tbuckley/cabot-search huggingface dataset:
Abstract SY44-03: Proteogenomic and phosphoproteomic analysis of ovarian cancer
Authors: Karin D. Rodland
Journal: Cancer Research (2015)

Abstract A comprehensive molecular level view of cancer is desirable for understanding the underlying causes of disease, for predicting prognosis, and ultimately guiding treatment. The Cancer Genome Atlas (TCGA) conducted an extensive genomic and transcriptomic characterization of ovarian high-grade serous carcinoma (HGSC) with the objective of informing prognosis and the development of targeted therapies for this highly lethal gynecologic malignancy1. However, proteins are likely closer to biological and disease phenotypes, often not well correlated with their transcripts, and their characterization is expected to provide insights not evident from genomic studies. Therefore, to obtain a more comprehensive assessment of the complex HGSC phenotype, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) conducted an extensive proteomic and phosphoproteomic characterization of the HGSC tumors previously characterized by TCGA, providing quantitative measurements for 10,030 proteins across 174 tumors, and 25,598 phosphosites from 6,769 phosphoproteins. Novel insights into ovarian cancer biology arising from these proteogenomic studies include: 1) a substantial trans-regulation of protein abundances by copy number alterations (CNAs), which when analyzed at a pathway level converged on the cancer-associated processes of proliferation, cell motility/invasion, and immune regulation; 2) identification of five proteomic subtypes in the TCGA cohort, with two subtypes showing robust concordance with the mesenchymal and proliferative subtypes, and tumors from transcript assigned differentiated and immunoreactive subtypes not robustly segregating into distinct clusters, demonstrating their proteomic heterogeneity; 3) identification of specific post-translational modifications associated with homologous repair deficiency; and 4) phosphoproteomic data revealing a consistent novel set of activated pathways associated with patient survival, including up-regulation of VEGFR signaling in patients with poor outcomes, and suggesting a strategy for selecting anti-angiogenesis therapies. This study will inform future use of protein markers to stratify patients who may benefit from anti-angiogenesis or PARP inhibitor therapy, predicting development of platinum resistant disease, identifying immunoregulatory networks that can be exploited for cancer immunotherapy, and determining the clinical phenotypes based upon proteomic ovarian cancer subtypes. Citation Format: Karin D. Rodland. Proteogenomic and phosphoproteomic analysis of ovarian cancer. [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 SY44-03. doi:10.1158/1538-7445.AM2015-SY44-03
Protective Effect of VELCADE® on Thalidomide-Associated Deep Vein Thrombosis (DVT).
Authors: Maurizio Zangari, Bart Barlogie, Choon-Kee Lee, Annick E. Tricot, Athanasios Fassas, Elias Anaissie, Klaus Hollmig, Raymond Thertulien, Giampaolo Talamo, Frits van Rhee, Julie M. Stover, Louis Fink, Guido J. Tricot
Journal: Blood (2004)
BMET-15. FREQUENCY OF SYNCHRONOUS BRAIN METASTASES AT TIME OF PRIMARY CANCER DIAGNOSIS IN THE US, 2010-2013
Authors: Courtney Kromer, Jordan Xu, Quinn Ostrom, Carol Kruchko, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2016)

Brain metastases are one of the most common types of brain tumors, and are a common complication of several high-incidence cancer types, including breast and lung cancers. Information on brain metastases have historically not been collected as part of national cancer registration in the United States, but synchronous metastasis at time of primary cancer diagnosis has recently started to be collected in the NCI’s Surveillance, Epidemiology, and End Results (SEER) system. Using data from the SEER 18 from 2010 to 2013, we sought to assess the frequency of synchronous brain metastases (SBM) at time of primary cancer diagnosis in the United States. There were 1,348,131 total primary cancer cases collected by SEER between 2010 and 2013, 1.7% of which presented with SBM. The cancer type with the highest proportion of SBM was lung cancer, with 10.8% (22,032 of 164,479) of cases having SBM, followed by esophagus (1.5%), kidney (1.4%), and melanoma (1.2%). For breast and colon, the proportions of SBM was 0.4% and 0.3% respectively. Our results reflect the high proportion of patients diagnosed with late stage lung cancer where synchronous brain metastasis have already formed as compared to other common cancers in the United States. Brain metastasis is a complication of late stage cancer from other sites that causes significant morbidity and mortality, and having population-based data is critical to assess total disease burden.
Effectiveness of early compared with conservative rehabilitation for patients having rotator cuff repair surgery: an overview of systematic reviews
Authors: Bruno Fles Mazuquin, Andrew Charles Wright, Sarah Russell, Puneet Monga, James Selfe, Jim Richards
Journal: British Journal of Sports Medicine (2016)

