tbuckley/cabot-search huggingface dataset:
Brief Communication: Protection of Mice From Malignant Tumor Implants by Enucleated Tumor Cells
Authors: K. K. Sethi, H. Brandis
Journal: JNCI Journal of the National Cancer Institute (1974)

Four subcutaneous injections of enucleated tumor cells protected mice from progressive growth of corresponding virulent tumor cells implanted 3 days before the start of injections. Treatment of tumor-bearing mice with tumor cells devitalized by heating, ultraviolet irradiation, freeze-thawing, or with enucleated tumor cells antigenically unrelated to the initial tumor implant failed to check the tumor growth. Mice protected by enucleated tumor cell preparationshad a high degree of tumor-specific immunity.
Prevalence, Impact, and Predictive Value of Detecting Subclinical Coronary and Carotid Atherosclerosis in Asymptomatic Adults
Authors: Usman Baber, Roxana Mehran, Samantha Sartori, Mikkel Malby Schoos, Henrik Sillesen, Pieter Muntendam, Mario J. Garcia, John Gregson, Stuart Pocock, Erling Falk, Valentin Fuster
Journal: Journal of the American College of Cardiology (2015)
Safety and efficacy of sputum induction in COPD patients
Authors: Wai Yee James, David Jolliffe, Kamrul Islam, Claire Greiller, Adrian Martineau
Journal: European Respiratory Journal (2013)

Introduction   There is lack of studies addressing safety issues in performing sputum induction on COPD patients.   Aim:  To determine the efficacy and safety of a sputum induction protocol in COPD patients.   Methods   Ex-smokers with a diagnosis of COPD who had not experienced an exacerbation or an upper respiratory tract infection in the preceding 28 days, and who had a post-bronchodilator FEV1 ≥40% predicted were enrolled. A Norditalia ultrasonic nebuliser was used to deliver up to 3 5-minute nebulisations of 4.5% saline following inhalation of 400mcg Salbutamol. Induction was discontinued if FEV1 fell by more than 20% as compared with baseline; if the subject experienced discomfort due to wheeze, shortness of breath or chest tightness; or when three nebulisations had been administered or an adequate sputum sample had been obtained – whichever was sooner.   Results   Sputum samples sufficient to prepare a cytospin slide were obtained in 43/45 patients. 6/43 patients required one 5-minute nebulisation, 19/43 patients required two 5-minute nebulisations and 18/43 patients required three 5-minute nebulisations. The sputum induction protocol was discontinued in 9 patients, either because FEV1 fell below 80% of the baseline value (n=7) or because the patient developed wheeze or chest tightness (n=2). Rescue medication was administered in 14/45 inductions. Only one patient developed an exacerbation that was attributed to preceding sputum induction.   Conclusions   Sputum induction with nebulised 4.5% saline is effective and well tolerated in patients with COPD. Sputum samples were obtained with less than three rounds of nebulisation using this protocol in the majority of COPD patients.
Right ventricular dysfunction in pulmonary hypertension with combined pulmonary fibrosis and emphysema syndrome
Authors: Andrew Swift, Smitha Rajaram, Dave Capener, Catherine Hill, Christine Davies, Judith Hurdman, Robin Condliffe, Charlie Elliot, David Kiely, Jim Wild
Journal: European Respiratory Journal (2013)

Introduction:  Recent studies suggest that the coexistence of emphysema and fibrosis alters clinical outcome. The aim of this study was to investigate the comparative clinical characteristics, pulmonary function, haemodynamics and right ventricular (RV) function and outcome in patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema (PH-CPFE), chronic obstructive pulmonary disease (PH-COPD) and interstitial lung disease (PH-ILD).  Methods:  In 79, incident patients with pulmonary hypertension associated with respiratory disease, cardiovascular magnetic resonance imaging was performed at 1.5T. Emphysema and fibrosis were qualitatively assessed on high resolution computed tomography scans as previously described. Pulmonary function tests and right heart catheterisation were also performed.  Results:  Patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema syndrome had a significantly lower right ventricular ejection fraction (RVEF) and a larger right ventricular end-systolic volume index (RVESVI), when compared to both patients with PH-COPD and PH –ILD (p  Conclusion:  Patients with PH-CPFE have poor outcome with worse RV function in comparison to patients with PH-COPD and PH-ILD.
New strategies to prevent Staphylococcus aureus infections in peritoneal dialysis patients.
Authors: A Vychytil, M Lorenz, B Schneider, W H Hörl, M Haag-Weber
Journal: Journal of the American Society of Nephrology (1998)

