tbuckley/cabot-search huggingface dataset:
Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)
Authors: R. Baz, M. A. Hussein, D. Sullivan, J. Raychaudhuri, L. Ochoa, K. Kosakowski, L. Nardelli, W. S. Dalton, M. Alsina
Journal: Journal of Clinical Oncology (2009)

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m&gt;3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]
PWE-115 Acute decompensation of cirrhosis requiring hospitalisation is not reversible and defines future organ specific decompensation
Authors: R Spinella, R Sawhney, P Holland-Fisher, N Shah, R Jalan, R Mookerjee
Journal: Gut (2015)

<h3>Introduction</h3> Following acutely decompensated cirrhosis and associated organ dysfunction, despite recovery, &gt;30% patients are readmitted to hospital and have increased overall mortality. What clinical factors predict likelihood of readmission and whether certain precipitants predispose to re-admission with the same events remain unanswered questions. This study followed patients with acute cirrhosis decompensation admitted to Royal Free London sequentially over 42 months to address these questions. <h3>Method</h3> 238 patients admitted to RFH following acutely decompensated cirrhosis (ascites, bacterial infection, haemorrhage, jaundice, alcoholic hepatitis, and/or hepatic encephalopathy (HE)) were followed until death, transplantation or discharge. In discharged patients, observational data was collated to capture readmissions, precipitating events and outcomes. Simple logistic and Cox proportional hazards regression analyses were applied to the data set. <h3>Results</h3> 238 patients were admitted with acute decompensation; 36 patients died and 9 were transplanted during their index admission. 195 patients were followed post discharge; 84 (44%) were re-admitted (median time to first re-admission 90 days) and in 38 patients, a second re-admission within 6 months. 11% patients had &gt;3 re-admissions. Index presentation with HE in 22% patients predicted re-admission with HE with odds ratio (OR) 12.8 (2.4–69, P = 0.003). The predictive utility of HE in determining re-admission with HE was 0.83 (p &lt; 0.05) by ROC analysis. By comparison, index presentation with GI haemorrhage (19%) had an OR 7.4; (1.7–32, P = 0.007) for re-admission with further haemorrhage. Of interest, patients discharged with recovery from alcoholic hepatitis (31%) re-presented with new infection [OR 2.78 (1–7.8, P = 0.05)]. 26% of patients had acute kidney injury (AKI) at index presentation which did not predict re-presentation with AKI [OR: 2.21 (0.5–9.66; P = 0.3) and this was also the case for re-admission with infection [OR 1.14]. In this cohort, MELD-Na on index admission <i>was not</i>predictive of re-admission to hospital. <h3>Conclusion</h3> This data re-affirms the high mortality post acute decompensation of cirrhosis whilst also demonstrating considerable early hospital readmission. A novel relationship between index precipitating event and recurrence of this event on re-admission is shown. This suggests certain complications of cirrhosis may be genetically or epigenetically determined. Strategies for primary and secondary prophylaxis should target these predisposing factors and points to important area of future research. <h3>Disclosure of interest</h3> None Declared.
miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer’s disease and other types of dementia – an exploratory study
Authors: Sofie Sølvsten Sørensen, Ann-Britt Nygaard, Thomas Christensen
Journal: Translational Neurodegeneration (2016)

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression. Measurements of miRNAs in cerebrospinal fluid (CSF) and blood have just started gaining attention as a novel diagnostic tool for various neurological conditions. The purpose of this exploratory investigation was to analyze the expression of miRNAs in CSF and blood of patients with Alzheimer's disease (AD) and other neurodegenerative disorders in order to identify potential miRNA biomarker candidates able to separate AD from other types of dementia. CSF was collected by lumbar puncture performed on 10 patients diagnosed with AD and 10 patients diagnosed with either vascular dementia, frontotemporal dementia or dementia with Lewy bodies. Blood samples were taken immediately after. Total RNA was extracted from cell free fractions of CSF and plasma, and a screening for 372 known miRNA sequences was carried out by real time quantitative polymerase chain reactions (miRCURY LNA™ Universal RT miRNA PCR, Polyadenylation and cDNA synthesis kit, Exiqon). Fifty-two miRNAs were detected in CSF in at least nine out of ten patients in both groups. Among these, two miRNAs (let-7i-5p and miR-15a-5p) were found significantly up-regulated and one miRNA (miR-29c-3p) was found significantly down-regulated in patients with AD compared to controls. One hundred and sixty-eight miRNAs were frequently detected in the blood, among which miR-590-5p and miR-142-5p were significantly up-regulated and miR-194-5p was significantly down-regulated in AD patients compared to controls. Detection of miRNA expression profiles in blood and in particular CSF of patients diagnosed with different types of dementia is feasible and it seems that several expressional differences between AD and other dementia types do exist when measured in a clinically relevant setup. In this explorative pilot study, the deregulated miRNAs in CSF of AD patients may be associated with relevant target genes related to AD pathology, including APP and BACE1, which suggests that miRNAs are interesting candidates for AD biomarkers in the future.
Phase I/II Trial Of Everolimus, Bortezomib and Rituximab In Relapsed Or Relapsed/Refractory Waldenstrom's Macroglobulinemia
Authors: Irene M. Ghobrial, Erica N Boswell, Stacey Chuma, Ranjit Banwait, Courtney Hanlon, Houry Leblebjian, Diane Warren, Patrick Mostyn, Farzana Masood, Paul G. Richardson, Steven Peter Treon, Jeffrey Matous
Journal: Blood (2013)
Margaret McCartney: Glasgow’s lost hospital beds
Authors: Margaret McCartney
Journal: BMJ (2016)

