tbuckley/cabot-search huggingface dataset:
Transcriptional Switch of Dormant Tumors to Fast-Growing Angiogenic Phenotype
Authors: Nava Almog, Lili Ma, Raktima Raychowdhury, Christian Schwager, Ralf Erber, Sarah Short, Lynn Hlatky, Peter Vajkoczy, Peter E. Huber, Judah Folkman, Amir Abdollahi
Journal: Cancer Research (2009)

Abstract Tumor dormancy has important implications for early detection and treatment of cancer. Lack of experimental models and limited clinical accessibility constitute major obstacles to the molecular characterization of dormant tumors. We have developed models in which human tumors remain dormant for a prolonged period of time (&amp;gt;120 days) until they switch to rapid growth and become strongly angiogenic. These angiogenic tumors retain their ability to grow fast once injected in new mice. We hypothesized that dormant tumors undergo a stable genetic reprogramming during their switch to the fast-growing phenotype. Genome-wide transcriptional analysis was done to dissect the molecular mechanisms underlying the switch of dormant breast carcinoma, glioblastoma, osteosarcoma, and liposarcoma tumors. A consensus expression signature distinguishing all four dormant versus switched fast-growing tumors was generated. In alignment with our phenotypic observation, the angiogenesis process was the most significantly affected functional gene category. The switch of dormant tumors was associated with down-regulation of angiogenesis inhibitor thrombospondin and decreased sensitivity of angiogenic tumors to angiostatin. The conversion of dormant tumors to exponentially growing tumors was also correlated with regulation and activation of pathways not hitherto linked to tumor dormancy process, such as endothelial cell–specific molecule-1, 5′-ecto-nucleotidase, tissue inhibitor of metalloproteinase-3, epidermal growth factor receptor, insulin-like growth factor receptor, and phosphatidylinositol 3-kinase signaling. Further, novel dormancy-specific biomarkers such as H2BK and Eph receptor A5 (EphA5) were discovered. EphA5 plasma levels in mice and mRNA levels in tumor specimens of glioma patients correlated with diseases stage. These data will be instrumental in identifying novel early cancer biomarkers and could provide a rationale for development of dormancy-promoting tumor therapy strategies. [Cancer Res 2009;69(3):836–44]
Spatial requirements between haptenic and carrier determinants for T-dependent antibody responses.
Authors: S Fong, D E Nitecki, R M Cook, J W Goodman
Journal: The Journal of Experimental Medicine (1978)

To gauge the proximity between cooperating T and B cells required for effective triggering of antibody production, guinea pigs were immunized with bifunctional antigens in which the haptenic and carrier determinants were separated by rigid spacers of varied dimension. These took the form 2,4-dinitrophenol-(proline)n-L-tyrosine-p-azobenzenearsonate, where n varied from 1 to 40 proline residues. Animals immunized with n = 10 and n = 22 compounds made strong anti-DNP antibody responses, whereas animals immunized with bifunctional compounds containing longer spacers did not make antibody detectable by precipitation. It can be calculated on the basis of very strong physicochemical evidence for the rigidity and axial translation of poly-L-proline chains in solution that the cut-off point for effective interaction between T and B cells lies between 69 and 97 A U.
INTERNATIONAL VARIATION IN CARE AMONG PATIENTS HOSPITALIZED FOR HEART FAILURE: AN ANALYSIS OF THE ACUTE DECOMPENSATED HEART FAILURE NATIONAL REGISTRY UNITED STATES AND ACUTE DECOMPENSATED HEART FAILURE REGISTRY INTERNATIONAL
Authors: Robb D. Kociol, Li Liang, John J. Atherton, Christopher S. Hayward, G. Michael Felker, Roger M. Mills, Christopher M. O'Connor, Gregg C. Fonarow, Adrian F. Hernandez
Journal: Journal of the American College of Cardiology (2011)
Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia
Authors: M. Mathy-Hartert, P. Damas, M Nys, G Deby-Dupont, J-L. Canivet, D. Ledoux, M. Lamy
Journal: European Respiratory Journal (2000)

