tbuckley/cabot-search huggingface dataset:
A large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with <i>ALK</i>-positive (<i>ALK</i>+) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ).
Authors: Giorgio Scagliotti, Dong-Wan Kim, Alice Tsang Shaw, Sai-Hong Ignatius Ou, Gregory J. Riely, Scott N. Gettinger, Benjamin Besse, Michael Thomas, Ravi Salgia, Keith D. Wilner, Cynthia Huang Bartlett, Anna Polli, David R. Gandara
Journal: Journal of Clinical Oncology (2012)

7599 Background: Retrospective small cohort studies suggest ALK+ NSCLC may be particularly sensitive to PEM. Methods: PROFILE 1005 (NCT00932451; Pfizer) is a large phase 2 multi-center, single-arm study of CRIZ in previously treated ALK+ NSCLC. Eligibility criteria included pts with progressive disease from the PEM arm of companion trial PROFILE 1007. We retrospectively assessed objective response rate (ORR) and time to progression (TTP; 1 st dose to objective progression) in pts who received PEM prior to CRIZ. ORR with CRIZ post-PEM was assessed. Results: Of the 439 ALK+ pts enrolled as of June 2011, 369 (84.1%) received prior PEM (single agent or combination; any line advanced/metastatic) with a cumulative ORR of 18.7%. In pts who received PEM combinations 1 st -line (1L; n=120) or 2 nd -line (2L; n=60), ORR was 24.2% and 16.7%; and median TTP was 6.9 months (mo; 95% CI: 6.0–7.4) and 6.9 mo (95% CI: 4.8–8.8), respectively. In pts who received 2L single-agent PEM (n=80), ORR was 12.5% and median TTP was 5.3 mo (95% CI: 3.0–6.6). In pts treated with PEM 3 rd -line (3L) or later (n=138), ORR was 16.7%. By line of PEM treatment, ORR was lower and TTP shorter than that reported in small ALK+ cohorts evaluating multiple lines of treatment. In 2L, previously reported ORR and median PFS with single-agent PEM in adenocarcinoma NSCLC were 12.8% (n=158) and 3.5 mo (n=283), and comparable to our findings. Pts who received 2L single-agent PEM (n=80) subsequently achieved higher ORR with CRIZ (54%; 95% CI: 42–65). Similar analyses in the 1L and 3L groups are ongoing. Conclusions: This retrospective study in predominantly never-smokers with ALK+ NSCLC reports lower ORR and shorter TTP with PEM than that reported in smaller retrospective ALK+ NSCLC cohorts. This finding may be in part due to the inclusion of crossover pts from PROFILE 1007. This analysis and previous reports observed a tendency to a higher response rate and better PFS or TTP with PEM than in unselected populations in 2L, which may not be specifically related to ALK status but to a higher sensitivity to cytotoxic agents in never-smokers. Results from an ongoing phase 3 trial (PROFILE 1007) will provide additional information.
Ten Essential Characteristics of Care Coordination
Authors: Edward L. Schor
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
EphB2 stem-related and EphA2 progression-related miRNA-based networks in progressive stages of CRC evolution: clinical significance and potential miRNA drivers
Authors: Mariangela De Robertis, Tommaso Mazza, Caterina Fusilli, Luisa Loiacono, Maria Luana Poeta, Massimo Sanchez, Emanuela Massi, Giuseppe Lamorte, Maria Grazia Diodoro, Edoardo Pescarmona, Emanuela Signori, Graziano Pesole, Angelo Luigi Vescovi, Jesus Garcia-Foncillas, Vito Michele Fazio
Journal: Molecular Cancer (2018)

