tbuckley/cabot-search huggingface dataset:
Phase II trial of gefitinib (ZD1839) in advanced adenocarcinoma of the oesophagus incorporating biopsy before and after gefitinib
Authors: D. R. Ferry, M. Anderson, K. Beddows, P. Mayer, L. Price, J. Jankowski
Journal: Journal of Clinical Oncology (2004)

4021 Background: At presentation, most cases of adenocarcinoma of the oesophagus (ACO) are inoperable and, although chemotherapy with cisplatin/5-fluorouracil can prolong survival, patients eventually die as a result of refractory disease. Expression of epidermal growth factor receptor (EGFR) is a negative prognostic factor. EGFR is almost universally expressed in ACO; however, it is inhibited by the tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839). Methods: A Phase II clinical trial was conducted in patients with ACO who had received 1 previous chemotherapy regimen for advanced disease, relapsed after surgery and neoadjuvant chemotherapy, declined chemotherapy or been too ill for chemotherapy. A total of 27 patients were to be recruited using a 2-stage design. Biopsies were taken before and 28 days after treatment with gefitinib 500 mg/day. Tumour response was assessed using RECIST. Results: There were 23 men and 4 women with a median (range) age of 60 (46–82) years. Twenty patients had previous chemotherapy and 7 had no prior chemotherapy. All 27 patients were evaluable for toxicity; 26 were evaluable for tumour response. Toxicity was mild: rash (grade 2/3) occurred in 7 patients and diarrhoea (≥grade 2) in 4 (2 were grade 3/4). Biopsies taken pre- and post-treatment were evaluated in 7 patients; 5 showed a decrease in Ki67 expression. Genomic analysis is ongoing. Three patients (12%) had a partial response (PR) (duration: 120, 188 and 313+ days), 12 had stable disease (SD) and 11 had disease progression. Of those patients with a PR, 1 had prior neoadjuvant chemotherapy, 1 had received chemotherapy for advanced disease and 1 had received gefitinib as primary therapy. Conclusions: Gefitinib 500 mg/day is an active treatment for ACO with a disease control rate (PR or SD) of 58% (15/26 patients). Biopsies indicate that gefitinib inhibits biological pathways. Further trials of gefitinib would seem warranted, especially as patient response appears to be highly durable, and current chemotherapy second-line options have infrequent activity and are often toxic. ‘Iressa’ is a trademark of the AstraZeneca group of companies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pharmaceuticals AstraZeneca AstraZeneca
Selinexor in Combination with Chemotherapy or Idelalisib Elicits a Synergistic Cytotoxic Effect in Primary CLL Cells, Also Overcoming Intrinsic and Stromal Cells-Mediated Fludarabine Resistance
Authors: Maria Todaro, Valentina Griggio, Candida Vitale, Chiara Salvetti, Chiara Riganti, Mario Boccadoro, Yosef Landesman, Marta Coscia
Journal: Blood (2016)
Initial Screening Transferrin Saturation Values, Serum Ferritin Concentrations, and HFE Genotypes in Native Americans and Whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.
Authors: James C. Barton, Ronald T. Acton, Laura Lovato, Mark R. Speechley, Christine E. McLaren, Emily L. Harris, David M. Reboussin, Paul C. Adams, Fitzroy W. Dawkins, Victor R. Gordeuk, Ann P. Walker
Journal: Blood (2005)
Phase Ib, multicenter, single-blinded, placebo-controlled, sequential dose-escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer (LAHNC) receiving induction chemotherapy (ICT).
