tbuckley/cabot-search huggingface dataset:
Abstract 12529: Low Dose Oral Cyclophosphamide Therapy Reduces Atherosclerosis Progression and Promotes Plaque Stability in a Murine Model of Atherosclerosis
Authors: Yayoi Sato-Okabayashi, Chiemi Nishida, Daida Hiroyuki, Shinya Munakata, Hiroshi Shimazu, Beate Heissig, Koichi Hattori
Journal: Circulation (2014)

Introduction: Atherosclerosis is a chronic inflammatory disease and the primary cause of heart disease and stroke in Western countries. The cytotoxic drug cyclophosphamide (CPA) can modulate immune functions. Extended survival of patients with severe atherosclerosis has been reported after CPA treatment, but the underlying mechanism is still poorly understood. The objective of this study was to examine the antiatherosclerotic effects of CPA and the underlying mechanism in a murine model of atherosclerosis. Hypothesis: CPA treatment can alter inflammatory processes pivotal for the development of atherosclerosis, therefore limiting disease progression. Method: Apolipoprotein E deficient (ApoE-/-) mice fed a high fat diet received CPA resuspended in drinking water (37.5 g/kg /day p.o.) or water for 12 weeks, respectively. In an interventional protocol, mice fed a high fat diet received the same dose of CPA or water from week 14 to 18, respectively. Mice were sacrificed at week 12, 14 and 18, and aorta, peripheral blood cells, spleen cells and peritoneal cells of treated mice were analysed using histological methods and FACS analysis. Result: In a preventive protocol, continuous oral administration of low-dose CPA prevented disease initiation in ApoE-/- mice fed with a high fat diet. Encouraged by these data we treated mice with pre-established atherosclerosis for 4 weeks with CPA, in an interventional protocol. CPA treatment delayed disease progression in mice with advanced atherosclerosis and reduced the macrophage infiltration in plaques. Importantly, improved plaque stability with a thicker fibrous cap, and an increase in collagen deposition and decreased matrix metalloproteinase-2 and -9 expression, and a reduction of classical inflammatory macrophage (M1) numbers was observed. In addition, CPA treatment reduced the numbers of IFN-γ-producing TH1, but not TH2 lymphocytes in vivo. Conclution: Our data demonstrate that oral treatment with CPA inhibits atherosclerosis initiation and progression in ApoE-/- mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, CPA may be a valuable drug for treating advanced atherosclerosis.
Asymptomatic Wolff-Parkinson-White syndrome: is it time to revisit guidelines?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Derick M Todd, George J Klein, Andrew D Krahn, Allan C Skanes, Raymond Yee
Journal: Journal of the American College of Cardiology (2003)
Obstructive lung disease in patients with treated pulmonary tuberculosis
Authors: Mikhail Chushkin, Batarbek Maliev, Sergey Yartsev, Sergey Smerdin
Journal: European Respiratory Journal (2011)

Little is known of functional sequelae of tuberculosis. The aim of the study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis.   Methods:  In consecutive 224 patients treated for pulmonary tuberculosis (between the ages of 20 and 82 years) who were observed at a local dispensary pulmonary function tests were performed.   Results:  Pulmonary impairment was present in 105 (46,9%) patients including 81 (36,2%) patients with airflow obstruction (FEV1/FVC    Conclusions:  A microbiological cure is not the end of illness. Tuberculosis is associated with frequent airflow obstruction. Culture-positive pulmonary tuberculosis in the past, episodes of tuberculosis may increase the prevalence of stage II or higher COPD.
From Cajal to Connectome and Beyond
Authors: Larry W. Swanson, Jeff W. Lichtman
Journal: Annual Review of Neuroscience (2016)

