tbuckley/cabot-search huggingface dataset:
Abstract 2269: A novel molecular subset of metastatic lung adenocarcinoma is defined by the function of the proteoglycan receptor HMMR
Authors: Laura E. Stevens, Minghui Zhao, Zongzhi Liu, Don Nguyen
Journal: Cancer Research (2015)

Abstract Lung adenocarcinoma (LUAD) is a heterogeneous and deadly subtype of non-small cell lung cancer that metastasizes rapidly to distant organs. Recent transcriptional profiling of primary LUADs by TCGA identified three molecular subgroups with unique clinical and biological features. Amongst the most aggressive LUADs are tumors classified in the proximal inflammatory (PI) subtype. However, the molecular mechanisms that dictate metastatic competence of this tumor type remain undefined. Using a bioinformatic approach, we found that PI tumors are significantly enriched for the expression of extracellular matrix genes and their corresponding cell surface receptors compared to tumors of other subtypes. Among these receptors, hyaluronan mediated motility receptor (HMMR) was found to be significantly upregulated. Knockdown of HMMR in LUAD cells decreased their potential to invade, migrate, and form colonies in vitro. In an experimental mouse model of metastasis, suppression of HMMR decreased metastatic incidence and burden. Interestingly, using an orthotopic model of LUAD, suppression of HMMR attenuated tumor initiating capacity of LUAD cells within an inflammatory microenvironment without affecting tumor progression. In distant organs, HMMR is similarly essential for tumor re-initiation and expansion of micrometastases to macrometastases. Our findings suggest that the aggressive behavior of PI LUADs requires the interaction between HMMR and the tumor microenvironment. Citation Format: Laura E. Stevens, Minghui Zhao, Zongzhi Liu, Don Nguyen. A novel molecular subset of metastatic lung adenocarcinoma is defined by the function of the proteoglycan receptor HMMR. [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 2269. doi:10.1158/1538-7445.AM2015-2269
HOXA10 Expression Induces by Abl Kinase Inhibitors Enhanced Apoptosis through PI3K Pathway in CML Cells.
Authors: Isao Hirano, Yuya Sugimoto, Keiji Okinaka, Takaaki Ono, Kaori Shinjo, Kazuyuki Shigeno, Satoki Nakamura, Kazunori Ohnishi
Journal: Blood (2007)
Abstract 2814: Inhibition of PhIP/DSS-induced colon carcinogenesis by different forms of tocopherols in CYP1A-humanized mice
Authors: Chung S. Yang, Jayson X. Chen, Anna B. Liu, Hong Wang, Marlon Lee, Siyuan Yu, Chunfang Zhao, Ying-Yi Kuo, Eric Chi, Nanjoo Suh
Journal: Cancer Research (2015)

