tbuckley/cabot-search huggingface dataset:
Abstract 11419: Subclinical Arterial Remodeling of Thoracic Aorta in Subjects Without Cardiovascular Events: A Magnetic Resonance Imaging Study
Authors: Yan Song, Jie Sun, Daniel S Hippe, Niranjan Balu, Xihai Zhao, Feiyu Li, Thomas Hatsukami, Chun Yuan
Journal: Circulation (2014)

Background: Arterial remodeling is thought to be implicated in the pathogenesis of vascular diseases such as atherosclerosis and aneurysm. Although a phenomenon known as positive remodeling has been observed in the coronary artery, the remodeling patterns of other arterial beds remain poorly understood. By delineating vessel wall morphology noninvasively, cardiovascular magnetic resonance (MR) may afford a unique opportunity to study arterial remodeling in the general population. Using MR imaging, we sought to examine the remodeling pattern of thoracic aorta in a large cohort of subjects free of prior cardiovascular events. Methods: This study was a branch of High-Risk Plaque(HRP) Initiative. Three hundred and seventy-seven subjects, with no cardiovascular events but a broad spectrum of cardiovascular risk factors, were recruited. Two-dimensional MR imaging of the thoracic aorta was performed from aortic arch to the diaphragm level. Lumen area, total vessel area, and mean wall thickness were measured on e...
Abstract 13276: FoxO4 Promotes Post Myocardial Infarction Left Ventricular Remodeling
Authors: Min Zhu, Sydney Morris, Zhi-Ping Liu
Journal: Circulation (2013)

Myocardial infarction (MI) can result in a maladaptive remodeling of left ventricles (LV) that leads to LV dysfunction and eventual heart failure. Forkhead box O transcription factors (FoxO1, O3, a...
Abstract 3322: Adding pericyte inhibition to combined anti-angiogenesis and irradiation slows tumor growth but increases metastasis in mice model
Authors: Lei Deng, Jiazhuo He, Jianxin Xue, Jie Lan, Lin Zhou, Yongmei Liu, You Lu
Journal: Cancer Research (2015)

