tbuckley/cabot-search huggingface dataset:
Comparative proteomic profiles of epstein-barr virus-associated lymphoma grown in SCID mouse with and without cidofovir treatment
Authors: Jaw-Ming Cherng, Hsiung-Ju Lin, Yiyang Sayion, Jung-Chung Lin
Journal: Cancer Research (2007)

3133  The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC or Cidofovir) on proteomic profiles of Epstein-Barr virus (EBV)-associated lymphoma grown in SCID mouse was evaluated. Intratumoral injection of Cidofovir arrested tumor growth within 10 days and by 21 days tumor regressed to 25 ± 8% of the original size. We isolated proteins from control and drug-treated tumors and did two-dimensional gel electrophoresis to determine protein expression patterns. Fifteen proteins showed significantly differential expression level between control and Cidofovir-treated samples. These proteins were characterized and identified by LC-MS/MS and confirmed by Western blotting. Among these differentially expressed proteins we found that prohibitin, a tumor suppressor protein, was over-expressed in tumors that had been treated with Cidofovir. The expression level of prohibitin correlated with the tumor regression. We established differential proteomic profiles that characterize and distinguish the Cidofovir-treated tumors from the control tumors. The proteins and proteomic profiles enhance understanding of the pathogenesis of EBV and have implications for diagnosis, prognosis, and treatment.
Abstract 14830: Oligogenic Inheritance of Congenital Heart Disease Involving an Nkx2-5 Modifier
Authors: Casey Gifford, Sanjeev Ranade, Ryan Samarakoon, Hazel Salunga, Yvanka de Soysa, Yu Huang, Ping Zhou, Arye Elfenbein, Stacia Wyman, Yen Bui, Kimberly Metzler, Philip Ursell, Kathryn Ivey, Deepak Srivastava
Journal: Circulation (2018)

Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular n...
Abstract #464: Protein tyrosine phosphatase inhibition enhances survival and chromosomal stability after genotoxin exposure at the expense of increased mutagenesis
Authors: Gina Chun, Sandra Wise, John Wise, Amie Holmes, Steven Patierno, Susan Ceryak
Journal: Cancer Research (2009)

Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is often associated with enhanced cell proliferation. In this study we employed the genotoxicant, hexavalent chromium [Cr(VI)], which is a well-documented carcinogen of occupational and environmental concern. We recently reported that PTP inhibition bypassed cell cycle arrest and abrogated Cr(VI)-induced clonogenic lethality. Notably, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability, via bypass of cell cycle checkpoints. The aim of the present study was to determine the effect of PTP inhibition on chromosomal integrity after Cr(VI) exposure. Diploid human lung fibroblasts were treated with Cr(VI) (as Na2CrO4) in the presence or absence of the PTP inhibitor, sodium orthovanadate, for 24 h. Five hours prior to the end of the treatment, 0.1 \#956;g/ml colcemid was added in order to block the cells in metaphase. Cells were harvested and re-suspended in 0.075 M KCl hypotonic solution and fixed. The cells were dropped on a clean wet slide and stained with 5% Giemsa stain in Gurr\#8217;s buffer. One hundred metaphases per data point were analyzed in each experiment. Treatment with 0.5 uM and 1 uM Cr(VI) induced a 6-fold and 12-fold increase in total chromosomal damage, respectively. In sharp contrast, PTP inhibition decreased the total amount of chromosomal damage after 0.5 uM and 1 uM Cr(VI) treatment to 0.78-fold and 1.45-fold, respectively. In summary, PTP inhibition in the face of Cr(VI) genotoxic stress enhances chromosomal stability but increases mutagenesis, which we postulate to be a result of error-prone DNA repair. Supported by NIH grants CA107972 to SC and ES09961 and ES05304 to SRP and PhRMA foundation to GC.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 464.
A note on the endogeneity of attacker and defender roles in asymmetric conflicts
Authors: Hannes Rusch, Robert Böhm
Journal: Behavioral and Brain Sciences (2019)

Abstract We argue that the roles of attacker and defender in asymmetric intergroup conflict are structurally ambiguous and their perception is likely to be subjectively biased. Although this allows for endogenous selection into each role, we argue that claiming the role of the defender likely is more advantageous for conflict participants.
Abstract #832: Resistance is an inappropriate concept for biological drug such as trastuzumab
Authors: Manuela Campiglio, Andrea Balsari, Elisa Ferri, Marco Sandri, Rosaria Bufalino, Sylvie Menard, Elda Tagliabue
Journal: Cancer Research (2009)