Abstract Tocopherols (T), which exist as α-, β-, γ-, and δ-T are important dietary antioxidants. Our previous studies have demonstrated that a mixture of tocopherols (γ-TmT), δ-T, and γ-T effectively inhibited colon carcinogenesis in AOM/DSS-treated mice or AOM-treated rats. However, the effects of different forms of tocopherols on carcinogenesis in animal models and in humans remain controversial. In the present study, we investigated the inhibitory effects of α-T, γ-T, and δ-T on colon carcinogenesis induced by a dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and promoted by dextran sodium sulfate (DSS) in CYP1A-humanized (hCYP1A) mice. At 5-6 weeks age, male hCYP1A mice were fed the AIN93M diet or diet supplemented with 0.2% α-T, γ-T, or δ-T for 1 week before PhIP treatment (2x 100mg/kg b.w., 3 days apart), which was followed by DSS (1.5% in drinking water for 4 days) treatment. The mice were sacrificed 10 weeks after the first dose of PhIP. Significant inhibition of colon tumor incidences was caused by dietary δ-T and γ-T, but not by α-T. In addition, oxidative and nitrosative stress markers (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory stress markers (i.e., PGE2, LTB4, NFκB and p-STAT3) were significantly reduced by δ-T. Dietary treatment with δ-T and γ-T significantly increased the δ-T and γ-T levels, respectively, in the blood and tissues, but their levels were still lower than the levels of α-T. However, the levels of their side-chain degradation metabolites (δ-T and γ-T forms of carboxyethyl hydroxychroman and carboxymethylbutyl hydroxychroman) were much higher than their parent tocopherols in blood and tissues. Altogether, we demonstrated the inhibitory effects of δ-T and γ-T in a dietary carcinogen-induced colon carcinogenesis model. The inhibition is possibly due to the antioxidative, reactive nitrogen species-trapping, and anti-inflammatory activities δ-T and γ-T. (Supported by NIH grants F31CA168333, RO1CA120915 and RO1AT007036 as well as shared facilities funded by CA72720 and ES05022) Citation Format: Chung S. Yang, Jayson X. Chen, Anna B. Liu, Hong Wang, Marlon Lee, Siyuan Yu, Chunfang Zhao, Ying-Yi Kuo, Eric Chi, Nanjoo Suh. Inhibition of PhIP/DSS-induced colon carcinogenesis by different forms of tocopherols in CYP1A-humanized mice. [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 2814. doi:10.1158/1538-7445.AM2015-2814
Abstract 701: A novel class of Ras selective inhibitors
Authors: Joshua C. Canzoneri, Xi Chen, Adam B. Keeton, Kevin Lee, Bernard Gary, Ethan B. Butler, William E. Grizzle, Landon Wilson, Stephen Barnes, Michael R. Boyd, Gary A. Piazza
Journal: Cancer Research (2015)

Abstract Despite the fact that activating mutations in the various forms of Ras were identified as driving factors in oncogenesis over thirty years ago, there are still no effective therapeutics which act on this target. We recently synthesized and characterized a novel class of compounds that show striking potency and selectivity to inhibit the growth of tumor cells with mutant Ras. Through iterative structure-activity studies, we selected for and optimized Ras selectivity to achieve high potency with IC50 values in the low nanomolar range and selectivity indices of nearly 100-fold. For example, ADT-062 inhibited the growth of human HCT116 colon tumor cells that harbor mutant K-Ras with an IC50 value of 8.4 + 3.6 nM,. In contrast, human HT29 colon tumor cells that have wild type Ras displayed an IC50 value of 521 + 253 nM in response to ADT-062 treatment. When surveying a larger panel of colon tumor cell lines, we observed a direct correlation between potency and Ras activation status. Further, ADT-062 induced cell cycle arrest only in the Ras-mutant cell line. To study the mechanism by which this class of compounds selectively inhibits the growth of tumor cells with mutant K-Ras, we profiled lysates from treated HCT116 and HT29 colon tumor cells using high resolution LC-MS/MS. Over 100 ions were identified that were differentially affected by treatment with ADT-062 at its IC50 value in the respective cell line. Among the ions of interest, a component of the purine biosynthetic pathway, 5′-phosphoribosyl-N-formylglycinamide (FGAR), was found to be induced 200-fold (p = .0031) in K-Ras mutant cells compared with Ras wild type cells. Together, these findings suggest that this compound may cause a Ras selective disruption of purine metabolism and cell cycle progression which contributes to the selectivity by which this novel class of compounds inhibit the growth of tumor cells with mutant Ras. These findings may enable us to develop this compound class as a novel therapeutic which targets Ras driven tumors and tumors which may become resistant to other targeted therapeutics through secondary Ras mutations. Citation Format: Joshua C. Canzoneri, Xi Chen, Adam B. Keeton, Kevin Lee, Bernard Gary, Ethan B. Butler, William E. Grizzle, Landon Wilson, Stephen Barnes, Michael R. Boyd, Gary A. Piazza. A novel class of Ras selective inhibitors. [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 701. doi:10.1158/1538-7445.AM2015-701
Can tuberculosis patients in resource-constrained settings afford chest radiography?
Authors: Debora Pedrazzoli, Marek Lalli, Delia Boccia, Rein Houben, Katharina Kranzer
Journal: European Respiratory Journal (2016)

