tbuckley/cabot-search huggingface dataset:
Wanted DEAD/H or Alive: Helicases Winding Up in Cancers
Authors: Wanpei Cai, Zhi Xiong Chen, Grishma Rane, Shikha Satendra Singh, Zhang’e Choo, Chao Wang, Yi Yuan, Tuan Zea Tan, Frank Arfuso, Celestial T. Yap, Lorinc S. Pongor, Henry Yang, Martin B. Lee, Boon Cher Goh, Gautam Sethi, Touati Benoukraf, Vinay Tergaonkar, Alan Prem Kumar
Journal: JNCI Journal of the National Cancer Institute (2016)

Cancer is one of the most studied areas of human biology over the past century. Despite having attracted much attention, hype, and investments, the search to find a cure for cancer remains an uphill battle. Recent discoveries that challenged the central dogma of molecular biology not only further increase the complexity but also demonstrate how various types of noncoding RNAs such as microRNA and long noncoding RNA, as well as their related processes such as RNA editing, are important in regulating gene expression. Parallel to this aspect, an increasing number of reports have focused on a family of proteins known as DEAD/H-box helicases involved in RNA metabolism, regulation of long and short noncoding RNAs, and novel roles as "editing helicases" and their association with cancers. This review summarizes recent findings on the roles of RNA helicases in various cancers, which are broadly classified into adult solid tumors, childhood solid tumors, leukemia, and cancer stem cells. The potential small molecule inhibitors of helicases and their therapeutic value are also discussed. In addition, analyzing next-generation sequencing data obtained from public portals and reviewing existing literature, we provide new insights on the potential of DEAD/H-box helicases to act as pharmacological drug targets in cancers.
Learn and Live?: Understanding the Cultural Focus on Nonbeneficial Cardiopulmonary Resuscitation (CPR) as a Response to Existential Distress About Death and Dying
Authors: Leah B. Rosenberg, David Doolittle
Journal: The American Journal of Bioethics (2017)

"Learn and Live?: Understanding the Cultural Focus on Nonbeneficial Cardiopulmonary Resuscitation (CPR) as a Response to Existential Distress About Death and Dying." The American Journal of Bioethics, 17(2), pp. 54–55
The objective Psoriasis Area and Severity Index: a randomized controlled pilot study comparing the effectiveness of ciclosporin and methotrexate
Authors: C.W. Choi, B.R. Kim, E. Seo, S.W. Youn
Journal: British Journal of Dermatology (2017)

A randomised controlled pilot study was performed to compare the clinical effectiveness of cyclosporine and methotrexate, using a new objective severity assessment method, which we then compared with the Psoriasis Area Severity Index (PASI) for usefulness and reliability.

Psoriatic patients with psoriatic lesions over 5% of body surface area were enrolled and underwent 16 weeks of treatment with either cyclosporine or methotrexate. In the cyclosporine group, the initial dose was 150 mg/day for females and 200 mg/day for males.

This article is protected by copyright. All rights reserved.
Gene Expression Profiling Distinguishes Waldenstrom's Macroglobulinemia Patients Presenting with Familial Disease, Advanced IPSS Prognostic Score, and Previous Treatment with Rituximab.
Authors: Zachary Hunter, Evdoxia Hatjiharissi, Jenny Sun, Yang Cao, Hsiuyi Tseng, Megan Lewicki, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Ping Gong, Christina Hanzis, Thea Ioakimidis, Christopher J Patterson, Patricia Sheehy, Bart Barlogie, John D Shaughnessy, Steven Treon
Journal: Blood (2009)
Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST)
Authors: R. G. Maki, J. A. Fletcher, M. C. Heinrich, J. A. Morgan, S. George, J. Desai, K. Scheu, C. D. M. Fletcher, C. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2005)

