tbuckley/cabot-search huggingface dataset:
Hospitalization Rates and Predictors of Rehospitalization Among Individuals With Advanced Cancer in the Year After Diagnosis
Authors: Robin L. Whitney, Janice F. Bell, Daniel J. Tancredi, Patrick S. Romano, Richard J. Bold, Jill G. Joseph
Journal: Journal of Clinical Oncology (2017)

Purpose Among individuals with advanced cancer, frequent hospitalization increasingly is viewed as a hallmark of poor-quality care. We examined hospitalization rates and individual- and hospital-level predictors of rehospitalization among individuals with advanced cancer in the year after diagnosis. Methods Individuals diagnosed with advanced breast, colorectal, non-small-cell lung, or pancreatic cancer from 2009 to 2012 (N = 25,032) were identified with data from the California Cancer Registry (CCR). After linkage with inpatient discharge data, multistate and log-linear Poisson regression models were used to calculate hospitalization rates and to model rehospitalization in the year after diagnosis, accounting for survival. Results In the year after diagnosis, 71% of individuals with advanced cancer were hospitalized, 16% had three or more hospitalizations, and 64% of hospitalizations originated in the emergency department. Rehospitalization rates were significantly associated with black non-Hispanic (incidence rate ratio [IRR], 1.29; 95% CI, 1.17 to 1.42) and Hispanic (IRR, 1.11; 95% CI, 1.03 to 1.20) race/ethnicity; public insurance (IRR, 1.37; 95% CI, 1.23 to 1.47) and no insurance (IRR, 1.17; 95% CI, 1.02 to 1.35); lower socioeconomic status quintiles (IRRs, 1.09 to 1.29); comorbidities (IRRs, 1.13 to 1.59); and pancreatic (IRR, 2.07; 95% CI, 1.95 to 2.20) and non-small-cell lung (IRR, 1.69; 95% CI, 1.54 to 1.86) cancers versus colorectal cancer. Rehospitalization rates were significantly lower after discharge from a hospital that had an outpatient palliative care program (IRR, 0.90; 95% CI, 0.83 to 0.97) and were higher after discharge from a for-profit hospital (IRR, 1.33; 95% CI, 1.14 to 1.56). Conclusion Individuals with advanced cancer experience a heavy burden of hospitalization in the year after diagnosis. Efforts to reduce hospitalization and provide care congruent with patient preferences might target individuals at higher risk. Future work might explore access to palliative care in the community and related health care use among individuals with advanced cancer.
The Role of Splenectomy in the Care and Treatment of the CLL Patient
Authors: Michael J Conte, Sameer A. Parikh, Deborah A. Bowen, Timothy G. Call, Brian F Kabat, Kari G Chaffee, Susan M. Schwager, Susan L. Slager, Wei Ding, Neil E. Kay, Tait D. Shanafelt
Journal: Blood (2016)
Pulse oximetry screening for critical congenital heart defects: a European consensus statement
Authors: Paolo Manzoni, Gerard R Martin, Manuel Sanchez Luna, Julije Mestrovic, Umberto Simeoni, Luc Zimmermann, Andrew K Ewer, Paolo Manzoni, Gerard R Martin, Anne de-Wahl Granelli, Avroy A Fanaroff, Luc JI Zimmermann, Ilona C. Narayen, Daniele De Luca, Julie Thomas-Chabaneix, Thorsten Orlikowsky, Umberto Simeoni, Irina G. Soldatova, Julije Mestrovic, Barry S Rodgers-Gray, Virgilio P Carnielli, Antonio Del Vecchio, Sergio Picardo, Robert M Tulloh, Maximo Vento, Manuel Sanchez Luna, Andrew K Ewer
Journal: The Lancet Child & Adolescent Health (2017)
Simultaneous induction of <scp>HSP</scp>70 expression, and degranulation, in IgE/Ag‐stimulated or extracellular <scp>HSP</scp>70‐stimulated mast cells
Authors: X. Li, S. Kanegasaki, F. Jin, Y. Deng, J.‐R. Kim, H. W. Chang, T. Tsuchiya
Journal: Allergy (2017)

