tbuckley/cabot-search huggingface dataset:
Prognostic value of the rate of rise of CA 125 after first line chemotherapy for survival in patients with relapsed ovarian cancer
Authors: V. Karavasilis, K. Thomas, M. Harrison, P. Papadopoulos, D. Barton, M. E. Gore, S. B. Kaye
Journal: Journal of Clinical Oncology (2008)

5544 Background: A confirmed doubling of CA-125 level is now established as one definition of progression in patients with ovarian cancer. However it is unclear whether the rate of rise of CA125 carries independent adverse prognostic significance, sufficient to justify therapeutic decision making on this basis alone. Methods: All patients who had received first line chemotherapy for ovarian cancer between 1994 and 2003 were identified from our electronic database. For patients with normal post-treatment CA125, the first date of any subsequent reading> ULN was recorded as the date of CA125 progression. For patients with abnormal post-treatment CA125, the first recorded date at which CA125 had increased by at least 20% from nadir was recorded as the date of CA125 progression. The first date at which CA125 rose to at least 2 fold the level of progression was recorded and the time between progression and doubling was defined as the doubling time. The time from end of first line treatment to CA125 progression was also recorded as CA125 progression time. Overall survival (OS) from doubling was calculated. Cox regression was used to determine the influence of CA125 doubling time on OS and a multivariate analysis was also performed, including data on time to first progression Results: 933 cases with median age of 60 years were eligible for analysis. The majority had epithelial tumors (93%) of advanced stage (67%). 58% were treated with single agent platinum and 39% received paclitaxel and platinum combination chemotherapy. 525 patients had documented CA 125 progression with a median time of 9 months. Of those, 298 patients had reached doubling post progression CA125 with a median doubling time of 3 months. Univariate analysis showed that doubling time within 30 days was associated with shorter median OS followed by doubling time within 60 and 90 days (median OS 9 vs 20 vs 26 months, p<0.001). Multivariate analysis also demonstrated that the prognostic significance of doubling time is independent of time to progression. Conclusions: Rapid doubling of CA 125 after first line chemotherapy is associated with a more adverse outcome in patients with relapsed ovarian cancer. This should be considered for decision-making in respect of second line chemotherapy. No significant financial relationships to disclose.
Lessons learnt to keep Europe polio-free: a review of outbreaks in the European Union, European Economic Area, and candidate countries, 1973 to 2013
Authors: Tarik Derrough, Alexandra Salekeen
Journal: Eurosurveillance (2016)

Between 1973 and 2013, 12 outbreaks of paralytic poliomyelitis with a cumulative total of 660 cases were reported in the European Union, European Economic Area and candidate countries. Outbreaks lasted seven to 90 weeks (median: 24 weeks) and were identified through the diagnosis of cases of acute flaccid paralysis, for which infection with wild poliovirus was subsequently identified. In two countries, environmental surveillance was in place before the outbreaks, but did not detect any wild strain before the occurrence of clinical cases. This surveillance nonetheless provided useful information to monitor the outbreaks and their geographical spread. Outbreaks were predominantly caused by poliovirus type 1 and typically involved unvaccinated or inadequately vaccinated groups within highly immunised communities. Oral polio vaccine was primarily used to respond to the outbreaks with catch-up campaigns implemented either nationwide or in restricted geographical areas or age groups. The introduction of supplementary immunisation contained the outbreaks. In 2002, the European region of the World Health Organization was declared polio-free and it has maintained this status since. However, as long as there are non-vaccinated or under-vaccinated groups in European countries and poliomyelitis is not eradicated, countries remain continuously at risk of reintroduction and establishment of the virus. Continued efforts to reach these groups are needed in order to ensure a uniform and high vaccination coverage.
Type of Relapse in 91 Newly Diagnosed MM Patients Treated with High Dose Chemotherapy Followed by Autologous Stem Cell Transplantation.
Authors: Maria Teresa Petrucci, Giuseppe Avvisati, Ombretta Annibali, Saveria Capria, Maria S. De Propris, Patrizia Del Bianco, Vincenzo Federico, Cristiano Gallucci, Maria Gozzer, Chiara Gregorj, Annalisa Natale, Azzurra Romeo, Giovanna Meloni, Robert Foa
Journal: Blood (2006)
TCTAP A-086 Role of Microcatheter Based FFR (Acist RXi with NAVVUS Microcatheter) Measurement in the Treatment of Bifurcation Lesions - Building the Strategy and Changing It According to the Mid Procedure Measurement of FFR - Confront with Standard Wire Based FFR Measurements
Authors: Farhat Fouladvand
Journal: Journal of the American College of Cardiology (2016)
CD22-Targeted Chimeric Antigen Receptor (CAR) T Cells Containing The 4-1BB Costimulatory Domain Demonstrate Enhanced Persistence and Superior Efficacy Against B-Cell Precursor Acute Lymphoblastic Leukemia (ALL) Compared To Those Containing CD28
Authors: Waleed Haso, Haiying Qin, Ling Zhang, Rimas J Orentas, Terry J Fry
Journal: Blood (2013)
The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders
Authors: Chiara Vidoni, Carlo Follo, Miriam Savino, Mariarosa A. B. Melone, Ciro Isidoro
Journal: Medicinal Research Reviews (2016)

