tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS
Authors: Peter K. Olitsky, Frederick L. Gates
Journal: The Journal of Experimental Medicine (1921)

All active transmissible agent present in the nasopharynx in early cases of influenza has been found to produce definite and characteristic clinical reactions and pathological effects in rabbits as already described in an earlier publication. The experiments here reported indicate that this active agent has the following properties. 1. The agent as it exists in the nasopharyngeal secretions in man, and in the lungs of rabbits injected with the human secretions, passes through Berkefeld V and N candles. 2. The filtered material produces the same effects on the circulating blood and on the lungs of rabbits as the unfiltered material. 3. The peculiar effects described as arising in the inoculated rabbit may also be induced in guinea pigs inoculated with the agent. 4. The agent responsible for the reaction on the blood and the lungs of rabbits withstands the action of glycerol in a sterile 50 per cent solution, for periods up to 9 months. The question must be left open at present whether the agent can withstand longer contact with the chemical. In two experiments after 10(1/2) months contact the agent induced no observable changes in the blood and lungs of rabbits.
Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer
Authors: Maria G. Kier, Merete K. Hansen, Jakob Lauritsen, Mette S. Mortensen, Mikkel Bandak, Mads Agerbaek, Niels V. Holm, Susanne O. Dalton, Klaus K. Andersen, Christoffer Johansen, Gedske Daugaard
Journal: JAMA Oncology (2016)

Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options.To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens.This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular Cancer database between January 1, 1984, and December 31, 2007. Treatment results were compared with a randomly sampled, age-stratified, population-based control group. Cases of gonadal and extragonadal primary were included in the nationwide cohort. The treatments were surveillance only; retroperitoneal radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL).Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls.The study population comprised 2804 patients with seminoma and 2386 with nonseminoma. The median follow-up was 14.4 years (interquartile range, 8.6-20.5 years). The 20-year cumulative incidence of SMN with death as a competing risk was 7.8% (surveillance), 7.6% (BEP), 13.5% (RT), 9.2% (MTOL), and 7.0% (controls). We found no increased risk for SMN after surveillance, while the HRs were 1.7 (95% CI, 1.4-2.0), 1.8 (95% CI, 1.5-2.3), and 3.7 (95% CI, 2.5-5.5), respectively, after BEP, RT, and MTOL. Mortality owing to non-GCC causes was decreased after surveillance, but increased by 1.3 times after BEP and RT and by 2.6 times after MTOL. Excess mortality due to SMN was found after BEP (HR, 1.6; 95% CI, 1.2-2.2), RT (HR, 2.1; 95% CI, 1.5-2.9), and MTOL (HR, 5.8; 95% CI, 3.6-9.6).We found no increased risk for SMN or death among patients undergoing surveillance only. The risks for SMN and death due to SMN were increased after BEP alone, RT alone, and MTOL. Approaches to define patients who might benefit from less intensive treatment are needed.
Prediction of response to neoadjuvant therapy in breast cancer using plasma and tumor proteomic analyses.
Authors: C. Desauw, L. Hornez, J. Bonneterre, M. Baranzelli, M. Chauvet, E. Blot, A. Hollebecque, C. Fournier, A. Leroy, J. Peyrat
Journal: Journal of Clinical Oncology (2010)

