tbuckley/cabot-search huggingface dataset:
Circulating pretreatment Epstein Barr Virus DNA quantification as a prognostic factor in nasopharyngeal cancer patients in a non endemic area.
Authors: Salvatore Alfieri, Carlo Resteghini, Laura Pala, Sara Marceglia, Nicola Alessandro Iacovelli, Ester Orlandi, Annunziata Gloghini, Giovanni Pietro Gesu, Diana Fanti, Sara Racca, Roee Dvir, Daniele Morelli, Francesca Taverna, Pasquale Quattrone, Cristiana Bergamini, Roberta Granata, Maria Chiara Cau, Laura D. Locati, Lisa F. Licitra, Paolo Bossi
Journal: Journal of Clinical Oncology (2015)

e17054 Background: The value of plasma Epstein Barr Virus (EBV) DNA viral load in nasopharyngeal cancer (NPC) patients before treatment correlates with tumor stage and outcome in endemic areas. The aim of our analysis is to explore the role of EBV DNA in a non-endemic setting where just few experiences have been reported. Methods: The medical records of all the patients with positive EBV encoded RNA (EBER) NPC, treated in our institution from 2006 to 2014 with chemotherapy (CT) concurrent with radiation (RT), were retrospectively evaluated. Information about the known prognostic factors, as established in NPC endemic areas, were collected, as well as pretreatment plasma EBV DNA viral load, detected and quantified by real-time PCR. Results: A total of 134 patients were evaluated (median age 48 years; M:F ratio 2:1; stage II 13%, III 31%, IV 56%). Neo-adjuvant CT (TPF scheme) was administered to 78% of the patients. Platinum based CT was delivered concurrently with RT. At a median follow up of 41 months, 25 patients (19%) experienced locoregional and/or distant recurrence and 70% of them died. Overall, pretreatment plasma EBV DNA was detected in 97 patients (72%), with median viral load of 544 cp/mL (range 50 - 1.5x105 cp/mL), and showed a significant positive correlation with T stage (p = 0.02), N3a stage (p = 0.045) and a negative correlation with previous neck surgery (p = 0.03). Progression-Free Survival (PFS) was significantly longer in patients with pretreatment negative EBV DNA value than in positive ones (56 vs 26.5 months, p = 0.014). A relationship between higher EBV DNA viral load and risk for distant metastasis was marginally noted (p = 0.06). Conclusions: In a non endemic area, pretreatment plasma EBV DNA was present only in 72% of the EBER positive NPC patients, lower than what reported in endemic areas (87-100%). Patients with negative pretreatment EBV DNA had a significant better prognosis in terms of PFS, while EBV DNA viral load correlated with tumor burden (T and N3a stage). The value of EBV-DNA as reliable prognostic biomarker of PFS in NPC in non-endemic areas needs to be confirmed in larger series
Serum interleukin-8 and its relationship to tumor burden and treatment response across malignancies of multiple tissue origins.
Authors: Miguel F. Sanmamed, Omar Carranza-Rua, Carlos Alfaro, Carmen Oñate, Salvador Martin-Algarra, Guiomar Perez, Sara Fernandez-Landazuri, Alvaro Gonzalez, Stefanie Gross, Inmaculada Rodriguez, Cecilia Muñoz-Calleja, María Rodriguez, Bruno Sangro, José María López-Picazo, Jose Luis Perez-Gracia, Ignacio Melero
Journal: Journal of Clinical Oncology (2014)

e22135 Background: IL-8 is a chemokine that is produced by malignant cells of multiple cancer types and that exerts various functions in shaping pro-tumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL-8 in preclinical tumor models and in patients with multiple tumor types, at baseline and following anticancer treatment to assess its ability to estimate tumor burden. Methods: IL-8 levels were monitored by sandwich ELISAs in cultured tumor cell supernatant, tumor-xenografted mice serum and in 119 cancer patients’ serum and urine samples, at baseline and following anticancer treatments. We correlated IL-8 levels with baseline tumor burden and with treatment induced changes in tumor burden, as well as with cancer prognosis. Results: IL-8 concentrations correlated with the number of IL-8 producing tumor cells in culture. In xenografted neoplasms, IL-8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma, renal cell carcinoma, non small cell lung cancer or hepatocellular carcinoma, serum IL-8 concentrations correlated with tumor burden and stage, survival and objective responses to therapy, including those to BRAF inhibitors and immunoregulatory antibodies. IL-8 concentrations in urine were mainly elevated in tumors with direct contact with the urinary tract. Conclusions: IL-8 levels correlate with tumor burden in preclinical models and in cancer patients. IL-8 is a potentially useful biomarker to monitor changes in tumor burden following anticancer therapy, and has prognostic significance.
