tbuckley/cabot-search huggingface dataset:
Abstract LB-061: Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism
Authors: Heather Schofield, Filip Bednar, Meredith Collins, Wei Yan, Yaqing Zhang, Nikhil Shyam, Jaime Eberle, Kenneth Olive, Nabeel Bardeesy, Daisuke Nakada, Diane Simeone, Sean Morrison, Marina Pasca di Magliano
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in the United States. Many characteristic mutations in PDAC are known, but this information has so far failed to produce the development of effective treatments, highlighting the need for deeper understanding of the processes that drive tumorigenesis. B-cell specific Moloney murine leukemia virus insertion site 1 (Bmi1), a Polycomb repressive group protein, is upregulated in PDAC and associated with poor prognosis. Our lab has shown that despite an oncogenic K-ras mutation, mice with pancreas specific loss of Bmi1 do not develop precancerous lesions, termed PanINs (Pancreatic Intraepithelial Neoplasia). This lack of PanIN development was also seen in the presence of pancreatitis, which is usually known to synergize with oncogenic K-ras to speed PanIN development. In other cancer types, Bmi1's effect on tumorigenesis was mechanistically linked to its regulation of the Ink4a/ARF genetic locus. However, we found that in PDAC, PanIN initiation was independent of Bmi1 control this locus. Further, impairment in the regulation of ROS generation was seen in vitro in pancreatic cancer cell lines lacking Bmi1. Regulating ROS generation is a vital step in the neoplastic process and has been shown in other systems to be controlled by Bmi1. Overall, in this work we have shown that expression of the Polycomb group protein Bmi1 is necessary for the initiation of pancreatic precancerous lesions, and that the mechanism of Bmi1 requirement is independent of its repression of the Ink4a/ARF genetic locus. Given the recent pre-clinical development of a Bmi1 inhibitor, this work could provide rationale for future treatment of pancreatic cancer, a truly devastating disease. Citation Format: Heather Schofield, Filip Bednar, Meredith Collins, Wei Yan, Yaqing Zhang, Nikhil Shyam, Jaime Eberle, Kenneth Olive, Nabeel Bardeesy, Daisuke Nakada, Diane Simeone, Sean Morrison, Marina Pasca di Magliano. Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism. [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 LB-061. doi:10.1158/1538-7445.AM2015-LB-061
Safety and Efficacy of Bendamustine with or without Rituximab in the Treatment of Heavily Pretreated Patients with Haematological Malignancies: A Multicenter Retrospective Study
Authors: Luigi Rigacci, Benedetta Puccini, Alberto Bosi, Sergio Cortelazzo, Sergio Storti, Andrea Carpaneto, Pier Luigi Zinzani, Chandrakala Toldo
Journal: Blood (2008)
Mini-Chromosome Maintenance (MCM) DNA Helicase Genes Influence Acute Myeloid Leukemia (AML) Replication and Response to Chemotherapy-Induced DNA Damage
Authors: Joe Chin-Sun Huang, Julia Sidorova, Sylvia Chien, Jin Dai, Ben Logsdon, Su-In Lee, Raymond J Monnat, Pamela S. Becker
Journal: Blood (2015)
Abstract 3269: Ezrin binds to DEAD-box RNA helicase DDX3 and regulates its function and protein level
Authors: Haydar Celik, Kamal P. Sajwan, Amrita V. Pai, Ben J. Marsh, Yasemin Saygideger Kont, Said Rahim, Jenny Han, Tsion Minas, Jeffrey A. Toretsky, Aykut Uren
Journal: Cancer Research (2015)

