tbuckley/cabot-search huggingface dataset:
Abstract P267: New Urbanism and Its Impact on Active Living among Inner City Children/Youth
Authors: Gregory W Heath, Sarah White-Woerner
Journal: Circulation (2012)

Introduction: Although it is known that urban design and land use at the community level contributes to active living, there remains a paucity of such information among low income and diverse populations affected by such infrastructure. Reconstruction of an inner city community in Chattanooga, Tennessee afforded the opportunity to assess the impact of new urbanist construction on active living among African-American children/youth living in the inner city. Hypothesis: Transportation and recreational physical activity levels among children/youth residing in a new urbanist community was hypothesized to be higher compared to demographically similar children/youth who reside in a more traditional inner city community. Methods: Using the System for Observing Physical Activity and Recreation in Communities (SOPARC) we examined an urban trail and recreational park areas of two distinct communities to assess physical activity, sports, and recreational of children/youth. SOPARC data were collected in each of 4 settings in each community (East, a traditional and South, a new urbanist) during four 1-h observation periods during 7 days of clement weather. Observations were made during each day of the week in each setting (i.e., Sunday through Saturday). Results: The SOPARC assessments of the urban trail and pedestrian/bicycle routes in the South and East yielded a total of 672 and 436 children/youth observations, respectively. South children/youth were over three times more likely to engage in vigorous physical activity compared to their East counterparts (Mantel-Haenszel Chi Square = 19.67; P&lt; 0.00001). Conclusions: The present findings support the hypothesis that enhanced environmental supports, such as those found within the South community, increase the likelihood of greater levels of activity among children/youth compared to children/youth that were not exposed to these environmental enhancements. This comparative difference was most remarkable when examining the SOPARC assessment differences along the transport path/sidewalk routes, with South children/youth being significantly more likely than the East children/youth to engage in more vigorous forms of physical activity along this transport/recreational corridor, providing evidence that access to these types of ‘urban’ trails appears to translate into increased opportunities for physical activity among children/youth.
Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer (EC) trials with preoperative therapy (PreTx): Literature-based meta-analysis.
Authors: Kozo Kataoka, Kenichi Nakamura, Junki Mizusawa, Junko Eba, Hiroshi Katayama, Ken Kato, Taro Shibata, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2015)

199 Background: Disease-free survival after adjuvant chemotherapy in colon and gastric cancer has already been validated as a surrogate endpoint for OS. However, there have been no reports evaluating PFS as a surrogate endpoint in resectable EC. Standard treatment for resectable EC is preoperative chemotherapy (preCx) or chemoradiotherapy (preCRT) followed by surgery. This study was conducted to evaluate the trial level correlations between PFS and OS in resectable EC with PreTx and to explore potential merit of PFS as a surrogate endpoint for OS. Methods: A systematic literature search of randomized trials with preCx or preCRT for EC reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. 95% confidence interval of R 2 was estimated by bootstrap method. The primary analysis included trials in which the HR of PFS and OS were reported. A sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Results: Of 615 articles, 9 trials (2,725 patients) were selected for the primary analysis and 12 (3,020) for the sensitivity analysis. Median numbers of enrolled patients were 256 (range 101-802) in primary analysis, and 209 (75-802) in sensitivity analysis. The numbers of trials including only preCx, only preCRT and both, were 5, 4 and 0 in the primary analysis, and 5, 6 and 1 in the sensitivity analysis. The primary analysis did not show the correlation between treatment effects on PFS and OS (R 2 0.217, 95%CI [0.003-0.910]). The sensitivity analysis did not show the association of PFS and OS (R 2 0.153, 95%CI [0.000-0.682]). Conclusions: Although the number of randomized controlled trials evaluating PreTx for EC is limited at the moment, PFS was not suitable as a surrogate endpoint for OS. OS should be used as the primary endpoint in trials of PreTx for resectable EC.
Major changes proposed for NHS in Scotland
Authors: Bryan Christie
Journal: BMJ (2016)

A new clinical strategy that recommends major changes to existing services will transform the way healthcare is provided in Scotland.

Under the plans announced by the health secretary, Shona Robison, primary care would be delivered by multidisciplinary teams, integrated with social services.1 GPs would focus on complex cases and give expert assessment of new cases.

