tbuckley/cabot-search huggingface dataset:
ASSOCIATIONS BETWEEN SERUM MARKERS OF EXTRACELLULAR MATRIX METABOLISM, FIBROSIS-LINKED MICRORNAS (MIR-21, MIR-26, MIR-29, MIR-30 AND MIR-133A) AND RIGHT VENTRICULAR PARAMETERS IN DILATED CARDIOMYOPATHY
Authors: Pawel Rubis, Justyna Totoń-Żurańska, Sylwia Wisniowska-Smialek, Katarzyna Holcman, Ewa Wypasek, Lucyna Rudnicka-Sosin, Maria Kołton-Wróż, Paweł Wołkow, Artur Kozanecki, Piotr Podolec
Journal: Journal of the American College of Cardiology (2017)
Abstract P310: Connective Tissue Growth Factor Antibody Protects from Adverse Left Ventricular Remodeling Following Myocardial Infarction
Authors: Laura Vainio, Zoltan Szabo, Raisa Serpi, Heikki Ruskoaho, Risto Kerkelä
Journal: Circulation Research (2011)

Ischemic heart disease (IHD) is the most common cause of death in most Western countries, but the therapies for IHD are lacking. We aimed to determine the potential of connective tissue growth factor (CTGF) antibody in protecting myocardium from long-term deleterious effects of myocardial infarction. Healthy 8-week old mice were subjected to myocardial infarction (MI) and at 1 week post-MI the animals were randomized for treatment with vehicle, metoprolol or CTGF monoclonal antibody. After six weeks of treatment, CTGF antibody treated animals showed significantly better left ventricular (LV) systolic function than the vehicle-treated animals. LV diastolic function or LV dimensions were not affected by treatments. Analysis of cardiac sections revealed no difference in infarct scar size between the experimental groups. However, RT-PCR analysis revealed a decrease in the expression levels of fibrosis-related genes in non-ischemic area in the hearts of CTGF antibody treated animals. In addition, cardiomyocyte size was significantly reduced in LV sections of CTGF antibody treated animals compared to vehicle-treated animals. This was accompanied with a significant decrease in B-type natriuretic peptide mRNA levels in the LV, whereas expression levels of atrial natriuretic peptide or beta-myosin heavy chain were similar in MI groups. There was also a slight decrease in mRNA levels of interleukin-6 and CTGF in the hearts of CTGF antibody treated animals. Treatments had no effect on mRNA levels of transforming growth factor-β1, tumor necrosis factor-α and vascular endothelial growth factor A following MI. In conclusion, CTGF antibody treatment attenuates LV hypertrophy and improves LV systolic function following MI. Blocking CTGF function by a specific antibody may be useful for prevention of adverse myocardial remodeling and heart failure.
RELATIONSHIP OF CORONARY FLOW RESERVE WITH BODY MASS INDEX AND ADVERSE OUTCOMES IN PATIENTS WITHOUT OVERT ISCHEMIC HEART DISEASE: IMPLICATIONS FOR METABOLIC SURGERY ELIGIBILITY
Authors: Navkaranbir S. Bajaj, Michael Osborne, Ankur Gupta, Paco Bravo, Tomas Vita, Thomas Christensen, Courtney Foster, Jon Hainer, Meagan Harrington, Victoria Morgan, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli, Viviany Taqueti
Journal: Journal of the American College of Cardiology (2017)
Spanish Melanoma Multidisciplinary Group (GEM): Long-term survivors treated with ipilimumab (IPI) in the expanded access programme (EAP).
