tbuckley/cabot-search huggingface dataset:
Abstract 4464: Effect of bacterial quorum sensing lactones on human pancreatic carcinoma cells
Authors: Senthil R. Kumar, Jeffrey Bryan
Journal: Cancer Research (2015)

Abstract INTRODUCTION Pancreatic cancer (PC) is the fourth leading cause of cancer related mortality in the United States. In spite of the discovery of gemcitabine, administered either alone or in combination with other drugs, the survival rate of 5% has remained unchanged for several decades now. In this study, we hypothesize that bacterial quorum sensing molecules such as N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) could affect pancreatic carcinoma cell phenotype and characteristics. Elucidation of the mechanism of action of O-DDHSL could lead to the development of more effective analogs and novel therapeutic targets in PC. MATERIALS AND METHODS Human pancreatic carcinoma cells (Panc-1 and Aspc-1) was grown in DMEM-F12 media with 10% FBS at 37oC. Normal pancreatic ductal epithelial cells (HPDE) were maintained in keratinocyte serum free media. Total RNA was extracted from the cells and converted to cDNA which served as a template for qRT-PCR amplification in the presence of various gene primers. The effect of O-DDHSL on pancreatic carcinoma cell phenotype, apoptosis, viability, migration, proliferation and colony forming ability was investigated. RESULTS Both Panc-1 and Aspc-1 cell viability decreased in a concentration dependent manner in the presence of O-DDHSL (IC50 = 120 ± 5 μM; P ≤ 0.02) and (IC50 = 48 ± 8 μM; P ≤ 0.02), respectively. O-DDHSL had only minimal effect on HPDE cell viability. Apoptosis and inhibition of cell migration in Panc-1 and Aspc-1 cells was observed in the presence of O-DDHSL. Variable effect on migration associated genes such as IQGAP-1, cofilin and rhoC was noted in these cells upon O-DDHSL treatment as determined by qRT-PCR as well as protein expression by Western analysis. CONCLUSIONS In conclusion, the combined findings from our study demonstrate that O-DDHSL decreases pancreatic carcinoma cell viability, promotes apoptosis by activating caspases, and inhibits cell migration. O-DDHSL also modulates genes responsible for migration such as RhoC, cofilin and IQGAP-1 in these cells. Citation Format: Senthil R. Kumar, Jeffrey Bryan. Effect of bacterial quorum sensing lactones on human pancreatic carcinoma cells. [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 4464. doi:10.1158/1538-7445.AM2015-4464
Disease-Specific Recovery of Regulatory T Cell After Allogenic Stem Cell Transplantation
Authors: Thomas St\)big, Michael Lioznov, Ulrike Fritsche-Friedland, Haefaa Alchalby, Christine Wolschke, Francis Ayuketang Ayuk, Ulrike Bacher, Axel R. Zander, Nicolaus Kröger, MD
Journal: Blood (2010)
Abstract 520: MIEN1 drives breast cancer invasion by regulating cytoskeletal dynamics
Authors: Marilyne Kpetemey, Jamboor Vishwanatha
Journal: Cancer Research (2015)

Abstract Introduction: The emergence of metastases remains the primary cause of cancer mortality and morbidity. Active migration of tumour cells is a prerequisite for tumor-cell invasion and metastasis. We identified Migration and Invasion Enhancer 1(MIEN1) as a novel promoter of cell migration/invasion. Previously known as C35, C17orf37, RDX12 and MGC14832, MIEN1 is a novel gene located in the chromosomal region 17q12-21. While absent or low in normal tissues, MIEN1 is abundantly expressed in multiple cancers including breast carcinomas. A membrane-bound signaling adaptor, MIEN1 localizes to the leading edge of migrating cells and promotes migration and invasion by increasing filopodium formation. While MIEN1 is shown to promote motility through filopodia formation, little is known on the mechanisms by which MIEN1 influence the actin cytoskeleton. Exploring underlying mechanisms, we show that MIEN1 associates with the actin cytokeleton during motility and directly influence actin polymerization. Methods: We performed immunofluorescence, migration and invasion assays using breast cancer cell lines, MDA-MB 231 and MCF10CA1a to investigate the mechanisms by which MIEN1 potentiates cell motility. Results: Ablation of MIEN1 inhibited cell migration, cell adhesion and altered the phosphorylation status of motility markers. Immunofluorescence staining with FITC- conjugated-phalladoin confirmed that alteration of MIEN1 expression leads to reconfiguration of the actin cytoskeleton in breast cancer cells. Furthermore we found that MIEN1 associates with cytoskeletal proteins involved in motility processes. Conclusion: Our results show that MIEN1 is a critical regulator of cell migration and invasion. The importance of MIEN1 in tumor cell dissemination is well established; understanding the molecular mechanisms aiding the processes involved will enable the design of novel and effective treatments for metastatic tumors. Citation Format: Marilyne Kpetemey, Jamboor Vishwanatha. MIEN1 drives breast cancer invasion by regulating cytoskeletal dynamics. [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 520. doi:10.1158/1538-7445.AM2015-520
The impact of socioeconomic status (SES) on stage of cancer at time of diagnosis: A population-based study in Ontario, Canada
Authors: C. M. Booth, G. Li, W. J. Mackillop
Journal: Journal of Clinical Oncology (2009)

