tbuckley/cabot-search huggingface dataset:
A phase II trial of everolimus and bevacizumab in advanced non-clear cell renal cell cancer.
Authors: Martin Henner Voss, Yingbei Chen, Joshua Chaim, Devyn Taylor Coskey, Kaitlin Woo, Sujata Patil, Ana M. Molina, James Hsieh, Robert J. Motzer, Darren Richard Feldman
Journal: Journal of Clinical Oncology (2015)

411 Background: VEGF- and mTOR-directed therapies achieve inferior outcomes in patients (pts) with advanced non-clear cell renal cell cancer (ncRCC) as compared to clear cell RCC. Limited effectiveness of monotherapy supports the study of combination regimens, and a phase II trial of everolimus (E) + bevacizumab (B) was conducted in pts with metastatic ncRCC. Methods: Treatment-naïve pts received E + B at standard doses until progression or intolerance to therapy. The primary endpoint was progression free survival (PFS) with the goal to see 22 of 34 pts progression-free on treatment &gt;6 months (mo). Correlative analyses include next generation sequencing (NGS) from tumor and germline across 341 genes of interest, as well as immunohistochemistry (IHC) for markers of mTOR activation and vessel density. Results: 34 pts were enrolled, all are evaluable (median follow up 11.2 mo). The most common histologic subtype was unclassified RCC (URCC, n=23), the majority of which had papillary growth as a major component (URCC with papillary features, n=14). Other variants included chromophobe (n=5), papillary (n=4), and medullary RCC (n=2). 19 pts achieved PFS &gt;6 mo; 8 continue on treatment. PFS varied by histology (p&lt;0.001), and objective response rates (ORR) were higher in pts with significant papillary (7 of 18) or chromophobe (2 of 5) elements, than for the remaining pts (1 of 11). Presence of a major papillary component was associated with treatment benefit across the entire cohort (Table), particularly in the subgroup of URCC, where this feature correlated with ORR (43 vs. 11%), median PFS (12.9 vs. 1.9mo) and OS (18.5 vs. 9.3 mo) (p&lt;0.001). IHC markers did not correlate with treatment effect. NGS was performed on 33 cases. Conclusions: ncRCC represent a heterogeneous group of malignancies. This study did not reach its primary endpoint, yet it suggests efficacy for E+B in patients with ncRCC characterized by papillary features. Genomic tumor and germline analysis is being performed to help define the underlying biology. Clinical trial information: NCT01399918. [Table: see text]
A Phase Ii Study (Nct01883323) Evaluating the Infusion of Autologous Tumor-Infiltrating Lymphocytes (Til) and Low-Dose Interleukin-2 (Il-2) Therapy Following Non-Myeloablative Lymphodepletion Using Cyclophosphamide and Fludarabine in Patients with Metastatic Melanoma
Authors: L.T. Khoja, L. Nguyen, L. Wang, B. Zhang, J. Nie, P.H. Yen, M. Pnaik, M. Powis, N. Franke, M. Crump, D. Hogg, A.M. Joshua, P. Ohashie, M.O. Butler
Journal: Annals of Oncology (2014)
Abstract 5852: The Impact of Donor-Recipient Gender Pairing On Survival Following Orthotopic Heart Transplantation - An Analysis Of Over 18,000 Matches
Authors: Eric S Weiss, Nishant D Patel, Stuart D Russell, William A Baumgartner, Ashish S Shah, John V Conte
Journal: Circulation (2008)

Introduction : Single institution series have suggested that donor-recipient gender matching may be an important factor influencing survival following orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides a unique and novel opportunity to address this issue by examining outcomes based on gender pairing for a large cohort of OHT patients. Methods : We retrospectively reviewed the UNOS dataset to identify 18,240 patients receiving first time OHT between the years 1998 and 2007. Stratification was by both donor and recipient gender so that 4 separate groups were created (male donor with male recipient, female donor with male recipient, male donor with female recipient, and female donor with female recipient). The primary endpoint of all cause mortality was compared between groups using a Cox proportional hazard regression model. Secondary outcomes (thirty day and one year mortality and rejection during the first year) were examined with multiple logistic regression. Post transplant survival was modeled via the Kaplan Meier method. Results : Of 18,240 patients, 12,951 (71%) were matched by gender to their donor (77% for male recipients, n= 10,750 and 51% for female recipients n= 2,201). A total of 4,543 patients died during the study period (25%). Donor-recipient gender matching resulted in a reduction in the risk of adjusted cumulative mortality (Hz ratio 0.86 [0.78–0.95], p= 0.003) and the greatest risk for cumulative mortality occurred when pairing a male donor with a female recipient (Hz ratio 1.2 [1.04–1.37], p= 0.01). Thirty day and one year mortality were also significantly decreased by gender pairing (OR 0.75 [0.61–0.95], p= 0.02 for 30 day mortality, and OR 0.8 [0.68–0.93], p= 0.005 for one year mortality). Gender pairing resulted in a 13% decrease in the risk of graft rejection within the first year (OR 0.87 [0.79–0.98], p= 0.02]. Kaplan Meier survival modeling revealed that the greatest cumulative survival occurred when a male recipient received an organ from a male donor (Figure) Conclusions : The UNOS dataset has provided a large sample examining donor recipient gender pairing in OHT. Recipients who receive organs for same sex donors have significantly improved short and long term survival.
Pegylated filgrastim (PF) after high dose chemotherapy (HDC) and autologous stem cell transplant (ASCT)
Authors: M. H. Jagasia, J. Greer, A. Kassim, S. Mineishi, D. Morgan, K. Ruffner, F. Schuening
Journal: Journal of Clinical Oncology (2004)

