tbuckley/cabot-search huggingface dataset:
A randomized phase III trial in patients with advanced adenocarcinoma of the stomach receiving first-line chemotherapy with fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP)
Authors: S. Al-Batran, J. T. Hartmann, S. Probst, R. Hofheinz, J. Stoehlmacher, H. Schmalenberg, S. Hollerbach, G. Schuch, N. Homann, E. Jäger
Journal: Journal of Clinical Oncology (2006)

LBA4016 Background: Cisplatin-based chemotherapy is a standard option in advanced gastric cancer. However, treatment results have been unsatisfactory so far, with a time to progression (TTP) of 3 to 4 months and an overall survival (OS) of 6 to 9 months. In addition, treatment regimens are too intense and toxicity is considerable. The aim of this 2-arm randomized trial was to determine whether FLO prolongs TTP and reduces toxicity as compared to FLP. Methods: Patients (pts) were randomized to receive FLO: F 2600 mg/m 2 24 h infusion, L 200 mg/m 2 , and oxaliplatin 85 mg/m 2 , every two weeks or FLP: F 2000 mg/m 2 24 h infusion, L 200 mg/m 2 , weekly, and cisplatin 50 mg/m 2 , every two weeks. The primary end point was TTP. Main secondary endpoints included toxicity, time to treatment failure (TTF), and OS. Based on a planned sample size of 218 pts, the trial was designed to have an 80% power to detect an improvement in median TTP from 3.5 to 5.0 months (1-sided log-rank test; significance level 0.05). Results: 220 pts (FLO/FLP, 112/108) were randomized between Aug 2003 and Jan 2006. Median age was 64 yrs and median ECOG was 1. 162 pts (FLO, 80; FLP, 81) had disease progression and 25 pts (FLO, 18; FLP, 8) are still under treatment. Median TTP was 5.7 months for FLO and 3.8 months for FLP (log-rank p = 0.081, Wilcoxon p = 0.019). Median TTF was 5.3 months for FLO and 3.1 months for FLP (log-rank p = 0.028). Response to FLO (34%) was superior to FLP (27%), with 15% and 30% of pts having disease progression as best response to FLO and FLP, respectively (chi-square for trend p = 0.012). Median treatment duration was 4.3 months with FLO and 3 months with FLP. FLO was associated with significantly less NCI-CTC grade 1–4 leukopenia, nausea, alopecia, fatigue, and renal toxicity and FLP was associated with significantly less peripheral neuropathy (chi-square for trend p &lt; 0.05). Severe adverse events related to treatment were less frequent with FLO (8.9%) as compared to FLP (18.6%; p = 0.046). Conclusions: FLO reduced toxicity and improved efficacy as compared to FLP. This leads us to consider FLO for future studies in combination with targeted drugs to further improve the outcome of pts with gastric cancer. No significant financial relationships to disclose.
Brief Report: Severe Inflammation Following Vaccination Against <i>Streptococcus pneumoniae</i> in Patients With Cryopyrin‐Associated Periodic Syndromes
Authors: Ulrich A. Walker, Hal M. Hoffman, Rene Williams, Jasmin Kuemmerle‐Deschner, Philip N. Hawkins
Journal: Arthritis & Rheumatology (2016)

Objective Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin‐associated periodic syndromes (CAPS). Methods Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively. Results Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3–17 days. Conclusion Our findings indicate that pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. Careful consideration is warranted when implementing current European League Against Rheumatism immunization guidelines in this patient population.
Prognosis of Breast Cancer in Carriers of<i>BRCA1</i>and<i>BRCA2</i>Mutations
Authors: Dimitrios H Roukos
Journal: New England Journal of Medicine (2007)

