tbuckley/cabot-search huggingface dataset:
Use of combined biomarkers analysis to predict response to chemotherapy in colorectal cancer: A single-institution feasibility study
Authors: J. Rodriguez-Pascual, E. Garcia, F. Lopez-Rios, A. Cubillo, I. Diaz-Padilla, O. Hernando, L. Ugidos, I. Calvo, I. Duran, M. Hidalgo
Journal: Journal of Clinical Oncology (2009)

11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the feasibility of developing an implementing a biomarker panel to guide treatment selection in this setting. Methods: Colorectal cancer tumors were prospectively analyzed with a predefined set of 11 molecular targets, including: KRas and PI3K mutations, EGFR amplification (FISH), and ERCC-1, TS, TP expression by IHC. Clinical characteristics and response to chemotherapy were registered. To establish the utility of this panel, we determine as congruent-treatment if the panel predict the best treatment in patients with more of 1 chemotherapy line and no-congruent-treatment if do not. Results: A total of 84 patients were studied. Only 6 % required a repeated biopsy to obtain sufficient tumor for marker analysis. In 81 % of patients was feasible to study almost 8/11 targets. There were 29 pts (39%) with KRas mutant CRC; 3 pts with PI3K mutations (4%, all of them with KRas mutation); and 2 patients with EGFR amplification. ERCC-1 was positive in 5/78 (6.4%) and TS was positive in 47%. None of 54 pts had TP positivity. Clinical floow up was available in 66 pts (44 males, median age 59, 93% ECOG 0–1). Nineteen patients had early CRC; 23 with metastatic CRC treated with a first line chemotherapy and 24 with advanced CRC treated with 2 or more prior regimens. In this last group for whom the response to multiple agents is known, the panel predictive the most effective treatment in 14 of 24 cases. Conclusions: This targeted-therapy-panel is feasible to implement and should be explore to predict treatment response to CRC . No significant financial relationships to disclose.
RAGE ligand S100A8/A9 as a novel prognostic biomarker for high-risk melanoma patients.
Authors: Christoffer Gebhardt, Nikolaus B. Wagner, Benjamin Weide, Ramtin Lichtenberger, Maike Reith, Kathrin Tarnanidis, Johannes Ridinger, Kristian Ikenberg, Annette Pflugfelder, Christian Busch, Tim Holland-Letz, Helmut Naeher, Claus Garbe, Viktor Umansky, Alexander Enk, Jochen Utikal
Journal: Journal of Clinical Oncology (2014)

9070 Background: We have recently demonstrated that the receptor for advanced glycation end-products (RAGE) is a central driver of tumorigenesis by sustaining a chronic inflammatory tumor microenvironment. This study aimed at identifying novel prognostic biomarkers for melanoma by a hypothesis-driven approach linking RAGE signaling-related serum markers with clinical outcome of melanoma patients. Methods: Plasma concentrations of the soluble form of RAGE (sRAGE) were analyzed in 173 plasma samples of stage I-IV melanoma patients (cohort 1). Serum concentration of RAGE-related markers sRAGE, S100B, S100A8/A9, and HMGB1 were measured in an independent second cohort of 240 metastasized stage III-IV patients and compared to established prognostic markers including sub-stage and lactate dehydrogenase (LDH). All analyses were performed by enzyme-linked immunosorbent assays. Results: sRAGE was strongly associated with overall survival (OS) and progression-free survival (PFS) in cohort 1. A detailed analysis of different RAGE-related serum markers was thereafter performed in cohort 2. Analysis of OS of stage III patients showed that elevated S100A8/A9 independently increased mortal risk in addition to sub-stage IIIB or sub-stage IIIC as compared to sub-stage IIIA. Increased S100B, S100A8/A9, and HMGB1 were independently indicating worse PFS in stage III/IV patients. The analysis of S100A8/A9 and S100B was the best combination to predict PFS and improved the sensitivity to identify patients with later progression from 34.2% (S100B) to 58.2% (S100A8/A9 + S100B). Conclusions: The RAGE ligand S100A8/A9 is a powerful independent prognostic marker for OS of stage III patients and contributes substantially to standard biomarker S100B for the identification of patients with high risk for progression.