SHORT- AND MID-TERM OUTCOMES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH RENAL INSUFFICIENCY NOT ON HEMODIALYSIS
Authors: Darien Paone, Binita Shah, Daniel McDonald, Rahul Thakker, Pascale Houanche, Peter Neuburger, Muhamed Saric, Cezar Staniloae, Hasan Jilaihawi, Michael Querijero, Mathew Williams
Journal: Journal of the American College of Cardiology (2017)
Lung cancer patients with HER2 mutations treated with chemotherapy and HER2 targeted drugs: Results form the EUHER2 cohort study.
Authors: Julien Mazières, Fabrice Barlesi, Thomas Filleron, Benjamin Besse, Isabelle Monnet, Michele Beau-Faller, Solange Peters, Eric Dansin, Martin Frueh, Miklos Pless, Niki Karachaliou, Marie Wislez, Pierre Fournel, Virginie Westeel, Federico Cappuzzo, Alexis B. Cortot, Denis Moro-Sibilot, Julie Milia, Oliver Gautschi
Journal: Journal of Clinical Oncology (2015)

11076 Background: HER2 mutations are identified in about 2% of non-small cell lung cancer (NSCLC) and behave as an oncogenic driver. Little is known about the efficacy of chemotherapy and of HER2 targeted drugs in this population. We aimed to study therapeutic outcomes of patients harboring HER2 mutations (HER2+) in order to establish the efficacy of various drug regimens and to orient future clinical trials. Methods: We conducted a retrospective cohort study in European centers testing NSCLC patients for HER2. Eligible patients had advanced stage NSCLC, known HER2 exon 20 insertions by local testing, and treatment with chemotherapy and/or targeted drugs. Clinicians had to obtain informed consent and IRB approval according to local regulations, and response were assessed according to RECIST version 1.1. Data were anonymized and analyzed centrally. Results: We identified 101 eligible patients from 38 centers. Our population was characterized by a median age of 61 yrs (30-87), a high proportion of women (63 vs. 38 men, 62.4%), and of never smokers (61, 60.4%). All tumors were adenocarcinomas. Concomitant EGFR mutation, ALK translocation and ROS translocation were observed in 5, 1 and 1 patients respectively. The median number of treatment lines was 3 (1-11). Overall survival of the whole population (n = 101) was 24 months (m.). Response rate (RR) and median progression free survival (PFS) for patients treated with conventional chemotherapy (excluding targeted therapy) were 43.5% and 5.9 m. in first line (n = 93) and 10% and 4.2 m. in second line (n = 52) respectively. RR to EGFR-TKI (n = 27) was 7.2% and PFS was 3 m. Eighty-six targeted treatments against HER2 were given to 65 patients including trastuzumab (n = 57), neratinib (n = 14), afatinib (n = 9), lapatinib (n = 5) and T-DM1 (n = 1). RR was 18% and PFS 3.9 months for afatinib. RR was 50% and PFS 5.1 m. for trastuzumab (given with vinorelbine n = 24, docetaxel n = 12, paclitaxel n = 12, cisplatinum based combination n = 7, alone n = 2). Conclusions: This series, the largest to date, underlines the chemosensitivity of HER2 + NSCLC and the potential interest of anti-HER2-antibodies that deserve to be further evaluated in clinical trials.