To the Editor: Rennert et al. (July 12 issue)1 report that a BRCA1 or BRCA2 mutation was not a significant predictor of mortality from breast cancer in an Israeli population-based cohort. However, 43% of potential cases were not included because tumor samples or medical records could not be retrieved, and excluded cases were more likely than included cases to be fatal. If BRCA1 carriers have more aggressive tumors,2 leading to earlier death, this could result in a spuriously improved prognosis (Neyman bias). In addition, the investigators did not study tumor grade (associated with mutation status),3 nor did they identify prognostic effects of tumor and nodal stage, raising concerns about internal validity. Furthermore, greater chemotherapy use among carriers (37%) than among noncarriers (24%) suggests that decisions about chemotherapy may have been influenced by factors such as family history, leading to a spurious treatment benefit in carriers. Finally, insufficient detail was provided regarding chemotherapy use (BRCA1-associated breast cancer may have increased sensitivity to agents causing doublestrand DNA breaks4 and reduced sensitivity to mitotic spindle poisons) for a full understanding of the effect of chemotherapy in carriers of these mutations.5
Poster Session 1: Autoimmune Liver Disease
Authors: Albert Stättermayer, Michael Eder, Sandra Beinhardt, Karin Kozbial, Clarissa Freissmuth, Friedrich Wrba, Michael Trauner, Peter Ferenci, Harald Hofer, Falk Foundation, Madaus Rottapharm, David Assis, Richard Bucala, James Boyer, Maria Secchi, Valentina Masola, Irene Franceschet, Nora Cazzagon, Maurizio Onisto, Annarosa Floreani, Henk Van Buuren -Grant, Bart Van Hoek, Bristol Meyers Squib, Martine Baven-Pronk, Joanne Van Silfhout, Aad Van Den Berg, Carin Van Nieuwkerk
Journal: Hepatology (2015)

Background/aim: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with limited understanding of etiopathogenesis.Recently, a genome-wide association study (GWAS) identified a single nucleotide polymorphism (SNP, rs2187668) in the HLA-DQA1 gene, which is strongly associated with AIH type-1.We evaluated the impact of this SNP on clinical presentation and treatment response in patients with type-1 AIH.Methods: One-hundred and seven patients with type-1 AIH (female: 83 [77.6%], mean age: 43.2 [CI95%: 39.9-46.6]years), who reached a probable or definite score according to the simplified or revised scoring system were evaluated.SNP rs2187668 was investigated by real-time-PCR in all patients with AIH and in a control group of 97 healthy subjects.Results: Sixty-one (57.0%) patients with AIH had rs2187668 genotype GG, 39 (36.4%) were heterozygous and 7 (6.5%) had genotype AA.Minor allele frequency (MAF) of the risk allele (A) was 24.8% and was significantly higher than in the control group (MAF: 7.2%; p<0.001).A allele carriers had a trend for higher immunoglobulin G levels than patients with GG (AG/AA: 1.53 [CI95%: 1.35-1.72]xULNvs. GG: 1.32 [CI95%: 1.18-1.46]xULN,p=0.062).No differences in ALT or AST levels were observed between the two groups.Furthermore, age at diagnosis as well as presence of cirrhosis were equally distributed across different genotypes.Response to immunosuppressive treatment at 12 months did not differ between rs2187668 A allele carriers and patients with GG genotype.Conclusion: The A allele in rs2187668 in HLA-DQA1 is strongly associated with AIH in our cohort of patients.Rs2187668 does not seem to influence clinical presentation or response to immunosuppressive treatment in type-1 AIH.
The dipole moment of cytochrome c.
Authors: W H Koppenol, J D Rush, J D Mills, E Margoliash
Journal: Molecular Biology and Evolution (1991)

Vertebrate cytochromes c and the cytochromes c of insects and plants have, on average, dipole moments of 320 and 340 debye, respectively. The direction of the dipole vector with respect to the haem plane, at the solvent-accessible edge of which electron transfer presumably takes place, is conserved in these two groups--at 32 degrees +/- 7 degrees and 22 degrees +/- 10 degrees, respectively. The variation of dipole orientations and magnitudes observed in these species is compared with the results of a model in which charge distributions occur randomly. Since this model does not generate the observed charge asymmetries of the various cytochromes c, it is concluded that the dipole moment of cytochrome c is a feature that is evolutionarily conserved, apparently because it has an important influence on the interaction of this mobile electron carrier with its physiological electron donors and acceptors in the intermembrane space of mitochondria.
Predictive testing for inherited mutations in cancer-susceptibility genes.
Authors: F P Li, J F Fraumeni
Journal: Journal of Clinical Oncology (1992)

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.1992.10.8.1203 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1634911 Predictive testing for inherited mutations in cancer-susceptibility genes. F P LixF P LiSearch for articles by this author , J F Fraumeni JrxJ F Fraumeni JrSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.8.1203 PDF "Predictive testing for inherited mutations in cancer-susceptibility genes.." Journal of Clinical Oncology, 10(8), pp. 1203–1204© 1992 by American Society of Clinical Oncology
Abstract 48: Age-associated Imbalance of Vasorin/TGF-β1 Signaling in VSMC Facilitates Collagen Production
Authors: Mingyi Wang, Gianfranco Pintus, Roberta Giordo, Jing Zhang, Liqun Jiang, Robert Monticone, Edward Lakatta
Journal: Circulation Research (2014)

