tbuckley/cabot-search huggingface dataset:
Abstract P5-14-02: Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials
Authors: S Niraula, M Pitz, V Gordon, D Grenier, E Amir, L Brandes
Journal: Cancer Research (2016)

Abstract Background: While fulvestrant is approved by the United Stated Food and Drug Administration as an alternate endocrine therapy for treatment of advanced breast cancer, data on its efficacy compared to other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified. Methods: We searched the literature from inception to May, 2015 from MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials that evaluated Fulvestrant compared to either tamoxifen or an AI. We collected the efficacy data reported as Time to Progression (TTP) or Progression Free Survival (PFS) on 7 distinct subgroup of patients from the RCTs defined by: age, time to cancer reoccurrence from primary diagnosis, presence of visceral metastasis, previous chemotherapy exposure, presence of measurable disease, hormone receptor status and, HER-2 status. Data on rates of occurrences of 9 most frequently reported adverse events were also collected from both arms of the studies. Data on both efficacy and toxicity were then weighted using generic inverse variance approach and pooled in a meta-analysis using RevMan 5.3 software. Results: We identified 8 RCTs that fulfilled our criteria and involved 4,024 patients (2,032 on fulvestrant and 1,992 on control arms). TTP/PFS was the primary endpoint in 7 out of 8 RCTs and secondary endpoint in one. Compared to an AI or tamoxifen, there was a statistically significant improvement in TTP favoring fulvestrant in patients who had visceral metastasis [Hazards Ratio (HR) 0.86; 95% Confidence Interval (CI) 0.77 to 0.96, p&amp;lt;0.01], measurable disease [HR 0.74; 95% CI 0.58 to 0.93, p=0.01], and HER-2 overexpression [HR 0.43; 95% CI 0.27 to 0.70, p&amp;lt;0.001]. Similar effect sizes were observed in a sensitivity analysis excluding the trials of combinations of fulvestrant and AI in the experimental arm. Rates of occurrences of adverse events were similar between fulvestrant and other endocrine agents. Conclusion: Patients with advanced breast cancer that have visceral disease, measurable disease, or HER-2 driven disease are likely to derive higher benefits from treatment with fulvestrant compared to tamoxifen or an AI. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice. Citation Format: Niraula S, Pitz M, Gordon V, Grenier D, Amir E, Brandes L. Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-02.
Case 63-1963
Authors: William H. Baker, Sanford I. Roth
Journal: New England Journal of Medicine (1963)

Presentation of CaseA seventy-seven-year-old man entered the hospital because of weakness and mental confusion.Except for prostatism the patient had been in excellent health until eight months previously, when he began to complain of fatigue and intermittent, mild pain in the right side of the abdomen. His appetite diminished, and he lost 15 pounds in weight. Two and a half months before admission hoarseness and a nonproductive cough developed, but cleared spontaneously. Two months before entry he was admitted to another hospital because of persistent fatigue. At that time the hemoglobin was 13.6 gm., the hematocrit was 42 per . . .
A combined large-scale meta-analysis identifies <i>COG6</i> as a novel shared risk <i>locus</i> for rheumatoid arthritis and systemic lupus erythematosus
Authors: Ana Márquez, Laura Vidal-Bralo, Luis Rodríguez-Rodríguez, Miguel A González-Gay, Alejandro Balsa, Isidoro González-Álvaro, Patricia Carreira, Norberto Ortego-Centeno, María M Ayala-Gutiérrez, Francisco José García-Hernández, M Francisca González-Escribano, José Mario Sabio, Carles Tolosa, Ana Suárez, Antonio González, Leonid Padyukov, Jane Worthington, Timothy Vyse, Marta E Alarcón-Riquelme, Javier Martín
Journal: Annals of the Rheumatic Diseases (2016)

