tbuckley/cabot-search huggingface dataset:
Abstract 4646: Occupational exposure to trichloroethylene and plasma concentrations of IL6, IL10, and TNF alpha
Authors: Bryan A. Bassig, Luoping Zhang, Xiaojiang Tang, Roel Vermeulen, Min Shen, Martyn T. Smith, Chuangyi Qiu, Yichen Ge, Zhiying Ji, Boris Reiss, Songwang Liu, Weihong Guo, Mark Purdue, Wei Hu, Laiyu Li, Nathaniel Rothman, Hanlin Huang, Qing Lan
Journal: Cancer Research (2011)

Abstract Trichloroethylene (TCE) is a chlorinated solvent primarily used as a vapor degreaser in many industries. TCE is currently classified by IARC as probably carcinogenic to humans (Group 2A), and has been associated with non-Hodgkin lymphoma (NHL) in some epidemiological studies, although the findings have been inconsistent. To explore the biologic plausibility that TCE may be a lymphomagen, we conducted a cross-sectional study of workers exposed to TCE in Guangzhou, China and tested if plasma levels of the cytokines IL6, IL10, and TNF-alpha, which play a critical role in regulating various components of the immune system, were altered in exposed workers. We enrolled 80 workers from factories where TCE was used as well as 96 unexposed controls matched by sex and age from food and clothes manufacturing factories. Personal exposure measurements were taken over a three-week period, two to three per subject, in the exposed subjects for a full work shift using a 3M badge, as well as for a subgroup of the control workers. Blood samples were collected from each subject, and plasma concentrations of IL6, IL10, and TNF-alpha were measured by ELISA. Linear regression using the natural logarithm of each endpoint and adjusting for potential confounders was used to test for differences in marker concentrations between controls and exposed workers. The mean TCE exposure level in exposed subjects was 23.9 ppm (95% C.I. 14.2-33.6 ppm). Compared to unexposed workers, the plasma concentration of IL10 in workers exposed to TCE was decreased by more than 50% compared to controls (p=0.003), while there was no difference in levels of IL6 or TNF-alpha in TCE exposed workers and controls. IL10 plays a critical role in mediating the Th1/Th2 balance, apoptosis, and regulation of inflammation. Genotypes associated with altered IL10 expression have also been associated with the development and progression of NHL. Given that immunologic alterations are suspected to play a role in lymphomagenesis, and IL10 plays an important role in immunologic processes, our findings provide some support for the biologic plausibility that TCE is associated with lymphoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4646. doi:10.1158/1538-7445.AM2011-4646
Epidermal growth factor receptor and variant III targeted immunotherapy
Authors: K. L. Congdon, P. C. Gedeon, C. M. Suryadevara, H. G. Caruso, L. J. N. Cooper, A. B. Heimberger, J. H. Sampson
Journal: Neuro-Oncology (2014)

Immunotherapeutic approaches to cancer have shown remarkable promise. A critical barrier to successfully executing such immune-mediated interventions is the selection of safe yet immunogenic targets. As patient deaths have occurred when tumor-associated antigens shared by normal tissue have been targeted by strong cellular immunotherapeutic platforms, route of delivery, target selection and the immune-mediated approach undertaken must work together to maximize efficacy with safety. Selected tumor-specific targets can spare potential toxicity to normal tissue; however, they are far less common than tumor-associated antigens and may not be present on all patients. In the context of immunotherapy for high-grade glioma, 2 of the most prominently studied antigens are the tumor-associated epidermal growth factor receptor and its tumor-specific genetic deletion variant III. In this review, we will summarize the immune-mediated strategies employed against these targets as well as the caveats particular to these approaches.
Systemic reforms are needed to reduce harmful medical overuse
Authors: J. Freeman
Journal: BMJ (2014)

The Choosing Wisely campaign is an excellent step forward in getting physicians to think about what they are doing, and to follow the evidence.1 That these lists of recommendations are generated by the physicians’ specialty societies likely increases their effectiveness.

