tbuckley/cabot-search huggingface dataset:
Sorafenib (SOR) in advanced non-small cell lung cancer (NSCLC): A phase II study of patient progress after several lines of treatment.
Authors: Sergio Vazquez-Estevez, Silvia Varela, Begoña Campos, Elena Álvarez, Guillermo Quintero, Jose Ramón Mel
Journal: Journal of Clinical Oncology (2012)

e18070 Background: Sorafenib is a potent inhibitor of c-Raf, b-Raf VEGFR-1/2/3 and PDGFR-β. In NSCLC, proliferative signaling through the Ras/Raf/MEK/ERK pathway is often activated from K-ras mutations. Their efficacy as monotherapy to treat advanced NSCLC has been demonstrated in several trials. In them, SOR improved the rate of disease stabilization in patients who had previously been treated with chemotherapy. Our objective is to confirm the clinical and safety results in the daily clinical activity. Methods: Between October 2008 and December 2011, patients with metastatic NSCLC and measurable disease, ECOG 0-1 were treated after having received two or more prior chemotherapy regimens for metastatic disease. SOR was administered at a starting dose of 400 mg bid continuously in 28-day cycles.The primary end points were Overall Survival (OS) and Progression Free Survival (PFS). Survival medians were estimated by the Kaplan-Meier method and comparisons between subgroups were assessed by the log-rank test. Results: Fifteen Caucasian patients were enrolled, with a mean age at diagnosis of 61 (SD = 13.5) years and most of them were males (n = 10, 67%). The predominant histologic type was adenocarcinoma (n = 9, 60%). Twelve (80%) patients were in stage IV at diagnosis. The predominant metastatic sites were lung (n = 8, 53%), lymph nodes, (n = 5, 33%), pleura (n =3, 20%) and bone (n=3, 20%).Patients received a median of 3 (range: 2 to 4) treatment lines prior to the SOR regimen, with a median duration of 80.5 (range: 9 to 247) days.Median OS and median PFS were 98 and 84 days, respectively. No significant differences in survival were found according to gender, smoking, histologic type, stage, metastatic site, ECOG nor presence of biomarkers.The toxicity profile was mild. Adverse events CTC G3/4 were dyspnea (n = 4, 27%), skin toxicity (n = 1, 7%) and vomiting (n = 1, 7%). Conclusions: In this study, patients with metastatic NSCLC receiving SOR had a median PFS of 3 months. The safety profile is acceptable, reversible and manageable without unexpected adverse events to this therapy. While still waiting for the results of ongoing trials, we can say thatSOR is safe, so far, in patients who have been widely treated.
Influence of Animal Passage on a Line of Tissue-Culture Cells
Authors: Katherine K. Sanford, Ruth M. Merwin, Gwendolyn L. Hobbs, Wilton R. Earle
Journal: JNCI Journal of the National Cancer Institute (1959)

This study confirms and further elucidates a previous observation that mouse passage increases the tumor-producing capacity of a low tumor-producing line of mouse tissue-culture cells. The change in the cells was maintained during serial passage of the cells in vivo and persisted for several months after return to culture. The increased tumor-producing capacity ultimately subsided, partially in one strain and almost completely in another after 8 months in vitro. The cells before and after mouse passage did not differ significantly with respect to their morphology in vitro or in vivo, their failure to elicit an early vascular response in the host, their antigenicity for mice of the strain of origin (C3H), or their low rate of anaerobic glycolysis in vitro. Chromosomal numbers were slightly altered. The cells after mouse passage did seem to differ in their increased resistance to the immunity they induced in the host. This effect was produced not only in cells cultured on stock medium but also in cells cultured on a different medium known to enhance the transplantability of the cells. Two cell strains were isolated after mouse passage that exhibited the morphologic, metabolic, and physiologic characteristics of another line of cells carried independently from the low tumor-producing line but originated in vitro from the same cell. The observations suggest that this cell type was present in culture before mouse passage and was selectively concentrated during mouse passage. Several possibilities to explain the increased tumor-producing capacity of the cell population after mouse passage are discussed.
Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice
Authors: Laura Lukjanenko, M Juliane Jung, Nagabhooshan Hegde, Claire Perruisseau-Carrier, Eugenia Migliavacca, Michelle Rozo, Sonia Karaz, Guillaume Jacot, Manuel Schmidt, Liangji Li, Sylviane Metairon, Frederic Raymond, Umji Lee, Federico Sizzano, David H Wilson, Nicolas A Dumont, Alessio Palini, Reinhard Fässler, Pascal Steiner, Patrick Descombes, Michael A Rudnicki, Chen-Ming Fan, Julia von Maltzahn, Jerome N Feige, C Florian Bentzinger
Journal: Nature Medicine (2016)
The Current State of Peritoneal Dialysis
Authors: Rajnish Mehrotra, Olivier Devuyst, Simon J. Davies, David W. Johnson
Journal: Journal of the American Society of Nephrology (2016)

Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.
Similar Outcome with Early Reduced Intensity Conditioning (RIC) Allogeneic Transplant to Autologous-Non-Myeloablative Allogeneic (Auto-Allo) Transplant in Patients with Multiple Myeloma.
Authors: Sahebi Firoozeh, Jeffery R. Schriber, Ricardo Spielberger, Ji-Lian Cai, Neil Martin Kogut, Peter M. Falk, Pablo Miguel Parker, Amrita Krishnan, Leslie Popplewell, Chatchada Karanes, Dajun Qian, Stephen J. Forman, George Somlo
Journal: Blood (2007)
d-fenfluramine-induced prolactin responses in mania: evidence for serotonergic subsensitivity
Authors: J H Thakore, V O'Keane, T G Dinan
Journal: American Journal of Psychiatry (1996)

The authors examined serotonergic-mediated prolactin release in bipolar mania, using d-fenfluramine as a probe.Hospitalized patients with bipolar disorder, currently manic, were matched for age and sex to healthy comparison subjects. Each group consisted of nine subjects (seven men and two women). After an overnight fast, all subjects had an intravenous cannula inserted into a forearm at 8:30 a.m., and baseline blood samples for determination of prolactin and cortisol levels were drawn. d-Fenfluramine (30 mg p.o.) was then administered; plasma prolactin levels were measured 15 minutes before d-fenfluramine was given, immediately before, and 60, 120, 180, 240, and 300 minutes afterward.Baseline serum cortisol levels were higher in the bipolar manic subjects than in the comparison subjects, although baseline prolactin levels were similar in the two groups. The plasma prolactin responses to d-fenfluramine of the bipolar manic subjects were significantly lower than those of the comparison subjects.Bipolar mania appears to be associated with a state of decreased serotonergic responsivity similar to that found in unipolar depression.
Association Between Socioeconomic Status and Mortality, Cardiovascular Disease, and Cancer in Patients With Type 2 Diabetes
Authors: Araz Rawshani, Ann-Marie Svensson, Björn Zethelius, Björn Eliasson, Annika Rosengren, Soffia Gudbjörnsdottir
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> The association between socioeconomic status and survival based on all-cause, cardiovascular (CV), diabetes-related, and cancer mortality in type 2 diabetes has not been examined in a setting of persons with equitable access to health care with adjustment for important confounders. <h3>Objective</h3> To determine whether income, educational level, marital status, and country of birth are independently associated with all-cause, CV, diabetes-related, and cancer mortality in persons with type 2 diabetes. <h3>Design, Setting, and Participants</h3> A study including all 217 364 individuals younger than 70 years with type 2 diabetes in the Sweden National Diabetes Register (January 1, 2003, to December 31, 2010) who were monitored through December 31, 2012, was conducted. A Cox proportional hazards regression model with up to 17 covariates was used for analysis. <h3>Main Outcomes and Measures</h3> All-cause, CV, diabetes-related, and cancer mortality. <h3>Results</h3> Of the 217 364 persons included in the study, mean (SD) age was 58.3 (9.3) years and 130 839 of the population (60.2%) was male. There were a total of 19 105 all-cause deaths with 11 423 (59.8%), 6984 (36.6%), and 6438 (33.7%) CV, diabetes-related, or cancer deaths, respectively. Compared with being single, hazard ratios (HRs) for married individuals, determined using fully adjusted models, for all-cause, CV, and diabetes-related mortality were 0.73 (95% CI, 0.70-0.77), 0.67 (95% CI, 0.63-0.71), and 0.62 (95% CI, 0.57-0.67), respectively. Marital status was not associated with overall cancer mortality, but married men had a 33% lower risk of prostate cancer mortality compared with single men, with an HR of 0.67 (95% CI, 0.50-0.90). Comparison of HRs for the lowest vs highest income quintiles for all-cause, CV, diabetes-related, and cancer mortality were 1.71 (95% CI, 1.60-1.83), 1.87 (95% CI, 1.72-2.05), 1.80 (95% CI, 1.61-2.01), and 1.28 (95% CI, 1.14-1.44), respectively. Compared with native Swedes, HRs for all-cause, CV, diabetes-related, and cancer mortality for non-Western immigrants were 0.55 (95% CI, 0.48-0.63), 0.46 (95% CI, 0.38-0.56), 0.38 (95% CI, 0.29-0.49), and 0.72 (95% CI, 0.58-0.88), respectively, and these HRs were virtually unaffected by covariate adjustment. Hazard ratios for those with a college/university degree compared with 9 years or less of education were 0.85 (95% CI, 0.80-0.90), 0.84 (95% CI, 0.78-0.91), and 0.84 (95% CI, 0.76-0.93) for all-cause, CV, and cancer mortality, respectively. <h3>Conclusions and Relevance</h3> Independent of risk factors, access to health care, and use of health care, socioeconomic status is a powerful predictor of all-cause and CV mortality but was not as strong as a predictor of death from cancer.
Effect of Cytotoxic Agents on the Maturing Granulocytic and Erythroid Cells of Rats
Authors: T. B. Constable, N. M. Blackett
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Effect of Cytotoxic Agents on the Maturing Granulocytic and Erythroid Cells of Rats Get access T. B. Constable, T. B. Constable Biophysics Division, Institute of Cancer Research, Sutton, Surrey, England Search for other works by this author on: Oxford Academic PubMed Google Scholar N. M. Blackett N. M. Blackett Biophysics Division, Institute of Cancer Research, Sutton, Surrey, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 515–521, https://doi.org/10.1093/jnci/50.2.515 Published: 01 February 1973 Article history Received: 03 April 1972 Revision received: 09 July 1972 Accepted: 02 October 1972 Published: 01 February 1973
Radio: Stories from the Wards
Authors: Iain McClure
Journal: BMJ (2003)