9011 Background: Resistance to IM eventually develops in most pts with metastatic GIST and is often correlated with secondary mutations in the genes encoding KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases. SU11248 is an oral multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and direct anti-proliferative activity mediated by signal blockade of several kinases, including VEGFR2, KIT, PDGFRA, and FLT3. SU11248 can overcome IM resistance in GIST caused by diverse genomic alterations (Demetri et al. Proc ASCO 2004; abstr 3001). We report longer term clinical results of a continuation study accruing pts treated in a prior phase I/II study. Methods: From 07/02 to 07/04, 97 pts with GIST resistant to or intolerant of IM were enrolled in a phase I/II study and received one of three schedules of SU11248 administered by daily oral dosing with intermittent dosing breaks. The phase II schedule chosen was 50 mg/d daily for 4 weeks with a 2 week break. After 6 months on the phase I/II study, pts with continued clinical benefit from SU11248 were allowed to enter a continuation protocol in which tumor progression and safety were assessed. Results: 32 GIST pts with continued clinical benefit (PR or stable disease > 6 months) have enrolled on the continuation protocol. As of 12/04, with median treatment time over 1 year, 26 pts remain on study, while 6 pts developed progressive disease. For 22 patients with RECIST-evaluable disease neither median time to progression nor overall survival has been reached. Grade 3 and 4 adverse events for this cohort of patients included: hypertension (16%), asymptomatic lipase elevation (15%), neutropenia (14%), fatigue (11%). Conclusions: SU11248 shows promising clinical activity in pts with IM-resistant GIST and provides durable benefit in a selected population of pts. Molecular analyses of tumor genotype are in progress to understand this subset in more detail. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Novartis Novartis Novartis, Pfizer Pfizer
Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers
Authors: Hussein N. Yassine, Meredith N. Braskie, Wendy J. Mack, Katherine J. Castor, Alfred N. Fonteh, Lon S. Schneider, Michael G. Harrington, Helena C. Chui
Journal: JAMA Neurology (2017)

<h3>Importance</h3> The apolipoprotein E ε4 (<i>APOE4</i>) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA,<i>APOE</i>genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature. <h3>Observations</h3> Although randomized clinical trials of ω-3 in symptomatic AD have had negative findings, several observational and clinical trials of ω-3 in the predementia stage of AD suggest that ω-3 supplementation may slow early memory decline in<i>APOE4</i>carriers. Several mechanisms by which the<i>APOE4</i>allele could alter the delivery of DHA to the brain may be amenable to DHA supplementation in predementia stages of AD. Evidence of accelerated DHA catabolism (eg, activation of phospholipases and oxidation pathways) could explain the lack of efficacy of ω-3 supplementation in AD dementia. The association of cognitive benefit with DHA supplementation in predementia but not AD dementia suggests that early ω-3 supplementation may reduce the risk for or delay the onset of AD symptoms in<i>APOE4</i>carriers. Recent advances in brain imaging may help to identify the optimal timing for future DHA clinical trials. <h3>Conclusions and Relevance</h3> High-dose DHA supplementation in<i>APOE4</i>carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in<i>APOE4</i>carriers is warranted.
Higher Incidence of Relapse with Peripheral Blood Rather Than Marrow as a Source of Stem Cells in Adults with Acute Myelocytic Leukemia, but Not in Adults with Acute Lymphocytic Leukemia Autografted during the First Remission
Authors: Norbert C Gorin, Myriam Labopin, Emmanuelle Polge, Benedicte Samey, Vanderson Rocha
Journal: Blood (2008)
H-Ferritin Ferroxidase Activity Induces Cytoprotective Pathways and Inhibits Microvascular Stasis in Transgenic Sickle Mice
Authors: Gregory M Vercellotti, Chunsheng Chen, Carol M Bruzzone, Heather A. Bechtel, Julia Ngyuen, Robert P Hebbel, Clifford J Steer, John D Belcher
Journal: Blood (2012)
What is the benfit of mTOR inhibitors (mTORi) rechallenge in metastatic renal clear cell carcinoma (mRCC) patients (pts) initially treated with TKI?
Authors: Agnes Maj-HES, Reza-Thierry Elaidi, Jacques Medioni, Florian Scotte, Gero Kramer, Wolfgang Hoeltl, Julie Gachet, Corine Teghom, Yohan Gornadha, Stephane Oudard
Journal: Journal of Clinical Oncology (2012)

