tbuckley/cabot-search huggingface dataset:
Abstract 1288: Does an increased underlying immune/inflammatory response in healthy females put them at a higher risk for thyroid cancer
Authors: Karnika Singh, Melanie Jones, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter
Journal: Cancer Research (2015)

Abstract The SEER (Surveillance, Epidemiology, and End Results Program) and American Cancer Society data indicate that the incidence of papillary thyroid cancer is ∼ 3 times greater in females, as compared to males. The American Cancer Society estimates that out of a total of ∼62,980 new thyroid cancer cases in 2014, approximately 47,790 of these will be women. There is strong evidence that supports the role of estrogen in the pathogenesis of thyroid cancer. Estrogen also plays a critical role in the inflammatory process. For example, mouse models have demonstrated that in vivo exposure to estrogen promotes an inflammatory response, including the enhanced secretion of Th-1 related cytokines (IFNγ, IL-12, IL-1β) and inflammatory chemokines (MCP-1 and MCP-5). Studies in rats and mouse models have shown that females exhibit stronger humoral and cellular immune responses as compared to males. As the association between inflammation and cancer is widely accepted, we hypothesize that an underlying immune and inflammatory response in the normal female thyroid puts it at a higher risk of developing cancer. The Cancer Genome Atlas (TCGA) provides a means to assess gender differences at the molecular level. Using the SUBIO platform version 1.17 (SUBIO Inc., Amami Island, Japan), we performed bioinformatics and statistical analyses on the Level 3 RNA-Seq data available in the TCGA Data Portal. Differential gene expression analysis of 39 normal thyroid samples (26 females and 13 males) revealed that out of the 20,531 genes analyzed, 73 genes exhibited &amp;gt;2 fold increased expression in females vs. males (p-value, 0.05). Of these 73 genes, 10 genes were involved in immune response and inflammation. We are currently analyzing expression levels of these genes on the RNA and protein levels. Such analysis will help us to elucidate a possible link between the gender disparity in thyroid cancer and inflammation. Citation Format: Karnika Singh, Melanie Jones, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter. Does an increased underlying immune/inflammatory response in healthy females put them at a higher risk for thyroid 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 1288. doi:10.1158/1538-7445.AM2015-1288
Prospective Trial of Pre-Transplant 5-Azacitidine on Hematopoietic Cell Transplantation Outcomes for Myelodysplastic Syndrome and CMML
Authors: Teresa Field, Janelle Perkins, Taiga Nishihori, Joseph Pidala, Hugo F. Fernandez, Marcie Tomblyn, Mohamed Kharfan-Dabaja, Lia Perez, Rami S. Komrokji, Jeffrey E. Lancet, Jongphil Kim, Ernesto Ayala, Melissa Alsina, Jose-Leonel ochoa-Bayona, Alan F. List, Claudio Anasetti
Journal: Blood (2010)
Phase II study of an optimized 5FU-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: A GERCOR study
Authors: T. Andre, F. Maindrault-Goebel, L. Mineur, F. Michel, M. Mabro, G. Ganem, M. Hebbar, D. Avenin, R. Moukhtar, A. De Gramont
Journal: Journal of Clinical Oncology (2004)