6639 Background: PF (6 mg fixed dose) is equivalent to daily filgrastim (F) (5 mcg/kg/day for 14 days) after chemotherapy in decreasing the duration of neutropenia. Daily F (5 mcg/kg) started after HDC and ASCT leads to significant decrease in time to neutrophil engraftment (NE). The role of PF after HDC and ASCT is not known. We propose to study the role of PF given as a single fixed dose (6 mg) SQ on day +1 after stem cell (SC) infusion. Methods: Fifteen patients (pts.) undergoing HDC and ASCT using peripheral blood SC for multiple myeloma or lymphoma have been enrolled in an ongoing study. SC were collected with peripheral blood pheresis after cyclophosphamide (3 g/sq.m) and daily F (10 mcg/kg). All pts. were eligible for HDC and ASCT as per institutional criteria and consented. The conditioning regimens were high dose melphalan (200 mg/sq.m) for myeloma, and cyclophosphamide (7200 mg/sq.m), BCNU (400 mg/sq.m) and infusional etoposide (2400 mg/sq.m) for lymphoma. Pts. received antiinfective prophylaxis with acyclovir, levofloxacin and flucanozole starting day -1. Packed red blood cells (PRBC) and platelets were administered for a hematocrit and platelet count of less than 25% and 20,000 thousand/micro.L, repsectively. Results: There were no adverse events attributable to PF. All pts. engrafted neutrophils and platelets. The median time to NE was 10 days (range, 8–11). Incidence of febrile neutropenia was 67%, with a median duration of 2 days (range, 1–4). Twenty-three bacterial blood cultures were obtained in 10 pts. for febrile episodes or a suspected line infection, with only 5 (in 5 pts.) being positive, all for coagulase negative staphylococcus. Antibacterials other than for prophylaxis was required in 60% (9/15) of patients. Antifungals other than for prophylaxis were not required. The median time to platelet engraftment was 17 days (range, 14–19). The median number of transfusions was 3 units of PRBC and 12 units of platelets. The median numbers of days with mucositis and total parentral nutrition were 3 (range, 0–9) and 3 (range, 0–12), respectively. Conclusions: PF at a fixed dose of 6 mg SQ administered on day +1 after HDC and ASCT appears to be equivalent to daily F. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology
Authors: Veli‐Pekka Harjola, Alexandre Mebazaa, Jelena Čelutkienė, Dominique Bettex, Hector Bueno, Ovidiu Chioncel, Maria G. Crespo‐Leiro, Volkmar Falk, Gerasimos Filippatos, Simon Gibbs, Adelino Leite‐Moreira, Johan Lassus, Josep Masip, Christian Mueller, Wilfried Mullens, Robert Naeije, Anton Vonk Nordegraaf, John Parissis, Jillian P. Riley, Arsen Ristic, Giuseppe Rosano, Alain Rudiger, Frank Ruschitzka, Petar Seferovic, Benjamin Sztrymf, Antoine Vieillard‐Baron, Mehmet Birhan Yilmaz, Stavros Konstantinides
Journal: European Journal of Heart Failure (2016)
Evaluation of antibodies induced by an HPV vaccine to cross-neutralize pseudovirions of vaccine-related HPV types
Authors: J. T. Bryan, J. F. Smith, W. Ruiz, M. K. Brownlow, M. J. Brown, M. T. Esser
Journal: Journal of Clinical Oncology (2006)

