tbuckley/cabot-search huggingface dataset:
Wilms’ tumor gene 1 (WT1) aberrations in testicular germ cell tumors (TGCTs).
Authors: Ludmila Boublikova, Violeta Bakardjieva-Mihaylova, Karolina Skvarova Kramarzova, Daniela Kuzilkova, Tomas Buchler, Pavel Dusek, Marek Grega, Blanka Rosova, Zdenka Vernerova, Petr Klezl, Roman Zachoval, Michal Pesl, Marek Krolupper, Martina Kubecova, Vladimira Stahalova, Marek Babjuk, Jitka Abrahamova, Roman Kodet, Jan Trka
Journal: Journal of Clinical Oncology (2015)

4534 Background: Wilms’ tumor gene 1 (WT1) is a transcription factor essential for normal development of the urogenital system and male gonadal formation. Its alterations have been found in Wilms’ tumor, other malignancies and testicular dysgenesis syndromes. We studied WT1 aberrations to address its role in the pathogenesis of testicular germ cell tumors (TGCT). Methods: In fresh-frozen samples of 85 TGCT (48 seminomas, 37 non-seminomas), 3 stromal tumors and 88 non-neoplastic controls, expression of total WT1 and its four main isoforms was quantified by qPCR. WT1 mutations were detected by direct and next-generation sequencing (NGS). The presence of WT1 protein was evaluated by standard immunohistochemistry. Results: The total WT1 expression was significantly lower (1 log) in TGCT than in the controls and stromal tumors (Kruskal-Wallis p < 0.0001), and was lower in seminomas than non-seminomas. Testicular tissue surrounding TGCT and containing in situ lesions expressed similar WT1 levels like other controls. WT1 isoforms lacking the exon 5 ([EX5-] isoforms A and C) were highly overexpressed in TGCT and stromal tumors in comparison with controls (Kruskal-Wallis, p < 0.0001). The isoform D, containing both main splice sites, was down-regulated in the tumors and this altered expression pattern was independent of total WT1 expression. Direct sequencing of exon 7 and 9 (with clustered hot-spots) could identify only 2 types of SNPs – synonymous rs16754 (31% of TGCT) and intronic rs5030274 (2%). By NGS however, 1 – 3 mutations in WT1 newly occurring in TGCT and not present in the paired controls were found in 59% of 22 analyzed cases. Staining for WT1 protein was positive in controls and undetectable in TGCT cells. Conclusions: The finding of total WT1 down-regulation in TGCT with the difference between seminomas and non-seminomas, the alteration of the isoform pattern with a pronounced shift to [EX5-] variants in TGCT independent of total WT1 levels, and the new occurrence of WT1 mutations in a high proportion of TGCT samples support the role of WT1 as a local tumor-suppressor gene in testicular tissues. Supported by grants IGA NT/12414-5, GAUK56413, UNCE204012 and CDRO00064203FNM
ECOG Performance Status Affects Efficacy, but Not Safety, of Lenalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (MM009/010 Sub-Analysis).
Authors: Asher A. Chanan-Khan, Meletios Dimopoulos, Donna Weber, Marta Olesnyckyj, Zhinuan Yu, Jerome Zeldis, Robert Knight, Jesus F. San Miguel
Journal: Blood (2007)
Social, biological, and tumor characteristics of 139 African American (AA) women with newly diagnosed breast cancer in Chicago.
Authors: S. J. Gehlert, B. N. Polite, T. A. Grushko, T. Cipriano, S. Charoenthammaraksa, Z. Franklin, S. D. Conzen, M. McClintock, O. I. Olopade
Journal: Journal of Clinical Oncology (2010)