The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.
Thymomas and Thymic Carcinomas
Authors: David S. Ettinger, Gregory J. Riely, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis, Stefan C. Grant, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Inga T. Lennes, Billy W. Loo, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Eric Rohren, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Douglas E. Wood, Stephen C. Yang, Kristina Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2013)

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.
Doctor told to repay 98 000 to NHS after working as locum while on paid sick leave
Authors: C. Dyer
Journal: BMJ (2015)

A doctor who defrauded the NHS of nearly £100 000 by working as a locum in England while on paid sick leave from his regular job in Wales may be jailed if he fails to pay the money back.

Prosecutors have asked Cardiff Crown Court to order Anthony Madu to refund earnings of £98 000 (€134 000; $150 000) under the Proceeds of Crime Act, which allows the authorities to claw back money made through criminal activities.

Prosecutor …
Effect of lenalidomide on the antiprostate cancer activity of docetaxel in vitro and in vivo.
Authors: J. Y. Henry, L. Lu, M. Adams, B. Meyer, J. B. Bartlett, C. Galustian, A. G. Dalgleish
Journal: Journal of Clinical Oncology (2010)

e13155 Background: Docetaxel in combination with prednisone is approved for castrate-resistant metastatic prostate cancer (CRPC). However, docetaxel-based drug combinations may exhibit significant toxicities and there is a need to consider combining with agents that enhance clinical activity without overlapping toxicities. Lenalidomide is FDA approved in del 5q myelodysplastic syndromes and in combination with dexamethasone for previously treated multiple myeloma. Preliminary data indicates that in combination with docetaxel and prednisone, lenalidomide has promising clinical activity in CRPC and a phase III trial is ongoing. We have evaluated lenalidomide in combination with docetaxel and alone using in vitro and in vivo prostate cancer models. Methods: The effect of lenalidomide alone (0.01- 1μM) or in combination with docetaxel (0.32-200nM) was assessed on the proliferation and apoptosis of PC3 and DU145 prostate cancer cells. The effect of lenalidomide on EGF-induced PC3 and DU145 cell transwell invasion was also studied. The combination of lenalidomide and docetaxel was assessed using an in vivo, xenograft model. Mice were treated with docetaxel (8mg/kg, bi-weekly) and lenalidomide (50mg/kg IP daily) until tumors reached 1400 mm3. Results: Lenalidomide alone did not inhibit cellular proliferation; however, at 0.01μM (DU145) and 1μM (PC3) lenalidomide reduced the mean IC50 for docetaxel by 42% and 36% respectively (p<0.05). In PC3 cells, 1μM lenalidomide significantly enhanced the apoptotic activity of docetaxel (p<0.05). Lenalidomide also significantly inhibited EGF-induced invasive activity of PC3 and DU145 cells (p<0.001). Median survival in mice treated with single agent lenalidomide or docetaxel increased (from 48 and 41 days) to 59 days when combined. Conclusions: These results show that lenalidomide alone inhibits the invasion of prostate cancer cells and also enhances the antiproliferative and pro-apoptotic effects of docetaxel in vitro. Combinatorial activity was also demonstrated in a xenograft model where tumor growth was slowed resulting in enhanced median survival. These results suggest that lenalidomide in combination with docetaxel should be explored further in clinical trials of CRPC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene Celgene Celgene
Abstract 4562: Ginkgetin inhibits the growth of cancer cells via the cell cycle arrest at G2-phase
Authors: Byoung-Mog Kwon, Yu-Jin Lee
Journal: Cancer Research (2014)

