tbuckley/cabot-search huggingface dataset:
Retrospective review of treatment for angiosarcoma at Fox Chase Cancer Center over the past 15 years
Authors: S. Saroha, S. Litwin, M. von Mehren
Journal: Journal of Clinical Oncology (2007)

10034 Background: Angiosarcoma is a rare vascular neoplasm that may arise in a variety of anatomic locations. There is limited published data on chemotherapy treatment in angiosarcoma and data on taxane therapy does not utilize contemporary schedules. We present a retrospective analysis of our institution's experience with angiosarcoma over the past 15 years. We reviewed patient characteristics, overall survival and response to various chemotherapeutic agents. We specifically compared the response to weekly paclitaxel with all other chemotherapeutic agents used over the study period. Methods: Medical records of all the patients treated with the diagnosis of angiosarcoma at Fox Chase Cancer Center between January 1990 and June 2005 were reviewed. Overall survival was determined by the Kaplan-Meier method. Response to chemotherapy was determined at two-month follow-up after starting treatment. Clinician judgment was used to define response for superficial lesions. We compared the response to weekly paclitaxel with all other chemotherapy regimens using Fisher's exact test. p &lt;0.10 was considered significant. Results: A total of 39 patients were identified. Most common sites for angiosarcoma were head and neck (including scalp) and breast. Median overall survival was 21 months. Since many patients received several lines of chemotherapy, 40 chemotherapy administrations were identified for analysis. 10 of 13 patients showed response to weekly paclitaxel versus 14 of 27 for non-paclitaxel regimens, which was not statistically significant by Fisher's exact test (2-tail, p=0.18). We also analyzed the response with respect to different anatomic locations of angiosarcoma and individual chemotherapy regimens used, however the numbers were too small for statistical comparisons. Conclusions: Angiosarcoma is an aggressive malignancy with poor survival rates. Our study demonstrated that paclitaxel has efficacy in angiosarcoma, although not statistically superior to non-taxane containing regimens. No significant financial relationships to disclose.
Casual leading indicators detection for demand forecasting
Authors: Yves Sagaert, Nikolaos Kourentzes, El-Houssaine Aghezzaf, Bram Desmet
Journal: Eurosurveillance (2015)

Demand forecasts are often univariate, or include only limited causal promotional information on a short-term horizon, which do not capture changing long-term global markets. More especially, including causal exogenous information in the forecasting models could enrich the long-term forecast. The limited historical data is typically used to both identify the current univariate structure and select the appropriate causal leading indicators from a large set of exogenous variables. A key challenge is to be able to distinguish between correlated and causal variables. The resulting variable selection problem is well studied in literature, but far from resolved. Furthermore, the problem gets harder by the limited available historical data in this context of business forecasting. The amount of historical sales observations is far less than the size of the pool of potential causal leading indicators. Methodologies from heuristics to shrinkage estimators, such as LASSO, are examined to overcome the variable selection problem. In a case study, we use real demand data from a global manufacturer and potential causal leading macro-economic indicators from the different global markets the manufacturer trades in.
Obstructive airways diseases (OADs) are the most common diseases for a doctor visit in India: A one-day point-prevalence study in 2,04,912 patients from 880 cities and towns in India
Authors: Komalkirti Apte, Monica Barne, Sapna Madas, Jaideep Gogtay, Sushmeeta Chhowala, Nadar Mahajan, Sundeep Salvi
Journal: European Respiratory Journal (2012)

