tbuckley/cabot-search huggingface dataset:
Differential up-regulation of survivin/BIRC5 in esophageal adenocarcinoma compared with normal squamous epithelium.
Authors: U. Malhotra, A. H. Zaidi, A. Atasoy, T. Hoppo, A. F. Sanz, Y. Komatsu, T. Foxwell, K. S. Nason, J. D. Luketich, J. M. Davison, D. P. Normolle, B. A. Jobe, M. K. Gibson
Journal: Journal of Clinical Oncology (2011)

e14602 Background: Survivin, also known as BIRC5, inhibits apoptosis by interfering with caspase activation. High expression of survivin is seen in fetal tissues and various cancers. Published literature supports a role for survivin as a prognostic marker of squamous cell carcinoma of the esophagus, and as a predictor of progression from normal mucosa to Barrett’s metaplasia and ultimately adenocarcinoma. We evaluated survivin expression in paired normal and cancer tissues from patients with esophageal adenocarcinoma. We hypothesized that survivin shows differential upregulation in tumor versus normal squamous epithelium. Methods: Fresh frozen paired normal squamous epithelium and adenocarcinoma samples from 16 patients who underwent esophagectomy were evaluated after confirmation of diagnosis. RNA isolation was performed by using the RNeasy mini kit (Qiagen). Quantitative RT-PCR was performed for survivin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Survivin expression value for each sample was normalized to GAPDH expression and relative quantification done according to the delta Ct method.Survivin expression was compared between paired tumor and normal squamous epithelium by mixed effects ANOVA to test the null hypothesis that the median tumor to normal ratio equals 1. Results: Survivin was differentially upregulated (defined as ratio of expression in tumor to normal of >2) in 68.75% of cases. The median ratio of tumor to normal was 2.5, 95% CI (1.7, 4.5) with a p=0.0002 disproving the null hypothesis. The mean difference in survivin between tumors and paired normal squamous epithelium was 7.9 (95% CI: [5.9, 10.0], p<0.0001). Conclusions: Survivin is upregulated in the majority of patients with esophageal adenocarcinoma. Differential up-regulation in tumor underscores the significance of evaluating survivin as a potential predictive biomarker especially with availability of agents directed to this target. We plan to expand the patient cohort and correlate survivin expression with clinical outcome.
Circulating-free tumor DNA as a surrogate for determination of EGFR status: the Italian experience within the ASSESS study
Authors: N. Normanno, A. Morabito, S. Novello, D. Cortinovis, M.R. Migliorino, C. Pinto, R. Pasquale, A. Montanino, E. Capelletto, G. Tonini, P. Bidoli, D. Galetta, S. Ricciardi, M. Milella, B. Melotti, G. Romano, L. Crinò
Journal: Annals of Oncology (2015)
Abstract 2895: Phosphorylation of EZH2 at T416 by CDK2 promotes development of mammary tumors with basal-like phenotype
Authors: Lei Nie, Yongkun Wei, Adam LaBaff, Cheng-Chieh Yang, Weiya Xia, Longfei Huo, Dongping Liu, Yi-Hsin Hsu, Gabriel N. Hortobagyi, Jun Yao, Celina G. Kleer, Mien-Chie Hung
Journal: Cancer Research (2015)

