tbuckley/cabot-search huggingface dataset:
Abstract 2098: Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line
Authors: Lauren A. Solomon, Stephen K.h. Li, Jan Piskorz, Li S. Xu, Rodney P. DeKoter
Journal: Cancer Research (2015)

Abstract Background. The E26-transformation-specific (ETS) transcription factor Spi-B is required for the survival of Activated B Cell-type Diffuse Large B Cell Lymphoma cell lines and is recurrently amplified in B cell lymphoma. The ETS transcription factor PU.1 is highly related to Spi-B. Both PU.1 and Spi-B are expressed in B lymphoma cell lines, and have been demonstrated to redundantly activate transcription of genes required for differentiation and function. We hypothesized that Spi-B and PU.1 occupy similar regions of chromatin within the genome of a B lymphoma cell line. Results. To compare binding regions of Spi-B and PU.1, murine WEHI-279 lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1 or Spi-B. Anti-FLAG chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) was performed. Analysis for high-stringency enriched genomic regions demonstrated that PU.1 occupied 4528 regions and Spi-B occupied 3360 regions. 1900 of these regions exhibited at least 100 base pairs of overlap for both factors. Regions bound by Spi-B and PU.1 were frequently located within genes associated with immune response and activation of B cells. Motif-finding revealed that both transcription factors were predominantly located at the ETS core domain (GGAA), however, other unique motifs were identified when examining regions associated with only one of the two factors. Motifs associated with unique PU.1 binding included POU2F2, while unique motifs in the Spi-B regions contained a combined ETS-IRF motif. Conclusions. Our results suggest that complementary biological functions of PU.1 and Spi-B may be explained by their interaction with a similar set of regions in the genome of B lymphoma cells. However, sites uniquely occupied by PU.1 or Spi-B provide insight into their unique functions. Citation Format: Lauren A. Solomon, Stephen K.h. Li, Jan Piskorz, Li S. Xu, Rodney P. DeKoter. Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line. [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 2098. doi:10.1158/1538-7445.AM2015-2098
CXCR7 Functions Together with CXCR4 in SDF-1/CXCL12 Induced CD34+ Hematopoietic Progenitor Cell Cycling Through β-Arrestin 2-Dependent Akt Activation
Authors: Frederic Torossian, Aurélie Chabanon, Denis Clay, Bernadette Guerton, Adrienne Anginot, Richard Proust, Jean-Francois Ottavi, Emmanuel Dornier, Laetitia Boutin, Christophe Desterke, Mark Scott, Jean-Jacques Lataillade, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2012)
Abstract LB-205: Myeloid cells are required to establish an immune-suppressive regulatory network in pancreatic cancer by activating the PD-1/PD-L1 checkpoint
Authors: YAQING ZHANG, ESHA MATHEW, FLOR MENDEZ, KEVIN FLANNAGAN, DIANE SIMEONE, MARINA PASCA DI MAGLIANO
Journal: Cancer Research (2015)

Abstract Background: Pancreatic cancer is characterized by the accumulation of a fibro-inflammatory stroma. Myeloid cells are a predominant population within the stroma. Different myeloid cell subsets have been correlated with tumor promotion and unmasking of anti-tumor immunity. Objective: The goal of this study was to determine the effect of myeloid cell depletion on the onset and progression of pancreatic cancer, and to understand the relationship between myeloid cells and T cell infiltration and activity within the pancreatic cancer microenvironment. Methods: Primary mouse pancreatic cancer cells were transplanted in CD11b-DTR mice. CD11b+ cells (most myeloid cell populations) were depleted by Diphtheria Toxin treatment; either at the time of tumor implantation or after tumors had formed. Results Depletion of myeloid cells delayed tumor initiation. In pre-established tumors, myeloid cell depletion resulted in arrest of growth or tumor regression. We observed that tumor regression was dependent myeloid cell-mediated blockade of CD8+ T cell anti-tumor activity. We investigated the mechanism of this inhibition. We found that myeloid cells regulate expression of the immune checkpoint ligand Programmed death-ligand 1 (PD-L1) in the tumor cells in an EGFR/MAPK dependent manner. Conclusions: Our results show that myeloid cells regulate a complex network of signals that ensure immune suppression within the pancreatic cancer microenvironment. Moreover, we show that depletion of the myeloid cell population is sufficient to restore anti-tumor immunity mediated by CD8+ T cells, a finding with implications for the design of immune therapies for pancreatic cancer. Citation Format: YAQING ZHANG, ESHA MATHEW, FLOR MENDEZ, KEVIN FLANNAGAN, DIANE SIMEONE, MARINA PASCA DI MAGLIANO. Myeloid cells are required to establish an immune-suppressive regulatory network in pancreatic cancer by activating the PD-1/PD-L1 checkpoint. [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-205. doi:10.1158/1538-7445.AM2015-LB-205
Abstract 4176: The homeobox gene DLX4 stimulates inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer
Authors: Bon Q. Trinh, Song Yi Ko, Dhwani Haria, Nicolas Barengo, Honami Naora
Journal: Cancer Research (2015)