EphB2 and EphA2 control stemness and differentiation in the intestinal mucosa, but the way they cooperate with the complex mechanisms underlying tumor heterogeneity and how they affect the therapeutic outcome in colorectal cancer (CRC) patients, remain unclear. MicroRNA (miRNA) expression profiling along with pathway analysis provide comprehensive information on the dysregulation of multiple crucial pathways in CRC. Through a network-based approach founded on the characterization of progressive miRNAomes centered on EphA2/EphB2 signaling during tumor development in the AOM/DSS murine model, we found a miRNA-dependent orchestration of EphB2-specific stem-like properties in earlier phases of colorectal tumorigenesis and the EphA2-specific control of tumor progression in the latest CRC phases. Furthermore, two transcriptional signatures that are specifically dependent on the EphA2/EphB2 signaling pathways were identified, namely EphA2, miR-423-5p, CREB1, ADAMTS14, and EphB2, miR-31-5p, mir-31-3p, CRK, CXCL12, ARPC5, SRC. EphA2- and EphB2-related signatures were validated for their expression and clinical value in 1663 CRC patients. In multivariate analysis, both signatures were predictive of survival and tumor progression. The early dysregulation of miRs-31, as observed in the murine samples, was also confirmed on 49 human tissue samples including preneoplastic lesions and tumors. In light of these findings, miRs-31 emerged as novel potential drivers of CRC initiation. Our study evidenced a miRNA-dependent orchestration of EphB2 stem-related networks at the onset and EphA2-related cancer-progression networks in advanced stages of CRC evolution, suggesting new predictive biomarkers and potential therapeutic targets.
Mcl-1/CDK9 Targeting By AZD5991/AZD4573 Overcomes Intrinsic and Acquired Venetoclax Resistance in Vitro and In Vivo in PDX Model of AML through Modulation of Cell Death and Metabolic Functions
Authors: Bing Z Carter, Po Yee Mak, Wenjing Tao, Mark Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Xiangmeng Wang, Huaxian Ma, Hong Mu, Justin Cidado, Lisa Drew, Michael Andreeff
Journal: Blood (2018)
In the absence of natural killer cell activation donor-specific antibody mediates chronic, but not acute, kidney allograft rejection
Authors: Takafumi Yagisawa, Toshiaki Tanaka, Satoshi Miyairi, Kazunari Tanabe, Nina Dvorina, Wayne M. Yokoyama, Anna Valujskikh, William M. Baldwin, Robert L. Fairchild
Journal: Kidney International (2018)
Colorectal cancer progression is marked by overexpression and activation of splicing variants of the RON receptor tyrosine kinase
Authors: Celee Spidel, Yong-Qing Zhou, Ming-Hai Wang
Journal: Cancer Research (2006)

4138  RON is a receptor tyrosine kinase belonging to the MET proto-oncogene family. Altered expression and activation of RON and its variants results in cell dissociation, migration, and invasion, and has been implicated in the invasive growth and metastasis of cancer. The purpose of the present study was to determine the pathogenic roles of splicing RON variants such as RONΔ160 and short form (sf)-RON in colorectal cancer (CRC) progression. By Western blot analysis, primary CRC (n=35), hepatic metastasis (n=10), and adenoma (n=13) specimens were examined for expression and activation of RON, RONΔ160, and sf-RON. RON was detected in all of the primary CRC samples and overexpressed in 89%, sf-RON was overexpressed in 37%, and RONΔ160 in 26%. Analysis of hepatic metastases also revealed overexpression of RON (80%), sf-RON (30%), and RONΔ160 (70%). In contrast, RON and sf-RON were not overexpressed in any of the adenoma specimens, and RONΔ160 was not detected at all. RONΔ160 is highly phosphorylated in the primary and metastatic colon tissues in which it’s expressed, and E-cadherin, an important cellular adhesion molecule, is decreased. To study sf-RON and RONΔ160 in more detail, they were stably transfected into AAC1 human colon adenoma cells. AAC1 cells expressing the RON variants displayed a more fibroblast-like morphology and contributed to cell survival when exposed to a thiol-reducing agent. Furthermore, Western blotting revealed constitutive activation of RONΔ160 and sf-RON with decreased E-cadherin and increased vimentin expression compared to AAC1 and AAC1-RON cells. These results suggest that sf-RON and RONΔ160 may contribute to an epithelial to mesenchymal transition in colon adenoma cells. Taken together, the overexpression of sf-RON and RONΔ160 is an important step in the progression of colorectal cancer toward a more malignant phenotype. * This research was partially supported by NIH R01 91980 and the Amarillo Area Foundation.
Abstract 13562: Cardiac Electrial Biomarker, a Novel Marker Diagnosing Myocardial Injury in Patients With Symptoms Suggestive for NSTEMI
Authors: Roger Abaecherli, Ivo Strebel, Raphael Twerenbold, Japser Boeddinghaus, Stefan Osswald, Christian Müller, Tobias Reichlin
Journal: Circulation (2017)