Abstract Basal-like breast cancer, also referred to as triple negative breast cancer (TNBC) due to the lack of expression of ErbB2, PR, and ER alpha receptors, is considered to be one of the most aggressive breast cancers, which display high rates of tumor cell proliferation, metastasis, and post-surgical re-occurrence. This subtype of breast cancer presents a major challenge for breast cancer oncologists as currently there is no effective therapy available. Here, we show that Cyclin E and EZH2, the methyltransferase component of the polycomb repressive complex 2 (PRC2) are exclusively co-expressed in TNBC tumor tissues. We further show that CDK2, the only known enzymatic partner of Cyclin E, can phosphorylate EZH2 at T416 in vivo. CDK2-mediated modification of EZH2 at T416 leads to gain-of-function, enhancing its ability to promote breast cancer cell migration/invasion, expansion and self-renewal of tumor sphere in vitro, and tumor growth in vivo. In addition, our immunohistochemistry-staining of 247 primary breast tumor tissues validates that high EZH2/T416 phosphorylation correlates with poor survival in TNBC but not in non-TNBC patients. To further attest the oncogenic role of EZH2/T416 phosphorylation by CDK2 in vivo, we generated transgenic mice expressing EZH2T416D mutant, a mimicking phosphorylated form of EZH2, in mammary glands. In contrast to previously reported EZH2WT transgenic mice, which did not develop mammary tumors, our EZH2T416D-expressing mice developed malignant mammary tumor with basal-like and highly metastatic potential phenotypes. These genetic evidence revealed that CDK2/Cyclin E mediated site-specific phosphorylation of EZH2 is capable of inducing the basal-like/TNBC phenotype and maintaining cancer stem cell population of breast cancers so that the T416 phosphorylation of EZH2 might serve as a biomarker for TNBC prognosis and effective therapy. Citation Format: Lei Nie, Yongkun Wei, Adam LaBaff, Cheng-Chieh Yang, Weiya Xia, Longfei Huo, Dongping Liu, Yi-Hsin Hsu, Gabriel N. Hortobagyi, Jun Yao, Celina G. Kleer, Mien-Chie Hung. Phosphorylation of EZH2 at T416 by CDK2 promotes development of mammary tumors with basal-like phenotype. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2895. doi:10.1158/1538-7445.AM2015-2895
574. Lentivirus Pre-Packed with Cas9 Protein for Safer Gene Editing
Authors: Manjunath Swamy, Jang-Gi Choi, Ying Dang, Sojan Abraham, Hongming Ma, Hua Guo, Yujia Cai, Jacob Giehm Mikkelsen, Haoquan Wu, Premlata Shankar
Journal: Molecular Therapy (2016)

The CRISPR/Cas9 system provides an easy way to edit specific site/s in the genome and thus offers tremendous opportunity for human gene therapy for a wide range of diseases. However, one major concern is off-target effects, particularly with long-term expression of Cas9 nuclease when traditional expression methods such as plasmid/viral vectors are used. To overcome this limitation, we pre-packaged Cas9 protein (Cas9P LV) in lentiviral particles for transient exposure and showed its effectiveness for gene disruption in cells, including primary T cells expressing specific sgRNAs. We then constructed an "all in one" lentivirus to express sgRNAs in association with prepackaged Cas9 protein (sgRNA/Cas9P LV). We successfully edited CCR5 in TZM-bl cells by this approach. Using an sgRNA targeting HIV LTR, we also were able to disrupt HIV provirus in the J-LAT model of viral latency. Moreover, we also found that pre-packaging Cas9 protein in LV particle reduced off-target editing of chromosome 4:-29134166 locus by CCR5 sgRNA, compared to continued expression from the vector. These results show that sgRNA/Cas9P LV can be used as a safer approach for human gene therapy applications.
Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy
Authors: Ross E. Krasnow, Michael Drumm, Hannah J. Roberts, Andrzej Niemierko, Chin-Lee Wu, Shulin Wu, Jing Zhang, Niall M. Heney, Matthew F. Wszolek, Michael L. Blute, Adam S. Feldman, Richard J. Lee, Anthony L. Zietman, William U. Shipley, Jason A. Efstathiou
Journal: European Urology (2016)
Longitudinal cohort study of skeletal-related events (SRE) and long-term prognosis in patients with multiple myeloma (MM) with bisphosphonate-related osteonecrosis of the jaw (ONJ).
Authors: P. Varadarajan, S. Lee, J. J. Toro, D. Schneider, J. Chao, B. Neumon, B. Frye, D. J. Haile, C. O. Freytes
Journal: Journal of Clinical Oncology (2011)

