tbuckley/cabot-search huggingface dataset:
A phase II study of temozolomide administered 21 out of 28 days for the treatment of patients with recurrent anaplastic (oligo) astrocytoma: An interim analysis of toxicity
Authors: B. Neyns, B. van Mierlo, J. Menten, L. Dhondt, E. Joosens, N. Vastesaeger, F. Branle
Journal: Journal of Clinical Oncology (2005)

1560 Background: Temozolomide (TemodalR, TMZ) is an active alkylating agent for the treatment of gliomas. Conventional dosing of TMZ consists of an oral dose of 150–200 mg/m2/day for 5 consecutive days every 28 days. Extended daily dosing of TMZ might be more active because of the depletion of the AGAT repair protein. TMZ administered for 21 consecutive days (at a dose of 100 mg/m2/day) every 28 days, is being tested in a multicenter Belgian phase II study for the treatment of recurrent anaplastic (oligo)astrocytoma. We report the toxicity that was associated with this regimen at the occasion of the first interim monitoring of the adverse events. Methods: For the monitoring of toxicity (CTCAEv3.0), the protocol requested a weekly clinical and hematological evaluation during the first 8 wks and every 2 wks thereafter. An interim analysis was carried out for the toxicity seen during the first 67 administered treatment cycles. Results: 17 patients (pts) were recruited into this study (4 F, 13 M; median age 42 y, range 23–69 y). A median nr of 4 cycles were administered per pt (range 1–12). The most frequent observed adverse event was lymphopenia (LP); 14/17 pts experienced at least 1 episode of LP; Gr3 LP: 12 pts (20 cycles) and gr 4 LP: 4 pts (8 cycles). For the 28 cycles associated with gr3/4 LP, only 5 times treatment was adjusted according to protocol. There was a low incidence of other myelotoxicities (3x gr3/4 thrombocytopenia in 3 pts, 2x gr4 neutropenia, and no gr3/4 anemia). There was no case of febrile neutropenia. One pt had a herpes zoster reactivation (with concomitant gr2 LP). There was only 1 event of gr3 vomiting, 1x gr3 skin rash and 1x gr3 increase in AST/ALT and gammaGT. Updated results on toxicity and an analysis of tumor response will be reported at the meeting (including an 8 additional months of follow-up). Conclusions: Extended dosing of TMZ by a 21/28 days scheme in pts with recurrent anaplastic (oligo)astrocytoma, has a low-toxicity profile but is associated with a high incidence of lymphopenia. This toxicity profile is different from what is seen with the more conventional 5 out of 28 days schedule and investigators should pay attention to this uncommon toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Belgium Schering-Plough Schering-Plough
Decreased Global Longitudinal Strain in Diabetics With Preserved Ejection Fraction Post-Myocardial Infarction: A VALIANT Echo Sub-study
Authors: Amil M Shah, Chung-Lieh Hung, Sung Hee Shin, Anil Verma, Lars Kober, Eric Velazquez, John J. McMurray, Frans Van de Werf, Marc A Pfeffer, Scott D Solomon
Journal: Journal of the American College of Cardiology (2009)
Four new phenolic glycosides from Baoyuan decoction
Authors: Xiaoli Ma, Xiaoyu Guo, Mingbo Zhao, Pengfei Tu, Yong Jiang
Journal: Acta Pharmaceutica Sinica B (2016)

Four new phenolic glycosides, including two flavonoid glycosides (1 and 2) and two lignan glycosides (3 and 4), were isolated from the traditional Chinese medicine formula, Baoyuan decoction. Their structures were established by detailed analysis of the NMR and HR-ESI-MS spectroscopic data and their absolute configurations were determined by the experimental electronic circular dichroism data as well as chemical methods. Furthermore, the sources of the four new compounds were determined by the UPLC-Qtrap-MS method, which proved that 1 and 2 are originated from Glycyrrhiza uralensis, and 3 and 4 are from Cinnamomum cassia.
P1-028: Intrapleural perfusion hyperthermo-chemotherapy for patients with carcinomatous pleuritis
Authors: Hiroyuki Tao, Motoi Aoe, Yuuji Hirami, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Yoshifumi Sano, Hiroshi Date
Journal: Journal of Thoracic Oncology (2007)
Treatment of human disease due to <i>Mycobacterium bovis</i>: a systematic review
Authors: Zhiyi Lan, Mayara Bastos, Dick Menzies
Journal: European Respiratory Journal (2016)