Abstract Ezrin is a member of the ezrin-radixin-moesin (ERM) family of actin-membrane linker proteins that play key roles in regulating cell shape, movement, adhesion and signal transduction pathways. The expression of ezrin is linked to the metastatic progression in several cancers including osteosarcoma (OS). We discovered a small molecule, NSC305787, that inhibits ezrin activity and metastatic phenotype both in vitro and in vivo. We hypothesized that the anti-metastatic effects of NSC308787 could be mediated through preventing specific protein-protein interactions involving ezrin. In this study, we used affinity pull-down coupled with mass spectrometry-based proteomic approach to unravel putative ezrin interactors that are competed away by NSC305787. We identified a number of candidate ezrin binding proteins that are associated with metastatic behavior and implicated in the regulation of stress granule dynamics and protein translation initiation. We selected DDX3, a DEAD-box RNA helicase, as a candidate for further analysis. We confirmed that ezrin directly binds to DDX3. Depletion of ezrin protein expression by RNA interference in several cancer cell lines resulted in substantial reduction in DDX3 protein levels without affecting its transcription, which suggested that ezrin is required for post-transcriptional maintenance of DDX3 in the cell. Paradoxically, recombinant ezrin specifically inhibited the RNA duplex unwinding activity and stimulated the ATPase activity of DDX3. Our data suggest that ezrin regulates the translation of mRNAs with 5′ secondary structure through DDX3, at least in part, through maintaining its intracellular protein level and/or modulating its unwinding and ATPase activities. Therefore, our findings suggest that a novel function of ezrin regarding the regulation of mRNA translation exists that is independent from its classical role as a cytoskeletal cross-linker protein at the plasma membrane. Citation Format: Haydar Celik, Kamal P. Sajwan, Amrita V. Pai, Ben J. Marsh, Yasemin Saygideger Kont, Said Rahim, Jenny Han, Tsion Minas, Jeffrey A. Toretsky, Aykut Uren. Ezrin binds to DEAD-box RNA helicase DDX3 and regulates its function and protein level. [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 3269. doi:10.1158/1538-7445.AM2015-3269
Abstract #963: Curcumin inhibits the growth of cervical cancer cells and suppresses HPV oncoproteins E6 and E7
Authors: Diane Maher, Maria Bell, EmmyLu O'Donnell, Meena Jaggi, Subhash Chauhan
Journal: Cancer Research (2009)

Introduction: Cervical cancer is one of the most common cancers in women worldwide and its incidence is associated with persistent infection with a high-risk genotype of human papillomavirus (HPV). The HPV oncoproteins, E6 and E7 are thought to direct uncontrolled growth of cervical cancer cells through decreased levels of p53 and inhibition of retinoblastoma protein (pRb), respectively. The use of chemopreventive agents, such as curcumin, in healthy women at high risk for developing cervical cancer (women with a pre-malignant lesion or infection with high risk HPV) may be a non-invasive and cost effective method for the treatment of cervical intraepithelial neoplasia. Specifically, the prevention of oncogenic viral protein expression (primarily HPV E6 and E7) is highly desirable. In this study, we have investigated the effect of curcumin on the growth of cervical cancer cells and the expression of HPV oncoproteins E6/E7. Methods: We have assessed the effect of curcumin (diferuloyl methane) on a variety of cervical cancer cell lines, including Caski, SiHa, C33A, C4-I and HeLa cells, using the CellTiter96 Aqueous One Solution Cell Proliferation Assay (Promega). Additionally, we have also established and utilized raft culture methods to investigate the inhibitory effect of curcumin in a more physiologically relevant in vitro model. To determine the effects of curcumin on the cellular and molecular level, immunoblotting, flow cytometry, immunofluorescence, and real time PCR analyses were performed using the Caski cell line model. Results: Curcumin shows a time and dose dependent inhibition on proliferation and colony forming ability in all cervical cancer cell lines examined. Additionally, curcumin treatment inhibits cellular migration in scratch assays. In Caski cells, curcumin treatment induces apoptosis by cleavage of both Poly (ADP-ribose) polymerase (PARP) and caspase 3. Interestingly, our results also suggest that curcumin causes suppression of HPV16 oncoproteins E6/E7. In a raft culture model using Caski cells, curcumin treatment reduced cell growth and thickening of the growing raft. Conclusion: We have shown that curcumin inhibits the growth of cervical cancer cells in both monolayer and raft culture models. Importantly, curcumin treatment also modulates the expression of HPV16 E6/E7 oncoproteins. Results of this study suggest a chemopreventive and therapeutic role of curcumin for cervical cancer.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 963.
Facilitation of Hematopoietic Reconstitution Via Inhibition of Bone Marrow Endothelial Cell-Mediated SDF-1 Signaling.
Authors: Phuong L. Doan, J. Lauren Russell, Heather A. Himburg, Sarah K. Meadows, Pamela Daher, Katherine Helms, Mamle Quarmyne, Jeffrey R. Harris, Tannishtha Reya, Nelson J. Chao, David G. Kirsch, John P. Chute
Journal: Blood (2010)
Abstract 3720: Diabetes and prostate cancer (CaP): Clinical characteristics and disparity in outcomes
Authors: Elaine Spangler, Charnita Zeigler-Johnson, Jonathan Mitchell, Timothy Rebbeck
Journal: Cancer Research (2015)