e19645 Background: Nitrogen containing bisphosphonates (BIS) have been shown to decrease SRE and improve survival in patients with MM. BIS use has been tempered by the occurrence of ONJ. Little is known about the prognosis incidence of SRE in MM patients with ONJ. Could the development of ONJ be a biomarker of enhanced sensitivity to BIS, with reduced SRE and better survival? Methods: In this retrospective cohort study, 11 MM patients who met diagnostic criteria for ONJ between June 2005 and June 2010 were matched to 39 MM patients without ONJ from our institution’s database. Patients were matched based on age, stage, histology, gender, ethnicity, and performance status. Skeletal surveys were used to evaluate bone disease at the start of BIS infusions and during follow-up. SRE’s were defined as: a pathological fracture, surgery to treat pathological fractures, radiation to bone, spinal cord compression or hypercalcemia. SRE were recorded from start of BIS, events needed to be > 21 days apart to be counted. All data was censored at either death or last clinic visit. Results: ONJ patients were followed for median 4.3 ± 2.4 years, Controls 3.9 ± 2.1 years (p =0.6). Time from diagnosis to transplant was non significant (NS) between ONJ and controls. Diffuse vs. limited bone disease on skeletal survey at start of BIS was NS. ONJ patients got 20.8 ± 18.0 infusions of BIS, cases 25.6 ± 17.7 (p=0.4). Only one patient in the ONJ group died (9%), 14 of the 39 control patients died (36%) (p = 0.13). Odds ratio (OR) of death in the ONJ group was 0.179 (with 95% CI (0.021, 1.544). Log-rank test to examine overall survival between ONJ and control group tended to significance (p= 0.08). SMR (skeletal morbidity rate = SRE/ patient-year) was 0.1019 events/patient-year in ONJ patients (95% C.I. 0, 0.26) and was 0.1620 events/patient-yr in controls (95% C.I. 0.05, 0.26). The odds ratio for SRE in patients with ONJ was estimated to be 0.54 (95% C.I. 0.13-2.15) p-= 0.38. Conclusions: The low odds ratios of SRE and deaths in the ONJ group support the hypothesis that ONJ might mark for increased BIS sensitivity (and hence different prognosis), but small sample sizes underpower the result.
Rare Igh Translocations in Newly Diagnosed Multiple Myeloma (MM) Patients: Cytogenetic Characterization and Relevance on Prognosis
Authors: Giulia Marzocchi, Gaia Ameli, Annalisa Pezzi, Elena Zamagni, Federica Cavallo, Maria Teresa Petrucci, Anders Waage, Francesco Di Raimondo, Francesca Patriarca, Alessandro Rambaldi, Barbara Gamberi, Claudia Crippa, Sonja Zweegman, Vittorio Montefusco, Iolanda Vincelli, Massimo Offidani, Antonio Palumbo, Pieter Sonneveld, Michele Cavo, Nicoletta Testoni
Journal: Blood (2014)
Abstract 962: PA2G4 predicts poor prognosis in neuroblastoma patients and promotes neuroblastoma progression by enhancing MYCN protein stability
Authors: Jessica Koach, Bing Liu, Jessica L. Bell, Stefan Hüttelmaier, Tao Liu, Daniel R. Carter, Michelle Haber, Murray D. Norris, Jamie Fletcher, Belamy B. Cheung, Glenn M. Marshall
Journal: Cancer Research (2015)

Abstract MYCN oncogene amplification is found in one third of primary neuroblastoma at diagnosis, and correlates with poor prognosis. We identified Proliferation-associated protein 2G4 (PA2G4) as a binding partner for MYCN using co-immunoprecipitation and mass spectrometry. The long isoform of PA2G4 (p48) has a known oncogenic function, whereas the short isoform (p42) acts as a tumour suppressor. However, the role of PA2G4 in neuroblastoma and its link with MYCN is currently unknown. Using a panel of 11 human neuroblastoma cell lines and 477 patient tumour samples, we analysed the expression of PA2G4 by real-time PCR and Western blotting. We found that high expression of PA2G4 was a strong independent clinical predicator of poor survival and positively correlated with MYCN expression. Analysis of pre-cancerous ganglia cells from TH-MYCN neuroblastoma mouse model showed that PA2G4 mRNA was expressed 8-fold higher in ganglia from TH-MYCN transgenic homozygote, compared to wild-type mice. Chromatin immunoprecipitation showed MYCN binds to PA2G4 promoter to activate its transcription. Surprisingly, suppression of PA2G4 in neuroblastoma cell lines markedly reduced MYCN protein level. Cycloheximide-chase assay confirmed that PA2G4 increased MYCN protein stability, thus creating a positive forward feedback loop which we showed resulted from effects on pERK. Suppression of PA2G4 down-regulated pMDM2 and pAKT, leading to an increase in p53 expression. Furthermore, PA2G4 knockdown promoted retinoid induced neurite formation, reduced cell migration and colony formation. Importantly, the expression of MYCN was required for the effect of PA2G4 on colony formation. A small molecule inhibitor of PA2G4, WS6, significantly decreased neuroblastoma cell growth and PA2G4 and MYCN protein levels. PA2G4 is a novel MYCN-binding protein which increases MYCN protein stability and acts as an oncogenic co-factor in a forward feedback expression loop with MYCN, to drive MYCN protein levels to high thresholds even in the presence of MYCN amplification. Citation Format: Jessica Koach, Bing Liu, Jessica L. Bell, Stefan Hüttelmaier, Tao Liu, Daniel R. Carter, Michelle Haber, Murray D. Norris, Jamie Fletcher, Belamy B. Cheung, Glenn M. Marshall. PA2G4 predicts poor prognosis in neuroblastoma patients and promotes neuroblastoma progression by enhancing MYCN protein stability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 962. doi:10.1158/1538-7445.AM2015-962
283. Targeted Delivery of C/EBPα-Small Activation RNA (saRNA) by RNA Aptamer Inhibits the Growth of Pancreatic Ductal Adenocarcinoma (PDAC) In Vivo
Authors: Sorah Yoon, Kai-Wen Huang, Paul Mintz, Nagy Habib, John J. Rossi
Journal: Molecular Therapy (2015)

