tbuckley/cabot-search huggingface dataset:
Abstract 1544: Overexpression of Rab11 and E-cadherin promotes collective cell migration and indicates a poor prognosis in colorectal carcinoma
Authors: Yuan-Chiang Chung, Wan-Chen Wei, Chia-Nung Hung, Chih-Ping Hsu, Hsiang-Ling Chiu, King-Jen Chang, Wei-Ting Chao
Journal: Cancer Research (2016)

Abstract Collective cell migration, whereby the cell-cell contacts such as E-cadherin are maintained during migration, has recently emerged, and the detailed mechanisms of this process are still unclear. The present study identified the role of Rab11 which functions in recycling endosome and the relation to E-cadherin in colorectal carcinoma and clarified the mechanism of Rab11 in the collective cell migration of cancer cells. The relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated from colorectal carcinoma patients. A total of 107 patients with surgically resected colorectal carcinoma were enrolled in immunohistochemical study. The relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated. GFP tagged Rab11 or Rab11 shRNA was introduced into HT-29 colon cancer cells for overexpression or knockdown. The interaction between E-cadherin and Rab11 was determined by immunoprecipitation. Rac1 and matrix metalloproteinase (MMP) activities were evaluated as functional effectors of collective cell migration. In the results, the expression of Rab11 and E-cadherin was not correlated with the stages of cancer or lymph node metastasis. However, the overall survival was poor in the group of 60 patients with duo-positive Rab11 and E-cadherin expression compared to the group (47 patients) without duo-positive expression (p = 0.038). In the cell biology assay, Rab11 was demonstrated through its physical interaction with E-cadherin, and overexpression of Rab11 was found to promote collective cell migration through the increased distribution of E-cadherin, which enhanced cell-cell connections. In addition, Rac1 activation and MMP2 expression were up-regulated upon Rab11 expression. This study demonstrated that Rab11and E-cadherin expression are poor indicators of survival time in colorectal carcinoma, but that Rab11 overexpression may contribute to increased collective cell invasion in colorectal carcinoma. Citation Format: Yuan-Chiang Chung, Wan-Chen Wei, Chia-Nung Hung, Chih-Ping Hsu, Hsiang-Ling Chiu, King-Jen Chang, Wei-Ting Chao. Overexpression of Rab11 and E-cadherin promotes collective cell migration and indicates a poor prognosis in colorectal carcinoma. [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 1544.
Preoperative enteral immunonutrition in cancer patients undergoing major abdominal surgery: Results of a meta-analysis.
Authors: Edwin Boelke, Wilfried Budach, Peter Arne Gerber, Klaus Orth, Kai Kammers, Simon Doerges, Christiane Matuschek
Journal: Journal of Clinical Oncology (2014)

e14005 Background: Perioperative enteral immunonutrition is thought to reduce the acute phase response and postoperative morbidity in patients undergoing major abdominal surgery. This meta analysis assessed the clinical effects of preoperative enteral immunonutrition in cancer patients undergoing major abdominal surgery. Methods: In this meta-analysis a total of 284 cancer patients were randomly assigned to receive either immunonutrition or a regular diet. The primary endpoint was the incidence of surgical-site infection. Secondary endpoints were rates of infectious complications, overall postoperative morbidity and C-reactive protein (CRP) levels on 3-4 days after surgery. Published relative risks were basis of the meta-analysis. Meta-analysis of the effect sizes on clinical outcome and mediator response was performed using a random effects model based on parameter estimates of relative risks and their standard errors. Results: Of 284 randomized patients, 137 were allocated to the control group and 147 received immunonutrition. Clinical data were comparable in both groups. The acute phase response did not vary between groups. Furthermore there was no significant difference in the clinical outcome regarding infections complications and overall postoperative morbidity. Conclusions: Preoperative enteral immunonutrition failed to show any significant advantage in terms of early clinical outcomes or change of the systemic acute-phase reaction.
Abstract 2848: Autophagy, senescence and proliferative recovery subsequent to DNA damage in radiation sensitization by PARP inhibition
Authors: Moureq R. Alotaibi, Khushboo Sharma, Tareq Saleh, Lawrence Povirk, Eric Hendrickson, David Gewirtz
Journal: Cancer Research (2016)