6505 Background: Lower SES is known to be associated with worsened cancer survival. Here we evaluate the impact of SES on stage of cancer at diagnosis in Ontario which has universal health insurance. Methods: All incident cases of breast, colon, rectal, non-small cell lung, cervical and larynx cancer diagnosed in Ontario 2003–2005 were identified using the Ontario Cancer Registry. Stage information is only captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). This represents approximately 68% of the population and forms the basis for all analyses. Using a best stage grouping approach, cases were assigned stage based on pathologic TNM if available and clinical TNM otherwise. The population of Ontario was divided into quintiles based on community median household income reported in the 2001 Canadian census. Using postal code at time of diagnosis cases were assigned to quintiles (Q); Q1 represents the communities where the poorest 20% of the Ontario population resided. Comparisons between Q1 and Q2–5 were made using the chi-square test. A Cox model was used to evaluate overall survival, SES, stage, and age. Results: Stage at diagnosis was available for 19,239/23,254 (83%) of cases seen at RCCs. Among cases with breast cancer, those in Q1 were less likely to have stage I disease (43 vs 47%, p = 0.004) and more likely to have stage IV disease (5 vs 4%, 0.008) than Q2–5. With lung cancer, cases in Q1 were more likely to have stage I disease compared to Q2–5 (16 vs 13%, p = 0.015). Distribution of stage I and stage IV disease did not differ by SES across other individual diseases. However, for all 6 cancers combined, cases in Q1 were less likely than Q2–5 to have stage I disease (27 vs 30%, p = 0.001) and more likely to have stage IV disease (21 vs 18%, p &lt; 0.0001). We found significant gradients in 3-year overall survival across Q1-Q5 for breast (5% absolute difference in survival, p &lt; 0.001), colon (4%, p = 0.049), and cervical (18%, p = 0.031) cancers. Adjustment for stage and age only slightly diminished these survival gradients. Conclusions: Despite universal health care, SES remains associated with survival among patients with cancer in Ontario. These data suggest that the difference in outcome is only partially explained by differences in stage at diagnosis. No significant financial relationships to disclose.
Strategies for Securing and Maintaining Predictable Efficacy with Recombinant Activated Factor VII in On-Demand Treatment of Haemophilia Patients with Inhibitors.
Authors: Benny Sørensen, Yesim Dargaud, Gili Kenet, Jeanne M. Lusher, Andrew Mumford, Steven W. Pipe, Andreas Tiede
Journal: Blood (2009)
Abstract 1808: Enhancing the Stupp regimen in glioblastoma cancer cells with a T-type calcium channels inhibitor
Authors: Jaroslaw Dziegielewski, Barbara Dziegielewska, Lloyd S. Gray
Journal: Cancer Research (2015)