Background: The Cardiac Electrical Biomarker (CEB) is a novel electrocardiographic (ECG) marker quantifying the dipolar activity of the heart with higher levels indicating myocardial injury. Method...
World Health Organization Baby-Friendly Hospital Initiative Guideline and 2018 Implementation Guidance
Authors: Joel L. Bass, Tina Gartley, Ronald Kleinman
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Outbreak of Epidemic Keratoconjunctivitis Caused by Human Adenovirus Type D53 in an Eye Care Clinic — Los Angeles County, 2017
Authors: Kelsey OYong, Marie Killerby, Chao-Yang Pan, Thalia Huynh, Nicole M. Green, Debra A. Wadford, Dawn Terashita
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On June 22, 2017, the Los Angeles County Department of Public Health (LAC DPH) was notified of seven patients who were seen at an eye care clinic on June 8, 2017, and later developed symptoms of epidemic keratoconjunctivitis (EKC). EKC is a contagious, severe form of viral conjunctivitis that can cause pain and blurred vision for up to 4 weeks (1). LAC DPH conducted an investigation, which identified 17 patients with EKC, including 15 who had visited the optometry clinic and two who were household contacts of clinic patients. Observations in the clinic found deficiencies in disinfection of tonometers (an instrument connected to a slit lamp and used to test for glaucoma by measuring intraocular pressure) and multiuse eye drop administration. Staff member education and revision of disinfection practices interrupted further transmission. Patient specimens tested positive for human adenovirus (HAdV) type D53 (HAdV-53). As the first documented EKC outbreak associated with HAdV-D53 in the United States, this outbreak highlights the need for rigorous implementation of recommended infection prevention practices in eye care settings.
Design of Hedgehog pathway inhibitors for cancer treatment
Authors: Jitender Bariwal, Virender Kumar, Yuxiang Dong, Ram I. Mahato
Journal: Medicinal Research Reviews (2018)

Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest. Substantial efforts are being made to develop new molecules targeting various components of the Hh signaling pathway. Here, we have discussed the discovery of small molecules as Hh inhibitors from the diverse chemical background. Also, some of the recently identified natural products have been included as a separate section. Extensive structure-activity relationship (SAR) of each chemical class is the focus of this review. Also, clinically advanced molecules are discussed from the last 5 to 7 years. Nanomedicine-based delivery approaches for Hh pathway inhibitors are also discussed concisely.
Irreversible Activation of Rho-activated Kinases Resulted from Evolution of Proteolytic Sites within Disordered Regions in Coiled-coil Domain
Authors: Paolo Armando Gagliardi, Luca Primo
Journal: Molecular Biology and Evolution (2018)

Activation of Rho-associated protein kinase 1 (ROCK1) and myotonic dystrophy kinase-related CDC42-binding kinase alpha (MRCKα) by caspases during apoptosis in vertebrates represents a prototypical example of co-option of kinases by proteases. How caspases acquired the ability to control these proteins during evolution of vertebrates is still unknown. Here, we report a phylogenetic and molecular study on the acquisition of caspase-cleavage sites in the family of Rho-activated kinases (RaKs). We demonstrate that the acquisition of such sites has more frequently occurred in identifiable intrinsically disordered regions (IDRs) within or flanking the coiled-coil domain. Thanks to computational identification of IDRs in protein sequences of different organisms, we predicted and validated the independent evolution of two caspase-cleavage sites in ROCK of arthropods and the loss of one of the MRCKα caspase-cleavage sites in ray-finned fishes. In conclusion, we shed light on the propensity of RaKs to evolve novel proteolytic sites, causing kinase activation and uniform subcellular distribution.
Barriers to providing palliative care to patients with advanced cancer: A province-wide survey of oncology clinicians’ perceptions.
Authors: Sharon Watanabe, Sharlette Dunn, Madalene Earp, Lisa Shirt, Patricia Biondo, Winson Cheung, Marc Kerba, Patricia A. Tang, Aynharan Sinnarajah, Jessica Simon
Journal: Journal of Clinical Oncology (2018)

