tbuckley/cabot-search huggingface dataset:
Factors related to black/white disparities in survival among non-elderly women with breast cancer, 2004-2012.
Authors: Ahmedin Jemal, Anthony S. Robbins, Rachel A. Freedman, Chun Chieh Lin, W. Dana Flanders, Elizabeth Mary Ward
Journal: Journal of Clinical Oncology (2016)

6548 Background: The breast cancer mortality gap between black and white women has widened, and as of 2012, the mortality rate was 43% higher in black women. Although disparities in mortality for black women may be partially modifiable with early detection and reducing barriers to treatment, the relative contribution of modifiable factors (MF) to the black-white disparity in breast cancer mortality is unclear. We assessed the individual contributions of MF (stage, tumor size, treatment [surgery, radiation, chemotherapy, hormonal therapy], and stage × treatment interaction) and non-modifiable factors (NMF) (hormone receptor status, histology, grade, and comorbidity) in the excess risk of death among black women with breast cancer. Methods: Our cohort included 573,387 black and white women aged 18-64 with invasive breast cancer diagnosed during 2004−2012 and followed through 2013 from the National Cancer Data Base. Excess relative risk (ERR) of death among black vs white women was measured using multivariate hazard ratios (HRs) and associated 95% confidence intervals (CIs), initially adjusted for age alone. By varying the step at which different factors were added to the multivariate models, we estimated the separate and combined effects of MF and NMF on overall survival, using the Sequential Attributable Fraction (SAF) method. Results: Adjusted for age alone, the HR for mortality for blacks (vs. whites) was 2.09 (95% CI 2.05−2.13). After adjustment for all variables, the HR for blacks was 1.31 (95% CI 1.29−1.34); thus, MF and NMF together explained 71.4% of the ERR. By applying the SAF method, when adjusting for MF first and NMF later, ERR was reduced by 58.9% and 12.5%, respectively. When adjusting for NMF first and MF later, ERR was reduced by 45.7% and 25.7%, respectively. Thus, regardless of the sequence, the SAFs for MF were larger than those for NMF. Conclusions: The contribution of MF to the excess risk of death among black women with breast cancer was at least as large as that of NMF, and possibly larger. These results suggest that interventions to promote early stage at diagnosis and receipt of standard treatment could substantially reduce racial disparities in breast cancer mortality.
Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome
Authors: Jules L. Derks, Noémie Leblay, Erik Thunnissen, Robert Jan van Suylen, Michael den Bakker, Harry J.M. Groen, Egbert F. Smit, Ronald Damhuis, Esther C. van den Broek, Amélie Charbrier, Matthieu Foll, James D. McKay, Lynnette Fernandez-Cuesta, Ernst-Jan M. Speel, Anne-Marie C. Dingemans
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1 mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome. Experimental Design: Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases. Next-generation sequencing (NGS) for TP53, RB1, STK11, and KEAP1 genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases, respectively, and correlated with overall survival (OS) and progression-free survival (PFS), stratifying for non–small cell lung cancer type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum-etoposide (SCLC-PE). Results: RB1 mutation and protein loss were detected in 47% (n = 37) and 72% (n = 78) of the cases, respectively. Patients with RB1 wild-type LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95% confidence interval (CI), 7.7–11.6 months] than those treated with SCLC-PE [5.8 (5.5–6.1); P = 0.026]. Similar results were obtained for patients expressing RB1 in their tumors (P = 0.001). RB1 staining or P16 loss showed similar results. The same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an RB1 mutation or lost RB1 protein. Conclusions: Patients with LCNEC tumors that carry a wild-type RB1 gene or express the RB1 protein do better with NSCLC-GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was observed for RB1 mutated or with lost protein expression. Clin Cancer Res; 24(1); 33–42. ©2017 AACR.
Manejo de las fiebres hemorrágicas víricas en Suiza
Authors: S Hugonnet, Hugo Sax, D Pittet
Journal: Eurosurveillance (2002)

