tbuckley/cabot-search huggingface dataset:
Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): Impact of age on disease-free survival (DFS).
Authors: D. G. Haller, J. Cassidy, J. Tabernero, J. A. Maroun, F. G. De Braud, T. J. Price, E. Van Cutsem, M. Hill, F. Gilberg, H. Schmoll
Journal: Journal of Clinical Oncology (2010)

3521 Background: Adjuvant capecitabine is at least equivalent to bolus i.v. 5-FU/LV for DFS and overall survival (OS) in stage III colon cancer. NO16968 compared XELOX with bolus i.v. 5-FU/LV (standard regimen at study start) for stage III colon cancer. In a planned safety analysis, XELOX had an acceptable safety profile (Schmoll et al. JCO 2007). In a recent analysis of the ACCENT database, investigators concluded that newer adjuvant regimens are not associated with significant efficacy benefits vs. 5-FU/LV in patients (pts) ≥70 years (McCleary et al. ASCO 2009). We examined DFS across age groups in NO16968 to determine XELOX efficacy in pts ≥70 years. Methods: Pts were randomized to either XELOX (capecitabine 1,000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 i.v. d1, q3w ×8) or bolus i.v. 5-FU/LV regimens: Mayo Clinic (LV 20 mg/m2 + 5-FU 425 mg/m2 d1–5, q4w ×6) or Roswell Park (LV 500 mg/m2 + 5-FU 500 mg/m2 d1, w1–6 in 8w cycles × 4). Results: 1,886 pts were randomized between April 2003 and October 2004. 1,864 were evaluable in the previously reported safety analysis. After a median follow-up of 57 months, 1,886 pts are evaluable for DFS (primary endpoint), which was significantly superior for XELOX at 3, 4, and 5 years (Table). Analysis of 3-year DFS in pts <70 and ≥70 years showed a similar advantage of XELOX over 5-FU/LV. Conclusions: XELOX is superior to bolus 5-FU/LV for DFS as adjuvant treatment for stage III colon cancer and these findings confirm the benefits shown with oxaliplatin plus 5-FU combinations in stage III pts. Additionally, efficacy benefits seem to be maintained in pts ≥70 years and differ from the ACCENT meta-analysis and MOSAIC, where no significant benefit was shown with FOLFOX in this age group. It is therefore reasonable to evaluate each pt for XELOX therapy on individual merits, regardless of age. OS data are currently immature; follow-up is ongoing and updates will be reported when available. 3-year DFS 4-year DFS 5-year DFS Total population XELOX 71.0% HR 0.80 68.4% 66.1% 5-FU/LV 67.0% p=0.0045 62.3% 59.8% Analysis by age group <70 years HR 0.79 (95% CI 0.66–0.94) ≥70 years HR 0.87 (95% CI 0.63–1.18) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Merck, Merck Sharpe and Dome, Roche, sanofi-aventis Roche AstraZeneca, Merck, Roche, sanofi-aventis Merck, Roche, sanofi-aventis
Results of a first-in-human, phase I/II trial of ASP2215, a selective, potent inhibitor of FLT3/Axl in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).
Authors: Mark J. Levis, Alexander E. Perl, Jessica K. Altman, Jorge E. Cortes, Ellen K. Ritchie, Richard A. Larson, Catherine Choy Smith, Eunice S. Wang, Stephen Anthony Strickland, Maria R. Baer, Mark Robert Litzow, David Claxton, Gary J. Schiller, Celalettin Ustun, Charles Liu, Stan Gill, Briana Sargent, Erkut Bahceci
Journal: Journal of Clinical Oncology (2015)

