tbuckley/cabot-search huggingface dataset:
Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial
Authors: J. O'Shaughnessy, C. Osborne, J. Pippen, M. Yoffe, D. Patt, G. Monaghan, C. Rocha, V. Ossovskaya, B. Sherman, C. Bradley
Journal: Journal of Clinical Oncology (2009)

3 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
44. Phase I Study of Ad5-TRAIL in Men with Clinically Organ Confined Prostate Cancer
Journal: Molecular Therapy (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4870 

We have developed a recombinant adenovirus that encodes human TNF-related apoptosis-inducing ligand (TRAIL; Ad5-TRAIL), which is a potent inducer of tumor cell apoptosis but is not cytotoxic to normal cells. In vitro infection of human prostate tumor cells with Ad5-TRAIL resulted in the rapid transcription and translation of the transferred TRAIL gene into functional TRAIL protein that, when expressed on the cell surface, induced apoptotic death in TRAIL-sensitive prostate tumor cell targets but not normal prostate epithelial cells. Furthermore, in vivo preclinical studies have revealed Ad5-TRAIL can inhibit or slow the outgrowth of human prostate tumor xenografts in SCID mice. Thus, the primary objective of the study is to determine the local and systemic toxicity associated with intraprostatic injection of Ad5-TRAIL delivered in a collagen matrix in men with locally confined prostate cancer, and determine the maximum tolerated dose from four different dose levels. Secondary study objectives will examine the distribution of Ad5-TRAIL within the human prostate after transrectal injection, to determine the effect of transrectal injection of Ad5-TRAIL on existent prostate cancer, and to determine the effect of Ad5-TRAIL-induced apoptosis on immune activation to prostate antigens. Prostate cancer patients (T1c, T2a, T2b and N0, M0) scheduled to undergo radical prostatectomy (RRP) within 10 d following study entry were chosen. The patients had 4 intraprostatic injections of Ad5-TRAIL, 2 per prostate lobe. One week later, endorectal MRI was performed prior to RRP to rule out abscess. Laboratory assessment was performed to assess systemic infection. RRP was then performed if there was no adverse reaction. Operation difficulty was compared to non-injected control patients. Standard histologic evaluation and Gleason grading was performed. Evaluation of the inflammatory infiltrates in Ad5-TRAIL-treated prostates was assessed and compared to control prostate biopsies. To date (11/06), three patients have received the initial vector concentration. There were no immediate or delayed allergic reactions. None of the patients showed abscess on MRI. Operatively, there was no indication of increased inflammation (p=.495), difficulty of the operation, length of stay (p=0.724), or total estimated blood loss. There was no significant increased morbidity post-operatively. All patients had negative margins. Pathologically, each patient had an increase in staging from clinically, and viral vector uptake was shown through visualization of the collagen matrix in the specimen. Ad-5 TRAIL in vivo is known to induce apoptosis in prostate cancer. The initial dose level shows intraprostatic injection is well-tolerated and remains in the prostate after injection. Further increases in dosing will reveal the maximum tolerated dose, and likelihood of increased apoptosis in prostatectomy specimens.
Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis
Authors: S. Bracarda, R. Iacovelli, L. Boni, M. Rizzo, L. Derosa, M. Rossi, L. Galli, G. Procopio, M. Sisani, F. Longo, M. Santoni, F. Morelli, G. Di Lorenzo, A. Altavilla, C. Porta, A. Camerini, B. Escudier, Angelo Martignetti, Riccardo Ricotta, Donatello Gasparro, Roberto Sabbatini, Giovanni Luca Ceresoli, Alessandra Mosca, Daniele Santini, Claudia Caserta, Luigi Cavanna, Francesco Massari, Teodoro Sava, Corrado Boni, Elena Verzoni, Giacomo Cartenì, Alketa Hamzaj
Journal: Annals of Oncology (2015)
Improving the evaluation of left ventricular systolic function with intravenous perfluorocarbon ultrasound contrast: will suboptimal echocardiograms become an endangered species?∗∗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: Thomas R Porter
Journal: Journal of the American College of Cardiology (2000)
Baseline Troponin T Levels Modulate the Effects of ICD Shocks on All-Cause Mortality
Authors: Victor Nauffal, Yiyi Zhang, Elena Blasco-Colmenares, David D. Spragg, Joseph E. Marine, Barbara Butcher, Sanaz Norgard, Eliseo Guallar, Gordon F. Tomaselli, Alan Cheng
Journal: Journal of the American College of Cardiology (2015)
Hodgkin's disease during HIV1 infection: The French Registry Experience
Authors: J.M. Andrieu, S. Roithmann, J.M. Tourani, R. Levy, B. Desablens, C. le Maignan, J.A. Gastaut, P. Brice, M. Raphael, B. Taillan
Journal: Annals of Oncology (1993)
Silencing of <i>CD24</i> Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells
Authors: Wei Zhang, Bin Yi, Chao Wang, Dongquan Chen, Sejong Bae, Shi Wei, Rong-Jun Guo, Changming Lu, Lisa L.H. Nguyen, Wei-Hsiung Yang, James W. Lillard, Xingyi Zhang, Lizhong Wang, Runhua Liu
Journal: Clinical Cancer Research (2015)