Abstract Increasing evidence indicates that the free radical gas nitric oxide plays an important role in stimulating angiogenesis. However, the mechanisms that control nitric oxide-mediated angiogenesis in tumors are poorly understood. We previously identified that DLX4, a transcription factor encoded by a homeobox gene, stimulates ovarian tumor progression and correlates with poor outcomes of ovarian cancer patients. In this study, we identified that high DLX4 expression in ovarian cancer specimens is strongly associated with elevated expression of inducible nitric oxide synthase (iNOS), an enzyme that generates nitric oxide. DLX4 induced iNOS expression in ovarian cancer cells in vitro and in xenograft models. We identified that DLX4 interacts with STAT1 and induces iNOS expression in a STAT1-dependent manner. In in vitro studies, inhibition of iNOS abrogated the stimulatory effects of DLX4 on nitric oxide production, vascular endothelial growth factor expression and endothelial cell growth. Furthermore, inhibition of iNOS abrogated the stimulatory effects of DLX4 on tumor microvessel density and ascites formation in ovarian cancer xenograft models. Collectively, our findings indicate that DLX4 contributes to ovarian tumor progression in part by promoting nitric oxide-mediated angiogenesis. This is the first report that functionally links the aberrant expression of a developmental patterning gene in tumors with free radical gas generation. Note: This abstract was not presented at the meeting. Citation Format: Bon Q. Trinh, Song Yi Ko, Dhwani Haria, Nicolas Barengo, Honami Naora. The homeobox gene DLX4 stimulates inducible nitric oxide synthase-mediated angiogenesis in 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 4176. doi:10.1158/1538-7445.AM2015-4176
Progress for Soft Tissue Sarcoma
Authors: Rebecca Voelker
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract 5105: The imprinted tumor suppressor gene NDN inhibits cell motility in ovarian cancer by reactivating FAK and RhoA
Authors: Hailing Yang, Partha Das, Weiqun Mao, Rebecca T. Marquez, Zhen Lu, Robert C. Bast
Journal: Cancer Research (2015)

Abstract Ovarian cancers exhibit a distinctive pattern of metastasis over the surface of the peritoneum. The ability of tumor cells to migrate and invade is a prerequisite for metastasis and cancer progression. Imprinted tumor suppressor genes are of particular interest in that only a single allele is expressed and function can be lost in a single event. Here we report that an imprinted tumor suppressor gene, NDN, can suppress ovarian cancer cell migration and inhibit cell motility. NDN is a maternally imprinted gene consistently expressed in normal ovarian epithelium, but dramatically downregulated in the majority of ovarian cancers. Little or no NDN expression could be detected by immunohistochemistry in 73% of 351 epithelial ovarian cancers. NDN was also downregulated in 10 ovarian cancer cell lines with total loss in 6 of 10. Re-expression of NDN in SKOv3ip cells significantly inhibited cell migration and invasion by wound healing and Boyden Chamber assays. NDN re-expression disrupted actin stress fiber formation and prevented focal adhesion kinase (FAK) and paxillin assembly at the focal adhesion site by fluorescence microscopy. NDN re-expression reduced FAKY397 autophosphorylation by 50% and reduced SrcY416 phosphorylation by 25%. NDN re-expression also blocked RhoA signaling pathway by decreasing levels of active GTP-RhoA. Our results indicate that NDN deactivates FAK-RhoA signaling pathway in ovarian cancer cells, leading to disruption in stress fiber and focal adhesion formation, and thus suppresses cancer cell motility. Citation Format: Hailing Yang, Partha Das, Weiqun Mao, Rebecca T. Marquez, Zhen Lu, Robert C. Bast. The imprinted tumor suppressor gene NDN inhibits cell motility in ovarian cancer by reactivating FAK and RhoA. [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 5105. doi:10.1158/1538-7445.AM2015-5105
514. Clinical Trials of Oncolytic Adenovirus-Mediated Gene Therapy
Authors: Svend O. Freytag, Benjamin Movsas, Hans Stricker
Journal: Molecular Therapy (2016)