Even when tuberculosis (TB) care is free, impoverished patients and their households continue to incur unmanageable costs due to seeking and staying in care for the full duration of anti-TB treatment [1]. By aggravating household vulnerability, these costs can prevent or delay diagnosis, treatment and successful outcome, leading to increased TB transmission, morbidity and mortality [2–4]. The new World Health Organization (WHO)'s End TB Strategy places greater emphasis on ensuring universal free access to care, and it includes a target of elimination of associated catastrophic costs for TB patients and their households by 2020 [5]. In many low- and middle-income countries chest radiographs are not free of charge for TB patients <http://ow.ly/SA7l305Yzk2> We would like to thank all the country experts that contributed information to this study. In addition, we would like to thank Andrew Codlin (Stop TB Partnership, Geneva, Switzerland) and Andrew Siroka (WHO/Global TB Programme, Geneva, Switzerland) for their help with providing contacts in countries.
Hematopoietic Cell Transplantation for Children with High Risk Acute Lymphoblastic Leukemia in First Complete Remission: A Report From the Italian Association of Pediatric Hematology and Oncology (AIEOP) Registry.
Authors: Franca Fagioli, Paola Quarello, Marco Zecca, Edoardo Lanino, Carla Rognoni, Adriana Balduzzi, Chiara Messina, Claudio Favre, Roberto Foà, Mimmo Ripaldi, Sergio Rutella, Giuseppe Basso, Arcangelo Prete, Franco Locatelli
Journal: Blood (2012)
Abstract 684: Nelfinavir inhibits the growth of small cell lung cancer cells and patient-derived xenograft tumors
Authors: Shigeru Kawabata, Nick Connis, Chunyu Zhang, Joell J. Gills, Christine L. Hann, Phillip A. Dennis
Journal: Cancer Research (2015)

