tbuckley/cabot-search huggingface dataset:
Surgical resection of metastases (mts) after biweekly chemotherapy with irinotecan, oxaliplatin and 5-fluorouracil/leucovorin (FOLFOXIRI) in initially unresectable metastatic colorectal cancer (MCRC)
Authors: A. Falcone, G. Masi, S. Cupini, L. Marcucci, S. Ricci, I. Brunetti, E. Cerri, E. Fontana, M. Andreuccetti, G. Allegrini
Journal: Journal of Clinical Oncology (2004)

3553 Background: We conducted a phase I-II study with the triple drug combination FOLFOXIRI (irinotecan 125–175 mg/sqm day (d) 1, oxaliplatin 100 mg/sqm d1, l-LV 200 mg/sqm d1, 5-FU 3800 mg/sqm 48-h IV chronomodulated continuous infusion starting on d1, repeated every 2 weeks) and a subsequent phase II study with a simplified FOLFOXIRI regimen (irinotecan 165 mg/sqm d1, oxaliplatin 85 mg/sqm d1, l-LV 200 mg/sqm d1, 5-FU 3200 mg/sqm 48-h flat continuous infusion starting on d1, repeated every 2 weeks) respectively in 42 and 32 unselected MCRC pts with initially unresectable mts. Overall response rate, median progression free (PFS) and overall survival (OS) were 71% and 72%, 10.4 months (mos) and 10.8 mos, 26.5 mos and 28.4 mos respectively. Methods: In consideration of the high activity of these regimens 30 out of 74 pts (40%) could be revaluated for surgical resection of mts after chemotherapy. Among these 30 pts revaluated for surgery a R0 surgical resection could be performed in 19 pts (26% of the initial 74 pts). Characteristics of the 19 radically resected pts were: median age 66 years (45–73), ECOG PS ≥ 1 6 pts (32%), median CEA 10 ng/ml (1–288), median number of mts 3 (1–10), liver involvement ≥ 25% 12 pts (63%). Sites of disease were: liver only 14 pts, liver + lymphonodes 3 pts, liver + peritoneum 1 pt, liver + lung 1 pt. Mts were synchronous in 12 pts (63%) and metachronous in 7 pts with a median disease free interval of 12 mos. Results: After a median follow up of 28.8 mos median PFS is 18.6 mos and median OS is 39.6 mos. In 2 pts progressed after surgery a surgical re-resection and/or radiofrequency ablation was performed. Conclusions: First line FOLFOXIRI enables R0 surgical resection in about a quarter of pts with clearly initially unresectable MCRC. Median OS of resected pts is very promising. Prospective evaluation of FOLFOXIRI as neo-adjuvant treatment in initially unresectable colorectal cancer pts with liver and/or lung metastases is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharma
Biochemical, cellular and in vivo profiling of a new PI3K inhibitor from the imidazoquinoline series
Authors: Michel Maira
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

ND-3 

Activation of the PI3K pathway seems to be a prerequisite for a wide spectrum of cancers, either via the loss of PTEN, the acquisition of activating mutations in the PI3K catalytic subunit itself of (the p110 alpha protein, encoded by PIK3CA gene), or the direct engagement of the PI3K pathway in cancer where some receptors tyrosine kinase are amplified and/or overexpressed (e.g. ErbB2/3 in breast and ovarian cancers), or amplification of the Akt/PKB proteins. These alterations trigger a cascade of biological events that drive tumor progression, survival, angiogenesis and metastasis. Thus, class I PI3Ks represent well validated therapeutic target for drug discovery in oncology. PI3K inhibition should simultaneously reduce cell proliferation and growth of tumor cells, and re-sensitize them toward programmed cell death.Using a structure-based drug-design strategy, the identification of new chemotypes for PI3K inhibition has been pursued in our company. This has led us to the optimization of PI3K inhibition by compounds from the imidazo-quinoline serie. A medicinal chemistry effort for lead optimization resulted in the identification of a orally available candidate, with superior drug-like and pharmacokinetic properties toward the historical PI3K inhibitors wortmannin and LY294002. This new molecular entity, NVP-BEZ235, was therefore selected for full clinical development. NVP-BEZ235, is a pan class-I PI3 Kinase modulator, that produces well tolerated anti-tumor activity when administered every day, p.o., to tumor-bearing animals. This presentation will provide a summary of its pre-clinical profile.
A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel
Authors: K.N. Chi, T. Kheoh, C.J. Ryan, A. Molina, J. Bellmunt, N.J. Vogelzang, D.E. Rathkopf, K. Fizazi, P.W. Kantoff, J. Li, A.A. Azad, B.J. Eigl, D.Y.C. Heng, A.M. Joshua, J.S. de Bono, H.I. Scher
Journal: Annals of Oncology (2015)

Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC.Baseline data were available from 762 patients treated with abiraterone-prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort.Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286).This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design.NCT00638690.
Estrogen Receptor Assay in Human Breast Cancer
Authors: Stanley G. Korenman
Journal: JNCI Journal of the National Cancer Institute (1975)

A Workshop on Receptor Assay in Breast Cancer Tissue at the Fourth International Congress on Hormonal Steroids was held in Mexico City, September 2-7, 1974. This report reviews the various methods of steroid receptor assay in breast cancer discussed at this Workshop.
Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia
Authors: Jihen Ben Halima, Wided Ben Ahmed, Leila El Gharbi, Besma Dhari, Saloua Azzabi, Mohamed Ali Baccar, Hichem Aouina, Hend Bouacha
Journal: European Respiratory Journal (2013)

Introduction: Community-acquired pneumonia (CAP) remains a major reason for hospital admission and a common cause of death in growing countries. The rate of microbial identification remains extremely low. To assess the usefulness of serum C-reactive protein (CRP) in the diagnosis and treatment approach of patients with CAP, and determine the microbial aetiology, and the possible risk factors of CAP.  Methods:115 patients who had received a diagnosis of CAP, confirmed by chest radiographs and compatible clinical outcome, were included. Chest x-ray, microbiological assessment and serum CRP concentrations were assayed in peripheral blood at the time of diagnosis.  Results: 72% of patients were men, with a mean age of 61 years and 28% women with a mean age of 57.The most frequent isolated microbial agent in severe CAP was gram-negative bacilli (4 cases), followed by Staphylococcus (2 cases), Streptococcus pneumonia (1 case), and Legionella (1 case).respiratory rate >30/min, hypoxemia and transfer in intensive care unit were reported in 37%, 41% and 9.5% of SCAP respectively. Chest radiograph with extensive involvement was observed in 30% of patients. Significant risk factors in univariate analysis included age >65 years, male sex (p was0.025 and 0.034 respectively). CRP level was not associated with hospitalization more than 15 days (The area under the receiver operating characteristic was 0.54, p=0.48). We observed also no correlation between CRP and bad evolution (p=0.86).  Conclusion: The most frequent microbial agent in SCAP is gram-negative bacilli and the most frequent risk factor is age (age >65years). CRP is not usefull for the diagnosis or the management of CAP.
c-Myb is required for plasma cell migration to bone marrow after immunization or infection
Authors: Kim L. Good-Jacobson, Kristy O’Donnell, Gabrielle T. Belz, Stephen L. Nutt, David M. Tarlinton
Journal: The Journal of Experimental Medicine (2015)

Plasma cell migration is crucial to immunity, but little is known about the molecular regulators of their migratory programs. Here, we detail the critical role of the transcription factor c-Myb in determining plasma cell location. In the absence of c-Myb, no IgG+ antigen-specific plasma cells were detected in the bone marrow after immunization or virus infection. This was correlated with a dramatic reduction of plasma cells in peripheral blood, mislocalization in spleen, and an inability of c-Myb–deficient plasma cells to migrate along a CXCL12 gradient. Therefore, c-Myb plays an essential, novel role in establishing the long-lived plasma cell population in the BM via responsiveness to chemokine migration cues.
Abstract 9759: Race and Gender Differences in Survival Among Hospitalized Heart Failure With Preserved Ejection Fraction: The Atherosclerosis Risk in Communities (ARIC) Surveillance Study
Authors: Kavita Sharma, Sunil K Agarwal, Lisa M Wrick, Kunihiro Matsushita, Patricia P Chang, Amil M Shah, Dalane W Kitzman, Anita Deswal, Loehr R Laura, Josef Coresh, Wayne D Rosamond, Scott D Solomon, Stuart D Russell
Journal: Circulation (2014)