The aim is to critically analyse and discuss the current literature and determine the effectiveness of rehabilitation for patients after surgical repair of rotator cuff tears for range of motion (ROM), pain, functional status and retear rates; in addition, an update of new literature is included.Overview of systematic reviews.A search was performed with no restrictions to date of publication and language in the following databases: EBSCO, AMED, CINAHL, SPORTDiscus, EMBASE, Cochrane, LILACS, MEDLINE, PEDro, Scielo, SCOPUS and Web of Knowledge. The PRISMA guideline was followed to develop this review and the R-AMSTAR tool was used for critical appraisal of included reviews.Only systematic reviews and randomised controlled trials (RCTs) comparing the effectiveness of early with conservative rehabilitation, after surgical repair of the rotator cuff, were included. Moreover, the studies should report ROM, pain, functional status and/or retears rates before and after 3-24 months of the surgery.10 systematic reviews and 11 RCTs were included for the final analysis. Conflicting results and conclusions were presented by the systematic reviews, the use of primary studies varied; also the methodological quality of the reviews was diverse. This updated review, with new meta-analysis, showed no difference for function, pain, ROM or retears ratio between early and conservative rehabilitation.Early mobilisation may be beneficial, particularly for small and medium tears; however, more studies with higher quality are required, especially for patients with large tears who have been given less attention.
FASCIOLOPSIS BUSKI INFESTATION
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Donor Lymphocyte Infusions from Unrelated Donors for Treatment of Relapsed Chronic Myelogenous Leukemia: Importance of Initial Cell Dose.
Authors: Bernd Hertenstein, Elke Dammann, Matthias Eder, Jane Apperley, Juergen Finke, Antonius V.M.B. Schattenberg, Kimmo Porkka, Bo Bjoerkstrand, Dietger W. Niederwieser, Cesare Guglielmi
Journal: Blood (2005)
489. Tumor-Targeted Hursirna-Nanoparticle Delivery Inhibits Lung Tumor Growth In Vitro and In Vivo
Authors: Ranganayaki Muralidharan, Narsireddy Amreddy, Anish Babu, Akhil Srivastava, Janani Panneerselvam, Allshine Chen, Yan D. Zhao, Lichao Zhao, Uday B. Kompella, Anupama Munshi, Rajagopal Ramesh
Journal: Molecular Therapy (2016)

HuR, an mRNA binding protein regulates the stability of many oncoproteins associated with cell survival, proliferation, migration and angiogenesis. HuR overexpression is a marker for poor prognosis in patients diagnosed with cancer of lung, ovary, breast and colon. We hypothesized that the silencing of HuR using small interfering RNA (siRNA) could be a promising approach for lung cancer therapy. To test our hypothesis, we developed a tumor-targeted nanoparticle (NP) system that is targeted to transferrin receptor (TfR) for delivering HuRsiRNA (HuR-TfNP) in human lung cancer cells. Human lung cancer cells (A549, HCC827) and normal lung fibroblast (MRC-9) cell lines expressing varying levels of TfR were used in the present study. TfR expression was highest in A549, moderate in HCC827, and low to undetectable in MRC9 cells. In vitro studies demonstrated enhanced uptake of Tf-NP (51%) in TfR overexpressing A549 cells, compared to the non-targeted NP. Specificity studies using desferrioxamine (DFO; 100 µM), a stimulator of TfR, showed a two-fold increased uptake of Tf-NP whereas blocking TfR with exogenous transferrin (1 µg/well) reduced the uptake by 3 fold in A549 cells. Further, HuR-TfNP treatment reduced HuR expression and significantly suppressed cell proliferation at 24h and 48h compared to control siRNA containing NP (C-Tf-NP) in tumor cells but not in normal cells. Greatest inhibition was observed in A549 cells (23% and 30% inhibition at 24 and 48 h respectively) compared to 15% and 25% in HCC827. In MRC-9 cells, only 4% inhibition was observed. HuR-TfNP induced G1 cell-cycle arrest in tumor cells that correlated with marked reduction in Cyclin D1, and Cyclin E protein expression. Further, tumor cell migration and invasion was significantly inhibited in HuR-TfNP treated tumor cells compared to C-TfNP treatment (p<0.001). In-vivo, Tf-NP bio-distribution studies using indocyanine green (ICG) showed accumulation of the NP in tumor tissues over time with maximum accumulation at 24 h post NP injection. Efficacy studies in A549 tumor model demonstrated that systemic administration of HuR-TfNP significantly inhibited growth of both subcutaneous tumor growth and experimental lung metastasis compared to C-TfNP treatment (P<0.05). Further, tumor growth delay was sustained over 70 days when compared to control groups. A marked reduction in the expression of HuR and HuR-regulated oncoproteins (Bcl2, Cyclin D1 and Cyclin E) with a concomitant increase in p27 expression was observed in HuR-TfNP-treated tumors compared to control tumors. Our study results demonstrate HuR-TfNP therapy suppressed lung tumor growth both in vitro and in vivo and is therapeutic target for lung cancer treatment.
Abstract 3246: Novel luciferase labelling technique to improve imaging of orthotopic prostate and pancreatic cancer models
Authors: Jenni Bernoulli, Johanna Tuomela, Matthias Bozza, Katja M. Fagerlund, Mari I. Suominen, George Morris, Jussi M. Halleen, Richard Harbottle
Journal: Cancer Research (2015)