Abstract Background In mast cells, induction of HSP 70 expression during antigen stimulation has not been reported. Methods Mouse bone marrow‐derived mast cells ( BMMC ) were stimulated with IgE/Ag or HSP 70. Induction of HSP 70 expression and signaling protein phosphorylation were evaluated by immunoblotting. Results HSP 70 expression is induced in BMMC at an early stage of IgE/Ag‐dependent stimulation, some of which is released from the cells in a granule‐associated form. Induction of HSP 70 expression was also observed with an IgE/Ag‐stimulated human basophilic cell line, indicating that the phenomenon is not restricted to mouse BMMC . The induction of HSP 70 expression, and its release, followed a similar time course to that of degranulation. Released HSP 70 seems to be responsible for degranulation and production of eicosanoids, at least in part, because a neutralizing anti‐ HSP 70 antibody mitigated these activities and because exogenous HSP 70 not only induced immediate degranulation followed by autocrine HSP 70 expression but also enhanced degranulation in IgE/Ag‐stimulated BMMC . Extracellular HSP 70 was found to induce phosphorylation of linker for activation of T cells ( LAT ) and a series of downstream signaling molecules in BMMC . We further found that Fyn, Lyn, and spleen tyrosine kinase (Syk), which are known to concern LAT phosphorylation in IgE/Ag‐stimulated BMMC , were not phosphorylated in HSP 70‐stimulated BMMC , whereas lymphocyte‐specific protein tyrosine kinase (Lck) was phosphorylated. Conclusion Fcε RI stimulation in BMMC and basophils induces HSP 70 expression and its release. Extracellular HSP 70 induces degranulation and mediator release via phosphorylation of LAT .
U. S. Atomic Energy Commission Cancer Program for Fiscal Year 1953
Authors: Paul C. Aebersold
Journal: JNCI Journal of the National Cancer Institute (1952)

Journal Article U. S. Atomic Energy Commission Cancer Program for Fiscal Year 1953 Get access Paul C. Aebersold Paul C. Aebersold Director Isotopes Division, U. S. Atomic Energy Commission, Oak Ridge, Tenn. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 1, August 1952, Pages 280–281, https://doi.org/10.1093/jnci/13.1.280 Published: 01 August 1952
Correlation of allele polymorphisms of tumor integrins with peritoneal carcinosis capability of gastric cancer cells in radically resected patients
Authors: M Scartozzi, C Loretelli, I Bearzi, A Mandolesi, E Galizia, A Onofri, M Pistelli, A Bittoni, R Berardi, S. Cascinu
Journal: Journal of Clinical Oncology (2010)
Diverging effects of enalapril or eplerenone in primary prevention against doxorubicin-induced cardiotoxicity
Authors: Roger Hullin, Mélanie Métrich, Alexandre Sarre, Denis Basquin, Marc Maillard, Julien Regamey, David Martin
Journal: Cardiovascular Research (2017)

Abstract Aims Clinical studies suggest beneficial effects of renin–angiotensin system blockade for prevention of left ventricular (LV) dysfunction after chemotherapy. However, the efficacy of this strategy as primary prevention has been poorly studied. This study aimed at identifying the pathophysiological mechanisms by which mineralocorticoid receptor antagonism (MRA) or angiotensin converting enzyme inhibition (ACEi) provide protection against doxorubicin-induced cardiotoxicity (DIC) in mouse models of acute and chronic toxicity. Methods and results Acute DIC was induced by a single injection of Dox at 15 mg/kg and chronic DIC applied 5 injections of Dox at 4 mg/kg/week. MRA was achieved using eplerenone or cardiomyocyte-specific ablation of the MR gene in transgenic mice and ACEi using enalapril. Drugs were provided with the first dose of Dox and applied until the end of the study. In both model of DIC, Dox induced cardiac atrophy with decreased LV volume, reduced cardiomyocyte cell size, and cardiac dysfunction. In the acute model, neither MRA nor ACEi protected against these manifestations of DIC. In the chronic model, concomitant treatment with eplerenone did not protect against DIC and drastically increased plasma aldosterone levels and cardiac levels of angiotensin II type 1 receptor and of connective tissue growth factor (CTGF), as observed in acute DIC. Enalapril treatment in the chronic model, however, protected against cardiac dysfunction and cardiomyocyte atrophy and was associated with increased activation of the PI3K/AKT/mTOR pathway along with normal levels of CTGF. Conclusion Enalapril and eplerenone disparately impact on cellular signalling in DIC. Eplerenone, on top of Dox treatment was not protective and associated with increased levels of plasma aldosterone and of cardiac CTGF. In contrast, we show that primary prevention with enalapril preserves LV morphology and function in a clinically relevant model of chronic DIC, with increased stimulation of the PI3K/AKT/mTOR axis and normal CTGF levels suggesting potential therapeutic implications.
Practice Makes Perfect: The Rest of the Story in Testicular Cancer as a Model Curable Neoplasm
Authors: Torgrim Tandstad, Christian K. Kollmannsberger, Bruce J. Roth, Claudio Jeldres, Silke Gillessen, Karim Fizazi, Siamak Daneshmand, William T. Lowrance, Nasser H. Hanna, Costantine Albany, Richard Foster, Gabriella Cohn Cedermark, Darren R. Feldman, Thomas Powles, Mark A. Lewis, Peter Scott Grimison, Douglas Bank, Christopher Porter, Peter Albers, Maria De Santis, Sandy Srinivas, George J. Bosl, Craig R. Nichols
Journal: Journal of Clinical Oncology (2017)
Amplification of chromosome 8q22 and metastasis of breast cancers
Authors: Zhigang C. Wang, Yan Li, J. Dirk Iglehart, Andrea Richardson
Journal: Cancer Research (2006)