Abstract Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor. Although introduction of the Stupp regimen combining radiation (IR) with concomitant and adjuvant temozolomide (TMZ) led to increased patient survival, the cure rate of GBM is disappointing. We postulated that sensitization of cancer cells to therapy can be achieved by targeting intracellular pathways and processes. Recently, T-type Ca2+ channels have been proposed as a molecular target for GBM sensitization to chemo- and radiotherapy (Keir et al., 2013; Sheehan et al., 2013). In the present studies, we investigated the effects of T-type channel inhibition on GBM cells’ responses to the Stupp regimen. GBM cells differing in their resistance to TMZ and IR were treated with theT-type channel antagonist, mibefradil, either concomitantly with TMZ or sequentially (Interlaced TherapyTM). Cell viability and clonogenic survival were determined, demonstrating significant enhancement of the Stupp regimen's anticancer effects with co-treatment with T-type channels inhibitors. Importantly for DNA-targeted therapies, we observed a decrease in cells’ ability to repair DNA damage in the presence of mibefradil. The molecular mechanism of this decrease was investigated by assessing expression levels, localization and phosphorylation status of ATM, DNA-PK, γH2AX, Chk1/2, Kap1, p53, Rad51. These mechanistic studies demonstrated that inhibiting T-type Ca2+ channels in GBM affects DNA damage signaling and repair through reduction of repair protein activation and changes their cellular localization. The observed effects are specific for T-type channels inhibition, since L-type channels inhibitors had no effect. Our study provide a rational molecular mechanism for sensitization of GBM to the Stupp regimen by T-type Ca2+ channel inhibition, which will facilitate current and future clinical trials and potentially lead to new treatment options for this deadly brain tumor. Citation Format: Jaroslaw Dziegielewski, Barbara Dziegielewska, Lloyd S. Gray. Enhancing the Stupp regimen in glioblastoma cancer cells with a T-type calcium channels inhibitor. [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 1808. doi:10.1158/1538-7445.AM2015-1808
Innate Lymphoid Cell-Derived IL-22 Mediates Endogenous Thymic Repair Under the Control of IL-23
Authors: Jarrod A Dudakov, Alan M Hanash, Lauren F. Young, Natalie V Singer, Mallory L West, Robert R Jenq, Odette M Smith, Amanda M Holland, Richard L Boyd, Marcel R.M. van den Brink
Journal: Blood (2011)
Differential Effects of TAK-442, a Factor Xa Inhibitor, and Ximelagatran, a Thrombin Inhibitor, on Bleeding: Possible Role of Differences in Effects on Factor V-Mediated Feedback on Blood Coagulation Cascade
Authors: Noriko Konishi, Katsuhiko Hiroe, Yasuhiro Imaeda, Takuya Fujimoto, Keiji Kubo, Masaki Kawamura
Journal: Blood (2008)
Polychemotherapy in Combination with Thalidomide Followed by Autologous or Allogeneic Transplantation for Rescue after Autograft or Induction Therapy Failure in Patients with Multiple Myeloma.
Authors: Ute Hegenbart, Stefan O. Schonland, Thomas Moehler, Axel Benner, Sabine Gerull, Martin Goerner, Hans-Joerg Schaefer, Gerlinde Egerer, Peter Dreger, Anthony D. Ho, Hartmut Goldschmidt
Journal: Blood (2006)
High Interleukin 15 Expression Characterizes Childhood Acute Lymphoblastic Leukemia with Involvement of the Central Nervous System.
Authors: Gunnar Cario, Anja Teichert, Peter Rhein, Andre Schrauder, Julia Skokowa, Wolf-Dieter Ludwig, Shai Izraeli, Karl Welte, Brigitte Schlegelberger, Martin Schrappe, Martin Stanulla
Journal: Blood (2006)
Favourable Impact on Acute and Chronic Graft-Versus-Host Disease with Cyclophosphamide and In-Vivo Anti-CD52 Monoclonal Antibodies for Marrow Transplantation from HLA-Identical Sibling Donors for Acquired Aplastic Anaemia.
Authors: Vikas Gupta, Sarah E. Ball, Qi-long Yi, Deborah Sage, Shaun R. McCann, Mark Lawler, Miguel Ortin, Mylene Freires, Geoff Hale, Hermann Waldmann, Edward C. Gordon-Smith, Judith C.W. Marsh
Journal: Blood (2004)
Allogeneic Hematopoietic Stem-Cell Transplantation Using Fludarabine/Treosulfan Conditioning Regimen Compared with Busulfan-Based Myeloablative and Reduced-Intensity Conditioning in Patients with AML and Mds; Relative Outcomes Depend On Disease Status at Transplantation.
Authors: Avichai Shimoni, Avital Rand, Noga Shem-Tov, Izhar Hardan, Yulia Volchek, Hannah Maayaan, Ronit Yerushalmi, Arnon Nagler
Journal: Blood (2009)
Immunochemotherapy with Rituximab Improves Molecular CR Rate and Outcome In CD20+ B-Lineage Standard and High Risk Patients; Results of 263 CD20+ Patients Studied Prospectively In GMALL Study 07/2003
Authors: Dieter Hoelzer, Andreas Huettmann, Felix Kaul, Sebastian Irmer, Nadja Jaekel, Martin Mohren, Thomas Lipp, Knut Wedelin, Francisco de Valle, Mathias Schmid, Eckhard Thiel, Monika Brueggemann, Michael Kneba, Nicola Goekbuget
Journal: Blood (2010)
Abstract 3426: Occult and clinical pancreatic cancers in elderly patients
Authors: Yoko Matsuda, Akemi Suzuki, Yuri Hamashima, Hideki Hamayasu, Hisashi Yoshimura, Toshiyuki Ishiwata, Tomio Arai
Journal: Cancer Research (2015)