Objectives During the last years, genome-wide association studies (GWASs) have identified a number of common genetic risk factors for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic overlap between these two immune-mediated diseases has not been thoroughly examined so far. The aim of the present study was to identify additional risk loci shared between RA and SLE. Methods We performed a large-scale meta-analysis of GWAS data from RA (3911 cases and 4083 controls) and SLE (2237 cases and 6315 controls). The top-associated polymorphisms in the discovery phase were selected for replication in additional datasets comprising 13 641 RA cases and 31 921 controls and 1957 patients with SLE and 4588 controls. Results The rs9603612 genetic variant, located nearby the COG6 gene, an established susceptibility locus for RA, reached genome-wide significance in the combined analysis including both discovery and replication sets (p value=2.95E−13). In silico expression quantitative trait locus analysis revealed that the associated polymorphism acts as a regulatory variant influencing COG6 expression. Moreover, protein–protein interaction and gene ontology enrichment analyses suggested the existence of overlap with specific biological processes, specially the type I interferon signalling pathway. Finally, genetic correlation and polygenic risk score analyses showed cross-phenotype associations between RA and SLE. Conclusions In conclusion, we have identified a new risk locus shared between RA and SLE through a meta-analysis including GWAS datasets of both diseases. This study represents the first comprehensive large-scale analysis on the genetic overlap between these two complex disorders.
Controlling for Phylogenetic Relatedness and Evolutionary Rates Improves the Discovery of Associations Between Species’ Phenotypic and Genomic Differences
Authors: Xavier Prudent, Genis Parra, Peter Schwede, Juliana G. Roscito, Michael Hiller
Journal: Molecular Biology and Evolution (2016)

The growing number of sequenced genomes allows us now to address a key question in genetics and evolutionary biology: which genomic changes underlie particular phenotypic changes between species? Previously, we developed a computational framework called Forward Genomics that associates phenotypic to genomic differences by focusing on phenotypes that are independently lost in different lineages. However, our previous implementation had three main limitations. Here, we present two new Forward Genomics methods that overcome these limitations by (1) directly controlling for phylogenetic relatedness, (2) controlling for differences in evolutionary rates, and (3) computing a statistical significance. We demonstrate on large-scale simulated data and on real data that both new methods substantially improve the sensitivity to detect associations between phenotypic and genomic differences. We applied these new methods to detect genomic differences involved in the loss of vision in the blind mole rat and the cape golden mole, two independent subterranean mammals. Forward Genomics identified several genes that are enriched in functions related to eye development and the perception of light, as well as genes involved in the circadian rhythm. These new Forward Genomics methods represent a significant advance in our ability to discover the genomic basis underlying phenotypic differences between species. Source code: https://github.com/hillerlab/ForwardGenomics/
P60. Microtubule-depolymerising agents used in antibody-drug-conjugates induce anti-tumour immunity by stimulation of dendritic cells
Authors: K Martin, P Mueller, S Theurich, S Savic, G Terszowski, HM Kvasnicka, S Dirnhofer, DE Speiser, M von Bergwelt-Baildon, A Zippelius
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Antibody drug conjugates (ADCs) are emerging as powerful treatment strategies with outstanding target specificity and high therapeutic activity in cancer patients. Brentuximab vedotin represents a first-in-class ADC directed against CD30-positive malignancies. We hypothesised that
SAT0527 Predictors of Disease Relapse in IgG4-Related Disease
Authors: Z. Wallace, H. Mattoo, V. Mahajan, M. Kulikova, L. Lu, V. Deshpande, H. Choi, S. Pillai, J. Stone
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a relapsing-remitting condition responsible for fibroinflammatory lesions that can lead to organ damage and life-threatening complications at nearly any anatomic site (1). The duration of remission following treatment varies and predictors of relapse are unclear (2, 3). <h3>Objectives</h3> To evaluate potential predictors of relapse in 60 patients treated with rituximab for active, biopsy-proven IgG4-RD. <h3>Methods</h3> In this retrospective cohort study, all patients were treated with two doses of rituximab (1g) separated by 15 days. Clinical, radiographic, and laboratory data pertaining to rituximab response and disease relapse were collected from the electronic medical record. Kaplan-Meier curves were constructed to estimate the time to disease relapse. Log-rank analyses were performed to compare times to relapse among subgroups. Potential relapse predictors were evaluated with Cox regression analysis. <h3>Results</h3> Of the 60 patients included, 57 (95%) had clinical responses to rituximab. Forty-one patients (68%) were treated without glucocorticoids. Twenty-one patients (37%) experienced relapses following treatment at a median time from the first infusion of 244 days (95% CI 158-330 days). Baseline concentrations of serum IgG4 and IgE and circulating eosinophil levels were predictors of disease relapses, with hazard ratios (HR) of 6.2 (95% CI 1.2-32.0), 8.2 (1.4-50.0), and 7.9 (1.8-34.7), respectively. <h3>Conclusions</h3> Rituximab is an effective steroid-sparing agent but relapses following remission are common. Baseline elevations in serum IgG4 and IgE concentrations and blood eosinophil levels predict subsequent disease relapses. Measurement of these variables at baseline may assist in longitudinal management decisions for these patients. <h3>References</h3> Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; Feb 9;366(6):539-51. Hart PA, Kamisawa T, Brugge WR, Chung JB, Culver EL, Czako L, et al. Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut 2013; Dec;62(12):1771-6. Yamamoto M, Nojima M, Takahashi H, Yokoyama Y, Ishigami K, Yajima H, et al. Identification of relapse predictors in IgG4-related disease using multivariate analysis of clinical data at the first visit and initial treatment. Rheumatology (Oxford) 2015; Jan;54(1):45-9. <h3>Disclosure of Interest</h3> None declared
New Agents for Colorectal Cancer
Authors: Mary F. Mulcahy, Al B. Benson
Journal: Journal of the National Comprehensive Cancer Network (2003)