THE HIGH COST OF LOW ACUITY NON ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME ADMISSIONS TO THE CORONARY CARE UNIT: AN ANALYSIS OF NATIONAL POPULATION HEALTH DATA
Authors: Sean Van Diepen, Dat Tran, Justin Ezekowitz, David Zygun, Jason Katz, Renato Lopes, L. Kristin Newby, Finlay McAlister, Padma Kaul
Journal: Journal of the American College of Cardiology (2017)
PREDICTORS OF LONG-TERM RESOURCE UTILIZATION AFTER INCIDENT PERCUTANEOUS CORONARY INTERVENTION
Authors: Matthew D. Solomon, Thomas Leong, Sue Hee Sung, Alda Inveiss, John B. Hernandez, Roseann M. White, Michelle P. Sosa, Jamal Rana, Edward McNulty, Alan S. Go
Journal: Journal of the American College of Cardiology (2017)
Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements
Authors: Edward L. Korn, Boris Freidlin
Journal: JNCI Journal of the National Cancer Institute (2017)

There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues.
High-Dose Cytarabine-Based Consolidation Shows Superior Results for Elderly AML Patients with Intermediate Risk Cytogenetics in First Complete Remission
Authors: Mona Fawzy Ramadan Hassanein, Eshetu G Atenafu, Vikas Gupta, Andre C. Schuh, Karen Yee, Mark D. Minden, Aaron D Schimmer, Joseph M. Brandwein
Journal: Blood (2012)
ACCELERATOR 2 SUSTAIN, A U.S. REGIONAL SYSTEMS OF CARE DEMONSTRATION PROJECT FOR POST-DISCHARGE STEMI PATIENTS: PRELIMINARY DATA, METHODS AND DESIGN
Authors: Ajar Kochar, Christopher Fordyce, Lisa Monk, Hussein Al-Khalidi, Mayme Roettig, James Jollis, Christopher Granger, Bradi Granger
Journal: Journal of the American College of Cardiology (2017)
SINUS RHYTHM VERSUS ATRIAL FIBRILLATION &amp; IT CLINICAL PROFILE AND NATURAL HISTORY OF PATIENTS WITH SEVERE AORTIC STENOSIS MANAGED MEDICALLY
Authors: Hongju Janet Zhang, Jeremy Thaden, Sorin Pislaru, Christopher Scott, Chayakrit Krittanawong, Rowlens Melduni, Robert McCully, Maurice Enriquez-Sarano, Jae K. Oh, Patricia Pellikka, Vuyisile Nkomo
Journal: Journal of the American College of Cardiology (2017)
ADVANCED ANALYTICS PREDICTED OUTCOMES, IDENTIFIED CLINICALLY DISTINCT SUBGROUPS, AND DETECTED HETEROGENEITY IN RESPONSE TO THERAPY IN A COHORT OF MORE THAN 40,000 HEART FAILURE PATIENTS
Authors: Tariq Ahmad, Pooja Rao, Lars Lund, Prashant Warrier, Ghosh Rohit, Nihar Desai
Journal: Journal of the American College of Cardiology (2017)
<i>JAMA Pediatrics</i> 2016 Year in Review
Authors: Frederick P. Rivara
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Discovery of new potentially actionable mutations in pancreatic ductal adenocarcinoma by next generation sequencing.