3554 Background: In the OPTIMOX study (André et al, ASCO 2003), 6 cycles of Folfox7 followed by simplified LV5FU2 maintenance were administered to decrease the neurotoxicity and to later allow FOLFOX7 reintroduction. Celecoxib is an anti-cox2 compound with anti-neoplastic properties such as angiogenic inhibition and apoptosis induction. We evaluated a new strategy exploring 1) the stop and go procedure (6 cycles of Folfox7 then stop and reintroduction Folfox7 at progression); 2) the addition of celecoxib during Folfox7 and chemotherapy-free interval (CFI). Methods: Patients (pts) with non resectable metastatic colorectal adenocarcinoma were treated in first-line by Folfox7: oxaliplatin 130 mg/m2 day (d1), and folinic acid 400 mg/m2 d1, and 5FU 46h 2400 mg/m2 every two weeks for 6 cycles. Chemotherapy was then interrupted and reintroduced at progression. Celecoxib 400 mg BID per os was administered during Folfox7 and CFI intervals until Folfox7 discontinuity for progression or limiting toxicity. 44 pts included, 42 eligible: Performans status (%) 0/1/2=45/43/12, median age 60 [31–76]. Half of patients had one metastatic site. Results: 42 pts are evaluable for safety and 41 for response. Grade 3–4 toxicity per pts (%) during the 6 first cycles of Folfox7 + celecoxib were neutropenia 5%, thrombocytopenia 17%, diarrhea 5%, nausea-vomiting 5%, neuropathy 2%, (maximal gr 3–4 toxicity 29%). During follow-up period (median 37 weeks), 2 pts presented grade 1–2 epigastralgia without ulcers and 1 digestive hemorrhage with gastritis. 1 CR, 15 PR (RR 39%; 95% CI: 24–54%), 18 SD (44%) and 7 PD (17%) were obtained (intent to treat). Median PFS was 28 weeks. 28/42 had a CFI (14 pts not evaluable for CFI: 5 metastasis resection after 3 months of therapy, 7 PD at 3 months of therapy, 2 out of protocol for toxicity). Median CFI duration was 72 days (range 29–147+) with 43% with PD after 2 months of CFI. Conclusions: In this phase II study, celecoxib combined with FOLFOX 7 is associated with a good safety and a response rate of only 39%. Pharmacokinetics and preclinical studies are needed to investigate potential interaction between celecoxib and FOLFOX 7 drugs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo
Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients with Liver Cirrhosis
Authors: Hager A. Ahmed Mohammed, Ju Dong Yang, Nasra H. Giama, Jonggi Choi, Hawa M. Ali, Kristin C. Mara, William S. Harmsen, Russell H. Wiesner, Michael D. Leise, Terry M. Therneau, Lewis R. Roberts
Journal: Liver Cancer (2016)

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance.We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009.Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance.While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners.
Disease Characteristics, Treatment and Outcome of Patients with Myelodysplastic Syndromes Relapsing after Allogeneic Stem Cell Transplantation
Authors: Anna Schuck, Ariane Dienst, Kathrin Nachtkamp, Pia Verena Schmidt, Esther Schuler, Roland Fenk, Mustafa Kondakci, Norbert Gattermann, Rainer Haas, Ulrich Germing, Guido Kobbe, Thomas Schroeder
Journal: Blood (2015)
568. Transient Manipulation of DNA Damage Repair Pathway Choice Improves Homology-Directed Repair During CRISPR/Cas9-Mediated Genome Editing
Authors: Pankaj K. Mandal, Bruna S. Paulsen, Richard Frock, Paula Gutierrez-Martinez, Wataru Ebina, Suneet Agarwal, Frederick Alt, Derrick J. Rossi
Journal: Molecular Therapy (2016)

CRISPR/Cas9 system allows efficient gene ablation through error-prone non-homologous end joining DNA repair. However, very low efficiency of homology-directed DNA repair (HDR) is the bottleneck in correcting genetic mutations of clinical relevance. Here we report that transient manipulation of DNA damage repair pathways increases the HDR frequency by 3-5 fold. Furthermore, we show that this approach is applicable to introduce precise genetic modifications at many genetic loci in multiple cell-types including human induced pluripotent stem (hiPS) cells. Furthermore, unbiased off-target mutational analysis using High Throughput Genome-wide Translocation Sequencing (HTGTS) suggests that transient manipulation of DNA damage repair pathways have no adverse effect on either CRISPR/Cas9 specificity or genomic integrity. Our data suggests that this approach could be used for correcting various genetic disorders in relevant cell types.