88 Background: Despite known benefits, cancer care systems struggle to provide early, integrated palliative care (PC). Previously, we identified barriers to providing early PC as perceived by gastrointestinal oncology clinicians in Alberta, Canada (top barrier: time/competing priorities). Here, we expand on the previous study to better understand barriers to early PC for clinicians working with all tumor groups across Alberta. Methods: A 33-item survey was emailed to oncology clinicians in Alberta between November 2017 - January 2018. Questions were informed by Michie’s Theoretical Domains Framework (TDF) and Behaviour Change Wheel (BCW) and queried (a) providing PC in oncology clinics, (b) referral to specialist PC consultation, and (c) working with PC consultants and homecare. Results: Respondents (n = 268) were nurses (42%), physicians (25%), and allied health professionals (20%). Barriers most frequently identified were "patients’ negative perceptions of PC” (68%), “my limited time/competing priorities” (66%), and "capability to manage patients’", social (65%) and spiritual (63%) concerns. These factors map to all three BCW domains: motivation, opportunity, and capability. In contrast, least frequently identified barriers were in clinician’s own motivation, e.g. perceived benefits of PC. There were few significant differences in response by tumor group or profession (χ 2 test, responses coded: disagree [1-3], neutral [4], agree [5-7]). Most notably, tumor groups differed in their perception that “the criteria for PC services are too restrictive” (p = 0.003), while nurses and allied staff reported that patients’ negative perception of PC is a barrier more frequently than physicians (p = 0.003). Conclusions: Surveying across clinicians and tumor groups using Michie’s TDF/BCW revealed that the challenges to an early integrated PC approach include all three sources of behavior, though not equally for all clinicians. Determining this has allowed us to tailor multifaceted interventions, e.g. tip sheets to enhance capability, re-framing PC with patients, and earlier secondary PC nursing access, to enhance clinicians use and patients benefit from an early PC approach.
Communicating the introduction of psychology services in the palliative care (PC) cancer setting: A randomized double blind trial.
Authors: Sujin Ann-Yi, Kimberson Cochien Tanco, Cindy L. Carmack, Diane D. Liu, Swati Bansal, Janet L. Williams, Kyu-Hyoung Lim, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

129 Background: Despite high distress and empirical support for psychosocial services for cancer patients, the utilization of these services continue to be low. Our aims are to ascertain if the manner of introducing psychology services impact patients’ acceptance of services and identify factors associated with acceptance and barriers of psychology utilization. Methods: 100 PC cancer patients who have not received prior psychology services were randomized to observe two video vignettes: one showed a physician introducing a counselor and psychology services to the patient (PI); another showed a counselor entering and introducing psychology services alone (CI). Randomization was stratified using baseline Hospital Anxiety and Depression Scale scores. After viewing both videos, patients completed a survey regarding preference, attitudes, and barriers for psychology services. Patients were blinded regarding the purpose of the study and investigators were blinded to content and order of videos presented. Results: 64 patients reported a preference with 34 preferring PI (p=0.37) and 36 reporting no difference. Younger patients preferred PI (85.7%) versus CI (14.3%, p=0.03). Most reported being aware of available psychology services (N=63), and half (N=50) had been offered psychology services by their physician. Only 40 (40%) patients felt psychology services would be helpful for them, and 43 (43%) reported it would be beneficial for their family/caregivers. Those who found it helpful for themselves or family had higher anxiety than those who did not find it helpful (p=0.03 and p=.02 respectively). The most commonly endorsed barriers for psychology services were travel (N=25) and finances (N=21). Conclusions: We found no significant difference in preference of introduction of psychology services except in patients less than 40 years old who preferred PI. Patients with higher anxiety felt psychology services were helpful for self and family. Only 40% perceived psychology services as useful for self and family. More research is needed to investigate the most effective approach for introducing psychology services to increase perception of usefulness and utilization in cancer patients. Clinical trial information: NCT03035448.
ADWE-03 Cryoablation for the treatment of refractory oesophageal neoplasia after unsuccessful first line endoscopic eradication therapy
Authors: Durayd Alzoubaidi, Cormac Magee, Martin Everson, David Graham, Laurence Lovat, Rehan Haidry
Journal: Endoscopy (2018)