For the past 20 years we have been developing a multi-modal, gene therapy-based approach for the treatment of cancer. Our therapeutic platform utilizes an oncolytic adenovirus to deliver a pair of cytotoxic "suicide" genes to the tumor. The oncolytic adenovirus generates an anti-tumor effect by replicating in, and destroying, cancer cells (oncolytic viral therapy). The therapeutic effect of the oncolytic adenovirus is enhanced by invoking two cytotoxic gene systems, which render malignant cells sensitive to specific pharmacological agents (cytotoxic gene therapy) and sensitize them to ionizing radiation (radiosensitization). The combined effects of these three modalities result in significant tumor cell destruction and release of tumor antigens, which, when coupled with the robust immune response elicited by the oncolytic adenovirus, generate an environment suitable for tumor antigen processing and cross-presentation that may culminate in the development of anti-tumor immunity. Under four Investigational New Drug (IND) applications, we have evaluated the toxicity and efficacy of our multi-modal approach in six phase 1/2 trials of prostate cancer using four different oncolytic adenoviruses (Figure 1). These studies have demonstrated that our approach is safe and evidence of efficacy has been obtained. With respect to safety, there were no dose-limiting toxicities (DLTs) or treatment-related serious adverse events (SAEs) in over 100 patients treated to date. Only 6% of the adverse events were ≥ grade 3 with the vast majority being transient and asymptomatic. With respect to efficacy, in the locally recurrent setting following radiation failure, men who received the gene therapy exhibited a significant lengthening of PSA doubling time (PSADT), a surrogate endpoint that is highly prognostic for the development of distant metastases and prostate cancer-specific mortality. At 7 years, there was an improvement in disease-specific survival relative to well-matched historical controls. When combined with radiation therapy in the newly-diagnosed setting, the gene therapy reduced by 42% the percentage of men who had a positive prostate biopsy 2 years after treatment in a prospective, randomized, controlled phase 2 trial. An even greater treatment effect (i.e., 60% reduction) was observed in men with a low tumor burden at baseline. Together, the results demonstrate that oncolytic adenovirus-mediated gene therapy has the potential to improve tumor control in multiple settings of prostate cancer. To improve our approach further, we have generated a new oncolytic adenovirus expressing IL-12, which is now in the clinic. Updated results of our randomized controlled phase 2 trial (median follow-up 6 years) will be presented along with early results of our ongoing phase 1 trial with the oncolytic adenovirus expressing IL-12.
Multiple Unit Umbilical Cord Blood Transplantation with Total Body Irradiation, Etoposide and Antithymocyte Globulin for Adult Hematologic Malignancy Patients.
Authors: Ronald Sobecks, Edward Copelan, Matt Kalaycio, Medhat Askar, Lisa Rybicki, Sheila Serafino, Mary Serafin, Roger Macklis, Robert Dean, Brad Pohlman, Steve Andresen, Brian J. Bolwell
Journal: Blood (2009)
Management of Anemia in Patients with Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study
Authors: Heinz Ludwig, Pierre Soubeyran, Matti Aapro, Carsten Bokemeyer, Michael Muenzberg, Matthew Turner, Karen MacDonald, Tara Albrecht, Ivo Abraham
Journal: Blood (2008)
A Novel Mechanism for Intrachromosomal Gene Amplification in Multiple Myeloma: 1q12 Pericentromeric Heterochromatin Mediates Breakage- Fusion-Bridge Cycles of the 1q12~23 Amplicon
Authors: Jeffrey Sawyer, Erming Tian, Edward Thomas, Mark Koller, Collin Stangeby, Gael Sammartino, Linda Goosen, Charles Swanson, Regina Lichti Binz, Bart Barlogie, John Shaughnessy
Journal: Blood (2008)
<i>PIK3CA</i> mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation
Authors: Gray R. Anderson, Suzanne E. Wardell, Merve Cakir, Lorin Crawford, Jim C. Leeds, Daniel P. Nussbaum, Pallavi S. Shankar, Ryan S. Soderquist, Elizabeth M. Stein, Jennifer P. Tingley, Peter S. Winter, Elizabeth K. Zieser-Misenheimer, Holly M. Alley, Alexander Yllanes, Victoria Haney, Kimberly L. Blackwell, Shannon J. McCall, Donald P. McDonnell, Kris C. Wood
Journal: Science Translational Medicine (2016)

