tbuckley/cabot-search huggingface dataset:
Abstract 2519: A novel role for brachyury as a key regulator of sonic hedgehog signaling (Shh) and maintenance of stemness in gliomas
Authors: Divya Kesanakurti, Alessandro Canella, Jihong Xu, Vinay K. Puduvalli
Journal: Cancer Research (2016)

Abstract Glioblastomas are the most common and aggressive form of adult primary brain tumors and are associated with a dismal prognosis. Accumulating evidences suggest that a subset of therapy-resistant cancer stem cells are responsible for recurrence in tumors targeting which may help in gliomas. We identified a significant overexpression of Brachyury (T-box transcription factor) in correlation with glioma histological grade when compared to non-tumor brain controls, with the highest expression being in grade IV gliomas. We also observed increased expression of Brachyury in several glioma cell lines and stem cells (GSCs) when compared to normal human astrocytes. Serum-induced differentiation of GSCs resulted in loss of Brachyury expression along with decreased stem-cell marker levels in these cells, which prompted us to study the potential role of Brachyury in glioma stemness and to delineate the underlying signaling mechanisms. Specific shRNA-mediated knockdown of Brachyury significantly decreased proliferation, migration and invasion in glioma cell lines. Brachyury suppression led to inhibition of sphere formation of GSCs and decreased stem cells marker expression including CD133, nestin and Nanog. Brachyury knockdown also inhibited the activation of sonic hedgehog (Shh) signaling and decreased Gli1 levels in these cells. On the other hand, stable overexpression of Brachyury resulted in the activation of Shh pathway and elevated stem cell marker expression in GSCs. Based on these in vitro findings, our future studies will be focused on determining the role of Brachyury in orthotopic tumor growth in vivo. In summary, our data reveals a novel role for Brachyury in the regulation of tumor invasiveness and stemness, and indicates a potential for therapeutic targeting of Brachyury in patients with gliomas. Citation Format: Divya Kesanakurti, Alessandro Canella, Jihong Xu, Vinay K. Puduvalli. A novel role for brachyury as a key regulator of sonic hedgehog signaling (Shh) and maintenance of stemness in gliomas. [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 2519.
Immunogenicity of a Meningococcal B Vaccine during a University Outbreak
Authors: Nicole E. Basta, Adel A.F. Mahmoud, Julian Wolfson, Alexander Ploss, Brigitte L. Heller, Sarah Hanna, Peter Johnsen, Robin Izzo, Bryan T. Grenfell, Jamie Findlow, Xilian Bai, Ray Borrow
Journal: New England Journal of Medicine (2016)

In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H–binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak.
Le projet HELICS-ICU : vers une surveillance européenne des infections nosocomiales dans les unités de soins intensifs
Authors: C Suetens, A Savey, J Labeeuw, I Morales
Journal: Eurosurveillance (2002)

La creation d’une base de donnees destinee a l’analyse comparative des taux d’infection nosocomiale dans les 15 pays de l’Union Europeenne est un des objectifs du projet HELICS (Hospitals in Europe Link for Infection Control through Surveillance).
Abstract 162: Genomic analysis of uterine aspirates improves diagnosis and captures the intratumor heterogeneity in endometrial cancer
Authors: Alba Mota, Eva Colas, Pablo Garcia-Sanz, Irene Campoy, Alejandro Rojo-Sebastian, Luis Chiva, Sonsoles Alonso, Sonia Gatius, Antonio Gil-Moreno, Xavier González-Tallada, Berta Díaz-Feijoo, Patrycja Ziober Malinwska, Marcin Bobiński, Jaume Reventos, Xavier Matias-Guiu, Gema Moreno-Bueno
Journal: Cancer Research (2016)