Mycobacterium bovis , a member of the Mycobacterium tuberculosis complex, is an important cause of disease in cattle, but it can also cause disease in humans [1]. Transmission to humans generally occurs after close contact with infected animals or consumption of unpasteurised contaminated dairy products [1, 2]. The symptoms of human disease due to M. bovis are similar to those of disease caused by M. tuberculosis , although M. bovis is more likely to cause extrapulmonary disease [3]. In clinical practice, M. bovis can only be differentiated from M. tuberculosis using biochemical or genetic tests [3, 4]. Only limited evidence exists to support current recommendations for the treatment of human disease due to M. bovis <http://ow.ly/h92K3023fLu> The authors thank Philip A. LoBue (Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA), Christof J. Majoor (Academic Medical Center, Amsterdam, the Netherlands) and Ezequiel Cordova (Infectious Diseases Unit, Hospital Cosme Argerich, Buenos Aires, Argentina) for providing additional information.
Preventing Shingles and Its Complications in Older Persons
Authors: Kathleen M. Neuzil, Marie R. Griffin
Journal: New England Journal of Medicine (2016)

In the United States each year, herpes zoster, or shingles, develops in half a million people 60 years of age or older. Although the symptoms are often mild in younger persons, the risk for serious complications of herpes zoster, including postherpetic neuralgia, ocular involvement, and central nervous system disease, increases with advancing age.1 The rising age-specific incidence of shingles and the aging population in the United States are likely to contribute to additional shingles-associated morbidity in coming years.2 The prevention of herpes zoster and its complications in older persons will improve quality of life and should be a public health . . .
AGS-16M18: A novel therapeutic human monoclonal antibody for the treatment of kidney and liver cancers
Authors: A. Jakobovits, J. Gudas, Z. An, N. Ganguly, K. R. Morrison, K. J. Morrison, A. B. Raitano, D. Satpaev, X. Jia, S. B. Kanner
Journal: Journal of Clinical Oncology (2008)

3050 Background: AGS-16 is a novel cell surface protein expressed in over 95% of kidney cancers, including clear cell and papillary carcinomas, and ∼40% of hepatocellular carcinomas. Amongst normal tissues, AGS-16 is expressed predominantly in kidney proximal tubules. In vitro validation studies using AGS-16 purified protein and AGS-16 expressing kidney and liver cancer cells have demonstrated AGS-16 involvement in tumor cell proliferation, migration and invasion, and induction of tube formation by human umbilical vein endothelial cells (HUVEC). Methods and Results: XenoMouse technology was employed to identify AGS-16M18, a fully human IgG1λ monoclonal antibody (MAb) with a Kd = 2.6 x 10-10M for cell surface AGS-16, which demonstrated potent activity in all of the in vitro assays. AGS-16M18 inhibited proliferation and survival of both RXF-393 and HepG2 tumor cell lines in a dose-dependent manner. In addition, AGS-16M18 dose-dependently inhibited AGS-16-induced HUVEC tube formation. AGS-16M18 inhibited HepG2 cell migration and invasion. Significant antitumor efficacy of AGS-16M18 in vivo was observed on well established patient-derived clear cell kidney cancer xenografts and hepatocellular carcinomas. Biomarker analysis of AGS-16M18- treated tumors revealed a significant impact of the antibody on proliferation (ERK, AKT) and apoptosis (PARP) pathways. Efficacy of AGS-16M18 was maintained after MAb de-glycosylation, indicating an intrinsic antitumor activity of the MAb without apparent contribution by immune effector functions. When AGS-16M18 was combined with targeted therapies such as bevacizumab, sunitinib malate, or rapamycin, synergistic antitumor efficacy was observed. Conclusions: These data validate AGS-16 as an attractive target for kidney and liver cancers, and establish AGS-16M18 as a potential therapeutic MAb for these cancer indications. Activities are underway to progress this promising AGS-16M18 into human clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Agensys Agensys
Case 27-2016
Authors: Farrin A. Manian, Miriam B. Barshak, Kathryn P. Lowry, Kristen M. Basnet, Christopher P. Stowell
Journal: New England Journal of Medicine (2016)