7003 Background: FLT3 Internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations are seen in 30% of AML patients (pts) and are associated with poor survival. Secondary FLT3-TKD mutations are associated with treatment failure with tyrosine kinase inhibitors. ASP2215 is a potent inhibitor of FLT3 and Axl with activity against FLT3-ITD and FLT3-TKD. Methods: A phase I/II trial was conducted to investigate safety and efficacy in pts with R/R AML. The dose escalation followed a 3+3 design and evaluated doses from 20 to 450 mg once daily. A parallel multi-dose expansion cohort was initiated based on the efficacy seen in dose escalation. Results: 166 pts have enrolled between October 2013, and December 2014, 25 in the dose escalation and 141 in the dose expansion cohorts. At the 450 mg dose, 2 pts had a DLT (grade 3 diarrhea and ALT/AST elevation), and the maximum tolerated dose was determined to be 300 mg. Common possibly or probably drug related treatment emergent adverse events of any grade include fatigue (13%), constipation (10%), anemia (8%), nausea (8%), diarrhea (7%), thrombocytopenia (6%), decreased platelet count (6%), vomiting (6%), dizziness (6%), peripheral edema (5%), increased transaminases (5%) and hypomagnesemia (5%). 120 pts are evaluable for response. Overall response rate (ORR) was 57% in 82 pts with FLT3 mutations, and 63% in 68 pts in the 80 mg and higher dose levels. A plasma inhibitory activity assay confirmed effective, sustained in vivo FLT3 inhibition consistently in pts receiving doses of 80 mg and above. Conclusions: ASP2215, a potent inhibitor of FLT3/Axl, is well tolerated in patients with R/R AML and results in a high degree of clinical activity. Randomized phase III trials of ASP 2215 at 200 mg per day in newly diagnosed and R/R AML are planned. Clinical trial information: NCT02014558. Response FLT3 mutated FLT3 wild type n (%) (38 pts) 20-300 mg n (%) (82 pts) ≥ 80 mg n (%) (65 pts) Complete Remission (CR) 4 (5%) 3 (5%) 0 CR, incomplete platelet recovery (CRp) 4 (5%) 4 (6%) 0 CR, incomplete hematologic recovery (CRi) 27 (33%) 25 (38%) 3 (8%) Partial Remission (PR) 12 (15%) 10 (15%) 1 (3%) Composite CR (CR+CRp+CRi) 35 (43%) 32 (49%) 3 (8%) ORR (CRc+PR) 47 (57%) 42 (65%) 4 (11%)
Irinotecan Dosing: Does the CPT in CPT-11 Stand for “<b><i>C</i></b>an’t <b><i>P</i></b>redict <b><i>T</i></b>oxicity”?
Authors: Mark J. Ratain
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.1.7 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11773147 Irinotecan Dosing: Does the CPT in CPT-11 Stand for "Can't Predict Toxicity"? Mark J. RatainxMark J. RatainSearch for articles by this author Show More Committee on Clinical Pharmacology, Cancer Research Center, The University of Chicago, Chicago, IL https://doi.org/10.1200/JCO.2002.20.1.7 Full Text PDF Figures and Tables "Irinotecan Dosing: Does the CPT in CPT-11 Stand for "Can't Predict Toxicity"?." Journal of Clinical Oncology, 20(1), pp. 7–8© 2002 by American Society of Clinical Oncology
Accountability in the 2015 Global Strategy for Women’s, Children’s and Adolescents’ Health
Authors: Julian Schweitzer
Journal: BMJ (2015)