VOLUMETRIC QUANTIFICATION OF REGURGITANT VOLUME IN ASYMPTOMATIC SEVERE DEGENERATIVE MITRAL REGURGITATION BY ECHOCARDIOGRAPHY AND CARDIAC MRI WITH INDEPENDENT VALIDATION OF FORWARD STROKE VOLUME BY POSITRON EMISSION TOMOGRAPHY
Authors: Tomasz Baron, Lovisa Holm Orndahl, Tanja Kero, Jens Sorensen, Tomas Bjerner, Eva-Maria Hedin, Elisabeth Stahle, Frank Flachskampf
Journal: Journal of the American College of Cardiology (2017)
INCREASED RATE OF PREVIOUS STROKE IN ASYMPTOMATIC/MINIMALLY SYMPTOMATIC VERSUS SYMPTOMATIC PATIENTS WITH NEWLY DETECTED ATRIAL FIBRILLATION WORLDWIDE: RESULTS FROM THE GLORIA-AF REGISTRY
Authors: Steffen Christow, Karlheinz Seidl, Hans-Christoph Diener, Menno Huisman, Gregory Lip, Ursula Rauch-Kroenert, Stefan Schuster, Johannes Brachmann, Andreas Muegge, Peter Schwimmbeck, Christine Teutsch, Jochen Senges
Journal: Journal of the American College of Cardiology (2017)
Weekly paclitaxel followed by 24 hour infusion high-dose 5-fluorouracil and leucovorin (T-HDFL) chemotherapy for hormone-refractory prostate cancer (HRPC)
Authors: C.-C. Lin, C.-H. Hsu, A.-L. Cheng, J.-Y. Guan, C.-Y. Huang, J. Chen, Y.-S. Pu
Journal: Journal of Clinical Oncology (2004)

4738 Background: Paclitaxel (T) & 5FU had been used to treat advanced prostate cancer with some success. In vitro data suggested T & 5FU had sequence-dependent synergistic cytotoxicity on many cancer cell lines. Weekly T & HDFL had been proven to be more tolerable & at least equally effective in many kinds of cancers. We generalized this observation to a phase II trial for patients with HRPC. Methods: (1) The cytotoxicity of T & 5FU alone or in combination with different schedules was studied in 2 androgen-independent CaP cell lines: DU145 & PC3, using MTT assay & median-effect analysis. (2) T-HDFL regimen: paclitaxel 90 mg/m2 IV 1hr on D 1, 8; 5FU 2,000 mg/m2 & leucovorin 300 mg/m2 IV 24 hr on D 2, 9; q 21 days. Premeds including dexamethasone 5 mg were given before T. Between Nov 1999 & Dec 2003, 18 patients (median age 71, range 50–75) with HRPC who had failed multiple lines of hormone manipulation (castration, use and withdrawal of anti-androgens) were enrolled. Two had measurable diseases, 16 had only bone metastasis, & 17 had elevated PSA levels (median 227 ng/ml, range 97 – 2,329). Results: (1) Combined cytotoxicity was more synergistic when T –> 5FU 24 hr later & was less synergistic when 5FU –> T. It was noted in both PC3 & DU145. (2) 52 courses had been given totally, with an average of 2.9 courses / pt (range: 1–8). All 18 pts were eligible for analysis of toxicity. NCI Gr 3/4 leukopenia & thrombocytopenia occurred in 3 pts each. There were neither febrile neutropenia nor treatment-related mortality. Gr 3/4 nausea, vomiting, mucositis, & diarrhea did not occur. One partial response & 1 stable disease were found among the 2 pts with measurable diseases. Sixteen pts were eligible for evaluation of PSA response (PSA reduction >50% for at least 6 weeks) with 7 responders & 2 pts with obvious PSA progression. The PSA response rate was 44% (95% CI 19 – 69%). The median overall & progression-free survival had not been reached. Analgesic amount decreased or PS enhanced in 78% of pts. Conclusions: T –> 5FU 24 hours later is the most synergistic sequence. T-HDFL with a much lower toxicity profile is worth further testing to define its role in HRPC. No significant financial relationships to disclose.