Authors: Cristina Hernando, Virtudes Soriano, Jose Pablo Berros, Ana Maria Arance, Karmele Mujika, Delvys Rodriguez Abreu, Lorenzo Alonso, Martina Alonso, Lorena Yapur, Alfonso Berrocal
Journal: Journal of Clinical Oncology (2013)

e20007 Background: Advances in metastatic melanoma treatment have demonstrated improvement in survival. After 5 year follow-up of clinical trials with IPI, LTS have been reported. Current follow-up of patients treated within IPI EAP in Spain is 2 years. Methods: we performed a retrospective subgroup analysis of 138 treated patients (pts) within the IPI not randomized EAP (48% of the total EAP population). LTS were defined as pts with ≥ 12 months overall survival (OS). Pts were treated with IPI at 3 mg/kg q 3 w x 4. Data was registered using a socio-demographic and therapeutic questionnaire, collecting overall response (RR), survival (OS) and toxicity (T). Results: In our analysis of138 treated pts 39 were LTS (28.2%), 14 pts were alive at 12 months (M), 12 pts between 13-19 m and 7 pts 20-24m, for all this patients the follow up continues. Median age was: 56.5 (30-81). Gender: Male 48.7%. Stage: IVa 25.6%, IVb 17.9%, IVc 56.8%. Primary tumor site: skin 56.4%; accral 12.8%; mucosal 10.3%; ocular 10.3%; rest unknown. Metastases (mts): soft tissue 38.5%, lung 33.3%, visceral 28.2%. Median number of prior treatments: 1 (1-5), 20.5% received more than one chemotherapy (chx) line. 92.3% of total pts population have completed the induction schema (4 IPI doses). Response assessment: CR 15.4%; PR 38.5%; SD 33.3%; P 12.8%. Mean duration of response: 10.6m. Mean survival: 16.6m. 56.4% received thx after IPI, in those pts 41% received chx; 17.9% radiotherapy; 12.9% B-RAF inhibitor. 18 pts (46.2%) presented T: 12.8% Grades (G) 3-4 were reported; 23.1% G2; 7.7% G1. The most frequent T was cutaneous (17.9%). When compared with the overall EAP pts population LTS have less visceral disease, lower median LDH, more objective responses and completion of the four induction ipilimumab doses. Conclusions: Ipilimumabin the Spanish EAP experience in pretreated patients has shown to improve long term survival similar to that seen in studies in patients with advanced melanoma. Further research and analysis are needed to identify the patient population most likely to achieve a long term survival benefit with ipilimumab treatment.
Pre-Clinical Characteristics of a Recombinant Fusion Protein Linking Activated Coagulation Factor VII with Albumin (rVIIa-FP)
Authors: Sabine Zollner, Daniel Schuermann, Elmar Raquet, Jochen Mueller-Cohrs, Thomas Weimer, Ingo Pragst, Gerhard Dickneite, Stefan Schulte
Journal: Blood (2012)
Role of circulating angiogenin TGF-β1, VEGF-R1, and VEGF-R2 in metastatic malignant melanoma patients
Authors: J. Spano, R. Mouawad, S. Vignot, N. Magné, D. Khayat
Journal: Journal of Clinical Oncology (2009)

9048 Background: Malignant melanoma is a disease capable of rapid progression and is associated with high angiogenesis. Thus, investigation of mechanisms involved in metastasis is essential to control this tumor. However, the angiogenesis regulators that are biologically relevant for melanoma are still unknown. We have previously reported that high levels of soluble VEGF in metastatic malignant melanoma (MMM) patients may represent a useful biomarker to predict the effect of biochemotherapy in terms of clinical response. In this study, we evaluate whether soluble levels of angiogenin, transforming growth factor-β1 and VEGFR-1 and -2 play a role in metastatic malignant melanoma patients and to determine if they have any relationship with clinicopathological parameters. Methods: Using a sensitive enzyme-linked immunosorbent assays, angiogenin TGF-β1, VEGF-R1 and VEGF-R2 were measured in sera of 70 patients with a fully documented history of metastatic malignant melanoma in comparison with 30 healthy controls. Results: Pretreatment circulating angiogenin, TGF- β1 VEGF-R1 and VEGF-R2 were detectable, variable in all samples from either melanoma patients or healthy donors Only serum transforming growth factor- β1 levels was significantly higher (p=0.005) in patients compared to healthy controls. No relationship was observed between sex, age or LDH level and all studied parameters. When tumor burden has been taken into consideration, a significant relationship was established between high circulating serum TGF-β1 (p= 0.001) levels and tumor burden were found, Similarly, higher serum VEGFR1 levels were correlated with tumor burden (P = 0.02). Conclusions: The presence of high circulating TGF-β1 and VEGF-R1 in metastatic malignant melanoma patients may prospectively identify high-risk patients with a worse prognosis. In addition, these two parameters may be promising targets for new therapeutic strategies in this pathology. No significant financial relationships to disclose.
Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials
Authors: Sonali M Smith, Brandelyn N Pitcher, Sin-Ho Jung, Nancy L Bartlett, Nina Wagner-Johnston, Steven I Park, Kristy L Richards, Amanda F Cashen, Anthony Jaslowski, Scott E Smith, Bruce D Cheson, Eric Hsi, John P Leonard
Journal: The Lancet Haematology (2017)
Murine Donor 1928z CAR T Cells Exert Potent Graft-Versus-Lymphoma Activity without Graft-Versus-Host-Disease
Authors: Melody Smith, Arnab Ghosh, Scott James, Marco L Davila, Enrico Velardi, Kimon V. Argyropoulos, Gertrude Gunset, Andrea Schietinger, Michel W. Sadelain, Marcel van den Brink
Journal: Blood (2016)
Design of Tumor Acidity-Responsive Sheddable Nanoparticles for Fluorescence/Magnetic Resonance Imaging-Guided Photodynamic Therapy
Authors: Feng Fan, Yue Yu, Fei Zhong, Meng Gao, Tianmeng Sun, Jiaxin Liu, Huimao Zhang, Haisheng Qian, Wei Tao, Xianzhu Yang
Journal: Theranostics (2017)

Imaging-guided cancer therapy, which integrates diagnostic and therapeutic functionalities into a single system, holds great promise to enhance the accuracy of diagnosis and improve the efficacy of therapy. Specifically, for photodynamic therapy (PDT), it is highly desirable to precisely focus laser light onto the tumor areas to generate reactive oxygen species (ROS) that are cytotoxic tumor cells and avoid light-associated side effects. Herein, a distinct three-layer nanostructured particle with tumor acidity-responsiveness (S-NP) that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates Gd3+ is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT. We show clear evidence that the outer PEG layer significantly prolongs circulation time, and the inner poly(ε-caprolactone) (PCL) core can physically encapsulate Ce6. More interestingly, the middle layer of the S-NP, acting as a molecular fence to keep Ce6 in the circulation system, was dismantled by the slightly acidic tumor microenvironment. Afterwards, the PEG shell is deshielded from the S-NP at the tumor tissue, resulting in improved cell uptake, enlarged MR signal intensity, rapid release of Ce6 within tumor cells, and elevated PDT efficacy. Our results suggest that tumor-acidity-responsive nanoparticles with fine design could serve as a theranostic platform with great potential in imaging-guided PDT treatment of cancer.
DIFFERENT IMPACT OF GENDER ON EARLY AND LATE OUTCOME AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Felix Woitek, Stephan Haussig, Georg Stachel, Sergey Leontyev, David Holzhey, Friedrich Mohr, Gerhard Schuler, Norman Mangner, Axel Linke
Journal: Journal of the American College of Cardiology (2017)
18F-fluorocholine positron emission tomography/computed tomography for early outcome prediction in metastatic castration-resistant prostate cancer patients treated with enzalutamide: A proof-of-principle study.