Most hospitals would still deliver outpatient, diagnostic, and day case surgical services, but specialist services would be available at fewer sites. This is based on evidence that outcomes were …
TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy
Authors: E Nievergall, J Reynolds, C H Kok, D B Watkins, M Biondo, S J Busfield, G Vairo, K Fuller, W N Erber, T Sadras, R Grose, D T Yeung, A F Lopez, D K Hiwase, T P Hughes, D L White
Journal: Leukemia (2016)
Relationship Between Platelet Reactivity and Culprit Lesion Morphology
Authors: Kyeong Ho Yun, Gary S Mintz, Bernhard Witzenbichler, Shinji Inaba, Takehisa Shimizu, D Christopher Metzger, Michael J Rinaldi, Ernest L Mazzaferri, Peter L Duffy, Giora Weisz, Thomas D Stuckey, Bruce R Brodie, Ajay J Kirtane, Gregg W Stone, Akiko Maehara
Journal: JACC. Cardiovascular imaging (2016)
Abstract 14050: Endothelial Function in Humans Using a Strain-Gauge Plethysmography is a Predictor of Cardiovascular Events
Authors: Tatsuya Maruhashi, Yukihito Higashi, Shinsuke Mikami, Yumiko Iwamoto, Masato Kajikawa, Takeshi Matsumoto, Ayumu Nakashima, Kensuke Noma, Yasuki Kihara
Journal: Circulation (2012)

Background: It is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. The vascular response to the intra...
Variability in the disposition of intraventricular methotrexate: a proposal for rational dosing.
Authors: D R Strother, A Glynn-Barnhart, E Kovnar, R E Gregory, S B Murphy
Journal: Journal of Clinical Oncology (1989)

Despite the clinical experience with Ommaya reservoir-facilitated intraventricular methotrexate (MTX) therapy, established age-related dosage guidelines do not exist. In an attempt to design such a schedule, 49 courses of intra-Ommaya MTX (median dose, 6 mg) administered to 12 patients were studied. Using a fluorescence polarized immunoassay (TDx; Abbott, Dallas, TX), the median peak intraventricular CSF MTX concentration (CSF [MTX]) was 423 mumol/L. Median CSF [MTX] at 24 hours was 4.6 mumol/L, and at 48 hours was 1.05 mumol/L. Median MTX half-life (t1/2) was 5.7 hours. A CSF [MTX] greater than 1 mumol/L was maintained for 24 hours in all but one course and for 48 hours in half of the courses. No correlations were found between MTX dose, patient age, [MTX], t1/2 or prior therapy. Considerable intra- and interpatient variability was seen in MTX disposition, emphasizing the need to monitor [MTX] with each course. A schedule for intraventricular MTX with an initial dose of 6 mg and supplemental doses of 6, 4, or 2 mg at 24 and 48 hours according to serial measurements of intraventricular [MTX] should be initiated to provide a minimum CSF [MTX] of 1 mumol/L for 72 hours.
Abstract 377: EpCAM+ and EpCAM- circulating tumor cells in metastatic lung cancer
Authors: Sanne de Wit, Guus van Dalum, Aufried T.M. Lenferink, Arjan G.J. Tibbe, Jeroen T.N. Hiltermann, Harry J.M. Groen, Cees van Rijn, Leon W.M.M. Terstappen
Journal: Cancer Research (2015)