Abstract Ginkgetin, isolated from herbal medicines, has been reported to play a role in antitumor activity. However, the relevant pathway integrating cell cycle regulation and signaling pathways involved in growth inhibition in cancer cells remains to be identified. In the present study, ginkgetin treatment of colon cancer cells resulted in significant dose-dependent growth inhibition together with apoptosis, G2-phase cell cycle arrest at a 5 μM (IC50) dose in HCT116colon cancer cells and ginkgetin also inhibits tumor growth in a mouse xenograft model of HCT116 cells. We found that ginkgetin regulated the expression of genes which are critically involved in cell cycle, cell signaling transduction, and cell proliferation using DNA microarray analysis. Furthermore, we provided evidence that ginkgetin inhibited BUB3, cyclin B, CDC2, and b-Myb expression. Especially ginkgetin induced G2-phase arrest by down-regulates expression of b-Myb Our data have suggested that ginkgetin exerts its anticancer effects through induction of cell cycle arrest at G2 phase as well as inhibition cell proliferation. Note: This abstract was not presented at the meeting. Citation Format: Byoung-Mog Kwon, Yu-Jin Lee. Ginkgetin inhibits the growth of cancer cells via the cell cycle arrest at G2-phase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4562. doi:10.1158/1538-7445.AM2014-4562
Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development
Authors: A M Roncero, P López-Nieva, M A Cobos-Fernández, M Villa-Morales, L González-Sánchez, J L López-Lorenzo, P Llamas, C Ayuso, S M Rodríguez-Pinilla, M C Arriba, M A Piris, P Fernández-Navarro, A F Fernández, M F Fraga, J Santos, J Fernández-Piqueras
Journal: Leukemia (2015)

The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation and four missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are novel JAK2 mutations and the other two are reported for the first time in T-LBL. Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples showed different mutated transcripts suggesting sub-clonal heterogeneity. Functional approaches revealed that two JAK2 mutations (H574R and R683G) constitutively activate JAK-STAT signaling in γ2A cells and can drive the proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT signaling. Of utmost interest is that primary T-LBL samples harboring JAK2 mutations exhibited increased expression of LMO2, suggesting a mechanistic link between JAK2 mutations and the expression of LMO2, which was confirmed for the four missense mutations in transfected γ2A cells. We therefore propose that active JAK2 contribute to T-LBL development by two different mechanisms, and that the use of pan-JAK inhibitors in combination with epigenetic drugs should be considered in future treatments.
Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial
Authors: Josep Tabernero, Heinz-Josef Lenz, Salvatore Siena, Alberto Sobrero, Alfredo Falcone, Marc Ychou, Yves Humblet, Olivier Bouché, Laurent Mineur, Carlo Barone, Antoine Adenis, Takayuki Yoshino, Richard M Goldberg, Daniel J Sargent, Andrea Wagner, Dirk Laurent, Michael Teufel, Michael Jeffers, Axel Grothey, Eric Van Cutsem
Journal: The Lancet Oncology (2015)
Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL.
Authors: K D Heckman, G J Weiner, C S Davis, R G Strauss, M P Jones, C P Burns
Journal: Journal of Clinical Oncology (1997)

PURPOSE We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either &lt; or = 10,000/microL or &lt; or = 20,000/microL. RESULTS There was no significant difference in the total number of bleeding episodes per patient with a median of four in the &lt; or = 10,000/microL arm and two in the &lt; or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the &lt; or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the &lt; or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the &lt; or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION Giving prophylactic platelets at a threshold of &lt; or = 10,000/microL compared with &lt; or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.
Overdiagnosis of bone fragility in the quest to prevent hip fracture
Authors: T. L. Jarvinen, K. Michaelsson, J. Jokihaara, G. S. Collins, T. L. Perry, B. Mintzes, V. Musini, J. Erviti, J. Gorricho, J. M. Wright, H. Sievanen
Journal: BMJ (2015)