An understanding of the most common diseases for which a patient visits a doctor in India will help set up appropriate health care services. We aimed to study the most common doctor-diagnosed disease for which a patient visits a general practitioner (GPs), general physician (Gen Ps) and pediatricians (Ps) in India, using a 1-day point prevalence cross-sectional study design. Method: 13,225 GPs, Gen Ps and Ps from 22 states and 5 union territories across India were randomly selected from 880 cities and towns and invited to participate in a 1-day point-prevalence study. On 1st Feb 2011 those doctors who agreed to participate kept a record of all symptoms and diagnosis for which patients visited their clinic or hospital. 7710 doctors consented and clean data was obtained from 7400 doctors (65% GPs, 17.4%Gen Ps, and 17.6% Ps). Data was transferred into Epi-Info software and simple descriptive analysis was performed. Results: A total of 2,04,912 patients visited 7400 GPs, Gen Ps and Ps in India on 1 day. Amongst these, 16,783 patients visited a doctor for a diagnosis of asthma or COPD accounting for the highest number of visits (8.2%). Systemic hypertension (HT), anemia, diabetes and eczema accounted for 7.8%, 5.5%, 4.8% and 2.3% of the visits respectively. These observations were generally uniform across India, with no disease hot or cold spot regions. Conclusion: Extrapolating the above figures to around 15,00,000 registered GPs, GenPs and Ps in India, 3.5 million (m) patients visit a doctor every day in India for OADs, followed by 3.3 m for HT, 2.3 m for anemia, 2 m for diabetes and 1 m for eczema.
Abstract 12355: Role of Exercise Stress Testing in Arrhythmogenic Right Ventricular Dysplasia
Authors: John Kottarthil, Pradeep Panuganti, Aditya Jain, Darshan Dalal, Stuart D Russell, Daniel Judge, Hugh Calkins, Harikrishna Tandri
Journal: Circulation (2010)

Introduction: Exercise treadmill testing (ETT) is routinely used in ARVD evaluation, however, the diagnostic and prognostic utility of ETT in ARVD and the safety of exercise stress test is largely ...
Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer
Authors: Michael J. Morris, Dana E. Rathkopf, William Novotny, Jacqueline A. Gibbons, Amy C. Peterson, Zakaria Khondker, Taoufik Ouatas, Howard I. Scher, Mark T. Fleming
Journal: Clinical Cancer Research (2016)

Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).Docetaxel-naïve patients received 21-day cycles of docetaxel (75 mg/m(2)). Enzalutamide (160 mg/day) was administered daily starting on day 2 of cycle 1. Patients were allowed to stop and restart docetaxel at any time following cycle 2. Treatment continued indefinitely until unacceptable toxicity or discontinuation due to investigator or patient preference.A total of 22 patients received docetaxel, of whom 21 also received enzalutamide. Docetaxel was administered for a median of 5.0 cycles and enzalutamide for a median of 12.0 months. With concomitant treatment, geometric mean docetaxel exposure decreased by 11.8%, whereas peak concentrations decreased by 3.7% relative to docetaxel alone. The most common toxicities observed during the period of concomitant therapy were neutropenia (86.4%) and fatigue (77.3%). Common toxicities observed with post-docetaxel enzalutamide were constipation (23.8%), decreased appetite (19.0%), fatigue (19.0%), and musculoskeletal pain (19.0%). Treatment with enzalutamide and docetaxel resulted in prostate-specific antigen decreases in almost all patients based on exploratory analysis of available baseline and on-study prostate-specific antigen data.The combination of docetaxel and enzalutamide is feasible, although higher rates of neutropenia and neutropenic fever than anticipated were observed. Reductions in docetaxel exposure with enzalutamide coadministration were not considered clinically meaningful. This combination warrants further study in a larger mCRPC population. Clin Cancer Res; 22(15); 3774-81. ©2016 AACR.
Abstract 237: Intronic 27-nt Mirna Suppresses The Expression Of Endothelial Nitric Oxide Synthase Predominantly Through Nuclear Transcription Factor Ap-1
Authors: Patrick Liu, Limei Yan, Meimei Li, Hong Hao, Zhenguo Liu, Hesheng Ou
Journal: Circulation Research (2014)