Inhibitors of BCL-X L , combined with inhibition of the mTOR/4E-BP axis, drive regressions of PIK3CA mutant breast tumors.
655. CD133-Targeted Oncolytic Adenovirus Exhibits Anti-Tumor Effect by Attacking Colon Cancer Stem Cells
Authors: Mizuho Sato-Dahlman, Yoshiaki Miura, Masato Yamamoto
Journal: Molecular Therapy (2016)

Colorectal cancer is the third most common cancer in the world and about 50% of patients relapse after treatment. Cancer stem cells (CSCs) have contribution to recurrence, metastasis and and chemotherapy resistant of colorectal cancers. CD133 (Prominin-1), a member of the transmembrane glycoprotein family, is a marker of CSCs in several cancers and is also generally accepted as a colorectal cancer stem cell marker. CD133 expression was correlated with recurrence, metastases and chemotherapy resistance, as well as poor prognosis in colorectal cancer. It is therefore reasonable to develop CSCs-directed therapeutic strategies by employing CD133 as a target molecule. Recently, we have established a method for isolating transductionally-targeted adenovirus by high-throughput screening. In this study, the CD133-specific Oncolytic Adenovirus (OAd) was isolated by using this novel system, and the resultant virus was tested for the oncolytic activity both in vitro and in vivo. CD133-targeted OAd (AdML-TYML) showed strong binding to CD133-positive cells (293-CD133 and LoVo (CD133 (+) human colon carcinoma)), not to CD133-negative cells (parental 293 and LS174T (CD133 (-) human colon carcinoma)) and this virus also showed strong oncolysis selectively in LoVo cells, whereas there was no effect on LS174T cells. In the analyses of the effect of AdML-TYML on colorectal cancer stem cells, CD133-targeted OAd treatment leads to inhibition of tumor establishment of CD133-positive colorectal cancer cell lines in nude mice. 100% of the mice inoculated with non-infected LoVo cells had developed tumors, while 0% of the mice inoculated with AdML-TYML infected LoVo cells had done so. In addition, when the anti-tumor effect of the CD133-targeted OAd was analyzed in established tumors of CD133(+) colorectal cancer subcutaneous xenografts, intra-tumor (i.t.) administration of AdML-TYML exhibited significantly stronger antitumor effect compared to its counterpart with wild type fiber. We focused on the CD133 as a target molecule of CSCs in colon cancer and successfully identified potent CD133-targeting OAd using high-throughput screening system. The CD133-targeted OAd exhibited selective infectivity and oncolysis to CD133-positive cells and anti-tumorigenic activity against colon cancer cells. The ability of CSCs-targeted Ad such as CD133-targeted OAd to infect and kill CSCs has important implications for the prevention of metastases and relapses in a variety of cancers.
Zirconia dental implants: where are we now, and where are we heading?
Authors: Norbert Cionca, Dena Hashim, Andrea Mombelli
Journal: Periodontology 2000 (2016)

Abstract Despite decades of titanium as the gold standard in oral implantology, the search for alternatives has been growing. High esthetic standards and increasing incidence of titanium allergies, along with a rising demand for metal‐free reconstructions, have led to the proposal of ceramics as potential surrogates. Following numerous experimental studies, zirconium dioxide (zirconia) has earned its place as a potential substitute for titanium in implantology. Yet, despite zirconia's excellent biocompatibility and tissue integration, low affinity to plaque and favorable biomechanical properties, early failures were significantly higher for zirconia implants than for titanium implants. Technical failure as a result of fracture of the material is also a major concern. So far, zirconia implants have been mainly manufactured as one‐piece implant systems because of the material's limitations. Nevertheless, various two‐piece systems have been progressively emerging with promising results. Screw‐retained abutments are desirable but present a major technical challenge. Innovation and technical advances will undoubtedly lead to further improvement in the reliability and strength of zirconia implants, allowing for novel designs, connections and reconstructions. Additional clinical studies are required to identify all relevant technical and biological factors affecting implant success and patients’ satisfaction. However, the evidence for a final verdict is, at present, still incomplete.
Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS
Authors: Zhaoming Su, Yongjie Zhang, Tania F. Gendron, Peter O. Bauer, Jeannie Chew, Wang-Yong Yang, Erik Fostvedt, Karen Jansen-West, Veronique V. Belzil, Pamela Desaro, Amelia Johnston, Karen Overstreet, Seok-Yoon Oh, Peter K. Todd, James D. Berry, Merit E. Cudkowicz, Bradley F. Boeve, Dennis Dickson, Mary Kay Floeter, Bryan J. Traynor, Claudia Morelli, Antonia Ratti, Vincenzo Silani, Rosa Rademakers, Robert H. Brown, Jeffrey D. Rothstein, Kevin B. Boylan, Leonard Petrucelli, Matthew D. Disney
Journal: Neuron (2014)
Effects of TAK-442, a Direct FXa Inhibitor, and Fondaparinux on Platelet-Associated Prothrombinase in the Balloon Injured Artery of Rats
Authors: Masaki Kawamura, Noriko Konishi, Hiroe Katsuhiko, Yasuhiro Imaeda, Takuya Fujimoto, Keiji Kubo
Journal: Blood (2008)
Impact of traditional cardiovascular disease risk factors on long-term cardiovascular outcome in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: G. T. Armstrong, Y. Chen, T. Kawashima, C. A. Sklar, D. A. Mulrooney, E. J. Chow, W. Border, J. Durand, A. Mertens, M. Stovall, W. Leisenring, Y. Yasui, L. L. Robison, K. C. Oeffinger, L. Meacham
Journal: Journal of Clinical Oncology (2011)