Development of novel therapies specifically targeting key molecular events responsible of malignant phenotype arise the problem to update selection criteria of patient population most likely to benefits and to define the readout of the clinical benefits. To date, the first issue can be apply to few molecules, i.e. ER and HER2, since selection of patients highly expressing targets define the population will benefits of the treatments. For most molecular targeted drugs, dependency of targeted expression is not sufficient to define population that can achieved responses. The second issue considered that these novel therapies have no primarily cytotoxic action and, therefore, they are not expected to results in tumor shrinkage, invalidating the response criteria used till now to define clinical benefits to chemotherapy. Therefore, we need to define the therapy end-points oncologist should used to interpret patients\#8217; response to new therapy and verify weather the concept of resistance can be apply to these molecular drugs. To address this aim we analyzed 440 consecutive HER2-positive metastatic breast carcinoma patients treated with trastuzumab from 2000/2001 in 22 Italian oncologic centers. According to Recist criteria, responses (complete plus partial) to trastuzumab-based treatment were achieved in 189/440 (43%), with 102/189 (54%) complete responders. Patients who responded to treatment survived significantly longer than did non-responders (chi-square of log-rank test = 20.62, p  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 832.
Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.
Authors: Merete Bjørnslett, Alv A. Dahl, Øystein Sørebø, Anne Dørum
Journal: Journal of Clinical Oncology (2013)

9569 Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.
Collective action problems in offensive and defensive warfare
Authors: Agner Fog
Journal: Behavioral and Brain Sciences (2019)

Abstract A collective action problem exists not only in offensive warfare, but also in defensive situations. The collective action problem is dealt with in the same way in offensive and defensive warfare: by strong leadership, discipline, rewards and punishments, strong group identification, strict religiosity, and intolerance of deviants. This behavior is explained in terms of evolutionary psychology.
Roles of HIFs and VEGF in angiogenesis in the retina and brain
Authors: Amir Rattner, John Williams, Jeremy Nathans
Journal: Journal of Clinical Investigation (2019)

Vascular development in the mammalian retina is a paradigm for CNS vascular development in general, and its study is revealing fundamental mechanisms that explain the efficacy of antiangiogenic therapies in retinal vascular disease. During development of the mammalian retina, hypoxic astrocytes are hypothesized to secrete VEGF, which attracts growing endothelial cells as they migrate radially from the optic disc. However, published tests of this model using astrocyte-specific deletion of Vegf in the developing mouse retina appear to contradict this theory. Here, we report that selectively eliminating Vegf in neonatal retinal astrocytes with a Gfap-Cre line that recombines with approximately 100% efficiency had no effect on proliferation or radial migration of astrocytes, but completely blocked radial migration of endothelial cells, strongly supporting the hypoxic astrocyte model. Using additional Cre driver lines, we found evidence for essential and partially redundant actions of retina-derived (paracrine) and astrocyte-derived (autocrine) VEGF in controlling astrocyte proliferation and migration. We also extended previous studies by showing that HIF-1α in retinal neurons and HIF-2α in Müller glia play distinct roles in retinal vascular development and disease, adding to a growing body of data that point to the specialization of these 2 hypoxia-sensing transcription factors.
Scotland’s efforts to improve the lives of trainee doctors
Authors: Andrew C Pearson, John R Colvin
Journal: BMJ (2019)

We recognise many of the challenges mentioned by Whitehouse,1 particularly that high quality rotas are not guaranteed by relying solely on the contractual framework—“contractual compliance.”

The Scottish government has developed a quality improvement process for the working environment of trainee doctors—the professionalism compliance analysis tool (PCAT). It has three domains: patient centred safe care, quality of training, and trainee health and wellbeing. The local team (trainee, …
From risk to survival: chromosome 3p aberrations in renal cell carcinoma
Authors: Yohei Horikawa, Xin Lin, Yimin Zhu, Christopher Wood, Pheroze Tamboli, Xifeng Wu
Journal: Cancer Research (2007)

146  Purpose: Chromosome 3p aberration is the most frequently mutated genetic region in clear cell renal cell carcinoma (RCC). Recent studies suggested that, besides the VHL gene, loss of heterozygosity (LOH) at 3p14.2-3p21 that may harbor other potential tumor suppressor genes might be an early event in RCC carcinogenesis. However, the tumorigenic significance of these genetic changes in RCC remains unknown. Benzo[a]pyrene diol expoxide (BPDE), a main metabolic product of the tobacco constituent bezo[a]pyrene, may induce chromosomal aberrations in genetic loci including 3p. We hypothesized that BPDE-induced lymphocytic 3p aberrations are biomarkers of genetic susceptibility to RCC and such aberrations in tumor tissues may also predict clinical outcome of RCC therapeutic interventions. Methods: Peripheral blood lymphocyte (PBL) cultures from 107 RCC patients and 108 matched healthy controls were treated with 2 μM BPDE for 24 hours. The 3p25, 3p21.3, 3p14.2 and 3q13 (a control locus) aberrations were assessed by fluorescence in situ hybridization (FISH). One thousand lymphocyte interphases were scored for each sample. In addition, we analyzed 67 tumor tissues using 12 microsatellite markers spanning 3p12-3p25. These data were evaluated for associations with clinicopathological features and prognosis of RCC. Results: RCC patients exhibited significantly higher number of 3p aberrations than controls in 3p25 (cases vs. controls [mean±standard deviation]: 43.7±1.2 vs. 36.7±1.4, P=0.0005), 3p21.3 (case vs. control: 43.5±8.4 vs. 38.3±7.1, P
Annals Graphic Medicine - Asian Flush
Authors: Sarah Jiang, Denys Bastov, Archana Bharadwaj, Eric R. Gross
Journal: Annals of Internal Medicine (2019)