In familial neurodegenerative disorders, protein aggregates form continuously because of genetic mutations that drive the synthesis of truncated or unfolded proteins. The oxidative stress imposed by neurotransmitters and environmental neurotoxins constitutes an additional threat to the folding of the proteins and the integrity of organelle membranes in neurons. Failure in degrading such altered materials compromises the function of neurons and eventually leads to neurodegeneration. The lysosomal proteolytic enzyme Cathepsin D is the only aspartic-type protease ubiquitously expressed in all the cells of the human body, and it is expressed at high level in the brain. In general, cathepsin D mediated proteolysis is essential to neuronal cell homeostasis through the degradation of unfolded or oxidized protein aggregates delivered to lysosomes via autophagy or endocytosis. More specifically, many altered neuronal proteins that hallmark neurodegenerative diseases (e.g., the amyloid precursor, α-synuclein, and huntingtin) are physiologic substrates of cathepsin D and would abnormally accumulate if not efficiently degraded by this enzyme. Furthermore, experimental evidence indicates that cathepsin D activity is linked to the metabolism of cholesterol and of glycosaminoglycans, which accounts for its involvement in neuronal plasticity. This review focuses on the unique role of cathepsin D mediated proteolysis in the pathogenesis of human neurodegenerative diseases.
<i>IRF7</i> inhibition prevents destructive innate immunity—A target for nonantibiotic therapy of bacterial infections
Authors: Manoj Puthia, Ines Ambite, Caterina Cafaro, Daniel Butler, Yujing Huang, Nataliya Lutay, Gustav Rydström, Birgitta Gullstrand, Bhairavi Swaminathan, Aftab Nadeem, Björn Nilsson, Catharina Svanborg
Journal: Science Translational Medicine (2016)

Interferon regulatory factor 7 is an innate immune target for non–antibiotic-based immunotherapy for bacterial infection.
460P Evaluation of overall health status in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 017
Authors: M. Reck, C. Coon, F. Taylor, M. Derosa, J.R. Penrod, H. Dastani, L. Orsini, R.J. Gralla
Journal: Annals of Oncology (2015)
Digoxin: Immunologic Approaches to Measurement and Reversal of Toxicity
Authors: Louis M. Sherwood, Edith E. Parris, Louis M. Sherwood, Edith E. Parris, Vincent P. Butler
Journal: New England Journal of Medicine (1970)