Abstract Purpose: The presence of Circulating Tumor Cells (CTC) in metastatic carcinomas detected by CellSearch is associated with poor outcome. CellSearch uses an enrichment step based on the EpCAM antibody and enumerates CTC using antibodies targeting specific cytokeratins. Here we investigate the presence and role of CTC not detected by CellSearch in lung cancer patients. Methods: Blood discarded by CellSearch after EpCAM based enrichment was collected and enriched for CTC by filtration through microsieves and enumerated after fluorescent labeling. Additional anti-cytokeratin antibodies were added to the CellSearch test to increase the cytokeratin coverage. This approach was validated using different cell lines spiked into blood and tested on blood samples of 28 metastatic lung cancer patients. Results: The majority of spiked EpCAM+ cells could be detected with CellSearch whereas few cells were detected with low or no EpCAM expression (EpCAM-). Recovery of cells on microsieves depended strongly on cell size. One or more CTC were detected in 39% of the patient samples, this increased to 75% when adding the CTC detected in the discarded blood and to 82% with the use of additional cytokeratin antibodies. Presence of CTC was significantly associated with poor Overall Survival (OS) when detected by CellSearch without (p = 0.004) and with additional cytokeratins (p = 0.007), but not with EpCAM-CTC in the blood discarded by CellSearch (p = 0.271) or all CTC detected (p = 0.354) Conclusions: Expanding the cytokeratin coverage and including EpCAM-CTC, double the number of patients with CTC and the number of CTC detected with CellSearch. In contrast with EpCAM+ CTC, the presence of EpCAM-CTC in this group of patients was not associated with poor OS. The metastatic lung cancer patients included in this study were very diverse with respect to cancer type, line of therapy and quite small in numbers to make any definitive conclusions. Still, this pilot study warrants a larger study to confirm the findings. In addition an in-depth characterization of the EpCAM+ and EpCAM-CTC is needed to confirm that the EpCAM-, panCK+ CTC are indeed tumor cells and unravel the genetic difference with the EpCAM+, panCK+ CTC. Citation Format: Sanne de Wit, Guus van Dalum, Aufried T.M. Lenferink, Arjan G.J. Tibbe, Jeroen T.N. Hiltermann, Harry J.M. Groen, Cees van Rijn, Leon W.M.M. Terstappen. EpCAM+ and EpCAM- circulating tumor cells in metastatic lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 377. doi:10.1158/1538-7445.AM2015-377
Intraoral Mitochondrial-Targeted GS Nitroxide JP4-039 Ameliorates Radiation-Induced Mucositis in Orthotopic Tumor-Bearing Fanconi Anemia (FA) (Fancd2-/-) Mice.
Authors: Ashwin Shinde, Byung Han Rhieu, Hebist Berhane, Eva C. Guinan, Kalindi Parmar, Hong Wang, Darcy Franicola, Xichen Zhang, Song Li, Tracy M. Dixon, Joel S. Greenberger
Journal: Blood (2014)
Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats
Authors: Elizabeth R. Balmayor, Johannes P. Geiger, Manish K. Aneja, Taras Berezhanskyy, Maximilian Utzinger, Olga Mykhaylyk, Carsten Rudolph, Christian Plank
Journal: Biomaterials (2016)
Multidrug-resistance modulation in metastatic breast cancer patients.
Authors: K Mross
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.1.303 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7799036 Multidrug-resistance modulation in metastatic breast cancer patients. K MrossxK MrossSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.1.303 PDF "Multidrug-resistance modulation in metastatic breast cancer patients.." Journal of Clinical Oncology, 13(1), pp. 303–304© 1995 by American Society of Clinical Oncology
Decoding The BH3-Mimetic Pro-Apoptotic Activity Of Quercetin In Jurkat Cells
Authors: Alexandra Primikyri, Eleftheria Hatzimichael, Evdoxia Karali, Eleftherios Kostaras, Michalis Manztaris, Jae-Sun Shin, Seung-Wook Chi, Evangelos Kolettas, Ioannis Gerothanassis, Evangelos Briasoulis, Andreas Tzakos
Journal: Blood (2013)
Cardiac Stem Cell Treatment in Myocardial Infarction
Authors: Peter Paul Zwetsloot, Anna Maria Dorothea Végh, Sanne Johanna Jansen of Lorkeers, Gerardus P.J. van Hout, Gillian L. Currie, Emily S. Sena, Hendrik Gremmels, Jan Willem Buikema, Marie-Jose Goumans, Malcolm R. Macleod, Pieter A. Doevendans, Steven A.J. Chamuleau, Joost P.G. Sluijter
Journal: Circulation Research (2016)

Rationale: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date, there has been no systematic overview and meta-analysis of studies using CSC therapy for MI. Objective: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. Methods and Results: A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSC-treated animals was 10.7% (95% confidence interval 9.4–12.1; P &lt;0.001) improvement in ejection fraction compared with placebo controls. Interestingly, CSC therapy had a greater effect in small animals compared with large animals ( P &lt;0.001). Meta-regression indicated that cell type was a significant predictor for ejection fraction improvement in small animals. Minor publication bias was observed in small animal studies. Conclusions: CSC treatment resulted in significant improvement of ejection fraction in preclinical animal models of MI compared with placebo. There was a reduction in the magnitude of effect in large compared with small animal models. Although different CSC types have overlapping culture characteristics, we observed a significant difference in their effect in post-MI animal studies.
Treatment discontinuations, dose reductions, and interruptions for angiogenesis inhibitor therapies in patients with metastatic renal cell carcinoma (mRCC)
Authors: A. J. Brick, D. F. McDermott, J. M. Clement, C. Kwabi, K. Shah, J. R. Weiner, M. S. Duh, M. P. Neary, W. K. Oh, T. K. Choueiri
Journal: Journal of Clinical Oncology (2008)