Authors: Mariacristina Di Marco, Sandra Durante, Silvia Vecchiarelli, Elisa Grassi, Andrea Palloni, Valentina Indio, Annalisa Astolfi, Riccardo Panzacchi, Donatella Santini, Riccardo Casadei, Claudio Ricci, Giovanni Taffurelli, Giorgio Ercolani, Nico Pagano, Lucia Calculli, Carla Serra, Francesco Minni, Antonio Daniele Pinna, Maria A. Pantaleo, Guido Biasco
Journal: Journal of Clinical Oncology (2015)

4127 Background: Advances in chemotherapy, represented by FOLFIRINOX and Gemcitabine plus Nab-paclitaxel regimens, have resulted in a modest outcome improvement and Gamcitabine-based chemotherapy remains the treatment of choice especially in metastatic disease. Therefore, there is an urgent need to develop accurate markers of pre-invasive pancreatic neoplasms in order to help disease diagnosis at an earlier stage and to apply the best treatment. We aimed to better understand PDAC biology and genomic alterations of invasive phenotype by whole genome sequencing (RNAseq and WES). Methods: We analyzed 27 PDAC samples together with their normal counterpart by HiScanSQ Illumina platform (15/27 by RNASeq and 12/27 by WES). All data were mapped with BWA on hg19, SNVs were called with either SNVMix2 (RNA-seq) or MuTect (WES) while Indels were called with GATK. All variants were filtered on dbSNP, 1000genomes and compared with Cosmic data base. Non-synonymous SNVs were analyzed with PROVEAN and SIFT to predict mutation effect on protein function. Results: Deleterious point mutations or Indels were found in KRAS (92%), TP53 (63%), SMAD4 (48%), and CDKN2A (52%) genes. Components of mTOR signaling pathway (PTEN, MTOR, PIK3IP1) were found mutated in 50% of patients with poor prognosis PDAC suggesting that mTOR signaling alterations might promote the development of metastatic PDACs. Furthermore, we found inactivating mutations in PARP and ATM genes (26%), that could confer sensitivity to DNA cross-linking agents and to poly(ADP-ribose) polymerase inhibitors. Moreover, it has been elsewhere reported that ATM mutant neoplasms may be more sensitive to PARP and protein DNA-PKcs inhibitors. Conclusions: Our results demonstrated that PDACs are tumors harboring an high number of mutations. Beyond conventional mutated genes, we identified shared mutations in mTOR signaling components as well as PARP and ATM genes. These are potentially targetable mutations. In particular, mTOR signaling inhibition is a promising strategy to increase the therapeutic efficacy of conventional chemotherapeutic drugs. In conclusion, our results provide novel insights into PDACs target therapy.
Phase II study of BAY 73–4506, a multikinase inhibitor, in previously untreated patients with metastatic or unresectable renal cell cancer
Authors: T. Eisen, H. Joensuu, P. Nathan, P. Harper, M. Wojtukiewicz, S. Nicholson, A. Bahl, P. Tomczak, A. Wagner, D. Quinn
Journal: Journal of Clinical Oncology (2009)

5033 Background: BAY 73–4506 is an orally active, potent multikinase inhibitor targeting both tumor cell proliferation and tumor vasculature through inhibition of receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR, and PDGFR) and serine/threonine kinases (RAF and p38MAPK). In tumor xenograft models, BAY 73–4506 demonstrated a broad spectrum of antitumor activity. The results of a phase I study (3 weeks on/1 week off schedule) indicated good tolerability and antitumor activity, including objective responses. Methods: Previously untreated patients with predominantly clear cell renal cell carcinoma (RCC) and measurable disease according to RECIST were enrolled in this multicenter, open-label, phase II study. Eligibility criteria included ECOG performance status 0–1, low or intermediate risk as per Motzer score, and adequate bone marrow and organ function. Treatment consisted of BAY 73–4506 160 mg once daily on a 3 weeks on/1 week off schedule. The primary end point was overall response rate. Results: 49 patients started treatment (accrual completed October 2008): 27 male, 22 female, median age 62 years (range 40–76). All patients were evaluable for safety, 33 patients are currently available for efficacy evaluation. The most common drug-related adverse