Authors: Sewanti Atul Limaye, Stephen T. Sonis, Fiona Cilli, A. Dimitrios Colevas, Michael Brennan, Kenneth Hu, Robert I. Haddad, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2012)

9024 Background: Oral mucositis (OM) is a significant toxicity of ICT in LAHNC. AG013, a mouth rinse composed of a recombinant Lactococcus lactis (sAGX0085) engineered to secrete human Trefoil Factor 1 (hTFF1) and deficient in the gene encoding thymidylate synthase, was investigated in patients receiving ICT (cisplatin, 5-fluorouracil +/-docetaxel:PF+/-T). TFFs have wound-healing properties and are protective of mucosal tissues. Methods: To evaluate the safety, tolerability, PK profile and efficacy of AG013 in attenuating ICT-associated OM, 52 patients (pts) with newly diagnosed LAHNC receiving ICT (24TPF, 1PF) were screened in ICT cycle (Cy) 1 for symptomatic OM (SOM). 25 pts who developed SOM in Cy1 were enrolled into 3 successive groups of at least 7 pts each in the active phase and randomly assigned at the Baseline visit (d1 of ICT Cy2) in a 5:2 ratio to receive AG013 or placebo during ICT Cy2. Dose was escalated in successive groups from 1 x/day (qd) to 3 x/day (tid) and to 6 x/day, resulting in doses of 2 x 10 11 , 6 x 10 11 , and 1.2 x 10 12 colony-forming units (CFU)/day respectively. Pts were assessed daily from Cy 2 d1 to d14 for OM using WHO criteria. Safety endpoints and PK (mucosal, salivary and blood samples) were assessed. Results: AG013-sAGX0085 could not be detected in blood. Recovered oral live bacterial levels were high immediately after dosing, decreased by 90 minutes post dose, and undetectable at study end. No differences in hTFF1 serum levels were seen. Pts in the placebo group had ulcerative OM (UOM) on nearly 60% of the days vs. 35-40% days in the AG013 group. 29 % pts who received AG013 had 0 or 1 day of UOM vs. at least 2 days of UOM in the placebo group. Pts who received AG013 on any dosing schedule had a lower % of days with OM, fewer unplanned office and emergency room visits compared to pts who received placebo. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. Conclusions: Topical administration of AG013 appears safe, well tolerated and effective in reducing the severity and course of OM in patients receiving ICT for HNC.
A BENEFIT-RISK ANALYSIS OF RECURRENT VENOUS THROMBOEMBOLISM IN PATIENTS WHO CONTINUED VERSUS DISCONTINUED RIVAROXABAN THERAPY AFTER AN INITIAL SIX-MONTH THERAPY
Authors: Scott Kaatz, Jeffrey Berger, Philip S. Wells, Roger Seheult, Veronica Ashton, François Laliberté, Concetta Crivera, Dominique Lejeune, Yongling Xiao, Jeff Schein, Peter Wildgoose, Patrick Lefebvre, Alok A. Khorana
Journal: Journal of the American College of Cardiology (2017)
Health-Related Quality of Life Profile and Request of Prognostic Information on Survival At the Time of Diagnosis in Patients with High-Risk Myelodysplastic Syndromes
Authors: Fabio Efficace, Gianluca Gaidano, Reinhard Stauder, Giovanni Caocci, Maria Teresa Voso, Marianna Criscuolo, Dominik Selleslag, Anna Angela Di Tucci, Monia Lunghi, Massimo Breccia, Francesco Buccisano, Uwe Platzbecker, Francesco Cottone, Marco Vignetti, Franco Mandelli
Journal: Blood (2011)
Akt activity regulates the function of internal ribosome entry sites (IRES) in the VEGF 5'UTR
Authors: Patrick Frost, Bao Hoang, YiJiang Shi, Sanjai Sharma, Angelica Benavides, Alan Lichtenstein
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

290 

We recently demonstrated that the mTOR inhibitor, CCI-779, curtailed growth of a subcutaneous challenge of multiple myeloma cells in immunodeficient mice. This anti-tumor effect was associated with prevention of cell proliferation, induction of apoptosis and inhibition of angiogenesis. Interestingly, myeloma tumors with heightened AKT activation were particularly sensitive to a CCI-779-induced anti-tumor response. Using isogenic multiple myeloma (MM) cell lines that only differ by their degree of AKT activity, we demonstrated that AKT activity significantly sensitized MM cells to the following inhibitory effects of mTOR inhibition: angiogenesis in vivo, VEGF expression in vitro and in vivo and VEGF translation (but not transcription). Since internal ribosome entry site (IRES)-mediated cap-independent translation is a salvage pathway for protein expression when mTOR is inhibited, we analyzed a possible regulatory role of AKT on VEGF IRES activity in the VEGF 5â€™-UTR. Our experiments demonstrated that elevated AKT activity inhibited VEGF IRES function in isogenic MM cells. Recent studies have shown that the 5â€™UTR region of VEGF contains at least 2 internal IRES sequences (IRES A and IRES B): IRES A has been shown to allow for the expression of VEGF translation under hypoxic conditions, whereas IRES B mediates the cap-independent translational initiation of a VEGF isoform (L-VEGF). However, it is not known if one or both of these IRES sequences are regulated by AKT activity in MM cells. In preliminary experiments, we are testing whether AKT activity inhibits the activity of either IRES A or IRES B activity and are studying the underlying mechanism by which these regulatory effects occur.