14636 Background: Sunitinib, sorafenib, and bevacizumab are angiogenesis inhibitors that have emerged as active therapies in the treatment of mRCC, however little is known about treatment modification and failure rates for these agents in real-world clinical practice. This study aims to examine these patterns by describing and quantifying dose reductions, interruptions and discontinuations in patients (pts) treated in a US tertiary oncology setting. Methods: A retrospective review of medical records was performed, using both electronic databases and paper records, in 2 large US tertiary oncology centers. Pts were included in the study if they were ≥ 18 years of age, had a diagnosis of mRCC and received ≥ 1 prescription for oral sunitinib or sorafenib or ≥ 1 IV administration of bevacizumab (used off-label in US). For each agent, the proportions of pts who had ≥ 1 dose reduction (decrease in dosage or dose frequency), ≥ 1 dose interruption (excluding dose interruptions per prescribing information) or who discontinued the agent were computed. Reasons for discontinuation were tabulated. Results: Preliminary results based on 84 pts are presented below. Approximately 1/3 of pts receiving oral agents had ≥ 1 dose reduction. Discontinuations were common for all 3 agents, ranging from 55.0% to 82.6%. The most common reason for treatment discontinuation was progressive disease, followed by toxicities. Additionally, a considerable amount of switching among agents was observed. Updated results will be presented for a target of 140 pts. Conclusions: Preliminary results suggest that currently available angiogenesis inhibitor therapies may be associated with high rates of discontinuation of treatment due to progressive disease and/or toxicities in pts with mRCC. Continued investigation of novel agents and/or better supportive therapies is needed. Sunitinib (N = 35) Sorafenib(N = 26) Bevacizumab (N = 23) Age, yrs (mean ± sd) 59.1 ± 9.7 59.5 ± 10.0 62.5 ± 10.5 Male, N (%) 24 (68.6) 18 (69.2) 18 (78.3) Prior cytokine therapy, N (%) 9 (25.7) 11 (42.3) 8 (34.8) Had ≥ 1 dose reduction, N (%) 12 (34.3) 9 (34.6) 0 (0.0) Had ≥ 1 dose interruption, N (%) 5 (14.3) 7 (26.9) 2 (8.7) Discontinued therapy, N (%) 20 (57.1) 21 (80.8) 19 (82.6) Reason for discontinuation, N (% of pts who discontinued) Progressive disease 11 (55.0) 15 (71.4) 11 (57.9) Progressive disease + toxicity 0 (0.0) 3 (14.3) 0 (0.0) Toxicity 7 (35.0) 1 (4.8) 7 (36.8) Toxicity + other 1 (5.0) 0 (0.0) 0 (0.0) Other/unknown 1 (5.0) 2 (9.5) 1 (5.3) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Genentech, Novartis, Onyx/Bayer, Pfizer, Wyeth GlaxoSmithKline Genentech, Onyx/Bayer, Pfizer Genentech, GlaxoSmithKline, Novartis, Onyx/Bayer, Pfizer, Wyeth
Reply
Authors: Anders Boyd, Gilles Peytavin, Karine Lacombe
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Boyd is on the speakers' bureau for Gilead. Dr. Lacombe advises, is on the speakers' bureau of, and received grants from Gilead. Dr. Peytavin consults, is on the speakers' bureau of, and received grants from Janssen. He is on the speakers' bureau of and received grants from Bristol‐Myers Squibb, Gilead, Merck, and ViiV. We thank Wong et al. for providing interesting supplemental data with regard to our article examining the virological and clinical implications of persistent viremia (PV) in tenofovir disoproxil fumarate (TDF)‐treated patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV).1 The authors used a novel technique to measure treatment adherence in which intracellular metabolites of tenofovir diphosphate (TFV‐DP) stored in red blood cells are quantified from dried blood spots (DBSs). The advantage of quantifying TFV‐DP comes largely from its extended half‐life compared to tenofovir in plasma, allowing a broader picture of adherence within a 2‐week span. The levels of TFV‐DP observed in their 2 coinfected patients who had detectable HBV replication, despite long periods of plasma HIV‐RNA suppression and TDF‐containing antiretroviral therapy, revealed that TDF was not consistently taken before the study visit. From their experience, suboptimal treatment adherence would be the most probable underlying cause for HBV persistence. Because this technique requires whole‐blood samples and only serum/plasma were stored in the French HIV‐HBV cohort, we were unable to evaluate adherence by intracellular TFV‐DP among our patients with PV. Notwithstanding the usefulness of this measure, we stress that poor long‐term adherence to TDF could be one of several potential reasons for incomplete HBV suppression. HBV replication has been shown to continue at extremely low levels in a large proportion of HBV monoinfected patients undergoing TDF with optimal adherence.2 It remains to be confirmed whether changes in viral quasi‐species during low‐level replication could evoke bouts of detectable persistence. Furthermore, patients from our cohort presenting with either transient (i.e., blips of detectable HBV replication) or low‐level PV (i.e., HBV‐DNA levels 60‐2,000 IU/mL at the end of follow‐up) had significantly lower nadir CD4+ cell counts compared to those with controlled HBV replication,1 suggesting that historically severe immunosuppression is also a factor. The specific immunological components giving rise to PV have yet to be determined. We hope that the authors will evaluate these other potential causes of PV as more patents are included in their ongoing study. In any case, DBS technology will greatly aid future research on this topic in assessing the role of long‐term, and not "white coat," adherence. Because we expect TDF to be soon replaced by tenofovir alafenamide, which yields 86% lower TFV plasma and 7‐fold higher intracellular TFV‐DP levels, TFV‐DP quantification might become more suitable for coinfected patients undergoing treatment with this antiviral agent.3
Prognostic value of HER-2/neu overexpression for the development of brain metastasis after treatment of early breast cancer
Authors: J. Ahn, S. Kim, W. Kim, G. Gong, M. Kim, B. Son, S. Ahn, S. Lee, H. Kim
Journal: Journal of Clinical Oncology (2007)

