tbuckley/cabot-search huggingface dataset:
Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07
Authors: Tracy Batchelor, Kathryn Carson, Alison O’Neill, Stuart A. Grossman, Jane Alavi, Pamela New, Fred Hochberg, Regina Priet
Journal: Journal of Clinical Oncology (2003)

Purpose: A multicenter, phase II study of single-agent, intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. Methods: Methotrexate (8 g/m 2 ) was initially administered every 2 weeks. The primary end point was radiographic CR or PR, as defined by standard radiographic criteria, and secondary end points were survival and drug-related toxicity. Results: Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80. Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology, and five of 25 patients had ocular involvement. Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another. All patients have completed the treatment program or progressed. Among 23 patients, there were 12 CR (52%), five PR (22%), one (4%) with stable disease, and five progressions (22%) while on therapy. Seven patients died of tumor progression, and two died of other causes. Median progression-free survival was 12.8 months. Median overall survival for the entire group had not been reached at 22.8+ months. The toxicity of this regimen was modest, with no grade 3 or 4 toxicity in 13 of 25 patients, grade 3 toxicity in eight of 25 patients, and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy. Conclusion: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens.
Optic Disc Edema, Globe Flattening, Choroidal Folds, and Hyperopic Shifts Observed in Astronauts after Long-duration Space Flight
Authors: Thomas H. Mader, C. Robert Gibson, Anastas F. Pass, Larry A. Kramer, Andrew G. Lee, Jennifer Fogarty, William J. Tarver, Joseph P. Dervay, Douglas R. Hamilton, Ashot Sargsyan, John L. Phillips, Duc Tran, William Lipsky, Jung Choi, Claudia Stern, Raffi Kuyumjian, James D. Polk
Journal: Ophthalmology (2011)
Expression of oestrogen and progesterone receptors by mast cells alone, but not lymphocytes, macrophages or other immune cells in human upper airways
Authors: X J Zhao
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Nasal polyposis often coexists with asthma in airway inflammatory conditions characterised by the infiltration of a range of immune cells. A potentially important role for ovarian hormones has been implicated in airway inflammation but the cellular target for such action is not known. <h3>METHODS</h3> Expression of oestrogen receptors (ER) and progesterone receptors (PR) was examined using immunohistochemistry in formalin fixed nasal polyp tissues from 47 subjects. The cells positive for ER or PR were confirmed by spatial location, dual immunolabelling, and histochemical staining. <h3>RESULTS</h3> Consistent with the known features of nasal polyps, CD4+ (T helper/inducer), CD8+ (cytotoxic/supressor), CD68+ (macrophages), mast cells, eosinophils and neutrophils were all clearly detected by their relevant monoclonal antibodies or appropriate histochemical staining, but only mast cells tested positive for ER/PR labelling with their polyclonal and monoclonal antibodies. The frequencies for expression were 61.7% for ER positive and 59.6% for PR positive cells. The expression of ER/PR was independent of patient sex and age but was highly correlated with the numbers of mast cells (<i>r</i> = 0.973, p&lt;0.001 for ER; <i>r</i> = 0.955, p&lt;0.001 for PR). Fewer than 5% of mast cells were found to be negative for ER/PR expression. <h3>CONCLUSIONS</h3> Mast cells alone, but not lymphocytes, macrophages, or other immune cells, express ER/PR in human upper airways. Numerous ER/PR positive mast cells exist in nasal polyps, indicating that this may be a major route for the involvement of sex hormones in airway inflammation when exposed to the higher and varying concentration of oestrogen and progesterone characteristic of females.
Effect of early coronary artery reperfusion on infarct development in a model of low collateral flow
Authors: S. L HALE, R. A KLONER
Journal: Cardiovascular Research (1987)