The past 5 years have seen significant developments in the treatment of colorectal cancer (CRC). New chemotherapy agents with activity in CRC have demonstrated an improvement in survival for patients with advanced CRC. Studies now are focusing on combinations and sequences of chemotherapy agents to prolong survival in second- and even third-line therapies. Oral agents have been developed and are being studied in combination chemotherapy regimens. Development of oral combinations should maintain a survival advantage with the added benefit of convenience for the patient. Drugs designed to act on specific cellular protein targets have also shown activity and are being explored further. Researchers continue to pursue immunotherapy and vaccine therapy. Studies are now focusing on how best to use the available agents. These new agents and new combinations of agents and of approaches have led and should continue to lead to improved outcomes in the treatment of patients with CRC.
Cancer Pain Management: Strategies for Safe and Effective Opioid Prescribing
Authors: Judith A. Paice
Journal: Journal of the National Comprehensive Cancer Network (2016)

Although controversial in recent years, the use of opioid analgesics is a fundamental component of the management of patients with malignant pain. Decisions about whether to initiate opioid therapy require comprehensive patient assessment and a great deal of compassion, with an eye toward achieving a safety balance among patients, prescribers, and the community. At the NCCN 21st Annual Conference, Judith Paice, PhD, RN, reviewed the basics of pain assessment, the dangers of undertreatment and overtreatment, goals of pain management, and practical strategies for navigating through the continuum of pain and substance abuse.
P20 Functional capacity is significantly impaired in primary biliary cirrhosis and related to orthostatic symptoms
Authors: I Patanwala, J Newton, C Elliot, J Frith, C Ghazala, J Pariman, D Jones
Journal: Gut (2010)

Introduction  Primary biliary cirrhosis (PBC) is associated with a significant and diverse symptom burden independent of conventional markers of disease severity. It is unclear how this symptom load impacts upon function in day to day living and, if functional impairment is present, which symptom(s) are predominantly responsible.  Aim  We assessed patient-reported functional ability and its inter-relationship with symptoms in PBC.  Method  81% (75/93) of the PBC symptom study cohort, originally derived in 2005, consisting of all PBC patients resident within the geographical area defined by zip codes NE1-NE25 (Newcastle-upon-Tyne and surrounding suburbs) completed a further set of postal-return symptom assessment tools in 2009. This included the disease specific symptom assessment tool the PBC-40, a marker of autonomic symptom burden, the Orthostatic Grading Scale (OGS), and the patient reported outcome measure health assessment questionnaires (PROMIS HAQ), that assesses functional ability (which was also completed by a liver disease control group (primary sclerosing cholangitis n=31 (PSC) and matched controls (n=55)).  Results  Over 4 yrs of follow-up, total symptom burden, assessed using the cumulative PBC-40 domain scores, increased significantly (p=0.03). The predominant factor was a significant rise in Cognitive domain scores indicating worsening cognitive symptoms (p  Conclusion  PBC is associated with a substantial impairment of functional capacity to a greater degree than has previously been appreciated. The distribution of symptoms of PBC evolves over time, with cognitive symptoms making an ever-greater contribution to the overall burden. The major determinant responsible for both functional impairment and the specific symptoms contributing to it appears to be autonomic dysfunction which is potentially modifiable by treatment.
Cancer Risk Among Women Exposed to Exogenous Estrogens During Pregnancy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: O C Hadjimichael, J W Meigs, F W Falcier, W D Thompson, J T Flannery
Journal: JNCI Journal of the National Cancer Institute (1984)