One goal of systems neuroscience is a structure-function model of nervous system organization that would allow mechanistic linking of mind, brain, and behavior. A necessary but not sufficient foundation is a connectome, a complete matrix of structural connections between the nodes of a nervous system. Connections between two nodes can be described at four nested levels of analysis: macroconnections between gray matter regions, mesoconnections between neuron types, microconnections between individual neurons, and nanoconnections at synapses. A long history of attempts to understand how the brain operates as a system began at the macrolevel in the fifth century, was revolutionized at the meso- and microlevels by Cajal and others in the late nineteenth century, and reached the nanolevel in the mid-twentieth century with the advent of electron microscopy. The greatest challenge today is extracting knowledge and understanding of nervous system structure-function architecture from vast amounts of data.
Autografting With Philadelphia Chromosome–Negative Mobilized Hematopoietic Progenitor Cells in Chronic Myelogenous Leukemia
Authors: Angelo M. Carella, Enrica Lerma, Maria T. Corsetti, Anna Dejana, Palmina Basta, Franca Vassallo, Monica Abate, Monica Soracco, Federica Benvenuto, Osvaldo Figari, Marina Podestà, Giovanna Piaggio, Raimondo Ferrara, Mario Sessarego, Caterina Parodi, Michele Pizzuti, Alessandra Rubagotti, Domenico Occhini, Francesco Frassoni
Journal: Blood (1999)
Split-dose cisplatin as an alternative to every-3-week dosing when using cisplatin/gemcitabine to treat advanced urothelial cancer.
Authors: Cinthia Marie Gonzalez, Emmet Jordan, Emily C. Zabor, Brooke Elizabeth Kania, Ashley Marie Regazzi, Irina Ostrovnaya, Gopa Iyer, Dean F. Bajorin, Richard Martin Bambury, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2015)

373 Background: Cisplatin-based chemotherapy is the standard of care first-line therapy for locally advanced or metastatic urothelial cancer (mUC) with reported response rates (ORR) of 50%, median progression free survival (mPFS) 7 months and median overall survival (mOS) 14 months in phase III trials using cisplatin 70 mg/m 2 every 3 weeks (q3wk). Many patients cannot receive cisplatin due to impaired performance status, renal dysfunction, or other co-morbidities. Carboplatin is an alternative but is associated with lower response rates and shorter survival. Administering cisplatin 35 mg/m2 day 1+8 (i.e., split dose) every 3 weeks may be associated with lower toxicity and allow more patients receive the drug. In this retrospective analysis we examined the safety and efficacy of cisplatin/gemcitabine using split dose cisplatin. Methods: Patients who received split dose cisplatin/gemcitabine between 2007-2013 were identified. We recorded baseline demographics, clinical characteristics, and number of cycles administered. Responses were determined retrospectively using RECIST v1.1; OS and PFS were assessed using the Kaplan-Meier method. Results: 50 patients were identified and baseline characteristics are outlined in Table 1. The median number of cycles administered was 4 (range 1-7). 25 patients (50%) discontinued therapy due to completion of planned course, 14 (28%) due to progressive disease and 11 (22%) due to toxicity. ORR was 54%, mPFS was 5.4 months (95% CI: 4.2 – 8.8) and mOS was 13.3 months (95% CI: 9.6 – 21.9). Conclusions: In this analysis, split-dose cisplatin was administered safely in patients who were deemed ineligible for the q3wk regimen and efficacy did not appear to be compromised. The split-dose regimen may allow more patients tolerate cisplatin, the most active FDA-approved drug in this disease. [Table: see text]
Trimetrexate in prostatic cancer: preliminary observations on the use of prostate-specific antigen and acid phosphatase as a marker in measurable hormone-refractory disease.
Authors: H I Scher, T Curley, N Geller, C Engstrom, D D Dershaw, S Y Lin, K Fitzpatrick, J Nisselbaum, M Schwartz, L Bezirdjian
Journal: Journal of Clinical Oncology (1990)