En los ultimos anos, Suiza ha registrado muy pocos casos importados de fiebre hemorragica virica (FHV): uno confirmado y cuatro sospechosos de fiebre de Ebola en Basilea en 1994, dos casos sospechosos de Ebola y de fiebre de Lassa en Lausana en 2000 y, en ese mismo ano, seis casos sospechosos de fiebre de Lassa en Ginebra. Dada la diversidad considerable que presenta el manejo de pacientes con FHV sospechosa o confirmada, es preciso elaborar pautas nacionales y establecer un centro nacional de referencia.
TCT-314 Implementation of noise reduction technology to reduce patient radiation dose in chronic total occlusion percutaneous coronary interventions: a propensity-matched analysis
Authors: Davide Maccagni, Susanna Benincasa, Barbara Bellini, Luciano Candilio, Enrico Poletti, Mauro Carlino, Antonio Colombo, Lorenzo Azzalini
Journal: Journal of the American College of Cardiology (2017)
A phase 2 clinical trial testing DPX-Survivac and metronomic low dose cyclophosphamide as immunotherapy for patients with recurrent diffuse large b-cell lymphoma.
Authors: Neil Lorne Berinstein, Richard H. C. Van Der Jagt, Matthew C. Cheung, Rena Buckstein, Mohan Karkada, Tara Quinton, Lisa MacDonald, Marianne Stanford, Rita Nigam, Marc Mansour
Journal: Journal of Clinical Oncology (2016)

e14578 Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell lymphoma (DLBCL) patients. DPX-Survivac contains survivin HLA class I peptides in a novel formulation, DepoVax. A phase 1 trial in ovarian cancer patients demonstrated the safety and immunogenicity of DPX-Survivac therapy. A phase 2 trial was initiated to determine the objective response rate, immunogenicity and safety in patients with recurrent, survivin-expressing DLBCL who are not eligible for transplant, or who have recurred after transplant. Methods: 24 subjects with confirmed survivin-positive DLBCL with LDH's less than 2x normal, are to be enrolled in this study. Patients receive two 0.25 mL priming doses of DPX-Survivac three weeks apart and up to six 0.1 mL boosting doses eight weeks apart in combination with low dose oral metronomic cyclophosphamide. Subjects will be treated for one year or until disease progression. The objective response rate is measured using Modified Cheson criteria. Biopsy and blood specimens will be collected for correlative biomarker and immune analyses. Safety will be documented by CTCAE v4.03 Results: Four subjects to date have been screened or enrolled in this trial, and two have completed priming and at least one boosting vaccination. The treatment was well tolerated. Both of these two subjects had progressive disease on study day 100 and 162, before completing treatment. One demonstrated a robust systemic antigen-specific T cell response. The subject that did not demonstrate immune responses post- vaccination had low peripheral blood lymphocyte counts at study entry. For the subject with a systemic immune response, it correlated with increased T cell infiltrates in the tumor tissue. Tumor biopsy analysis revealed that both patients had expression of PD-1 and PD-L1 within the tumor tissue. Conclusions: Early results suggest that this immunotherapy approach is feasible with patients with recurrent DLBCL. The interim analysis of the current study provides clinical and biological rationale for combining the vaccine/cyclophosphamide therapy with other cancer immunotherapeutic strategies, such as checkpoint modulators. Clinical trial information: NCT02323230.
Explore, Visualize, and Analyze Functional Cancer Proteomic Data Using the Cancer Proteome Atlas
Authors: Jun Li, Rehan Akbani, Wei Zhao, Yiling Lu, John N. Weinstein, Gordon B. Mills, Han Liang
Journal: Cancer Research (2017)