Transcriptional factor C/EBPα (CCAAT/enhancer-binding protein-a) is downregulated and silenced in pancreatic ductal adenocarcinoma (PDAC). In this study, we tested the feasibility of targeting promoter regions of transcriptional factor C/EBPα to induce transcriptional activation by small activation RNA (saRNA) for cancer therapeutics in PDAC. C/EBPα is known to up-regulate p21, a strong inhibitor of cell proliferation. C/EBPα-saRNA inhibited cell proliferation in PDAC. For the targeted delivery into cells, small structured single-stranded RNAs known as aptamers, recognizing targets specifically, were employed for the effective delivering vehicles. 2'-fluropyrimidine RNA aptamers (2'F-RNA) were selected to acquire nuclease resistance based on the whole cell SELEX. The cell internalization was evaluated through flow cytometry and confocal microscopy. The selected 2'F-RNA aptamers got internalized into a variety of pancreatic cancer cell lines. Human pancreatic cancer specimen histopathology and cell binding assays indicated that they recognized cancer cells specifically, not to normal cells. The conjugates, aptamer with C/EBPα-saRNA, were constructed for the targeted delivery. The conjugates escaped endosome and localized in nuclear. The conjugates of aptamer with C/EBPα-saRNA inhibited cell proliferation and upregulated gene expression. Xenograft mice model was used to test tumor cell growth inhibition in vivo throughout the transcriptional activation of C/EBPα. The conjugates of aptamer with C/EBPα-saRNA reduced tumor burden significantly in vivo, showing its anti-tumor effects. The aptamer target expressed on cell membrane was identified mitochondrial Hsp70. For the first time, results from these studies provide a new therapeutics strategy through transcriptional activation of C/EBPα by aptamer mediation induce anti-tumor effects in pancreatic cancer.
Favorable Resuls After Primed G-CSF BMT (G-BMT) for Patients (pts) with Severe Aplastic Anemia (SAA) Conditioning with Buslfan (Bu), Cyclophosphamide (Cy) and Rabbit ATG Using Mycophenolate Mofetil (MMF) and Cyclosporine-A (CSA) for Gvhd Prophylaxis: Rapid Neutrophil Engraftment, Low Rejection Rate and Chronic Gvhd.
Authors: Mauricio Ostronoff, ANA Patricia Souto Maior, Rodolfo Calixto, Fabiana Ostronoff, Rodrigo Florencio, Monique Martins, Luis Fabio Botelho, Alexandre Sucupira, Mariana Coutinho
Journal: Blood (2010)
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
Authors: Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M.Y. Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F. Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer
Journal: Cell Metabolism (2016)

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
Effects of Sodium Valproate on Proliferation and Apoptosis of Human Myelodysplastic Syndromes Cell Line MUTZ-1.
Authors: Bao-An Chen, Hui-Hui Zhao, Guo-Hua Xia, Ze-Ye Shao, Feng Gao, Jian Chen, Yun-Yu Sun, Jun Wang, Gang Zhao, Jia-Hua Ding, Ning-Na Chen, Xiao-Ping Pei
Journal: Blood (2007)
Tracking U.S. Professional Athletes: The Ethics of Biometric Technologies
Authors: Katrina Karkazis, Jennifer R. Fishman
Journal: The American Journal of Bioethics (2016)