Most of the recommendations, however, are fairly specific to individual patients, tepid, and not system changing. Widespread adoption of …
A NOVEL ENDOVASCULAR NITINOL IMPLANT PROVIDES A MINIMALLY INJURIOUS STENT ALTERNATIVE FOR CREATING TISSUE APPOSITION: A 90-DAY FEMORAL ARTERY STUDY IN SWINE
Authors: Athanasios Peppas, Robert Giasolli, Armando Tellez, Gerard Conditt, masahiko shibuya, Carol Burns, Peter Schneider, Renu Virmani, Frank Kolodgie, Greg Kaluza, Juan Granada
Journal: Journal of the American College of Cardiology (2014)
The carcinogenesis bioassay in perspective: application in identifying human cancer hazards.
Authors: V A Fung, J C Barrett, J Huff
Journal: Environmental Health Perspectives (1995)

The selection process for chemicals tested in the rodent carcinogenicity bioassay has been biased toward chemicals suspected of potential carcinogenicity. Results from carcinogenicity bioassays of 400 chemicals tested by the National Cancer Institute/National Toxicology Program (NCI/NTP) were analyzed to determine the dependence of positive results on chemical selection criteria: those suspected of being carcinogenic and those selected based on large volumes produced and widespread exposures. Of these chemicals, 210 (52%) induced carcinogenicity in at least one organ of one sex of one species of the four sex/species groups typically used by NCI/NTP. Only 92 of the 400 chemicals (23%) were positive in two species and thus by international criteria are considered likely to pose a carcinogenic hazard to humans. A total of 267 chemicals (67%) were selected as suspect carcinogens, and 187 (68%) of these were carcinogenic. Suspect chemicals account for 86% of chemicals with at least one positive result and account for 90% of chemicals considered positive in two species. The International Agency for Research on Cancer (IARC) lists only 5 of the 400 chemicals as carcinogenic to humans (group 1) and 10 as probably carcinogenic to humans (group 2A). The majority (80%) of the 133 chemicals selected only on production/exposure considerations were not carcinogenic in animals, even when tested at the maximum tolerated (or minimally toxic) dose. Only 9 (6.8%) were positive in two species, and none is listed in IARC groups 1 or 2A. Thus, on the basis of our analyses we predict that less than 5-10% of the 75,000 chemicals in commercial use might be reasonably anticipated to be carcinogenic to humans.
Acute Bronchitis Imaged with F-18 FDG Positron Emission Tomography
Authors: GREGORY KICSKA, HONGMING ZHUANG, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2003)

KICSKA, GREGORY M.D., PH.D.; ZHUANG, HONGMING M.D., PH.D.; ALAVI, ABASS M.D. Author Information
The Role of Sodium in the Production of Edema
Authors: John P. Peters
Journal: New England Journal of Medicine (1948)

THE term "edema" is applied to swellings produced by excessive accumulation of extracellular fluid without definite bounding membranes. These may be local or general. They are usually, but not always, associated with expansion of the total extracellular fluid of the body. They are even more loosely correlated with the total amount of water in the body. The simplest example of the formation of edema without change of the volume of fluid in the body is the swelling of the feet of a subject who stands still or rests in a relaxed position against a board at an angle of 60°. . . .
Abstract 757: Development and validation of an HPLC-UV method for lapatinib quantification in human plasma
Authors: Vanesa Escudero, Belén Valenzuela, Joseba Rebollo, Manuel Sureda, Antonio Brugarolas
Journal: Cancer Research (2012)