Abstract Background: Endometrial cancer (EC) is the most common cancer in female genital tract in developed countries. Although the majority of ECs are diagnosed in early stages, with a 5-year overall survival of around 80%, an early detection of these tumors is crucial to increase survival of patients given that advanced tumors are associated with poorer outcome. Furthermore, the correct assessment of pre-clinical diagnosis is also decisive to guide the surgical management and treatment of the patient. Results: Genetic analysis of uterine aspirates identifies the mutational profile of endometrial cancers and represents the intra-tumor heterogeneity found in the analysis of multiple tumor regions from hysterectomy. Conclusions: The current study reveals the potential of the genetic analysis of uterine aspirates as a pre-operative tool to diagnosis, even in biopsies with insufficient material, with a sensitivity of 93.7% and a specificity of 91.7%. Additionally, genetic analysis of uterine aspirates allows to capture the intra-tumor heterogeneity identified in ECs. Citation Format: Alba Mota, Eva Colas, Pablo Garcia-Sanz, Irene Campoy, Alejandro Rojo-Sebastian, Luis Chiva, Sonsoles Alonso, Sonia Gatius, Antonio Gil-Moreno, Xavier González-Tallada, Berta Díaz-Feijoo, Patrycja Ziober Malinwska, Marcin Bobiński, Jaume Reventos, Xavier Matias-Guiu, Gema Moreno-Bueno. Genomic analysis of uterine aspirates improves diagnosis and captures the intratumor heterogeneity in endometrial 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 162.
Abstract 3080: OPB-51602: a novel STAT3 inhibitor that targets mitochondrial respiratory chain and triggers STAT3 dependent ROS production
Authors: Jayshree L. Hirpara, Kumi Higuchi, Takeshi Tsunoda, Boon Cher Goh, Shazib Pervaiz
Journal: Cancer Research (2016)

Abstract Signal transducer and activator of Transcription (STAT) proteins are activated upon extracellular signals resulting in their phosphorylation and nuclear translocation. Once in the nucleus, STAT proteins, in specific STAT3 activates gene transcription of factors involved in a myriad of cellular processes, including proliferation and survival. By implication, increased expression and activity of STAT3 are associated with human cancers, which argue strongly for the development of STAT inhibitors as a promising chemotherapeutic strategy. We are working with a novel STAT3 inhibitor, OPB-51602, that not only block STAT3 phosphorylation but also inhibits growth and colony formation in a variety of human cancer cell lines. Of note, in addition to targeting STAT3, the compound inhibits mitochondrial respiratory chain and triggers a significant increase in mitochondrial superoxide (O2-) production (within 1 hour of exposure) in NSCLC cell line H1975. Using functional mutants of pY705 and pS727 STAT3, the growth inhibitory activity of the compound could be compromised, however, only S727 mutant rescued the mitochondrial effects. In addition, exposure of cells to OPB-51602 resulted in extracellular acidification (ECAR) together with a complete shutdown of mitochondrial ATP production. Interestingly, these effects could be rescued by 2-deoxyglucose. These data provide evidence that the pharmacological inhibition of STAT3 not only blocks cell proliferation but also induces mitochondrial redox catastrophe and bio-energetic crisis, which could have potential therapeutic implications against cancers that are rendered drug resistant due to the activation of surrogate STAT3 signaling axis. Citation Format: Jayshree L. Hirpara, Kumi Higuchi, Takeshi Tsunoda, Boon Cher Goh, Shazib Pervaiz. OPB-51602: a novel STAT3 inhibitor that targets mitochondrial respiratory chain and triggers STAT3 dependent ROS production. [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 3080.
Continuous Infusion of FLAG and Idarubicin for Patients Younger Than 60 Years with Resistant Acute Myeloid Leukemia; a Prospective, Multicenter Phase II Study.
Authors: Hawk Kim, Jae-Hoo Park, Je-Hwan Lee, Jung-Hee Lee, Young-Don Joo, Won-Sik Lee, Sung-Hwa Bae, Hun Mo Ryoo, Kyoo-Hyung Lee
Journal: Blood (2007)
Continued use of antipsychotic drugs increased long-term mortality in patients with Alzheimer disease
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2009)