Journal Article Effect of early coronary artery reperfusion on infarct development in a model of low collateral flow Get access SHARON L HALE, SHARON L HALE From the Department of Medicine, Wayne State University School of Medicine and Harper Hospital, Detroit, Michigan, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT A KLONER ROBERT A KLONER From the Department of Medicine, Wayne State University School of Medicine and Harper Hospital, Detroit, Michigan, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 9, September 1987, Pages 668–673, https://doi.org/10.1093/cvr/21.9.668 Published: 01 September 1987 Article history Received: 03 October 1986 Accepted: 22 February 1987 Published: 01 September 1987
Dual Role of Mitochondrial Reactive Oxygen Species in Hypoxia Signaling: Activation of Nuclear Factor-κB via c-SRC– and Oxidant-Dependent Cell Death
Authors: Josep M. Lluis, Francesca Buricchi, Paola Chiarugi, Albert Morales, José C. Fernandez-Checa
Journal: Cancer Research (2007)

Abstract Hypoxia is a prominent feature of solid tumor development and is known to stimulate mitochondrial ROS (mROS), which, in turn, can activate hypoxia-inducible transcription factor-1α and nuclear factor-κB (NF-κB). Because NF-κB plays a central role in carcinogenesis, we examined the mechanism of mROS-mediated NF-κB activation and the fate of cancer cells during hypoxia after mitochondrial reduced glutathione (mGSH) depletion. Hypoxia generated mROS in hepatoma (HepG2, H35), neuroblastoma (SH-SY5Y), and colon carcinoma (DLD-1) cells, leading to hypoxia-inducible transcription factor-1α–dependent gene expression and c-Src activation that was prevented in cells expressing a redox-insensitive c-Src mutant (C487A). c-Src stimulation activated NF-κB without IκB-α degradation due to IκB-α tyrosine phosphorylation that was inhibited by rotenone/TTFA or c-Src antagonism. The c-Src–NF-κB signaling contributed to the survival of cells during hypoxia as c-Src inhibition or p65 down-regulation by small interfering RNA–sensitized HepG2 cells to hypoxia-induced cell death. Moreover, selective mGSH depletion resulted in an accelerated and enhanced mROS generation by hypoxia that killed SH-SY5Y and DLD-1 cells without disabling the c-Src–NF-κB pathway. Thus, although mROS promote cell survival by NF-κB activation via c-Src, mROS overgeneration may be exploited to sensitize cancer cells to hypoxia. [Cancer Res 2007;67(15):7368–77]
S100A12 Mediates Aortic Wall Remodeling and Aortic Aneurysm
Authors: Marion Hofmann Bowman, Jeannine Wilk, Ahlke Heydemann, Gene Kim, Jalees Rehman, Joseph A. Lodato, Jai Raman, Elizabeth M. McNally
Journal: Circulation Research (2009)

Rationale : S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear. Objective : To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22α promoter because S100A12 is not present in mice. Methods and Results : Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor β pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells. Conclusions : S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo.
Dynamic prediction in breast cancer: proving feasibility in clinical practice using the TEAM trial
Authors: D.B.Y. Fontein, M. Klinten Grand, J.W.R. Nortier, C. Seynaeve, E. Meershoek-Klein Kranenbarg, L.Y. Dirix, C.J.H. van de Velde, H. Putter
Journal: Annals of Oncology (2015)
DNA aneuploidy and cell proliferation in familial adenomatous polyposis.
Authors: P Quirke, M F Dixon, D W Day, J B Fozard, I C Talbot, C C Bird
Journal: Gut (1988)

Two hundred and thirteen samples from 20 patients with familial adenomatous polyposis (FAP) were investigated by flow cytometry and the results compared with 100 sporadic adenomas. Eleven of the 20 (55%) yielded one or more DNA aneuploid samples with an overall incidence within FAP adenomas of 12%. Despite a similar level of DNA aneuploidy in sporadic adenomas, it was commonly detected at a smaller polyp size. The degree of cell proliferation was found to be similar in the two groups (median %S+G2 15.8% v 16.4%) but larger FAP adenomas demonstrated a higher level of cell proliferation than smaller adenomas. DNA aneuploidy had no value as a predictor of a synchronous carcinoma and appeared to be an early change in the development of carcinoma in these patients.
Abstract 2556: Granulin-epithelin precursor modulates chemo-resistance in liver cancer
Authors: Chung Lim Wong, Fung Yi Cheung, Siu Tim Cheung
Journal: Cancer Research (2010)