Reverse-phase protein arrays (RPPA) represent a powerful functional proteomic approach to elucidate cancer-related molecular mechanisms and to develop novel cancer therapies. To facilitate community-based investigation of the large-scale protein expression data generated by this platform, we have developed a user-friendly, open-access bioinformatic resource, The Cancer Proteome Atlas (TCPA, http://tcpaportal.org), which contains two separate web applications. The first one focuses on RPPA data of patient tumors, which contains >8,000 samples of 32 cancer types from The Cancer Genome Atlas and other independent patient cohorts. The second application focuses on the RPPA data of cancer cell lines and contains >650 independent cell lines across 19 lineages. Many of these cell lines have publicly available, high-quality DNA, RNA, and drug screening data. TCPA provides various analytic and visualization modules to help cancer researchers explore these datasets and generate testable hypotheses in an effective and intuitive manner. Cancer Res; 77(21); e51-54. ©2017 AACR.
TCT-94 Safety and Efficacy of the Combo Bio-Engineered Stent in an All-Comer PCI Cohort: Results from the MASCOT Post-Marketing Registry
Authors: Antonio Colombo, Stephen Rowland, Jaya Chandrasekhar, Tiong Kiam Ong, Michael Lee, Clayton Snyder, Melissa Aquino, Debbie Morrell, Francesca Elmore, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
TCT-158 Durability of Hemodynamic Results of Valve in Valve TAVR with Bioprosthetic Valve Fracture (BVF)
Authors: John Saxon, Keith Allen, David Cohen, Anthony Bavry, Pranav Loyalka, Tom Nguyen, Juhana Karha, Joshua Rovin, Anthony Hart, Suzanne Baron, Danny Dvir, Adnan Chhatriwalla
Journal: Journal of the American College of Cardiology (2017)
Abstract 15947: Transient Neonatal Exposure to High Oxygen Levels is Associated With Impaired Ischemia-induced Neovascularization During Adulthood
Authors: Raphaël Mathieu, Sylvie Dussault, Michel Desjarlais, Wahiba Dhahri, Anik Cloutier, Anne-Monique Nuyt, Alain Rivard
Journal: Circulation (2016)

Introduction:  Deleterious perinatal conditions, including preterm birth, can lead to developmental programming of cardiovascular diseases. Prematurely born infants are often exposed to high oxygen levels, which in animal models has been associated with the adult development of endothelial dysfunction, hypertension, and cardiac remodeling. Here we tested the novel hypothesis that neonatal exposure to hyperoxia might impair ischemia-induced neovascularization in the adult.   Methods and Results:  C57Bl/6 newborn mice were kept with their mother in 85% O 2  or room air (control) from day 2 to 14 after birth. When the mice reached adulthood (6-8 weeks), hindlimb ischemia was surgically induced by femoral artery removal. Neonatal exposure to O 2  was not associated with hypertension in adult mice. However mice exposed to O 2  after birth showed a significant impairment of blood flow recovery after hindlimb ischemia, as assessed by Laser Doppler imaging at day 7 and 21 after surgery. Clinically, this was also associated with increased hindlimb ischemic damages. At the microvascular level, neonatal hyperoxia was associated with a significant decrease of capillary density in ischemic muscles. Moreover, ischemic muscles isolated from mice exposed to O 2  exhibited increased oxidative stress levels (DHE staining), together with a reduced expression of superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF), as assessed by Western blotting. Pro-angiogenic cells (PACs) have been shown to have an important role for postnatal neovascularisation. Here we found that neonatal exposure to O 2  is associated with a significantly reduced number of central (bone marrow) and peripheral PACs in adults. Interestingly, the functional/angiogenic activities of both PACs and mature mouse aortic endothelial cells (MAECs) are significantly impaired in mice that have been exposed to O 2  after birth.   Conclusions:  Transient neonatal exposure to high oxygen levels leads to impaired ischemia-induced neovascularization during adulthood. The mechanism involves negative effects of neonatal hyperoxia on oxidative stress levels and angiogenic signals in ischemic muscles, together with defective functional activities of PACs and mature endothelial cells.
Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study
Authors: Carina Götestam Skorpen, Stian Lydersen, Inge-Margrethe Gilboe, Johan Fredrik Skomsvoll, Kjell Å Salvesen, Øyvind Palm, Hege Suorza Svean Koksvik, Bente Jakobsen, Marianne Wallenius
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Exploring the associations between disease activity and medications with offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus (SLE). Methods Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with SLE included in RevNatus 2006–2015 were cases (n=180). All other singleton births registered in MBRN during this time (n=498 849) served as population controls. Z-score for birth weight adjusted for gestational age and gender was calculated. Disease activity was assessed using Lupus Activity Index in Pregnancy. We compared z-scores for birth weight, pre-eclampsia and preterm birth in cases with inactive disease, cases with active disease and population controls. Results Z-scores for birth weight in offspring were lower in inactive (−0.64) and active (−0.53) diseases than population controls (−0.11). Inactive disease did not predict pre-eclampsia while active disease yielded OR 5.33 and OR 3.38 compared with population controls and inactive disease, respectively. Preterm birth occurred more often in inactive (OR 2.57) and active (OR 8.66) diseases compared with population controls, and in active compared with inactive disease (OR 3.36). Conclusions SLE has an increased odds for low birth weight and preterm birth, amplified by active disease. The odds for pre-eclampsia is elevated in active, but not inactive disease. This calls for tight follow-up targeting inactive disease before and throughout pregnancy.
A molecular morphometric approach to diabetic kidney disease can link structure to function and outcome
Authors: Viji Nair, Claudiu V. Komorowsky, E. Jennifer Weil, Berne Yee, Jeffrey Hodgin, Jennifer L. Harder, Bradley Godfrey, Wenjun Ju, Carine M. Boustany-Kari, Margrit Schwarz, Kevin V. Lemley, Peter J. Nelson, Robert G. Nelson, Matthias Kretzler
Journal: Kidney International (2017)
The Changing Therapeutic Role of Chemo-radiotherapy for Loco-regionally Advanced Nasopharyngeal Carcinoma from Two/Three-Dimensional Radiotherapy to Intensity-Modulated Radiotherapy: A Network Meta-Analysis
Authors: Rui You, Ying-Shu Cao, Pei-Yu Huang, Lei Chen, Qi Yang, You-Ping Liu, Xiong Zou, Yi-Nuan Zhang, Rou Jiang, Meng-Xia Zhang, Chong-Yang Duan, Ai-Hua Lin, Ming-Huang Hong, Ming-Yuan Chen
Journal: Theranostics (2017)