Thirty-one patients with bidimensionally measurable hormone-refractory prostatic cancer received trimetrexate (TMTX). Serial values of prostate-specific antigen (PSA) and acid phosphatase (SAP) were correlated with response. Five patients (17%; 95% confidence interval, 3% to 30%) achieved a partial remission for a median of 3 months (range, 3 to 7.5 months). Marker levels showed large variations with no discernible patterns. Serial PSA and SAP in 19 patients with abnormal baseline values showed a correlation with measurable disease response in only 68% (13 of 19) and 47% (nine of 19) of patients, respectively. Values were then smoothed using an exploratory data analysis technique of running medians and averages. Trends in marker changes were much more apparent. Several "decision rules" were evaluated for use of markers as indices of disease progression. A 50% increase from the patient's minimum value in either PSA or SAP on two successive determinations correlated with progression in 90% of cases in this trial. TMTX has modest activity in prostatic cancer, and further trials are not warranted. Biochemical markers do not uniformly reflect disease activity in hormone-refractory disease, and changes in biochemical markers must be interpreted cautiously when used as the sole end point to assess efficacy in clinical trials.
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia
Authors: Daniel Herranz, Alberto Ambesi-Impiombato, Jessica Sudderth, Marta Sánchez-Martín, Laura Belver, Valeria Tosello, Luyao Xu, Agnieszka A Wendorff, Mireia Castillo, J Erika Haydu, Javier Márquez, José M Matés, Andrew L Kung, Stephen Rayport, Carlos Cordon-Cardo, Ralph J DeBerardinis, Adolfo A Ferrando
Journal: Nature Medicine (2015)
Characterization of human ethmoid sinus mucosa derived mesenchymal stem cells (hESMSCs) and the application of hESMSCs cell sheets in bone regeneration
Authors: Qing Xie, Zi Wang, Yazhuo Huang, Xiaoping Bi, Huifang Zhou, Ming Lin, Zhang Yu, Yefei Wang, Ni Ni, Jing Sun, Si Wu, Zhengwei You, Chunyu Guo, Hao Sun, Yadong Wang, Ping Gu, Xianqun Fan
Journal: Biomaterials (2015)
Sustained release of actives with Montanide™ ISA 51 VG and Montanide™ ISA 720 VG, two adjuvants dedicated to human therapeutic vaccines
Authors: Stephane Ascarateil, Aude Puget, Jerome Gaucheron, Marie-Eve Koziol
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Montanide™ ISA 51 VG and Montanide™ ISA 720 VG are adjuvants dedicated to human therapeutic vaccines. The adjuvants are rendering stable water-in-oil (W/O) emulsions when mixed with water phase. In these formulations the active ingredients are entrapped in droplets of water
ACCF 2012 Health Policy Statement on Patient-Centered Care in Cardiovascular Medicine
Authors: Mary Norine Walsh, Alfred A. Bove, Russell R. Cross, Keith C. Ferdinand, Daniel E. Forman, Andrew M. Freeman, Suzanne Hughes, Elizabeth Klodas, Michelle Koplan, William R. Lewis, Brian MacDonnell, David C. May, Joseph V. Messer, Susan J. Pressler, Mark L. Sanz, John A. Spertus, Sarah A. Spinler, Louis Evan Teichholz, John B. Wong, Katherine Doermann Byrd
Journal: Journal of the American College of Cardiology (2012)
Heart Disease and Stroke Statistics—2016 Update
Authors: Dariush Mozaffarian, Emelia J. Benjamin, Alan S. Go, Donna K. Arnett, Michael J. Blaha, Mary Cushman, Sandeep R. Das, Sarah de Ferranti, Jean-Pierre Després, Heather J. Fullerton, Virginia J. Howard, Mark D. Huffman, Carmen R. Isasi, Monik C. Jiménez, Suzanne E. Judd, Brett M. Kissela, Judith H. Lichtman, Lynda D. Lisabeth, Simin Liu, Rachel H. Mackey, David J. Magid, Darren K. McGuire, Emile R. Mohler, Claudia S. Moy, Paul Muntner, Michael E. Mussolino, Khurram Nasir, Robert W. Neumar, Graham Nichol, Latha Palaniappan, Dilip K. Pandey, Mathew J. Reeves, Carlos J. Rodriguez, Wayne Rosamond, Paul D. Sorlie, Joel Stein, Amytis Towfighi, Tanya N. Turan, Salim S. Virani, Daniel Woo, Robert W. Yeh, Melanie B. Turner
Journal: Circulation (2015)

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee
EGFRvIII TandAbs are specific and highly potent drug candidates for the treatment of solid tumors
Authors: Kristina Ellwanger, Uwe Reusch, Ivica Fucek, Michael Weichel, Thorsten Gantke, Stefan Knackmuss, Vera Molkenthin, Jens-Peter Marschner, Martin Treder
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts To harness the immune system's cytotoxic capacity to fight solid tumors, we developed tetravalent, bifunctional antibodies that recognize EGFRvIII, the deletion variant III of EGFR, and either CD3 or CD16A on immune cells, thereby directing T cells or NK-cells to eliminate
Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes.
Authors: T Yoneda, T B Aufdemorte, R Nishimura, N Nishikawa, M Sakuda, M M Alsina, J B Chavez, G R Mundy
Journal: Journal of Clinical Oncology (1991)

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.
Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.
Authors: P M Ravdin, S Green, T M Dorr, W L McGuire, C Fabian, R P Pugh, R D Carter, S E Rivkin, J R Borst, R J Belt
Journal: Journal of Clinical Oncology (1992)

PURPOSE Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.
Care Quality Commission hints at “lighter touch” approach in future
Authors: Clare Dyer
Journal: BMJ (2015)

The Care Quality Commission (CQC) hopes to move to a new, “lighter touch” inspection regime in time, in which “things are being done with healthcare providers rather than to them,” the main NHS regulator’s strategy lead has said.