Medicine has always provided a rich seam for fiction, ranging from Chekhov's sublime short stories, to the ridiculous romances of Mills and Boon. To the public what happens in hospitals is a permanent source of intrigue and fantasy, serviced by a huge production of medical fiction in all possible formats. The ancient human need to hear or watch a story unfold remains undiminished and medicine is a compelling subject. But how often do we get an opportunity to hear, truthfully, from healthcare workers themselves, what really happens?

Stories from the Wards tells six extraordinary stories of NHS workers, as they talk about their most unforgettable moments during the course of their working lives. Do healthcare employees share this human need to tell their stories and, if so, what, in turn, does this tell us?

The stories cover a broad range of medical scenarios, but all contain a surprising, even miraculous denouement, which delivers a valuable message. Julie, a matron at Birmingham City Hospital, talks about a young man whom she nursed in intensive care, following a hit and run road incident. Left in a coma, he was not expected to recover. His mother suggested a gathering of his friends (from his snooker club) around his hospital bed, as a way of saying goodbye. The consultant denied the request, but Julie persisted in asking him to reconsider and, in view of the miraculous outcome, learnt a valuable lesson: “that the rules are there to be broken... and if we never question and never challenge, then how do we know what the possible outcomes could have been?”

The other stories are equally memorable, though less dramatic. One stands out in particular, for different reasons. Stephen, a theatre nurse manager, describes his first experience, 20 years earlier, of taking part in an organ harvesting procedure on a brain-dead patient. For Stephen, the shock of seeing the normal process of an operation going in reverse—leading, as he put it, to the deliberate “killing” of the patient—left him with a swarm of unresolved feelings. This is an experience with which many will be able to empathise.