Collagen deposition, a hallmark of arterial aging that resembles post-injury arterial restenosis, is perpetrated by angiotensin II (Ang II) signaling in arterial wall. Collagen aggregation at sites of arterial injury is regulated by the coordinated signaling of pro-fibrotic TGF-β1 and anti-fibrotic vasorin within VSMCs. The Ang II/TGF-β1/vasorin signaling relationship within VSMCs with aging, however, remains unknown. In vivo studies in old vs. young FXBN rats show that aortic transcription and translation of vasorin markedly decrease with aging. In vitro studies in VSMCs isolated from old vs. young aortae. Ang II-associated reduction of vasorin protein abundance in young VSMCs and age-associated changes in vasorin protein levels are reversed by the AT1 antagonist, Losartan (Los) (Figure). Dual immunolabeling and co-immunoprecipitation demonstrate that the co-incidence and physical interaction of vasorin and TGF-β1 within VSMCs are significantly decreased with aging. Importantly, exposure of young VSMCs to Ang II that increases p-SMAD2/3 and collagen type I production, mimicking old cells, and this effect is abolished or substantially mitigated by Los treatment, overexpression of ectopic vasorin, or exogenous recombinant human-vasorin protein. In contrast, exposure of old VSMCs to Los decreases p-SMAD2/3 and collagen type I production.Thus, an imbalance of the Ang II/TGF-β1/vasorin signaling cascade, a feature of the aged arterial wall, enhances the collagen production by VSMCs. Maintaining this signaling balance is a novel measure to retard adverse extracellular matrix remodeling, a determinant of arterial stiffening with aging. (MW and GP co-first authors)
Abstract 16676: Neovascularisation Potential of Blood Outgrowth Endothelial Cells From Patients With Severe Ischemic Cardiomyopathy
Authors: Dieter Dauwe, Kristoff Verdonck, Hilde Gilllijns, Ellen Caluwe, Peter Pokreisz, Nick van Gastel, Geert Carmeliet, Maarten Depypere, Frederik Maes, Walter Droogne, Johan Vanhaecke, Aernout Luttun, Stefan Janssens
Journal: Circulation (2013)
Histogenesis and Fine Structure of Peritoneal Tumors Produced in Animals by Injections of Asbestos2
Authors: J. M. G. Davis
Journal: JNCI Journal of the National Cancer Institute (1974)

Primary tumors of the peritoneal cavity were produced in rats and mice by the intraperitoneal injection of crocidolite asbestos. The earliest discernible neoplastic stage consisted of many small, pedunculated nodules scattered over the surfaces of the viscera, diaphragm, and body wall. These nodules contained a central core of reticulin or collagen surrounded by layers of pleomorphic connective-tissue cells. The surfaces of the nodules were covered by a single layer of epithelial cells similar to normal mesothelium. In later stages some nodules remained distinct and became quite large, but often the tumor spread over the peritoneal surfaces as a uniform sheet. The cells found in sheets were mostly of the same type as those in large nodules: pleomorphic connectivetissue cells in the central regions and epithelial cells on the surface. In some advanced tumors, however, the cells had a spindle-cell pattern similar to a fibroma or fibrosarcoma. In this form the neoplasms were locally invasive; however, at earlier stages no signs of invasion could be detected. Electron microscope studies showed only a slight difference in ultrastructure between the different tumor cell types, and it is suggested that the growths arose from undifferentiated mesenchymal cells in the sub mesothelial tissues. These cells retained their normal pleomorphic pattern or gave rise to either epithelial (mesothelial) cells on free surfaces or spindle cells in deeper layers.
Abstract 13298: First-pass MRI Reveals Distinct Mechanisms for Reduced Myocardial Perfusion Reserve Between ApoE-/- Mice on a High-cholesterol Diet and C57Bl/6 Mice on a High-fat Diet
Authors: Nivedita K Naresh, Xiao Chen, Jane V Carrick, Patrick F Antkowiak, Rene J Roy, Brian H Annex, Frederick H Epstein
Journal: Circulation (2013)