Abstract Purpose: In prostate cancer cells, there is CD24-dependent inactivation of mutant p53, but the mechanism and its significance remain largely unknown. Here, we validated this observation and explored the therapeutic potential of targeting CD24 in TP53 mutant prostate cancer cells. Experimental Design: Overall, 553 prostate cancers (522 formalin-fixed paraffin-embedded and 31 frozen tissues) were assessed for protein or mRNA expression of CD24 and TP53. The effects of CD24 on p53-dependent transcriptional regulation, cancer cell growth, the cell cycle, apoptosis, and mutant p53 restoration were also determined. Results: As determined with three sample cohorts, CD24 and p53 were not expressed in prostate epithelial cells but in prostate cancer cells in 48% of cases for CD24 and 16% of cases for p53 (mutant form). Expressions of CD24 and mutant p53 were more frequently observed in late-stage and metastatic prostate tumors. Mutant p53 accompanied with CD24 was expressed in most cases (91.6%, 76/83). Silencing of CD24 increased the transcriptional activity of p53 target genes, such as CDKNA1, VDR, and TP53INP1, leading to suppression of p53-dependent cell growth, cell-cycle arrest, and apoptosis in most TP53-mutant prostate cancer cells. Silencing of CD24 enhanced restoration of PRIMA-1–induced mutant p53 in endogenous TP53P223L/V274F DU145 cells and in PC3 cells transfected with TP53R273H. Conclusions: In human prostate cancers, there is CD24-dependent inactivation of mutant p53. The coexpression of CD24 and p53 may help identify aggressive cancers. Targeting CD24 provides a strategy to enhance mutant p53-restoring therapies, especially in patients with TP53R273H prostate cancer. Clin Cancer Res; 22(10); 2545–54. ©2015 AACR.
Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies
Authors: Ivana N. M. Micallef, Debra M. Lillington, John Apostolidis, John A. L. Amess, Michael Neat, Janet Matthews, Taane Clark, James M. Foran, Ashiq Salam, T. Andrew Lister, Ama Z. S. Rohatiner
Journal: Journal of Clinical Oncology (2000)

To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL).Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML.Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively).tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.
Continuous daily administration of sunitinib in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC): Updated results
Authors: S. Srinivas, J. Roigas, S. Gillessen, U. Harmenberg, P. H. De Mulder, G. Fountzilas, N. Vogelzang, C. Peschel, P. Flodgren, B. Escudier
Journal: Journal of Clinical Oncology (2007)