Abstract Objectives: This study aimed to investigate the clinicopathological features of pancreatic cancer at different stages using autopsy results. Methods: We retrospectively evaluated 8399 consecutive cases of autopsy performed between 1972 and 2013 at our geriatric hospital. Results: Macroscopic pancreatic lesions were detected in 6.13% of cases. Primary and secondary pancreatic tumors were observed in 2.88% and 2.10% of cases, respectively. Most primary tumors were invasive ductal adenocarcinomas (193 cases, 2.31%, mean patient age: 78.09 years) with a peak incidence at 50-59 years. Occult invasive ductal adenocarcinoma was discovered incidentally in 15 cases (Table), with distant metastasis present in 26.67% of those. Microscopically, occult and advanced tumors exhibited similar characteristics such as hyalinized fibrous stroma; necrosis; and invasion into vessels, peripancreatic fat tissues, and extrapancreatic nerve plexus. Mucin 1 and 2 immunohistochemical expression levels were also similar. Occult cancer incidence increased with age. Patients aged ≥85 years had shorter survival, a small tumor size, and a low incidence of lymph node metastasis. Approximately 8% of pancreatic invasive ductal adenocarcinomas progressed asymptomatically and were discovered incidentally at autopsy. Conclusions: Pancreatic cancers in elderly patients tend to progress asymptomatically, but once symptoms develop, they are more often fatal than those in younger patients. Comparison of clinical and occult invasive ductal adenocarcinoma cancer cases (193 cases)Clinical cancer casesOccult cancer casesP valueAge, years (mean ± S.D.)77.67 ± 8.6583.13 ± 8.130.02*Size, cm (mean ± S.D.)5.88 ± 2.683.03 ± 1.91&amp;lt;0.01*MUC1 score2.00 ± 0.871.90 ± 0.830.75MUC2 score0.05 ± 0.180.28 ± 0.530.09Number of cases17815SexMale7780.45Female1017Main locationPancreatic head1076&amp;lt;0.01*Pancreatic body502Pancreatic tail177No data40PathologyWell43100.01*Moderately773Poorly391Adenosquamous carcinoma110Anaplastic carcinoma81Lymph node metastasisNegative239&amp;lt;0.01*Positive1556Stage (UICC)I07&amp;lt;0.01*II234III10IV1544 Citation Format: Yoko Matsuda, Akemi Suzuki, Yuri Hamashima, Hideki Hamayasu, Hisashi Yoshimura, Toshiyuki Ishiwata, Tomio Arai. Occult and clinical pancreatic cancers in elderly patients. [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 3426. doi:10.1158/1538-7445.AM2015-3426
Fas Down-Modulation in Epstein Barr Virus (EBV)-Specific Cytotoxic T-Lymphocytes (CTLs) Reduces Their Sensitivity to Fas/Fasl-Induced Apoptosis.
Authors: Gianpietro Dotti, Barbara Savoldo, Martin Pule, Karin C. Straathof, Ettore Biagi, Yvon Eric, Sthephane Vigoroux, Cliona M. Rooney, Malcolm K. Brenner
Journal: Blood (2004)
Abstract 4142: A role for apolipoprotein E in invasion in oral squamous cell carcinoma
Authors: Sangeeta K. Jayakar, Olivier D. Loudig, Margaret Brandwein-Gensler, Ryung Kim, Thomas J. Ow, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall, Thomas J. Belbin
Journal: Cancer Research (2015)