Abstract Small cell lung cancer (SCLC) is an aggressive lung cancer with a poor prognosis that is characterized by frequent metastasis at the time of diagnosis. Although SCLC is more responsive to chemotherapy and radiation therapy compared to other types of lung cancer, cure is difficult because of frequent recurrence. Molecular alterations in SCLC include inactivation of TP53 and RB1, high copy number of Myc family, and amplifications of FGFR1 and SOX2. Additionally, achaete-scute homolog 1 (ASCL1), a transcription factor for development of pulmonary neuroendocrine cells, is a lineage-dependent oncogene for SCLC. New drugs and molecular targets need to be identified. Previously, we reported nelfinavir (NFV), a HIV protease inhibitor, inhibited proliferation of non-small cell lung cancer (NSCLC) cells in vitro and human NSCLC xenograft tumors through induction of the unfolded protein response (UPR). Here we demonstrate that the effect of NFV in SCLC cells and preclinical treatment studies using SCLC patient-derived xenograft (PDX) mouse models. NFV inhibited SCLC cell proliferation and induced cell death in vitro. Activating transcription factor 4 (ATF4), a marker of the UPR, was rapidly increased, whereas Myc was decreased after 4 hr treatment with NFV. AMP-activated protein kinase (AMPK), which plays a role in cellular energy homeostasis, was activated in the early phase of NFV treatment, whereas the mammalian target of rapamycin (mTOR) that is a serine/threonine kinase that regulates cell growth, was inactivated. NFV inhibited the expression of SOX2, ASCL1 and Aurora B in a cell line- and time-dependent manner. Taken together, NFV had pleiotropic effects against multiple targets during the inhibition of SCLC cell proliferation. In vivo, NFV inhibited growth of SCLC PDX tumors, which correlated with induction of the UPR and decreased expression of ASCL1 and Aurora B. Collectively, these findings show that NFV is highly effective in SCLC in vitro and in vivo, suggesting possible value of incorporating NFV into clinical trials for patients with SCLC. Citation Format: Shigeru Kawabata, Nick Connis, Chunyu Zhang, Joell J. Gills, Christine L. Hann, Phillip A. Dennis. Nelfinavir inhibits the growth of small cell lung cancer cells and patient-derived xenograft tumors. [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 684. doi:10.1158/1538-7445.AM2015-684
Use of All-Transretinoic Acid (ATRA) + Arsenic Trioxide (ATO) To Eliminate or Minimize Use of Chemotherapy (CT) in Untreated Acute Promyelocytic Leukemia (APL).
Authors: Elihu H. Estey, Guillermo Garcia-Manero, Alexandra Ferrajoli, Stefan Faderl, Srdan Verstovsek, Hagop Kantarjian
Journal: Blood (2004)
The Results of Molecular Relapses Treatment in Acute Promyelocytic Leukemia (APL) Patients.
Authors: Elena N. Shuravina, Elena N. Parovitchnikova, Irina A. Demidova, Yulia V. Olshanskaia, Andrei V. Misiurin, Valeri G. Savchenko
Journal: Blood (2005)
A Reduced Capacity To Generate Activated Protein C and the Role of PAI-1 Deficiency on Coagulation Activation and Fibrin Formation during Murine Influenza Pneumonia.
Authors: Tymen Keller, Matthijs van Wissen, Koen van der Sluijs, Eric van Gorp, Joost Meijers, Tom van der Poll, Harry Buller, Dees Brandjes, Marcel Levi, Victor Gerdes
Journal: Blood (2005)
312. Highly-Efficient CNS Transduction With Vesicle-Associated AAV Vector
Authors: Eloise M. Hudry, Courtney Martin, Dakai Mu, Federico Mingozzi, Bradley T. Hyman, Casey A. Maguire
Journal: Molecular Therapy (2015)

Adeno-associated virus (AAV) vector is currently the pre-eminent gene delivery system to the central nervous system (CNS), with several serotypes capable of penetrating the blood-brain barrier (BBB). Limitations to clinical translation of systemically administered AAV in patients is pre-existing antibodies as well as the relatively high doses of vector (~10e14 genome copies/kg body weight) required to achieve high levels of transduction in CNS. Using a bioluminescent reporter system (firefly luciferase, FLuc), we previously showed that AAV associated with extracellular vesicles (ev-AAV, AKA vexosomes) can transduce murine brain in the presence of neutralizing antibodies. To further assess the potential of this new technology, the present study evaluates the cell-types, percentages of transduction and regional spread in the CNS after a single intravenous infusion of the same self-complementary genome vector copy (g.c.) numbers (1.5×10e11 g.c.) of AAV9 and ev-AAV9 expressing the Green Fluorescent Protein (GFP) reporter gene (~7.5×10e12 g.c./kg) at four weeks post injection in immunocompetent mice. Astrocytes were the main population to be transduced by our ev-AAV9-CBA-GFP, reaching on average 13.44±0.81% of GFP positive astrocytes in the cortex, hippocampus and striatum, 1.8 fold higher than AAV9-CBA-GFP (7.49±0.77; p=0.001). Stereological analyses also demonstrated a significant amount of neurons expressing the GFP reporter after vexosomes injection (5.89±0.29%) as compared with conventional AAV9 (3.12±0.19%, p=0.0001), and we observed a wide tropism range of ev-AAV9 towards different neuronal sub-types throughout the neural axis. Brain endothelial cells were also transduced well by vexosomes. Using bioluminescence imaging, we next analyzed the FLuc expression kinetics in the head region of mice injected with conventional AAV9-Fluc and AAV8-Fluc and compared them to their ev-AAV counterparts after systemic injection. At day 7 post injection, ev-AAV9 had an approximately 20-fold higher FLuc signal in the head region compared to AAV9 which decreased to 2 fold by day 35. Remarkably ev-AAV8 had a 40-fold higher signal than conventional AAV8, remaining stable from 14-35 days post injection. Furthermore, while conventional AAV9 had a higher signal than conventional AAV8, ev-AAV8 had a 10–fold higher signal than AAV9 at day 35. We are currently validating the FLuc results, and analyzing transduced cell types with ev-AAV8 encoding GFP. The combination of our prior results showing the ability to evade neutralizing antibodies with our current data showing efficient transduction of target cell types in the CNS, emphasize the great potential of ev-AAV vectors for systemic-based therapy.
Supporting human rights, one patient at a time
Authors: Katherine McKenzie
Journal: BMJ (2016)