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for about half of HF hospitalizations, and has been reported to be more common amongst Caucasians and women in outpatient population studies. There are limited data, however, on the influence of race and gender on survival in HFpEF. We evaluated whether clinical characteristics and outcomes differ amongst HFpEF patients by race and gender. Methods: HFpEF (EF≥ 50%) hospitalization cases from 2005-2009 adjudicated by a physician panel were analyzed from the community-based surveillance component of the ARIC study, comprising 4 US communities (Jackson, MS; Washington County, MD; Minneapolis, MN; and Forsyth County, NC; combined population in 2009 = 214,000). The association of race and gender with mortality at 28-days and 1-year was evaluated. Results: Of 3,786 (weighted n = 18,265) adjudicated acute decompensated HF cases, 1,726 (weighted n = 8114) were categorized as HFpEF. Patient characteristics included: female (44%), African American (AA, 32%), hypertension (83%), diabetes (46%), and mean BMI of 28. Compared to Caucasians, AA’s were younger (70 vs. 77 years, p&lt;0.001), more frequently women (47% vs. 42%, p&lt;0.001), with higher systolic blood pressure (SBP, 145 vs. 135 mmHg, p&lt;0.001), and more prior HF hospitalizations (50% vs. 37%, p&lt;0.001). Compared to men, women were older (76 vs. 73 years, p&lt;0.001), with higher SBP (141 vs. 138 mmHg, p=0.03), and better renal function (eGFR 42 vs. 38 mL/min/1.73m 2 , p&lt;0.001). Overall 28-day and 1-year mortality was 13.1% and 32.8%, respectively, with no differences in un-adjusted or adjusted estimates by race or gender (Table 1). Conclusions: In hospitalized HFpEF patients, overall 28-day and 1-year mortality were high without apparent race- or gender-based differences in mortality. These data may help inform the development of future interventions and resource allocation.
SP0095 How A Multi-Disciplinary Team Improves Patient Outcomes
Authors: T. Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2015)