I’ve been to several meetings about the big new hospital being built in my home town. It was to be called the Southern Glasgow University NHS Trust. But then Liz visited, and it was renamed the Queen Elizabeth University Hospital. Colloquially, it’s still being called the Death Star.

It’s enormous, dwarfing its hospital contemporaries and glowing bright at all hours, with a helipad on the roof. It has separate bedrooms for all patients.

I raised basic questions at the meetings.

Where was the evidence that single rooms were safe? Not answered.

How many beds would be lost as a result of the shift from the old Western Infirmary to the …
Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State
Authors: Matthew P. Patricelli, Matthew R. Janes, Lian-Sheng Li, Rasmus Hansen, Ulf Peters, Linda V. Kessler, Yuching Chen, Jeff M. Kucharski, Jun Feng, Tess Ely, Jeffrey H. Chen, Sarah J. Firdaus, Anjali Babbar, Pingda Ren, Yi Liu
Journal: Cancer Discovery (2016)

KRAS gain-of-function mutations occur in approximately 30% of all human cancers. Despite more than 30 years of KRAS-focused research and development efforts, no targeted therapy has been discovered for cancers with KRAS mutations. Here, we describe ARS-853, a selective, covalent inhibitor of KRAS(G12C) that inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation. Based on the rates of engagement and inhibition observed for ARS-853, along with a mutant-specific mass spectrometry-based assay for assessing KRAS activation status, we show that the nucleotide state of KRAS(G12C) is in a state of dynamic flux that can be modulated by upstream signaling factors. These studies provide convincing evidence that the KRAS(G12C) mutation generates a "hyperexcitable" rather than a "statically active" state and that targeting the inactive, GDP-bound form is a promising approach for generating novel anti-RAS therapeutics.A cell-active, mutant-specific, covalent inhibitor of KRAS(G12C) is described that targets the GDP-bound, inactive state and prevents subsequent activation. Using this novel compound, we demonstrate that KRAS(G12C) oncoprotein rapidly cycles bound nucleotide and responds to upstream signaling inputs to maintain a highly active state.
CCR5 gene polymorphism in patients with cutaneous melanoma: Impact on survival following immunotherapy
Authors: J. C. Becker, S. Ugurel, M. Zapatka, H. L. Kaufmann, D. Schrama
Journal: Journal of Clinical Oncology (2007)