6064 Background: Previous work by our group has shown that social isolation, social stress, and increased vigilance are associated with larger and more aggressive mammary tumors in animal models. In this study, we seek to better characterize these relationships among AA women with newly diagnosed breast cancer. Methods: AA women newly diagnosed with breast cancer were recruited from 3 hospitals in the Chicago area from 2005-2009. Women underwent in-home interviews which focused on psychosocial functioning and social networks. In addition, 4 daily salivary cortisol samples were self-collected over a 3 day period. Additional neighborhood and community level data were collected using direct neighborhood mapping and geocoded information. Tumor samples were analyzed by IHC for ER, PR, HER2 and glucocorticoid receptor (GR) status. Results: 139 women were included in the sample. Median age 52. Stage: 5%DCIS, 29% I, 31% II, 30% III, 5% IV. 34% were triple negative (TN) and of 71 evaluable cases, 64% were GR+. GR status was associated with invasive cancer (69% invasive cancers GR+ vs. 29% of DCIS cases). 32% of pts were clinically depressed, 68% had moved in the previous 10 years, 31% had suffered a sexual assault, and loneliness scores were higher than a same-race Cook County control sample. In multivariate modeling, number of sexual assaults in the neighborhood was associated with estrogen-receptor (ER) negative status (b = -0.189, p < 0.05) and poorer histological grade of tumor (b = 0.143, p < 0.05). Felt loneliness was associated with HER2neu receptor negative status (b = -0.096, p < 0.05). 67% of patients had no diurnal cortisol variation (flat response) and cortisol group (flat versus circadian) was significantly associated with the individual factors mentioned above. Conclusions: AA women have high rates of TN tumors and GR+ tumors which is being recognized as an additional poor prognostic factor. They also suffer from numerous social stressors which appear to be linked to tumor biology and a flattened stress response. Continued work on understanding the interaction of these social variables and stress response on tumor biology and adherence to therapy is needed. No significant financial relationships to disclose.
Eribulin mesylate pharmacokinetics in patients with hepatic impairment.
Authors: P. Witteveen, S. Marchetti, M. Mergui-Roelvink, L. Reyderman, W. Copalu, J. Wanders, A. Jenner, G. Edwards, J. H. Schellens, E. E. Voest
Journal: Journal of Clinical Oncology (2010)

2582 Background: The nontaxane microtubule dynamics inhibitor, eribulin mesylate (E7389), has a novel mechanism of action and is in development for the treatment of metastatic breast cancer, lung cancer, and other solid tumors. The objective of this study was to evaluate the effect of hepatic impairment on the pharmacokinetics of eribulin. Methods: This phase I, open-label, parallel-group study recruited adult patients with advanced solid tumors that progressed after standard therapy or for which no standard therapy existed. Patients with normal hepatic function (n=6), mild (Child-Pugh A, n=7) or moderate (Child-Pugh B, n=4) hepatic impairment received eribulin mesylate on day 1 at respective intravenous (IV) doses of 1.4, 1.1, and 0.7 mg/m2 respectively. Plasma samples were collected over 168 hr post dose for pharmacokinetic analysis. Safety was also assessed. Results: Hepatic impairment decreased clearance (4.57, 2.75, and 1.96 L/hr for normal, mild and moderate hepatic impairment, respectively) and prolonged elimination half-life (36.1, 41.1, 65.4 L/hr for normal, mild and moderate hepatic impairment). The mean dose- normalized Cmax for eribulin was comparable between patients with normal and mildly impaired hepatic function (72 vs. 84 ng/mL/mg, ratio estimate 1.1 [90% CI 0.8-1.6]), but moderate hepatic impairment increased Cmax 1.5-fold (111 ng/mL/mg, 90% CI 1.0-2.2). Eribulin exposure was increased in patients with mild and moderate hepatic impairment. The mean dose-normalized AUC(0-∞) increased 1.7-fold (420 ng.hr/mL/mg, 90% CI 1.2-2.7) and 2.8-fold (720 ng.hr/mL/mg, 90% CI 1.7-4.5), compared with patients with normal hepatic function (229 ng.hr/mL/mg). Overall, the most common treatment-emergent adverse events (TEAEs) were alopecia (n=7), nausea (n=5) and fatigue (n=4). AEs probably related to treatment included neutropenia (n=3) and peripheral neuropathy (n=1). Most of the former (3 of 4) resolved without dose reduction. The highest incidence of AEs was reported in patients with mild hepatic impairment. No deaths, treatment-related serious AEs, or discontinuations were reported. Conclusions: Eribulin exposure increased with decreasing hepatic function. Eribulin was generally safe and well tolerated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai
GW26-e4513 Histone demethylase JMJD2A inhibition attenuates neointimal hyperplasia in the carotid arteries of balloon-injured diabetic rats via transcriptional silencing: Inflammatory gene expression in vascular smooth muscle cells
Authors: Qi Hu, Jing Zhang, Xiaolin Wu, Changwu Xu, Xiaorong Hu, Jian Yang, Jing Chen, Hong Jiang
Journal: Journal of the American College of Cardiology (2015)
GW26-e4557 Allocrytopine attenuates cardiac transmural dispersion of repolarization and protects ischemia reperfusion induced arrhythmias in rabbits
Authors: Yicheng Fu, Ying Zhao, Yu Zhang, Zhongqi Cai, Qing Dan, Xi Chen, Tong Yin, Yang Li
Journal: Journal of the American College of Cardiology (2015)
Study casts more doubt on weekend effect
Authors: Jacqui Wise
Journal: BMJ (2016)

New research that took into account whether patients came to hospital by ambulance shows that much of the “weekend effect” identified in previous studies is likely to be explained by variation in severity of illness.1

The study, published in the BMJ Quality & Safety , found that a higher proportion of patients admitted to hospital at the weekend arrived by ambulance than during weekdays and that this was a marker for illness severity.