THE clinical use of digitalis is accompanied by a distressingly high prevalence of toxic manifestations, the most serious of which are arrhythmias and disturbances of conduction.1 , 2 Many factors contribute to the development of digitalis toxicity (Table 1). Perhaps the most important is the accumulation of excessive amounts of digitalis in the body and in the myocardium in particular.Although excessive digitalis accumulation occasionally reflects excessive dosage, it is more commonly due to diminished excretion. Largely as a result of the studies of Doherty3 4 5 6 7 and of Marcus8 9 10 and their collaborators, much has recently been learned about the factors that lead to . . .
Counterfeit Norco Poisoning Outbreak — San Francisco Bay Area, California, March 25–April 5, 2016
Authors: Kathy T. Vo, Xander M.R. van Wijk, Kara L. Lynch, Alan H.B. Wu, Craig G. Smollin
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On March 28, 2016, two patients were evaluated at the Contra Costa Regional Medical Center emergency department (ED) in Contra Costa County, California, for nausea, vomiting, central nervous system depression, and respiratory depression, 30 minutes after ingesting what appeared to be Norco, a prescription opioid pain medication that contains acetaminophen and hydrocodone.The patients purchased the drug from a friend a few days earlier.The two cases of drug intoxication were reported to a Contra Costa County Health Department public health official who subsequently notified the California State Health Department.Three days earlier, the Sacramento County Division of Public Health had released a Drug Overdose Health Alert regarding multiple poisoning overdoses related to ingestion of fentanyl-contaminated counterfeit Norco in Sacramento County (1).All staff members at the California Poison Control System (CPCS) were alerted to increase vigilance for potential cases.In the subsequent 2 weeks, the CPCS San Francisco Division identified an additional five cases in three Bay Area counties (Alameda, San Francisco, and Santa Clara), including one case in a patient (patient 1) that was reported retrospectively (Table ).All patients reported to the CPCS San Francisco Division had various signs and symptoms of opioid intoxication after ingestion of the illicit product, and all recovered without clinical sequelae within 24 hours.Although analyses of product and patient specimens from Sacramento County were reported to have contained fentanyl, all cases in the Bay Area also contained promethazine, which had not been reported as an additive in previous counterfeit or adulterated fentanyl-containing products.Fentanyl is a synthetic opioid analgesic that is a fullµ-opioid receptor agonist (one of the three opioid receptors through which opioids exert their pharmacologic actions) and has 100 times the potency of morphine (2).Fentanyl is available in many formulations, and its unique physicochemical properties, particularly its high lipophilicity, allow it to quickly enter the central nervous system and are responsible for its high potency (2) and high potential for abuse.Fentanyl is not currently formulated for oral administration in pill or tablet form, however, and its presence in pill form is a marker for an illicitly produced product.Promethazine, a phenothiazine derivative, is routinely prescribed for the treatment of nausea, vomiting, and motion sickness.Promethazine use has recently been reported to be common among chronic opioid users and is thought to potentiate the "high" from opioids (3).
Petition urges GSK and Pfizer to lower price of pneumonia vaccine
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

The humanitarian charity Medecins Sans Frontieres/Doctors Without Borders has delivered a petition of almost 400 000 signatures to the headquarters of GlaxoSmithKline (GSK) in London and Pfizer in New York, demanding that the companies reduce the price of their pneumonia vaccine in developing countries to $5 (£3.45; €4.40) per child.

The petition was delivered to GSK by an …
Effect of neoadjuvant chemotherapy with gemcitabine and docetaxel on 3-year survival and resection rate in previously unresectable locally advanced pancreatic cancer
Authors: M. Gnant, I. Kuehrer, B. Teleky, P. Goetzinger, M. Penz, R. Sedivy, W. Scheithauer, T. Sautner, C. Zielinski, R. Jakesz
Journal: Journal of Clinical Oncology (2004)