Introduction: Reduced coronary flow reserve is an independent predictor of cardiac mortality in patients with known or suspected coronary artery disease (CAD), including nonobstructive CAD. We used...
Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology.
Authors: C. A. Lammersfeld, P. G. Vashi, K. Trukova, D. P. Braun, D. Gupta
Journal: Journal of Clinical Oncology (2010)

e19542 Background: Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of vitamin D deficiency (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation on serum vitamin D levels in cancer. Methods: 1,082 cancer patients had a baseline test to evaluate serum 25(OH)D levels between Jan 08 and Dec 08. Patients with baseline levels of < 32 ng/ml (n = 848) were supplemented with 8,000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit that coincided most closely with a time interval of 8 weeks. Of 848 patients, 212 were available for first follow-up assessment. The mean serum 25(OH)D levels were compared in these 212 patients across the 2 time points (baseline and first follow-up) using paired sample t- test. Results: Of 212 patients, 86 were males and 126 females. 111 were analytic (newly diagnosed and treated at our hospital) while 101 were non-analytic (diagnosed and treated elsewhere). The mean age at diagnosis was 52.7 years (SD = 10.6). The most common cancer types were breast (49, 23.1%), lung (36, 17%), colorectal (28, 13.2%), pancreas (17, 8%), prostate (12, 5.7%) and ovarian (11, 5.2%). The mean time duration between baseline and first follow-up assessment was 12.9 weeks. The mean serum 25(OH)D levels were 18.8 ng/ml (SD = 7.4) and 36 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p <0.001. A lower baseline vitamin D was correlated with a higher vitamin D increase at the first follow-up assessment (r = −0.21, p = 0.002) while age, gender and prior treatment history had no effect. Conclusions: Vitamin D supplementation resulted in a significant increase in serum 25(OH)D levels particularly in those with lower levels at baseline. Characteristics of patients that take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum vitamin D levels on patient survival and quality of life needs to be investigated. No significant financial relationships to disclose.
Abstract 2702: Prodromal Symptoms of Out-of-hospital Cardiac Arrest: Report From a Large-scaled Population-based Study
Authors: Chika Nishiyama, Taku Iwami, Takashi Kawamura, Tetsuhisa Kitamura, Kayo Tanigawa, Tomohiko Sakai, Sumito Hayashida, Atsuchi Hiraide
Journal: Circulation (2009)

Introduction: Little is known about symptoms preceding sudden cardiac arrest. Objectives: The aim of this study was to describe a frequency of prodromal symptoms of out-of-hospital cardiac arrest (...
Method and matter in the social sciences: Umbilically tied to the Enlightenment
Authors: Benjamin Beit-Hallahmi
Journal: Behavioral and Brain Sciences (2015)

Abstract This commentary deals with the nonconformity of academics and the ethos of social science. Academics in all fields deviate from majority norms in politics and religion, and this deviance may be essential to the academic mind and to academic norms. The Enlightenment legacy inspires both methods and subject matter in academic work, and severing ties with it may be impossible.
Incidence of venous thromboembolism in breast cancer patients during chemotherapy with vinorelbine, cisplatin, 5-fluorouracil as continuous infusion (ViFuP regimen): Is prophylaxis required?
Authors: L. Orlando, M. Colleoni, F. Nolè, R. Biffi, A. Rocca, G. Curigliano, G. Ferretti, G. Peruzzotti, F. de Braud, G. Masci, A. Goldhirsch
Journal: Annals of Oncology (2000)
Early HCC treatment: a future strategy against interferon/miR-484 axis to revert precancerous lesions?
Authors: André Lechel, Angélique Gougelet
Journal: Gut (2016)

Liver tumours are the sixth most common tumour entity worldwide and the second most common cause of cancer-related deaths. Hepatocellular carcinoma (HCC) is the most frequent liver tumour and is mainly related to viral infections, including HBV and HCV, alcohol consumption, metabolic syndrome and aflatoxin B exposure. Hepatocarcinogenesis is described as a multistep process, which starts mostly by a chronic disease and on the basis of cirrhosis formation. In the recent years, precursor lesions are well described by their morphological characterisation and there is evidence that those precursor lesions are involved in HCC formation by passing through a sequence of molecular events in hepatic nodules.1 Two different types of dysplastic nodules are specified, low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs), which delineate the border between premalignant lesion and malignant transformation. LGDNs are morphologically characterised by a mild increase of cell density, and the presence of peripheral fibrous scar distinct from the surrounding cirrhotic liver. HGDNs may be distinctly or vaguely nodular in the background of a cirrhotic liver, and often show an increase in cell density, with an irregular trabecular pattern. LGDN is described as non-malignant, whereas HGDN is the precancerous lesion for the transformation in HCC.