The study was designed to identify markers of oxidative injury, related to the nitric oxide derived cascade, in bronchoalveolar lavage (BAL) fluid from intensive care patients suspected of ventilator-associated pneumonia (VAP) and/or acute respiratory distress syndrome (ARDS). Thirty-eight patients developing VAP and/or ARDS (VAP/ARDS group) were compared to 20 ventilated patients without VAP/ARDS (control group). Myeloperoxidase (MPO) and elastase, taken as markers of neutrophil activation were measured by enzymatic techniques, and nitrated proteins (NTPs) by an immunological method. The cytotoxicity of the BAL fluid was tested using cultured human epithelial alveolar cells by the release of pre-incorporated 51Cr. Mean NTP concentration and, MPO and elastase activities were different between the VAP/ARDS and control groups (p&lt;0.05 for NTPs; p&lt;0.005 for MPO; p&lt;0.005 for elastase). NTP concentration correlated with MPO and elastase activity and neutrophil number (r=0.93, 0.91 and 0.87, respectively), but not to protein concentration and arterial oxygen tension/inspiratory oxygen fraction. The cytotoxicity of BAL correlated with NTP concentration (r=0.92) and MPO activity (r=0.89). It was concluded that the concentrations of nitrated proteins in bronchoalveolar lavage fluid correlated with the oxidant activity of neutrophils and that, bronchoalveolar lavage fluid cytotoxicity was correlated with the nitrated protein concentration and may be mediated by oxidants.
THE IN VITRO TRANSFORMATION OF FROZEN-STORED LYMPHOCYTES IN THE MIXED LYMPHOCYTE REACTION AND IN CULTURE WITH PHYTOHEMAGGLUTININ AND SPECIFIC ANTIGENS
Authors: Richard J. Mangi, Michael R. Mardiney
Journal: The Journal of Experimental Medicine (1970)

We have investigated the in vitro transformation of lymphocytes that have been frozen and stored at low temperatures. Cells frozen at different times and stored for various times do transform in a reproducible manner when placed in culture with PHA or as one population of the two-way or the one-way MLR. When frozen-stored lymphocytes are cultured with specific antigen or as both partners in the MLR the response is minimal. The freezing process destroys neutrophils, and the remaining population transforms in a manner similar to cultures of purified lymphocytes. Practical aspects of the technique are discussed and we have suggested possible practical applications for future investigation.
Baroreflex control of the cutaneous active vasodilator system in humans.
Authors: D L Kellogg, J M Johnson, W A Kosiba
Journal: Circulation Research (1990)

Cutaneous arterioles are controlled by vasoconstrictor and active vasodilator sympathetic nerves. To find out whether the active vasodilator system is under baroreceptor control, laser-Doppler velocimetry and the local iontophoresis of bretylium were combined to allow selective study of the active vasodilator system. Each of six subjects had two forearm sites (0.64 cm2) treated with bretylium to abolish adrenergic vasoconstrictor control. Laser-Doppler velocimetry was monitored at those sites and at two adjacent untreated sites. Subjects underwent 3 minutes of lower-body negative pressure (LBNP) and 3 minutes of cold stress to verify blockade of vasoconstrictor nerves. They were then subjected to whole-body heat stress (water-perfused suits), and the 3 minutes of LBNP was repeated. Finally, subjects were returned to normothermia, and LBNP and cold stress were repeated to verify the persistence of blockade. During the application of LBNP in normothermia, cutaneous vascular conductance (CVC) fell at untreated sites by 22.7 +/- 4.7% (p less than 0.01) but was unaffected at bretylium-treated sites (p greater than 0.20). During cold stress, CVC at untreated sites fell by 30.2 +/- 1.7% (p less than 0.01) and at treated sites rose by 0.7 +/- 4.6% (p greater than 0.10). Both control and bretylium-treated sites reflexly vasodilated in response to hyperthermia. With LBNP during hyperthermia, CVC at untreated sites fell by 23.3 +/- 7.1% (p less than 0.05) and at treated sites 17.9 +/- 9.2% (p less than 0.05) with no significant difference between sites (p greater than 0.10). After return to normothermia, neither LBNP application nor cold stress caused CVC to fall at treated sites (p greater than 0.10). Thus, the vasoconstrictor system was blocked by bretylium treatment throughtout the study, whereas the active vasodilator response to heat stress was intact. Because LBNP in hyperthermia induced similar falls in CVC at both sites, we conclude that baroreceptor unloading elicits a withdrawal of active vasodilator tone and that the baroreflex has control of the active vasodilator system.
Induction of cytotoxic T cell precursors in vivo. Role of T helper cells.
Authors: D Bellgrau
Journal: The Journal of Experimental Medicine (1983)