Abstract Background and Objective: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is responsible for 80% of the primary liver tumors in adults. HCC is found to be resistant to most current chemo-therapeutic agents, making the disease as one of the most mortal in the world. There is therefore an urgent demand for better therapeutic approaches. Granulin-epithelin precursor (GEP) was identified as a potential therapeutic target from our genome-wide expression profiles study for HCC. It was an autocrine growth factor with over-expression in most HCCs, and involved in HCCs proliferation, invasion and tumorigenicity. The aim of the current study is to examine the role and signaling mechanism of GEP in chemo-resistance, and if chemo-resistant HCC would response to GEP targeted therapy using GEP monoclonal antibody (mAb). Methods: HCC cells Hep3B was stably transfected with GEP cDNA for overexpression, and antisense fragment for suppression studies, respectively. Chemo-resistant HCC populations were obtained by selection and expansion of Hep3B cells under different class of chemo-therapeutic agents, including cisplatin, doxorubicin and fluorouracil. The cells were examined for chemotherapy induced apoptosis with chemo-therapeutic agents alone, or in combination with GEP targeted therapy using GEP mAb. The ERK signaling molecules were examined by western blot, and caspases activity by the Caspase-Glo luminescent assay. Results: The Hep3B transfectants with GEP overexpression demonstrated increased resistance to apoptosis under different class of chemo-therapeutic agents with reference to the parental population. Hep3B cells with GEP suppression resulted in enhanced sensitivity to the chemotherapy induced apoptosis. The Hep3B cells with acquired resistance demonstrated an increment of 8-16 folds in IC50 to cisplatin, doxorubicin and fluorouracil, respectively, with reference to the parental population. The chemoresistant Hep3B cells were responsive to GEP targeted therapy, and combined chemotherapy with GEP targeted therapy demonstrated synergistic effect on apoptosis induction. GEP regulated the ERK pathway including the activation of p-p38 and p-p44/42. GEP targeted therapy alone did not affect the caspases activities, however, combination treatment using the GEP mAb and chemo-therapeutic agents provided a synergistic effect on activation of caspase 3, and magnified the apoptotic effect. Summary: The present study demonstrated that GEP regulated chemoresistance, and GEP mAb could sensitize both the parental and chemoresistant liver cancer cells to chemo-therapeutic agents. The GEP targeted therapy indicated a new therapeutic approach for chemo-resistant liver cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2556.
Methotrexate: a useful alternative in Crohn's disease?
Authors: A B HAWTHORNE
Journal: Gut (2001)

The search goes on for safe and effective long term treatments that will modify the course of aggressive Crohn's disease and reduce the need for frequent surgery or long term corticosteroids. Azathioprine and 6-mercaptopurine remain the most widely used immunomodulators but there is a need for alternatives, particularly for the 10% of patients who cannot tolerate these drugs. Methotrexate has been used in Crohn's disease for many years1-3 and a controlled trial showed benefit in active corticosteroid dependent disease4 yet it is still not widely used. Likely reasons include concerns about toxicity (particularly liver fibrosis, hypersensitivity pneumonitis, and teratogenicity), the need for parenteral administration, and lack of evidence of long term benefit.

The recent publication of Feagan and colleagues5 provides important information on the long term role of methotrexate. While not obvious from the paper's title, this was in fact a placebo controlled withdrawal study in 76 patients who had achieved remission (judged by Crohn's disease activity index) after methotrexate 25 mg intramuscularly weekly for 4–6 months. Forty patients then received methotrexate 15 mg intramuscularly every week, …
HDL in Children with CKD Promotes Endothelial Dysfunction and an Abnormal Vascular Phenotype
Authors: Rukshana Shroff, Thimoteus Speer, Sophie Colin, Marietta Charakida, Stephen Zewinger, Bart Staels, Giulia Chinetti-Gbaguidi, Inga Hettrich, Lucia Rohrer, Francis O’Neill, Eve McLoughlin, David Long, Catherine M. Shanahan, Ulf Landmesser, Danilo Fliser, John E. Deanfield
Journal: Journal of the American Society of Nephrology (2014)

Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2-5 (HDL(CKD)), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDL(CKD) strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.
Selection criteria for drug‐like compounds
Authors: Ingo Muegge
Journal: Medicinal Research Reviews (2003)