This delicate, confessional series is an admirable example of why we need to change medical culture, to help carers consider themselves, as well as their patients. For example, medical humanities is an inchoate, but growing academic specialty (BMJ 2003;327: s65-6), which aims to access the often profound experiences that healthcare workers carry around with them. Concepts such as creative writing groups for staff may seem like self indulgent frippery in our hard-pressed health services. But quiet periods of reflection about what we do may add to, not diminish, the care and the cure.
Case 52-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Samuel L. Moschella, Martin C. Mihm
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 57-year-old man was admitted to the hospital because of optic neuritis.Four years previously cutaneous plaques had appeared, and a diagnosis of mycosis fungoides was made. Three years before admission a course of methotrexate was given by vein over an interval of three months, without appreciable benefit. Six months later total-body irradiation was administered, with improvement. Six months before entry optic neuritis developed in the left eye; prednisone was given, but no change occurred. Two months later a plaque appeared on the tongue and increased in size. Two weeks before entry the white-cell count was 18,100, . . .
Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack
Authors: Ralph L. Sacco, Robert Adams, Greg Albers, Mark J. Alberts, Oscar Benavente, Karen Furie, Larry B. Goldstein, Philip Gorelick, Jonathan Halperin, Robert Harbaugh, S. Claiborne Johnston, Irene Katzan, Margaret Kelly-Hayes, Edgar J. Kenton, Michael Marks, Lee H. Schwamm, Thomas Tomsick
Journal: Circulation (2006)

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.
Viral Encephalitis
Authors: Sarah Ringold, Cassio Lynm, Richard M. Glass
Journal: JAMA (2005)

Viral EncephalitisV iral encephalitis is the inflammation (damage to cells) of brain tissue that may result from infection with any of a number of viruses.Viruses are extremely small infectious agents that are different from bacteria, cannot live outside of cells, and cannot be treated with antibiotic drugs.Herpes simplex virus type 1 is the most common cause of encephalitis in the United States.Other causative viruses include arboviruses (viruses including the West Nile virus that are transmitted through the bites of mosquitoes, ticks, and sandflies), other herpes viruses, and the rabies virus.In severe cases, encephalitis may result in persistent neurological damage or death.The July 27, 2005, issue of JAMA includes an article that describes rabies encephalitis in the recipients of organs transplanted from an infected donor.
Election 2016: Voting on Variants
Authors: Raymond J. Cho, Eric A. Collisson
Journal: Cancer Discovery (2016)

Genome sequencing studies increasingly identify variants of unknown significance in provocative genes. Kim and colleagues present a system with which to functionally annotate such variants in a high-throughput, biologically relevant series of assays. Cancer Discov; 6(7); 694-6. ©2016 AACRSee related article by Kim et al., p. 714.
Phase Ib dose-escalation trial evaluating c-MET inhibitor ARQ 197 administered in combination with gemcitabine to patients (pts) with advanced solid tumors.
Authors: L. H. Camacho, J. C. Bendell, L. John-Reid, L. T. Campos, S. F. Jones, J. Kazakin, R. Savage, B. E. Schwartz, G. Abbadessa, M. N. Saleh
Journal: Journal of Clinical Oncology (2010)