Authors: Ugo De Giorgi, Paola Caroli, Emanuela Scarpi, Vincenza Conteduca, Salvatore Luca Burgio, Cecilia Menna, Emanuela Bianchi, Lorena Rossi, Giovanni Paganelli, Dino Amadori, Federica Matteucci
Journal: Journal of Clinical Oncology (2014)

e16040 Background: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early treatment evaluation and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC) treated with enzalutamide. Methods: Patients received enzalutamide daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate specific antigen (PSA) response and safety. FCH-PET/CT was done at baseline and was repeated after approximately 3 to 6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). Results: Thirty-six patients, median age 72 years (range, 48-90 years) were treated with enzalutamide, whose 21 received one or more lines of therapy after docetaxel. Fourteen of 36 (36%) received previously abiraterone. A decline in PSA level of 50% or more was seen in 13 of 36 (36%) patients. Thirty-four patients were evaluable for early FCH-PET/CT response: 17 had a progressive disease (PD), while 17 obtained a stable disease or a partial response. None achieved a FCH-PET/CT complete remission. An early FCH-PET/CT PD predicted a radiological PD at the first CT scan after 3 months of enzalutamide in 11 of 15 cases (73%). In univariate analysis, visceral metastases, previous abiraterone and PSA decline predicted either PFS or OS, whereas FCH-PET/CT imaging predicted PFS only. In multivariate analysis, only PSA decline and FCH-PET/CT remained significant for PFS (P = 0.0005 and P = 0.029, respectively), whereas PSA decline only was predictive for OS (P = 0.007). No cases of FCH-PET/CT flare were reported. Conclusions: This the first evidence of the predictive effect of early FCH-PET/CT in CRPC treated with enzalutamide. FCH-PET/CT could be a useful tool for outcome prediction and tumor monitoring in patients with CRPC treated with enzalutamide.
Integrated nonclinical and clinical risk assessment to obviate the need for a dedicated QTc study of ixazomib citrate (MLN9708) in cancer patients (pts).
Authors: Neeraj Gupta, Yeamin Huh, Matthew M Hutmacher, Sean Ottinger, Ai-Min Hui, Karthik Venkatakrishnan
Journal: Journal of Clinical Oncology (2014)

2553 Background: Ixazomib citrate is an investigational oral proteasome inhibitor in phase 3 (P3) clinical development. It is expected to have a favorable cardiac safety profile based on weak in vitro inhibition of the hERG channel (IC50 59.6 μM) and in vivo nonclinical data. To confirm, serial PK-matched triplicate electrocardiograms (ECGs) were collected in phase 1 (P1) dose-escalation studies to characterize the effect of the active moiety ixazomib (Ix; MLN2238) on QTc intervals and potentially obviate the need for a dedicated QTc study. Methods: Data from 245 pts in 2 IV (0.125–3.11 mg/m2, N=125, solid tumor and lymphoma pts) and 2 oral (0.24–3.95 mg/m2, N=120, multiple myeloma pts) P1 studies were included. Mean (range) age was 56.5 (23–86) years; 43% were female. Centrally read 12-lead digital ECGs were used to derive heart rate (HR)-corrected QT intervals using Fridericia’s method (QTcF). Relationship between Ix plasma concentration (C) and QTcF was analyzed using linear mixed effects models with fixed effects for day and time to account for circadian variation. Results: A safety margin of >1700-fold was calculated between the hERG Ki (24.9 μM) and unbound day 15 Cmax (14.6 nM) at the fixed P3 dose of 4 mg. Non-clinical dog telemetry studies showed no QT prolongation, or changes in ECGs, HR, or waveform intervals at doses up to 4.2 mg/m2. Linear models relating Ix C to QTcF and RR were developed from clinical data acquired over a wide C range (26% of data >mean Cmax at P3 dose). Ix has no clinically meaningful