Abstract 4083: Deletion of the BMP receptor BMPR1a results in EMT and impairs mammary gland tumor formation and metastasis
Authors: Laura D. Hover, Michael W. Pickup, Agnieszka E. Gorska, Anna Chytil, Yan Guo, Sergey V. Novitskiy, Harold L. Moses, Philip Owens
Journal: Cancer Research (2015)

Abstract Bone Morphogenetic Proteins (BMPs) are secreted cytokines/growth factors belonging to the Transforming Growth Factor β (TGFβ) superfamily. BMP ligands have recently been shown to be overexpressed in human breast cancers. Normal and cancerous breast display active BMP signaling as indicated by phosphorylated Smads 1, 5 and 9. We combined mice expressing the MMTV.PyVmT oncogene with mice lacking BMPR1a in mammary epithelial cells and found this deletion resulted in delayed tumor onset and extended survival significantly (p-value = &amp;lt;0.001). We examined the histopathology of BMPR1a knockout (cKO) tumors and found a striking loss of epithelial characteristics combined with stromal desmoplasia. Immunofluorescence staining revealed that cKO tumors co-expressed Keratin 5 and mesenchymal cell markers such as Vimentin. This indicated that epithelial-to-mesenchymal (EMT)-like transitions were occurring in cKO tumors. We performed microarray analysis on these tumors and found changes that supported EMT-like changes with increased Snail mRNA expression. We established primary tumor cell lines and found that BMPR1a cKO had slower growth in vitro and upon in vivo implantation. Additionally, cKO tumor cells had reduced migration yet not invasion in vitro. We next analyzed human databases from TCGA and survival data from microarrays to confirm BMPR1a tumor promoting functions and found high BMPR1a gene expression correlated with worse survival regardless of molecular breast cancer subtype. In conclusion, we found that loss of the BMPR1a impairs tumor formation and progression and does not exhibit tumor suppressive functions in mouse and human breast cancer. Citation Format: Laura D. Hover, Michael W. Pickup, Agnieszka E. Gorska, Anna Chytil, Yan Guo, Sergey V. Novitskiy, Harold L. Moses, Philip Owens. Deletion of the BMP receptor BMPR1a results in EMT and impairs mammary gland tumor formation and metastasis. [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 4083. doi:10.1158/1538-7445.AM2015-4083
Multi-Center US Intergroup Study of Intensive Chemotherapy Plus Dasatinib Followed By Allogeneic Stem Cell Transplant in Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Younger Than 60
Authors: Farhad Ravandi, Megan Othus, Susan O'Brien, Stephen J. Forman, Chul S. Ha, Jeffrey Y. C. Wong, Martin S Tallman, Elisabeth Paietta, Janis Racevskis, Geoffrey L. Uy, Uma Borate, Partow Kebriaei, Laura Kingsbury, Hagop M. Kantarjian, Jerald P. Radich, Harry P. Erba, Frederick R. Appelbaum
Journal: Blood (2015)
Costs of Managing Chronic Immune Thrombocytopenic Purpura (ITP) in Adults: A Retrospective Analysis.