Abstract Background and objective: Lapatinib is a 4-anilinoquinazoline that can reversible and selectively inhibit both human epidermal growth factor receptor (EGFR, HER1) and human epidermal growth factor receptor type 2 (HER2) tyrosine kinases. As others tyrosine kinase inhibitors (TKIs), lapatinib shows a large interindividual variability in its pharmacokinetics (PK). So, the variability in drug exposure to TKIs may contribute to the variation in anti-cancer PD effect. Causes for this PK variability are manifold during the different processes of ADME. Up to date, only mass spectrometry detection is currently available to determine lapatinib in human plasma. The purpose of this study was to develop a simple and sensitive high-performance liquid chromatographic method with UV-Visible detection for quantification of lapatinib concentrations in human plasma to allow therapeutic drug monitoring (TDM) of lapatinib in cancer patients. Methods: After a liquid-liquid extraction with acetonitrile, lapatinib and sorafenib (internal standard, IS) are separated on Ultrabase C18 column using a mobile phase consisting of a mixture of 0.02 M ammonium acetate and acetonitrile in a proportion 47:53 pumped at a constant flow rate of 1.2 mL/min. The column was maintained at 25°C and the eluent was monitored at a wavelength of 260 nm. Results: The calibration curve was linear in the range 200-10000 ng/mL. The limit of quantification was determined to be 200 ng/mL. Lapatinib and IS retention times were 3.2 and 10.6 min, respectively. Inter- and intra-day coefficients of variation were less than 7%. The mean extraction recovery from plasma was higher than 86%. Conclusion: The simple, rapid and sensitive HPLC-UV method developed and validated for the measurement of lapatinib in human plasma using sorafenib as IS can be applied easily in routine clinical practice for the TDM of lapatinib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 757. doi:1538-7445.AM2012-757
LONGITUDINAL ASSESSMENT OF GROWTH 6 YEARS AFTER THE NORWOOD OPERATION: RESULTS FROM THE SINGLE VENTRICLE RECONSTRUCTION TRIAL
Authors: Phillip Todd Burch, Chitra Ravishankar, Jane Newburger, Linda Lambert, Victoria Pemberton, Suzanne Granger, Alejandro Floh, Jeffrey Anderson, Garick Hill, Kevin Hill, Matthew Oster, Ryan Davies, Jeffrey Jacobs, Wyman Lai, Alan Lewis, Kurt Schumacher, Sinai Zyblewski, L. LuAnn Minich
Journal: Journal of the American College of Cardiology (2016)
OC-121 Fibroblast activation in the tumour microenvironment promotes tumour cell invasion and resistance to chemotherapy in oesophageal adenocarcinoma
Authors: A L Hayden, M F Derouet, F Noble, J N Primrose, J P Blaydes, G Thomas, T J Underwood
Journal: Gut (2012)

<h3>Introduction</h3> Stromal and other non-malignant cells have the potential to undergo modifications that can synergistically create a supportive microenvironment for tumour growth, invasion and metastasis. Oesophageal adenocarcinoma (EAC) is characterised by early invasion, leading to metastatic disease and therefore only 20% of patients are suitable for treatment with curative intent. Cancer associated fibroblasts (CAFs) have an activated, myofibroblastic phenotype and have been recognised as mediators of tumour progression in a range of solid tumours. This study investigates the role of CAFs in EAC invasion and resistance to chemotherapy. <h3>Methods</h3> Functional biological analyses comparing primary fibroblasts from tumour stroma (CAF) and normal oesophagus (NOF) were carried out using organotypic culture, transwell invasion assays, collagen-1 gel contraction assays, siRNA gene silencing and colony forming assays. T-Tests (&gt;95% CI) were carried out for all statistical analyses. <h3>Results</h3> Primary oesophageal CAFs displayed an activated phenotype as demonstrated by α-SMA expression and increased collagen-1 gel contraction in comparison to NOFs (p&lt;0.01). CAF conditioned medium supported tumour colony formation in the presence of cisplatin and 5-Fluorouracil compared to NOF conditioned medium (p&lt;0.05). Ex vivo analysis revealed a twofold (p&lt;0.05) increase in EAC cell invasion in response to primary (CAF) conditioned medium in transwell invasion assays that was replicated in 3D organotypic models containing co-cultures of fibroblasts and EAC tumour cells. Down-regulation of the CAF secreted molecule Periostin (PN) resulted in a 70% reduction in tumour cell invasion in transwell assays (p&lt;0.05), and a total loss of invasion in organotypic culture. Furthermore, collagen-1 gel contraction was abrogated by PN down-regulation. NOFs exposed to TGF-β from 72 h demonstrate features of myofibroblastic activation including, PN expression and the ability to support increased EAC tumour cell invasion (p&lt;0.05). <h3>Conclusion</h3> This study has demonstrated that oesophageal derived primary CAF protect EAC cells from chemotherapy and promote tumour cell invasion. Increased α-SMA expression and collagen-1 gel contraction indicates CAF have a myofibroblast like phenotype. PN siRNA reduced gel contraction supports a hypothesis of autocrine regulation of the myofibroblast phenotype. Therefore targeting pathways that determine fibroblast activation may offer a novel therapy for preventing oesophageal cancer invasion and metastasis. <h3>Competing interests</h3> None declared.
Fiberoptic sensor for noninvasive measurement of variceal pressure
Authors: D.-R. Kong, B.-B. He, A.-J. Wu, J.-G. Wang, F.-F. Yu, J.-M. Xu
Journal: Endoscopy (2013)