10551 Background: A pathological complete response (PCR) after neoadjuvant chemotherapy is observed in about 20% of the patients. A proteomic analysis was performed on plasma and tumor before treatment to evaluate its potential interest in the prediction of response. Patients: One hundred and forty-nine patients eligible for neoadjuvant chemotherapy were included in the study. Methods: Before treatment plasma and tissues (fine needle aspirations) were collected and frozen at –80°C and in liquid nitrogen respectively. The proteomic analysis was performed using the SELDI Technology. One μl of plasma and 10 μg of cytosolic proteins were loaded on proteinchip CM10 pH4, Imac-Cu, H50 arrays. Three acquisition protocols were used according to the mass range. The differences between protein levels in the two populations (responder and non responder) were detected using Mann Withney tests. Then plasma and tumor proteomic signatures, in relation to tumor response, were determined. Results: 28 patients out of 149 experienced a PCR according to Sataloff criteria. In the cytosols, we observed 180 different proteins using CM10 pH4 arrays. For 8 proteins, the levels were statistically different between the 2 populations (responders vs non responders). In the plasma we observed 98 different proteins using Imac-Cu arrays. For 12 proteins, the levels were statistically different between the two populations (responders vs non responders). Using these conditions, proteomic signatures were established allowing the classification of samples. Considering the logistic regression, for a classification cut-off of 0.5, the specificities (number of classified non-responders according to the proteomic analysis / number of pathological non responders) were 92.9% in cytosols and 95.5% in plasma; the sensitivities (number of classified responders/number of PCR) were respectively 33.3% and 27.3%. Conclusions: Proteomic analyses allow the selection of the majority of non responder patients. We are now analyzing the results including clinical and biological parameters. This determination together with other predictive factors might be useful in the early prediction of treatment efficacy and avoid toxic chemotherapy regimens. No significant financial relationships to disclose.
Practice Patterns in the Diagnosis and Treatment of Polycythemia Vera in the Post–<i>JAK2</i>V617F Discovery Era
Authors: Elizabeth M. Kander, Alison R. Moliterno, Alfred Rademaker, Michael B. Streiff, Jerry L. Spivak, Brady L. Stein
Journal: Journal of the National Comprehensive Cancer Network (2016)

Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder characterized by an overproduction of red blood cells, white blood cells, and platelets; thrombotic and hemorrhagic complications; and an increased risk of transformation to myelofibrosis and acute leukemia. In 1967, the Polycythemia Vera Study Group proposed the optimal approach to diagnosis and treatment of PV, and in 2002, investigators from Johns Hopkins University School of Medicine surveyed the practice patterns of hematologists as they pertained to PV. Since this survey, the JAK2 V617F mutation was discovered, leading to a new era of discovery in the disease pathogenesis, diagnosis, and classification and treatment of PV. Our objective was to survey hematologists in the diagnosis and treatment of PV in the modern, post-JAK2 V617F discovery era. An anonymous 17-question survey was emailed to members of the Myeloproliferative Neoplasm (MPN) Research Foundation database and Aplastic Anemia and MDS International Foundation. A total of 71 surveys were used in the analysis. Diagnostic testing varied according to the respondent's clinical experience and practice type. In addition, there were marked differences in target hematocrit and platelet count among those surveyed. There continue to be variations in diagnosis and treatment of PV despite WHO guidelines and the JAK2 discovery. US-based guidelines for MPNs are needed to create consistency in the management of PV and other MPNs.
Better targeting care for individuals with low back pain: opportunities and obstacles
Authors: Kieran O'Sullivan, Peter O'Sullivan, Kjartan Vibe Fersum, Peter Kent
Journal: British Journal of Sports Medicine (2016)

The disability burden due to low back pain (LBP) continues to increase despite increased healthcare costs. There is growing interest in better targeting care for LBP, rather than adopting a ‘one size fits all’ approach, in order to optimally manage the well-recognised heterogeneity of patients with LBP.1–4

This challenge of patient heterogeneity has been approached in different ways. Stratified care , where patients are classified based on certain characteristics and then matched to appropriate treatment pathways, is one relatively simple and efficient method of targeting care.2 Subgrouping approaches based on identifying common clinical features, usually within a single dimension (ie, pain characteristics, movement patterns, psychological profiles), have also been proposed as a way to target care.5 Individualised care goes one step further with each person, as opposed to groups of people, receiving personally tailored care.1 ,3 ,4 However, what does individualised care actually mean?