442 Background: question regarding the benefit of a mTORi re-challenge for pts treated with a previous line of TKI and 1 line of mTORi remains unanswered in mRCC. Methods: this study retrospectively investigated Treatment Duration (TD), best overall response (OR) in pts treated with TKI and mTORi in a sequence temsirolimus-everolimus (T-E) or everolimus-temsirolimus (E-T). Eligibility criteria: TKIs prior to either sequence of mTORi. Pts characteristics and prognostic factors (Heng’s score) were considered prior to TKI and 1 st mTORi. Response was defined with respect to TD and best OR: E: Non Responders (NR): &lt; 4.9 months (m) + progressive disease (PD), Responders (R): &gt;4.9m + SD/PR; T: Non Responders (NR): &lt; 3.6 months (m) + PD; Responders (R): &gt;3.6 m + SD/PR. Results: 12 pts were eligible. 5 and 7 pts received 1 and 2 TKIs prior to 1 st mTOR, respectively. 9 and 3 pts were in the intermediate and poor risk group respectively prior 1 st mTORi (Heng’s score). 7 pts received E and 5 pts received T as first mTORi. Whatever the sequence, 7 pts out of 12 were responders to E and 2 out of 12 were responders to T (3 pts did not respond to any mTORi). In the E-T sequence, 5 pts were responders to E with no response to T, 1 pt no responder to E but responder to T (1 pt didn’t respond to both mTORi). In the T-E sequence, 2 pts were responders to E, 1 pt was responder to T and 2 pts didn’t response to both mTORi. Median TD for E-T and T-E sequences was 10.3m (95%CI: 8.8-19.2) and 5.8m (95%CI: 2.9-19.3), respectively. Response was not related to pt’s prognosis group. Conclusions: despite the small effective of this study, results suggest that responders to everolimus as 1 st mTORi could not benefit from a re-challenge with temsirolimus. Pts who were not responders to temsirolimus could still be responders to everolimus. This observation should be confirmed with larger databases and prospective studies. [Table: see text]
Apoptosis Repressor with Caspase Recruitment Domain Is Regulated by the cIAP1-NIK Axis and Confers Resistance to SMAC Mimetic Birinapant-Induced Cell Death in AML
Authors: Bing Z. Carter, Po Yee Mak, Duncan H. Mak, Vivian Ruvolo, Rodrigo Jacamo, Steven M. Kornblau, Michael Andreeff
Journal: Blood (2012)
Characterization of Monocyte Subpopulations (CD14+CD16− and CD14++CD16+) generated from Cord Blood Haematopoietic Progenitor CD34+
Authors: Malgorzata Stec, Bozena Mytar, Kazimierz Weglarczyk, Irena Ruggiero, Marek Zembala
Journal: Blood (2008)
Prediction of VOD Using Biomarkers of Endothelial Injury.
Authors: Corey Cutler, J. Aldridge, H. T. Kim, S. Ayanian, G. Bradwin, C. Revta, G. Murga, V. Ho, E. Alyea, J. Koreth, P. Armand, P. G. Richardson, R. J. Soiffer, J. Ritz, J. H. Antin
Journal: Blood (2008)
Steroid Therapy Increase Only Adenovirus Infection but Not Cytomegalovirus Infection in Dose Dependent Manner after Hematopoietic Stem Cell Transplantation.
Authors: Akane Tsujimura, Koichi Miyamura, Yachiyo Kuwatsuka, Yoshihiro Inamoto, Taku Oba, Seitaro Terakura, Yoshihisa Kodera
Journal: Blood (2006)
Transfer of Human T-Cell Receptors (TCR) Containing Murine Chimeric Constant Beta-Gamma-Chain Sequences Reduces the Risk of Mixed Heterodimers and Shows Enhanced in Vitro-Accumulation of TCR-Tranduced Effector Cells.
Authors: Angela Krackhardt, Xiaoling Liang, Ingrid G Schuster, Luise U Weigand, Elfriede Eppinger, Wolfgang Uckert, Dirk Busch, Christian Peschel
Journal: Blood (2009)
Prophylactic CNS Therapy (with or without Radiation Therapy) in Medium-High Risk Acute Lymphoblastic Leukemia (ALL) Children: Long-Term Outcome Evaluation of the Randomized BFM-Oriented Trial 58832 (period 1983-1989) of the EORTC Children Leukemia Group
Authors: Caroline Piette, Stefan Suciu, Yves Bertrand, Anne Uyttebroeck, Els Vandecruys, Geneviève Plat, Patrick Lutz, Claire Pluchart, Nicolas Sirvent, Maryline Poirée, Pauline Simon, Alina Ferster, Claire Hoyoux, Francoise Mazingue, Robert Paulus, Dominique Plantaz, Caroline Thomas, Caroline Gilotay, Jutte Van Der Werff Ten Bosch, Pierre Simon Rohrlich, Yves Benoit
Journal: Blood (2016)
Phase I dose escalation of temozolomide with thiotepa and carboplatin with autologous hematopoietic cell reinfusion in patients with recurrent/refractory malignant brain tumors
Authors: S. Gardner, M. Fisher, J. Belasco, P. Phillips, J. Finlay
Journal: Journal of Clinical Oncology (2007)