Medical exams can significantly increase the likelihood that asylum will be granted

I saw my first asylum seeker around 10 years ago in my clinic. He came from a country with an autocratic president against whom he had peacefully protested. The government would not accept dissent from its citizens and they arrested, detained, and tortured him. He was released, but he was told that he would be killed for any future—real or perceived—opposition. He fled to the US for safety, and eventually came to my office for a forensic medical exam to document the scars of his torture.

In the intervening years I have come across many people who have experienced human rights abuses …
Nine-year study of US high school soccer injuries: data from a national sports injury surveillance programme
Authors: Morteza Khodaee, Dustin W Currie, Irfan M Asif, R Dawn Comstock
Journal: British Journal of Sports Medicine (2016)

Background Research on high school soccer injury epidemiology is sparse. Aim To describe high school soccer injury rates, trends and patterns by type of athlete exposure (AE), position and sex. Methods This descriptive epidemiological study used data from a large national high school sports injury surveillance programme to describe rates and patterns of soccer-related injuries including concussion sustained from 2005/2006 to 2013/2014. Injury rates are calculated per 1000 AEs. Results Overall, 6154 soccer injuries occurred during 2 985 991 AEs; injury rate=2.06 per 1000 AEs. Injury rates were higher during competition (4.42) than practice (1.05; rate ratio (RR)=4.19; 95% CI 3.98 to 4.41), and in girls (2.33) than boys (1.83; RR=1.27, 95% CI 1.21 to 1.34). Boys' non-concussion injury rates decreased significantly (p=0.001) during the study period while reported concussion rates increased significantly (p=0.002). Girls' non-concussion rates were relatively stable and reported concussion rates increased significantly (p=0.004). Player–player contact was the injury mechanism that led to the most competition injuries (injury proportion ratio (IPR)=2.87; 95% CI 2.57 to 3.21), while non-contact injuries were the most common mechanisms among practice injuries (IPR=2.10; 95% CI 1.86 to 2.38). Recovery from concussion was &gt;7 days in a third of the cases. Injury patterns were similar between sexes with respect to position played and location on the field at the time of injury. Conclusions High school soccer injury rates vary by sex and type of exposure, while injury patterns are more similar across sexes. Reported concussion rates increased significantly over the study period in male and female athletes.
Flow Cytometry Analysis of Peripheral Blood CD4+/CD25+/FOXP3+ T Regulator Cells from 11 Patients Treated with Ipilimumab Following Relapse of Malignancy after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Jiehua Zhou, Ruikun Zhong, Sue Corringham, Teresa Sapp, Robert Soiffer, Rachel C. Mitrovich, Izzy Lowy, Asad Bashey, Edward D. Ball
Journal: Blood (2007)
334. Double Expression Cassettes Engineering at the Two Alleles with Same Genome Site of Human Cell Using CRISPR/Cas9 Vector System
Authors: Zhimin Wang
Journal: Molecular Therapy (2016)