According to the Chronic Care Model, outcomes of health care for people with chronic musculoskeletal and rheumatic diseases (RMDs) depend, apart from characteristics of the health system and the community, on a productive interaction between the informed, activated patient and a prepared, proactive practice team. A team is defined as a small number of consistent people committed to a relevant shared purpose, with common performance goals, complementary and overlapping skills, and a common approach to their work. A multi-disciplinary team for people with inflammatory RMDs usually comprises the rheumatologist and professionals from other disciplines such as a nurse, physical therapist, occupational therapist, social worker, psychologist or podiatrist or other, some with extended scope of practice. However, dependent on the nature and severity of the RMD and local availability of skilled health care providers, the composition of the multi-disciplinary team may vary. Overall, evidence from systematic reviews as well as individual clinical trials supports improved functioning following multi-disciplinary team care for a number of RMDs<sup>1</sup>. However, research also illustrates that multi-disciplinary team care can be effective in several forms, as the multi-disciplinary interventions described in the literature vary largely. This variation does not only include the professionals involved, but also the treatments provided (content, intensity, complexity), the setting (primary care, secondary care and/or community), the method of communication with the patient and among professionals (face-to-face contacts, telephone, videoconferencing or other web-based modes for communication) and many other factors such as funding and the use of process and outcome measures for evaluation. As currently the right care is not consistently delivered to the right person, at the right time, in the right place or by the right team<sup>2</sup>, challenges for the future are to further identify the key components of effective multi-disciplinary team care interventions and how their implementation can be supported across health care services in different health care systems. For that purpose, the consideration of alternative, network-based models of engagement and collaboration for clinicians, consumers and other stakeholders and the optimization of the use of digital technologies, as well as formal evaluations of effectiveness and costs are indispensable<sup>2,3</sup>. <h3>References</h3> Momsen A-M et al. Multidisciplinary team care in rehabilitation: an overview of reviews. J Rehabil Med 2012;44:901-912. Speerin R et al. Moving from evidence to practice: Models of care for the prevention and management of musculoskeletal conditions. Best Practice &amp; Research Clinical Rheumatology 2014;28:479-515. Brand CA et al. Chronic disease management: improving care for people with osteoarthritis. Best Practice &amp; Research Clinical Rheumatology 2014;28:119-142. <h3>Disclosure of Interest</h3> None declared
Alternative Splicing Is a Major Mechanism of Gene Regulation In Diffuse Large B Cell Lymphoma
Authors: Cassandra L Jacobs, Amee Patel, Dereje Jima, Qingquan Liu, Adrienne Greenough, Jenny Zhang, Cherie Dunphy, Kristy Richards, Wai Choi, Gopesh Srivastava, Wing Y Au, Andrew M Evens, Leo I Gordon, Magdalena Czader, David A. Rizzieri, Anand S. Lagoo, Karen P. Mann, Christopher R Flowers, Leon Bernal-Mizrachi, Kikkeri Naresh, Micah Luftig, Amy Chadburn, Eric Hsi, Michael A. Thompson, Javed Gill, Sandeep Dave
Journal: Blood (2010)
Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells
Authors: Renu Jain, Yi Chen, Yuka Kanno, Barbara Joyce-Shaikh, Golnaz Vahedi, Kiyoshi Hirahara, Wendy M. Blumenschein, Selvakumar Sukumar, Christopher J. Haines, Svetlana Sadekova, Terrill K. McClanahan, Mandy J. McGeachy, John J. O’Shea, Daniel J. Cua
Journal: Immunity (2015)
Abstract 15534: How Overall Health Status and Insurance Influence Utilization of the Primary Prevention Implantable Defibrillator in the Current Era
Authors: Lin Zhang, Kumar Narayanan, Harpriya Chugh, Shiota Takahiro, Zhi-Jie Zheng, Sumeet S Chugh
Journal: Circulation (2014)

Introduction:  The benefit of the implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death in selected patients with left ventricular dysfunction is well established. However, several studies have reported that not all eligible patients receive this therapy.   Hypothesis:  We hypothesized that co-morbid health conditions and nature of health insurance play a role in the utilization patterns of the primary prevention ICD.   Methods:  Patients eligible for PPICD based on current guidelines were analyzed from the electronic medical records of a large US tertiary care center. Demographic and clinical data as well as insurance status were reviewed in detail for ICD recipients before implantation compared to ICD non-recipients. The Charlson Comorbidity Index (CCI) was calculated and categorized as low(0-1), medium(2-6) and high(7-12).   Results:  Over an 8-month period, comparisons were made between 110 recipients and 110 non-recipients. ICD recipients were younger (62.1±15.0 vs. 68.0±18.2; P=0.009), with higher proportion of males (80% vs. 65.5%; P=0.01), and higher BMI (27.8±7.7 vs. 24.3±6.9; P=0.001). Compared to ICD non-recipients, ICD recipients were more likely to have lower comorbidities (high CCI 5.5 % vs. 11.8%; P=0.05) and lower LVEF (23.8±6.4 vs. 25.3±7.2; P=0.04). ICD recipients were less likely to be current alcohol users (5.5% vs. 8.2%; P=0.05), smokers (5.5% vs. 13.6%, P=0.03) or have history of drug abuse (0.9% vs. 5.5%; P=0.02). ICD recipients were more likely to have combined public and private insurance (29.1% vs. 18.2%, P=0.03), and less likely to have public insurance alone (28.2% vs. 32.7%, P=0.05). In multivariable model, independent predictors of implantation included male sex (OR 2.23[1.15-4.33]; P=0.02), age   Conclusions:  Our findings suggest that age, sex and co-morbid conditions continue to determine ICD utilization in real world clinical practice, with insurance status also playing a role. This important area warrants significant further investigation in diverse US communities.
Abstract P031: Significant Predicted Change in Usual Sodium Intake for the U.S. Population From Meeting Sodium Standards for Commercially-Packaged and Restaurant Foods: National Health and Nutrition Examination Survey, 2007-2010
Authors: Mary Cogswell, Sheena Patel, Keming Yuan, Cathleen Gillespie, WenYen Juan, Christine Johnson, Michel Vigneault, Jenifer Clapp, Paula Roach, Alanna Moshfegh, Jaspreet Ahuja, Pamela Pehrsson, Robert Merrritt
Journal: Circulation (2015)