21071 Background: Chemokines are supposed to influence both tumor progression and anti-tumoral immune responses. In this regard, a 32-bp-deletion polymorphism in the chemokine receptor 5 gene (CCR5Δ32) resulting in a non-functional receptor protein allows to study the potential impact of the CCR5 system on the clinical course and treatment outcome of malignant diseases. Methods: CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanoma patients with known disease history and long-term clinical follow-up. Genotypes were correlated with patient survival in consideration of different therapeutic modalities. Results: Out of 782 patients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Δ32. Disease-specific survival starting from primary diagnosis was not influenced by CCR5 status. Equally, no impact of the CCR5 status could be detected on treatment outcomes of stage III patients. In 139 stage IV patients treated with immunotherapeutics, however, CCR5Δ32 was associated with a diminished survival compared to patients not carrying the Δ32 allele (p=0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in this patient group (p=0.0084), followed by gender (p=0.017), and type of primary (p=0.029). Vice versa, stage IV patients without immunotherapy revealed a trend towards a favorable survival when harboring CCR5?32 (p=0.12). Conclusions: The disadvantage of CCR5Δ32-bearing stage IV melanoma patients with respect to outcome of immunotherapy indicates a strong impact of the CCR5 mediator system on anti-tumoral immune responses, and should be taken into account when choosing therapeutic modalities for these patients. No significant financial relationships to disclose.
A functional SNP in MRPL43 modulates lung cancer susceptibility and survival through alternative splicing of its isoforms
Authors: Andrew Mcclary, Kara Calhoun, Jessica Roberts, Ana Robles, Elise Eowman, Majda Haznadar, Dominic Esposito, Cassidy Alexandre, Mohammed Khan, Rama Modali, Hirokazu Okayama, Kouya Shiraishi, Yun Yokota, Takashi Kohno, Brid Ryan
Journal: Journal of Thoracic Oncology (2016)
The level of blast CD33 expression positively impacts the effect of gemtuzumab ozogamicin in patients with acute myeloid leukemia
Authors: Guillaume Olombel, Estelle Guerin, Julien Guy, Jean-Yves Perrot, Florent Dumezy, Adrienne de Labarthe, Jean-Noël Bastie, Ollivier Legrand, Emmanuel Raffoux, Adriana Plesa, Orianne Wagner-Ballon, Edouard Cornet, Véronique Salaun, Claude Preudhomme, Xavier Thomas, Cécile Pautas, Sylvain Chantepie, Pascal Turlure, Sylvie Castaigne, Hervé Dombret, Jean Feuillard
Journal: Blood (2016)
Epidermal growth factor receptor protein expression and gene amplification in Caucasian patients with malignant pleural mesothelioma (MPM)
Authors: Veerle Surmont, Marleen Praet, Isabelle Rottiers, Elisabeth Beerens, Bart Matthys, Patrick Pauwels, Jan Van Meerbeeck
Journal: Journal of Thoracic Oncology (2009)
Allergen-Specific CD4+ T Cells in Human Asthma Have an Increased Capacity to Respond to Innate Type 2 Signals
Authors: Morris F. Ling, Sabina A. Islam, Daniel L. Hamilos, Josalyn L. Cho, Jason W. Griffith, R. Scott Harris, William W. Kwok, James J. Moon, Benjamin D. Medoff, Andrew D. Luster
Journal: Journal of Allergy and Clinical Immunology (2016)
Cetuximab (C) and gemcitabine (G) in elderly or adult PS2 advanced non small-cell lung cancer (NSCLC) patients (pts): The CALC1 randomised phase II trials
Authors: C. Gridelli, M. Mencoboni, F. Carrozza, M. G. Viganò, V. Gebbia, C. Verusio, P. Maione, C. Gallo, F. Perrone, F. Ciardiello
Journal: Journal of Clinical Oncology (2008)