2060 Background: The prognosis for most patients with recurrent malignant brain tumors is dismal. Treatment options are limited especially for patients who have already received irradiation. TMZ is an oral alkylating agent which is approved for use in patients with high grade glioma and has also been shown to have activity in patients with recurrent medulloblastoma. It’s primary dose-limiting toxicity is non- cumulative bone marrow suppression. In the present study, TMZ is given in a dose escalation fashion with fixed doses of high dose thiotepa and carboplatin with AHCR in the treatment of patients with recurrent or refractory malignant brain tumors. Methods: Treatment consisted of TMZ twice daily on days -10 to -6 followed by thiotepa 300 mg/m 2 /day and carboplatin AUC=7/day on days -5 to -3 with AHCR on day 0. Filgrastim was given day +1 and continued until engraftment. Results: 27 patients (18M; 9F) ages 3–46 years were treated from 11/00 until 10/04. Diagnoses included high grade glioma (n=12); medulloblastoma/PNET (n=9); CNS germ cell tumor (GCT) (n=4); and 1 each ependymoma and spinal cord PNET. TMZ doses ranged from 50 mg/m 2 twice daily (100 mg/m 2 /day) to 200 mg/m 2 twice daily (400 mg/m 2 /day) for 5 days. One patient had dose limiting toxicity consisting of reversible veno-occlusive disease at dose level 3 (TMZ 100 mg/m 2 twice daily). Two patients had dose limiting toxicity at dose level 7 (TMZ 200 mg/m 2 twice daily) consisting of transient encephalopathy (n=1) and severe mucositis (n=1). Additional toxicities included bacteremia (n=11), C. difficile enteritis (n=6) and grade 4 elevation of bilirubin and/or liver transaminases (n=2). There were no toxic deaths. Survival included 3 patients with glioma (38–48 months); two of whom had relapsed following standard dose TMZ; 3 patients with PNET/MB (48–72 months) and 3 patients with CNS GCT (26–71 months). Conclusions: Increased doses of TMZ are feasible when given with AHCR. There is presently a phase II study underway through the Pediatric Blood and Marrow Transplant Consortium evaluating the efficacy of TMZ at a dose of 175 mg/m 2 /day twice daily for 5 days with high dose thiotepa and carboplatin and AHCR. No significant financial relationships to disclose.
Expression of B and T Lymphocyte Attenuator (BTLA) Correlates with CNS Metastasis and Adverse Prognosis in Activated B-Cell Lymphoma and Acute Lymphoblastic Leukemia
Authors: Huimin Geng, Zhengshan Chen, Shawn Anderson, Eleanor Fraser, Ming Lu, Chen Lingjing, Colin Collins, Muschen Markus, James L. Rubenstein
Journal: Blood (2015)
Change in Distance to Nearest Facility and Abortion in Texas, 2012 to 2014
Authors: Daniel Grossman, Kari White, Kristine Hopkins, Joseph E. Potter
Journal: JAMA (2017)

Sarah C. M. Roberts, DrPH; Ushma D. Upadhyay, PhD, MPH; Guodong Liu, PhD; Jennifer L. Kerns, MD, MPH; Djibril Ba, MPH; Nancy Beam, PhD, RN, MPH, MSN; Douglas L. Leslie, PhD
Physicians Compliance During Maintenance Therapy in Children with Down Syndrome and Acute Lymphoblastic Leukemia.
Authors: Cathrine Bohnstedt, Mette Levinsen, Susanne Rosthøj, Bernward Zeller, Mervi Taskinen, Solveig Hafsteinsdottir, Helga Björgvinsdóttir, Mats Heyman, Kjeld Schmiegelow
Journal: Blood (2012)
Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy?
Authors: Driffa Moussata, Matthieu Allez, Dominique Cazals-Hatem, Xavier Treton, David Laharie, Jean-Marie Reimund, Philippe Bertheau, Arnaud Bourreille, Anne Lavergne-Slove, Hedia Brixi, Julien Branche, Jean-Marc Gornet, Carmen Stefanescu, Jacques Moreau, Philippe Marteau, Anne-Laure Pelletier, Franck Carbonnel, Philippe Seksik, Marion Simon, Jean-François Fléjou, Jean-Fréderic Colombel, Anne-Laure Charlois, Xavier Roblin, Stéphane Nancey, Yoram Bouhnik, Françoise Berger, Bernard Flourié
Journal: Gut (2017)