describes the steps taken to ensure accountability in the 2015 Global Strategy and why it is important to success A s the era of the millennium development goals (MDGs) draws to a close, each year some 6.3 million children under the age of 5, 289 000 women, 2.8 million newborns, and 1.3 million adolescents still die from preventable causes.Others experience illness and disability, generating enormous loss and costs.An additional 2.6 million babies are stillborn.Building on the 2010 Global Strategy for Women and Children, the forthcoming 2015 Global Strategy for Women's, Children's and Adolescents' Health 1 aims by 2030 to end these preventable deaths and to achieve a "grand convergence" in health, giving every women, child, and adolescent an equal chance to survive and thrive.As every preventable death is an affront to human rights, 2 the 2015 strategy has human rights at its core.It will be country led, universal, sustainable, equity enhancing, evidence based, partnership driven, and people centred.Robust, country led, multi-stakeholder, and participatory accountability processes, with independent review, unified reporting, and follow-up actions at all levels will be key to monitor and review progress and make the necessary policy adjustments to ensure success. 3 MethodsA working group convened by the governments of Tanzania and Canada (see appendix) prepared proposals for the accountability framework in the 2015 strategy. 1 In the absence of a comprehensive review of the accountability processes proposed by CoIA, the group reviewed relevant country and global reports, including on the implementation of the 2010 strategy. 4Other accountability processes, such as nutrition and education, were also reviewed and are cited below.Consultations were held with stakeholders during 2015, including two review meetings with government, academic, civil society, private sector, youth, and international agency representation.
DMC (2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone) improves glucose tolerance as a potent AMPK activator
Authors: Jin Woo Choi, Min Kim, Hyundong Song, Cheol Soon Lee, Won Keun Oh, Inhee Mook-Jung, Sung Soo Chung, Kyong Soo Park
Journal: Metabolism (2015)
Identification of human melanoma initiating cells
Authors: Tobias Schatton, George Murphy, Natasha Frank, Kazuhiro Yamaura, Ana Maria Waaga-Gasser, Martin Gasser, Qian Zhan, Stefan Jordan, Lyn Duncan, Carsten Weishaupt, Robert Fuhlbrigge, Thomas Kupper, Mohamed Sayegh, Markus Frank
Journal: Cancer Research (2008)

5003   Tumor initiating cells capable of self-renewal and differentiation, which are responsible for tumor growth, have been identified in human hematological malignancies and solid cancers. If such minority populations are associated with tumor progression in human patients, specific targeting of tumor initiating cells could provide for a novel strategy to eradicate cancers currently resistant to systemic therapy. Here, we identify a subpopulation enriched for human malignant melanoma initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 and show that specific targeting of this tumorigenic minority population inhibits tumor growth. ABCB5+ tumor cells detected in human melanoma patients display a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human to mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumor heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumor populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis designed to test the hypothesis that MMIC are also required for growth of established tumors, systemic administration of a monoclonal antibody directed at ABCB5, shown capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumor-inhibitory effects. Identification of tumor initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting via a defining chemoresistance determinant has important implications for cancer therapy.
Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis
Authors: Morie A. Gertz, Merrill D. Benson, Peter J. Dyck, Martha Grogan, Terresa Coelho, Marcia Cruz, John L. Berk, Violaine Plante-Bordeneuve, Hartmut H.J. Schmidt, Giampaolo Merlini
Journal: Journal of the American College of Cardiology (2015)

Transthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a mutant form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interventions currently available for affected patients.
Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects
Authors: C. Mathes, A. Melero, P. Conrad, T. Vogt, L. Rigo, D. Selzer, W.A. Prado, C. De Rossi, T.M. Garrigues, S. Hansen, S.S. Guterres, A.R. Pohlmann, R.C.R. Beck, C.-M. Lehr, U.F. Schaefer
Journal: Journal of Controlled Release (2015)
Asthma in Latin America
Authors: Erick Forno, Mudita Gogna, Alfonso Cepeda, Anahi Yañez, Dirceu Solé, Philip Cooper, Lydiana Avila, Manuel Soto-Quiros, Jose A Castro-Rodriguez, Juan C Celedón
Journal: Thorax (2015)

Consistent with the diversity of Latin America, there is profound variability in asthma burden among and within countries in this region. Regional variation in asthma prevalence is likely multifactorial and due to genetics, perinatal exposures, diet, obesity, tobacco use, indoor and outdoor pollutants, psychosocial stress and microbial or parasitic infections. Similarly, non-uniform progress in asthma management leads to regional variability in disease morbidity. Future studies of distinct asthma phenotypes should follow-up well-characterised Latin American subgroups and examine risk factors that are unique or common in Latin America (eg, stress and violence, parasitic infections and use of biomass fuels for cooking). Because most Latin American countries share the same barriers to asthma management, concerted and multifaceted public health and research efforts are needed, including approaches to curtail tobacco use, campaigns to improve asthma treatment, broadening access to care and clinical trials of non-pharmacological interventions (eg, replacing biomass fuels with gas or electric stoves).
Usefullness of noninvasive ventilation in patients with acute respiratory failure admitted in the intensive care unit (ICU) - Experience of a Portuguese ICU
Authors: Ana Castro, Pedro Moura, Aurora Cadeco
Journal: European Respiratory Journal (2012)