Abstract Radiotherapy continues to be a primary modality in the treatment of cancer. DNA damage induced by radiation can promote apoptosis as well as both autophagy and senescence, where autophagy and senescence can theoretically function to prolong tumor survival. A primary aim of this work was to investigate the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiation sensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population. In the context of this work, the relationship between radiation-induced autophagy and senescence was also determined. Studies were performed using DNA repair proficient HCT116 colon carcinoma cells and a repair deficient Ligase IV (-/-) isogenic cell line. Irradiation promoted a parallel induction of autophagy and senescence that was strongly correlated with the extent of persistent H2AX phosphorylation in both cell lines; however inhibition of autophagy failed to suppress senescence, indicating that the two responses were dissociable. Irradiation resulted in a transient arrest in the HCT116 cells while arrest was prolonged in the Ligase IV (-/-) cells; however, both cell lines ultimately recovered proliferative function, which may reflect maintenance of DNA repair capacity. The PARP inhibitors (Olaparib) and (Niraparib) increased the extent of persistent DNA damage induced by radiation as well as the extent of both autophagy and senescence; neither cell line underwent significant apoptosis by radiation alone or in the presence of the PARP inhibitors. Inhibition of autophagy failed to attenuate radiation sensitization, indicating that autophagy was not involved in the action of the PARP inhibitors. As with radiation alone, despite sensitization by PARP inhibition, proliferative recovery was evident within a period of 10-20 days. While inhibition of DNA repair via PARP inhibition may initially sensitize tumor cells to radiation via the promotion of senescence, this strategy does not appear to interfere with proliferative recovery, which could ultimately contribute to disease recurrence. Citation Format: Moureq R. Alotaibi, Khushboo Sharma, Tareq Saleh, Lawrence Povirk, Eric Hendrickson, David Gewirtz. Autophagy, senescence and proliferative recovery subsequent to DNA damage in radiation sensitization by PARP inhibition. [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 2848.
Abstract 5238: The chemopreventive potential of silver nanoparticles against UVB-induced skin carcinogenesis in mouse model
Authors: Nikhil Tyagi, Sumit Arora, Sanjeev K. Srivastava, James E. Carter, Ajay P. Singh, Seema Singh
Journal: Cancer Research (2016)

Abstract Solar ultraviolet (UV) radiation, particularly its UVB component, is an established cause of human skin carcinogenesis due to its ability to cause DNA damage in skin cells. Although several sunscreen formulations have been developed and commercialized to limit or minimize UVB exposure to skin cells, incidence of skin cancer has continued to increase suggesting their limited or no efficacy in preventing UV-induced skin cancer occurrence. Recently, we revealed the potential of silver nanoparticles (AgNPs; ≤ 50 nm) against UVB radiation-induced DNA damage in human keratinocytes (HaCaT). Here we performed preclinical evaluation of chemopreventive efficacy of AgNPs against UVB-induced skin tumorigenesis in SKH-1 hairless mouse model. The different concentrations (20 and 40 mg/kg) of AgNPs mixed with hydrophilic cream base were uniformly applied topically onto the dorsal area of mouse skin prior to UVB-irradiation to assess chemopreventive efficacy for several weeks. The UVB treatment group showed tumor formation within 13 weeks, and had high incidence (93.3%) rate by the end of the study (29 weeks). Interestingly, the pretreatment of mice with AgNPs significantly increased the latency period (6-9 weeks) of UVB-induced tumor formation. Moreover, overall tumor incidence was found to be significantly decreased (50 and 78%; in 20 and 40 mg/kg respectively) as compared to AgNPs-untreated mice. Tumor multiplicity and average tumor volume/tumor-bearing mouse were also observed to be significantly reduced in AgNPs-treated mice. Additionally, AgNPs treatment alone for 29 weeks did not induce any apparent signs of toxicity and changes in the body weight suggesting the safety of AgNPs. Altogether, these findings suggest that AgNPs are potential chemopreventive agents against UVB radiation-induced skin carcinogenesis and thus opening the ways for human applications. Citation Format: Nikhil Tyagi, Sumit Arora, Sanjeev K. Srivastava, James E. Carter, Ajay P. Singh, Seema Singh. The chemopreventive potential of silver nanoparticles against UVB-induced skin carcinogenesis in mouse model. [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 5238.
Abstract 1874: Oncogenic EGFR signaling inhibits the Spred1-NF1 interaction to sustain constitutive Ras signaling
Authors: Evan Markegard, Ellen L. Mercado, Jacqueline Galeas, Marena I. Trinidad, Anatoly Urisman, Frank McCormick.
Journal: Cancer Research (2016)