Web Exclusives20 August 2019Annals Graphic Medicine - Asian FlushFREESarah Jiang, BS, Denys Bastov, BS, Archana Bharadwaj, BS, MPH, and Eric R. Gross, MD, PhDSarah Jiang, BSStanford University, Stanford, California (S.J., D.B., A.B., E.R.G.)Search for more papers by this author, Denys Bastov, BSStanford University, Stanford, California (S.J., D.B., A.B., E.R.G.)Search for more papers by this author, Archana Bharadwaj, BS, MPHStanford University, Stanford, California (S.J., D.B., A.B., E.R.G.)Search for more papers by this author, and Eric R. Gross, MD, PhDStanford University, Stanford, California (S.J., D.B., A.B., E.R.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0025 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Stanford University, Stanford, California (S.J., D.B., A.B., E.R.G.)Financial Support: This work is supported by University of California Tobacco Related Disease Research Program 26IP-0038 and NIH NIGMS GM119522 (Dr. Gross).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0025.Author/Illustrator Information: Sarah Jiang has a BS in human biology from Stanford University, and this is her first comic (e-mail, [email protected]com). Denys Bastov is a freelance illustrator and designer at Oculus (e-mail, [email protected]com). Archana Bharadwaj, MPH, CHES, is a second-year medical student at Central Michigan University College of Medicine (e-mail, [email protected]edu). Eric R. Gross, MD, PhD, and the Gross Lab at Stanford University are developing precision medicine for Asians (e-mail, [email protected]edu).This article was published at Annals.org on 13 August 2019.Written by Sarah Jiang, Archana Bharadwaj, and Eric R. Gross, and illustrated by Denys Bastov. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 August 2019Volume 171, Issue 4Page: W13-W26KeywordsDisclosureHealth carePrecision medicine ePublished: 13 August 2019 Issue Published: 20 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pharmacokinetics and efficacy of pegfilgrastim as hematopoietic support for dose-dense every-2-week chemo-immunotherapy with R-CHOP as first-line therapy in elderly patients with diffuse large B cell lymphoma
Authors: U. J. Mey, A. Maier, R. Kleinschmidt, C. Ziske, H. Forstbauer, G. A. Banat, M. Gorschlueter, H. Popp, I. G. Schmidt-Wolf, A. G. Glasmacher
Journal: Journal of Clinical Oncology (2006)

17531 Background: Recently, 6 cycles of R-CHOP-14 have been recommended as reference standard for elderly patients with diffuse large B cell lymphoma (Pfreundschuh, 2004). Pegfilgrastim as a pegylated form of G-CSF has been shown to provide rapid neutrophil recovery and facilitate dose dense chemotherapy schedules with a single administration per chemotherapy cycle. The aim of this study was to analyze pharmacokinetics of a single fixed dose of 6 mg of pegfilgrastim per cycle in a homogenous group of elderly patients with diffuse large B cell lymphoma treated with R-CHOP as first-line therapy in two-weekly intervals. Methods: Ten patients with diffuse large B cell lymphoma between the age of 60 and 80 years received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after the administration of R-CHOP chemo-immunotherapy, repeated for 6 to 8 cycles in two-weekly intervals. Pegfilgrastim plasma levels as well as absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles. Incidence and duration of grade 3/ 4 neutropenia, depth of neutrophil nadir and incidence of febrile neutropenia were assessed. Results: Median age was 73.4 years. A single 6 mg injection of pegfilgrastim 24 h after the administration of CHOP was effective to allow neutrophil recovery in 69 of 70 (98.6%) two-weekly treatment cycles. Median absolute neutrophil nadir was 0.38 G/l on day 9. Grade 3/ 4 granulocytopenia occurred in all ten patients. Mean duration of grade 3/4 neutropenia (&lt; 1.0 G/l) was two days. Febrile neutropenia occurred in one patient. Plasma levels of pegfilgrastim remained elevated during the neutropenic phase. At the start of hematologic recovery, plasma concentrations of pegfilgrastim decreased rapidly as a result of clearance by the neutrophils. Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application. Conclusions: A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to safely allow two-weekly drug administration in previously untreated elderly patients with diffuse large B cell lymphoma. [Table: see text]
Identification of antibody responses induced in patients with metastatic hormone-refractory prostate cancer (HRPC) treated with a GM-CSF-transduced allogeneic prostate cancer immunotherapy
Authors: Thomas Harding, Minh Nguyen, Kathryn Koprivnikar, Guang Huan-Tu, Karin Jooss
Journal: Cancer Research (2007)

