Without Psoriatic Arthritis
Authors: Kexiang Yan, Yuanjing Zhang, Ling Han, Qiong Huang, Zhenghua Zhang, Xu Fang, Zhizhong Zheng, Nikhil Yawalkar, Yuling Chang, Qun Zhang, Ling Jin, Danfeng Qian, Xueying Li, Mingshun Wu, Qiaohu Xu, Xuejun Zhang, Jinhua Xu
Journal: JAMA Dermatology (2019)

It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis.To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis.In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes.A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly).Changes in disease severity, adverse events, blood cell counts, and liver and renal function.A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis).In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.
CircHMGCS1 Promotes Hepatoblastoma Cell Proliferation by Regulating the IGF Signaling Pathway and Glutaminolysis
Authors: Ni Zhen, Song Gu, Ji Ma, Jiabei Zhu, Minzhi Yin, Min Xu, Jing Wang, Nan Huang, Zhongqi Cui, Zhixuan Bian, Fenyong Sun, Qiuhui Pan
Journal: Theranostics (2019)

Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recently shown to participate in cellular development and several pathophysiological processes. The identification of dysregulated circRNAs and their function in cancer have attracted considerable attention. Nevertheless, the expression profile and role of circRNAs in human hepatoblastoma (HB) remain to be studied. In this report, we analyzed the expression prolife of circRNAs in HB tissues and identified circHMGCS1 (3-hydroxy-3-methylglutaryl-CoA synthase 1; hsa_circ_0072391) as a remarkably upregulated circRNA. Methods: The expression prolife of circRNAs in HB tissues were investigated through circRNA sequencing analyses. ISH and qRT-PCR assays were performed to measure the expression level of circHMGCS1. The effect of knocking down circHMGCS1 in HB cells in vitro and in vivo were evaluated by colony formation assay, flow cytometry, xenograft tumors assay and untargeted metabolomics assay. MRE analysis and dual luciferase assay were performed to explore the underlying molecular mechanisms. Results: HB patients with high circHMGCS1 expression have shorted overall survival. Knockdown of circHMGCS1 inhibits HB cells proliferation and induces apoptosis. CircHMGCS1 regulates IGF2 and IGF1R expression via sponging miR-503-5p, and affects the downstream PI3K-Akt signaling pathway to regulate HB cell proliferation and glutaminolysis. Conclusions: The circHMGCS1/miR-503-5p/IGF-PI3K-Akt axis regulates the proliferation, apoptosis and glutaminolysis of HB cells, implying that circHMGCS1 is a promising therapeutic target and prognostic marker for HB patients.
Reply
Authors: Jasmohan S. Bajaj, Zain Kassam, I. Jane Cox, Thomas Gurry, Roger Williams, Eric Alm, Binu John, Mark Smith, Simon D. Taylor‐Robinson, Patrick M. Gillevet
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Smith is employed by and owns stock in Finch Therapeutics. He is employed by OpenBiome. Dr. Kassam consults, received grants, and owns stock in Finch Therapeutics. He is employed by OpenBiome. The letter by Mullish et al. sets out a few key points about our article.1 Medical therapy for recurrent hepatic encephalopathy (HE) in the United States consists of first‐line lactulose, followed by rifaximin in lactulose failure/intolerance.2 Because our inclusion criteria required recurrent HE with the last episode being >1 month ago, patients were on the maximal therapy for at least 1 month. Rifaximin has been associated with changes in gut microbial functionality and not composition in cirrhosis.3 Our participants were already on rifaximin before being randomized. Therefore, all changes that occurred after fecal microbiota transplantation were likely related to the intervention. We included this population because these patients do not place high on the liver transplant list yet suffer multiple HE readmissions, which are a significant health care burden. The machine learning to define a rational donor was based on sequences derived from prior HE patients and healthy controls with the assumption that a higher relative abundance of Lachnospiraceae and Ruminococcaceae indicated a healthier microbiota, including their functionality. Current mechanistic understanding of the functional role played by the microbiota in HE is insufficient to select a donor based purely on his or her presumed functional phenotype, which is why this data‐driven approach was adopted. While the exact microbial structure may not have changed radically, we did find an increase in beneficial taxa such as Lactobacillaceae and Bifidobacteriaceae after fecal microbiota transplantation. The improvement in HE events was over 150 days and not 15 days as suggested in the letter. However, the mechanism of psychometric HE score/EncephalApp‐Stroop improvement remains under investigation because it may not be related entirely to microbiota dysbiosis. This follows other studies that report only partial change in microbiota after successful fecal microbiota transplantation.4 We agree that using microbial functionality, rather than composition, could be a better methodology to define future donors and look forward to a greater understanding of the relative importance of microbes and their metabolites in driving clinical outcomes.
Systemic Treatment for Clinically Amyopathic Dermatomyositis at 4 Tertiary Care Centers
Authors: Joanie Pinard, Alisa N. Femia, Michael Roman, Abeer Alsarheed, Cara Joyce, Janice Lin, Ruth Ann Vleugels
Journal: JAMA Dermatology (2019)