Abstract Spred proteins negatively regulate Ras/MAPK signaling following mitogen stimulation. Inhibition of Ras primary occurs through Spreds ability to bind and localize NF1, a RasGAP and major tumor suppressor, to the plasma membrane. Loss-of-function Spred1 and NF1 mutations occur across multiple cancer types including melanoma, non-small cell lung carcinoma, stomach carcinoma, and uterine carcinosarcoma. Here we demonstrate that oncogenic EGFR signaling disrupts Spred1-NF1 binding. Mass spectrometry was performed on cells overexpressing EGFRL858R to identify potential phosphorylation sites on Spred1 and NF1 that could disrupt Spred1-NF1 binding by steric hindrance. A serine phosphorylation site on Spred1 was identified in which a phosphomimetic and phosphodeficient mutant decreased or increased Spred1-NF1 binding, respectively. Therefore, phosphorylation of Spred1 at this site by a serine kinase downstream of oncogenic EGFR may disrupt Spred1-NF1 binding. Our findings provide one potential mechanism by which oncogenic EGFR signaling disrupts negative feedback to allow for constitutive Ras signaling. Furthermore, this work may elucidate a novel kinase therapeutic target for restoring NF1 mediated inhibition of Ras. Citation Format: Evan Markegard, Ellen L. Mercado, Jacqueline Galeas, Marena I. Trinidad, Anatoly Urisman, Frank McCormick. Oncogenic EGFR signaling inhibits the Spred1-NF1 interaction to sustain constitutive Ras signaling. [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 1874.
Adverse inpatient outcomes during the transition to a new electronic health record system: observational study
Authors: Michael L Barnett, Ateev Mehrotra, Anupam B Jena
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess the short term association of inpatient implementation of electronic health records (EHRs) with patient outcomes of mortality, readmissions, and adverse safety events. <b>Design</b>&nbsp;Observational study with difference-in-differences analysis. <b>Setting</b>&nbsp;Medicare, 2011-12. <b>Participants</b>&nbsp;Patients admitted to 17 study hospitals with a verifiable "go live" date for implementation of inpatient EHRs during 2011-12, and 399 control hospitals in the same hospital referral region. <b>Main outcome measures</b>&nbsp;All cause readmission within 30 days of discharge, all cause mortality within 30 days of admission, and adverse safety events as defined by the patient safety for selected indicators (PSI)-90 composite measure among Medicare beneficiaries admitted to one of these hospitals 90 days before and 90 days after implementation of the EHRs (n=28 235 and 26 453 admissions), compared with the control group of all contemporaneous admissions to hospitals in the same hospital referral region (n=284 632 and 276 513 admissions). Analyses were adjusted for beneficiaries' sociodemographic and clinical characteristics. <b>Results</b>&nbsp;Before and after implementation, characteristics of admissions were similar in both study and control hospitals. Among study hospitals, unadjusted 30 day mortality (6.74% to 7.15%, P=0.06) and adverse safety event rates (10.5 to 11.4 events per 1000 admissions, P=0.34) did not significantly change after implementation of EHRs. There was an unadjusted decrease in 30 day readmission rates, from 19.9% to 19.0% post-implementation (P=0.02). In difference-in-differences analysis, however, there was no significant change in any outcome between pre-implementation and post-implementation periods (all P≥0.13). <b>Conclusions</b>&nbsp;Despite concerns that implementation of EHRs might adversely impact patient care during the acute transition period, we found no overall negative association of such implementation on short term inpatient mortality, adverse safety events, or readmissions in the Medicare population across 17 US hospitals.
Does a negative post-therapy PET obviate the need for any further follow-up imaging in patients with nonbulky early-stage Hodgkin's lymphoma (HL)?
Authors: A. Gallamini, A. Biggi, S. Chauvie, A. Bianchi, S. Conti, F. Fiore, R. Sorasio, J. Vose, D. L. Thomas, M. E. Juweid
Journal: Journal of Clinical Oncology (2010)