events (all grades) reported in &gt;20% of patients were hand-foot skin reaction (HFSR) (48%), fatigue (48%), hypertension (43%), mucositis (35%), dysphonia (33%), rash (30%), diarrhea (25%), and anorexia (23%). Grade 3–4 drug related toxicities (in &gt;5% of patients) included HFSR (13%), rash (8%), fatigue (8%), and renal failure (8%). Renal failure occurred only in patients who continued taking study medication despite having inadequate fluid intake and/or diarrhea. Preliminary efficacy data of the 33 patients evaluable for response show a 27% partial response (PR) and a 42% stable disease (SD) rate. Further tumor assessments are scheduled for the patients (n = 35) remaining on study. Conclusions: Preliminary data show promising antitumor activity and good tolerability of BAY 73–4506 in patients with RCC. The observed toxicities were typical of the drug class and were manageable. Updated results will be presented at the meeting. [Table: see text]
WHAT IS THE IMPORTANCE OF PREOPERATIVE ELECTROCARDIOGRAM IN HYPERTENSIVE PATIENTS FOR MODERATE/HIGH RISK NONCARDIAC SURGERY? A SINGLE-CENTER RANDOMIZED STUDY
Authors: Lafayete W.F. Ramos, Bárbara Cristina, Cristiano Souza, Marcos Vinicius Ferreira, Elly Eliane, Marcelo Calil, João Goes
Journal: Journal of the American College of Cardiology (2017)
COST-EFFECTIVENESS OF INTENSIVE BLOOD PRESSURE GOALS IN PATIENTS WITH PRIOR CARDIOVASCULAR DISEASE
Authors: Jordan King, Brandon Bellows, Adam Bress, Natalia Ruiz-Negrón, Rachel Hess, Srinivasan Beddhu, Zugui Zhang, Dan Berlowitz, Andrew Moran, William Weintraub
Journal: Journal of the American College of Cardiology (2017)
A phase II randomized, double-blind, placebo-controlled multicenter trial evaluating the efficacy and safety of enzalutamide in combination with exemestane in estrogen or progesterone receptor-positive and HER2-normal advanced breast cancer.
Authors: Denise A. Yardley, Ahmad Awada, Javier Cortes, Howard A. Burris, Amy C. Peterson, Iulia Cristina Tudor, Shanna Stopatschinskaja, Joyce Leta Steinberg, Luca Gianni, Kathy D. Miller, Eric P. Winer
Journal: Journal of Clinical Oncology (2014)

TPS653 Background: The androgen receptor (AR) is expressed in the majority of patients (pts) with ER/PgR+ breast cancer (BC)(Collins LC et al. Mod Pathol. 2011;24:924–931; Loibl S et al. Breast Cancer Res Treat. 2011;130:477–487). In ER+ cell lines, AR over-expression can lead to hormone-resistance (De Amicis F et al. Breast Cancer Res Treat. 2010;121:1-11). Androgen stimulated growth of ER+/AR+ cells lines can be blocked by enzalutamide (ENZA), a potent oral inhibitor of AR. Treatment with exemestane (EXE) can increase androgen levels (Takagi K, et al. Endocr Relat Cancer. 2010;17:415–430), the addition of ENZA to EXE may inhibit any androgen-mediated breast tumor growth. Methods: This randomized placebo (PBO) controlled phase 2 trial will evaluate EXE with or without ENZA (160 mg/day) in 240 patients (pts) with advanced BC (aBC) that is ER/PgR+ and Her2 normal (NCT02007512). Two parallel enrolling cohorts (C) will each evaluate 120 pts who have received either no (C1) or 1 (C2) prior hormone therapy for aBC. Randomization (1:1) is stratified (Y/N) by prior hormone, prior aromatase inhibitor (AI) and hormone resistance. Eligible pts must have ≤ 1 non-hormone regimen and ECOG ≤1; non-measurable bone or skin disease is allowed. Pts with CNS disease or history of seizure are excluded. Tissue submission for determination of AR expression is mandatory. The co-primary endpoint (EP) is progression-free survival (PFS) in all pts and in those with AR+ disease. Cross-over is allowed following RECIST 1.1 progression. Additional EPs include clinical benefit rate (complete/partial response or stable disease at ≥24 weeks); response rate; duration and time to response, safety and tolerability. Efficacy analyses will be conducted on all randomized pts (ITT), a minimum of 90 PFS events/cohort is required to estimate the median PFS and hazard ratio. Approximately 55 PFS events, for a target HR = 0.67, are required in the AR+ subset. The definition of “AR+” will be determined prior to unblinding. Clinical trial information: NCT02007512.