CIRCULATING CONCENTRATIONS OF OREXIN A ARE ASSOCIATED WITH LEFT VENTRICULAR REVERSE REMODELING AND CLINICAL OUTCOMES FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY
Authors: Neal Chatterjee, Nasrien Ibrahim, Timothy Maher, Alberto Aimo, Jackie Szymonifka, Hanna Gaggin, Quynh Truong, Jagmeet Singh, Petr Jarolim, James Januzzi
Journal: Journal of the American College of Cardiology (2017)
Abstract P2-01-27: Sentinel lymph node biopsy by contrast-enhanced ultrasonography with sonazoid in patients with breast cancer - Prospective multicenter study
Authors: K Shimazu, T Ito, K Uji, T Miyake, K Motomura, S Noguchi
Journal: Cancer Research (2017)

Abstract Background: The aim of this prospective study is to evaluate feasibility of the periareolar injection of contrast agent (Sonazoid (SNZ)) followed by ultrasonography (US) for identification of sentinel lymph node (SLN) in breast cancer patients with clinically negative node. Patients and Methods: Patients with T1-2N0M0 breast cancer were recruited in this study. They received the periareolar injection of SNZ followed by US to identify contrast-enhanced SLN. Fine needle aspiration biopsy (FNAB) was done for each CE-SLN. Then, they underwent SLN biopsy with the conventional method, blue dye and/or radiotracer (B/R). Results: In almost all cases, contrast-enhanced lymphatic vessels were clearly visualized US soon after the periareolar injection of SNZ, and SLN, into which lymphatic flow was draining, was easily identified. The identification rate of SLN was 98% (98/100) by SNZ and 100% (100/100) by B/R. The number of SLNs identified by SNZ (mean per patient, 1.52) was significantly (P &amp;lt; 0.001) lower than that of those by B/R (2.22). Twenty-five patients had at least one metastasis in the SLNs identified by SNZ and/or B/R. In these patients, SLNs (n=39) identified by both SNZ and B/R showed a significantly (P &amp;lt; 0.0001) higher positivity (74.4%) for metastases than those (n=19) identified by B/R alone (21.1%). Conclusion: Identification of SLN by periareolar injection of SNZ followed by US is a technically easy method and the identification rate of SLN was as high as 98%, being comparable to the conventional B/R. SLNs detected by SNZ seem to represent the true SLNs which first receive lymphatic flow from the tumor among the SLNs detected by B/R. Citation Format: Shimazu K, Ito T, Uji K, Miyake T, Motomura K, Noguchi S. Sentinel lymph node biopsy by contrast-enhanced ultrasonography with sonazoid in patients with breast cancer - Prospective multicenter study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-27.
Proteomic analysis of primary and metastatic breast cancers and expression of the folate receptor as a potential drug target.
Authors: Todd A. Hembrough, Fabiola Cecchi, Adele Blackler, Sheeno P Thyparambil, Jon Burrows, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2015)

1045 Background: The folate pathway is a critical nucleotide biosynthetic pathway in many tumor cells, and blockade of this pathway with antifolates has demonstrated clinical utility in NSCLC and mesothelioma. The folate receptor alpha (FRa) is reported to be highly expressed in triple negative breast cancer (TNBC). However, targeting this pathway with pemetrexed in metastatic breast cancer (MBC) has been a modest success (~20% response rate in unselected patients). We used multiplexed mass spectrometry (MS) to assess the expression of the FRa and other biomarkers in TNBC to identify patients who may be responsive to antifolate therapy. Methods: In our clinical lab, primary and metastatic BC tissues were microdissected, solubilized and enzymatically digested following CAP/CLIA guidelines. Archival BC tissues (n = 270) were analyzed following GLP protocols. Absolute quantitation of protein targets was performed using selected reaction monitoring (SRM) mass spectrometry Results: Using quantitative proteomic analysis, we found that ~40% of TNBC tumors express high levels of FRa. In contrast, among 247 hormone receptor-positive and HER2-positive tumors, only 8% expressed FRa. FRa showed a 10-fold range of expression in both sample sets; a range that is most likely indiscernible by IHC. Correlation analysis between FRa and several other markers of chemotherapy sensitivity in the TNBCs showed only weak correlations suggesting that the FRa pathway is not influenced by other known pathways. Conclusions: Multiplex MS data confirm that FRa expression is more common in TNBC than other BC subtypes, and demonstrate that there is a wide dynamic range of FRa expression Further analyses are warranted to identify a cutoff which predicts for antitumor activity of antifolate drugs. Proteomic screening should be performed to identify TNBCs which highly overexpress FRa to enrich for a population most likely to benefit from antifolate therapy. Prospective evaluation of pemetrexed and other FRa-targeted agents is warranted in metastatic TNBC pts whose cancers express high levels of FRa.