Background: A 400 mg daily reduction in the average sodium intake of the U.S. population is projected to save up to 28,000 lives and $7 billion health care dollars annually. In 2010, the Institute of Medicine recommended setting standards for the sodium content of commercially-packaged and restaurant foods to reduce U.S.sodium intake given the majority of sodium intake is from these foods. We assessed this hypothesis. Methods: We developed models using 2007-2010 data for 17,979 participants one year and older participating in two 24-hour dietary recalls, a part of the What We Eat in America component of the National Health and Nutrition Examination Survey. We projected the sodium content in foods reported by survey respondents based on percent changes in sales weighted averages from baseline for specific food categories using New York City’s National Salt Reduction Initiative (NSRI) 2014 targets or Health Canada’s 2016 sodium benchmarks. To predict the changes in usual sodium intake from foods for the U.S. population aged &gt; 1 year we used analyses accounting for the complex survey design with measurement error models to adjust for within person day-to-day variation in intake. Results: Based on a conservative estimate of the foods included in specific categories, if NSRI targets had been met in 2007-10, we estimated that the U.S. population aged &gt; 1 year could have reduced their average usual daily mean sodium intake of 3343 mg by 14%, or 484 mg (95% Confidence Interval [CI], 471 mg, 498 mg). If Health Canada’s benchmarks were met, the US population could have reduced their average usual daily sodium intake by 18% or 612 mg (95% CI, 594 mg, 630 mg). Across age, sex, and race-ethnic population subgroups, the average predicted relative reductions in sodium intake by group ranged from 13% -15% using NSRI targets and 16%-19% using Health Canada’s benchmarks. If sodium standards had been met, we estimated the proportion of adults aged 19 years and older consuming &gt; 2300 mg daily would have declined from 87% (95% CI, 84%, 89%) to 75% (95% CI, 72%, 77%) using NSRI targets or to 70% (95% CI, 68%, 73%) using Health Canada benchmarks. The proportion of adults consuming &gt; 1500 mg daily would have declined from 99% to 96%-97%. Conclusion: Results suggest that if U.S. commercially-packaged and restaurant foods had met established sodium standards, a significant reduction in sodium intake could have occurred across age, sex, and race-ethnic groups in the U.S. population.
Case 1: Hypoglycemic Syncope Due to a Peripheral Neuroectodermal Tumor
Authors: Klaus Empen, Carsten Otto, Josef Müller-Höcker, Jürgen Zapf, Peter Schwandt
Journal: Journal of Clinical Oncology (2000)

Article Tools Small Round-Cell Tumors Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.7.1594 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10735907 Case 1: Hypoglycemic Syncope Due to a Peripheral Neuroectodermal Tumor Klaus EmpenxKlaus EmpenSearch for articles by this author , Carsten OttoxCarsten OttoSearch for articles by this author , Josef Müller-HöckerxJosef Müller-HöckerSearch for articles by this author , Jürgen ZapfxJürgen ZapfSearch for articles by this author , Peter SchwandtxPeter SchwandtSearch for articles by this author Show More Klinikum Grosshadern, Munich, Germany, and University Hospital, Zurich, Switzerland https://doi.org/10.1200/JCO.2000.18.7.1594 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Processed Meat Consumption Associated With Increased Cancer Risk
Authors: M. J. Friedrich
Journal: JAMA (2015)

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