Purpose:We used randomized trials of radiotherapy (RT) with or without chemotherapy in non-metastatic nasopharyngeal carcinoma to investigate the survival benefit of chemoradiotherapy regimens between two/three-dimensional radiotherapy (2D/3D RT) and intensity-modulated radiotherapy (IMRT).Methods: Overall, 27 trials and 7,940 patients were included.Treatments were grouped into seven categories including RT alone, induction chemotherapy (IC) followed by RT (IC-RT), RT followed by adjuvant chemotherapy (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concurrent chemo-radiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC).To distinguish between 2D/3D RT and IMRT, three categories in IMRT were newly added, including CRT in IMRT, IC-CRT in IMRT, and CRT-AC in IMRT.The P score was used to rank the treatments.Results: Both fixed-and random-effects frequentist and Bayesian network meta-analysis models were applied, which provided similar results and the same ranking.IC-CRT was the most effective regimen compared with CRT-AC and CRT in the IMRT era for overall survival (OS) (HR, 95% CI, IC-CRT vs. CRT-AC, 0.61 (0.45, 0.82); IC-CRT vs. CRT 0.65 (0.47, 0.91)), progression-free survival (PFS) (0.69 (0.54, 0.88); 0.63 (0.49, 0.80)), and distant metastasis-free survival (DMFS) (0.58 (0.28, 1.21); 0.60 (0.42, 0.85)).CRT-AC achieved the highest survival benefit compared with CRT, and IC-CRT for loco-regional relapse-free survival (LRRFS) (0.44 (0.15, 1.28); 0.72 (0.22, 2.33)).Among these 10 categories, after distinguishing between 2D/3D RT and IMRT, IC-CRT in IMRT ranked first for OS, PFS, and DMFS, and CRT-AC in IMRT ranked first for LRRFS.Conclusion: IC-CRT should be the most suitable regimen for loco-regionally advanced NPC in the IMRT era.
Saline with methylene blue-assisted endoscopic ultrasound-guided gastrojejunostomy using a double-flared fully covered metal stent
Authors: Guoxin Wang, Xiang Liu, Sheng Wang, Nan Ge, Jintao Guo, Siyu Sun
Journal: Endoscopy (2017)