8117 Background: The optimal way of adding anti-EGFR antibodies to chemotherapy in the first line treatment of advanced NSCLC is unknown. We performed two parallel randomised phase 2 studies, one with elderly (CALC1-E) and one with adult performance status 2 (CALC1-PS2) pts, to choose a combined or a sequential strategy of G+C for phase 3 trials. Definitive results of CALC1-E are reported. Methods: Stage IV or IIIb (with supraclavear nodes or pleural effusion) NSCLC pts, aged 70+ with PS 0–2 for CALC1-E or aged <70 with PS2 for CALC1-PS2, were eligible. Pts were randomised to combination (G, 1200 mg/m2 dd 1 & 8 q 21 max 6 cycles, plus C, 400 mg/m2 d1 then 250 mg/m2 weekly until progression) or sequential (G as above followed, after progression or 6 cycles, by C as above) strategy. A selection design was applied with rate of pts alive at 1 year as primary end-point; 58 elderly and 42 PS2 pts were required. Results: 29 elderly pts were randomly assigned to each arm from Nov 05 to Jun 06; median age 74 (70–81), 74% males, 88% PS 0–1. In the sequential arm, 10 patients (34.5%) were not able to receive C after G. At 1 year, 12 pts (41.4%) were alive in the combination and 9 (31.0%) in the sequential arm; with the combination, median survival of 20 patients with grade 1–3 skin toxicity was 54 weeks vs 10 weeks in 9 patients with grade 0. Overall toxicity was similar in the two arms. There were 4 early deaths possibly due to treatment, 2 in each arm. Progression-free survival and response rate were similar in the two arms. Conclusions: In elderly NSCLC pts, the optimal way of adding C to G is combination. A phase 3 trial is being planned to verify whether the addition of C does prolong survival in this clinical setting. Data of CALC1-PS2 will be available in March 2008. ClinicalTrials.gov ID: NCT00330746. Partially supported by Merck- Pharma Spa, Italy. No significant financial relationships to disclose.
Cytogenetic Analysis of Twelve Human Malignant Melanoma Cell Lines2
Authors: L. A. Quinn, L. K. Woods, S. B. Merrick, N. M. Arabasz, G. E. Moore
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cytogenetic Analysis of Twelve Human Malignant Melanoma Cell Lines Get access L. A. Quinn, L. A. Quinn Search for other works by this author on: Oxford Academic PubMed Google Scholar L. K. Woods, L. K. Woods Search for other works by this author on: Oxford Academic PubMed Google Scholar S. B. Merrick, S. B. Merrick Search for other works by this author on: Oxford Academic PubMed Google Scholar N. M. Arabasz, N. M. Arabasz Search for other works by this author on: Oxford Academic PubMed Google Scholar G. E. Moore G. E. Moore Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 301–307, https://doi.org/10.1093/jnci/59.2.301 Published: 01 August 1977 Article history Received: 19 August 1976 Published: 01 August 1977
Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32).
Authors: Johannes W.G. Janssen, Jan Willem Vaandrager, Tanja Heuser, Anna Jauch, Philip M. Kluin, Erik Geelen, P. Leif Bergsagel, W. Michael Kuehl, Hans G. Drexler, Takemi Otsuki, Claus R. Bartram, Ed Schuuring
Journal: Blood (2000)
Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis
Authors: Robert Brownell, Naftali Kaminski, Prescott G. Woodruff, Williamson Z. Bradford, Luca Richeldi, Fernando J. Martinez, Harold R. Collard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Precision medicine is defined by the National Institute of Health's Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field's nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management.
Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression
Authors: JH Ohyashiki, K Ohyashiki, T Shimamoto, K Kawakubo, T Fujimura, S Nakazawa, K Toyama
Journal: Blood (1995)
Present situation is detrimental to patient care
Authors: O. Williams, P. Spiers
Journal: BMJ (1995)

are shorter and of a finite duration.Our qualifications, both public and private, were that a large increase in the number of consultants was needed, which would require greatly increased resources, and that the scheme should be introduced gradually over 10 years.Fourthly, many of the questions posed in table I of the paper are only tangentially relevant to the
Annular, scaly, erythematous rash on the buttocks and thighs
Authors: Krishna Sumanth Mukkanna, Natalie Stone
Journal: BMJ (2016)

A 63 year old woman presented with a three month history of an itchy, annular, scaly, erythematous rash on both buttocks and upper posterior thighs. The rash had not responded to topical betamethasone valerate 0.122% ointment.



What …
Splenectomy and Risk of Blast Transformation in Myelofibrosis With Myeloid Metaplasia
Authors: Giovanni Barosi, Achille Ambrosetti, Antonietta Centra, Antonietta Falcone, Carlo Finelli, Paolo Foa, Alberto Grossi, Roberta Guarnone, Serena Rupoli, Luigiana Luciano, Maria C. Petti, Enrico Pogliani, Domenico Russo, Marco Ruggeri, Silvana Quaglini
Journal: Blood (1998)
Multiple Myeloma Guidelines
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2007)

Multiple myeloma will account for an estimated 16,570 new cancer cases in the United States in 2006, with an estimated 11,310 deaths. It is not currently considered curable; however, treatment has evolved rapidly because of new drugs such as bortezomib, thalidomide, and lenalidomide. In addition, increased understanding of the bone marrow microenvironment is creating rationale for new combinations and new drug development. Important updates in the 2007 NCCN guidelines include new recommended single-agent and combination regimens for consideration for induction and salvage therapy. For the most recent version of the guidelines, please visit NCCN.org
Abstract 16367: Genetically Elevated Body Mass Index Leaves Global Imprints on the Systemic Metabolite Profile in Young Adults
Authors: Peter Wurtz, Antti J Kangas, Pasi Soininen, Olli T Raitakari, Terho Lehtimaki, Marjo-Riitta Jarvelin, Samuli Ripatti, Mika Ala-Korpela
Journal: Circulation (2012)

Introduction: Elevated body mass index (BMI) due to common genetic variants has been linked with the risk for future ischemic heart disease, yet it remains unclear how this association is mediated....