5040 Background: Sunitinib malate, an oral, multitargeted tyrosine kinase inhibitor of multiple receptors, showed significant efficacy in 168 pts with cytokine refractory mRCC, with a 42% objective response rate (ORR) and progression-free survival (PFS) of 8.2 months at 50 mg/day (4 weeks on treatment, 2 weeks off) per investigator assessment (Motzer et al. JAMA 2006;295:2516–24). This study was designed to determine the efficacy and safety of single-agent sunitinib when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints included PFS, adverse events (AEs) and quality of life measures. Results: 107 pts were randomized to AM (54) or PM (53) dosing and have been on study a median of 6.8 months (0.4 to 13.3). As of October 2006, 55 pts have discontinued due to progression (37 pts [35%]), AEs (17 pts [16%]), and 1 consent withdrawal (1%); 47 pts (44%) were dose reduced to 25 mg/day due to grade 2/3 AEs, the most frequent being: asthenia (12%), hand-foot syndrome (8%), and diarrhea (5%). The most commonly reported (=5% of pts) grade 3/4 AEs were hypertension (10%), asthenia (9%), hand-foot syndrome (9%), anorexia (8%), and diarrhea (6%). 31 pts (29%) were maintained on continuous sunitinib at 37.5 mg/day, and 29 (27%) were escalated to 50 mg/day. There were no significant differences between pts who received AM or PM dosing. Quality of life results will be presented. The best response by RECIST per investigator assessment shows an ORR of 19% with 43 pts (40%) with =6 months of stable disease. The median PFS is 8.3 months. Conclusions: Sunitinib 37.5 mg/day continuous dosing has a manageable safety profile and demonstrates promising clinical benefit as second-line therapy in mRCC. This regimen provides alternative sunitinib dosing that can be explored in combination studies. No significant financial relationships to disclose.
Efficacy of T-cell transcription factor–specific DNAzymes in murine skin inflammation models
Authors: Ulrich Purath, Rouba Ibrahim, Jana Zeitvogel, Harald Renz, Frank Runkel, Thomas Schmidts, Dorota Dobler, Thomas Werfel, Anke Müller, Holger Garn
Journal: Journal of Allergy and Clinical Immunology (2015)
Phase I/II study of docetaxel (D), gemcitabine (G), and bevacizumab (B) in patients (pts) with advanced or recurrent soft tissue sarcoma (STS)
Authors: C. F. Verschraegen, R. Quinn, I. Rabinowitz, H. Arias-Pulido, C. Muller
Journal: Journal of Clinical Oncology (2008)

10534 Background: The combination of G and D has efficacy against refractory STS (Hensley, JCO 2002). Poor prognosis STS have a high content of VEGF. This phase I/II study assesses the safety and efficacy, of B in combination with G+D, given on a two-weekly schedule to minimize adverse events (AEs). Methods: Untreated pts with advanced STS and ECOG PS 0, 1, 2 were eligible. Surgically appropriate pts were treated in a neoadjuvant setting. Planned doses were G 1,000, 1,250, and 1,500 mg/m2, D 50 mg/m2, and B 5 mg/kg, iv every 2 wks. G doses were escalated in serial pt cohorts to determine the maximum tolerated dose of G during the 2 first cycles (1 cycle = 2 wks). Treatment was continued until progression or unacceptable toxicity. For neoadjuvant therapy, B was given for 4 cycles, followed by 4 cycles without B in anticipation of surgery and pts came off study at that point. Response was assessed by RECIST criteria. Serum VEGF and tumor VEGFR were measured. Results: Thirty-three pts were screened and 23 treated, including 7 in the neoadjuvant setting. The recommended dose is G 1,500 mg/m2, D 50 mg/m2, and B 5 mg/kg iv, every 2 wks. Pathologies were 5 leiomyosarcoma (LMS), 4 MFH, 3 PNST, 3 angiosarcoma (AS), and 8 others. Three pts are not assessable (1 too early, 2 full treatment not given). There were 3 CR (1 MFH, 2 AS), 5 PR, (2 LMS, 1 MFH, 1 undifferentiated sarcoma, 1 liposarcoma), 8 NC, and 4 PD (MFH, PNST, LMS, and chondro). ORR is 40% (8/20). Four pts are alive free of disease. Seven pts died, 5 of PD and 2 as an indirect consequence of treatment (pulmonary embolism and renal failure). Observed AES were grade 4 pneumothorax and bowel perforation (4% each); grade 3 fatigue (8%), skin ulceration, hemorrhage, and bowel perforation (4% each); grade 1 and 2 fatigue (60%), alopecia (38%), constipation (38%), nausea (34%), diarrhea (30%), dyspnea (25%), epiphora (21%), rash (21%), rigors (17%), headaches (17%), neuropathy (17%), epistaxis (8%), stomatitis (8%), hypertension (5%). There were no hematologic AEs. VEGF(R) results are pending. Conclusions: The combination of G, D, and B given every 2 weeks is very safe and has activity in untreated pts with advanced or recurrent STS. The most concerning AEs were consequences of B. No significant financial relationships to disclose.
Association of Do-Not-Resuscitate Orders and Hospital Mortality Rate Among Patients With Pneumonia
Authors: Allan J. Walkey, Janice Weinberg, Renda Soylemez Wiener, Colin R. Cooke, Peter K. Lindenauer
Journal: JAMA Internal Medicine (2015)