Adrenergic Signaling Strengthens Cardiac Myocyte Cohesion
Authors: Camilla Schinner, Franziska Vielmuth, Vera Rötzer, Matthias Hiermaier, Mariya Y. Radeva, Thu Kim Co, Eva Hartlieb, Andreas Schmidt, Axel Imhof, Ahmed Messoudi, Anja Horn, Angela Schlipp, Volker Spindler, Jens Waschke
Journal: Circulation Research (2017)

The sympathetic nervous system is a major mediator of heart function. Intercalated discs composed of desmosomes, adherens junctions, and gap junctions provide the structural backbone for coordinated contraction of cardiac myocytes.Gap junctions dynamically remodel to adapt to sympathetic signaling. However, it is unknown whether such rapid adaption also occurs for the adhesive function provided by desmosomes and adherens junctions.Atomic force microscopy revealed that β-adrenergic signaling enhances both the number of desmoglein 2-specific interactions along cell junctions and the mean desmoglein 2-mediated binding forces, whereas N-cadherin-mediated interactions were not affected. This was accompanied by increased cell cohesion in cardiac myocyte cultures and murine heart slices. Enhanced desmoglein 2-positive contacts and increased junction length as revealed by immunofluorescence and electron microscopy reflected cAMP-induced reorganization of intercellular contacts. The mechanism underlying cAMP-mediated strengthening of desmoglein 2 binding was dependent on expression of the intercalated disc plaque protein plakoglobin (Pg) and direct phosphorylation at S665 by protein kinase A: Pg deficiency as well as overexpression of the phospho-deficient Pg-mutant S665A abrogated both cAMP-mediated junctional remodeling and increase of cohesion. Moreover, Pg knockout hearts failed to functionally adapt to adrenergic stimulation.Taken together, we provide first evidence for positive adhesiotropy as a new cardiac function of sympathetic signaling. Positive adhesiotropy is dependent on Pg phosphorylation at S665 by protein kinase A. This mechanism may be of high medical relevance because loss of junctional Pg is a hallmark of arrhythmogenic cardiomyopathy.
LATE OCCURRENCE OF PHRENIC NERVE STIMULATION: A POTENTIAL PITFALL AMONG SUPER RESPONDERS?
Authors: Justo Julia Calvo, Maria Lopez-Gil, Adolfo Fontenla, Lola Villagraz Tecedor, Alvaro Lozano Rosado, Rafael Salguero Bodes, Fernando Arribas
Journal: Journal of the American College of Cardiology (2017)
Current treatment (Tx) patterns in relapsed or refractory multiple myeloma (MM): A retrospective chart review study
Authors: D. E. Reece, F. Zaman, B. L. Teixeira, K. Yoong, F. Camacho, R. K. Plante
Journal: Journal of Clinical Oncology (2009)

e19503 Background: New Tx options, including IMiDs [thalidomide, lenalidomide (Revlimid)] and bortezomib (Bz) (Velcade), have in the last few years become available on the market or as investigational agents in Canada for relapsed or refractory MM. These new agents are changing the Tx pattern and the clinical outcome of this disease. Methods: This retrospective chart review included all relapsed/refractory MM Pts who initiated drug Tx between Jul-06 and Jun-07 inclusive at Princess Margaret Hospital, Toronto, ON. Results: A total of 151 Pts were treated for relapsed/refractory MM between Jul-06 &amp; Jun-07. 57 Pts (40 receiving IMiD, 14 Bz, 3 other) were on clinical trials and thus not included in the analysis due to proprietary restrictions. Mean age, % male and BSA was 64.8 (SD±9.5) yrs, 68.1%, 1.9 (SD±0.2), respectively. Time from diagnosis to current therapy was 46.3 (SD±24.7) months. Nearly half the Pts were receiving treatment for 1 st disease relapse (48.9%), 24.5% for 2 nd relapse, 14.9% for 3 rd relapse, and the remainder for ≥ 4 th relapse. 