A 71-year-old woman with müllerian carcinoma was admitted to the hospital because of fever, fatigue, and myalgias 3.5 weeks after extensive cytoreductive surgery. Anorexia, abdominal pain, and bloating had developed 1 day earlier. Diagnostic studies were performed.
Abciximab + tPA Improves Coronary Flow in a Wide Range of Subgroups: Results from TIMI 14
Authors: R. P. Giugliano, E. M. Antman, C. H. Mccabe, K. M. Anderson, A. A. J. Adgey, N. S. Kleiman, M. Ghali, F. V. n De Werf, E. Braunwald
Journal: Circulation (1998)
Outcome of the Swedish Nationwide Abdominal Aortic Aneurysm Screening Program
Authors: Anders Wanhainen, Rebecka Hultgren, Anneli Linné, Jan Holst, Anders Gottsäter, Marcus Langenskiöld, Kristian Smidfelt, Martin Björck, Sverker Svensjö, Linda Lyttkens, Ewa Pihl, Tomas Wetterling, Per Kjellin, Ken Eliasson, Erik Wellander, Azin Narbani, Elisabet Skagius, Alexandra Hollsten, Martin Welander, Toste Länne, Bibbi Fröst, David Korman, Sven-Erik Persson, Birgitta Sigvant, Thomas Troëng, Markus Palm, Eva Ansgarius, Nils-Peter Gilgen, Christina Sjöström, Khatereh Djavani Gidlund, Peter Danielsson, Adam Bersztel, Tomas Jonasson
Journal: Circulation (2016)

A general abdominal aortic aneurysm (AAA) screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006 and reached nationwide coverage in 2015. The aim of this study was to determine the outcome of this program.Data on the number of invited and examined men, screening-detected AAAs, AAAs operated on, and surgical outcome were retrieved from all 21 Swedish counties for the years 2006 through 2014. AAA-specific mortality data were retrieved from the Swedish Cause of Death Registry. A linear regression analysis was used to estimate the effect on AAA-specific mortality among all men ≥65 years of age for the observed time period. The long-term effects were projected by using a validated Markov model.Of 302 957 men aged 65 years invited, 84% attended. The prevalence of screening-detected AAA was 1.5%. After a mean of 4.5 years, 29% of patients with AAA had been operated on, with a 30-day mortality rate of 0.9% (1.3% after open repair and 0.3% after endovascular repair, P<0.001). The introduction of screening was associated with a significant reduction in AAA-specific mortality (mean, 4.0% per year of screening, P=0.020). The number needed to screen and the number needed to operate on to prevent 1 premature death were 667 and 1.5, respectively. With a total population of 9.5 million, the Swedish national AAA-screening program was predicted to annually prevent 90 premature deaths from AAA and to gain 577 quality-adjusted life-years. The incremental cost-efficiency ratio was estimated to be €7770 per quality-adjusted life-years.Screening 65-year-old men for AAA is an effective preventive health measure and is highly cost-effective in a contemporary setting. These findings confirm the results from earlier randomized controlled trials and model studies in a large population-based setting of the importance for future healthcare decision making.
C6-06: Gene expression signatures associated with lung adenocarcinomas in female non-smoker Chinese patients
Authors: David C. Lam, Luc Girard, Wing-Shun Chau, Issan Y. Tam, David G. Beer, Adi F. Gazdar, Lap-Ping Chung, Maria P. Wong, Wah-Kit Lam, John D. Minna
Journal: Journal of Thoracic Oncology (2007)
Expanded Circulating Tumor Cells from a Patient with ALK- Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study
Authors: Zhuo Zhang, Hiroe Shiratsuchi, Nallasivam Palanisamy, Sunitha Nagrath, Nithya Ramnath
Journal: Journal of Thoracic Oncology (2016)
Abstract 16255: Left Cervical Vagal Nerve Stimulation Suppresses Cardiac Sympathetic Tone
Authors: Yuan Yuan, Jonathan Hassel, Anisiia Doytchinova, David Adams, Keith Wright, Vicenta Salanova, Chad Meshberger, Lan S Chen, Shien-Fong Lin, Thomas Everett, Peng-Sheng Chen
Journal: Circulation (2015)