4297  Introduction. Metastasis is the major cause of the deaths of patients with breast cancer. However, the detailed mechanism and genetic basis for tumor recurrence and metastasis is still not completely understood. Gene amplification is a common mechanism for oncogenic activation causing tumor initiation and progression. The present study is to search for gene amplification associated with metastasis potential of primary breast cancers. Methods. A cohort of 121 unselected primary tumors with at least 24 months clinical follow-up (median 48 months) were examined for gene expression on Affymetrix U133 plus 2.0 arrays. A subset of 39 high-grade cases were further studied for DNA copy number changes on Affymetrix 10K SNP arrays. Supervised analyses compared cases with metastatic recurrence within 24 months, to cases with no recurrence for at least 24 months. Amplification was confirmed by fluorescence in situhybridization (FISH) on fixed tissue sections. Results. SNP array analysis of 39 high-grade tumors revealed frequent copy number gains on 8q, with a minimum 6MB amplified region on 8q22.1-q22.2. The 8q22 amplification was verified by FISH analysis using a BAC probe to this region. examination of gene expression array data highlighted several genes in this region with positive correlation between copy number gain and increased gene expression including, but not limited to, Cyclin E2, Metadherin, and LAPTM4B. By analysis of gene expression array dataset of 121 cases, we find the 8q22 amplification/gene over-expression is present in 10% of unselected breast cancers, and is particularly associated with high tumor grade (11/69 grade III, 16% vs. 1/52 grade I or II, 2%; p= 0.012) and estrogen receptor negativity (10/51 ER-, 20% vs.2/70 ER+, 3%; p= 0.0038). Cases with 8q22 amplification were significantly more likely to have distant metastatic recurrence within 24 mo. than cases without the 8q22 amplification (7/13, 54% vs.8/108, 7%; p= 0.0001). The association with metastasis was also significant among the smaller subset of high-grade tumors (7/12, 58% vs.5/57, 9%; p= 0.0004) and among ER-negative tumors (6/11, 55% vs. 5/40, 13%; p= 0.007). Conclusions: Our results suggest that 8q22 amplification and over-expression is associated with high tumor grade, estrogen receptor negativity and with increased distant metastasis potential. Possible target genes of this amplification include Cyclin E2, Metadherin, LAPTM4B, and others.
In Vitro Microfluidic Models for Neurodegenerative Disorders
Authors: Tatsuya Osaki, Yoojin Shin, Vivek Sivathanu, Marco Campisi, Roger D. Kamm
Journal: Advanced Healthcare Materials (2017)

Abstract Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ‐on‐a‐chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co‐culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative‐disease‐on‐a‐chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ‐on‐chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps.
Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study
Authors: Uwe Platzbecker, Ulrich Germing, Katharina S Götze, Philipp Kiewe, Karin Mayer, Jörg Chromik, Markus Radsak, Thomas Wolff, Xiaosha Zhang, Abderrahmane Laadem, Matthew L Sherman, Kenneth M Attie, Aristoteles Giagounidis
Journal: The Lancet Oncology (2017)
Dose optimization of MK-8628 (OTX015), a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins, in patients (pts) with recurrent glioblastoma (GB).
Authors: Andreas Felix Hottinger, Marc Sanson, Elizabeth Moyal, Jean-Pierre Delord, Rita De Micheli, Keyvan Rezai, Abraham C.F. Leung, Susan Perez, Mohamed Bekradda, Nicolas Lachaux, Francois Marc Lokiec, Olivier L. Chinot
Journal: Journal of Clinical Oncology (2016)