FIBROBLAST GROWTH FACTOR 23 AS NOVEL BIOMARKER FOR EARLY RISK STRATIFICATION AFTER ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Martin Reindl, Sebastian Reinstadler, Hans-Josef Feistritzer, Lukas Mueller, Constantin Koch, Agnes Mayr, Markus Theurl, Rudolf Kirchmair, Gert Klug, Bernhard Metzler
Journal: Journal of the American College of Cardiology (2017)
Incorporation of Molecular Data into the Current Prognostic Models in Treated Patients with Myelodysplastic Syndromes: Which Model Is the Best
Authors: Karam Al-Issa, Ahmad Zarzour, Tomas Radivoyevitch, Matt Kalaycio, Betty K. Hamilton, Aaron T. Gerds, Sudipto Mukherjee, Vera Adema, Michael J. Clemente, Bhumika Patel, Cassandra M. Hirsch, Anjali S. Advani, Bartlomiej P Przychodzen, Hetty E. Carraway, Jaroslaw P Maciejewski, Mikkael A. Sekeres, Aziz Nazha
Journal: Blood (2016)
VENO-ARTERIAL ECMO PROGRAM FOR REFRACTORY CARDIOGENIC SHOCK IN THE CARDIAC INTENSIVE CARE UNIT: FEASIBILITY AND OUTCOME DATA AT A LARGE TERTIARY ACADEMIC CENTER
Authors: Carlos Leon Alviar, Alejandra Gutierrez, Terence Hill, Amar Krishnaswamy, Deborah Klein, Nader Moazami, Venu Menon
Journal: Journal of the American College of Cardiology (2017)
IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro
Authors: Marie-Astrid Boutet, Aurélie Najm, Géraldine Bart, Régis Brion, Sophie Touchais, Valérie Trichet, Pierre Layrolle, Cem Gabay, Gaby Palmer, Frédéric Blanchard, Benoit Le Goff
Journal: Annals of the Rheumatic Diseases (2017)

Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro.Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38.Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA.This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.
Screening a library of FDA-approved drugs identifies agents that induce lytic viral infection in EBV-associated tumors
Authors: J. Chen, C. Chong, W. Hsieh, D. Fu, V. Lemas, J. O. Liu, R. F. Ambinder
Journal: Journal of Clinical Oncology (2006)

2002 Background: Epstein-Barr virus (EBV) is associated with a variety of tumors including AIDS lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma and Hodgkin’s lymphoma. We hypothesized that drugs used in practice might alter viral gene expression in tumor cells in ways that might be important to understand. For example induction of lytic viral gene expression leads to expression of immunodominant CD8 T cell antigens and expression of the viral thymidine kinase (which phosphorylates ganciclovir and other nucleotide analogues). Methods: A library of FDA-approved drugs that includes 2720 agents was screened to identify those that upregulated EBV lytic gene expression. The screen involved a Burkitt’s cell line with a recombinant GFP-EBV that assayed the impact of agents on replication of the complete viral genome, and assay of a lytic promoter reporter construct. Results: The assay identified 146 agents in the whole virus replication assay, 195 agents in the promoter assay, and 54 agents that were active in both assays. Agents with activity could be grouped into 4 families: anti-tubulin drugs, glucocorticoid and other steroid hormones, DNA damaging agents and nucleotide analogues (including cytarabine and gemcitabine), and the proteasome inhibitor bortezomib. Anti-tubulin drugs and nucleotide analogues were less active in thes whole virus assay than the promoter assay whereas bortezomib showed similar activity in both assays. Followup studies confirmed that bortezomib is a potent viral lytic activator that increases expression of the viral thymidine kinase and virion production in several different Burkitt’s lymphoma and primary effusion lymphoma cell lines. Although bortezomib decreases NFKB levels, in vitro investigations with an IKB repressor suggests that inhibition of NFKB alone does not account for lytic activation. Conclusions: Many cancer chemotherapeutic agents are upregulators of EBV lytic expression. Bortezomib is among the most potent. As strategies for using lytic induction therapeutically evolve, these agents may have an important role to play. No significant financial relationships to disclose.