GENDER-RELATED OUTCOMES IN ELDERLY (&gt; 75 YEARS) PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROMES: RESULTS FROM THE SWISS ACUTE CORONARY SYNDROME COHORT
Authors: Barbara E. Staehli, Manfred B. Wischnewsky, Philipp Jakob, Roland Klingenberg, Slayman Obeid, Dik Heg, Lorenz Räber, Stephan Windecker, Francois Mach, Baris Gencer, David Nanchen, Peter Jüni, Ulf Landmesser, Christian Matter, Thomas F. Lüscher, Willibald Maier
Journal: Journal of the American College of Cardiology (2017)
Autologous Stem Cell Transplantation (AuSCT) with Total Lymphoid Irradiation (TLI) and High-Dose Chemotherapy (CT) Results in High Survival Rates for “Poor-Prognosis” Relapsed/Refractory (R/R) Hodgkin’s Disease (HD): Multivariate Analysis of Outcome Shows Marked Benefit for TLI in a Prospective Phase I/II Trial.
Authors: Andrew M. Evens, Alfred Rademaker, Bharat B. Mittal, Jessica K. Altman, David Patton, Lynne Kaminer, Seema Singhal, Daina Variakojis, Stephanie Williams, Martin S. Tallman, Jayesh N. Mehta, Jane N. Winter, Leo I. Gordon
Journal: Blood (2005)
INFLUENCE OF SACUBITRIL/VALSARTAN ON GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Jelena Seferovic, Sara Seidelmann, Brian Clagett, Milton Packer, Michael Zile, Jean Rouleau, Karl Swedberg, Martin Lefkowitz, Victor Shi, Akshay Desai, John J.V. McMurray, Scott Solomon
Journal: Journal of the American College of Cardiology (2017)
TREATMENT EFFECTS OF ALIROCUMAB AS AN ADD-ON TO MAXIMALLY TOLERATED DOSE OF STATIN IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA AND/OR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
Authors: Robert J. Weiss, Seth Baum, Dirk Blom, Jean Bergeron, Gisle Langslet, Santosh Sanganalmath, Julia Yang, Jonas Mandel, Prediman Shah
Journal: Journal of the American College of Cardiology (2017)
Primary intraocular lymphoma (PIOL): An International Primary CNS Lymphoma Collaborative group report
Authors: S. Grimm, J. Pulido, K. Jahnke, D. Schiff, A. Hall, T. Shenkier, T. Siegal, D. Nancy, T. Batchelor, L. Abrey
Journal: Journal of Clinical Oncology (2006)

1534 Background: PIOL is a hemopoietic tumor that arises in the retina, vitreous or optic nerve head, and carries a high risk of ocular and CNS relapse. The natural history and optimal management are unknown. Methods: A retrospective series of 81 patients with PIOL was assembled from 15 centers in 7 countries. Only patients with isolated ocular lymphoma were included; none had brain, spinal cord, or systemic lymphoma at diagnosis. Results: The median age at diagnosis was 65 (24–85). 58% were women. The median ECOG performance status was 0, and only three had a score &gt; 1. The median latency from symptom onset to diagnosis was 6 months (0– 36). Slit lamp exam was positive in 51, negative in 6, and not reported in 24. Vitrectomy was positive in 72 and negative in 2. 6 had a positive choroidal or retinal biopsy and 1 had no ocular surgery. CSF cytology was positive in 10 (17%), negative in 48, and unknown in 23. 21 received local therapy at diagnosis: 6 intra-ocular methotrexate (400 ug), 14 ocular radiation (median 3600 cGy), and 1 both modalities. 52 received more extensive therapy including systemic chemotherapy alone in 20 and a combination of chemotherapy and radiotherapy in 32. 5 received no treatment and details are unknown in 3. 47 patients (58%) relapsed a median of 19 months (0.5–180) after initial therapy. Sites of relapse included brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Patients treated with ocular therapy alone did not have an increased risk of failing in the brain (p = 0.6). Progression free survival (PFS) and overall survival (OS) were 29.6 and 57 months respectively and were unaffected by the choice of therapy. CNS disease was the cause of death in 19/33 (58%). Conclusions: In this series, treatment type did not affect sites of relapse, PFS or OS in patients with PIOL. To minimize toxicity, the best initial therapy should be limited to intraocular chemotherapy or focal radiotherapy. Prospective clinical trials are needed to improve our understanding and treatment of this disease. No significant financial relationships to disclose.