Abstract Increased pericyte coverage has been suggested to be one of the resistant mechanisms of anti-angiogenic treatment (AAT), but targeting pericytes disrupts tumor vascular normalization and abolishes the benefit of oxygenation for the combination of irradiation (IR) with AAT. This raises the question of whether pericyte inhibition should be added to the combination of AAT and IR. We and others have shown that Endostar (Endo), a humanized endostatin, induces a normalization window starting from D5, characterized by decreased tumor hypoxia and increased pericyte coverage of vessels. In this study, we tried to utilize the reduced hypoxia in vascular normalization window to radiosensitize tumor and attempted to test whether inhibiting pericytes after the window may result in optimal anti-tumor effect. Subcutaneous Lewis lung carcinoma was used as the tumor model. Pericyte inhibition was achieved by administering CP673451 (CP) at a dose of 20mg/kg, a platelet-derived growth factor receptor (PDGFR) inhibitor. Endo was given daily for 10 days. 12Gy/1f IR was administered on D5 post-endostar initiation. CP was given from D6 to D10 in order not to interfere with the hypoxia alleviation by Endo when IR was given. We found that percentage of pericyte-covered endothelial cells was the lowest in IR+Endo+CP group compared to IR alone and IR+Endo. IR+Endo+CP significantly reduced tumor growth rate compared to the other two groups. However, the local growth retardation was not translated to mice survival benefits, without even any trend could be suggested. We next found that trimodality treatment resulted in significantly more metastasis in mice lungs. This might be due to increased tumor hypoxia in RT+Endo+CP group, which was found to be the highest among the three. Thus, we hereby conclude that adding pericytes inhibition to the combination of IR and AAT even without interfering vascular normalization when IR is administered confers benefit to local tumor control but not to mice survival, due to increased hypoxia and distant metastasis. Citation Format: Lei Deng, Jiazhuo He, Jianxin Xue, Jie Lan, Lin Zhou, Yongmei Liu, You Lu. Adding pericyte inhibition to combined anti-angiogenesis and irradiation slows tumor growth but increases metastasis in mice model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3322. doi:10.1158/1538-7445.AM2015-3322
Dasatinib 140 mg QD compared to 70 mg BID in advanced-phase CML or Ph(+) ALL resistant or intolerant to imatinib: One-year results of CA180–035
Authors: R. Pasquini, O. G. Ottmann, Y. T. Goh, D. Kim, P. E. Dorlhiac Llacer, J. F. DiPersio, H. J. Khoury, J. M. Van Tornout, A. Damokosh, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7025 Background: Dasatinib, an oral multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases, has been shown to be safe and effective at 70 mg BID in advanced phase CML and Ph(+) ALL resistant or intolerant to imatinib. QD and BID schedules were equipotent in Phase I which led to this dose-optimization study. Methods: In this Phase-III, open-label, prospective study, patients with imatinib-resistant or intolerant advanced phase CML or Ph(+) ALL were randomized to dasatinib 140 mg QD or 70 mg BID. The primary objective compared the major hematologic response (HR) rate between the 2 regimens. Dose escalation was allowed for inadequate response and dose reduction for drug toxicity. Results: From June 2005 through March 2006, 611 patients (56% male) were randomized (median age 55 years). 42% of patients received imatinib at doses &gt;600 mg/d and 37% were treated for &gt;3 y. Response rates, with a median follow-up of 6.5 mo (range &lt;1 to 17 mo), are summarized in the table below. Median durations of HR and progression-free survival were 10.2 and 7.9 mo for the 140-mg QD regimen vs 12.3 and 11.7 mo in the 70-mg BID arm. Drug-related toxicities in 140-mg QD (n=304) vs 70-mg BID (n=305) arms, respectively, listed as all grades (grade 3–4), were: pleural effusion 16% vs 23%, P=0.024 (5% vs 6%); peripheral edema 6% vs 13%, P=0.004 (&lt;1%/1%); pericardial effusion &lt;1% vs 4%, P=0.012 (0% vs 1%); neutropenia 85% vs 87% (65% vs 70%); thrombocytopenia 89% vs 92% (68% vs 70%). Dose reductions (24% vs 36%, P=0.002) and interruptions (47% vs 54%, P=0.105) were required less frequently for the 140-mg QD regimen, whereas dose escalations were more prevalent (33% vs 22%, P=0.005). Conclusions: Dasatinib 140 mg QD shows comparable hematologic and cytogenetic response and a trend for improved tolerability in relation to 70 mg BID. Further follow-up is ongoing to assess the long-term benefit of these two schedules in patients with ABP-CML or Ph(+) ALL; 1-year follow-up will be presented. [Table: see text] [Table: see text]
Final results of a phase I study of oral belinostat (PXD101) in patients with solid tumors
Authors: W. K. Kelly, J. DeBono, G. Blumenschein, U. Lassen, J. Zain, O. O'Connor, F. Foss, J. Tjornelund, J. Fagerberg, D. Petrylak
Journal: Journal of Clinical Oncology (2009)

3531 Background: Belinostat (Bel) is a histone deacetylase inhibitor with broad preclinical activity. IV Bel is well-tolerated with clinical activity at 1 g/m 2 daily x5, q3w. Methods: Patients (pts) were treated with multiple schedules (see table) to assess safety, pharmacokinetics (PK) and efficacy. PK was done on day (d) 1 (fasting) and d7 (non-fasting) along with serial ECGs. Results: 92 pts, median age 60 (range 32–89) have been included. Major cancer types included colorectal (22%), prostate (17%), bladder (11%). Most frequent related adverse events (AEs), any grade (gr), were fatigue (53%), nausea (49%), anorexia (36%), vomiting (27%), diarrhea (25%). Only related gr 3/4 AE noted by more than 1 pt was fatigue. Hematological tox included gr 2: anemia (6 pts), leucopenia (2 pts), and thrombocytopenia (1 pt). Two events of gr 2 QTc prolongation were reported. Recommended dose (RD) for continuous dosing was determined as 250 mg, QD or BID, based on dose limiting toxicity (DLT; gr 3 if not indicated) seen in 2 pts in cohort 2A: dehydration and fatigue. Based on overall tolerability and DLTs (cohort 2C fatigue; 3C gr 2 nausea/vomiting/diarrhea; 4C atypical chest pain, elevated creatinine; 2D atrial fibrillation, hypokalemia, fatigue) the RD for d1–14 dosing was determined as 750 mg QD, with option for intra-pt dose escalation if limited tox. For d1–5 dosing, evaluation of the highest dose-cohort is not finalized; 1 pt had gr 3 psychosis, but also experienced same event 16d after treatment stopped. Exposure of Bel in plasma correlates with dose; PK on d1/d7 indicate a possible effect of food. To date, 33 pts (41%) have SD; 5 pts ≥6 months (d on treatment: 710 adenoidcystic, +488 bladder, 485 renal, 196 rectal, 182 prostate), and 12 pts 3–6 months. Conclusions: Oral Bel can be delivered safely with multiple schedules. The safety profile and long stabilizations in multiple tumor types makes Bel an interesting option for further evaluation as a monotherapy and in combination with chemotherapy. [Table: see text] [Table: see text]
TPF induction-radioimmunochemotherapy for the treatment of advanced head and neck cancer.
Authors: W. Jordan, I. Wildfang, H. Welkoborsky, J. Borghardt, H. Zakaria, S. Fanaei, H. Niebuhr, S. Luft, B. Tschechne
Journal: Journal of Clinical Oncology (2010)