21044 Background: Several studies have addressed the incidence of brain metastasis in HER-2/neu-overexpressing metastatic breast cancer. However, the relevance of HER-2/neu overexpression as a risk factor for brain metastases in breast cancer has not yet been clearly defined. The aim of this study is to analyze the risk of brain metastasis in HER-2/neu-positive early breast cancer patients in comparison with HER-2/neu-negative patients. Methods: We used tissue microarray to examine HER- 2/neu overexpression by immunohistochemistry (IHC) in 773 consecutive patients diagnosed with breast carcinoma who underwent surgery between January 1993 and December 1998. Patients were considered HER-2/neu-positive if they were 3+ on IHC testing. A total of 194 (25.1%) patients with HER-2/neu-overexpressing newly diagnosed breast cancer were identified in our study. The medical records and pathologic data of all 773 patients were reviewed retrospectively. Results: During a median follow-up period of 8.1 years, brain metastasis were identified in 7.2% (14 patients) with 194 HER-2/neu-overexpressing breast cancer compared with 2.6% (15 patients) in 597 HER-2/neu-negative patients (hazard ratio 2.924 [1.385–6.175], P=0.005). More HER-2/neu-overexpressing patients developed distant metastasis (33.5% vs. 18.8%, P=0.0001). The 8-year overall survival was 76.1% for HER-2/neu-negative patients versus 56.4% for HER-2/neu-positive patients (P&lt;0.00001). By multivariate analysis, HER-2/neu overexpression, tumor size larger than 2 cm, at least one positive node, and progesterone receptor (PR)-negativity were independent risk factors for the development of brain metastases. Conclusions: Our data show that HER-2/neu overexpressing early breast cancer patients are at significantly increased risk for brain metastases. Also, our results demonstrate that HER-2/neu overexpression is an important independent prognostic factor of early breast cancer, and suggest that more aggressive adjuvant chemotherapy and radiologic screening to detect brain metastases should be considered in this population. No significant financial relationships to disclose.