Introduction: Noninvasive ventilation(NIV) is a safe and effective mean of improving gas exchange in patients with many types of acute respiratory failure(ARF).

Study Design and Patient Selection: Retrospective observational study to access the usefulness of NIV in patients with ARF submitted to mechanical invasive ventilation(MIV) admitted to the ICU(Santa Luzia Hospital Viana do Castelo,Portugal).We enrolled adults with ARF admitted to the ICU in 2011.Patients were analyzed globally and in two subgroups: patients that received MIV and NIV and patients that received only MIV,recording various parameters, namely,comorbidities,diagnosis,SAPS II,APACHE II,presence of hypercapnia,pH, pCO2,MIV duration,number of days in the UCI and release condition.The two groups were compared by the Chi-square and Mann-Whitney tests.

Results: 104 patients were included, mainly admitted for pneumonia(52%),other causes of ARF(23%) and COPD exhacerbation/hypercapnic acidemia (HA)(13%). 22(21%)received MIV and NIV and92(79%) only MIV.When analized the differences between groups,was found statistical significant differences regarding the diagnosis(p=,002),presence of hypercapnia(p=,005),MIV time(p=,015) and number days in the ICU(p<,001),but no differences when compared comorbidities,SAPS II,APACHE II,nutricional status,social dependence or release condition.NIV was used in patients with HA(36%) and difficult weaning(63%).

Conclusion: NIV was effective in reducing the MIV time and number of days in the ICU probably because,in selected patients,it reduces the risk of ventilator-associated pneumonia,however no significant difference in mortality was observed.
Abstract P303: Low Albumin and Risk of Type 2 Diabetes
Authors: Lisa Rafalson, Leeann Cornelius, Michael LaMonte, Richard P Donahue
Journal: Circulation (2015)

Type 2 diabetes (T2DM) is a burdensome, costly and debilitating disease that causes premature morbidity and mortality. Recent evidence suggests that T2DM is in part an inflammatory disease. It is well known that serum albumin is a negative acute phase reactant, yet few studies have examined the association between albumin and risk of T2DM. The purpose of this analysis was to prospectively examine the association between serum albumin and incident type 2 diabetes in middle-aged and older adults from a defined population. The Western New York Health Study enrolled apparently healthy participants ages 35-79 yrs from Niagara and Erie counties, NY. For this report, at baseline (1996-2001) all participants from the Western New York Health Study had fasting plasma glucose &lt;110 mg/dl. At follow-up, six years later each case (n=61) was matched with up to three controls (n=158) on gender, race/ethnicity, the year of study enrollment, and baseline fasting glucose &lt;110 mg/dl or 110-125 mg/dl. Diabetes at follow-up was defined as: 1) fasting plasma glucose &gt; 125 mg/dl; 2) random glucose &gt;199 mg/dl; or 3) a physician diagnosis and receiving antidiabetic medication. Conditional logistic regression was used to estimate the odds ratio (95% CI) of developing type 2 diabetes by tertile of baseline albumin adjusted for the matching criteria and additional covariates including BMI, smoking and physical activity. Mean age was 58 years; 60% women; 93% White. Multivariate analyses indicated that cases had lower baseline albumin concentrations (OR = 0.41, 95%CI: 0.17, 0.99 (p=0.04; lowest tertile vs highest) (p trend &lt; 0.05). Further analyses indicated that this relation was independent of hs-CRP and IL-6. Stratification by smoking status did not alter the findings. The results of this analysis support the hypothesis that individuals with lower albumin concentrations were more likely to develop type 2 diabetes than those with higher levels.
Shifting the diagnosis and treatment of atherosclerosis to children and young adults: a new paradigm for the 21st century**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Sotirios Tsimikas, Joseph L Witztum
Journal: Journal of the American College of Cardiology (2002)
Unusual Presentations of Lung Cancer
Authors: Ekaphop Sirachainan, Gregory P. Kalemkerian
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.23.4598 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12454119 Unusual Presentations of Lung Cancer Case 2. Adrenal Insufficiency as the Initial Manifestation of Non-Small-Cell Lung Cancer Ekaphop SirachainanxEkaphop SirachainanSearch for articles by this author , Gregory P. KalemkerianxGregory P. KalemkerianSearch for articles by this author Show More University of Michigan, Ann Arbor, MI https://doi.org/10.1200/JCO.2002.20.23.4598 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Impact of high-risk classification by FISH on overall survival in myeloma: An Eastern Cooperative Oncology Group (ECOG) study E4A03.
Authors: S. J. Jacobus, S. A. Van Wier, G. J. Ahmann, K. J. Henderson, N. S. Callander, M. E. Williams, D. S. Siegel, P. R. Greipp, S. V. Rajkumar, R. Fonseca
Journal: Journal of Clinical Oncology (2010)