Background: In ambulatory dogs, the left cervical vagal nerve stimulation (VNS) reduces stellate ganglion nerve activity (SGNA) and heart rate, while upper thoracic skin sympathetic nerve activity (SKNA) has been shown to be a surrogate of SGNA to measure sympathetic tone. Objective: To test the hypothesis that VNS suppresses SKNA in human. Methods: We used conventional electrocardiogram (ECG) patches to continuously record SKNA in 12 patients who were admitted for video electroencephalographic monitoring. The ECG patches were placed under the right subclavian and left subclavian areas to form Lead I. The signals were band pass filtered between 200 to 1000 Hz to reveal SKNA. All antiepileptic medications were withdrawn. No patients had known organic heart diseases. No seizures occurred during the recording period. Nerve activity was quantified by integrating (iSKNA) the absolute value of the filtered signal over a 1 min window at intervals of 2 min, 20 min, and 40 min past each hour between 6 AM and 1 PM. Heart rate was determined by calculating the R-R intervals. Results: Six patients (2 men, age 40±5 years ) received chronic left cervical VNS (VNS group) and 6 (1 man, age 44±7 years) had no VNS pacing (control group). The admission diagnoses were generalized seizure (N=1) and partial seizure (N=5) in VNS group; generalized seizure (N=2) and partial seizure (N=4) in control group. The VNS pacing was continuous with an ON-time of 30 s and OFF-time of 158±72 s. The output was 1.92±0.42 mA with a frequency of 24.17±2.01 Hz. Fast Fourier Transform of the signals showed only physiologic activity between 200-1000 Hz. The iSKNA during VNS OFF-time was 13.77 mV-s [95% confidence interval, CI, 11.09 to 16.45], which was significantly lower than 20.75 mV-s [95% CI, 16.34 to 25.16, p=0.006] of the control Group. The heart rate was 67 bpm [95% CI, 60 to 74] in VNS group, significantly lower than 73 bpm [95% CI, 63 to 84] in control group. Conclusion: Patients with left cervical VNS had lower heart rate and iSKNA than patients without VNS. These findings are consistent with those observed in ambulatory canines, and suggest that chronic intermittent VNS can suppress cardiac sympathetic tone in human.
Long-term survival of non-small cell lung cancer (nsclc) patients with t4n0-n1 disease treated with sequential or concurrent chemo-radiation
Authors: Bart Reymen, Angela Van Baardwijk, Rinus Wanders, Jacques Borger, Ruud Houben, Anne-Marie C Dingemans, Gerben Bootsma, Cordula Pitz, Ragnar Lunde, Wiel Geraedts, Philippe Lambin, Dirk De Ruysscher
Journal: Journal of Thoracic Oncology (2011)
Role of the p38αMAPK in the prognosis and prediction of response to neoadjuvant chemotherapy in locally advanced non-small cell lung cancer (NSCLC).
Authors: P. Pardo-Coto, E. Esteban, A. Astudillo, J. Gracia, N. Corral, J. Berros, M. Izquierdo, C. Muriel, M. F. de Sanmamed, A. J. Lacave
Journal: Journal of Clinical Oncology (2010)

e21073 Background: Lung cancer is the most frequent cause of mortality. There are a lot of studies related with prognosis or prediction of response in metastatic disease, but not so many with locally advanced disease and neoadjuvant chemotherapy. The protein P-p38α is involved in many cellular pathways related with cancer and could have a role in the response to platinum compounds. Methods: Retrospectively, a cohort of 48 patients with the diagnosis of locally advanced NSCLC was analyzed between January 2000 and December 2006. All patients received platinum based neo-adjuvant chemotherapy followed by surgery. Three tissue microarrays were used and levels of P-p38α were analyzed by inmunohistochemistry (IHC). Results: Overall, patients with nuclear 3+ level of P-p38α in the initial biopsy, had a better overall survival (OS) than those 2+ or less (p = 0.046). After chemotherapy, OS tended to be superior in positive nuclear P- p38α (nP-p38) (p = 0.8). In a model analysis including P-p38 related with pathological response (PR) and karnofsky index (KI), patients with PR and nP-p38+ had better OS than those with the same characteristics but with P-p38- (44.1 vs 30.2 months) (p = 0.023). Patients with PR, good KI (80 or more) and nP-p38+ had better OS than those with the same characteristics except for nP-p38- (55.9 vs 30.2 months) (p = 0.05). Conclusions: P-p38α might be a good biomarker in lung cancer, especially for those patients considered to be good responders and with the best prognosis after receiving previous chemotherapy to surgery in locally advanced disease. Further studies to support this hypothesis are needed. No significant financial relationships to disclose.
Delaying and Preventing Ischemic Events in Patients with Acute Coronary Syndromes Using the Platelet Glycoprotein IIb/IIIa Inhibitor Lamifiban
Authors: RA Harrington, DJ Moliterno, Frans Van de Werf, A Keech, N Kleiman, MV Bhapkar, A Rames, M Peek, EJ Topol, RM Califf
Journal: Journal of the American College of Cardiology (1997)
Overlapping Coronary Stents Result in an Increased Neointimal Hyperplasia Response. Insight From a Porcine Coronary Stent Model
Authors: De S, K Wang, Z Rong, QB Ping, Yanming Huang, H Jianhua, XS Liu, Monika Szilard, Eric Verbeken, X Zhu, Frans Van de Werf
Journal: Journal of the American College of Cardiology (1999)
ANG1005: Results of a phase I study in patients with advanced solid tumors and brain metastases.
Authors: J. Sarantopoulos, N. Y. Gabrail, S. L. Moulder, A. J. Brenner, C. L. Smith, D. Bouchard, K. Elian, B. Lawrence, J. Castaigne, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