A cohort of 3,139 obstetric patients, who delivered children between 1946 and 1965, was followed retrospectively to assess the relationship between exposure to diethylstilbestrol [(DES) CAS: 56-53-1; alpha, alpha'-diethyl-4,4'-stilbenediol] or other estrogenic substances during pregnancy and subsequent cancer incidence. Among the 1,531 women exposed to DES, the relative risk (RR) for all cancers was 1.46 [95% confidence interval (CI), 1.07-2.00]. The RR for cancers of the breast, cervix, and ovary were 1.37 (adjusted), 1.40, and 2.83, respectively, but none of these estimates was statistically significant. For breast cancer an RR in excess of 2.28 can be excluded, with 95% CI for doses averaging 2,100 mg. Within the exposed group there was no evidence for a dose-response relationship.
Circadian pattern of acute, neuroleptic-induced dystonic reactions
Authors: M F Mazurek, P I Rosebush
Journal: American Journal of Psychiatry (1996)

This study examined the timing of acute dystonic reactions in 200 patients taking neuroleptic medication for the first time.Two hundred patients received a twice-daily regimen of low-dose neuroleptic.Over 80% of the episodes of acute dystonia occurred between 12:00 noon and 11:00 p.m. The observed circadian variation was not accounted for by sleep, fatigue, or time elapsed from the last dose of medication.The finding of a diurnal pattern in one of the recognized side effects of neuroleptic medication suggests that the therapeutic efficacy of neuroleptics might similarly vary over the course of the day.
Abstract B74: Can we repurpose anti-malarial drug quinacrine to treat ovarian cancer?
Authors: Debarshi Roy, Ashwani Khurana, Eleftheria Kalogera, Xuyang Wen, Susmita Mondal, Viji Shridhar
Journal: Clinical Cancer Research (2016)

Abstract Resistance to chemotherapy is a major hurdle that results in the increased mortality associated with ovarian cancer (OvCa). New therapeutics that synergize with cis-carboplatin/paclitaxel in recurrent tumors will have an enormous impact in prolonging the survival of OvCa patients. Due to the enormous cost of designing and testing new drugs, we have adopted the drug repurposing approach and tested the effect of the antimalarial drug quinacrine (QC) in sensitizing drug resistant OvCa cells to carboplatin induced cytotoxicity and determined that it is autophagy dependent. We have discovered that QC, an autophagy modulator exhibited distinct anti-cancer properties in OvCa cell lines in contrast to other anti-malarial/autophagy inhibitor drugs such as hydroxyquinacrine, bafilomycin A and 3-MA. It is well established that autophagy can be a survival mechanism under stress in cancer or a death promoting phenomenon that is cell type and contextual dependent. Here we demonstrate that QC acts to promote chemotherapy induced cell death specifically more in resistant cells in an autophagy dependent manner. Our preliminary data both in vitro and in vivo indicate that QC induced autophagy downregulates p62 and upregulates cathepsin L levels to sensitize the chemoresistant cells to autophagic and caspase mediated cell death in a p53 independent manner. These unexpected findings led us to explore the mechanistic basis of QC-induced upregulation of the cell cycle inhibitor p21 in cells bearing mutant p53. We uncovered that irrespective of p53 status, QC induces p21 expression in an autophagy-dependent p62-Skp2 mediated ubiquitin pathway resulting in cell cycle arrest and cell death. Since QC is already in PhaseI Clinical trial, these studies may spur new treatment strategies to improve OvCa patient outcome and patient care. Citation Format: Debarshi Roy, Ashwani Khurana, Eleftheria Kalogera, Xuyang Wen, Susmita Mondal, Viji Shridhar. Can we repurpose anti-malarial drug quinacrine to treat ovarian cancer? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B74.
Severity of depression and response to cognitive behavior therapy
Authors: M E Thase, A D Simons, J Cahalane, J McGeary, T Harden
Journal: American Journal of Psychiatry (1991)