The 27-base pair (bp) repeats in intron 4 were considered as the source of small RNA that suppressed endothelial nitric oxide synthase (eNOS) expression in endothelial cells. The present study was to investigate the role of polymorphic intronic 27-nucleotide (nt) miRNA and nuclear transcription factors (TFs) in eNOS expression in endothelial cells. The 27-nt or 54-nt miRNA or their mutants (with 3 mutations at 13, 14, and 15 th nt for 27-nt mutant and at 13,14,15,40,41,42 th nt for 54-nt mutant) were stably transfected and expressed in human aortic endothelial cells (HAECs). Overexpression of 27-nt miRNA and its duplexes and mutants significantly decreased eNOS mRNA level and protein content. Interestingly, more reduction in eNOS protein was observed in the cells overexpressing the mutant miRNAs than the cells overexpressing the wild-type ones for both 27-nt and 54-nt miRNAs. Western blotting showed that transcription factor Ap-1 expression was substantially decreased in the cells that overexpressed either 27-nt or 54-nt miRNAs (both wild-type and mutants). Augmented inhibition of Ap-1 expression was observed in the cells overexpressing the mutant 27-nt miRNA as compared with the wild-type. However, Sp-1 protein expression was significantly suppressed only in the cells overexpressing 54-nt miRNA. Silencing Ap-1 abolished the polymorphic effect of miRNAs both in length and mutation on eNOS expression; while Sp-1 silencing only reversed the polymorphic effect of mutant miRNAs. These results suggested that overexpression of intron 4-based 27-nt miRNAs suppressed eNOS gene expression polymorphically through interactions predominantly with nuclear transcription factors Ap-1 in HAECs.
Creating communicative opportunity: The supportive benefits of legacy building for families of advanced cancer patients.
Authors: Jennifer Kim Bernat, Paul R. Helft, Laura R. Wilhelm, Karen Schmidt, Shelley A. Johns
Journal: Journal of Clinical Oncology (2014)

230 Background: Being diagnosed with advanced cancer is a painful reality that impacts entire families. Families face the challenge of great loss and can regret conversations left unspoken. Dignity therapy (DT) is an empirically supported intervention that gives families communicative opportunity. During DT, terminally ill patients engage in legacy building and create a written project containing their meaningful memories and values. This project is given to the family, succeeding the person in death and providing continuity to those who are left behind. We developed a narrative intervention based on DT that used a novel web portal for project dissemination. This study qualitatively explores the family’s reactions to legacy building to learn about its potential for future bereavement support. Methods: Semi-structured phone interviews (20-30 minutes) with family members (n=7) of terminally ill cancer patients were completed approximately one week after receiving the legacy project. Recipients were spouses (n=4), siblings (n=2), or an adult child (n=1). Interviews were coded using conventional content analysis and an open-coding strategy. Themes were recorded as they emerged. Results: Three communication themes emerged from the data. Legacy building: (1) facilitates conversation; (2) creates new knowledge and understanding; and (3) leaves lasting communication for future generations. The family members felt overall communication improved before the patient died, and they were able to discuss the terminal nature of their loved one’s illness. New knowledge was communicated in the project, which sometimes led to further understanding of personal life events. Also, the project was viewed as a family heirloom to be bequeathed to future generations. All family members stated they would recommend legacy building to others. Conclusions: This study adds the unique impact of communication to the literature on the supportive benefit of DT for families of advanced cancer patients. Future research should investigate and quantitatively assess bereavement outcomes for families over time, as well as the direct impact these outcomes have on family members’ quality of life.
Antibiotic-resistant endocarditis in a hemodialysis patient.
Authors: R Vijayvargiya, J H Veis
Journal: Journal of the American Society of Nephrology (1996)

A chronic dialysis patient developed persistent bacteremia as a result of infection with Enterococcus faecium. During the patient's illness, resistance to ampicillin, gentamicin, vancomycin, and teicoplanin developed. Despite arteriovenous (AV) graft removal and an extensive but inconclusive search for the source of the infection, bacteremia persisted. On autopsy, the patient was found to have had aortic-valve endocarditis. Endocarditis is a well-known complication in dialysis patients. Multidrug-resistant organisms are becoming more prevalent in hospitalized patients as well. Risk factors for the development of endocarditis in dialysis patients include catheters, AV grafts, and calcific valvular disease, all in conjunction with frequent access to the circulation. Avoidance of temporary catheter use by prompt placement of AV fistulas or grafts and consideration of their early use, the meticulous care of catheters once in place, and treatment of the nasal carriage of Staphylococcus aureus may lower the incidence of bacteremia and therefore endocarditis in dialysis patients. The removal of infected catheters and/or AV grafts if prompt clearing of the blood with antibiotics does not occur is the next step, followed by valve replacement in selected cases. The routine use of vancomycin in the dialysis population should be reevaluated in light of the development of high-level antibiotic-resistant organisms.
Efficacy and safety of everolimus in elderly patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: S. Osanto, T. E. Hutson, E. Calvo, B. J. Escudier, S. Oudard, C. Porta, S. Bracarda, V. Grunwald, A. Ravaud, R. J. Motzer
Journal: Journal of Clinical Oncology (2010)