74.5% of Pts had received at least 1 stem SCT prior to current study Tx. Current Txs included cyclophosphamide ± steroid (36.2%), Bz-based (26.6%), IMiD-based [17.0% (thalidomide only)], steroid monotherapy (13.8%), melphalan + prednisone (1.1%) and other (5.3%). Overall best RR was 43.6%, and 41.5% of Pts experienced PD up to the follow-up period. Mean TTP was 9.6 (SE±0.5) months. 30.9% of Pts received ESAs, 12.8% of Pts required RBC or platelet transfusion, 6.4% of Pts received G-CSF, and 47.9% of Pts received supportive pain medication. 27.7% of Pts required unscheduled hospitalization (56.4% due to MM and 7.7% due to Tx). Incidence of any grade drug-related varicella zoster, increased neuropathic pain, and thromboembolic events were 6.4%, 16.0%, 2.1%, respectively. Four Pts died while on current Tx and 14 died during the follow-up period of up to Dec-07. Conclusions: Bz was rarely used prior to public funding in Jul-06. Since then Bz (either as monotherapy or in combination) is the most commonly used novel Tx outside a clinical study and is replacing the use of the older agents. As the first analysis of current real world MM Txs in Canada from a large tertiary academic centre, this data is reflective of emerging treatment trends. [Table: see text]
Alternative Donors (Umbilical Cord Blood and Haploidentical Donors) for Allogeneic Stem Cell Transplantation in Relapsed / Refractory Hodgkin Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party and the Spanish Group of Stem Cell Transplantation (GETH)
Authors: Carmen Martinez, Jorge Gayoso, Carmen Canals, Herve Finel, Andrea Bacigalupo, Karl Peggs, Noel Milpied, Fabio Ciceri, Gerard Socie, Paolo Corradini, Stephen Robinson, Andrea Velardi, Nathalie Fegueux, Gonzalo Gutierrez, Stephen Mackinnon, Michael Potter, Boris Afanasiev, Jorge Sierra, Ram Malladi, Miguel A. Sanz, Nigel H. Russell, William Arcese, Vanderson Rocha, Peter Dreger, Anna Sureda
Journal: Blood (2015)
Aggressive Aneuploid Acute Myeloid Leukemia Is Dependent on Alterations of P53, Gain of APC and PLK1 and Loss of RAD50
Authors: Giorgia Simonetti, Antonella Padella, Marco Manfrini, Italo Faria do Valle, Cristina Papayannidis, Maria Chiara Fontana, Viviana Guadagnuolo, Carmen Baldazzi, Anna Ferrari, Samantha Bruno, Alberto Ferrarini, Simona Bernardi, Marianna Garonzi, Annalisa Astolfi, Giovanni Marconi, Elisa Zuffa, Eugenia Franchini, Emanuela Ottaviani, Antonella Laginestra, Maddalena Raffini, Sara Bacilieri, Nicoletta Testoni, Massimo Delledonne, Torsten Haferlach, Daniel Remondini, Giovanni Martinelli
Journal: Blood (2016)
Trisomy of the Down Syndrome Critical Region Suppresses Precursor B-Cell Differentiation and Promotes B-Cell Transformation Associated with Altered Expression of Polycomb Repressor Complex 2 Targets
Authors: Andrew A. Lane, Diederik van Bodegom, Bjoern Chapuy, Gabriela Alexe, Timothy J Sullivan, Trevor Tivey, Tovah Day, John Crispino, Edward Fox, Kimberly Stegmaier, David Weinstock
Journal: Blood (2012)
COMBINED LDL-C AND LIPOPROTEIN (A) LEVELS IN PREDICTION OF RESIDUAL ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK: THE AIM-HIGH TRIAL (ATHEROTHROMBOSIS INTERVENTION IN METABOLIC SYNDROME WITH LOW HDL/HIGH TRIGLYCERIDES: IMPACT ON GLOBAL HEALTH OUTCOMES)
Authors: Philip Chui, Moti Kashyap, Nathan Wong
Journal: Journal of the American College of Cardiology (2017)