e14123 Background: Bromodomains (BRD) bind to acetylated lysine residues on histone tails and are directly involved in remodeling chromatin and regulating transcription, thus representing a potentially important anticancer target. MK-8628 is a synthetic small molecule targeting BRD2, 3 and 4 of the tandem-BRD-containing family of transcriptional regulators, the BET proteins. It has shown cytotoxic activity in in vitro GB models. We conducted a phase IIa trial with dose optimization to determine the MTD, safety and clinical activity of MK-8628 in pts with a first GB recurrence. Methods: In the first step, a traditional 3+3 dose escalation schema was used. At first recurrence of GB, pts were treated with MK-8628 administered orally at 3 dose levels (DL1: 80 mg QD, DL2: 120 mg QD, DL3: 160 mg QD) with 4-week cycles. PK analyses were performed on day 1 of cycle 1 and residual samples were drawn on day 28. MRI assessment was performed every 2 cycles (RANO). Results: Twelve pts were included between December 2014 and July 2015. M/F: 10/2, median age: 52 years (range: 31-70). Median time from diagnosis is 11 months (range 5-24), median KPS: 90%. Six pts were treated at DL1, 4 at DL2, and 2 at DL3. Pts received a median of 2 cycles of MK-8628 (range 1-4). Three pts had dose-limiting toxicity: 1 at DL1 (grade [G] 3 thrombocytopenia > 7 days) and 2 at DL3 (G3 thrombocytopenia > 7 days without bleeding; G3 hyperbilirubinemia lasting 2 days). Other drug-related toxicities included G3 thrombocytopenia (3 pts), G1-2 diarrhea (4 pts), G2 myalgia (1 pt), and G1 INR increase (1 pt). PK analysis in pts treated at the MTD (DL2) showed a mean Cmax of 1813±270 nM with a mean AUC(0-24) of 7984±443 μg/L*h and T1/2 of 3.9±0.4 h. Best response was stable disease in 1 pt. All pts progressed, with a median PFS of 2 months (range,1-4). Conclusions: Administration of MK-8628 is safe and well tolerated in pts with recurrent GB previously exposed to alkylating agents and radiation therapy. The MTD was established at 120 mg MK-8628 QD with PK indicating that MK-8628 had reached biologically active levels. Given the lack of detectable clinical activity of MK-8628 in this population, the trial was closed. Clinical trial information: NCT02296476.
Pain control in thoracic oncology
Authors: Christine Peeters-Asdourian, Gilbert Massard, Paragi H. Rana, Paul Van Houtte, Andrew P. White, Bogdan Grigoriu, Dominique Lossignol, Mohammed Almalki, Jean Alexiou, Jean-Luc Engelholm, Jean-Paul Sculier
Journal: European Respiratory Journal (2017)

This review of pain management in lung cancer is based on the presentation of four cases of thoracic oncology patients with pain at various stages of their disease. The approach will be multidisciplinary, involving a thoracic oncologist, radiologist, thoracic and orthopaedic spine surgeon, radiation therapist, pain medicine specialist, and palliative care specialist. This multispecialty approach to the management of different painful presentations in thoracic oncology will demonstrate the complexity of each case and the improved patient outcomes which result from the involvement of different disciplines working in concert. In the USA, Europe and other countries, palliative care specialists often become rapidly involved in the management of these patients, coordinating social care and providing psychological support. Thoracic and orthopaedic spine subspecialists provide surgical methods to control tumour invasion, and improve quality of life and preservation of function in settings of even diffuse metastatic disease. Similarly, thoracic oncology and radiation therapists utilise both therapeutic and palliative chemotherapeutic and radiation therapy regimens to prolong and improve quality of life. The pain medicine specialist can, in addition to medication management, offer a variety of interventional approaches including unique drug delivery systems such as epidural analgesia, regional anaesthesia techniques, and intrathecal pumps, as well as neuromodulation techniques and neurolytic or neuroablative procedures. In the USA, these specialists complete an additional fellowship year in pain medicine following the completion of an anaesthesiology, physical medicine and rehabilitation, neurology or psychiatry residency. These programmes are accredited by the Accreditation Council for Graduate Medical Education, or ACGME ( www.acgme.org ).
Drug resistance in malaria, tuberculosis, and HIV in South East Asia: biology, programme, and policy considerations
Authors: Samiran Panda, Soumya Swaminathan, Khurshid A Hyder, Eva-Maria Christophel, Razia N Pendse, Achuthan N Sreenivas, Setiwan J Laksono, Rahul Srivastava, Gopinath B Nair, Tjandra Y Aditama, Pratap Singhasivanon, Arun B Thapa, Swarup K Sarkar
Journal: BMJ (2017)