The authors studied the relationship between clinical severity of depression and response to cognitive behavior therapy.Fifty-nine outpatients with major depression with endogenous features, according to Research Diagnostic Criteria, were stratified into more severe (score of 20 or more on the Hamilton Rating Scale for Depression; N = 38) or less severe (Hamilton score of 19 or less; N = 21) subgroups. Patients were treated with a 16-week, 20-session cognitive behavior therapy protocol. Outcome was assessed with the Hamilton scale, the Global Adjustment Scale, and the Beck Depression Inventory.The more severe group was significantly more symptomatic across the 16-week protocol and had a significantly lower response rate on the Beck inventory (50% versus 81%). However, the groups did not significantly differ at end point on any of the three measures, and they showed comparable rates of symptomatic improvement (i.e., percent change in scores and interactions between severity classification and time).These results partially replicate the National Institute of Mental Health's Treatment of Depression Collaborative Research Program's findings of poorer response to cognitive behavior therapy in patients with Hamilton scale scores of 20 or more. However, both groups experienced robust and clinically significant reductions in depressive symptoms, and the response of the more severe patients in the current study could hardly be considered poor. While these findings do not support the view that a Hamilton scale score of 20 or more is a relative contraindication for cognitive behavior therapy, the symptoms of the more severely depressed patients did tend to remit less completely (particularly on the Beck inventory) and thus these patients may benefit from a more intensive or extended course of therapy.
Rapid Induction of CD40 on a Subset of Granulocyte Colony-Stimulating Factor–Mobilized CD34+ Blood Cells Identifies Myeloid Committed Progenitors and Permits Selection of Nonimmunogenic CD40− Progenitor Cells
Authors: Damiano Rondelli, Roberto M. Lemoli, Marina Ratta, Miriam Fogli, Francesca Re, Antonio Curti, Mario Arpinati, Sante Tura
Journal: Blood (1999)
A Phase-I Study of an Anti-CD25 Ricin A-Chain Immunotoxin (RFT5-SMPT-dgA) in Patients With Refractory Hodgkin's Lymphoma
Authors: Andreas Engert, Volker Diehl, Roland Schnell, Andrea Radszuhn, Maria-Theresia Hatwig, Silke Drillich, Gisela Schön, Heribert Bohlen, Hans Tesch, Martin-Leo Hansmann, Stefan Barth, John Schindler, Victor Ghetie, Jonathan Uhr, Ellen Vitetta
Journal: Blood (1997)
Process has since been simplified
Authors: A G. Bynoe, I. Goldberg
Journal: BMJ (1995)

EDITOR,--Jacqueline Morrell and Angela Roberts's article on how to apply for flexible training publicises the scheme well but comes at an inopportune time, given the considerable changes taking place at the moment.1 The article should not be seen as a definitive guide on “how to do it.”

The authors clearly experienced considerable difficulties in obtaining their flexible training posts and are right to point out many of the pitfalls. During …
Studies on Mouse Lymphomas. I. Cytology and Nucleic Acid Content
Authors: Emma Shelton
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Studies on Mouse Lymphomas. I. Cytology and Nucleic Acid Content Get access Emma Shelton Emma Shelton National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 1, August 1954, Pages 49–61, https://doi.org/10.1093/jnci/15.1.49 Published: 01 August 1954 Article history Received: 08 March 1954 Published: 01 August 1954
Calcium-dependent homotypic adhesion through leukocyte function- associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro
Authors: A Wake, Y Tanaka, K Nakatsuka, M Misago, S Oda, I Morimoto, S Eto
Journal: Blood (1995)