Many clinicians would argue that they always provide individualised care. However, what this looks like in clinical practice is probably biased by our professional backgrounds, beliefs and …
Phase I and II studies of intravenous Rexin-G as monotherapy for stage IVb gemcitabine-resistant pancreatic cancer.
Authors: H. Bruckner, S. P. Chawla, C. S. Chua, D. V. Quon, L. Fernandez, A. Saralou, M. Fisher, E. M. Gordon, F. L. Hall
Journal: Journal of Clinical Oncology (2010)

4149 Background: To evaluate (1) the safety and antitumor activity of Rexin-G, and (2) the cumulative toxicity and sustained efficacy of Rexin-G continuance in gemcitabine-resistant Stage IVb pancreas cancer. Methods: Fifteen patients were given escalating doses of 1, 2 or 3 × 10e11 cfu of Rexin-G i.v. 2 to 3 times a week for 4 weeks. A phase II component was incorporated by adaptive design, and additional cycles were given if there was ≤ grade 1 toxicity. The estimated tumor burden was determined by PET-CT scan using the formula: S [Target Lesions (cm) + (No. of Non- Target Lesions + (20*))] × 10e9. Note: (20*) indicates ascites, pleural effusion, and/or
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Authors: Martin Reck, Delvys Rodríguez-Abreu, Andrew G. Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O’Brien, Suman Rao, Katsuyuki Hotta, Melanie A. Leiby, Gregory M. Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R. Brahmer
Journal: New England Journal of Medicine (2016)

Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).
Molecular markers distinguish patients at differential risk of brain metastases in lung cancer by immunohistochemistry
Authors: D. N. Hayes, C. B. Lee, M. Hayward, M. A. Socinski, T. E. Stinchcombe, P. Roberts, L. Thorne, P. S. Bernard, X. Yin, A. Parsons, W. K. Funkhouser
Journal: Journal of Clinical Oncology (2008)

8083 Background: Patients with surgically resected lung caner, even at the earliest stages of disease still face a risk of recurrence between 30–50%, including a significant number of patients with brain only metastases. Although evidence suggests brain metastases may be preventable through prophylactic cranial radiation (PCR), widespread acceptance of the therapy has not occurred due to patient preference and other factors. Predictors of brain metastasis might promote the use of PCR. Methods: 150 surgically treated lung cancer patients treated at our institution were selected for analysis. We generated a tissue microarray from primary tumor material and assayed this using commercially available antibodies for 16 proteins suspected or previously reported to be associated with brain metastases (TTF1, Vimentin, SMA, BCL2, cyclin D1, UPA, AKT, pAKT, ADAM9, ERK, pERK, EGFR, Her-2/neu, Ki67, p53, Rb). Samples were assayed in triplicate at a minimum and associations with pattern of metastasis were determined Results: The cohort contained 85 adenocarcinomas, 59 squamous cell carcinomas, and 6 poorly differentiated carcinomas. There were 58 recurrence in total of which 38 were solitary recurrences (21 lung only, 9 brain only, 5 liver only, 3 misc). A total of 13 brain metastases occurred, 11 of which were in lung adenocarcinoma. The following patterns were observed. Patients who were TTF1 (+) at any level and vimentin (-), had a documented brain metastasis rate of 4%, compared to patients who were TTF1 (+), vimentin (+) where the rate was 17% (p=0.06). All of the remaining patients with brain metastases were negative for both TTF1 and vimentin, but stained at approximately 2 time background for SMA (p <0.05). Additional antibodies correlated with brain metastases were UPA and ADAM9. Conclusions: Patients at relatively high and low risk of brain metastasis can be identified using a small number of immunohistochemical markers. No significant financial relationships to disclose.
A Phase I/II Trial of the KSP Inhibitor ARRY-520 In Relapsed/Refractory Multiple Myeloma
Authors: Jatin J Shah, Jeffrey A. Zonder, Adam Cohen, Donna Weber, Sheeba Thomas, Michael Wang, Jonathan L. Kaufman, Steven Michael Burt, Duncan Walker, Burgess Freeman, Selena Armistead Rush, Ann Ptaszynski, Robert Z. Orlowski, Sagar Lonial
Journal: Blood (2010)
WWOX and p53 Dysregulation Synergize to Drive the Development of Osteosarcoma
Authors: Sara Del Mare, Hussam Husanie, Ortal Iancu, Mohammad Abu-Odeh, Konstantinos Evangelou, Francesca Lovat, Stefano Volinia, Jonathan Gordon, Gail Amir, Janet Stein, Gary S. Stein, Carlo M. Croce, Vassilis Gorgoulis, Jane B. Lian, Rami I. Aqeilan
Journal: Cancer Research (2016)