5514 Background: This investigation evaluates the safety and feasibility of a TPF induction therapy under pegfilgrastim protection with a subsequent concomitant radioimmunochemotherapy using cetuximab and cisplatin. Methods: 152 patients with an advanced (T3/T4) head and neck cancer were treated. Median age was 57 (38-82), Karnofsky > 60%. Induction therapy consisted of three 21-day-cycles TPF (75 mg/m2 taxotere d1; 35 mg/m2 cisplatin d1,2; 750 mg/m2 5-FU d1-5) and on d7 a protective dose of 6 mg pegfilgrastim. Before and after induction therapy and after therapy completion PET-CT was used to evaluate response. PET-CT allowed for best possible RT-planning with best adapted field margins. Subsequent radioimmunochemotherapy consisted of 400 mg/m2 cetuximab on day 1 (initial dose) and seven weekly cycles of 250 mg/m2 cetuximab and 40 mg/abs cisplatin on day 1. Radiotherapy on d1-5/; 1.8 Gy/day for a median dose 61.4 Gy (58.1 - 70.2). Typical side effects (e.g. rash, mucositis) were treated accordingly. Results: Of 152 we were able to evaluate 150 patients after induction therapy completion. One death occured which was not treatment related. The response rates after induction therapy were determined by PET-CT: ORR 82%, CR 22% (33), PR 60% (90). After subsequent radioimmunochemotherapy 142 patients were evaluated also by PET-CT: ORR 89%; CR 57% (81); PR 32% (45). During radioimmunochemotherapy 34 grade III/IV toxicities were observed (skin rash, diarrhoe). All toxicities were reversible. In 15 patients therapy had to be interrupted for up to two weeks. 8 patients stopped treatment after the induction therapy. Conclusions: This regimen is safe, shows promise and deserves further development but should be limited to the clinical setting. PET-CT as a diagnostic and RT-planning tool, prophylactic pegfilgrastim as a myeloprotective agent and taxotere/cetuximab make a good combination. Especially during the induction therapy QoL is drastically improved. No significant financial relationships to disclose.
Compassionate use experience with gefitinib in poor performance (PS) patients with advanced non-small-cell lung cancer (NSCLC) treated in an expanded access program (EAP)
Authors: R. Zinner, R. Govindan, A. J. Wozniak, J. L. Wade, C. P. Belani, C. D. Thienelt, T. A. Hensing, R. B. Reiling, R. B. Natale, I. Wiznitzer
Journal: Journal of Clinical Oncology (2004)