Previous studies, including one published in The BMJ ,2 had shown higher death rates among patients admitted at weekends than …
Inflammatory versus grade III and IV breast cancer and effect of mammogram
Authors: T. M. Islam, C. S. Ferdous
Journal: Journal of Clinical Oncology (2008)

1545 Background: Inflammatory breast cancer (IBC) is an aggressive manifestation of primary breast cancer. Demographic characteristics and survivality were compared between IBC and grade III and IV breast cancer using SEER data. Methods: SEER dataset were generated according to the manual. After excluding male gender, missing information, sarcomas, lymphoma and/or breast malignancy with different histologic origin, 1,430 IBC and 32,752 non-IBC grade III and IV breast cancer patients were used in the final analysis. In a subpopulation analysis IBC patients were dichotomized into patient who were diagnosed before and after year 2000. Results: There were no significant difference in mean age and white population between IBC and non-IBC patients. In IBC group 45% of patients were married whereas 56%of non-IBC patients were married (p value <0.001). Prevalence of estrogen and progesterone receptor status where very similar between the two groups. Prevalence of metastasis in IBC is much more higher (95.2%) than non-IBC (4.5%) patients. 5-year survivality was 29% for IBC and 74% for non-IBC patients. In a Cox regression model adjusted for age (continuous), race (white vs. non-white), marital status (married vs. not married), estrogen receptor status (positive vs. negative) and progesterone receptor status (positive vs. negative), IBC remained the only significant risk factor with hazard ratio of 4.12 (95% CI: 3.86, 4.41). There is no difference in the 5 year survivality among the IBC patients who were diagnosed before (N=884) and after (N=546) year 2000 (29% and 32% respectively and log-rank p value of 0.85). In a separate Cox regression model, for this sub-population, adjusted for same variables, risk of dying due to IBC was same (hazard ratio 1.00, 95% CI: 0.86, 1.16) between patients who were diagnosed before and after year 2000. Conclusions: IBC has significantly low 5-year survivality as compared to grade III and IV breast cancer patient. Mammogram in this population failed to increase survivality by early diagnosis. No significant financial relationships to disclose.
Synthesis and Reversal Efficacy of Magnetic Nanoparticles Coloaded with Daunorubicin and 5-Bromotetrandrin
Authors: Bao-An Chen, Jun Wang, Xiao-hui Cai, Feng Gao, Jian Cheng, Ping-shen Chen, Yu Zhang, Meng Tang, Jia-hua Ding, Wen Bao
Journal: Blood (2010)
Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion
Authors: Srinika Ranasinghe, Pedro A. Lamothe, Damien Z. Soghoian, Samuel W. Kazer, Michael B. Cole, Alex K. Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M. Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M. Allen, Hendrik Streeck, Daniel E. Kaufmann, Louis J. Picker, John W. Kappler, Bruce D. Walker
Journal: Immunity (2016)

CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number
Authors: Jonathan J Lyons, Xiaomin Yu, Jason D Hughes, Quang T Le, Ali Jamil, Yun Bai, Nancy Ho, Ming Zhao, Yihui Liu, Michael P O'Connell, Neil N Trivedi, Celeste Nelson, Thomas DiMaggio, Nina Jones, Helen Matthews, Katie L Lewis, Andrew J Oler, Ryan J Carlson, Peter D Arkwright, Celine Hong, Sherene Agama, Todd M Wilson, Sofie Tucker, Yu Zhang, Joshua J McElwee, Maryland Pao, Sarah C Glover, Marc E Rothenberg, Robert J Hohman, Kelly D Stone, George H Caughey, Theo Heller, Dean D Metcalfe, Leslie G Biesecker, Lawrence B Schwartz, Joshua D Milner
Journal: Nature Genetics (2016)
Identification of a new cancer/testis antigen from small cell lung cancer
Authors: M. Lee, K. Kim
Journal: Journal of Clinical Oncology (2007)