Source Citation Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol. 2009;8:151-7. 19138567
Abstract 3766: Targeting promoter regions of c-Myc and Bcl-2 in AML cells using G-quadruplex interacting drugs
Authors: Megan Turnidge, Justin J. Montoya, Apurvi Patel, David W. Lee, Eiman Aleem, Daniel H. Wai, Laurence H. Hurley, Vijay Gokhale, Robert J. Arceci, David O. Azorsa
Journal: Cancer Research (2016)

Abstract Cancer is a disease that can be characterized by overexpression of key oncogenic drivers that support tumor development and maintenance. In many instances, these oncogenic drivers are ‘undruggable’ because of structural challenges, the inability to effectively inhibit high concentrations of overexpressed proteins, and the development of drug resistance mutations. An alternative therapeutic approach is to directly inhibit gene transcription by targeting unique secondary DNA structures, called G-quadruplexes, that are associated with subsets of promoters. We investigated the activity of a class of compounds termed G-quadruplex Interacting Drugs (GQIDs) that are able to shut down the expression of specific oncogenic drivers, such as c-Myc and Bcl-2, used by tumor cells for growth and survival. We tested the activity of two GQIDs, GQC-05 and GSA-1103, on cell growth of a panel of eight pediatric and eight adult acute myeloid leukemia (AML) cell lines. Drug dose response analysis showed IC50 values ranging from approximately 10 nM to 1 μM for GQC-05 and from 40 nM to 2 μM for GSA-1103. The AML cell lines had different sensitivities to each GQID indicating a different mechanism of action for each compound. Three AML cell lines that were highly resistant to cytarabine were among the more sensitive to GQC-05. Four cell lines sensitive to GQC-05 had high expression of either c-Myc and/or Bcl-2, both of which are potential targets of these two GQIDs. Furthermore, treatment of the highly sensitive line MV-4-11 with GQC-05 showed a 3-4 fold decrease in expression of c-Myc and Bcl-2 mRNA. Furthermore, GQC-05 treatment resulted in decreased levels of both c-Myc and Bcl-2 proteins. These studies will help define a novel approach of repressing key drivers of leukemia by targeting selective promoter structures. Citation Format: Megan Turnidge, Justin J. Montoya, Apurvi Patel, David W. Lee, Eiman Aleem, Daniel H. Wai, Laurence H. Hurley, Vijay Gokhale, Robert J. Arceci, David O. Azorsa. Targeting promoter regions of c-Myc and Bcl-2 in AML cells using G-quadruplex interacting drugs. [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 3766.
Clinical and immune characteristics of rapid dropout and long-term survival in a phase II safety and efficacy study of combination CRS-207/GVAX immunotherapy in pancreatic cancer.
Authors: Dung T. Le, Chan C. Whiting, Eric R. Lutz, Nitya Nair, Amanda Engstrom, Ed Lemmens, Margit Cecile Tagliaferri, Aimee L. Murphy, Dirk G. Brockstedt, Elizabeth M. Jaffee
Journal: Journal of Clinical Oncology (2016)