Authors: Mehdi Khellaf, Laurent Eckert, Priscille Poitrinal, Camille Francesconi, Albert Haddad, Laetitia Languille, Philippe Bierling, Marc Michel, Lionel Riou França, Robert Launois, Bertrand Godeau
Journal: Blood (2009)
Epigenetic Inactivation of the CpG Demethylase TET1 as a DNA Methylation Feedback Loop in Upper Aerodigestive Tract and Gastrointestinal Cancers
Authors: Lili Li, Chen Li, Haitao Mao, Zhenfang Du, Wai Yee Chan, Paul Murray, Bing Luo, Anthony Tak-Cheung Chan, Tony Shu-Kam Mok, Francis Ka-Leung Chan, Richard Ambinder, Qian Tao
Journal: Clinical Gastroenterology and Hepatology (2016)
Abstract 2943: Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient ovarian cancer
Authors: Nicholas Pulliam, Pietro Taverna, John Lyons, Kenneth P. Nephew
Journal: Cancer Research (2015)

Abstract Ovarian cancer (OC) is initially chemoresponsive but the majority of patients relapse after first line platinum-, taxane-based chemotherapy. Recurrence has been shown to be associated with increased DNA damage response (DDR) mediated by poly-(ADP)-ribose polymerase 1/2 (PARP1/2), which can be therapeutically targeted by PARP inhibitors (PARPi). Although PARPi are indicated for platinum-responsive, BRCA-mutated OC, most OC patients have BRCA-proficient disease. Based on our previous studies supporting a role for DNA methylation in chemoresistant OC, mediated by the enzyme DNA methyltransferase 1 (DNMT1), and reports on a functional role for DNMT1 in DNA double strand break repair mediated by BRCA1/2, we hypothesized that combining DNMTi and PARPi will impair BRCA-mediated DDR, resulting in cytotoxicity in OC cells. A panel of OC cell lines, including A2780 (platinum sensitive, BRCA-wild type (wt)), A2780-cp and HeyC2 (platinum resistant, BRCA-wt) and Kuramochi (platinum resistant, BRCA2 mutant) were examined for cell growth using colony formation assays after treatment with DNMTi SGI-110 (5, 20, or 100nM) and PARPi talazoparib (1 or 10nM), alone or in combination. Combination treatment schemas consisted of: 1) “priming”: SGI-110 for three days, 24 hour recovery, then talazoparib treatment on Day 5 or 2) “co-administration”: talazoparib administration on day 1 and SGI-110 treatment on days 1-3. Colony formation was inhibited by talazoparib alone in all cell lines but in a dose-dependent manner. Decreased colony formation after SGI-110 alone (20 or 100 nM) was observed only in Kuramochi cells. Combination drug treatments resulted in significant reductions in colony formation. For example, regardless of BRCA and platinum sensitivity status, co-administration of SGI-110 and talazoparib reduced (P&amp;lt;0.05) cell survival, albeit%survival was dependent on drug dose and OC cell line. In general, priming with SGI-110 prior to treatment with talazoparib reduced (P&amp;lt;0.05) survival of A2780, Kuramochi and HeyC2 (majority of combinations tested); however, decreased (P&amp;lt;0.05) survival of A2780-cp was observed only after priming with 100 nM SGI-110. In summary, talazoparib combined with SGI-110 displayed effective cytotoxicity in OC cell lines harboring either wt- or mutant-BRCA, indicating that this DNMTi-PARPi drug combination impairs BRCA-mediated DDR and may represent an effective treatment regimen for OC. Citation Format: Nicholas Pulliam, Pietro Taverna, John Lyons, Kenneth P. Nephew. Novel combination therapy of DNMT inhibitor SGI-110 and PARP inhibitor BMN-673 (talazoparib) for BRCA-proficient 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 2943. doi:10.1158/1538-7445.AM2015-2943
Iron Overload In Adult Allogeneic Hematopoietic Stem Cell Transplantation Survivors: Quantification of Iron Burden by Determining Non-Transferrin-Bound Iron.