Abstract Oral squamous cell carcinomas (OSCC) have a poor patient prognosis, which is attributed to their invasive nature. Our goal was to identify a novel gene that is important in OSCC invasion. We utilized genome-wide expression data generated from OSCC patient tumor samples with varying degrees of invasiveness, as measured by the histological parameter worst pattern of invasion (WPOI). RNA extracted from tumors that were classified as either WPOI 5 or WPOI 3, two categories of tumors that have been previously shown to correlate with local recurrence and poor overall survival, were evaluated utilizing two microarray platforms. When both gene expression datasets were analyzed, we identified 104 genes that were overexpressed at least 1.5-fold in the WPOI type 5 tumors compared to the less invasive WPOI type 3 tumors. Fifty genes were chosen based on functional criteria to be assessed using in vitro invasion assays following treatment with siRNA pools. In our initial screen, 16 of these genes showed significant reductions in in vitro invasion when their expression was knocked down by siRNA treatment in the UMSCC1 cell line. The gene with the greatest effect on invasion from the screen was Apolipoprotein E (APOE). In addition to in vitro invasion, we also observed that matrix degradation and mature invadopodia numbers were decreased with APOE knockdown in the UMSCC1 cell line, suggesting that APOE affects invasion in part through regulating invadopodial activity. We observed that APOE knockdown resulted in decreased phospho-cJun and phospho-ERK1/2 in the UMSCC1 and PCI-15B cell lines. Since cJun is a component of the AP1 transcription factor, we assessed AP1 promoter activity using a luciferase reporter assay. We found that AP1 promoter activity decreased with APOE knockdown in both cell lines. Our proposed model is that APOE knockdown suppresses the cells’ ability to invade via decreased activation of ERK1/2 and cJun, thus reducing AP1 transcriptional activity. Further studies are being done to determine which downstream targets of AP1 are being altered with APOE knockdown and if those targets are known to be implicated in invasion. Citation Format: Sangeeta K. Jayakar, Olivier D. Loudig, Margaret Brandwein-Gensler, Ryung Kim, Thomas J. Ow, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall, Thomas J. Belbin. A role for apolipoprotein E in invasion in oral squamous cell carcinoma. [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 4142. doi:10.1158/1538-7445.AM2015-4142
Police officer in minimally conscious state should be allowed to die, says judge
Authors: Clare Dyer
Journal: BMJ (2016)

Doctors should stop giving artificial nutrition and hydration to a police officer left in a minimally conscious state after a crash between a car and his motorcycle, a judge has ruled at the High Court in London.1

Mr Justice Charles declared that Paul Briggs, a former soldier and Gulf War veteran, would not have wanted to be kept alive in his current state and that it was not in his best interests to provide the treatment.

The case, which may go to appeal, is only the third in which UK courts have authorised withholding or withdrawing artificial feeding from a patient …
Abstract 13004: The Effect of Vasopressor Agents in the Treatment of Cardiovascular Shock
Authors: Tsukasa Yagi, Eizo Tachibana, Yasushi Ueki, Kazuo Sakamoto, Hiroshi Imamura, Takamichi Miyamoto, Hiroshi Takahashi, Hiroyuki Hanada, Naohiro Yonemoto, Ken Nagao, Atsushi Hirayama
Journal: Circulation (2015)

Background: Various vasopressor agents are used for the treatment of cardiovascular shock. According to a randomized double-blind comparison study reported in 2010, norepinephrine is more useful than dopamine for patients in cardiovascular shock. In Japan, although both norepinephrine and dopamine are used as first-line vasopressor agents, the status of use and usefulness of the two agents have not yet been clarified. Methods: The Japanese Circulation Society (JCS) Shock Registry was a prospective, observational, multi-center, cohort study between May 2012 and June 2014.Of the patients registered in the JCS-Shock Registry, data of those who received norepinephrine or dopamine as a vasopressor agent, without the use of intra-aortic ballon pumping or cardiopulmonary bypass, were examined. The primary end point of the study was the rate of death at 30 days. Results: Of the 980 patients registered in the JCS-Shock Registry, the data of 320 patients were included in this analysis, after exclusion of patients who had not received the two agents and patients meeting the exclusion criteria. Of the 320 patients, 98 had received norepinephrine (N group), 142 had received dopamine (D group), and 80 had received both agents (N+D group). The acute mortality rates were 26.5, 25.4 and 46.2% in the N, D and N+D groups, respectively (p = 0.003). In a stratified analysis according to the renal function (eGFR [median: 43] ≥43 [normal renal function] versus eGFR &lt;43 [reduced renal function]) at the time of admission, the acute mortality rates in the patients of the N, D and N+D groups with normal renal function were 7.8, 21.1 and 41.2%, respectively (p = 0.001), being significantly lower in the N group. On the other hand, the acute mortality rates in the patients of the N, D and N+D groups with reduced renal function were 46.8, 29.6 and 50.0%, respectively (p = 0.049), being significantly lower in the D group. Conclusion: Although norepinephrine is recommended as the first-line treatment, a trend towards more frequent use of dopamine was found in Japan. In addition, norepinephrine appeared to contribute to a reduction of the acute mortality in patients with normal renal function, while dopamine appeared to contribute to a reduction of the acute mortality in patients with reduced renal function.