tbuckley/cabot-search huggingface dataset:
Abstract 4533: Disruption of intrachromosomal interactions by deficient cohesin initiate epithelial-mesenchymal transition and stemness in cancer
Authors: Jiyeon Yun
Journal: Cancer Research (2016)

Abstract PURPOSE Although EMT-MET process is a crucial reversible event in development of human tumorigenesis controlled by complex networks, very little is known about how EMT-MET occurs reversibly and timely in cancer. Recently, different levels of Rad21 protein, a subunit of cohesin high-order-chromatin-architectural complex, between mesenchymal and epithelial cancers have been described. METHODS To elucidate how Rad21 determines EMT states, we silenced Rad21 in epithelial cancers using lentiviral shRNAs. We performed microarray to compare transcriptional changes by Rad21-KD. Additionally, we measured cell cycles and mitotic chromosome segregations to rule out the role of Rad21 as a sister chromatid segregation molecule. We observed cell morphology through confocal microscopy and checked high-order-chromatin structures using Chromosome-Conformation-Capture (3C) and Chromatin immunoprecipitation (ChIP) assay. RESULTS We identified high-order-chromatin structures mediated by Rad21 plays critical regulatory roles in transcription of EMT related genes for the first time. Rad21-KD in epithelial cancers caused reduction of Rad21 enrichment on TGFB1 and ITGA5 genes, leading to disruption of the-gene-specific-chromatin-looping structures. This dramatically recruited PolII and AcH3, active transcription marks, causing rapid induction of the gene transcriptions. Indeed, induced EMT-related genes directly led to morphological changes with EMT traits. We ultimately found that cancer stem cell-like cells showed same results with mesenchymal cancer and Rad21-KD epithelial cells. These findings indicate that the initiation of EMT in cancer might crucially require changes in high-order-chromatin structures of EMT-related genes mediated by cohesin, contributing to rapid and precise reversible changes in EMT or MET state to adapt to phenotypes of human cancer development. Citation Format: Jiyeon Yun. Disruption of intrachromosomal interactions by deficient cohesin initiate epithelial-mesenchymal transition and stemness in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4533.
술과 간 (상식과 지식)
Authors: 정영걸 ( Young Kul Jung )
Journal: Clinical and Molecular Hepatology (2011)

Alcoholic liver disease is a cause of cirrhosis and liver-related mortality. In addition, alcohol abuse represents a major health problem in Korea, and many people have many questions about alcohol and alcoholic liver disease. Recently as the internet evolves, there have been indiscriminate informations about alcohol drinking. Thus, in this report, we tried to describe the medical evidence of alcohol drinking and liver disease.
Abstract 3836: Novel conditionally active biologic anti-Axl antibody-drug conjugate demonstrates anti-tumor efficacy and improved safety profile
Authors: Cathy Chang, Gerhard Frey, William J. Boyle, Leslie L. Sharp, Jay M. Short
Journal: Cancer Research (2016)

Abstract Axl is a TAM family receptor tyrosine kinase that has been implicated in the pathogenesis of many cancer types. The high level of expression on the cancer cell surface has made it an attractive target for antibody therapeutics. However, Axl is expressed on many normal tissues and has been implicated in wide ranging requisite biological processes including response of endothelial cells to vascular injury, hematopoiesis, and regulation of immune responses. This normal tissue expression may limit Axl as a target for antibody-drug-conjugates (ADC). Conditionally Active Biologics (CAB) technology is a proprietary platform that selects antibodies that bind to target antigen in the context of diseased tissues, but not normal tissues, by taking advantage of the unique cancer microenvironment that is produced largely as a result of the Warburg effect. Using our CAB technology, we have identified anti-Axl Abs that reversibly bind to recombinant Axl and Axl expressing cells under conditions that are present in the tumor microenvironment but not in normal tissues. CAB-Axl antibodies were then conjugated to a model toxin payload to generate CAB-Axl-ADCs. The CAB-Axl-ADCs were active against Axl positive human tumor xenografts with tumor stasis observed at 1mg/kg weekly and tumor regressions observed at 1 mg/kg twice a week dose levels. A non-specific IgG-ADC showed minimal efficacy at the same dose levels. Single dose studies in cynomolgus macaques have demonstrated that CAB-Axl-ADC has reduced liver toxicity and immune system effects compared to Axl-ADCs that bind to Axl under normal conditions. In conclusion, our data is consistent with our work on CAB-EGFR antibodies, and suggests that ADCs generated using the CAB technology provides biologics with increased therapeutic index. Specifically, the CAB-Axl-ADC is an excellent candidate for evaluation as a treatment for human cancers that are Axl positive. Citation Format: Cathy Chang, Gerhard Frey, William J. Boyle, Leslie L. Sharp, Jay M. Short. Novel conditionally active biologic anti-Axl antibody-drug conjugate demonstrates anti-tumor efficacy and improved safety profile. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3836.
Abstract 4270: UMR957: a new osteogenic osteosarcoma cell-line derived from an osteoprotegerin null mutant mouse
Authors: Benjamin Navet, Jérome Amiaud, Céline Charrier, Thibaut Quillard, Bénédicte Brounais-Le Royer, Dominique Heymann, Frederic P.R. Lezot.
Journal: Cancer Research (2016)