<h3>Background</h3> Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. <h3>Methods</h3> Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10 cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. <h3>Results</h3> 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn9s colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). <h3>Conclusions</h3> Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. <h3>Trial registration number</h3> IRB 001508, Paris 7 University.
Increased Expression of Secretory Leukocyte Protease Inhibitor (SLPI) In Mononuclear Cells From Patients with Deep Vein Thrombosis
Authors: Fernanda Dutra Santiago-Bassora, Aline Barnabé, Andrey dos Santos, Marcelo F Carazzolle, Gonçalo AG Pereira, Fernanda Loureiro de Andrade Orsi, Erich V de Paula, Joyce M Annichino-Bizzacchi
Journal: Blood (2011)
China’s Burgeoning Epidemic of Diabetes-Associated Mortality
Authors: Margaret Chan
Journal: JAMA (2017)

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How does leptin restore euglycemia in insulin-deficient diabetes?
Authors: Douglas Oberlin, Christoph Buettner
Journal: Journal of Clinical Investigation (2017)

Insulin replacement is the cornerstone of type 1 diabetes (T1D) treatment; however, glycemic control remains a challenge. Leptin has been shown to effectively restore euglycemia in rodent models of T1D; however, the mechanism or mechanisms by which leptin exerts glycemic control are unclear. In this issue of the JCI, Perry and colleagues provide evidence that suppression of lipolysis is a key facet of leptin-mediated restoration of euglycemia. However, more work remains to be done to fully understand the antidiabetic mechanisms of leptin.
The effects of HDIL-2 in combination with pazopanib or sunitinib on PBMCs’ function and RCC cells’ apoptosis: Preliminary in vitro data.
Authors: Alaaeldin Shablak
Journal: Journal of Clinical Oncology (2012)

463 Background: Combination of certain immunotherapies with TKI’s has been used with success in the treatment of metastatic renal cell carcinoma (MRCC) patients. Here we evaluate the in vitro effects of HDIL-2 and pazopanib or sunitinib on the PBMCs’s function and RCC cell lines apoptosis. Methods: PBMCs isolated from healthy donors or RCC patients were treated with different HDIL-2/TKI combination and their proliferation was assessed with CFSE labelling assay. Furthermore, using CD107a degranulation or chromium release assays, the function of these treated cells was evaluated. The BRdU assay was used to examine the effects of these drugs combinations on the proliferation of different RCC cell lines. Results: While HDIL2/sunitinib combination did not inhibit the proliferation of various immune cells induced by HDIL-2 alone, combination of HDIL-2/pazopanib did, on the other hand, inhibit these cells proliferation. Interestingly, none of these combinations had a negative impact on the functional properties of these cells. Significant proportion of RCC cell lines treated with pazopanib underwent apoptosis, while the proportions of apoptotic cells post HDIL-2 or sunitinib treatment were not different from the background. Furthermore, the combination of HDIL-2/pazopanib did not inhibit the pazopanib induced RCC apoptosis. Conclusions: These preliminary data showed that combination of HDIL-2 and either pazopanib or sunitinib could recruit different anticancer mechanism that could enhance the treatment efficacy. Further assessment in this direction is warranted.
First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study
Authors: Jean-Charles Soria, Daniel S W Tan, Rita Chiari, Yi-Long Wu, Luis Paz-Ares, Juergen Wolf, Sarayut L Geater, Sergey Orlov, Diego Cortinovis, Chong-Jen Yu, Maximillian Hochmair, Alexis B Cortot, Chun-Ming Tsai, Denis Moro-Sibilot, Rosario G Campelo, Tracey McCulloch, Paramita Sen, Margaret Dugan, Serafino Pantano, Fabrice Branle, Cristian Massacesi, Gilberto de Castro
Journal: The Lancet (2017)