Abstract Bioluminescent-labelling allows sensitive non-invasive sequential imaging of tumor development and early metastasis. However, current methods for the genetic modification of cells typically use integrating genotoxic viruses that can potentially disrupt the molecular behavior of cancer cell lines due to their random nature of integration. Here, we utilized a non-viral DNA vector that comprises an S/MAR (Scaffold/Matrix Attachment Region) element to stably modify cells to be further used in xenograft studies to allow long term expression without affecting cell behavior or silencing over cell divisions. Human PC-3 prostate cancer cells and BxPC-3 pancreatic cancer cells were stably transfected with a pCAG-LUC-S/MAR and cultured for 4 weeks under selection. Colonies that formed after this period were isolated and expanded in normal medium and evaluated for luciferase expression and molecular integrity of the DNA vector. For in vivo studies, PC-3 cells were inoculated orthotopically into the prostate, and BxPC-3 cells into the pancreas using athymic and BALB/c nude mice. For comparison, similar experiments with the corresponding study designs were performed with the non-labelled parental cell lines. The luciferase transfected cells maintained their original properties with stable expression. Luciferase-labelled PC-3 and BxPC-3 cells inoculated orthotopically into the prostate and pancreas, respectively, were successfully followed for 5 weeks with non-invasive bioluminescence imaging by IVIS. The results demonstrated high-quality follow-up of tumor growth compared with tumor models using non-labelled cells. In conclusion, S/MAR DNA vectors are able to produce genetically modified cells without the limitations of random genomic integration, whilst providing extra-chromosomal mitotic stability and sustained transgene expression at high level. When utilized in orthotopic xenograft studies, these luciferase expressing cells formed a reliable and essential non-invasive imaging platform that improves substantially efficacy testing of anticancer drug candidates. Citation Format: Jenni Bernoulli, Johanna Tuomela, Matthias Bozza, Katja M. Fagerlund, Mari I. Suominen, George Morris, Jussi M. Halleen, Richard Harbottle. Novel luciferase labelling technique to improve imaging of orthotopic prostate and pancreatic cancer models. [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 3246. doi:10.1158/1538-7445.AM2015-3246
Abstract A1-63: Characterizing the DNA damage repair defect in HPV-positive oropharyngeal squamous cell carcinoma
Authors: Alice N. Weaver, Tiffiny S. Cooper, Hoa Q. Trummell, James A. Bonner, Eben L. Rosenthal, Eddy S. Yang
Journal: Cancer Research (2015)

