tbuckley/cabot-search huggingface dataset:
Abstract 693: Histone deacetylase inhibitors attenuate epirubicin induced p53 expression
Authors: Kenneth T. Thurn, Scott Thomas, Ashleigh Miller, Pamela Munster
Journal: Cancer Research (2010)

Abstract Preclinical and clinical studies have demonstrated that Histone Deacetylase Inhibitors (HDACIs) can act synergistically with topoisomerase II inhibitors (e.g. doxorubicin, epirubicin) to increase the induction of apoptosis in breast cancer cells. We have previously shown that HDACIs (i.e. valproic acid and suberoylanilide hydroxamic acid, SAHA/vorinostat) caused a reduction in the expression of specific chromatin maintenance genes including HP1-, DNMT1 and SMC1-5 with subsequent chromatin decondensation. Chromatin decondensation facilitates access for DNA damaging agents such, as topoisomerase inhibitors, to their DNA substrate resulting in an increase in the topoisomerase induced DNA strand breaks and cell death. Using siRNA mediated depletion of HDAC2, similar synergistic effects were observed compared to valproic acid or SAHA. This was not observed with depletion of HDAC1 or HDAC6. This suggested the specific role of HDAC2 in mediating the synergy in increased DNA damage and apoptosis with epirubicin. However, efficient DNA strand break repair may be an alternate mechanism of resistance. To determine whether the HDAC inhibitors play a role in the inhibition of repair enzymes in addition to the increased induction of epirubicin induced strand breaks, we sought to determine the effects of HDACIs on epirubicin mediated DNA damage repair. Previous studies have shown that various HDACis down-regulate DNA repair associated genes including BRCA1, Ku70, and Rad51. Micro-array analysis performed by our group of cultured breast cancer cells treated with valproic acid or siRNA targeting HDAC2 revealed the down-regulation of the dsDNA repair genes Rad51b and Rad51c. These Rad51 paralogs have distinct functions in homologous recombination. Rad51b has been shown to associate with, and phosphorylate p53. Rad51c is able to exchange DNA strands vital for homologous recombination, and has been suggested to recruit Rad51 to sites of DNA damage. It is also suggested to be a Trp53-dependent tumor suppressor. We show that treatment of breast cancer cells with vorinostat caused a decrease in p53 protein expression. Furthermore, pre-treatment of these cells with valproic acid or SAHA significantly inhibited the induction of p53 in the presence of epirubicin. At the time points tested (0-120 minutes), this corresponded to an initial decrease in DNA repair kinetics as demonstrated by γ-H2AX expression. We hypothesize therefore that the treatment of breast cancer cells with HDACis in the presence of epirubicin results in a decreased expression of the homologous recombination Rad51 paralog proteins and downstream p53. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 693.
VALIDATION AND COMPARISON OF A HISTORY-BASED RISK SCORE FOR DIAGNOSIS OF OBSTRUCTIVE CORONARY ARTERY DISEASE AMONGST A RANDOMIZED, CONTROLLED COHORT: THE SCOT-HEART TRIAL
Authors: Lohendran Baskaran, Ibrahim Danad, Heidi Gransar, Fay Lin, David Newby, James Min
Journal: Journal of the American College of Cardiology (2016)
A Targeted Health Risk Assessment Following the <i>Deepwater Horizon</i> Oil Spill: Polycyclic Aromatic Hydrocarbon Exposure in Vietnamese-American Shrimp Consumers
Authors: Mark J. Wilson, Scott Frickel, Daniel Nguyen, Tap Bui, Stephen Echsner, Bridget R. Simon, Jessi L. Howard, Kent Miller, Jeffrey K. Wickliffe
Journal: Environmental Health Perspectives (2014)

The Deepwater Horizon oil spill of 2010 prompted concern about health risks among seafood consumers exposed to polycyclic aromatic hydrocarbons (PAHs) via consumption of contaminated seafood.The objective of this study was to conduct population-specific probabilistic health risk assessments based on consumption of locally harvested white shrimp (Litopenaeus setiferus) among Vietnamese Americans in southeast Louisiana.We conducted a survey of Vietnamese Americans in southeast Louisiana to evaluate shrimp consumption, preparation methods, and body weight among shrimp consumers in the disaster-impacted region. We also collected and chemically analyzed locally harvested white shrimp for 81 individual PAHs. We combined the PAH levels (with accepted reference doses) found in the shrimp with the survey data to conduct Monte Carlo simulations for probabilistic noncancer health risk assessments. We also conducted probabilistic cancer risk assessments using relative potency factors (RPFs) to estimate cancer risks from the intake of PAHs from white shrimp.Monte Carlo simulations were used to generate hazard quotient distributions for noncancer health risks, reported as mean ± SD, for naphthalene (1.8 × 10-4 ± 3.3 × 10-4), fluorene (2.4 × 10-5 ± 3.3 × 10-5), anthracene (3.9 × 10-6 ± 5.4 × 10-6), pyrene (3.2 × 10-5 ± 4.3 × 10-5), and fluoranthene (1.8 × 10-4 ± 3.3 × 10-4). A cancer risk distribution, based on RPF-adjusted PAH intake, was also generated (2.4 × 10-7 ± 3.9 × 10-7).The risk assessment results show no acute health risks or excess cancer risk associated with consumption of shrimp containing the levels of PAHs detected in our study, even among frequent shrimp consumers.
Breast tumor cells with <i>PI3K</i> mutation or <i>HER2</i> amplification are selectively addicted to Akt signaling.
Authors: Q She, S Chandarlapaty, Q Ye, J Lobo, KM Haskell, KR Leander, D DeFeo-Jones, HE Huber, N Rosen
Journal: Cancer Research (2009)