For the past two years, CRISPR/Cas9 mediated genome editing has been widely used for the next-generation strategy for genetic modification. Previous work has showed that both single and multiple genes targeted mutagenesis can be achieved using the CRISPR/Cas9 system. In this study, we demonstrated that two different expression cassettes can be homologous recompensed in human genome in the same gene editing site, but different alleles in HEK293 cells. Our results showed that CRISPR/Cas9 prefer to homologous recombination (HR) of expression cassette in one allele at one time (seven showing heterozygous from eight picked stable cell clones). Targeting the same guided RNA sequence of EMX1gene with CRISPR/Cas9 system, we can generate stable cell lines with homologous recombination of both EGFP and mCherry expression cassettes at the two alleles of EMX1 gene. To further analyze the off target effects of CRISPR/Cas9 derived RNA guided endonucleases, the total cell proteins were exploited to identify with Mass Spectrometry and results showed no novel proteins were identified compared with wild type HEK293 cells. But our results indicated that the expression levels of some large molecular weight proteins are changed. We also analyze the expression pattern of the proteins exits within both upstream and downstream of the insertion sites to study the possible effect of the CMV promoter of the expression cassettes. Results didn't show significant change of the expression of the 21 related genes. Our study indicated that CRIPSR/Cas9 system can mediate double insertion of two expression cassette at the two alleles in the same gene and which can potentially provides more choices for expressing exogenous cNDA in human cells. Also our work confirmed that Cas9 protein expression in culture cells can change expression pattern of some proteins which should be considered when CRISPR/Cas9 system were used in the gene editing.
Aberrant Expression of IL-2R in Pediatric Anaplastic Large Cell Lymphoma: Cellular and Proteomic Analysis of Denileukin Diftitox (ONTAK) as a Potential Therapeutic Agent.
Authors: Megan S. Lim, Jaqueline Tygeson, Charles Seiler, David K. Crockett, Prakash Satwani, Sherrie L. Perkins, Mitchell S. Cairo, Kojo S. Elenitoba-Johnson
Journal: Blood (2006)
Parenting and lifestyle programme does not reduce child obesity, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

The Families for Health programme, a 10 week community based family programme on parenting and lifestyle change, was no more effective and cost more than usual care in managing child obesity, a randomised trial in primary care in England has found.1

Childhood obesity poses a major public health burden in England, where a third of 10-11 year olds are overweight or obese.2 Studies have suggested that …
Clinical and Quality of Life Outcomes in Patients with Multiple Sclerosis (MS) after High Dose Chemotherapy(HDCT)+Autologous Stem Cell Transplantation (ASCT).
Authors: Yury L. Shevchenko, Andri A. Novik, Boris V. Afanasiev, Igor A. Lisukov, Yury N. Fedotov, Tatiana I. Ionova, Alexandr D. Kulagin, Olga A. Malysheva, Gennadi N. Bisaga, Vladimir Y. Melnichenko, Lubov V. Chelombit, Sergei V. Voloshin, Denis A. Fedorenko, Inna V. Vereschagina, Anton V. Kishtovich
Journal: Blood (2004)
Amrubicin therapy for platinum-refractory extrapulmonary neuroendocrine carcinoma: Retrospective single-center analysis
Authors: Yukako Hattori, Hirotaka Takasaki, Yasufumi Ishiyama, Jun Aoki, Ayumi Numata, Reina Watanabe, Shigeki Motomura, Rika Sakai
Journal: Annals of Oncology (2015)
Driver Mutations and Prognosis in 1118 Patients with Primary Myelofibrosis
Authors: Ayalew Tefferi, Paola Guglielmelli, Terra L. Lasho, Yoseph Elala, Tiziana Fanelli, Naseema Gangat, Christy Finke, Giada Rotunno, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Alessandro M. Vannucchi
Journal: Blood (2015)
Characterization of the Mutational Spectrum in Young Patients with Myelodysplastic Syndrome
Authors: Cassandra M Hirsch, Bartlomiej Przychodzen, Tomas Radivoyevitch, Sean Hobson, Bhumika J. Patel, Swapna Thota, Michael J. Clemente, Hetty E. Carraway, Mikkael A Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2015)