Hospital quality measures that do not account for patient do-not-resuscitate (DNR) status may penalize hospitals admitting a greater proportion of patients with limits on life-sustaining treatments.To evaluate the effect of analytic approaches accounting for DNR status on risk-adjusted hospital mortality rates and performance rankings.A retrospective, population-based cohort study was conducted among adults hospitalized with pneumonia in 303 California hospitals between January 1 and December 31, 2011. We used hierarchical logistic regression to determine associations between patient DNR status, hospital-level DNR rates, and mortality measures. Changes in hospital risk-adjusted mortality rates after accounting for patient DNR status and interhospital variation in the association between DNR status and mortality were examined. Data analysis was conducted from January 16 to September 16, 2015.Early DNR status (within 24 hours of admission).In-hospital mortality, determined using hierarchical logistic regression.A total of 90,644 pneumonia cases (5.4% of admissions) were identified among the 303 California hospitals evaluated during 2011; mean (SD) age of the patients was 72.5 (13.7) years, 51.5% were women, and 59.3% were white. Hospital DNR rates varied (median, 15.8%; 25th-75th percentile, 8.9%-22.3%). Without accounting for patient DNR status, higher hospital-level DNR rates were associated with increased patient mortality (adjusted odds ratio [OR] for highest-quartile DNR rate vs lowest quartile, 1.17; 95% CI, 1.04-1.32), corresponding to worse hospital mortality rankings. In contrast, after accounting for patient DNR status and between-hospital variation in the association between DNR status and mortality, hospitals with higher DNR rates had lower mortality (adjusted OR for highest-quartile DNR rate vs lowest quartile, 0.79; 95% CI, 0.70-0.89), with reversal of associations between hospital mortality rankings and DNR rates. Only 14 of 27 hospitals (51.9%) characterized as low-performing outliers without accounting for DNR status remained outliers after DNR adjustment. Hospital DNR rates were not significantly associated with composite quality measures of processes of care for pneumonia (r = 0.11; P = .052); however, DNR rates were positively correlated with patient satisfaction scores (r = 0.35; P < .001).Failure to account for DNR status may confound the evaluation of hospital quality using mortality outcomes, penalizing hospitals that admit a greater proportion of patients with limits on life-sustaining treatments. Stakeholders should seek to improve methods to standardize and report DNR status in hospital discharge records to allow further assessment of implications of adjusting for DNR in quality measures.
Economic analysis of prophylactic granulocyte colony-stimulating factor (G-CSF) use based on a risk model for neutropenic complications in breast cancer patients receiving adjuvant chemotherapy
Authors: D. C. Dale, L. E. Cosler, D. A. Wolff, E. Culakova, M. S. Poniewierski, J. Crawford, G. H. Lyman
Journal: Journal of Clinical Oncology (2006)