459 Background: Baseline patient characteristics may impact duration on study and survivorship of patients in immunotherapy trials. In this study, GVAX pancreas (GM-CSF–secreting allogeneic pancreatic tumor cells) was administered with low-dose cyclophosphamide (Cy), with or without subsequent CRS-207 (live-attenuated Listeria monocytogenes–expressing mesothelin) infusion. Baseline clinical and immunological data were examined for two patient subsets based on duration on study. Methods: Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to 2 doses of Cy/GVAX followed by 4 doses of CRS-207 or 6 doses of Cy/GVAX every 3 weeks. Stable patients were offered additional courses. Patients were evaluated for post-randomization duration on study of &lt; 60 days (rapid dropouts, RD) and &gt; 18 months (long-term survivors, LTS). Baseline characteristics of these subsets were examined. Results: A total of 93 patients were randomized. Fifteen patients were RD; 13 were LTS. More RDs versus LTS had liver metastasis and lymph node involvement. On average, fewer RD patients had radiotherapy prior to randomization and fewer had prior surgical intervention. RD averaged 1.73 prior metastatic cancer treatment regimens versus 1.31 in LTS. RD also had higher average baseline CA 19-9 levels. Immune analysis showed higher circulating terminal effector CD8+ T cells and lower serum IL-6 in LTS compared to RD. Serum IL-6 concentration remained lower in LTS at four weeks following initiation of treatment. For patients who received CRS-207, CD8+ T cells specific to listeriolysin O (LLO) and mesothelin were higher in LTS than RD, as determined by ELISPOT. Conclusions: Baseline clinical and immunological characteristics may impact patient duration on immunotherapy trials. Immune monitoring and biomarker analysis in this study is ongoing to identify circulating cellular, tumor biomarkers and genomic (miRNA and mRNA) signatures that may correlate with survival. These findings warrant continued exploration of patient characteristics to identify best candidates for immunotherapy trials. Clinical trial information: NCT01417000.
Abstract 1989: Multiple functional implications of MYB in ovarian cancer
Authors: Sanjeev Kumar Srivastava, Seema Singh, Arun Bhardwaj, James E. Carter, Rodney P. Rocconi, Jennifer Scalici, Ajay P. Singh
Journal: Cancer Research (2016)

Abstract Ovarian cancer (OC) is the most common and deadliest gynecologic malignancies in the United States, with an estimated 21,290 new cases and 14,180 deaths in 2015. Therefore, it is highly imperative to identify novel molecular targets driving OC progression, so that an effective treatment strategy can be developed against this devastating disease. In the present study, we investigated the role of MYB in OC pathogenesis. MYB/c-MYB is a cellular progenitor of v-MYB oncogenes, which encodes for a transcription factor, and confers its oncogenic activity by regulating the expression of several target genes. First, we examined the expression of MYB in clinical specimens and OC cell lines by immunohistochemical and immunoblot analysis, respectively. We observed intense staining of MYB in the tissues of all the subtypes of OC, while no or negligible staining was observed in normal ovarian tissues. Moreover, we found MYB to be expressed in all the OC cell lines examined, with its heightened expression in highly aggressive (TOV112D, SKOV3-ip) and chemo-resistant (A2780-Cip) OC cell lines. To examine the pathological significance of MYB in OC, we silenced its expression in TOV112D, SKOV3-ip and A2780-Cip OC cell lines. Functional studies demonstrate that silencing of MYB led to decrease in growth and clonogenic ability in TOV112D, SKOV3-ip and A2780-Cip cells, as compared to their scrambled sequence-transfected (Scr) control cells. Furthermore, MYB-silencing reduced motility and invasion, as well as resulted in the loss of mesenchymal and gain of epithelial markers. In addition, our data showed that TOV112D-shMYB, SKOV3-ip-shMYB and A2780-Cip-shMYB were more sensitive to cisplatin-cytotoxicity as compared to their respective controls. Altogether, our studies provide the first experimental evidence for a functional role of MYB in altered growth, malignant behavior and chemoresistance of ovarian cancer. Citation Format: Sanjeev Kumar Srivastava, Seema Singh, Arun Bhardwaj, James E. Carter, Rodney P. Rocconi, Jennifer Scalici, Ajay P. Singh. Multiple functional implications of MYB in ovarian 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 1989.
Abstract 2808: Oxidative status of mouse azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer model and the effects of COX-2 inhibitor
Authors: Gorkem Kismali, Aykut Gokturk Uner, Ogunc Meral, Merve Alpay, Dilek Ulker Cakir, Funda Kosova, Tevhide Sel
Journal: Cancer Research (2016)