Osteoporosis screening among prostate cancer survivors treated with androgen deprivation therapy.
Authors: Alicia Katherine Morgans, Matthew Raymond Smith, A. James O'Malley, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2012)

6045 Background: Androgen deprivation therapy (ADT), the standard systemic treatment for prostate cancer, has adverse effects including bone loss and fractures. Current national guidelines suggest that men receiving ADT undergo dual energy x-ray absorptiometry (DXA) before and during ADT to better characterize fracture risk. We assessed receipt of DXA testing in a population-based cohort of men treated continuously with ADT for at least 1 year and identified factors associated with testing. Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified men aged &gt;65 with local or regional prostate cancer diagnosed during 2001-2007 and followed through 2009 who received at least 1 year of continuous ADT. We identified receipt of DXA testing in the 18-month period beginning 6 months before the first dose of ADT. We used logistic regression to identify factors associated with DXA testing, including patient and tumor characteristics and the physicians with whom they had outpatient visits. Results: Among 28,960 men treated with ADT for ≥1 year, 6.5% had at least one DXA scan from 6 months before the first dose of ADT through 1 year after. DXA testing increased over time, with men initiating ADT in 2007-2009 more likely to be tested than those treated in 2001-2002 (10.0% vs. 3.4%, OR 2.29, 95% CI 1.83-2.85). Men aged ≥85 were less likely than men aged 66-69 to undergo testing (OR 0.76, 95% CI 0.65-0.89). Black men were less likely than white men to undergo testing (OR 0.92, 95% CI 0.61-0.86), as were men living in areas with lower educational attainment (P&lt;.001). Compared with men seeing a urologist but no medical oncologist or primary care provider (PCP), men seeing a medical oncologist and a urologist (OR 2.11, 95% CI 1.39-3.21) and those seeing a medical oncologist, urologist and PCP (OR 2.59, 95% CI 2.01-3.34) had higher odds of testing. Conclusions: Few men receiving ADT for prostate cancer undergo DXA testing, with particularly low rates of testing among older men, black men, and those living in areas with low educational attainment. Visits with a medical oncologist were associated with increased odds of testing. Interventions are needed to increase bone density testing among men receiving long-term ADT.