8058 Background: Recent reports suggest that medical imaging, besides potentially harmful, could turn out neither cost- effective, nor beneficial. We investigated whether this can be justified in the post-treatment follow-up of patients with nonbulky early-stage HL (nbHL) Methods: We identified all nbHL patients who underwent post-tx PET/CT from 11/04-1/09 at Az. Ospedaliera S. Croce e Carle in Cuneo, Italy or from 7/03-8/05 at the University of Iowa, and met the following criteria: received ≥ 4-8 cycles of chemotx alone or 3-6 cycles of chemotx followed by involved-field radiation therapy (IFRT); had PET/CT performed within 3-12 wks post-tx and adequate clinical, laboratory, and radiological follow-up for ≥ 1 y post-tx or until evidence of treatment failure. PET/CT scans were interpreted by nuclear medicine experts using the International Harmonization Project criteria. Results: Forty patients met the entry criteria for the study: all stage II; 23 received 4-6 cycles of ABVD alone, sixteen 3-6 cycles of ABVD followed by IFRT, 1 patient received Stanford V with RT. Thirty-seven patients (93%) had a negative post-tx PET, 3 (7%) had a positive scan. Median overall F/U was 3.1 y (range; 0.6-5.6) and 3.1 y in patients without progression. Two of the three patients with positive PET scans had persistent disease or progressed at 0.6 and 0.7 y while the third remains with no evidence of disease at 4.7 y post-tx. None of the 37 pts with negative PET progressed or relapsed. Conclusions: Incidence of relapse in nbHL patients with a negative posttherapy PET is extremely low, justifying eliminating any further follow-up imaging in these patients unless there is clinical/biochemical suspicion of recurrence. This conclusion is further supported by previous observations that > 80% of any eventual relapses are discovered by the patient and/or physician without imaging. No significant financial relationships to disclose.
Abstract 5179: Development of a humanized mouse model for direct evaluation of anti-human PD-L1 antibodies
Authors: Meng Qiao, Juan Zhang, Jian Ding, Rui Zhang, Zhongliang Li, Jia Zheng, Teng Lu, Jinjing Ning, Qian Shi
Journal: Cancer Research (2016)

Abstract Therapies that perturb the binding of programmed death-1 receptor ligand (PD-L1) to its receptor PD-1 achieved unprecedented rates of sustained clinical responses in patients with various types of cancer. Mouse surrogate antibodies were initially evaluated in syngeneic mouse models as the proof of concept for anti-PD-L1 therapy. However, there's an urgent need to develop appropriate animal model to directly evaluate anti-human PD-L1 antibodies before clinical trial. Here we describe our ongoing efforts in developing a chimeric mouse/human cell line to test human anti PD-L1 antibody. We profiled PD-L1 expression by FACS using anti-mouse PD-L1 antibody and confirmed expression of PD-L1 in a series of murine cancer cell lines. H22, a liver cancer line with moderate expression level of PD-L1 was selected due to its in vivo sensitivity towards anti-PD1 and anti-PD-L1 antibodies. Crispr/cas9 system was employed to knockout murine PD-L1 and replace it with the human counterpart. The targeted knockout had been confirmed by sequencing, the expression of human PD-L1 is illustrated by FACS using antibody that specifically recognize human form and no cross reaction to mouse form. The engineered H22-hPD-L1 cell line was then inoculated subcutaneously to immune-competent BALB/c mice to establish the in vivo model that maintains complete murine immune system and harbor humanized PD-L1. The tumor growth curve of H22-hPD-L1 model and its sensitivity to anti-human PD-L1 antibody have been established. In summary, our H22-hPD-L1 model may be a valuable tool to evaluate the in vivo activity of anti-human PD-L1 antibody therapies either as a single agent or combinational strategies. The similar engineering may be applied to more murine cell lines (e.g. EMT-6, B16F10 and MBT-2, etc) to provide a spectrum of cell lines with different diseases and genetic makeup for immunotherapies involving anti-hPD-L1 antibodies. Citation Format: Meng Qiao, Juan Zhang, Jian Ding, Rui Zhang, Zhongliang Li, Jia Zheng, Teng Lu, Jinjing Ning, Qian Shi. Development of a humanized mouse model for direct evaluation of anti-human PD-L1 antibodies. [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 5179.
Treatment of Chemotherapy-Induced Anemia Using Epoetin Alfa Biosimilar for Patients with Lymphoma and Myeloma: The Synergy Study
Authors: Florian Scotté, Kamel Laribi, Christian Gisselbrecht, Dominique Spaeth, Emna Kasdaghli, Hélène Albrand, Eric Leutenegger, Isabelle Ray-Coquard
Journal: Blood (2015)
First-line randomized phase II study of gemcitabine/cisplatin plus apatorsen or placebo in patients with advanced bladder cancer: The International Borealis-1 trial.
Authors: Joaquim Bellmunt, Bernhard J. Eigl, Elzbieta Senkus-Konefka, Yohann Loriot, Przemyslaw Twardowski, Daniel E. Castellano, Normand Blais, Srikala S. Sridhar, Cora N. Sternberg, Margitta Retz, Brent A. Blumenstein, Cindy Jacobs, Patricia S. Stewart, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2015)