4139  In a Phase 2 study of GVAX immunotherapy for hormone-refractory prostate cancer (Study G-0010), patients were immunized with two allogeneic prostate cancer cell lines (PC-3 and LNCaP) genetically modified to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Immunotherapy activity at the dose currently employed in an on-going phase III study was demonstrated by both biochemical and radiologic endpoints and treated patients displayed an estimated median survival time that compared favorably to that published for docetaxel chemotherapy, the standard of care for these patients (2006 American Society of Clinical Oncology (ASCO) Prostate Cancer Symposium, San Francisco, CA, Abstract 254). We have evaluated prostate cancer immunotherapy-derived antibody responses in patients displaying a survival advantage using serological analysis of gene expression (SEREX) technology to identify cellular proteins eliciting antibody responses following immunotherapy. Lambda gt11 phage expression libraries were generated from LNCaP and PC-3 cells and were immuno-screened with sera from 8 patients post-immunotherapy. Immuno-reactive phage clones were identified by sequencing and then screened with pre-treatment sera to determine antibody responses that were specifically induced upon immunotherapy treatment. Induced antibody responses were then examined in an expanded cohort of GVAX-treated patients (n=14) to determine frequency and selectivity. From this analysis we identified 40 LNCaP/PC-3 derived-proteins to which 2 or more patients from the 14 examined had an induced antibody response. Following immunotherapy, induced antibody responses observed at high frequency included patient IgG recognizing PC-3 derived human leukocyte antigen A24 (HLA-A24; 62% of patients), the actin-binding protein filamin B (actin binding protein 278; 58%) and NSFL1 (p97) cofactor (p47) (NSFL1C; 50%). Twenty antigens from this list of high-frequency antibody responses were then selected for ELISA development to allow quantification of response in a high-through put manner. Using patient sera from G-0010 and an earlier phase 2 clinical trial of GVAX immunotherapy in HRPC patients (Study G-9803; Simons J et al. (2006) Clin Cancer Res. 12:3394-401) we examined antibody induction following GVAX prostate immunotherapy treatment to the high frequency antigens by ELISA analysis. Results from this analysis will be presented, in addition to correlation of response to clinical response parameters.
Comparison between dietary intake of cancer survivors and that of noncancer controls
Authors: Yeong-Ah Cho, Hyung-Sook Kim, Gyung-Ah Wie, Jae-Moom Bae, Byung-Ho Nam, Hyo-Jee Joung
Journal: Cancer Research (2007)

3424  The purpose of this study was to compare the dietary intake of cancer survivors with that of noncancer controls and to find association between dietary factors and survival time in cancer survivors. The study participants underwent a health examination at the National Cancer Canter from September 2004 to March 2006. Cancer survivors (n=140) were those who had history of cancer and noncancer controls (n=560) were those who were matched with cancer survivors by sex and age. There were no differences in life styles (drinking, smoking, physical activity, complementary and alternative medicine) between the two groups. Comparing dietary intake between the two groups, there were no differences in energy intake. But intake of vegetable protein, vegetable fat, crude fiber, calcium, phosphorus, iron, vitamin B6, vitamin C and folate was higher in cancer survivors compared to control group (p=0.001, p=0.026, p
Genomic sequencing of a national emm66 group A streptococci (GAS) outbreak among people who inject drugs and the homeless community in England and Wales, January 2016–May 2017
Authors: Laura Bubba, Nick Bundle, Georgia Kapatai, Roger Daniel, Sooria Balasegaram, Charlotte Anderson, Vicki Chalker, Theresa Lamagni, Colin Brown, Derren Ready, Androulla Efstratiou, Juliana Coelho
Journal: Journal of Infection (2019)
Graft-Versus-Host Disease Impairs the Histone Methyltransferase Dot1l-Regulated Reconstitution of Plasmacytoid Dendritic Cells in Mice Undergoing Allo-HSCT
Authors: Yuanyuan Tian, Lijun Meng, Hongshuang Yu, Elizabeth O. Hexner, Leizhen Zheng, Shaoyan Hu, Yanyun Zhang, Yi Zhang
Journal: Blood (2018)