Abstract Background: Mouse osteosarcoma cell-lines enabling in vivo studies in syngeneic mouse strains are rare but important for preclinical studies. Existing cell-lines when injected are mainly osteolytic with a moderate tumor osteoid tissue formation. There is a crucial need for new cell-lines with higher osteogenic characteristic. Methods: A female osteoprotegerin null mutant mouse, breed in the animal house of the Faculty of Medicine from the University of Nantes (France), spontaneously developed an osteosarcoma on the left tibia. The mouse was sacrificed, a biopsy was place in culture for further in vitro and in vivo (injections) studies and the tumor was analyzed using μ-CT, μ-radiography, classical histology and immunohistochemistry. Results: μ-CT and μ-radiography analyses evidenced that the tumor developed in the Opg-/- mouse was highly osteogenic with an important tumor osteoid tissue that colonized most of the surrounding soft tissues. A total destruction of the tibia was observed. Histology and immunohistochemistry confirmed the presence of an osteosarcoma with an important expression of most bone markers as Osterix. An important vascularization was evidenced in the tumor as the presence of numerous TRAP positive cells. Monocyte/macrophage and T-lymphocyte cells were also present in this tumor. From the biopsy a cell-line was obtained and named UMR957. This cell-line evidenced all markers of the osteoblast cell. When injected in the tibia vicinity of either naïve C57BL/6J, Nude or Opg-/- mouse a highly osteogenic osteosarcoma was observed with similar features to the initial tumor. Conclusions: A new mouse osteosarcoma cell-line was obtained from a spontaneous tumor developed in an Opg-/- mouse. This cell-line when injected in syngeneic mouse recapitulates all features of the initial tumor more particularly its massive osteoid tissue formation. Citation Format: Benjamin Navet, Jérome Amiaud, Céline Charrier, Thibaut Quillard, Bénédicte Brounais-Le Royer, Dominique Heymann, Frederic P.R. Lezot. UMR957: a new osteogenic osteosarcoma cell-line derived from an osteoprotegerin null mutant mouse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4270.
Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): Phase II, randomized, double-blind SPACE trial.
Authors: Riccardo Lencioni, Josep M. Llovet, Guohong Han, Won-Young Tak, Jiamei Yang, Marie-Aude Leberre, Woody Niu, Kate Nicholson, Gerold Meinhardt, Jordi Bruix
Journal: Journal of Clinical Oncology (2012)