Professional sport in the United States has widely adopted biometric technologies, dramatically expanding the monitoring of players' biodata. These technologies have the potential to prevent injuries, improve performance, and extend athletes' careers; they also risk compromising players' privacy and autonomy, the confidentiality of their data, and their careers. The use of these technologies in professional sport and the consumer sector remains largely unregulated and unexamined. We seek to provide guidance for their adoption by examining five areas of concern: (1) validity and interpretation of data; (2) increased surveillance and threats to privacy; (3) risks to confidentiality and concerns regarding data security; (4) conflicts of interest; and (5) coercion. Our analysis uses professional sport as a case study; however, these concerns extend to other domains where their use is expanding, including the consumer sector, collegiate and high school sport, the military, and commercial sectors where monitoring employees is viewed as useful for safety or to maximize labor potential.
Evolution of the Donor T Cell Repertoire In Allogeneic Stem Cell Transplant Recipients In the Second Decade After Transplantation
Authors: Robert Q. Le, J. Joseph Melenhorst, Brenna Hill, Sarfraz Memon, Minoo Battiwalla, Bipin N. Savani, Aarthi Shenoy, Nancy F. Hensel, Eleftheria K. Koklanaris, Keyvan Keyvanfar, Frances T. Hakim, Daniel C. Douek, A. John Barrett
Journal: Blood (2010)
Electronic books
Authors: M. De Bono
Journal: BMJ (2002)

Most scientific journals have an electronic version, but book publishers have been much slower to make their material available in electronic format. Some publishers of medical books have experimented with making some content available online, but only a few have sold content to readers. The consensus has been to “wait and see.” Concerns have been raised about digital piracy, the high costs of securing content, and whether readers want book length material in electronic format. The BMJ Bookshop has, however, just launched a scheme to make medical books available in electronic format from its own website (www.bmjbookshop.com.

Electronic books (widely called …
Abstract 4297: mAbXcite: A novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils
Authors: Isabelle Sansal-Castellano, Mark Carlson, Todd Armstrong, Gabriel Reznik, James Siedlecki, John Kane, Zuzana Dostalova, Hua Miao, Elizabeth Jaffee, Ifat Rubin-Bejerano
Journal: Cancer Research (2015)

Abstract The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that are immune active. Immune cells that have not received as much attention in cancer immunotherapy are neutrophils. Neutrophils are the most abundant white blood cells, which protect us from microbial infections. They are the first line of innate defense: they arrive early on in the course of infection, phagocytose, and release the content of their granules, including reactive oxygen species and enzymes. Neutrophils also communicate with other immune cells, such as macrophages, dendritic cells, and T cells, by releasing cytokines and chemokines. There has long been a call to recruit these professional killers to fight cancer. However, an approach that mediates the recruitment of neutrophils has to lead to acute as opposed to chronic inflammation to overcome the suppressive environment that tumors surround themselves with. We have developed a novel immunotherapy platform technology, termed mAbXcite, which directs and activates neutrophils to kill cancer cells in a targeted manner. The targeting is achieved by using monoclonal antibodies that are chemically linked to beta-1,6-glucan, a saccharide found on the cell walls of fungal species which recruits and activates neutrophils. The resulting mAb construct attracts mediators of acute inflammation, notably neutrophils, leading to rapid destruction of cancer cells. We will present proof-of concept of the mAbXcite technology using an anti-EGFR antibody and a syngeneic antibody. mAbXcite-cetuximab demonstrates significantly greater efficacy than the original antibody in resistant tumor models (BRAF and KRAS). Furthermore, mice that show complete regression or stasis do not grow tumors upon rechallenge, suggesting a lasting immune response that is initiated by neutrophils. We will also provide evidence for the involvement of T cells, suggesting that the immune memory is a result of neutrophils naturally leading to T cell activation. Citation Format: Isabelle Sansal-Castellano, Mark Carlson, Todd Armstrong, Gabriel Reznik, James Siedlecki, John Kane, Zuzana Dostalova, Hua Miao, Elizabeth Jaffee, Ifat Rubin-Bejerano. mAbXcite: A novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4297. doi:10.1158/1538-7445.AM2015-4297
Fish Oil Supplementation in Pregnancy
Authors: Ramya Ramaswami, Charles N. Serhan, Bruce D. Levy, Maria Makrides
Journal: New England Journal of Medicine (2016)

This interactive feature offers a case vignette accompanied by essays that support either fish oil supplementation in pregnancy to reduce the risk of asthma and lower respiratory tract infections in offspring or no supplementation. Share your comments and vote at NEJM.org.
2005 Update on Accelerated FDA Approval of Drugs Used To Treat Hematologic Malignancies from the Research on Adverse Drug-Events and Reports (RADAR): Rate of Regular Approval Conversion Remains Low.
Authors: Charles L. Bennett, Jessica A. Zagory, June M. McKoy, Kathryn R. McCaffrey, E. Allison Lyons, Steven Belknap
Journal: Blood (2005)