GUT MICROBES-DERIVED METABOLITE TRIMETHYLAMINE N-OXIDE FACILITATES THE PROGRESSION OF “ATRIAL FIBRILLATION BEGETS ATRIAL FIBRILLATION”: A POTENTIAL LINK BETWEEN GUT MICROBES AND ATRIAL FIBRILLATION
Authors: Lilei Yu, Guannan Meng, Bing Huang, Zhuo Wang, Songyun Wang, Menglong Wang, Xuefei Li, Liping Zhou, Shenxu Yuan, Yuhong Wang, Xiaoya Zhou, Hong Jiang
Journal: Journal of the American College of Cardiology (2017)
IMPLICATIONS OF THE DUAL-ANTIPLATELET THERAPY (DAPT) TRIAL IN THE REAL WORLD: INSIGHTS FROM THE NCDR RESEARCH TO PRACTICE INITIATIVE
Authors: Amneet Sandhu, Patrick Stewart, Steven Bradley, Robert Yeh, John Messenger, James de Lemos, Michael Ho, Javier Valle, Gregory Hess, John Rumsfeld, Frederick Masoudi, Thomas Maddox
Journal: Journal of the American College of Cardiology (2017)
A Phase I Trial of Janus Kinase (JAK) Inhibition with INCB039110 in Acute Graft-Versus-Host Disease (aGVHD)
Authors: Mark A. Schroeder, H. Jean Khoury, Madan Jagasia, Haris Ali, Gary J. Schiller, Michael Arbushites, Patricia Delaite, Ying Yan, Kathleen Rhein, Miguel-Angel Perales, Yi-Bin Chen, John F DiPersio
Journal: Blood (2016)
ASSOCIATIONS OF LIPOPROTEIN(A) LEVELS WITH INCIDENT ATRIAL FIBRILLATION AND STROKE AMONG WHITES AND BLACKS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY
Authors: Konstantinos N. Aronis, Di Zhao, Ron Hoogeveen, Alvaro Alonso, Christie Ballantyne, Eliseo Guallar, Steven Jones, Seth Martin, Saman Nazarian, Salim Virani, Erin Michos
Journal: Journal of the American College of Cardiology (2017)
The effect of surgical volume on the rate of secondary therapy after radical prostatectomy
Authors: C. Jeldres, A. Gallina, J. Walz, S. Fred, P. Perrotte, L. Valiquette, M. McCormack, H. Huland, F. Montorsi, P. Karakiewicz
Journal: Journal of Clinical Oncology (2007)

15620 Introduction and Objective: Some argue that prostate cancer (PCa) detection and treatment at a younger age may translate into higher rate of clinically insignificant PCa. We assessed the effect of patients age at diagnosis on the pathological stage at radical prostatectomy (RP). Methods: Clinical and pathological data were available for 11975 patients from 3 European and 3 North American tertiary care centers. All RPs were performed between 1987 and 2006. Univariable and multivariable logistic regression analyses addressed the effect of age at RP on the rate of extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI), after controlling for PSA, clinical stage, biopsy Gleason sum and year of surgery. Age at RP was coded as cubic spline to allow non-linear effects. Results: Mean age was 61.6 years (range 32–85) and mean PSA was 8.7 ng/mL (range 0.1–50.0). Biopsy Gleason sum was 2–6, 7 or 8–10 in 7510 (62.7%), 3656 (30.5%) and 809 (6.8%) patients, respectively. At RP, ECE, SVI and LNI were identified in 3383 (28.3%), 1309 (10.9%) and 469 (3.9%), respectively. In multivariable analyses, age was only an independent predictor of SVI (p&lt;0.001). Older men had a higher rate of SVI. Conclusions: Pathological age only affects the rate of SVI. However, only one in ten men harbored SVI and this percentage may decrease even further with ongoing stage migration. Nonetheless, these data suggest that the removal of seminal vesicles should not be omitted in older men. No significant financial relationships to disclose.
Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non–Small-Cell Lung Cancer
Authors: Robert T. Dess, Yilun Sun, Martha M. Matuszak, Grace Sun, Payal D. Soni, Latifa Bazzi, Venkatesh L. Murthy, Jason W.D. Hearn, Feng-Ming Kong, Gregory P. Kalemkerian, James A. Hayman, Randall K. Ten Haken, Theodore S. Lawrence, Matthew J. Schipper, Shruti Jolly
Journal: Journal of Clinical Oncology (2017)

Purpose Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.
Erythropoietin Treatment in Advanced Multiple Myeloma Is Associated with Improved Immunological Functions: Could It Be Beneficial in Early Disease?.
Authors: Sara Prutchi-Sagiv, Nataliya Golishevski, Howard S. Oster, Odelia Katz, Naparstek Elizabeth, Amos Cohen, Michael Hoffman, Drorit Neumann, Moshe Mittelman
Journal: Blood (2006)
A Novel NKp44-Based Chimeric Antigen Receptor That Targets Multiple Types of Cancer
Authors: Yasushi Kasahara, Changsu Shin, Sakiko Yoshida, Takayuki Takachi, Nobuhiro Kubo, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai
Journal: Blood (2016)