Malaria, tuberculosis, and HIV present unique challenges in the control of antimicrobial resistance, and require targeted policies, say Samiran Panda and colleagues
5‐/12‐Lipoxygenase‐linked cascade contributes to the <scp>IL</scp>‐33‐induced synthesis of <scp>IL</scp>‐13 in mast cells, thus promoting asthma development
Authors: MyungJa Ro, A‐Jin Lee, Jae‐Hong Kim
Journal: Allergy (2017)

Abstract Background As asthma progresses, the levels of IL ‐33 in serum are markedly increased and contribute to asthmatic development and exacerbation. Mast cells, one of the principal effector cells in the pathogenesis of asthma, express high levels of the IL ‐33 receptor ST 2 and have been shown to be activated by IL ‐33. Thus, IL ‐33 stimulates mast cells to produce Th2‐type cytokines such as IL ‐13, thus contributing to asthmatic development. However, the signaling mechanism for IL ‐33‐induced synthesis of Th2 cytokines, particularly IL ‐13, has not been fully elucidated in mast cells. Methods The role of 5‐ or 12‐ LO in the IL ‐33‐induced synthesis of IL ‐13 was investigated using knockdown or pharmacological inhibitors in bone marrow‐derived mast cells ( BMMC s) and animal model. Results Blockade of 5‐ or 12‐ LO significantly suppressed IL ‐33‐induced synthesis of IL ‐13 in BMMC s. The subsequent action of 5‐ and 12‐ LO metabolites through their specific receptor, BLT 2, was also critical for IL ‐33‐induced synthesis of IL ‐13. We also demonstrated that the MyD88‐p38 kinase cascade lies upstream of 5‐/12‐ LO and that NF ‐κB lies downstream of 5‐/12‐ LO to mediate the IL ‐33‐induced synthesis of IL ‐13 in mast cells. Consistent with these findings, we observed that in an IL ‐33‐administered asthmatic airway inflammation model, IL ‐13 levels were markedly increased in bronchoalveolar lavage fluid, but its levels were markedly suppressed by treatment with inhibitors of 5‐ LO , 12‐ LO or BLT 2, further suggesting roles of 5‐/12‐ LO in IL ‐33‐induced IL ‐13 production. Conclusion Our results suggest that “MyD88‐5‐/12‐ LO ‐ BLT 2‐ NF ‐κB” cascade significantly contributes to the IL ‐33‐induced synthesis of IL ‐13 in mast cells, thus potentially contributing to asthmatic development and exacerbation.
Discovery of WP1066, a novel Stat3/c-myc inhibitor with potent antitumor activity against human melanoma in vitro and in vivo
Authors: Ling Y. Kong, Waldemar Priebe, Moshe Talpaz, Nicholas J. Donato
Journal: Cancer Research (2005)

5894  Melanoma is a potentially lethal cancer that responses poorly to radiotherapy and other commonly used chemotherapeutic agents. Although much attention has been focused on melanoma immunotherapy, few effective therapeutic agents for melanoma exist, especially those useful for treatment of metastatic disease. A novel low MW agent, WP1066, was synthesized that effectively blocked Stat3 activation by cytokines and induced c-myc degradation in multiple tumor cell types. Since melanoma cells express constitutively activated Stat proteins and unregulated c-myc expression the antiprolifeative effects of WP1066 against the human A375 metastatic melanoma cell line were examined in vitro and in A375 xenografts in nude mice. WP1066 induced growth inhibition and apoptosis of A375 cells with an IC50 ∼1.5 μM. WP1066 suppressed Stat3 tyrosine phosphorylation without effecting Stat3 protein levels at similar concentrations (
生2光子顕微鏡法により明らかにされた神経電極への急性小膠細胞接着を減弱するNeuroadhesive L1コーティング【Powered by NICT】
Authors: R Eles James, L Vazquez Alberto, R Snyder Noah, Lagenaur Carl, C Murphy Matthew, D Y Kozai Takashi, Cui X. Tracy
Journal: Biomaterials (2017)