6107 Background: Although recent economic analyses of prophylactic G-CSF provide cost saving febrile neutropenia (FN) risk estimates of approximately 20%, many regimens have reported rates &lt;20%. A prospective nationwide cohort study was undertaken to develop risk models for neutropenic complications (NC) including severe and febrile neutropenia in patients receiving cancer chemotherapy (Lyman ASCO 2005). A cost-effectiveness model is presented to evaluate the economic impact of G-CSF prophylaxis based on the model. Methods: Data on 974 consecutive breast cancer patients receiving adjuvant chemotherapy at 115 randomly selected practice sites were analyzed. The clinical and cost impact of G-CSF prophylaxis in high-risk patients based on the model was compared with: 1) no G-CSF; 2) primary prophylaxis; and 3) secondary prophylaxis. Pegfilgrastim costs were based on Medicare pricing while hospitalization costs and mortality on national hospitalization data. Results: Independent predictors of first cycle NC included: type and schedule of chemotherapy, diabetes, elevated bilirubin, planned RDI &gt;85%, low glomerular filtration rate and low neutrophil count. Prophylactic G-CSF was associated with a decreased risk. Model R 2 =0.327 and c-statistic=0.80 [95% CI: 0.78–0.83; P&lt;.001]. At a baseline FN risk of 8.4% per cycle, the expected costs over four cycles of chemotherapy were: no pegfilgrastim: $1,285; primary prophylaxis: $2,573; secondary prophylaxis: $2,040 and model-targeted G-CSF: $1,527. Expected cost varied with FN risk and model performance. Primary prophylaxis was associated with lower cost than no prophylaxis at FN risk &gt;18%, while the model outperformed both strategies at an FN risk &gt;10%. At a baseline cycle risk of FN of 8.4%, model-guided G-CSF was associated with an expected cost of $44,980 per life saved. Cost savings increased as model discrimination increased. The model was consistently associated with lower cost compared to secondary prophylaxis. Conclusions: A risk model for NC has been developed in breast cancer patients receiving adjuvant chemotherapy. Use of the model to guide G-CSF support appears to be cost-effective at an overall FN risk of 10%. [Table: see text]
Emergency department attendances and heart disease deaths vary fivefold across England
Authors: Nigel Hawkes
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Emergency department attendances and heart disease deaths vary fivefold across England Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Postdoctoral progression is needed for doctors taking up clinical academic careers
Authors: Denise Best, Joana Lopes, Chris Pugh
Journal: BMJ (2015)

Gulland’s article highlights the value to patients of doctors being involved in research.1 2 While this has been recognised in the NHS’s commitment to research,3 such involvement, we believe, must include sufficient numbers of doctors taking up clinical academic careers. Progress in healthcare requires that medically trained academics become principal investigators making significant …
The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia
Authors: Barbora Tomalova, Milada Sirova, Pavel Rossmann, Robert Pola, Jiri Strohalm, Petr Chytil, Viktor Cerny, Jakub Tomala, Martina Kabesova, Blanka Rihova, Karel Ulbrich, Tomas Etrych, Marek Kovar
Journal: Journal of Controlled Release (2015)
Neurocognitive disorders in children with sleep-disordered breathing
Authors: Alessandra Tabarrini, Maria Chiara Paolino, Laura Papini, Rosa Castaldo, Francesco Biagiarelli, Raffaella Bruschi, Martina Forlani, Maria Pia Villa
Journal: European Respiratory Journal (2011)

Aims:  To compare the presence of neurocognitive disorders in children with Obstructive Sleep Apnea Syndrome (OSAS) or Primary Snoring (PS) and normal controls, and to investigate their correlation with duration of Sleep-Disordered Breathing (SDB).   Methods:  137 subjects (M/F 70/67; mean age 9.47±2.35 yrs) were studied: 58 children with SDB (19% PS,43.1% minimum OSAS,37.9% moderate-severe OSAS) and 79 control children. The SDB group underwent clinical evaluation, polysomnography and neurocognitive assessment based on Wechsler Intelligence Scale for Children (WISC-R). The control group was studied through a medical questionnaire and WISC-R.   Results:  Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ) and Full-Scale Intelligence Quotient (FSIQ) were lower in SDB group than in control children (VIQ: 94.55±13.74 vs 115.84±10.63; PIQ: 100.10±13.25 vs 118.24±11.79; FSIQ: 96.66±11.66 vs 110.08±11.17) (p standard population  – 2SD),SDB group was subdivided in: Group A: 15 children with SDB and cognitive impairment; Group B: 43 children with SDB without cognitive impairment. The age of onset was earlier in Group A than in Group B (3.64±2.65 yrs vs 5.29±3.64 yrs; p   Conclusions:  The incidence of neurocognitive disorders was greater in children with SDB than in controls. A significant correlation was present between neurocognitive impairment and both SDB9s age of onset and duration of disease suggesting that early onset and a long duration of disease are the major risk factor.