LBA154^ Background: The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients (pts) with intermediate-stage HCC (BCLC B). Methods: Pts were eligible if they had asymptomatic, unresectable, multinodular tumors without vascular invasion (VI) or extrahepatic spread (EHS); Child-Pugh A liver functional status; and ECOG PS 0. Pts were randomized to receive S 400 mg bid or matching P continuously (1 cycle = 4 wks) until progression. All pts received TACE with DEBDOX (150 mg doxorubicin; Biocompatibles UK Ltd) 3-7d after first dose of study drug, and then on d1 (±4d) of months 3, 7, and 13, and q6 months thereafter. The primary endpoint was time to radiologic progression (TTP) by independent review (predefined alpha = 0.15). Secondary endpoints were overall survival (OS), time to VI/EHS, time to untreatable progression (TTUP), and safety. Results: Of 452 pts screened, 307 were randomized to S (n=154) or P (n=153). The HR for TTP was 0.797 (95% CI, 0.588, 1.080; p=0.072). Median TTP (50th percentile) was 169d/166d in the S and P groups, respectively; TTP at the 25th and 75th percentiles (preplanned) was 112/88d and 285/224d in the S and P groups, respectively. There were no unexpected safety findings. Median treatment duration in the S and P groups was 4.8 and 6.3 months, respectively, and median daily dose of study drug was 566 mg and 791 mg, respectively. Conclusions: The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX, compared with TACE with DEBDOX alone. The combination was well tolerated; no new safety findings that would preclude use of the combination were observed. The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE. [Table: see text]
Pregnancy and breast-feeding
Authors: P. J. Mountford, A. J. Coakley
Journal: Clinical Nuclear Medicine (1998)

The administration of a radiopharmaceutical to a pregnant woman will result in exposure of the foetus to radiation emitted from adjacent maternal organs and from radioactivity transferred across the placenta. Administration to a breast-feeding mother will result in the secretion of radioactivity in her milk, and her infant will be exposed to the radiation emitted by the ingested radioactivity. In view of the increased awareness of the general public about the risks associated with ionizing radiation and the growing tendency to question clinical management, nuclear medicine services should adopt a range of measures. These include:
Olympus chose not to alert US doctors of infections linked to its duodenoscopes
Authors: Michael McCarthy
Journal: BMJ (2016)

Executives at Olympus chose not to alert its US customers to the fact that dozens of serious infections had been linked to its duodenoscopes despite the warning being issued to its European customers, a report in the Los Angeles Times , published 24 July, has said.1

Company emails filed in a Pennsylvania court as part of a patient lawsuit showed that in January 2013 an Olympus executive in the US, concerned about reports of infections in the US, asked in an email to the company’s Tokyo office whether the company …
Abstract 4209: Targeting GPNMB with 89Zr-CR011 for PET imaging of triple negative breast cancer
Authors: Bernadette V. Marquez, Supum Lee, Tibor Keler, Thomas Hawthorne, Jeremy Hoog, Shunqiang Li, Cynthia Ma, Suzanne E. Lapi
Journal: Cancer Research (2016)

Abstract Glycoprotein non-metastatic melanoma B (GPNMB) is a transmembrane protein overexpressed in 30 - 40% of triple negative breast cancer (TNBC) and has shown to be associated with metastasis and disease recurrence. An anti-GPNMB antibody drug conjugate, Glembatumumab Vedotin (CDX-011), is currently in Phase II clinical trials for the treatment of metastatic TNBC patients, with promising outcomes. Positron Emission Tomography using radiolabeled antibodies could be advantageous in stratifying patients who may benefit from CDX-011, tracking the biodistribution of CDX-011, and assessing GPNMB expression in vivo. To this end, we radiolabeled the naked antibody, Glembatumumab (CR011), with the positron-emitting 89Zr (half life = 3.3 days). We characterized the stability, affinity, rate of cellular internalization, and specificity of 89Zr-CR011 using various cell-binding assays in human TNBC cell lines. We determined that 89Zr-CR011 is stable in serum solution for up to 5 days, binds specifically to GPNMB+ TNBC cells with high affinity (KD = 16 nM), and internalizes rapidly (50% within 30 - 60 min). We conducted a biodistribution study from 1 - 12 days post administration via tail vein in GPNMB+ MDA-MB-468 xenografts to determine the time point at which we achieve the optimal tumor-to-nontarget ratios. A subset of mice was administered a blocking dose of unlabeled CR011 (100-fold excess, 1 mg/mouse), where we observed a 2.5-fold reduction in 89Zr-CR011 tumor uptake, confirming the specificity of 89Zr-CR011 for GPNMB+ TNBC tumors. PET imaging studies and dosimetry calculations are currently in progress. This preliminary study demonstrates that 89Zr-CR011 may be an excellent companion diagnostic agent for CDX-011 therapy and an essential tool to assess the function of GPNMB in vivo. Citation Format: Bernadette V. Marquez, Supum Lee, Tibor Keler, Thomas Hawthorne, Jeremy Hoog, Shunqiang Li, Cynthia Ma, Suzanne E. Lapi. Targeting GPNMB with 89Zr-CR011 for PET imaging of triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4209.
Abstract 14344: The Magnitude and Time Course of Stress Induced Left Ventricular Transient Ischemic Dilation: A CMR Perspective
Authors: John C Lisko, Daniel Morgenstern, Nicola Nicoloff, Brandon Mikolich, J. Ronald Mikolich
Journal: Circulation (2015)