Speaking at a Westminster Health Forum seminar on regulation in health and social care, Sarah Bickerstaffe outlined a case for a “more mature” model of regulation and cited developments in Denmark.

Healthcare regulation in England has come under the spotlight as the government has proposed a move towards greater integration of health and social care. The CQC, which inspects hospitals, GP practices, community services, and care homes, …
Book: The Visit of the Royal Physician
Authors: Alex Paton
Journal: BMJ (2003)

The 16-year-old son of King Frederik V of Denmark succeeded his father as Christian VII in January 1766. He suffered from delusions, was prone to outbursts of violent behaviour, and exhibited repetitive movements under stress, yet spoke three languages and corresponded with Voltaire, who wrote a well known poem in his honour.​honour.




Figure 1



Per Olov Enquist, trans Tiina Nunnally

Vintage, £6.99, pp 309

ISBN 0 099 44705 3

Rating: ★★★




In November of that year, 13-year-old Princess Caroline Mathilde, youngest sister of George III of England, was dispatched to Copenhagen to marry Christian. The marriage was consummated by a single visit from the terrified king five months later, which produced a male heir.

Worried by the monarch's mental state, the court appointed a hitherto obscure doctor named Johann Friedrich Struensee, “a specialist in cupping,” to look after him. He and Queen Caroline soon took over the running of the country and became lovers. When a child was born in 1791 no one had any doubt who the father was.

Rumours spread that the king was being held captive by Struensee and “the English whore.” On 17 January 1772 a party of grenadiers seized Struensee and Enevold Brandt, “the King's nursemaid,” and the two were sentenced to death.

The queen, angry and defiant, was exiled to one of the British king's palaces at Celle. There she died suddenly in 1775 aged 23, some say poisoned. Ove Hoegh Guldberg, tutor to the king, became prime minister, and retained power for 12 years, while the king became increasingly deluded. The final irony is that nearly every European royal house can trace its lineage back to Struensee through his illegitimate daughter.

Enquist chooses a novelistic approach to a real life scandal that engrossed 18th century Europe. His account reads at times like a film script.
Role of thrombospondin-1 in a mouse model of breast cancer
Authors: Karen O. Yee, Caitlin M. Connelly, Eric R. Galardi, Jack W. Lawler
Journal: Cancer Research (2005)

6129   Thrombospondin-1 (TSP-1) has been shown to be an effective anti-angiogenic and anti-tumorigenic protein in vitro and in many xenograft mouse models. These models are limited in the information they provide because they don’t recapitulate the natural progression of the tumor at the correct body site. We were interested to know how TSP-1 inhibits breast cancer progression in vivo. The approach we decided to take was to develop a transgenic mouse model for breast cancer in order to enable us to study tumor progression at different stages (ie. initiation to metastasis). We crossed TSP-1 +/+ and TSP-1 -/- female mice with male polyomavirus middle T Antigen (PyT)/mouse mammary tumor virus (MMTV) transgenic mice to generate progeny that are PyT +/−, TSP-1 +/+ and PyT +/−, TSP-1 -/-. At 60 days of age when tumors are becoming palpable, we found that tumors in the PyT +/−, TSP-1 -/- mice are 50% larger than tumors found in the PyT +/−, TSP-1+/+. In our preliminary analysis on blood vessel density, TSP-1+/+ mice at 60 days of age have fewer tumor vessels/mm2. This suggests that TSP-1 may play role in inhibiting early tumor progression through an anti-angiogenic mechanism. By contrast, at 90 days of age when tumors are very well established, tumors from the PyT +/−, TSP-1 -/- mice are only slightly larger than tumors found in the PyT +/−,TSP-1 +/+ mice. We also found that there was a higher incidence of overt lung metastasis in the PyT +/−, TSP-1+/+ mice suggesting that TSP-1 played an important role during lung metastasis in this model. This data was confirmed using real time PCR on RNA isolated from mice lungs. This indicates that TSP-1 may not be as an effective inhibitor of tumor growth as in earlier stages. The effects of TSP-1 parallels those of TGF-beta which reportedly inhibits early stages of tumor progression, but promotes metastasis. Since TSP-1 is known to activate TGF-beta, we determined TGF-beta activity level by measuring the downstream effector molecule of the TGF-beta receptor, phosph-Smad 2, in the tumors. PyT+/−, TSP-1 +/+ tumors expressed higher levels of phospho-Smad 2 than PyT +/−, TSP-1 -/- tumors while Smad 2/3 levels did not differ significantly between the two groups. In conclusion, we have demonstrated that TSP-1’s role in tumor progression is very complex and differs at key points during tumor progression.