Abstract The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large‐scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of ‘drug‐likeness’ of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug‐like. Various approaches have been devised to address the drug‐likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture ‘chemical wisdom’ in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non‐drugs. Here we review computational techniques to address the drug‐likeness of compound selections and offer an outlook for the further development of the field. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 302‐321, 2003
ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging
Authors: Robert C. Hendel, Daniel S. Berman, Marcelo F. Di Carli, Paul A. Heidenreich, Robert E. Henkin, Patricia A. Pellikka, Gerald M. Pohost, Kim A. Williams
Journal: Circulation (2009)

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac radionuclide imaging (RNI) is frequently considered. This document is a revision of the original Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI) Appropriateness Criteria, published 4 years earlier, written to reflect changes in test utilization and new clinical data, and to clarify RNI use where omissions or lack of clarity existed in the original criteria. This is in keeping with the commitment to revise and refine appropriate use criteria (AUC) on a frequent basis. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Sixty-seven clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Additionally, use for perioperative testing was found to be inappropriate except for high selected groups of patients. It is anticipated that these results will have a significant impact on physician decision making, test performance, and reimbursement policy, and will help guide future research.
Extended Prophylaxis of Venous Thromboembolism with Idraparinux
Authors: Harry R Buller, Ander T Cohen, Bruce Davidson, Hervé Decousus, Alex S Gallus, Michael Gent, Gerard Pillion, Franco Piovella, Martin H Prins, Gary E Raskob
Journal: New England Journal of Medicine (2007)

The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk–benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant.
Opportunities and Obstacles to Combination Targeted Therapy in Renal Cell Cancer
Authors: Jeffrey A. Sosman, Igor Puzanov, Michael B. Atkins
Journal: Clinical Cancer Research (2007)

Abstract The treatment of advanced renal cell carcinoma (RCC) has undergone a major change with the development of potent angiogenesis inhibitors and targeted agents. Several multitargeted tyrosine kinase inhibitors, sorafenib and sunitinib, have already been approved for the treatment of advanced RCC. Temsirolimus (CCI-779), a mammalian target of rapamycin inhibitor, has shown a survival advantage over IFN in advanced, poor-prognosis RCC patients. Bevacizumab, an antibody targeting vascular endothelial growth factor (VEGF) A, has also shown promising clinical activity. Benefits attributable to these agents have been recognized by high objective response rates (sunitinib), significant increases in progression-free survival (sunitinib, sorafenib and bevacizumab), or improved overall survival (temsirolimus). These agents mediate much of their effect through inhibition of the hypoxia-inducible factor (HIF)-VEGF-VEGF receptor axis. Their inhibitory activity for the signaling of platelet-derived growth factor (PDGF) receptor β or kinases like c-Raf may contribute to the antitumor effects of the multitargeted kinase inhibitors. Nevertheless, all four single agents rarely, if ever, induce complete responses and, at present, all patients develop resistance and, ultimately, progress during therapy. A critical need exists to develop strategies that may increase the degree of the antitumor effects with the hope of inducing more complete responses impeding the onset of or elimination of refractory disease. Combinations of these and other targeted agents may overcome the resistance that develops with single-agent therapy and could be incorporated either as part of initial therapy or later when disease resistance develops. Approaches aimed at combining these agents can be based on the genetics and biology of clear cell RCC. von Hippel-Lindau loss leads to an increase in cellular levels of HIF (HIF-1α or HIF-2α) leading to increased expression of a number of hypoxia-regulated genes critical to cancer progression. Combinations of targeted agents may block several of these mediators (VEGF, epidermal growth factor receptor, and PDGF), so-called horizontal blockade. Blockade could also take place at two levels of the pathways (vertical blockade), either at HIF and VEGF or at VEGF and VEGF receptor signaling. Many of the above strategies are ongoing and will require careful phase 1 determination of toxicity and even more rigorous phase 2 analysis before moving onto phase 3 trials.
Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced colorectal cancer
Authors: P. Byström, Å. Berglund, U. Garske, H. Jacobsson, A. Sundin, P. Nygren, J.-E. Frödin, B. Glimelius
Journal: Annals of Oncology (2009)