9507 Background: Childhood cancer survivors have an increased risk of late-onset treatment-related cardiotoxicity. How traditional cardiovascular disease risk factors (CVRFs) modify this risk is unknown. Methods: Analyses included 14,358 >5 yr survivors of childhood cancer diagnosed 1970-86 (median age at last follow-up 31.9 yrs, range 5.6-58.9). Rates of obesity (BMI≥30), CVRFs requiring medical treatment (diabetes, hypertension, dyslipidemia) and cardiac outcomes (coronary artery disease, congestive heart failure, valvular abnormality, stroke and arrhythmia) were collected at baseline and subsequent follow-up questionnaires and compared to a sibling cohort (n=4,023). Associations between CVRFs and cardiac outcomes and the predictive ability of CVRFs for future cardiac events were assessed. Results: Survivors reported higher rates of diabetes (3.7% vs. 2.5%, OR= 1.7, 95% CI 1.4-2.1), hypertension (15.1% vs. 9.7%, OR= 2.1, 95% CI 1.9-2.4),dyslipidemia (8.2% vs. 5.7%, OR= 1.9, 95% CI 1.7-2.3), but not obesity (24.3% vs. 25.4%, OR= 1.0, 95% CI 0.9-1.1), and a higher rate of clustering of CVDRFs (any 3 of 4 CRFs, 2.5% vs. 1.9%, OR= 1.7, 95% CI 1.3-2.2) compared to siblings. Cumulative incidence (CI) at 45 years of age for coronary artery disease, congestive heart failure, valvular abnormality, stroke and arrhythmia was 4.2%, 6.7%, 6.2%, 2.5%, and 11.7%, respectively. The 45-yr CI for cardiac-related mortality was 1.6% (95% CI 1.2-1.9; standardized mortality ratio = 4.4, 95% CI 3.6-5.3). Presence of a CVRF cluster was associated with an increased risk of congestive heart failure (RR= 4.2, 95% CI 2.6-6.7) among survivors treated with anthracyclines (>250mg/m2) and of coronary artery disease (RR= 4.6, 95% CI 3.0-7.0) among those who received chest-directed radiotherapy. Presence of hypertension (RR=2.2, 95% CI 1.6-3.1) and obesity (RR=1.3, 95% CI 1.1-1.6) were predictive of future cardiac events. Conclusions:Among adult survivors of childhood cancer exposed to cardiotoxic therapy, presence of traditional cardiovascular disease risk factors further increase the risk for poor cardiovascular outcome.
Prolonged Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: Association with Reduced Ploidy and Immaturation of Megakaryocytes
Authors: Xiao-hui Zhang, Haixia Fu, Lan-Ping Xu, Dai-Hong Liu, Kaiyan Liu, Xiao Jun Huang
Journal: Blood (2010)
TIM-3 and Its Ligand, Galectin-9 Constitute a Pan-Myeloid Autocrine Loop to Develop and Maintain Malignant Stem Cells in Most Human Myeloid Leukemia
Authors: Yoshikane Kikushige, Junichiro Yuda, Takahiro Shima, Toshihiro Miyamoto, Koichi Akashi
Journal: Blood (2014)