4608
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome
Authors: Jian Chen, Zhi-Xing Yao, Jiun-Sheng Chen, Young Jin Gi, Nina M. Muñoz, Suchin Kundra, H. Franklin Herlong, Yun Seong Jeong, Alexei Goltsov, Kazufumi Ohshiro, Nipun A. Mistry, Jianping Zhang, Xiaoping Su, Sanaa Choufani, Abhisek Mitra, Shulin Li, Bibhuti Mishra, Jon White, Asif Rashid, Alan Yaoqi Wang, Milind Javle, Marta Davila, Peter Michaely, Rosanna Weksberg, Wayne L. Hofstetter, Milton J. Finegold, Jerry W. Shay, Keigo Machida, Hidekazu Tsukamoto, Lopa Mishra
Journal: Journal of Clinical Investigation (2016)

Beckwith-Wiedemann syndrome (BWS) is a human stem cell disorder, and individuals with this disease have a substantially increased risk (~800-fold) of developing tumors. Epigenetic silencing of β2-spectrin (β2SP, encoded by SPTBN1), a SMAD adaptor for TGF-β signaling, is causally associated with BWS; however, a role of TGF-β deficiency in BWS-associated neoplastic transformation is unexplored. Here, we have reported that double-heterozygous Sptbn1+/- Smad3+/- mice, which have defective TGF-β signaling, develop multiple tumors that are phenotypically similar to those of BWS patients. Moreover, tumorigenesis-associated genes IGF2 and telomerase reverse transcriptase (TERT) were overexpressed in fibroblasts from BWS patients and TGF-β-defective mice. We further determined that chromatin insulator CCCTC-binding factor (CTCF) is TGF-β inducible and facilitates TGF-β-mediated repression of TERT transcription via interactions with β2SP and SMAD3. This regulation was abrogated in TGF-β-defective mice and BWS, resulting in TERT overexpression. Imprinting of the IGF2/H19 locus and the CDKN1C/KCNQ1 locus on chromosome 11p15.5 is mediated by CTCF, and this regulation is lost in BWS, leading to aberrant overexpression of growth-promoting genes. Therefore, we propose that loss of CTCF-dependent imprinting of tumor-promoting genes, such as IGF2 and TERT, results from a defective TGF-β pathway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human cancers that are frequently associated with SPTBN1 and SMAD3 mutations.
CD8+ T Cells in Cutaneous T-Cell Lymphoma: Expression of Cytotoxic Proteins, Fas Ligand, and Killing Inhibitory Receptors and Their Relationship With Clinical Behavior
Authors: Maarten H. Vermeer, Remco van Doorn, Danny Dukers, Marcel W. Bekkenk, Chris J.L.M. Meijer, Rein Willemze
Journal: Journal of Clinical Oncology (2001)