21182 Background: Serological analysis of recombinant cDNA expression libraires has led to identification of tumor antigens, which are considered promising candidates for early detection and immunotherapy. They are recognized by the immune system of cancer patients including small cell lung cancer (SCLC) patients. Methods: SEREX method was used to screen normal testis and NCI-H889 cell line cDNA library with serum obtained from a SCLC patient who has survived over 50 months. Also SADA test was done to SCLC patients and normal serum. Results: Immunoscreening of libraries with the selected serum led to the isolation of 58 (SCLC-1 through SCLC-58) and 18 (SCLCT-1 and SCLCT-18) independent antigens from NCI-H889 and testis respectively. Of these SCLCT-1 mRNA was expressed strongly only in normal testis. According to the SADA test, SCLCT-1 was only found in SCLC patients’ sera (34%). Conclusions: On the basis of its immunogenecity in SCLC patients’ sera, and its restricted mRNA expression profile, SCLCT-1 can be considered a novel CT antigen. No significant financial relationships to disclose.
GW26-e4818 The L-carnitine Ameliorates Pulmonary Arterial Hypertension by Improving Energy Metabolism Dysfunction of Right Ventricular Failure
Authors: Yan Liu, Xiaojian Wang, Qianqian Liu, Yi Yan, Shuhui Yang, Suqi Li, Shenshen Huang, Zhicheng Jing
Journal: Journal of the American College of Cardiology (2015)
Do specialized oncology units improve the detection and management of pain?
Authors: G. R. Goldberg, A. Litke, R. S. Morrison
Journal: Journal of Clinical Oncology (2006)

6084 Background: Pain is a common complaint of cancer patients and has a significant impact on quality of life. The objective of this study was to compare pain management for cancer patients admitted to dedicated oncology vs. general medicine/surgery units. Methods: Design: Secondary analysis of data obtained from a controlled clinical trial evaluating a series of interventions to improve pain outcomes conducted from 4/2002–2/2003. Setting: 1,171 bed hospital. Patients: 445 hospitalized adult oncology patients; 239 patients admitted to a specialized oncology unit, 206 patients admitted to general medicine/surgery units. Main outcome measures: Pain assessment and severity, analgesic prescribing. Analysis: T tests and chi square were used to compare patient characteristics. Hierarchical linear modeling (HLM) was used to explore the effect of a specialized oncology unit on pain assessment, severity, and analgesic and laxative prescribing. Results: The two groups did not differ significantly in patient characteristics. Mean age was 59 years, 56% were men, 61% were white, 79% had solid tumors. In multivariate analysis, patients admitted to a specialized oncology unit had significantly less pain (mean pain score for patients on oncology unit was 1.24 vs 1.68 for non-oncology unit; parameter estimate = −0.42; p&lt;0.01). There were no significant differences in the frequency of nursing assessment of pain, opiate prescribing, or laxative prescribing for those patients receiving opioids. Conclusion: In multivariate analysis, admission to a specialized oncology unit was associated with significantly less reported pain. These findings have implications for structuring medical units for patients at high risk for pain. No significant financial relationships to disclose.
Allogeneic Stem Cell Transplantation with Dose-Reduced Conditioning in Relapsed Follicular and Mantle Cell Lymphoma - A Prospective Phase II Trial of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Martin H. Dreyling, D.-W. Beelen, Michael Schleuning, Anthony D. Ho, Martin Gramatzki, B. Glas, Michael Pfreundschuh, Martin Wilhelm, Norbert Schmitz, Hans-Jochem Kolb, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2007)
A Phase 2 Multicenter Study of Continuous Dose Lenalidomide in Relapsed or Refractory Classical Hodgkin Lymphoma
Authors: Todd A. Fehniger, Sarah Larson, Kathryn Trinkaus, Marilyn J. Siegel, David D. Hurd, Kristie A. Blum, Andre Goy, Timothy S. Fenske, Amanda Cashen, Nina D. Wagner-Johnston, Kenneth R. Carson, Nancy L. Bartlett
Journal: Blood (2012)
The prognostic significance of supradiaphragmatic lymphadenopathy identified on preoperative computed tomography scan in patients undergoing primary cytoreduction for advanced stage epithelial ovarian cancer
Authors: V. Kolev, S. Mironov, O. Mironov, C. Moskowitz, N. M. Ishill, G. J. Gardner, D. A. Levine, H. Hricak, R. R. Barakat, D. S. Chi
Journal: Journal of Clinical Oncology (2009)