Abstract Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts. Mice with conditional deletion of Wwox in preosteoblasts (WwoxΔosx1) displayed a severe inhibition of osteogenesis accompanied by p53 upregulation, effects that were not observed in mice lacking Wwox in mature osteoblasts. Deletion of p53 in WwoxΔosx1 mice rescued the osteogenic defect. In addition, the Wwox;p53Δosx1 double knockout mice developed poorly differentiated osteosarcomas that resemble human osteosarcoma in histology, location, metastatic behavior, and gene expression. Strikingly, the development of osteosarcomas in these mice was greatly accelerated compared with mice lacking p53 only. In contrast, combined WWOX and p53 inactivation in mature osteoblasts did not accelerate osteosarcomagenesis compared with p53 inactivation alone. These findings provide evidence that a WWOX–p53 network regulates normal bone formation and that disruption of this network in osteoprogenitors results in accelerated osteosarcoma. The Wwox;p53Δosx1 double knockout establishes a new osteosarcoma model with significant advancement over existing models. Cancer Res; 76(20); 6107–17. ©2016 AACR.
Molecular Profiling to Determine Clonality of Serial Magnetic Resonance Imaging/Ultrasound Fusion Biopsies from Men on Active Surveillance for Low-Risk Prostate Cancer
Authors: Ganesh S. Palapattu, Simpa S. Salami, Andi K. Cani, Daniel H. Hovelson, Lorena Lazo de la Vega, Kelly R. Vandenberg, Jarred V. Bratley, Chia-Jen Liu, Lakshmi P. Kunju, Jeffery S. Montgomery, Todd M. Morgan, Shyam Natarajan, Jiaoti Huang, Scott A. Tomlins, Leonard S. Marks
Journal: Clinical Cancer Research (2016)

To determine whether MRI/ultrasound (MRI/US) fusion biopsy facilitates longitudinal resampling of the same clonal focus of prostate cancer and to determine whether high-grade cancers can evolve from low-grade clones.
Measles Elimination — Using Outbreaks to Identify and Close Immunity Gaps
Authors: David N. Durrheim
Journal: New England Journal of Medicine (2016)

The Americas are on the eve of being formally verified as having eliminated endemic measles after the successful interruption of the transmission of measles in Brazil.1 This achievement provides empirical proof of the conclusion reached by an expert advisory committee, convened by the World Health Organization (WHO) in 2010, that “global measles eradication is biologically, technically and operationally feasible.”2 To capitalize on this opportunity for global good, the Global Vaccine Action Plan enthusiastically targets the elimination of measles and rubella in at least five WHO regions by 2020.3 All six WHO regions have established goals to eliminate measles by 2020 . . .
Implementation of gene expression testing for breast cancer patients within the Veterans Health Administration.
Authors: Julie Ann Lynch, Brygida Berse, Kelly Kristin Filipski, Andrew N Freedman, Scott DuVall, Vickie Venne, Michael J. Kelley
Journal: Journal of Clinical Oncology (2015)