Strain AS rats respond with two populations of cytotoxic T lymphocytes to stimulation in vitro by the major histocompatibility complex (MHC)-incompatible strain HL rat tumor (HL-A2T2). One is specific for MHC alloantigens present on both HL-A2T2 and normal HL targets, the other is tumor specific. The activation of these killer cells requires helper T lymphocytes. The tumor-specific helper cells depend on syngeneic radioresistant accessory cells to present the tumor antigens in an immunogenic form. The appropriate helper-accessory cell interaction results in the production of soluble factors which then induce the maturation of precursor cells into effective killer cells. Studies with a procedure for inducing negative selection of T cells in vivo showed that short-term exposure to HL-A2T2 tumor induced selection only for TH but not cytotoxic T lymphocyte precursors (CTLp). Simultaneous injection of supernatants from concanavalin A-activated spleen cell cultures, however, did produce selection of CTLp. These and other findings suggest that under normal circumstances in vivo, both signals (recognition of antigen and acceptance of maturation factors) are provided in the vicinity of an antigen presenting macrophage-like accessory cell.
Recurrent pericarditis. Relief with colchicine.
Authors: J Guindo, A Rodriguez de la Serna, J Ramió, M A de Miguel Diaz, M T Subirana, M J Perez Ayuso, J Cosín, A Bayés de Luna
Journal: Circulation (1990)

Recurrence is one of the major complications of pericarditis. Treatment of recurrence is often difficult, and immunosuppressive drugs or surgery may be necessary. We conducted an open-label prospective study of nine patients (seven men and two women; age, 18-64 years; mean age, 41.7 +/- 13.7 years). Patients were treated with colchicine (1 mg/day) to prevent recurrences. All patients had suffered at least three relapses despite treatment with acetylsalicylic acid, indomethacin, prednisone, or a combination. Pericarditis was classified as idiopathic in five patients, postpericardiotomy in two, post-myocardial infarction in one, and associated with disseminated lupus erythematosus in one. For statistical analysis, we conducted a paired comparison design (Student's t test). All patients treated with colchicine responded favorably to therapy. Prednisone was discontinued in all patients after 2-6 weeks (mean, 26.33 +/- 10.9 days), and colchicine alone was continued. After a mean follow-up of 24.3 months (minimum, 10 months; maximum, 54 months), no recurrences were observed in any patient; there was a significant difference between the symptom-free periods before and after treatment with colchicine (p less than 0.002). Our study suggests that colchicine may be useful in avoiding recurrence of pericarditis, although these results need to be confirmed in a larger, double-blind study.
Sidestep cutting technique affects knee valgus loading
Authors: E Kristianslund, T Krosshaug
Journal: British Journal of Sports Medicine (2011)

Background Anterior cruciate ligament (ACL) injuries pose serious short and long term consequences for athletes in team sports worldwide. Modifying technique is an important part of effective prevention programs, but the understanding of which technique that reduces potentially harmful joint loadings is limited. Prevention can likely be improved with better knowledge of technique effects. Objective Study the effect of sidestep cutting technique on knee valgus moments. Design Cross-sectional. Setting Three sidestep cutting manoeuvres to each side in a 240 Hz motion analysis lab. Participants 131 female elite handball back and wing players (22.4±4.0 years, 173±6 cm, 69±7 kg). Two excluded due to technical problems. Assessment of risk factor Initial contact (IC) knee flexion, knee valgus, hip abduction, ankle pronation, torso lateral flexion, torso rotation, speed of torso rotation, inward rotation of foot relative to direction of motion and lateral distance from centre of mass of the body to the centre of pressure of the foot, as well as length of contact phase, cutting angle and approach speed. Main outcome Maximum knee valgus moment during first 50 ms of contact phase. Results Average maximum valgus moment was 1.54 ± 0.64 Nm/kg. Six variables had a pronounced effect in the linear regression model. An increase of knee valgus angle at IC of one SD gave a 0.20 Nm/kg (13%) increase in maximum valgus moment. Corresponding effect sizes was 0.14 Nm/kg (9%) for hip abduction, 0.22 Nm/kg (14%) for ankle pronation, 0.12 Nm/kg (8%) for cut width, 0.16 Nm/kg (10%) for cutting angle and 0.21 Nm/kg (14%) for approach speed. Conclusion We have identified potentially harmful sidestep cutting technique components. ACL injury prevention programs should continue to focus on cutting techniques with small knee valgus angles, low ankle pronation and narrow stance, particularly for cuts that are performed with high approach speed and sharp direction changes.
Stem cells and cancer immunotherapy: Arrowhead’s 2nd annual cancer immunotherapy conference
Authors: Adrian Bot, Maurizio Chiriva-Internati, Andrew Cornforth, Brian J Czerniecki, Soldano Ferrone, Kenneth Geles, Philip D Greenberg, Elaine Hurt, Richard C Koya, Masoud H Manjili, William Matsui, Richard A Morgan, Claudia M Palena, Daniel J Powell, Nicholas P Restifo, David M Spencer, Raul Vizcardo, Albert J Wong, Lili Yang, John Yu
Journal: Journal for ImmunoTherapy of Cancer (2014)

Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead's 2<sup>nd</sup> Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer "stem cells" as targets and therapeutic platforms based on stem cells.
Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission
Authors: Franco W Locatelli, Myriam Labopin, Juan Ortega, Giovanna Meloni, Giorgio Dini, Chiara Messina, Isaac Yaniv, Franca Fagioli, Victoria Castel, Peter J Shaw, Augustin Ferrant, Andrea Pession, Gerard Socie, Francesco Frassoni
Journal: Blood (2002)
Tissue Plasminogen Activator in Cardiac Arrest with Pulseless Electrical Activity
Authors: Riyad B. Abu-Laban, James M. Christenson, Grant D. Innes, Catherina A. van Beek, Karen P. Wanger, R. Douglas McKnight, Iain A. MacPhail, Joe Puskaric, Richard P. Sadowski, Joel Singer, Martin T. Schechter, Victor M. Wood
Journal: New England Journal of Medicine (2002)

Coronary thrombosis and pulmonary thromboembolism are common causes of cardiac arrest. We assessed whether the administration of tissue plasminogen activator (t-PA) during cardiopulmonary resuscitation would benefit patients with cardiac arrest and pulseless electrical activity of unknown or presumed cardiovascular cause.
Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study
Authors: J Sieper, T Klopsch, M Richter, A Kapelle, M Rudwaleit, S Schwank, E Regourd, M May
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> To demonstrate the non-inferiority of celecoxib compared with diclofenac in subjects with ankylosing spondylitis (AS). <h3>Methods:</h3> The basis of the present work was a 12-week randomised, double-blind, controlled study in active AS subjects with three treatment arms: celecoxib 200 mg once a day, celecoxib 200 mg twice a day, and diclofenac SR 75 mg twice a day. The primary efficacy endpoint was the change from baseline in global pain intensity on a visual analogue scale (VAS) at week 12. Secondary endpoints covered changes in disease activity, functional and mobility capacities, and adverse events. <h3>Results:</h3> A total of 458 subjects were randomly assigned to either celecoxib 200 mg once a day (n = 153), celecoxib 200 mg twice a day (n = 150), or diclofenac (n = 155). Least square (LS) mean changes from baseline at week 12 on a pain VAS were clinically relevant in all treatment groups (celecoxib 200 mg once a day: −29.1 mm; celecoxib 200 mg twice a day:–31.7 mm; diclofenac:–32.7 mm) and non-inferior when compared to diclofenac. Ankylosing Spondylitis Assessment Study group 20% (ASAS 20) response and mean improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores at week 12 were numerically better on celecoxib 200 mg twice a day (59.7% and–1.32 points) and on diclofenac (60.2% and–1.48 points) than on celecoxib 200 mg once a day (46.0% and–0.99 points). The incidence of gastrointestinal adverse events was significantly higher on diclofenac (28.4%) than on celecoxib 200 mg once a day (15.0%) or 200 mg twice a day (16.7%). <h3>Conclusions:</h3> The efficacy of celecoxib 200 mg once a day and 200 mg twice a day was comparable to that of diclofenac 75 mg twice a day with respect to pain reduction. Celecoxib 200 mg twice a day and diclofenac reduced some parameters associated with inflammation more effectively than celecoxib 200 mg once a day. Treatment was well tolerated, with celecoxib (either dose) exhibiting less frequent gastrointestinal adverse events than diclofenac.
Serum glycan as a prognostic marker in patients with advanced hepatocellular carcinoma treated with sorafenib
Authors: Koji Miyahara, Kazuhiro Nouso, Yasuhiro Miyake, Shinichiro Nakamura, Shuntaro Obi, Maho Amano, Kazuko Hirose, Shin-Ichiro Nishimura, Kazuhide Yamamoto
Journal: Hepatology (2013)