e16512 Background: It has been hypothesized and shown in animal studies that the supradiaphragmatic lymph nodes serve as the principal nodes for lymphatic drainage of the entire peritoneal cavity. The purpose of this study was to determine the prognostic significance of enlarged supra-diaphragmatic nodes noted on preoperative computed tomography (CT) scan in patients with advanced epithelial ovarian cancer (EOC). Methods: We performed a retrospective chart review of all patients (pts) with FIGO stage III and IV EOC who had preoperative CT scans of the supradiaphragmatic region and primary cytoreductive surgery at our institution between 1997 and 2004. All scans were retrospectively reviewed by one board-certified radiologist (SM). To evaluate survival, Kaplan-Meier methods were used, with log rank Pvalues for comparisons. Results: A total of 212 eligible pts who underwent attempted primary cytoreduction followed by platinum-based systemic chemotherapy were identified for evaluation. With a median follow-up time of 52 mos, there were 135 deaths and a median overall survival of 48 mos (95% CI: 44–53). Of the 212 pts, 44 (21%) had supradiaphragmatic adenopathy with nodes &gt;1 cm, while 168 (79%) did not have adenopathy in this distribution. None of the 44 pts with adenopathy had the enlarged nodes removed at primary cytoreduction. The median survival was 49 mos for pts with and 48 mos for patients without adenopathy (p = 0.46). In total, 155 (73%) patients underwent optimal cytoreduction (residual disease ≤ 1 cm). In the optimally cytoreduced pts, the median survival for the 125 pts without supradiaphragmatic adenopathy was 52 mos (95%CI: 45–59) compared to 51mos (95%CI: 41–58) for the 30 pts with supradiaphragmatic adenopathy (p = 0.33). Conclusions: Although a previous study has shown that supradiaphragmatic adenopathy was associated with poorer overall survival in EOC patients, our study did not confirm these findings. In our study, enlarged supradiaphragmatic nodes noted on preoperative CT scan did not have significant prognostic impact and therefore their clinical significance remains uncertain. No significant financial relationships to disclose.
Alpha-fetoprotein up-regulated the expression of c-Src in hepatoma cells is PTEN/AKT signaling pathway dependent or independent.
Authors: M. Li, X. Xie, S. Fu, M. Zhu, G. Li
Journal: Journal of Clinical Oncology (2010)

e21061 Background: The evidences indicated that alpha-fetoprotein (AFP) harbors a function to promote the proliferation of hepatoma cells, but the role of AFP regulates the expression of oncogenes was unclear. The present study explored the effects of AFP on the expression of c-Src in human hepatoma cells. Methods: Human hepatoma cells line, Bel 7402 and HepG2 (AFP-producing), or HLE (non-AFP-producing) were selected for performing the investigation; Constructed siRNA vector to knockdown the expression of AFP or PTEN, and full length cDNA of AFP gene was inserted into pcDNA3.1 vector (named pcDNA3.1-afp) for the expression of AFP; The expression of Src and AKT (phosphorylation of AKT Ser473) were measured by Western blot; Interaction of AFP with PTEN was analyzed by co- immunoprecipitation (Co-IP); Chromatin immunoprecipitation (ChIP) were applied to investigate the interaction of AFP with Src gene promoter. Results: Co-IP indicated that AFP has a property to interact with PTEN in Bel 7402 or HepG2 cells, and the same effect also showed when HLE cells were transfected with pcDNA3.1-afp; The expression of AKT Ser473 phosphorylated and Src were decreased concomitant with blocked the expression of AFP by siRNA-AFP in Bel 7402 or HepG2 cells, but HLE cells was transfected with pcDNA3.1-afp could enhance the expression of AKT Ser473 phosphorylated and Src, while co-treatment with Ly294002, the expression of Src was partial inhibited. Cotransfected siRNA-PTEN with pcDNA3.1-afp into HLE cells revealed the expression of Src was promoted, and Ly294002 could also partial repress this effect. ChIP analyzed indicated that AFP was able to interact with promoter of src. Conclusions: AFP has a characteristic to stimulate the expression of Src in hepatoma cells, these were first evidences to show that AFP up-regulated the expression of Src through activating the transducation of PTEN/AKT signaling pathway or directed binding to the promoter of src. No significant financial relationships to disclose.
Prospective functional classification of all possible missense variants in PPARG
Authors: Amit R Majithia, Ben Tsuda, Maura Agostini, Keerthana Gnanapradeepan, Robert Rice, Gina Peloso, Kashyap A Patel, Xiaolan Zhang, Marjoleine F Broekema, Nick Patterson, Marc Duby, Ted Sharpe, Eric Kalkhoven, Evan D Rosen, Inês Barroso, Sian Ellard, Sekar Kathiresan, Stephen O'Rahilly, Krishna Chatterjee, Jose C Florez, Tarjei Mikkelsen, David B Savage, David Altshuler
Journal: Nature Genetics (2016)
Avicins: A Novel Class of Anti-Myeloma Agents.
Authors: Nicholas Mitsiades, Ciaran J. McMullan, Vassiliki Poulaki, Joseph Negri, David C. Geer, Valsala Haridas, Nikhil C. Munshi, Jordan Gutterman, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Blood (2004)