Despite widespread endorsement, <b>Teppo Järvinen and colleagues</b> argue that evidence for stratifying risk of fracture and subsequent drug therapy to prevent hip fracture is insufficient to warrant our current approach
Abstract 50: Hypertension, Antihypertensive Treatment, Sodium Intake and Cognitive Decline
Authors: Bernhard Haring, Chunyuan Wu, Laura H Coker, Arjun Seth, Linda Snetselaar, JoAnn E Manson, Jacques Rossouw, Sylvia Wassertheil-Smoller
Journal: Circulation (2015)

Objective: Our objective was to investigate the relationships of hypertension, antihypertensive treatment and sodium intake on cognitive decline in older postmenopausal women. Methods: Prospective follow-up of 6,426 cognitively intact women aged 65 to 79 years old enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Cognitive functioning was assessed annually by 3MS scores, neurocognitive and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs) for the risk of cognitive decline. Results: Hypertension was associated with an increased risk for cognitive decline (HR 1.23; 95% CI 1.06, 1.43; p=0.006) in elderly women. Antihypertensive treatment was related to an increased risk for cognitive decline with women having blood pressur...
Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial.
Authors: D F Bajorin, C R Nichols, H J Schmoll, P W Kantoff, C Bokemeyer, G D Demetri, L H Einhorn, G J Bosl
Journal: Journal of Clinical Oncology (1995)

PURPOSE Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended.
Overall survival of metastatic melanoma patients treated with HD IL-2 followed by immune checkpoint blockade of the CTLA-4 or the PD-1 pathways: analysis of data on the current use of HD IL-2
Authors: Michael KK Wong, Michael A Morse, David F McDermott, Joseph I Clark, Howard L Kaufman, Gregory A Daniels, Jessica C Perritt, Hong Hua, Sandra Aung
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts HD IL-2 was FDA approved for advanced melanoma, but the data supporting its use dates to the 1990's. The PROCLAIMSM registry (<http://www.proclaimregistry.com>) is the largest collection of IL-2 treated patients in the US and provides real-time insights into patient survival and
The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria
Authors: Nico C Gey van Pittius, Junaid Gamieldien, Winston Hide, Gordon D Brown, Roland J Siezen, Albert D Beyers
Journal: Genome biology (2001)

The genome of Mycobacterium tuberculosis H37Rv has five copies of a cluster of genes known as the ESAT-6 loci. These clusters contain members of the CFP-10 (lhp) and ESAT-6 (esat-6) gene families (encoding secreted T-cell antigens that lack detectable secretion signals) as well as genes encoding secreted, cell-wall-associated subtilisin-like serine proteases, putative ABC transporters, ATP-binding proteins and other membrane-associated proteins. These membrane-associated and energy-providing proteins may function to secrete members of the ESAT-6 and CFP-10 protein families, and the proteases may be involved in processing the secreted peptide.Finished and unfinished genome sequencing data of 98 publicly available microbial genomes has been analyzed for the presence of orthologs of the ESAT-6 loci. The multiple duplicates of the ESAT-6 gene cluster found in the genome of M. tuberculosis H37Rv are also conserved in the genomes of other mycobacteria, for example M. tuberculosis CDC1551, M. tuberculosis 210, M. bovis, M. leprae, M. avium, and the avirulent strain M. smegmatis. Phylogenetic analyses of the resulting sequences have established the duplication order of the gene clusters and demonstrated that the gene cluster known as region 4 (Rv3444c-3450c) is ancestral. Region 4 is also the only region for which an ortholog could be found in the genomes of Corynebacterium diphtheriae and Streptomyces coelicolor.Comparative genomic analysis revealed that the presence of the ESAT-6 gene cluster is a feature of some high-G+C Gram-positive bacteria. Multiple duplications of this cluster have occurred and are maintained only within the genomes of members of the genus Mycobacterium.