15008 Background: Human papillomavirus (HPV) is the causative agent of cervical cancer. The HPV types 6, 11, 16 and 18 quadrivalent L1 virus-like particle (VLP) vaccine has been shown to be highly efficacious in preventing HPV vaccine type-related disease. The HPV A7 species contains types 18, 45 and 59. The A9 species include types 16, 31, 33, 35, 52 and 58. The potential of the vaccine induced antibodies to cross-neutralize infection of pseudovirions (PsV) of HPV types within the A9 and A7 species was evaluated. Methods: Sera from quadrivalent, monovalent HPV 16, or monovalent HPV 18 vaccinees were evaluated. Sera were tested in a multiplexed competitive Luminex Immunoassay (cLIA) against vaccine types to demonstrate HPV type-specific seroconversion. A9 and A7 VLP type cross-reactive binding ability was assessed by a total IgG LIA. HPV L1 and L2 PsV containing secreted alkaline-phosphatase (SEAP) sequences were constructed using native HPV sequences for 16 and 31 and with mammalian codon-optimized sequences for 18 and 45. Demonstrated expression of SEAP was used as an indirect measure of PsV infection of 293TT cells. Results: All subjects seroconverted to high titers against the vaccine HPV types. Cross-reactive antibodies were generated. Quadrivalent vaccinee sera bound to HPV 31, 45, 52 and 58 VLPs. These total IgG titers were 1.5–2 logs lower than the titers to the vaccine types. PsV types 18 and 45 were neutralized using the 18 monovalent and the quadrivalent sera. At month 7, the PsV 18 neutralization titer was ∼1–1.5 logs less than that required for PsV 45 cross-neutralization. Neutralization studies using PsV of the A9 species are in progress. Conclusions: High titers of anti-HPV antibodies are elicited by vaccination with HPV VLP vaccines. These antibodies can prevent in vitro PsV infection of vaccine-HPV types. Cross-reactive, cross-neutralizing antibodies are generated, however at reduced titers compared to the vaccine-specific types. Antibody titers required for cross-protection against non-vaccine types are not known. [Table: see text]
Abstract B2-29: The reverse control of colorectal tumorigenesis based on Boolean network modeling of human signaling network
Authors: Cho Sung-Hwan, Park Sang-Min, Lee Ho-Sung, Lee Hwang-Yeol, Cho Kwang-Hyun
Journal: Cancer Research (2015)

Abstract The intracellular processes are governed by a signal transduction network composed of complex interactions of a number of signaling proteins and various human diseases including cancer are known to be caused by the rewiring of the complex signaling network owing to the individual genetic mutations. There have been many studies on the dynamical analysis of the human signaling network to investigate the progression mechanism of human diseases, but most of the results were limited to small-scale signaling pathways. In this study, we have reconstructed a large-scale signaling network model composed of 197 nodes and 745 relations based on Boolean modeling and performed attractor landscape analysis to uncover the mechanism of colorectal tumorigenesis caused by driver mutations. In addition, we have investigated the reverse control of tumorigenesis by changing the attractor landscape of colorectal cancer state that has been deformed by the driver mutations. Our results show that colorectal tumorigenesis can occur by the expansion of the cancer attractor basin due to the accumulation of driver mutations. We found a minimal control set of network components that can reverse the cancerous state into a normal state. Together, these results suggest a new therapeutic strategy for the treatment of colorectal cancer and provide a new insight into the drug target excavation. Acknowledgement: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea Government, the Ministry of Science, ICT &amp; Future Planning (2014R1A2A1A10052404, 2013M3A9A7046303, and 2010-0017662). Citation Format: Cho Sung-Hwan, Park Sang-Min, Lee Ho-Sung, Lee Hwang-Yeol, Cho Kwang-Hyun. The reverse control of colorectal tumorigenesis based on Boolean network modeling of human signaling network. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-29.
Opioid Prescribing for Chronic Pain
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2016)

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Abstract 11005: Clinical Value of Angiotensin-converting Enzyme Inhibitor and Angiotensin Receptor Blocker in the Patients of Coronary Artery Disease
Authors: Daisuke Abe, Akira Sato, Masako Misaki, Noriyuki Takeyasu, Tomoya Hoshi, Kazutaka Aonuma
Journal: Circulation (2013)

In Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), there was evidence of blood pressure-independent effects on the risk of major coronary disease event for angiotensin-converting enzyme inhibitors (ACEI), but not angiotensin receptor blocker (ARB). We investigated clinical outcomes of patients who treated with percutaneous coronary intervention (PCI) and administrated with ACEI or ARB. Method: A total of 3943 patients (69.8±10.9 year-old, 77% male) who underwent PCI from April 2007 to July 2012 were enrolled. We evaluated 375 patients continuously treated with ACEI and 810 patients with ARB. The selection bias of medication was adjusted by propensity score-matching method; propensity score-matched ACEI (n=315) and ARB (n=315). We investigated major adverse cardiac-cerebral events (MACCE) and incidence of stent thrombosis (ST). MACCE were defined as all cause death, myocardial infarction (MI), target vessel revascularization (TVR) or cerebrovascular accidents (CVA). Results: During med...
Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium
Authors: Michael C. Reade, Glenn M. Eastwood, Rinaldo Bellomo, Michael Bailey, Andrew Bersten, Benjamin Cheung, Andrew Davies, Anthony Delaney, Angaj Ghosh, Frank van Haren, Nerina Harley, David Knight, Shay McGuiness, John Mulder, Steve O’Donoghue, Nicholas Simpson, Paul Young
Journal: JAMA (2016)

Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded.Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician.Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori.Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.clinicaltrials.gov Identifier: NCT01151865.
Inhibitory Effect of Fumaric Acid on Forestomach and Lung Carcinogenesis by a 5-Nitrofuran Naphthyridine Derivative in Mice
Authors: K Kuroda, M Kanisawa, M Akao
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Inhibitory Effect of Fumaric Acid on Forestomach and Lung Carcinogenesis by a 5-Nitrofuran Naphthyridine Derivative in Mice Get access Keiko Kuroda, Keiko Kuroda Search for other works by this author on: Oxford Academic PubMed Google Scholar Masayoshi Kanisawa, Masayoshi Kanisawa Search for other works by this author on: Oxford Academic PubMed Google Scholar Mitsutaro Akao Mitsutaro Akao Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 6, December 1982, Pages 1317–1320, https://doi.org/10.1093/jnci/69.6.1317 Published: 01 December 1982 Article history Received: 04 January 1982 Revision received: 10 July 1982 Accepted: 04 August 1982 Published: 01 December 1982
Cell cycle regulators and benefit of adjuvant chemotherapy in patients with non-small cell lung cancer
Authors: R. Pirker, M. Filipits, A. Dunant, S. Lantuejoul, K. Schmid, A. Huynh, J. Soria, H. H. Popper, T. Le Chevalier, E. Brambilla
Journal: Journal of Clinical Oncology (2006)

7100 Background: The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the 5-year survival rate of patients with completely resected non-small-cell lung cancer (NSCLC) by absolute 4.1% (N Engl J Med 350, 351–360, 2004). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in NSCLC patients who were enrolled into IALT. Methods: Expression of cell cycle regulators and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted on clinical and pathological parameters. Results: Expression of p16, p27, cyclin D1, cyclin D3, cyclin E and Ki-67 was considered as positive in 37%, 40%, 74%, 37%, 55% and 29% of tumor specimens, respectively. None of these biomarkers was significantly associated with overall survival of the patients. However, there was a relationship of borderline significance between p27 status and benefit of cisplatin-based chemotherapy (test for interaction, p = 0.04). Patients with p27-negative tumors who were treated with cisplatin-based chemotherapy had a longer overall survival than patients from the observation group (hazard ratio for death [95% CI]: 0.71 [0.55–0.93]), whereas in patients with p27-positive tumors overall survival was not different between the two groups (hazard ratio for death [95% CI]: 1.11 [0.81–1.51]). In contrast to p27, the other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. Conclusions: NSCLC patients with p27-negative tumors appear to benefit most from adjuvant cisplatin-based chemotherapy following complete tumor resection. Thus, the predictive value of p27 should be confirmed in prospective trials. No significant financial relationships to disclose.
Phase II study of ifosfamide, carboplatin, and etoposide in patients with a first recurrence of glioblastoma multiforme.
Authors: T. Aoki, T. Mizutani, K. Nojima, T. Takagi, R. Okumura, Y. Yuba, T. Ueba, J. A. Takahashi, S. Miyatake, K. Nozaki
Journal: Journal of Clinical Oncology (2010)

e12512 Background: The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good quality life. Methods: This trial was an open-label, single-center phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1,000 mg/m2 on Days 1, 2, and 3), carboplatin (110 mg/m2 on Day 1), etoposide (100 mg/m2 on Days 1, 2, and 3), every 6 weeks. Results: Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22%–50%). The median duration of PFS was 17 weeks (95% CI 10–24 weeks). The response rate was 25% (95% CI 9%–34%). Adverse events were generally mild and consisted mainly of alopecia. Conclusions: This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM. No significant financial relationships to disclose.