4503 Background: Heat shock protein 27 (Hsp27) is over-expressed in bladder cancer (BC) and postulated to increase tumor growth, metastasis, and chemotherapy resistance. Apatorsen (A; OGX-427), a novel antisense oligonucleotide, inhibits Hsp27 production and can potentially enhance the efficacy of chemotherapy. This trial was designed to evaluate efficacy and safety of A in combination with gemcitabine and cisplatin (GC) in patients (pts) with advanced BC. Methods: Chemotherapy naïve pts with advanced BC were randomized to GC+A 600 mg, GC+A 1000 mg, or GC + placebo. Pts were stratified by Karnofsky performance status (KPS) and visceral disease. The primary endpoint was overall survival (OS). Prognostic sub-groups were retrospectively evaluated using multiple variable modeling and hierarchical step down. A post hoc analysis was performed to explore the hypothesis that Hsp27 inhibition might be relevant to OS in poor prognosis disease. Results: A total of 179 pts were randomized/treated. Median OS was 15.2 months (m). When compared to GC + placebo, GC+A 600 demonstrated improved OS and PFS (OS HR = 0.856 and PFS HR = 0.830) versus GC+A 1000 (OS HR = 0.898; PFS HR = 0.927). Results from the post hoc model revealed that KPS, liver mets, alk phos, and hemoglobin were prognostic. A median prognostic score dichotomized pts into poor and good prognosis groups (50% each group). Pts with poor prognosis treated with GC+A 600 had a greater reduction in risk of death (HR = 0.717) than pts with good prognosis (HR = 1.44). The most significant prognostic factor was KPS ≤ 80% (35% pts in GC+A 600 vs GC) resulting in HR = 0.50 in favor of GC+A 600. Overall treatment was well tolerated. Most common Grade ≥ 3 adverse events (AEs) were neutropenia, anemia, thrombocytopenia and hypertension. Frequency of ≥ 3 Grade toxicities were: 89% (GC), 93% (GC+A 600) and 95% (GC+A 1000). GC+A 1000 had a higher treatment discontinuation rate due to AEs. Conclusions: Advanced BC pts with poor prognosis benefited from apatorsen 600mg combined with first line GC. Apatorsen may be impacting the intrinsic biology of patients with poor risk factors. Further evaluation is warranted in this pt population. Clinical trial information: NCT01454089.
What Happens When Underperforming Big Ideas in Research Become Entrenched?
Authors: Michael J. Joyner, Nigel Paneth, John P. A. Ioannidis
Journal: JAMA (2016)

In this Viewpoint, John Ioannidis and colleagues review how rarely gene therapy and genomic medicine have led to breakthroughs for patients and call on the NIH to defund preclinical research that fails to deliver on its initial promise.
Formation à l'épidémiologie d'intervention : une perspective européenne
Authors: F van Loock, Mike Rowland, T Grein, A Moren
Journal: Eurosurveillance (2001)

Avec l’extension de l’Union Europeenne, les mouvements de populations a grande echelle, les echanges commerciaux d’animaux et de produits alimentaires augmentent le risque potentiel de dissemination de maladies transmissibles. Ce n’est qu’en 1992 que l’Union Europeenne a ete mandatee par le Traite de l’Union Europeenne (Traite de Maastricht) pour mener des actions de sante publique. Son champ d’action a ete etendu en 1997 par le Traite d’Amsterdam.
Recipient CD8+ DC Delete Alloreactive Donor CTL and Promote Leukemic Relapse after Allogeneic BMT
Authors: Kate A Markey, Rachel D Kuns, Renee J Robb, Motoko Koyama, Kate Helen Gartlan, Andrea S Henden, Simone A Minnie, Kelli P A Macdonald, Thomas Brocker, Gabrielle T Belz, Steven W. Lane, Geoff R Hill
Journal: Blood (2015)
A Phase 1/2 Study Of The Safety and Activity Of Escalating Doses Of Lenalidomide Plus Rituximab For Patients With Refractory Or Relapsed Chronic Lymphocytic Leukemia (LLC-Lenar-08)
Authors: Jose Francisco Tomas, Marcos González, Pilar Giraldo, Mª José Terol, Jose Antonio Pérez Simón, Raquel de Oña
Journal: Blood (2013)