effect on cardiac repolarization based on the model-predicted mean change in QTcF from baseline, consistent with outlier analyses (Table). There was no relationship between C and RR interval suggesting Ix has no effect on HR. Conclusions: Ixazomib citrate has no clinically meaningful impact on QTc or HR. Integrating preclinical cardiac electrophysiology data and clinical C-QTc modeling of P1 data represents an efficient approach in oncology drug development that may obviate the need for a dedicated QTc study. QTc mean change from baseline (P3 dose), ms (90% CI) 0.07 (-0.22–0.36) QTcF outlier analysis (N=1023), % >480 ms >500 ms Change from baseline >30 ms / >60 ms 0.7 0 1.6/0
OUTCOMES OF THE DIFFERENT FLOW/GRADIENT PATTERNS OF AORTIC STENOSIS AFTER AORTIC VALVE REPLACEMENT: INSIGHTS FROM PARTNER 2A TRIAL
Authors: Philippe Pibarot, Zachary Gertz, Howard Herrmann, Rebecca Hahn, Wael Jaber, Leonardo Rodriguez, Neil Weissman, Jonathon Leipsic, Philipp Blanke, John Webb, Yiran Zhang, Marie-Annick Clavel, Maria Alu, Pamela Douglas, Raj Makkar, D. Craig Miller, Brian Lindman, Vinod Thourani, Martin Leon
Journal: Journal of the American College of Cardiology (2017)
PROGNOSTIC VALUE OF CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY, MYOCARDIAL PERFUSION IMAGING AND INVASIVE CORONARY ANGIOGRAPHY IN KIDNEY TRANSPLANTATION CANDIDATES: A PROSPECTIVE COHORT STUDY
Authors: Simon Winther, My Svensson, Hanne S. Jørgensen, Laust D. Rasmussen, Lars Gormsen, Niels Holm, Kirsten Bouchelouche, Hans Erik Boetker, Per Ivarsen, Morten Boettcher
Journal: Journal of the American College of Cardiology (2017)
Clinical Burden and Progression of Myelofibrosis in a Controlled Study Population of Placebo-Treated Patients (COMFORT-I)
Authors: Srdan Verstovsek, Ruben A. Mesa, Jason Gotlib, Richard S. Levy, Vikas Gupta, John F. DiPersio, John Catalano, Michael W. Deininger, Carole B. Miller, Richard T. Silver, Moshe Talpaz, Elliott F. Winton, Jimmie H. Harvey, Murat O. Arcasoy, Elizabeth Hexner, Roger M. Lyons, Ronald Paquette, Azra Raza, Kris Vaddi, Sue Erickson-Viitanen, William Sun, Victor A. Sandor, Hagop M. Kantarjian
Journal: Blood (2011)
MINIMALIST APPROACH TO CARDIAC ANESTHESIA AND OUTCOME IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT.
Authors: Marcus Burns, Lynelle Schneider, Tjorvi Perry, Mario Goessl, Andrea Sweeney Claussen, Kevin Harris, Robert Farivar, Richard Bae, Ross Garberich, Paul Sorajja
Journal: Journal of the American College of Cardiology (2017)
Phase I study of nab-paclitaxel (NP) in combination with biochemotherapy (BCT) in patients (pts) with metastatic melanoma (MM).
Authors: Anas Alrwas, Nicholas E. Papadopoulos, Suzanne Cain, Sapna Pradyuman Patel, Kevin B. Kim, Tawania L Deburr, Roland Bassett, Wen-Jen Hwu, Agop Y. Bedikian, Michael A. Davies, Scott Eric Woodman, Patrick Hwu
Journal: Journal of Clinical Oncology (2012)

e19009 Background: NP has shown anti-tumor activity in MM in a phase II trial. The objective of this study was to determine MTD of NP as part of BCT, consisted of cisplatin (C), temozolomide (T), interleukin-2 (IL2) and interferon-alpha (IFN). Secondary objectives were to evaluate the anti-tumor activity of this combination in MM, and its benefit in preventing central nervous system (CNS) metastasis (mets). Methods: Previously untreated MM patients evaluable by RECIST 1.0 with no history of CNS mets between the ages of 18 and 65 and with ECOG 0-1 were enrolled. NP was given intravenously (IV) on Day (d) 1 and 5 of each cycle. The starting dose on d1 was 100 mg/ m 2 , and the dose on d5 was 70 mg/ m 2 , if toxicities permitted. The remainder of the regimen consisted of IV C 20 mg/ m 2 daily d1-4, oral T 250 mg/ m 2 d1-3, 9 million international units (MIU)/m 2 of IL2 via continuous IV infusion for 96 hours, and IFN 5 