4234 Background: Pancreatic cancer is difficult to treat and almost impossible to screen for. Surgical resection offers the best possibility for cure, however, only a small proportion of patients are diagnosed with the disease at a resectable stage. We initiated a clinical phase II study to investigate the down staging and long-term effects of neo-adjuvant chemotherapy using gemcitabine (Gem) and docetaxel (Doc) for patients with locally advanced non-metastasized pancreatic cancer. Methods: 61 patients (age 28 to 81) with confirmed pancreatic cancer (T2–4, Nx, M0) were enrolled after informed consent. Non-resectability was assessed by multi-slice CT or MRI. The trial design included a dose escalation of combination chemotherapy of 5 dose levels (days 1,8,15 q28; Gem 800 to 1000 mg/m2, Doc 25 to 45 mg/). Two or three such cycles were administered for a preoperative treatment duration of 8 to 12 weeks. Patients with then resectable cancers underwent surgery within 4 weeks after chemotherapy. 48/61 patients (79%) were successfully resected after preoperative chemotherapy . All resections were radical (R0); there was no surgical mortality. Results: At a median follow up time of 32 months, 36/48 patients with R0 resection are alive (75%). 1-yr survival was 85 per cent; actuarial 3-yr survival was 69 per cent. Both OS and DFS of patients of this were markedly better than that of primarily resected patients (T1–3) without neoadjvuant chemotherapy. Conclusions: Neoadjuvant chemotherapy of non-resectable pancreatic cancer using gemcitabine and docetaxel leads to major down staging in most patients, leading to resectability on 4 out of 5 patients. In addition, the postoperative survival of patients responding to neoadjuvant chemotherapy markedly exceeds the primary survival pattern of patients who underwent surgery with earlier-stage disease. In addition, distinction between responders and non-responders by molecular markers remains a major goal of research in order to reliably predict response to therapies and subsequent optimization of treatment for individual patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly; Aventis
Does Metformin Really Increase Height, or Is There Some Problem With the Controls?—Reply
Authors: Nicholas Kuzik, Étienne Myette-Côté, Normand Boulé
Journal: JAMA Pediatrics (2016)

In Reply We thank Poulton for the thoughtful letter that stated that the greater increase in height observed in studies from our meta-analysis1 with the highest cumulative metformin dose was owing to “a combination of inaccurate and abnormally slow growth rates in the control individuals.”
Incidence of Spontaneous Ileocecal Immunocytomas in Hybrids of LOU/C Rats and Rat Strains With Low Spontaneous Tumor Incidence: Brief Communication 2 3
Authors: Andrée Beckers, Hervé Bazin
Journal: JNCI Journal of the National Cancer Institute (1978)

Monoclonal immunoglobulin-secreting tumors (immunocytomas or plasmacytomas) appear in many species, but they occur at a low incidence and usually originate in lymphoid tissues. However, in the rat, the incidence of malignant spontaneous immunocytomas (or plasmacytomas) was high and the tumors consistently arose in the ileocecal lymph nodes. In inbred LOU/C/Wsl rats, these immunocytomas developed in twice as many males (31%) as females (16%). The susceptibility of the rats to immunocytoma was under genetic control; e.g., LOU/C/Wsl rats had a dominant locus (or loci) of susceptibility that could induce immunocytoma in inbred AUG/Wsl or inbred A X C9935/Wsl rats. However, inbred Okamoto/Wsl rats had at least one dominant locus of resistance that did not exist in LOU/C/Wsl, LOU/M/Wsl, AUG/Wsl, or A X C9935/Wsl rats.
Similarity Estimation Between DNA Sequences Based on Local Pattern Histograms of Binary Images
Authors: Yusei Kobori, Satoshi Mizuta
Journal: Genomics Proteomics & Bioinformatics (2016)

Graphical representation of DNA sequences is one of the most popular techniques for alignment-free sequence comparison. Here, we propose a new method for the feature extraction of DNA sequences represented by binary images, by estimating the similarity between DNA sequences using the frequency histograms of local bitmap patterns of images. Our method shows linear time complexity for the length of DNA sequences, which is practical even when long sequences, such as whole genome sequences, are compared. We tested five distance measures for the estimation of sequence similarities, and found that the histogram intersection and Manhattan distance are the most appropriate ones for phylogenetic analyses.
Leukemia cell infiltration causes defective erythropoiesis partially through MIP-1α/CCL3
Authors: Y Wang, A Gao, H Zhao, P Lu, H Cheng, F Dong, Y Gong, S Ma, Y Zheng, H Zhang, Y Zhang, J Xu, X Zhu, W Yuan, X Zhang, S Hao, T Cheng
Journal: Leukemia (2016)
TCTAP A-038 miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects Against Myocardial Ischemia-Reperfusion Injury
Authors: Junjie Xiao, Jing Shi, Yihua Bei, Tianzhao Xu, Hui Wang, Ping Chen, Xinli Li, Xiangqing Kong
Journal: Journal of the American College of Cardiology (2016)
Increased levels of transforming growth factor-β in HIV-associated nephropathy
Authors: T Yamamoto, N A Noble, D E Miller, L I Gold, A Hishida, M Nagase, A H Cohen, W A Border
Journal: Kidney International (1999)