We present a new measuring probe based on a miniature fiberoptic pressure sensor that can measure esophageal variceal pressure. The probe consists of an outer flexible chamber filled with a pressure transmission medium, at the center of which is positioned the fibreoptic sensor with diameter of 0.5 mm (FOP-F125, FISO Technologies Inc., Quebec, Canada) ([Fig. 1]). The single-column, flexible chamber has a 0.03-mm wall thickness and the chamber wall is made of polyurethane. The sensor within the medium is attached at one end to a connecting rod. When the membrane on the sensor chip is exposed to a rise in pressure in the surrounding medium, the light returning to the control unit is altered in accordance with the pressure deformations of the membrane and the altered interference conditions inside the cavity of the sensor [1]. The analog signals from sensor are transferred to both digital and analog values in the control unit and recorded with PC-based real-time data-acquisition hardware ([Fig. 2], [Fig. 3]).
773 RS12979860 CC GENOTYPE IS ASSOCIATED WITH BASELINE HIGH NUMBERS OF CD56BRIGHT NK-CELLS, LOW NUMBERS OF CD3-CD56-CD16– CELLS, LOW IL-10 HCV-SPECIFIC PRODUCTION IN CH-C THERAPY RESPONDERS
Authors: I. Carey, M. Bruce, D. Joshi, A. Mendes, A. Scalori, K. Agarwal, D. Vergani
Journal: Journal of Hepatology (2012)
Mercaptopurine in the Treatment of Steroid-Resistant Nephrotic Syndrome
Authors: Martin A. Shearn
Journal: New England Journal of Medicine (1965)

PROMPTED by the observation that the administration of 6-mercaptopurine (6-MP) to rabbits resulted in complete inhibition of the primary immune response and partial inhibition of the secondary immune response,1,2 Dameshek and Schwartz3 used this agent successfully in the treatment of some patients with "autoimmune" diseases. Antimetabolites have since been widely used as immunosuppressive agents in homotransplantation procedures and have had more limited application in the treatment of various connective-tissue disorders, including systemic lupus erythematosus, scleroderma, plasma-cell hepatitis and polymyositis.4 5 6 The suppressive effect of the purine antagonists on immunologic reactions has also suggested their use in the nephrotic syndrome, a . . .
Abstract 1366: Development of murine models of breast cancer metastasis for the evaluation of the efficacy of TGF-β inhibitors as therapeutic agents
Authors: Tanuka Biswas, Junhua Yang, Liu Zhao, LuZhe Sun
Journal: Cancer Research (2012)

Abstract Preclinical models are elemental in understanding drug efficacy and safety in vivo. Many existing models of breast cancer metastasis use immune compromised animals, which are not appropriate for the evaluation of novel therapeutics that modulate host immune response such as inhibitors of transforming growth factor-β (TGF-β) signaling pathway. TGF-β has been shown to be a major immune modulator as well as a major driver in epithelial-mesenchymal transition, which is believed to result in tumor invasion and metastasis. In the current study we characterized a pair of murine mammary cell lines derived from PyMT tumors in C57Bl/6 mice with respect to the effect of TGF-β on their malignant phenotypes. These cell lines, named Py-230 and Py-8119, represent luminal epithelial and mesenchymal cell populations respectively in the tumor. In vitro characterization revealed differences in viability, motility, and transcriptional activation in response to treatment with TGF-β. Py-230 cells were growth inhibited and exhibit epithelial-mesenchymal transition upon treatment with TGF-β whereas Py-8119 was non-responsive to TGF-β in these assays. These observations were consistent with higher Smad activation by TGF-β in Py230 cells than in Py-8119 cells. Furthermore, intra cardiac injections were performed using luciferase-and GFP-transfected PyMT cells in syngeneic animals, which were then treated with either placebo or TβRI KI (kinase inhibitor for TGF-β receptor I). A preliminary study with Py-230 cell-injected mice indicates that TβRI KI treatment appears to enhance bone metastasis. This outcome will be compared with the effect of TβRI KI on the metastatic potential of Py-8119 in our future studies. We believe that the development of mouse models of tumor metastasis using murine mammary cells in a syngeneic background will help illustrate the efficacy of TGF-β inhibitors in abrogating metastasis in an immune competent environment and also allow determining the optimal dose and time of this novel intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1366. doi:1538-7445.AM2012-1366
Abstract 5683: Design and characterization of novel targeted nanoparticle delivery systems for cancer chemotherapy
Authors: Juanjuan Yin, Kevin Bernard Sneed, Shufeng Zhou
Journal: Cancer Research (2012)