We read with interest the article by Kamiyama et al.1 on whole-serum N-glycan profiling in hepatocellular carcinoma (HCC) patients who underwent hepatectomy. The authors demonstrated that these glycans were differentially expressed in HCC patients compared with healthy controls; both G2890 (m/z value, 2,890.052) and G3560 (m/z value, 3,560.295) were recurrent and prognostic factors, respectively. To determine whether these two serum glycans could be clinical markers for advanced HCC patients and their levels in patients with chronic hepatitis (CH), we investigated serum N-glycan profiles using the same method used by Kamiyama et al. in 85 consecutive HCC patients treated with sorafenib, 41 patients with CH B or C, and 459 healthy volunteers. Mean serum levels (SDs) of G2890 were 2.60 (1.50), 0.85 (0.60), and 1.04 (0.41) pmol/mL (P < 0.0001), and the levels of G3560 were 0.42 (0.37), 0.05 (0.06), and 0.09 (0.06) pmol/mL (P < 0.0001) in HCC, CH, and healthy volunteers, respectively. Changes in the levels of the two glycans did not correlate with CH virus infection but with the presence of HCC. Of the 61 glycans detected, 15 glycans, including G2890 and G3560, were elevated in patients with progressive disease 6 weeks after starting sorafenib. Comparing overall survival (OS) between patients with high and low values of these 15 glycans, only G2890 correlated with poor OS in univariate analysis using Cox's proportional hazard model, while G3560 showed a borderline correlation (Table 1). Multivariate analysis with known prognostic factors revealed that high levels of G2890 (hazard ratio, 1.88; 95% confidence interval, 1.04-3.48), as well as Eastern Cooperative Oncology Group performance status (ECOG PS)1, 2 and Child-Pugh (B), were identified as independent risk factors for survival. We have yet to identify the ligands of G2890 and the biological effects in HCC patients; however, our findings support and expand the results by Kamiyama et al.: serum G2890 is a novel diagnostic and prognostic factor in HCC patients treated with sorafenib, as was observed in surgically treated patients. Koji Miyahara, M.D.1 Kazuhiro Nouso, M.D., Ph.D.1,2 Yasuhiro Miyake, M.D., Ph.D.1 Shinichiro Nakamura, M.D., Ph.D.1 Shuntaro Obi, M.D., Ph.D.3 Maho Amano, Ph.D.4,5 Kazuko Hirose, Ph.D.4 Shin-Ichiro Nishimura, Ph.D.4,5 Kazuhide Yamamoto, M.D., Ph.D.1 1Department of Gastroenterology & Hepatology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama, Japan 2Department of Molecular Hepatology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama, Japan 3Division of Hepatology Kyoundo Hospital, Tokyo, Japan 4Field of Drug Discovery Research Faculty of Advanced Life Science & Graduate School of Life Science Hokkaido University Sapporo, Japan 5Medicinal Chemistry Pharmaceuticals Sapporo, Japan
Randomized Phase III Trial of Sequential Adjuvant Chemoradiotherapy With or Without Erythropoietin Alfa in Patients With High-Risk Cervical Cancer: Results of the NOGGO-AGO Intergroup Study
Authors: Jens-Uwe Blohmer, Stefan Paepke, Jalid Sehouli, Dirk Boehmer, Martin Kolben, Florian Würschmidt, Karl U. Petry, Rainer Kimmig, Dirk Elling, Christoph Thomssen, Gunter von Minckwitz, Volker Möbus, Axel Hinke, Sherko Kümmel, Volker Budach, Werner Lichtenegger, Peter Schmid
Journal: Journal of Clinical Oncology (2011)

This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy.Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events.The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups.This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.