Nonetheless, over half of this cohort found AA to be moderately or seriously financially burdensome, and the average out-of-pocket costs of $1354 is similar to the average out-ofpocket costs of $1418 for patients with psoriasis. 4 The reallife willingness to pay of this cohort reflects the consequences of AA on the everyday lives of patients.Although future work is required to confirm these results and determine their generalizability to the overall community of patients with AA, these findings suggest that the negative psychological consequences of AA may be compounded by financial distress, which has been shown to place patients at risk for worse quality of life. 5 As payers begin to explore coverage around an increasingly promising pipeline for AA treatments, we hope that this evaluation can encourage broader financial coverage for treatments of this psychologically and financially burdensome disease-not just for pharmaceuticals, but for supplementary therapies as well.Physicians should be aware of the potential ramifications of treatment costs for patients and consider financial impairment as an unintended consequence of their recommendations.
Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich syndrome): Frequency, clinical implication, and prognosis
Authors: Noémie Abisror, Arsène Mekinian, Agnès Dechartres, Matthieu Groh, Alice Berezne, Nicolas Noel, Chafika Morati, Julien Haroche, Mathilde Hunault-Berger, Christian Agard, Felix Ackermann, Loïk Geffray, Pierre-Yves Jeandel, Sébastien Trouillier, Thomas Quemeneur, Jean-François Dufour, Isabelle Lamaury, François Lhote, Guillaume Lefèvre, Olivier Fain, Jean Emmanuel Kahn
Journal: Journal of the American Academy of Dermatology (2019)
Abstract 16799: Manganese Superoxide Dismutase Regulates Inflammatory and Metabolic Stresses in Human Pulmonary Artery Endothelial Cells Through a Vascular Smooth Muscle Cell-derived Paracrine Protein-dependent Mechanism
Authors: Wusheng Xiao, Joseph Loscalzo
Journal: Circulation (2017)

Cell-cell communication is required for maintaining physiological functions of the vasculature, and is also involved in the development of vascular disorders. Yet, how heterologous intercellular cr...
Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma: Results from a large national cancer database.
Authors: Samit Kumar Datta, Geoffrey Belini, Maharaj Singh, Wesley Allan Papenfuss, Federico Augusto Sanchez, Nalini Guda, James L. Weese, Aaron Chevinsky
Journal: Journal of Clinical Oncology (2019)

335 Background: There has been a paradigm shift in the treatment of stage 1 pancreatic adenocarcinoma (PAC) from surgery first followed by adjuvant therapy (AT) to Neoadjuvant therapy (NAT) first followed by surgery and this is reflected in the current NCCN guidelines as well. Data comparing these two modalities are limited. AIM: To compare long time survival between surgery vs Surgery + AT and NAT + Surgery in a large National Cancer Database. Methods: We identified patients with surgically resected AJCC clinical stage 1, 1A, and 1B PAC between 2004-2014. Patients were stratified into 3 groups to assess outcomes. Exclusion criteria: those with incomplete survival and sequence of therapy data. Hazard ratios (HR) were calculated for evaluation of survival, as well as for 30-Day and 90-Day Mortality between the 3 groups. Results were adjusted for age and Deyo-Charlson comorbidity index. Results: A total of 9684 pts with Clincal stage 1, 1A, 1B PAC between 2004-2014 were identified. Of these 2266 pts underwent surgery alone; 6222 had surgery followed by AT; and 1196 pts had neoadjuvant therapy followed by surgery. There was a HR of 0.995 (95% CI 0.935-1.058 p = 0.864) and 0.984 (95% CI 0.924-1.048, p = 0.617) for 30- and 90-Day mortality comparing upfront surgery to NAT, respectively. With AT as the reference group for survival, there was a HR of 1.362 (95% CI 1.286-1.443, p &lt; 0.001) for surgery only and HR of 0.929 (95% CI 0.859-1.004, p = 0.064) for NAT. Conclusions: 1. Surgery alone had worse overall survival. 2. There was no significant difference in overall survival when comparing AT and NAT 3. A prospective randomized trial evaluating the differences in survival is needed.
Novel Evidence That Extracellular Nucleotides and Nucleosides Regulate the Expression of Heme Oxygenase 1 (HO-1) in Opposite Ways in Hematopoietic Stem/Progenitor Cells (HSPCs), Which Explains Why ATP Enhances Mobilization of HSPCs, While Its Metabolite Adenosine Inhibits This Process
Authors: Mateusz Adamiak, Kamila Bujko, Monika Plonka, Magdalena Kucia, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2018)
Systematic Literature Review of the Cost-Effectiveness of Treatments, Costs/Resource Use, and Quality of Life in Patients with Mantle Cell Lymphoma
Authors: Neerav Monga, Jamie Garside, Matthew S. Davids, Constantine S. Tam, Katherine Ward, Iain Fotheringham, Peter O'Donovan, Lori Parisi, Christoph Tapprich
Journal: Blood (2018)
Efficacy and Safety of Ruxolitinib in Elderly Patients (&gt; 75 years) with Myelofibrosis
Authors: Roberto Latagliata, Ambra Di Veroli, Giuseppe Alberto Palumbo, Massimiliano Bonifacio, Alessandro Andriani, Nicola Polverelli, Malgorzata Trawinska, Mario Tiribelli, Barbara Anaclerico, Giulia Benevolo, Luca Petriccione, Bruno Martino, Antonia Centra, Mariella D'Adda, Monica Crugnola, Francesco Cavazzini, Micaela Bergamaschi, Alessia Tieghi, Adalberto Ibatici, Costanza Bosi, Margherita Perricone, Marco Montanaro, Michele Cavo, Massimo Breccia, Nicola Vianelli, Francesca Palandri
Journal: Blood (2016)
Bone Marrow Hematopoietic Connexin 43 Is Required for Mitotransfer and AMPK Dependent Mesenchymal Microenvironment Regeneration after Irradiation
Authors: Abhishek K Singh, Karin Golan, Mark J Althoff, Ekaterina Petrovich-Kopitman, Ashley M Wellendorf, Fatima Mohmoud, Mayla Bertagna, Daniel Gonzalez-Nieto, Luis C Barrio, Tsvee Lapidot, Jose A Cancelas
Journal: Blood (2018)