Authors: Tatsunori Goto, Katsuya Ikuta, Emi Yokohata, Daisuke Koyama, Koichi Onodera, Aika Seto, Keisuke Watanabe, Yukiyasu Ozawa, Katsunori Sasaki, Yutaka Kohgo, Koichi Miyamura
Journal: Blood (2010)
Abstract 154: Identification of TGFβ-regulated long noncoding RNAs in mammary epithelia: lncRNA-HIT mediated TGFβ-induced EMT and breast cancer metastasis
Authors: Edward Richards, Gu Zhang, Jennifer Permuth-Wey, Zhu-Peng Li, Sridevi Challa, William Kong, Dan Su, Domenico Coppola, Wei-min Mao, Thomas Sellers, Jin Q. Cheng
Journal: Cancer Research (2015)

Abstract Background: Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. TGFβ signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Methods: Genome-wide lncRNA profile was performed using NCode™ Mouse Noncoding Microarray chip from Life Technologies, which contains 10,802 lncRNAs and 25,178 protein-coding genes. Total RNA was isolated from mouse mammary epithelial NMuMG cells, which had been treated with TGFβ for 0, 12 and 24 hours, and was used to hybridize the microarray. The role of a top TGFβ-upregulated lncRNA, lncRNA-HIT, in EMT and metastasis was further characterized in cell culture and orthotopic breast cancer models Results: Among 10,802 lnRNAs profiled, 680 were up-regulated and 633 were down-regulated during TGFβ-induced EMT, respectively. Further, we identify that lncRNA-HIT (HOXA antisense transcript induced by TGFβ) mediates TGFβ function, i.e., depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth and metastasis. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Conclusions: These data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. Citation Format: Edward Richards, Gu Zhang, Jennifer Permuth-Wey, Zhu-Peng Li, Sridevi Challa, William Kong, Dan Su, Domenico Coppola, Wei-min Mao, Thomas Sellers, Jin Q. Cheng. Identification of TGFβ-regulated long noncoding RNAs in mammary epithelia: lncRNA-HIT mediated TGFβ-induced EMT and breast cancer metastasis. [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 154. doi:10.1158/1538-7445.AM2015-154
The BTK Inhibitor, Bgb-3111, Is Safe, Tolerable, and Highly Active in Patients with Relapsed/ Refractory B-Cell Malignancies: Initial Report of a Phase 1 First-in-Human Trial
Authors: Constantine Tam, Andrew P Grigg, Stephen Opat, Matthew Ku, Michael Gilbertson, Mary Ann Anderson, John F. Seymour, David S. Ritchie, Carmen Dicorleto, Belinda Dimovski, Eric Hedrick, Jianxin Yang, Lai Wang, Lusong Luo, Ling Xue, Andrew W. Roberts
Journal: Blood (2015)
Abstract 5224: Non-canonical activity of threonyl-tRNA synthetase promotes angiogenesis and invasion in a mouse model of ovarian cancer
Authors: Peibin Wo, Theresa Wellman, Alan Howe, Christopher Francklyn, Karen M. Lounsbury
Journal: Cancer Research (2015)

Abstract Despite clear connections between the tumor microenvironment and ovarian cancer invasion, the underlying molecular mechanisms remain elusive. We have recently shown that the protein synthesis regulator threonyl-tRNA synthetase (TARS) has a unique extracellular angiogenic activity separate from its canonical function. Secreted TARS promotes endothelial cell migration and tube formation, and a selective TARS inhibitor, BC194, disrupts normal vessel development in zebra fish and chick embryo models. TARS expression also correlates with tumor stage and angiogenesis in human ovarian cancer. The objective of this study was to validate the biological and clinical relationship between TARS and ovarian tumor progression using a syngenic mouse model of epithelial ovarian cancer. Tumors were initiated by intraperitoneal injection of ID8 mouse ovarian cancer cells, and tumors formed at 4-6 weeks were scored for invasiveness and analyzed by immunostaining for TARS expression and microvascular density. To test the hypothesis that overexpression of TARS promotes invasion, cells were stably transfected with a TARS expression plasmid prior to injection. To test the hypothesis that TARS inhibition reduces tumor invasion, animals harboring ID8 tumors were treated with the high-affinity TARS inhibitor BC194. We found that TARS levels were elevated in ovarian tumors as compared with normal ovarian tissue. Overexpression of TARS in ID8 cells also resulted in enhanced invasiveness and microvascular density of the resulting tumors (p = 0.026). Preliminary results also indicated that inhibition of TARS by BC194 treatment reduced tumor angiogenesis and growth (p = 0.005) without observed toxicities in the animals. Overall, these results show that modifying TARS expression or activity can affect in vivo ovarian tumor angiogenesis and progression. These results encourage further study of TARS as a regulator of the tumor microenvironment and as a possible target for diagnosis and treatment of ovarian cancer. Citation Format: Peibin Wo, Theresa Wellman, Alan Howe, Christopher Francklyn, Karen M. Lounsbury. Non-canonical activity of threonyl-tRNA synthetase promotes angiogenesis and invasion in a mouse model of ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5224. doi:10.1158/1538-7445.AM2015-5224