Abstract Introduction: Disparities in prostate cancer (CaP) outcomes are poorly understood, but are likely caused by multiple factors. The presence of comorbidities may contribute to disparate outcomes in at least two ways: by altering the biological course of disease, and by influencing overall survival probabilities that impact treatment decisions. Diabetes has been associated with CaP in a variety of settings, and there is evidence that AA men suffer from diabetes at a higher rate than men of other races. We examined whether presence of diabetes is related to prostate cancer recurrence measured by post-prostatectomy biochemical (PSA) failure (BF). Materials and methods: A prospective cohort of 554 European Americans (EA) and 184 African American (AA) CaP cases from the University of Pennsylvania were studied. We performed survival analysis for BF to evaluate the effect of diabetes on using Cox proportional hazards models adjusting for age, race, obesity, and Kattan score. Median post-prostatectomy follow-up was 40 months. Results: Prevalence of diabetes was 6.3% overall (12% in AA and 5% in EA, p&amp;lt;0.0001). AA men were more likely to be obese then EA men (33% vs. 19%, p = 0.001). During post-prostatectomy follow-up, 52 (28%) AA and 187 (33%) EA men experienced BF; 47 (9%) diabetic men and 691 (5%) non-diabetic men experienced BF. Diabetic men were twice as likely to experience BF as men without diabetes (HR = 2.2, 95% CI: 1.26-3.92). Diabetes had a significant effect in both EA (HR = 2.1, 95% CI: 1.02-4.37) and AA (HR = 3.4, 95% CI: 1.16-10.0). Conclusions. Being diabetic at time of CaP diagnosis increased the risk of prostate cancer recurrence, even after accounting for obesity and age. This effect was significant for both AA and EA, but the effect of diabetes appeared to be greater in AA. Diabetes may an important predictor of post-prostatectomy CaP outcomes. Citation Format: Elaine Spangler, Charnita Zeigler-Johnson, Jonathan Mitchell, Timothy Rebbeck. Diabetes and prostate cancer (CaP): Clinical characteristics and disparity in outcomes. [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 3720. doi:10.1158/1538-7445.AM2015-3720
Uric Acid Induces High Mobility Group Box1 Protein Release in Monocytes/Macrophages through P38 MAPK, ERK1/2, JNK and AP-1 Activation.
Authors: Kamal K. Biswas, Yoko Oyama, Kazuhiro Abeyama, Teruto Hashiguchi, Ikuro Maruyama
Journal: Blood (2004)
Insurance Expansion and Hospital Emergency Department Access: Evidence From the Affordable Care Act
Authors: Craig Garthwaite, Tal Gross, Matthew Notowidigdo, John A. Graves
Journal: Annals of Internal Medicine (2016)

Background: Little is known about whether insurance expansion affects the location and type of emergency department (ED) use. Understanding these changes can inform state-level decisions about the Medicaid expansion under the Patient Protection and Affordable Care Act (ACA). Objective: To investigate the effect of the 2014 ACA Medicaid expansion on the location, insurance status, and type of ED visits. Design: Quasi-experimental observational study from 2012 to 2014. Setting: 126 investor-owned, hospital-based EDs. Participants: Uninsured and Medicaid-insured adults aged 18 to 64 years. Intervention: ACA expansion of Medicaid in January 2014. Measurements: Number of ED visits overall, type of visit (for example, nondiscretionary or nonemergency), and average travel time to the ED. Interrupted time-series analyses comparing changes from the end of 2013 to end of 2014 for patients from Medicaid expansion versus nonexpansion states were done. Results: There were 1.06 million ED visits among patients from 17 Medicaid expansion states, and 7.87 million ED visits among patients from 19 nonexpansion states. The EDs treating patients from Medicaid expansion states saw an overall 47.1% decrease in uninsured visits (95% CI, −65.0% to −29.3%) and a 125.7% (CI, 89.2% to 162.6%) increase in Medicaid visits after 12 months of ACA expansion. Average travel time for nondiscretionary conditions requiring immediate medical care decreased by 0.9 minutes (−6.2% [CI, −8.9% to −3.5%]) among all Medicaid patients from expansion states. We found little evidence of similar changes among patients from nonexpansion states. Limitation: Results reflect shifts in ED care at investor-owned facilities, which limits generalizability to other hospital types. Conclusion: Meaningful changes in insurance status and location and type of ED visits in the first year of ACA Medicaid expansion were found, suggesting that expansion provides patients with a greater choice of hospital facilities. Primary Funding Source: Robert Wood Johnson Foundation.
354. Rheological Modification of Hydrodynamic Gene Delivery
Authors: Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Akiomi Ushida, Tomiichi Hasegawa, Kenya Kamimura, Dexi Liu, Shuji Terai
Journal: Molecular Therapy (2015)