We investigated the number, phenotype, and prognostic significance of CD8+ T cells in patients with mycosis fungoides (MF) and CD30- primary cutaneous large T-cell lymphoma (PCLTCL).Immunohistochemical stainings for CD8, granzyme B (GrB), T cell-restricted intracellular antigen (TIA-1), Fas ligand (FasL), and killer-cell inhibitory receptors (KIRs; CD95, CD158a, and CD158b) were performed on 83 first-diagnostic biopsy samples obtained from patients with plaque-stage MF (n = 42), tumor-stage MF (n = 20), and CD30- PCLTCL (n = 21).Serial sections and double-staining experiments showed that the large majority of CD8+ T cells in MF and CD30- PCLTCL expressed TIA-1 and FasL, whereas only a minority expressed GrB, which suggested that these CD8+ T cells were partly activated cytotoxic T lymphocytes (CTLs). These CD8+ CTLs never or rarely expressed KIRs. This phenotype was a constant feature of CD8+ CTLs and did not alter with disease progression. In contrast, the median percentage of CD8+ CTLs in plaque-stage MF (22%), tumor-stage MF (7%), and CD30- PCLTCL (3%) differed significantly (P < .0001) and was associated with a significant decrease in 5-year survival. Also within the group of tumor-stage MF, a significant relation between CD8+ CTLs and survival was found. Multivariate analysis in the total group of MF demonstrated that both skin stage and percentage of CD8+ CTLs were independent parameters of survival.Our results demonstrated that partly activated CD8+ CTLs were present in CTCL and that high proportions of these cells correlated with a better prognosis. This suggested that these CD8+ CTLs could play an important role in the antitumor response in these conditions.
Cross-validation of a new prognostic index integrating tumor marker decline in patients with relapsed disseminated germ cell tumors
Authors: C. Massard, H. Huguet, A. Kramar, J. Beyer, J. T. Hartmann, A. Lorch, J. Pico, G. Rosti, J. Droz, K. Fizazi
Journal: Journal of Clinical Oncology (2009)

5086 Background: Early serum tumor marker decline during chemotherapy was previously shown to be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with relapsed GCT in an analysis of the IT94 phase III trial, which compared conventional chemotherapy versus high dose chemotherapy (Massard C, ASCO 2008. Abstract No. 5085). The aim of this study was to validate this concept in an independent set of patients. Methods: Data on tumor site, response to first line chemotherapy, serum tumor markers at baseline and after two cycles of chemotherapy were obtained from 235 patients accrued in the IT94 trial (training set) and from 181 patients included in phase III prospective trials of high-dose chemotherapy conducted by the German GCT group (Lorch et al, J Clin Oncol. 2007) (validation set). The change from baseline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) was assessed and classified into ‘favorable marker decline‘ and ‘unfavorable marker decline‘ group, as previously described (ASCO 2008. Abstract No. 5085). Results: In both series, favourable serum AFP decline was significantly associated with a better 2-year PFS (46% vs 24%; p &lt; 0.0001) and OS (62% vs 34%; p = 0.0013) while serum hCG decline did not affect outcome. In multivariate analysis of the IT94 trial, an unfavorable AFP decline and a mediastinal primary site were adverse prognostic factors for both PFS and OS, and this was confirmed in the validation set. Among patients from the good prognostic group (favorable AFP decline and non-mediastinal primary site), those who were treated with high-dose chemotherapy had a better PFS (2-year PFS rate: 54% vs 37%; HR = 0.62; p = 0.017), and a trend for a better OS (2-year OS rate: 68% vs. 58%; HR = 0.77; p = 0.29) as compared to patients who were treated with conventional chemotherapy. In contrast, there was no difference in outcome in patients from the poor prognostic group (unfavourable AFP decline and/or mediastinal primary site), whether they received conventional chemotherapy or high-dose chemotherapy. Conclusions: AFP decline during the first 6 weeks of salvage chemotherapy and a mediastinal primary tumor site predict for PFS and OS in patients with relapsed disseminated GCT. No significant financial relationships to disclose.
Ten-Year Safety and Efficacy Analyses of the Big 02-98 Phase III Trial with an Exploratory Analysis on the Role of Ki67 in Predicting Benefit of Adjuvant Docetaxel in Er Positive Patients
Authors: A. Sonnenblick, H.A. Azim, E. De Azambuja, P. Francis, B. Nordenskjöld, J.P. Crown, J. Gutiérez, E. Quinaux, M.G. Mastropasqua, L. Ameye, M. Anderson, A. Lluch, A. Goldhirsch, A. Di Leo, A. Barnadas, H. Cortes-Funes, M. Piccart
Journal: Annals of Oncology (2014)