e13008 Background: ARQ 197 is a selective, non-ATP competitive inhibitor of c-MET, the exclusive receptor tyrosine kinase for hepatocyte growth factor. Preclinical data suggest combinability of ARQ 197 with gemcitabine. This study aims to evaluate the safety, pharmacokinetics (PK), biomarkers, and preliminary efficacy of the combination in pts with advanced solid tumors. Methods: Multicenter, phase Ib 3+3 dose escalation trial. Oral ARQ 197 is administered at doses of 120-360mg bid across different schedules (continuous vs. continuous with 1 week [wk] break every 2 or 3 wks) in combination with fixed gemcitabine dosing and frequency (1000mg/m2/weekly 3 every 4 wks). Results: 25 metastatic pts (F:M = 13:12; ECOG 0:1 = 12:13; mean age 61, range 44-75 yrs) with mean number of prior systemic treatments = 3.7 (1–9) were treated. No dose-limiting toxicities were observed. Adverse events (AEs) considered at least possibly drug-related were reported in 14 (56%) pts. Most commonly observed (>10%) AEs include neutropenia (10; 40%), thrombocytopenia (6; 24%), anemia (5; 20%), fatigue (4; 16%), leukopenia, nausea, and anorexia (2; 10%). One pt experienced a drug-related serious AE (anemia grade 4). One nonrelated death secondary to hemorrhage occurred on study. Of 16 evaluable pts, 4 pts obtained confirmed partial response by RECIST (ovarian, breast, uterine, NSCLC) and tumor marker decrease (38-83% reduction); 9 pts achieved stable disease (mean duration 15.5, range 8–28+ wks); 4 of these 9 pts had prior progression on gemcitabine (cholangio, ovarian, pancreatic), of whom 3 have now tumor marker decrease (33-80% reduction). PK analysis (patients dosed at 360 mg bid) show a day 1 mean Cmax of 1176 ± 882 ng/mL and AUC(0-12) of 9146 ± 8752 hr*ng/mL. Additional data will be available for presentation. Conclusions: To date, orally administered ARQ 197 in combination with gemcitabine appears well tolerated and without clinically apparent drug-drug interaction or significant exacerbation of known gemcitabine toxicity. Further efficacy is being explored in expanded cohorts for specific tumor types. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ArQule ArQule
Presumptive Type 1 Diabetes With Comorbidities and Rapid Progression Despite Numerous Insulin-Positive Islets
Authors: Laura M. Jacobsen, Mark A. Atkinson, Martha Campbell-Thompson, Desmond A. Schatz
Journal: Diabetes Care (2016)

The subject was a 26-year-old African American female diagnosed with type 1 diabetes at the age of 11 years, treated with insulin injections, who died because of an anoxic brain injury likely secondary to diabetic ketoacidosis. The patient was found with agonal respirations and had acidosis along with severe hyperglycemia on arrival to the emergency department. In the 15 years since being diagnosed with diabetes, she had developed significant signs of cardiovascular disease including …
PD5-3-8: Development of a non-small cell lung cancer (NSCLC) survivorship program: baseline clinical characteristics and quality of life (QOL)
Authors: Amy E. Logue, Christina T. Gawiak, Nancy Houlihan, Mary McCabe, Valerie W. Rusch, Mark Kris, Bernard J. Park
Journal: Journal of Thoracic Oncology (2007)
Pulsed‐Electromagnetic‐Field‐Assisted Reduced Graphene Oxide Substrates for Multidifferentiation of Human Mesenchymal Stem Cells
Authors: Ki‐Taek Lim, Hoon Seonwoo, Kyung Soon Choi, Hexiu Jin, Kyung‐Je Jang, Jangho Kim, Jin‐Woo Kim, Soo Young Kim, Pill‐Hoon Choung, Jong Hoon Chung
Journal: Advanced Healthcare Materials (2016)

Electromagnetic fields (EMFs) can modulate cell proliferation, DNA replication, wound healing, cytokine expression, and the differentiation of mesenchymal stem cells (MSCs). Graphene, a 2D crystal of sp(2) -hybridized carbon atoms, has entered the spotlight in cell and tissue engineering research. However, a combination of graphene and EMFs has never been applied in tissue engineering. This study combines reduced graphene oxide (RGO) and pulsed EMFs (PEMFs) on the osteogenesis and neurogenesis of MSCs. First, the chemical properties of RGO are measured. After evaluation, the RGO is adsorbed onto glass, and its morphological and electrical properties are investigated. Next, an in vitro study is conducted using human alveolar bone marrow stem cells (hABMSCs). Their cell viability, cell adhesion, and extracellular matrix (ECM) formation are increased by RGO and PEMFs. The combination of RGO and PEMFs enhances osteogenic differentiation. Together, RGO and PEMFs enhance the neurogenic and adipogenic differentiation of hABMSCs. Moreover, in a DNA microarray analysis, the combination of RGO and PEMFs synergically increases ECM formation, membrane proteins, and metabolism. The combination of RGO and PEMFs is expected to be an efficient platform for stem cell and tissue engineering.