Background: Transient ischemic dilation (TID) of the left ventricle is used in nuclear myocardial stress perfusion imaging to identify global myocardial ischemia due to multi-vessel atherosclerosis. Although the isotope is injected at peak stress, nuclear stress images are obtained 20-30 minutes later to allow for hepatic clearance of isotope. Cardiac MRI myocardial stress perfusion imaging is performed at peak regadenoson effect. Given the superior spatial resolution of CMR, it also useful for accurate assessment of LV dimensions, both at rest and after stress. This prospective study was designed to assess the time course of peak regadenoson TID with direct measurement of LV dimensions and volumes using CMR. Methods: A standard CMR myocardial perfusion protocol was modified by adding a short axis SSFP imaging sequence at the level of the papillary muscle tips, just before the 1st pass perfusion study at peak regadenoson effect, and again 20-30 minutes later, after delayed enhancement imaging was completed. Parameters for this study included LV end-diastolic diameter (EDD) and slice volume (EDV), LV end-systolic diameter (ESD) and slice volume (ESV). TID was defined as an increase in end-diastolic diameter at stress compared to rest. An independent sample t-test was used to compare mean values. Results: Data was obtained from 181 consecutive patients undergoing CMR stress studies over a 6 month period. Stress induced LV dilation occurred in 61 patients, but not in 120. Of 61 patients with stress induced LV dilation, the mean slice EDV at rest was 18.24 mL3 and increased to 19.83 mL3 at stress (p&lt;.05). At 20-30 minutes post regadenoson, mean slice volume remained non-significantly elevated at 18.84mL3 (p=.415) relative to the baseline slice EDV. Of the 120 patients without stress induced dilation, mean slice EDV decreased from 21.10 mL3 at rest to 19.65 mL3 at stress (p&lt;.05). Mean slice volume remained non-significantly decreased at 20-30 minutes post stress (p=.188). Conclusions: These data suggest that maximum TID occurs at the time of peak regadenoson effect and attenuates to baseline over 20-30 minutes. Because of the inherent delay in obtaining myocardial stress perfusion images with a nuclear technique, CMR stress assessment of TID may be preferable.
Abstract 1795: The feasibility study of a randomized cancer screening trial in China
Authors: Ping Hu, Min Dai, Jufang Shi, Jiansong Ren, Jiang Li, Xianzhen Liao, Lingbin Du, Yuqing Liu, Zhaoli Chen, Ning Wu, Qian Liu, Paul Pinsky, Philip Prorok, Richard Fagerstrom, Martina Taylor, Barnett Kramer, Jie He
Journal: Cancer Research (2016)