<h3>Introduction</h3> Endoscopic eradication therapy EET with endoscopic mucosal resection EMR for visible lesions followed by Radiofrequency ablation RFA for flat Barrett's oesophagus BE is the gold standard treatment for patients with BE related neoplasia. In a minority of patients EET is unsuccessful and alternative therapies are desirable. Cryoablation with the Cryoballoon device (C2 therapeutics) is a novel ablative therapy that uses cycles of freezing and thawing to induce cell death by intra and extracellular ice formation, vascular injury, and apoptosis. <h3>Aim</h3> Single centre study to evaluate the feasibility of the focal cryoablation device for the treatment of areas of refractory oesophageal neoplasia in patients who had undergone first line EET. Endpoints: CR-D and CR-IM at 3 month follow up. The rate of stenosis and adverse events were also studied. <h3>Method</h3> A total of 16 cases (11 M,5 F) have been treated by a single experienced endoscopist. Baseline histology included 7 Low Grade Dysplasia LGD, 5 High Grade Dysplasia HGD, 2 Intramucosal cancer (IMC) and 2 patients with Early Squamous Cell Neoplasia ESCN. All patients had residual neoplasia after sequential first line EET. The median length of dysplastic BE treated was 3 cm (Range: 1–10) in 14 cases and 3 cm of a visible lugols-voiding-mucosa in 2 patients with ESCN. An average of 10 ablations applied per patient (range 2–24). Each selected area of visible dysplasia received 10 s of ablation. Only 1 session of cryoablation per patient. Endoscopy and rebiopsy from the treated sites were taken at 3 months post ablation to assess for end points. <h3>Results</h3> CR-D achieved in 75% (12/16) of all patients at first follow up. In those with BE the CR-D was 79% (11/14) and CR-IM 36% (5/14). 1 of the patients with ESCN did not respond to Cryoablation and was referred for radiotherapy. There was progression from LGD to HGD in 1 BE case that was treated with EMR. Technical difficulty due to challenging anatomy was noted in 1 case with tortuous and dilated oesophagus. There were no device malfunction or adverse events. Stenosis was noted in 6% of cases. <h3>Conclusion</h3> In this single centre feasibility cohort study, Cryoablation with the cryoballoon device appears to be a viable strategy in patients with refractory neoplasia after sequential first line EET. It is well tolerated and partially successful in obtaining CR-D and CR-IM in 'treatment-refractory' patients with BE dysplasia. Further trials of dosimetry, efficacy and safety in 'treatment-naïve' patients with randomised controlled trials is recommended and are underway.
Abstract 14700: Impact of Hemodialysis on Left Ventricular Systolic and Diastolic Properties Before and After Dialysis: a Three-dimensional Speckle Tracking Echocardiography Study
Authors: Masanori Kawasaki, Ryuhei Tanaka, Hidemaro Sato, Shingo Minatoguchi, Tatsuya Kariya, Takashi Yoshizane, Koji Ono, Toshiyuki Noda, Kijun Nagata, Shigeki Sawada, Koshi Goto, Hiroshige Ohashi, Shinya Minatoguchi
Journal: Circulation (2016)

Introduction: Most patients with dialysis have left ventricular (LV) hypertrophy and fibrosis which may result in heart failure. Although estimation of LV function and fluid status is helpful in tr...