Abstract Although tobacco-associated head and neck cancers (HNCs) are declining in incidence, overall HNC rates are escalating due to increasing prevalence of human papillomavirus (HPV)-associated tumors, especially oropharyngeal squamous cell carcinomas (OPSCCs). Clinically, patients with HPV-associated OPSCCs have improved overall survival and increased response to therapy, especially agents which act by damaging DNA. Based on these observations, we hypothesized that HPV-positive OPSCCs harbor a defect in DNA repair activity and are sensitive to DNA repair-targeted therapy. We evaluated DNA repair activity by immunofluorescent staining for DNA damage-induced formation of DNA repair protein foci. Baseline expression of DNA repair proteins was determined by NanoString nCounter analysis of transcript levels and immunoblotting for protein levels. Therapeutic sensitivity was assessed in vitro using the colony formation assay and in vivo using both cell line-derived xenografts and a patient-derived xenograft. Consistent with our hypothesis, in vitro disease models demonstrated delayed resolution of radiation-induced DNA double strand breaks (DSBs) as assessed by γH2AX foci staining and neutral comet assay. Investigation of the two main DSB repair mechanisms, non-homologous end joining (NHEJ) and homologous recombination (HR), indicated intact activation of both pathways but strikingly diminished recruitment of downstream repair factors DNA-Pk (NHEJ) and BRCA2 (HR) to sites of damage. In addition, protein expression of both DNA-PK and BRCA2 was decreased in HPV-positive compared to HPV-negative HNC cell lines. We next studied susceptibility of HPV-positive OPSCCs to PARP inhibition, a class of anticancer agents which block DNA repair signaling pathways and have proven effective clinically in DNA repair-deficient cancers. In vitro colony formation assays revealed a negative effect on cell survival in HPV-positive but not HPV-negative HNCs treated with the PARP inhibitor veliparib. Importantly, these results were confirmed in vivo in both cell line-derived xenografts and a patient-derived xenograft. In summary, our findings demonstrate for the first time the presence of a significant DNA DSB repair defect in HPV-positive OPSCCs encompassing both NHEJ and HR repair, and suggest therapies targeting DNA repair pathways may help improve therapeutic ratio in this disease. Citation Format: Alice N. Weaver, Tiffiny S. Cooper, Hoa Q. Trummell, James A. Bonner, Eben L. Rosenthal, Eddy S. Yang. Characterizing the DNA damage repair defect in HPV-positive oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-63.
628. Transposons Expressing Full-Length Human Dystrophin Enable Genetic Correction of Dystrophic Mesoangioblasts and iPS-Derived Mesoangioblast-Like Cells
Authors: Mariana Loperfido, Susan Jarmin, Sumitava Dastidar, Mario Di Matteo, Ilaria Perini, Marc Moore, Nisha Nair, Ermira Samara-Kuko, Takis Athanasopoulos, Francesco Saverio Tedesco, George Dickson, Maurilio Sampaolesi, Thierry VandenDriessche, Marinee K. Chuah
Journal: Molecular Therapy (2016)

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. Alternatively, dystrophic mesoangioblast-like cells were generated from iPS of DMD patients. These iPS-derived mesoangioblasts, constitute an essentially unlimited supply of stem/progenitor cells that could be genetically corrected using PB transposons expressing dystrophin. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes.
632. Oncolytic Adenoviruses Targeted to the HPV E6 and E7 Oncoproteins as a Novel Treatment for Head &amp; Neck Squamous Cell Carcinomas
Authors: Christopher J. LaRocca, Amanda Oliveira, Joohee Han, Julia Davydova, Ramon Alemany, Cristina Balagué, Mark Herzberg, Rajaram Gopalakrishnan, Masato Yamamoto
Journal: Molecular Therapy (2015)

Introduction: Recent reports have shown that the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has been steadily increasing. HNSCCs are known to have a high recurrence rate and compared to their HPV-negative counterparts, these tumors have a unique biology which necessitates the development of novel treatment modalities. The HPV E6 and E7 oncoproteins are attractive therapeutic targets as they interact with key cell cycle regulatory components, namely p53 and pRb. Our research group has applied conditionally replicating oncolytic adenoviruses (CRAd) with modifications in the E1a region of the genome allowing for selective replication in E6 and E7 expressing HNSCCs. Methods: The in vitro transduction efficiency of E1-deleted luciferase expressing vectors with fiber modifications was assessed in multiple HPV-positive and negative cell lines. The CRAds were designed with a distinct deletion in the E1a region of the adenoviral genome (D24 and CB016) intended to allow for selective replication in HPV-positive HNSCC cells. Additionally, the CRAds have a luciferase transgene in the E3 region that is expressed in a replication dependent manner. By using a luciferase assay, the degree of viral replication was analyzed in numerous HNSCC cell lines. In vitro cell viability following viral infection was analyzed with crystal violet and MTS assays. A HPV-positive cell line (UPCI SCC 090) was used to establish subcutaneous tumors in female nude mice. They were subsequently treated with either one intratumoral viral injection or four injections (given every fourth day). Results: The 5/3 fiber modification significantly increased viral infectivity in all tested HNSCC cell lines. The 5/3 CB016 vector replicated selectively in HPV-positive cell lines, while the 5/3 D24 virus replicated in all cell lines regardless of HPV status. Both of the vectors demonstrated profound cytocidal effects in the crystal violet and MTS assays. For the in vivo experiments, a single intratumoral injection of virus demonstrated an anti-tumor effect for only one week following injection. Given this limited effect, an additional in vivo experiment was performed to analyze the efficacy of multiple intratumoral injections (3.5 x1011 vp/injection). This setup resulted in statistically significant tumor growth suppression at day 26 when compared to the saline control group (p<0.05 for 5/3 CB016, p<0.01 for 5/3 D24). Conclusion: CRAds designed to target HPV-positive HNSCCs demonstrated tremendous, yet selective in vitro cytocidal effects. The profound tumor growth suppression in a mouse model (particularly by multiple injections) shows the excellent potential of our viruses to be clinically translated as a new therapeutic entity for this emerging disease process.