2556 Background: ANG1005 is a novel taxane derivative created from Angiochem's Engineered Peptide Compound (EPiC) platform shown to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein (LRP), which is highly expressed on the surface of the BBB and upregulated on various tumor cells. Methods: Patients (pts) with advanced solid tumors, adequate organ function, ECOG ≤2 received ANG1005 by IV infusion q21d without premedication. Brain metastases were required at the maximum tolerated dose (MTD). Doses were escalated using a modified Fibonacci scheme in sequential cohorts of 1-6 pts each. Study objectives included characterizing safety, tolerability, PK, identifying the MTD and obtaining preliminary evidence of efficacy. Results: 56 pts received ANG1005 at doses of 30-700 mg/m2; 20 at 650 mg/m2, the identified MTD and recommended phase II dose. Median age: 54, male: 43%, ≥3 prior therapies: 73%, brain mets: 48 pts. Most common adverse events (≥Gr. 2, CTCAE v.3.0) were leucopenia (73%), neutropenia (66%), anemia (48%), and fatigue (30%); events were transient and manageable. The dose-limiting toxicity was Gr. 4 thrombocytopenia. No evidence of CNS toxicity or antibody production even in pts who received multiple doses. Only 5 infusion-related reactions and no significant peripheral neuropathy (1 Gr.3 at MTD). PK data indicate linear ANG1005 bioavailability and no accumulation. At 650 mg/m2, Cycle 1: Cmax 306 ug/mL, AUCinf 2571 ug·h/mL, T1/2 4.0 h, CL 285 mL/m2·h. Plasma concentrations of free paclitaxel measured at MTD revealed that it accounted for only a small fraction (∼10%) of total plasma exposure. Overall disease control (≥ SD by RECIST) was achieved in 71% of pts dosed >300 mg/m2 including 7 pts who failed prior taxane therapy. PR in 7 pts at MTD: 3 Breast, 2 NSCL, 1 Ovarian, 1 SCL. Important reductions were also achieved in metastases located in organs including the liver, lung and lymph nodes. Median time to progression was 18 wks in responders (≥ SD) and 9.7 wks in all patients. Conclusions: ANG1005 is safe and well tolerated and demonstrates activity in advanced solid tumors and brain metastases, a disease for which there is currently no approved chemotherapy drug. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Angiochem Inc. Angiochem Inc.
Radiation injury versus malignancy after stereotactic radiosurgery for brain metastases: impact of time-dependent changes in lesion morphology on MRI
Authors: Sabine Wagner, Heinrich Lanfermann, Gerrit Eichner, Hubert Gufler
Journal: Neuro-Oncology (2016)

We sought to determine whether radiation-induced injuries could be distinguished from malignancy after stereotactic radiosurgery (SRS) by analyzing time-dependent changes in lesion morphology on sequential MRI for up to 55min.In 31 consecutive patients treated with SRS for brain metastases, the time-dependent changes in lesion morphology were analyzed on MRI 2min, 15min, and 55min after contrast administration and on subtraction images. A simultaneous, matched-pairs approach was used for quantitative region of interest analysis of the area of the lesion. Qualitative analysis comprised the shape of the border, the structure of the interior area, the presence of leptomeningeal enhancement, and feeding vessels. The signal intensity changes of the border and the interior area of the lesions over time were assessed visually. The time-dependent changes in the 2 entities were compared.Twenty radiation-induced injuries and 21 malignancies were analyzed. A significant interaction effect between time point and diagnosis (P<.001) was found for the time-dependent changes of the margin of the lesion for 2min to 15min and in signal intensity differences of the rim and interior area as well as of the size of the interior area for up to 55min. All radiation-induced injuries showed a black interior area on the subtraction images for 15min minus 55min, whereas all malignant lesions had white components (P<.001).Analysis of time-dependent changes in lesion morphology on sequential MRI for up to 55min is a reliable tool to distinguish radiation-induced injuries from malignancy after SRS.
B7-02: Identification of differentially methylated CpG Islands in the early stage of human pulmonary adenocarcinoma
Authors: Weihong Sun, Tatsuo Iijima, Junko Kano, Yoichi Anami, Yukinori Inadome, Yukio Morishita, Chigusa Okubo, Masayuki Noguchi
Journal: Journal of Thoracic Oncology (2007)
Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma.
Authors: Cristina Gasparetto, Jon P Gockerman, Louis F Diehl, Carlos de Castro, Joseph O Moore, Gwynn D Long, Mitchell Horwitz, John Chute, Keith M Sullivan, Rachel Neuwirth, Patricia H Davis, Linda M. Sutton, Russell D Anderson, Nelson Chao, David A. Rizzieri
Journal: Blood (2008)