e17511 Background: The number of Veterans diagnosed and treated for breast cancer within the Veterans Health Administration is increasing. The VA Central Cancer Registry (VACCR) reported 504 and 624 newly diagnosed patients in 2011 and 2012, respectively. Molecular testing for cancer treatment is also increasing but there are few studies evaluating utilization and health outcomes of testing. This study examined utilization of OncotypeDx breast, a prognostic 21 gene expression genomic test within the VA. Methods: Patient-level test orders and results from January 2011 until December 2014 were provided by Genomic Health. Data for years 2011 and 2012 were merged with the VACCR. Using reported clinical and pathologic stage of I or II, hormone receptor/HER2 status, and 10-year life expectancy (age<75), we identified OncotypeDx-eligible patients. Bivariate analyses were conducted to compare distributions of characteristics by status of testing. A multivariate logistic regression model was developed to identify patient, site of care, and regional factors that predict testing. Results: There were 585 OncotypeDx breast assays ordered by VA and non-VA providers from 2011 until 2014. Testing increased from 65 tests in 2011 to 199 in 2014. Characteristics of patients tested were: 97% female; median age 58 (range 26-85; 24% <50yrs). Of the 204 tests that were performed by Genomic Health during 2011/2012 time frame, 104 Veterans were matched to VACCR data. Of 418 eligible Veterans, 21.05% (88) were tested. There were 16 Veterans who underwent testing but were not eligible due to age, stage or HR/HER status. There were no statistically significant differences in use of testing by age or race. Recurrence score for Veterans tested ranged from 0-50 (M=17.40, SD 10.91); 58 (55.77%) low, 35 (33.65%) moderate, and 11 (10.58%) high risk of recurrence. Chemotherapy was used by 26 (25%) Veterans who underwent testing and by 395 (38.16%) Veterans not tested (p < 0.025). Conclusions: There has been a rapid increase in use of the 21-gene risk score test among patients with breast cancer within the VA. Ongoing research will examine regional/site of care variations in access and we will analyze the influence of testing on health outcomes.
Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced Diarrhea: A Randomized, Open-Label Multicenter Phase II Study
Authors: Annemieke J.M. Nieuweboer, Anne-Joy M. de Graan, Paul Hamberg, Sander Bins, Robert J. van Soest, Robbert J. van Alphen, Andries M. Bergman, Aart Beeker, Henk van Halteren, Albert J. ten Tije, Hanneke Zuetenhorst, Nelly van der Meer, Dana Chitu, Ronald de Wit, Ron H.J. Mathijssen
Journal: Clinical Cancer Research (2016)

Purpose: Forty-seven percent of patients in the pivotal trial of cabazitaxel reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea during the first two treatment cycles.Experimental Design: Between December 2011 and October 2015, 246 metastatic castration-resistant prostate cancer patients were randomized to receive standard-of-care cabazitaxel 25 mg/m2 every 3 weeks plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with concomitant budesonide 9 mg daily during the first two treatment cycles (group BUD). The occurrence of diarrhea was reported by physicians and by patients in a diary. χ2 tests were used to compare incidence numbers. An intention-to-treat principle was used.Results: In the phase II trial, 227 patients were evaluable. Grade 2-3 diarrhea occurred in 35 patients (15%) and grade 4 diarrhea was not reported. The incidence of grade 2-3 diarrhea was comparable in both treatment groups: 14 of 113 patients in group CABA (12%) versus 21 of 114 patients in group BUD (18%; P = 0.21). Seven patients were admitted to the hospital with diarrhea (n = 5 group CABA vs. n = 2 group BUD). PSA response was seen in 30% of patients and was not affected by budesonide coadministration (P = 0.29). Also, other toxicities were not affected by budesonide coadministration.Conclusions: The incidence of cabazitaxel-induced diarrhea was notably lower than reported in the TROPIC trial and appears manageable in routine clinical practice. Budesonide coadministration did not reduce the incidence or severity of cabazitaxel-induced diarrhea. Clin Cancer Res; 23(7); 1679-83. ©2016 AACR.