The aim of this study is to clarify whether a rheological modification of hydrodynamic gene delivery (HGD) has a potential to sustain gene delivery efficiency with a limited injection volume. A saline-based DNA solution corresponding to 5% of body weight (NS) instead of 9%, which is used in a canonical HGD, was injected from the mouse tail vein with pCMV-Luc at 10 mg/ml in 5 sec. The activities of 6 kinds of solutes were evaluated to enhance gene delivery efficiency. Four solutes were contrast media (CM1-4) at 60 mg/ml of iodine concentration, which had various kinds of ionicity and osmolality. The others were mannitol (MAN) and glycerin (GLY), which were solubilized as the same concentration as that of a major component in CM1. Liver samples were collected 24 hours after the injections, and luciferase assay and immunohistochemistry (IHC) were conducted. The median values of luciferase activities after the delivery with CM1-4, MAN, GLY, and NS, and HGD were 3.2×109, 9.2×108, 3.5×109, 2.5×108, 1.4×109, 7.3×107, 1.7×106, and 1.6×1010 RLU/mg of protein, respectively. In IHC, the distributions of luciferase-positive cells after the injections with the solutes were similar to that of HGD. The luciferase activity of CM1 was significantly higher than that of NS (n=5, 5, p<0.01, Mann-Whitney U test). The levels of luciferase activities were not significantly different among CM1-4 (n=5, 3, 3, 3, p=0.16, Kruskal-Wallis test). The luciferase activities between CM1 and MAN were not significantly different from each other (n=5, 3, p=0.57, Mann-Whitney U test). These results suggested that the ionicity, osmolality, and iodine were not a primary factor of gene delivery efficiency in HGD. Therefore, we focused on another property. Elasticity is one of rheological properties of liquids to return to their original shape after removing stress. When fluids pass though a micro-orifice, the passed liquids attract a flow though the orifice. In general, the attracting force gets higher as the temperature becomes lower. The luciferase activity of GLY, which had the lower elasticity than CM1, was not significantly higher than that of NS (n=3, 5, p=0.14, Mann-Whitney U test). Furthermore, median values of luciferase activities of CM1 at 10, 20, 30, and 37°C were 5.0×109, 1.3×109, 9.7×108, and 1.2×108, respectively (p<0.05, Kruskal-Wallis test), while the elasticity of CM1 got higher as the temperature was lower. Based on these results, we speculated that the solution elasticity was a promising candidate to sustain gene delivery efficiency with a limited injection volume in HGD. The next step is to explore a substance providing higher elasticity to a DNA solution, and to evaluate its safety.
Transplantation of Cord Blood Expanded Ex Vivo with Copper Chelator.
Authors: E. Shpall, M. de Lima, K. Chan, R. Champlin, A. Gee, P. Thall, K. Komanduri, D. Couriel, B. Andersson, C. Hosing, S. Giralt, S. Safa Karandish, T. Tara Sadeghi, B. Muriera, T. Peled, F. Grynspan, A. Nagler, J. McMannis
Journal: Blood (2004)
Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort
Authors: Pierre-Jean Saulnier, Elise Gand, Gilberto Velho, Kamel Mohammedi, Philippe Zaoui, Mathilde Fraty, Jean Michel Halimi, Ronan Roussel, Stéphanie Ragot, Samy Hadjadj
Journal: Diabetes Care (2016)

We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes.Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors.Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD).In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.
Abstract 5117: Fluorescence-guided surgery of liver metastasis in orthotopic nude-mouse models
Authors: Takashi Murakami, Yukihiko Hiroshima, Shinji Miwa, Yano Shuya, Makoto Toneri, Mako Yamamoto, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Satoshi Hasegawa, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2015)

Abstract We report here the development of fluorescence-guided surgery of liver metastasis. HT29 human colon cancer cells expressing green fluorescent protein (GFP) were initially injected in the spleen of nude mice. Three weeks later, established liver metastases were then harvested and implanted to the left lobe of the liver in other nude mice in order to make an orthotopic liver metastasis model. Eleven mice with a single liver metastasis were randomized into BLS or FGS groups. Three weeks after the implantation, the left lobe of the liver with a single metastasis was exposed through a median abdominal incision. BLS was performed under white light. FGS was performed using a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System. Five mice were treated with BLS, six were treated with FGS. Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100. In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100. Citation Format: Takashi Murakami, Yukihiko Hiroshima, Shinji Miwa, Yano Shuya, Makoto Toneri, Mako Yamamoto, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Satoshi Hasegawa, Itaru Endo, Robert M. Hoffman. Fluorescence-guided surgery of liver metastasis in orthotopic nude-mouse 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 5117. doi:10.1158/1538-7445.AM2015-5117
HLA Class II Disparity Is Necessary and Sufficient for Induction of Effective Anti-Tumor Immunity by Donor Lymphocyte Infusion in a NOD/Scid Mouse Model for Human Acute Lymphoblastic Leukemia
Authors: Sanja Stevanovic, Marianke L.J. van Schie, Marieke Griffioen, J.H. Frederik Falkenburg
Journal: Blood (2011)