Abstract The success of cancer chemotherapy was considerably hindered by tumor resistance and drug toxicity. A possibly efficient approach to overcoming drug resistance and serious toxicities is the application of targeted nanoparticles linked to or encapsulating cytotoxic drugs. In this study, novel self-assembly targeting supramolecular nanodrug complex was synthesized using αv-intergrin targeting peptidyl cyclodextrins (CyDs) and classic chemotherapeutic drugs used in the therapy of tumor. The targeting supramolecular drug complex were obtained through host-guest interaction between the tripeptide RGD with sequence Arg-Gly-Asp or cyclotripeptide cRGDyk with sequence c (Arg-Gly-Asp-DTyr-Lys) grafting β-cyclodextrin (or γ-cyclodextrin) and a cytotoxic prodrug; the supramolecular drug inclusion are in specific and efficient binding to integrin-expressing tumor cells and would release the chemotherapeutics in a prolonged period. The guest molecule was generated by the reaction of adamantyl chloride and doxorubicin hydrochloride in which the adamantly group acts as a perfect candidate for the host-guest interaction with CyDs. The host moiety was gained through the reaction of mono-6-deoxy-6-(p-tolylsulfonyl)-β-cyclodextrin and the N-terminal of the oligopeptides through nuclephilic reaction. The promising nanodrug complex is expected to offer attractive pharmacokinetic and pharmacodynamic properties for cancer treatment and is undergoing preclinical evaluation using cancer cell lines and nude mouse models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5683. doi:1538-7445.AM2012-5683
A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement
Authors: Leo Rasche, Emmanuelle Menoret, Valentina Dubljevic, Eline Menu, Karin Vanderkerken, Constantin Lapa, Torsten Steinbrunn, Manik Chatterjee, Stefan Knop, Johannes Düll, Deanne L. Greenwood, Frank Hensel, Andreas Rosenwald, Hermann Einsele, Stephanie Brändlein
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeutic intervention. The monoclonal antibody PAT-SM6 targets surface GRP78 and leads to disease stabilization when used as single agent in a clinical trial. In this article, we evaluated expression of GRP78 in relapsed-refractory disease and explored PAT-SM6 therapy in combination regimens. Experimental Design: GRP78 expression was immunohistochemically analyzed during disease progression and development of drug resistance throughout different stages of multiple myeloma. Activity of PAT-SM6 was evaluated in combination with anti–multiple myeloma agents lenalidomide, bortezomib, and dexamethasone in vitro. Finally, we report on a multiple myeloma patient with relapsed-refractory disease treated with PAT-SM6 in combination with bortezomib and lenalidomide. Results: Although sGRP78 expression was present at all stages, it increased with disease progression and was even strongly elevated in patients with drug-resistant and extramedullary disease. Pretreatment with dexamethasone as well as dual combination of PAT-SM6/lenalidomide further increased sGRP78 expression and consecutively showed synergistic anti–multiple myeloma effects with PAT-SM6 in proliferation assays. As proof of concept, a 62-year-old male with triple resistant multiple myeloma treated with PAT-SM6, bortezomib, and lenalidomide experienced partial remission of both intra- and extramedullary lesions. Conclusions: PAT-SM6 therapy in combination regimens showed efficacy in relapsed-refractory multiple myeloma. Clin Cancer Res; 22(17); 4341–9. ©2016 AACR.
Surgical Aspects of Bronchiectasis
Authors: John W. Strieder
Journal: New England Journal of Medicine (1948)

IT IS generally agreed that the definitive treatment of bronchiectasis is surgical and that most patients should be considered for lobectomy or pneumonectomy, although many may, after evaluation, be denied operation for a variety of reasons.In 1941 Riggins1 wrote: "The morbidity and mortality of untreated and medically treated bronchiectasis is such that the physician who routinely advises young adults with operable bronchiectasis against surgery, is assuming a large responsibility and in all probability renders his patient a great disservice." Corroboration of this statement is obtained in several recent studies, one of the best of which is presented by Perry . . .