The detection between early HCCs and HGDN is more difficult for pathologists. A recent report describes the classification …
Mutagenicity of Five Cyclic N-Nitrosamines: Assay With Salmonella typhimurium
Authors: D. R. Stoltz, N. P. Sen
Journal: JNCI Journal of the National Cancer Institute (1977)

The mutagenicity of five cyclic N-nitrosamines was studied with the use of Salmonella typhimurium TA1535 in vitro with and without microsomal activation. The carcinogens nitrosopiperidine and nitrosopyrrolidine required metabolic activation before manifesting mutagenic activity. Nitrosoproline and nitrosohydroxyproline, noncarcinogens, were not mutagenic. Nitroso-3-pyrrolidinol was mutagenic in the absence of microsomes, thereby suggesting a role of hydroxylation in the metabolic activation of nitrosopyrrolidine to an ultimate carcinogenic species.
Association Between Medication Adherence Report Scale (MARS-5) and Caregiver-Reported Inhaled Corticosteroid Use in Inner City Children with Asthma
Authors: Lena Truong, Mona G. Tsoukleris, Melissa Bellin, Joan Kub, Cassia J. Lewis-Land, Mary E. Bollinger, Arlene Butz
Journal: Journal of Allergy and Clinical Immunology (2016)
Exogenous Estrogens and Breast Cancer in Women With Natural Menopause 2
Authors: J. Casagrande, V. Gerkins, B. E. Henderson, T. Mack, M. C. Pike
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Exogenous Estrogens and Breast Cancer in Women With Natural Menopause Get access J. Casagrande, J. Casagrande 4 4Address reprint requests to J. Casagrande, Cancer Research Project, Edmondson Research Bldg., 1840 North Soto St., Los Angeles, Calif. 90033. Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Gerkins, V. Gerkins Search for other works by this author on: Oxford Academic PubMed Google Scholar B. E. Henderson, B. E. Henderson Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Mack, T. Mack Search for other works by this author on: Oxford Academic PubMed Google Scholar M. C. Pike M. C. Pike Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 4, April 1976, Pages 839–841, https://doi.org/10.1093/jnci/56.4.839 Published: 01 April 1976 Article history Received: 26 August 1975 Accepted: 18 November 1975 Published: 01 April 1976
Rapid decrease in hepatitis C viremia by direct acting antivirals improves the natural killer cell response to IFNα
Authors: Elisavet Serti, Heiyoung Park, Meghan Keane, Ashley C O'Keefe, Elenita Rivera, T Jake Liang, Marc Ghany, Barbara Rehermann
Journal: Gut (2016)

<h3>Objective</h3> Chronic HCV infection is characterised by innate immune activation with increased interferon-stimulated genes (ISG) expression and by an altered phenotype of interferon-responsive natural killer (NK) cells. Here, we asked whether a rapid reduction in viremia by daclatasvir (DCV) and asunaprevir (ASV) improves the response to pegylated interferon (PegIFN) in patients who had previously failed a standard course of PegIFN/ribavirin (RBV) therapy. <h3>Design</h3> Twenty-two HCV-infected non-responders to previous PegIFN/RBV therapy were studied for IFN-responsiveness of NK cells during quadruple (QUAD) therapy with DCV, ASV, PegIFN and RBV. A direct comparison of early NK cell responses in PegIFN/RBV therapy and QUAD therapy was performed for seven patients using paired cryopreserved peripheral blood mononuclear cells (PBMC) from both treatment courses. As a validation cohort, nine DCV/ASV-treated patients were studied for their NK cell response to in vitro stimulation with IFNα. <h3>Results</h3> The 24 h virological response to QUAD therapy correlated with an increase in signal transducer and activator of transcription 1 (STAT1), phosphorylated STAT1 (pSTAT1) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) expression in NK cells, and the STAT1/pSTAT1/TRAIL induction was greater during QUAD therapy than during previous PegIFN/RBV therapy. Successful QUAD therapy as well as successful IFN-free DCV/ASV regimen resulted in an improved functional NK cell response (degranulation and TRAIL expression) to in vitro stimulation with IFNα. <h3>Conclusions</h3> IFN-responsiveness can be improved by inhibiting HCV replication and reducing the HCV-induced activation of the innate immune response. This may provide a rationale for clinical trials of a brief period of direct acting antiviral therapy followed by PegIFN/RBV therapy to reduce the overall treatment costs in low-income and middle-income countries. <h3>Trial registration numbers</h3> NCT01888900 and NCT00718172.