Increased levels of transforming growth factor-β in HIV-associated nephropathy. <h3>Background</h3> Human immunodeficiency virus-associated nephropathy (HIVAN) is a renal disease of unknown pathogenesis. Recent evidence suggests that the fibrogenic cytokine transforming growth factor-β (TGF-β) might be involved. We hypothesized that overproduction of TGF-β in the kidney might be involved in the pathogenesis of HIVAN. <h3>Methods</h3> The mRNA and protein expression of TGF-β isoforms, TGF-β1, TGF-β2, and TGFβ3, deposition of matrix proteins induced by TGF-β, and levels of HIV Tat protein were studied in HIVAN. Controls included normal and diseased kidneys from HIV-positive and -negative patients. The ability of Tat to induce production of TGF-β and matrix proteins was also studied in human mesangial cells. <h3>Results</h3> Normal kidneys, thin basement membrane nephropathy, and minimal change disease were negative for the three TGF-β isoforms and Tat. In HIVAN, levels of TGF-β isoforms and Tat were significantly increased, along with the expression of TGF-β mRNA and deposition of matrix proteins stimulated by TGF-β. Increased levels of TGF-β isoforms, but not Tat, were also found in other glomerular diseases characterized by matrix accumulation. HIV infection, in the absence of HIVAN, was not associated with an increase in TGF-β or Tat expression. Tat stimulated the expression and production of TGF-β1 and matrix proteins by human mesangial cells. <h3>Conclusions</h3> Our findings suggest that overproduction of TGF-β is involved in the pathogenesis of HIVAN.
CoaGlio IV Trial: Randomized, controlled, triple-blind, multinational phase III study of adjuvant prophylactic anticoagulation in patients with glioblastoma WHO IV.
Authors: Susanne Antje Kuhn, Christine Marosi, Ingrid Pabinger, Lars Bullinger, Roland Goldbrunner, Alok A. Khorana, Manmeet Singh Ahluwalia, Frederick R. Rickles, Gary H. Lyman, Peter Vajkoczy
Journal: Journal of Clinical Oncology (2015)

TPS2079 Background: Venous thromboembolism (VTE) is a preventable complication in cancer and represents the second most frequent death cause, despite widely available anticoagulants. Further, VTE was proven as paraneoplastic syndrome of tumors, which use the coagulation to support their own aggressiveness. Currently, no guidelines recommend long-term prophylactic anticoagulation, since no data exists to support the use of any officially approved anticoagulant drug. None of the currently available anticoagulants has been adequately tested for its VTE prophylactic power in a cancer patient population. This study aims at providing a rationale for the generation of prophylaxis and treatment guidelines of VTE in cancer patients. This study finally aims to support the long needed completion of paradigm change in oncology since its initial description as Trousseau’s syndrome 150 years ago. Methods: The controlled, triple-blind, multinational phase III study randomizes pts. in a 1:1 fashion to receive either postop prophylactic anticoagulation with the oral factor X blocker apixaban (2.5mg b.i.d) or placebo over a 12-month-period in addition to the international first line standard therapy (radiochemotherapy with temozolomide (TMZ) + adjuvant TMZ). The power calculation is based on a 10% difference in overall survival, power at 80%, two-sided alpha level of 0.05, 5% drop out, requiring 530 patients over a two year period, with analysis performed two years after last patient recruited. Eligibility includes: adults, good performance status, newly diagnosed glioblastoma WHO IV, no major co-morbidities and no pregnancy. The primary endpoint is overall survival. Secondary endpoints include: progression free survival (PFS) at 6 and 12 months, median PFS, objective tumor response rate, frequency and mortality of VTE, safety and health related quality of life.Pre-treatment bio-resourcing of tumor and blood will enable further correlative translational studies. Progress to date: Trial activation in Fall 2015 at more than 20 centers in Europe and the United States. Trial registration: European Clinical Trials Database EudraCT 2015-000425-37. Clinical trial information: EudraCT: 2015-000425-37.