Abstract Background: Colorectal cancer (CRC) is becoming increasingly common in Asian and European countries and still remains the second leading cause of cancer deaths in the United States. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action.The objective of this study is to explore the oxidative status of the mouse model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer, and effects of COX-2 inhibitor in these animals. Materials and Methods: Totally 40 mice were randomized divided to four groups All animals except control and Cox-2 inhibitor alone group received AOM/DSS to establish colitis-associated cancer model as reported elsewhere. Control group animals were fed with conventional mice diet. COX-2 preferential inhibitor meloxicam was used to minimize side effects such as gastrointestinal hemorrhage Meloxicam were used i.p. 5mg/kg tree times in a week for meloxicam alone and AOM/DSS + meloxicam group. Oxidative stress markers Superoxide dismutase (SOD), Glutation peroxidase (GPx), Malondialdehyde (MDA) and Advanced Oxidation Protein Products (AOPP) were measured by spectrophotometrically in sera. Results: The combination treatment of Meloxicam and AOM/DSS significantly increased (p&amp;lt;0,05) SOD activities. GPx activities were found significantly increased (p&amp;lt;0,001) in mice treatment with Meloxicam and AOM/DSS combinations or alone. There were no differences between the control and treatment groups of MDA levels. Advanced Oxidation Protein Products levels of Meloxicam and AOM/DSS combination group were found higher than the other groups. Conclusion: Meloxicam and /or AOM/DSS treatment not caused lipid peroxidation, but increased the antioxidant enzymes and Advanced Oxidation Protein Products levels. Citation Format: Gorkem Kismali, Aykut Gokturk Uner, Ogunc Meral, Merve Alpay, Dilek Ulker Cakir, Funda Kosova, Tevhide Sel. Oxidative status of mouse azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer model and the effects of COX-2 inhibitor. [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 2808.
Abstract 1969: miRNA expression as potential biomarker for leiomyosarcoma and undifferentiated pleomorphic sarcoma
Authors: Laura Pazzaglia, Chiara Novello, Amalia Conti, Irene Quattrini, Serena Pollino, Piero Picci, Maria Serena Benassi
Journal: Cancer Research (2016)

Abstract Rare and highly aggressive adult soft tissue sarcomas (STS), leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS), have complex genomics characterized by a multitude of rearrangements, amplifications and deletions. Our previous data (Guled et al., Genes Chromosomes Cancer, 2014) showed 21 common differentially expressed miRNAs in UPS and LMS samples when compared to mesenchymal stem cells. On the base of these results, we performed target analysis by using bioinformatic tools (Diana-microt v3.0, Targetscan Vert release 5.2 and Pictar-Vert) and we identified 12 miRNAs potentially implicated in tumor development and progression. The expression of the selected miRNAs was evaluated by TaqMan microRNA Array in 59 high grade STS primary samples (27 LMS and 32 UPS) stored at Rizzoli biobank. Ten tissues from non oncologic patients were used as control. Our results showed a significant lower expression of miR-1, miR-133b and miR-152 (respectively p = 0.0045, p = 0.0027 and p = 0.0016) in tumors when compared to nontumor tissue. Three different target prediction databases (miRBase, TargetScan, miRanda) recognized MET as common target gene of miR-1, mir-133b and miR-152 and KIT as target of miR-152. MET and KIT gene expression was validated in our series of STS by RT-PCR by using 2−ΔΔCT comparative method. The data demonstrated higher mean expression levels in STS than in control (respectively 2.08 and 0.15 for KIT; 18527.9 and 2324.9 for MET) without significant differences between two histotypes. Our preliminary results confirmed MET and KIT as miRNA targets. Correlation with clinical data and in vitro studies with miRNA precursor transfected cell lines are on-going to better investigate their role as potential prognostic and therapeutic markers. Citation Format: Laura Pazzaglia, Chiara Novello, Amalia Conti, Irene Quattrini, Serena Pollino, Piero Picci, Maria Serena Benassi. miRNA expression as potential biomarker for leiomyosarcoma and undifferentiated pleomorphic sarcoma. [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 1969.