7082 Background: Advanced NSCLC patients with a PS ≥ 2 have a poor prognosis and often receive less aggressive or no chemotherapy (CT) due to poor tolerance. CALGB study 9730 compared median and 1-year survival in 99 PS 2 NSCLC patients. Median and 1-year survival with paclitaxel was 2.4 mo and 10%, respectively; median and 1-year survival with paclitaxel and carboplatin was 4.7 mo and 18%, respectively. Gefitinib (Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor, has single-agent activity and a favorable tolerability profile in patients with advanced NSCLC. A retrospective review of 533 patients in the US enrolled in an EAP with gefitinib before Jan 2003 identified 117 patients with PS ≥ 2. Methods: Eligible patients had advanced NSCLC, failed standard treatment, or were not suitable for systemic chemotherapy. Patients received oral gefitinib 250 mg once daily for as long as therapy provided clinical benefit without significant toxicity. Results: Of 117 poor PS patients, 84 were PS 2 (71.8%) and 13 (11.1%) were PS 3; the remaining 20 (17.1%) had a PS of 4 (n=1), 2–3 (n=16), or 3–4 (n=3). There were 72 men and 45 women; median age 66.9 y (38.4–87.2 y). Eighteen (15.4%) and 92 (78.6%) patients had stage III and IV NSCLC, respectively. Adenocarcinoma was the predominant histology (53.8%). Most patients had previously received chemotherapy (82.1%) and/or radiation therapy (71.8%). Of 60 patients evaluated for response, 3.3% (95% CI, 0.0–7.9%) had a partial response and 38.3% (95% CI, 26.0–50.6%) had stable disease. The median duration of treatment for all poor PS patients was 1.0 mo (0–29 mo). Median survival was 2.0 mo; estimated 1-year survival was 15.7% (95% CI, 8.4–22.9%). Adverse events consisted primarily of mild skin rash (15.5%/23.1%) and diarrhea (16.7%/23.1%) in PS 2/3 patients, respectively. Conclusions: The median survival rate with gefitinib in PS ≥ 2 patients was comparable to that of single agent CT in PS 2 only patients, whereas the 1-year survival rate with gefitinib in PS ≥ 2 patients was comparable to that of single and double agent CT in newly diagnosed PS 2 only patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Lilly AstraZeneca AstraZeneca; Bristol-Myers Squibb; Lilly
Abstract 14894: Percutaneous Intramyocardial Injection of Mesenchymal Stromal Cells in Patients with Severe Stable Coronary Artery Disease and Refractory Angina: Final 3 Year Follow-Up
Authors: Anders B Mathiasen, Mandana Haack-Sorensen, Erik Jorgensen, Jens Kastrup
Journal: Circulation (2012)

Introduction Regenerative therapy with stem cells is an emerging treatment modality for patients with coronary artery disease (CAD). This study assessed long-term safety and efficacy of percutaneou...
Integration of Mutations and Karyotype Towards a Genetics-Based Prognostic Scoring System (GPSS) for Primary Myelofibrosis
Authors: Ayalew Tefferi, Paola Guglielmelli, Christy Finke, Terra L Lasho, Naseema Gangat, Rhett Ketterling, Curtis A. Hanson, Animesh Pardanani, Alessandro M. Vannucchi
Journal: Blood (2014)
Nucleotide sequence variation in the mitochondrial 12S rRNA gene and the phylogeny of African mole-rats (Rodentia: Bathyergidae).
Authors: M W Allard, R L Honeycutt
Journal: Molecular Biology and Evolution (1992)

Mitochondrial DNA (mtDNA) sequence variation was examined in eight taxa of the African rodent family Bathyergidae, as well as in two taxa representative of the Old-World hystricognathid rodent families Petromyidae and Thryonomyidae. A total of 812 bp, constituting domains I-III of the 12S ribosomal rRNA gene, were compared for each taxon. The high levels of intrafamilial mtDNA sequence divergence observed (average 16.8, range 3.5-23.2) support an ancient origin for the five genera, 20-38 Mya. These data do not support the current subfamilial groupings of the Bathyergidae. The eastern African naked mole-rat, Heterocephalus glaber, is the most basal representative of the family, with the silvery mole-rat, Heliophobius, being the next most basal. South African forms [dune, common, and cape mole-rats (Bathyergus, Cryptomys, and Georychus, respectively)] group together. The independent origin of the common mole-rat, relative to the naked mole-rat, suggests that complex social systems evolved in parallel along different bathyergid lineages. The 12S rRNA gene is not evolving at a higher rate within the rodent lineages, relative to that seen for artiodactyls and primates. Bathyergid rodents appear to fall at an extreme end of the spectrum of mammalian variation, with respect to both transition/transversion ratios and divergence, showing much lower transition/transversion ratios than those previously reported for intrafamilial comparisons.
Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3
Authors: Lynn A. Fussner, Amber M. Hummel, Darrell R. Schroeder, Francisco Silva, Rodrigo Cartin‐Ceba, Melissa R. Snyder, Gary S. Hoffman, Cees G. M. Kallenberg, Carol A. Langford, Peter A. Merkel, Paul A. Monach, Philip Seo, Robert F. Spiera, E. William St.Clair, Nadia K. Tchao, John H. Stone, Ulrich Specks
Journal: Arthritis & Rheumatology (2016)

Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse.Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression.An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P = 0.103 and P = 0.197, respectively).The association of an increase in PR3-ANCA level with the risk of subsequent relapse is partially affected by the PR3-ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3-ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3-ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.
Suppression of the Avian Sarcoma Virus Genome in Hamster-Transformed Cells Made Resistant to 8-Azaguanine
Authors: M. Hladká, C. Altaner
Journal: JNCI Journal of the National Cancer Institute (1974)

Hamster cells transformed by the Schmidt-Ruppin strain of avian sarcoma virus [Ha(SR)] were tested for their resistance to a-azaguanine (aza-G). The uncloned resistant cell line Ha(SR)AG-50 proliferated in the presence of 50 μg aza-G/ml in medium supplemented with hypoxanthine, amethopterin, thymidine, and glycine (HATG) and in normal medium. Sixteen single-cell clones were isolated in a medium containing 50 μg aza-G/ml from Ha(SR)AG-50 cells. All cell clones were resistant to aza-G. Two of 16 clones were deficient in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity; they did not grow in HATG, did not incorporate labeled hypoxanthine, and had negligible HGPRTactivity. The resistance of clones to aza-G was genetically stable. The properties of some aza-G-resistantcell clones were further studied. The aza-Gresistant cells were less tumorigenic in hamsters. Several cell clones were extensively tested for virus genome by fusion with chicken embryo cells and subsequent inoculation of cells to chickens. The virus genome was strongly suppressed in all aza-G-resistant cell clones. The HGPRT deficiency was not connected with virus genome suppression. The group-specific antigen was also inhibited in all aza-G-resistant cell clones compared with the parental clonal cell lines. The relationship of the presence of the virus genome in cells with properties called "transformed phenotype" and tumorigenicity was discussed.
Abstracts 1 to 209, LB1–LB5
Authors: James Neuberger, A David Mayer, Georges-Philippe Pageaux, Lionel Rostaing, Yvon Calmus, Christophe Duvoux, Claire Vanlemmens, Jean Hardgwissen, Paul-Henri Bernard, Francis Navarro, Dominique Larrey, Sandy Feng, John Roberts, Glenn Halff, Kenneth Washburn, Muhammad Dawwas, Collett David, Kerri Barber, Christo- Pher Watson, Alexander Gimson, Paul Hayashi, Paolo Sal- Valaggio, David Axelrod, Schnitzler Mark, Goran Klintmalm, Carlos Fasola, Linda Jennings, Thomas Heffron, Linda Sher, David Mulligan, Robert Brown, John Ham, Lewis Teperman, Stephen Rudich, Devin Eckhoff, Michael Millis, Michael Charlton, Prabhakar Baliga, Timothy Pruett, Elizabeth Pomfret, Baburao Koneru, Michael Abecassis, Prab- Hakar Baliga, Susan Gilmour, Lisa Sorensen, Ravinder Anand, Chong- Hong Song, Estella Alonso, Chonghong Song, Maximilian Bockhorn, Christian Fingas, Ursula Rauen, Andreja Frilling, Christoph Broelsch, Joerg Schlaak
Journal: Hepatology (2007)
C1q PRECIPITINS IN THE SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER HYPOCOMPLEMENTEMIC STATES: CHARACTERIZATION OF HIGH AND LOW MOLECULAR WEIGHT TYPES
Authors: V. Agnello, D. Koffler, J. W. Eisenberg, R. J. Winchester, H. G. Kunkel
Journal: The Journal of Experimental Medicine (1971)

Precipitin reactions of C1q in gel diffusion proved useful in detecting unknown complexes containing gamma-globulin in the sera of patients with SLE. Using this method low molecular weight C1q reactants also have been detected in a number of sera from patients with SLE as well as other diseases. Both the circulating complexes and the unidentified low molecular weight reactants are associated with disease activity and in vivo complement depression. In some sera from patients with SLE, circulating complexes as detectable by C1q precipitation were closely associated with cryoprecipitins and an active nephritic process. Evidence is presented that both rheumatoid factors and C1q interact with circulating complexes in these patients and that the interaction is related to cryoprecipitation. The demonstration of the same rheumatoid factors in the cryoprecipitates and in the renal glomerular deposits suggests that rheumatoid factors have a special significance in the presence of circulating complexes.