10546 Background: Risk stratification using fluorescent in situ hybridization (FISH) has proven valuable in multiple myeloma (MM). More specifically, three markers have been established as conferring adverse clinical outcome: t(4;14)(p16;q32), t(14;16)(q32,q23) and 17p13 deletion. In an era of novel therapies, however, the prognostic significance of these markers has been challenged. The objective of this study was to evaluate these markers in a group of newly diagnosed MM patients treated with lenalidomide and dexamethasone. Methods: On Eastern Cooperative Oncology Group study E4A03, pts in both arms received lenalidomide 25 mg/day PO days 1-21 every 28 days along with either high-dose (RD: 40 mg 12 days per cycle) or standard-dose dexamethasone (Rd: 40 mg 4 days per cycle). Pts enrolled optionally submitted samples for research studies. Patients were identified as high-risk (HR) if any of the three FISH markers, t(4;14), t(14;16) and 17p13 deletion, were present with the remaining pts standard-risk (SR). The distributions for overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods and compared using the logrank test. Cox proportional hazards models were used to estimate hazard ratios. Results: Interphase FISH was performed on n = 126 samples. Twenty-one patients (17%) were classified as HR. There was no substantial difference in proportions of pts: age ≥ 65, PS > 1, ISS stage III, RD, SCT. Median follow-up in this FISH cohort was 36 months; median OS has not been reached. The 2-year OS estimate was 89%. OS was shorter in the HR group, p = 0.004. 2-year OS estimates were 76% (HR) and 91% (SR). The hazard ratio was 3.5 (95%CI:1.4-8.5). Median PFS was 11 months (HR) and 29 months (SR), p = 0.047. Conclusions: This study further confirms the adverse impact of having genetic variants t(4;14), t(14;16) and/or 17p13 deletion at time of MM diagnosis. In a cohort of lenalidomide and dexamethasone treated patients, the classification of high-risk was significantly associated with shorter OS and PFS. Evidence of the value of FISH risk stratification for this limited panel over other expanded panels, platforms and clinical measures needs further exploration. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Celgene, Genzyme, Medtronic, Otsuka Celgene, Millennium Celgene, Onyx
Cycloserine Therapy in Pulmonary Tuberculosis
Authors: P D RABINOVICH, L A KUBLANOV
Journal: JAMA (1963)

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Should Microvolt T-Wave Alternans Be Utilized Routinely in Selecting Patients for Prophylactic Implantable Cardioverter-Defibrillator Insertion in the Setting of Ischemic Heart Disease?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Andrea M. Russo, Francis E. Marchlinski
Journal: Journal of the American College of Cardiology (2006)