Duodenal malignant stenosis can be caused by primary duodenal cancer or pancreatic cancer involving the duodenum [1]. Current treatment options include laparoscopic bypass and palliative duodenal stent placement under endoscopic or radiographic guidance. Both methods have their advantages and disadvantages. Surgical methods will cause greater trauma to patients, while a duodenal stent might remain patent for only a short time (generally 3 – 6 months), with the risk of tumor ingrowth and/or overgrowth [2]. For these reasons, we may also choose endoscopic ultrasound-guided gastroenterostomy (EUS-GE), with placement of a double-flared, fully covered, metal stent to create an anastomosis and bypass the obstruction.
HPLC/UV or HPLC/32P-postlabeling methods for quantification of bromodeoxyuridine in DNA
Authors: M. Vijayaraj Reddy, John E. Barnum, George M. Laws, Caron L. Cunningham, Nagaraj Muniappa, Richard D. Storer
Journal: Cancer Research (2004)

1895  The extent of incorporation of exogenously administered bromodeoxyuridine (BrdU) into DNA is an indicator of the rate of DNA synthesis and cell proliferation. We developed and validated an HPLC method for quantification of BrdU in DNA, based on the separation of nucleosides and their detection by an online UV detector. The baseline separation of BrdU from both normal deoxyribonucleosides and ribonucleosides was achieved in a 60-min run on a reversed-phased C18 column, using a methanol/ammonium formate buffer, as the eluent. The limit of detection was about 0.01 nmole BrdU using a standard BrdU solution. DNA was enzymatically hydrolyzed to deoxyribonucleosides prior to HPLC. The method allowed the detection of background levels of BrdU incorporation into DNA (45 μg) of urinary bladder and duodenum of control rats after a continuous administration of a BrdU solution (50 mg/ml) at a flow rate of 10 μl/h for 4 d, using a subcutaneously implanted osmatic minipump. Compared with the levels obtained by this continuous dosing, BrdU incorporation was much lower in rats dosed intraperitoneally (IP) 120 mg/kg BrdU at 19 h and 4 h prior to sacrifice. A substantial increase (about 10-fold) in BrdU incorporation was seen in the urinary bladder DNA of rats fed a diet containing 3% uracil for 4 d, as compared with the corresponding values obtained for rats fed normal rodent diet (Purina® Chow). BrdU incorporation was much higher (about 7-fold) using the continuous dosing regimen than the two-IP injection regimen. These results were consistent with those obtained by the immunohistochemical staining of BrdU-labeled nuclei with anti-BrdU antibody. Feeding rats 3% uracil in the diet rapidly induces urinary calculi and bladder hyperplasia, which progresses with continued treatment to papillomatosis and transitional cell carcinoma. An HPLC-based 32P-postlabeling assay was also developed for the measurement of BrdU in small amounts of DNA (1 μg). 32P-labeled nucleotides were prepared as the monophosphates, resolved using a 20-min run on a reversed-phase column with a methanol/ammonium formate buffer, and detected using an online radiochemical detector. The assay had similar sensitivity to the UV/HPLC method using about 5 μg DNA, but the latter method allowed the use of more DNA, resulting in higher sensitivity. In conclusion, we developed and validated HPLC/UV and HPLC/32P-postlabeling methods for the quantification of BrdU in DNA and demonstrated their application to quantify the incorporation of BrdU into DNA of rat tissues.
Why we should improve current practice of diagnosing and treating pulmonary large cell neuroendocrine carcinomas in patients with advanced disease
Authors: Jules Derks, Robert Jan van Suylen, Erik Thunnissen, Michael den Bakker, Harry Groen, Egbert Smit, Ronald Damhuis, Esther van den Broek, Ernst-Jan Speel, Anne-Marie C. Dingemans
Journal: European Respiratory Journal (2017)

In response to our manuscript on first-line chemotherapy treatment for metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) [1], Rossi and co-workers raised their concerns about the validity of our results by questioning the accuracy of LCNEC diagnosis on a biopsy specimen. We would like to thank the authors for their critical appraisal, underscoring the need to increase awareness among pulmonologists, oncologists and pathologists of the diagnostic issues and consequences of metastatic LCNEC diagnosed on a biopsy specimen. Current criteria for LCNEC diagnosed on a biopsy specimen are in need of improvement <http://ow.ly/lRP730fu552>