Abstract Lung cancer has been the leading cause of cancer death in China since the 1990s and the disease burden likely will increase. The US National Lung Screening Trial (NLST) showed a 16-20% mortality reduction in a high-risk population that had undergone Low-Dose Computed Tomography (LDCT). China would like to confirm the main result from the US NLST in the Chinese population. The aim of this study is to obtain necessary information on performance of the organizations involved in designing, conducting, monitoring and managing the study. Another goal is to test colorectal cancer screening strategies in China. This is a first randomized trial on lung and colorectal cancer screening in China. The feasibility study will aid in the development of a practical design for the Randomized Cancer Screening Trial in China. This study has been carried out in three cites (Changsha city, Hunan province; Lanzhou city, Gansu province; and Haining city, Zhejiang province) since August, 2014. Individuals at elevated risk of lung cancer were randomized into three arms: annual low-dose helical CT exams for three years (T0, T1, T2) and baseline colonoscopy (T0); two low-dose helical CT exams (T0, T2) plus annual faecal immunochemical test (OC-faecal immunochemical tests at T0, T1, T2); and annual InSure-faecal immunochemical tests combined with Septin 9 test (T0, T1, T2). All participants will be followed for at least three years from randomization to yield data relevant to answering the study objectives. As of March 31, 2015, a total of 2696 eligible participants were enrolled at 3 cancer hospitals and randomly assigned to three study arms (894 in arm 1, 902 in arm 2, and 900 in arm 3). The gender distribution is 53% male and 47% female. Baseline characteristics of the study population by age, gender and total pack-year exposure were balanced. The rate of adherence to LDCT screening at the first round (T0) was 89.0%. 1598 participants received LDCT in the first round. The rate of abnormality was 77.4% with LDCT and 6.5% and 6.1% with suspicious for lung cancer for arm 1 and arm 2 respectively at T0. 2150 participants received colorectal cancer screening. The positivity was 34.1% with colonoscopy screening, 8.0% with OC-FIT test, 4.5% with InsureFIT test, and 5.8% with Septin9 test. Citation Format: Ping Hu, Min Dai, Jufang Shi, Jiansong Ren, Jiang Li, Xianzhen Liao, Lingbin Du, Yuqing Liu, Zhaoli Chen, Ning Wu, Qian Liu, Paul Pinsky, Philip Prorok, Richard Fagerstrom, Martina Taylor, Barnett Kramer, Jie He. The feasibility study of a randomized cancer screening trial in China. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1795.
Abstract 4007: A novel immunotherapy, INT230-6, is able to induce high rates of complete response in mice through a cytotoxic T-cell-dependent mechanism
Authors: Ian B. Walters, Anja C. Bloom, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky
Journal: Cancer Research (2016)

Abstract INT-230-6 is a combination of cisplatin, vinblastine and an amphiphilic cell penetration excipient that when administered intratumorally (IT) can induce complete regression in drug-injected and bystander established colon26 tumors. INT230-6 also has the ability to induce long term protection in mice against intravenous (IV) or subcutaneous (SC) re-inoculation of the cancer cells. This long term protection is dependent on induction of both CD4 and CD8 cells as evidenced by in vivo depletion prior to tumor re-inoculation. Previous studies had not elucidated whether the initial drug-injected tumor regression in naive mice was mainly due to the formulation's direct cytotoxicity or whether early tumor regression is dependent also on immune- based cell killing. To address this question, BALB/c mice were inoculated with 1×106 Colon26 cells SC. Tumors were grown to a mean of 300mm3. INT230-6 was administered intratumorally daily for 5 days (day 0 to 4). At the same time mice were treated either with an IgG control, or with rat anti mouse anti-CD4, anti-CD8 or both anti -CD4/CD8 on days 0,1,5,8,15. T cell subset depletion was confirmed by flow cytometry. In preliminary data, INT230-6 treatment resulted in regression from baseline in all mice with a complete regression of the large tumors in 40-80% of mice in the INT230-6 arm alone or the arm with IgG control. The CD4 depleted mice had a similar CR rate of 70%. However, in the CD8 depleted or the dual depleted (CD4/8) mice, tumors regrew after initial regression and no CR was observed. These results suggest that intratumoral administration of INT230-6 in addition to improving the direct cytotoxicity of cisplatin and vinblastine (data shown previously), also induces a potent CD8 tumor-specific T-cell response which participates in regression of the injected lesion, and may be able to similarly target distant lesions such as metastases. Citation Format: Ian B. Walters, Anja C. Bloom, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky. A novel immunotherapy, INT230-6, is able to induce high rates of complete response in mice through a cytotoxic T-cell-dependent mechanism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4007.
Cause-Specific Conditional Survival In 2603 Consecutive Patients Undergoing Autologous Hematopoietic Cell Transplantation (aHCT) Over a 20-Year Period
Authors: Ari M. Vander Walde, Can-Lan Sun, Liton Francisco, Saro Armenian, Jennifer Berano Teh, F. Lennie Wong, Neal Kogut, Amrita Krishnan, Auayporn Nademanee, Leslie Popplewell, Anthony Selwyn Stein, Stephen J. Forman, Smita Bhatia
Journal: Blood (2010)