MIU/m 2 via subcutaneous injection d1-5. Treatment was repeated in cycles of 21 d to a maximum of 6 cycles. Prophylactic hematologic growth factors were not allowed in the first cycle. A standard 3+3 escalation method was used for NP d1 dose. Results: Ten pts were enrolled and evaluable for toxicities. Five completed six courses. Because 2 of 5 pts at the starting dose level had dose-limiting toxicities (DLTs) (diarrhea; transaminasemia-TA), the next cohort received d1 NP dose of 80mg/m 2 . Two of 5 pts at that dose level had DLTs (TA; neutropenia). Overall, the day 5 dose was omitted in 3 patients post third cycle due to thrombocytopenia (TP). There was no grade 5 toxicity. Common grade 3 and 4 toxicities were leucopenia, neutropenia, lymphopenia, anemia, TP, hyponatremia, diarrhea, skin rash, infection, tinnitus, neuropathy and TA. Five of 9 evaluable pts had partial response (PR). The median time-to-progression was 5.3 months (m). The median overall survival was 8.73 m. Six pts developed CNS mets with an overall median time of 5.33 m from treatment start. Conclusions: Additional studies are needed to determine the optimal dosing and schedule of NP as a part of BCT. Despite significant antitumor activity on sites outside the CNS, this combination therapy did not prevent the development of CNS mets.
An independent population-based validation of the adjuvant decision-aid for stage I-II breast cancer
Authors: I. A. Olivotto, C. Bajdik, P. M. Ravdin, B. Norris, A. J. Coldman, C. Speers, S. Chia, K. Gelmon
Journal: Journal of Clinical Oncology (2004)

522 Background: ADJUVANT! (ADJ! [JCO 2001;19:980–91]) is a computer model which predicts 10-yr overall (OS), breast cancer-specific (BCSS) and event-free (EFS) survival with and without systemic therapy using recognised prognostic factors. Oncologists use it to provide information to patients about prognosis and treatment choice. ADJ! has not been independently validated despite widespread use. Methods: Demographic, pathology, staging and treatment data on 4,083 women with pT1–2, pN0–1 breast cancer referred to the BC Cancer Agency during 1989–1993 were entered into ADJ! 10-yr predicted (pred) OS, BCSS and EFS were calculated for each patient. Breast Cancer Outcomes Unit observed (obs) status at 10 years (disease event yes/no; alive; dead of disease; dead of other cause) was independently determined for each patient. ADJ! pred and BCOU obs rates were compared. Study subject pathologic characteristics were: 66% pT1, 34% pN1, 58% ER+, 37% grade 3 and 36% with lymphovascular invasion (LVI+). Three percent were age 20–35 years, 9.7% were age >75 years. Systemic therapy was: none=45%, tamoxifen (TAM) alone=30%, chemo (CT) alone=16% and CT+TAM=9%. Results: Across all 4083 patients, 10-yr pred and obs outcomes were within +/− 1% for OS (pred=71.7%, obs=72%), BCSS (pred=83.2%, obs=82.5%) and EFS (pred=71%, obs=70.1%). ADJ! overestimated EFS in women ≤ 35 yrs (pred=67.9%, obs=54.3%; p<0.002) and with LVI+ disease (pred=66.5%, obs=62.3%, p<0.001). ADJ! predicted BCSS and EFS rates within +/− 2% for patients not receiving systemic therapy or receiving TAM alone. ADJ! overestimated EFS with CT (pred=65%, obs=61.3%; p=0.056) and especially with combined CT+TAM (pred=68.1%, obs=61.7%; p=0.012). Conclusions: Overall, ADJ! performed reliably. Two factors to be added to future revisions of ADJ! were identified: age ≤ 35 and LVI+. ADJ! was overly optimistic about the outcomes of combined CT+TAM (by about 5% absolute) for OS, BCSS and EFS. Validation in large population-based databases like the BCOU, supports the translation of prediction models into practice. Supported in part by the Canadian Breast Cancer Research Alliance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Adjuvant, Inc. Adjuvant, Inc. Adjuvant, Inc.