Abstract Abstract #3061 Background: Activation of the PI3K/Akt pathway is a common event in human cancers and is responsible for key aspects of the transformed phenotype. This pathway is activated in most breast cancers, but by different mechanisms including HER2 amplification, PI3K mutation and PTEN inactivation. Inhibition of this pathway is thus thought to be clinically useful, but the functional output of PI3K/Akt signaling and the corresponding clinical effects of its inhibition may be due to the mechanisms by which it is activated. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.&amp;#x2028; Methodology/Principal Findings: Using a panel of human breast cancer cell lines that harbor HER2 amplification, PI3K or PTEN mutations, or wild-type of PI3K and PTEN, and a selective, PH-domain dependent, allosteric inhibitor of Akt1 and Akt2 (AKTi-1/2), and a variety of biochemical, molecular, and cellular techniques as well as in vivo xenograft models, we show that AKTi-1/2 resulted in the selective inhibition of breast tumor cell lines with either mutant PI3K or amplified HER2, but not those in which PI3K/Akt signaling is not mutationally activated. Cellular sensitivity was due to induction of G1 arrest and of apoptosis and associated with inhibition of Akt signaling, loss of D-cyclin expression, and dephosphorylation of Rb. Most importantly, AKTi-1/2 effectively inhibited Akt kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well-tolerated, causing only transient hyperglycemia without gross toxicity to the host despite the pleiotropic normal functions of Akt.&amp;#x2028; Conclusions/Significance: Our data demonstrate the exquisite dependence of PI3K-mutated or HER2-amplified breast cancer cells on Akt signaling, and that effective inhibition of Akt in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of Akt may represent a therapeutic strategy for breast cancers that are addicted to the pathway and in patients with clinical resistance to Herceptin. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3061.
PREDICTING OUTCOMES IN PATIENTS WITH ATRIAL FIBRILLATION AND ACUTE MESENTERIC ISCHEMIA
Authors: Muhammad Shahreyar, Geetanjali Dang, Sanjay Bhandari, Ahmad Hanif, Mohammad W. Bashir, Vijayadershan Muppidi, Atul Bhatia, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2016)
PWE-035 The Introduction of a Weekly General Anaesthetic Ercp List Improves Desired Duct Cannulation and Duct Drainage Rates
Authors: J Neale, R Ellis, P Goggin, A Fowell
Journal: Gut (2013)

<h3>Introduction</h3> ERCP remains a key, but potentially complex endoscopic modality. ERCP procedures can be prolonged and consequently require higher dose and longer duration of conscious sedation. The use of anaesthetist-led deep sedation or general anaesthesia (GA) has been clearly demonstrated as a safe alternative to the use of conscious sedation<sup>1,2</sup>. However, the effect of general anaesthesia on the success of ERCP has not been well studied. The aim of this study was to examine the impact of the introduction of a weekly anaesthetist-led GA ERCP list on the successful completion of ERCP. <h3>Methods</h3> The data for all ERCP procedures performed within our unit was retrieved from the local endoscopic database covering the period one year before (BGA) and one year after (AGA) introduction of a weekly GA ERCP list in January 2012. Data regarding selective cannulation rates, patient and endoscopist demographics and complications were analysed. Success at ERCP was defined as selective deep cannulation of the targeted duct and the successful drainage of obstructed systems when required. <h3>Results</h3> A total of 713 ERCP cases were examined. ERCPs were performed by 3 experienced endoscopists within a single endoscopy unit. 357 cases were performed prior to regular GA list introduction and 356 cases after. There were 28 cases performed under GA in the BGA group and 81 in the AGA group (p &lt; 0.01). There was no statistical difference in patient age or gender ratio. Following the introduction of regular GA ERCP lists, the overall procedural success rate increased from 94.7% to 98.3% (p &lt; 0.01). Procedural failure did not occur in any of the 109 cases performed under GA. Reasons for failure at ERCP were multiple, with sedation failure directly quoted in 3 of the 25 cases. Use of sedation reversal agents was lower in the AGA group (8 vs 1 cases, p &lt; 0.05). <h3>Conclusion</h3> The introduction of a weekly general anaesthetic ERCP list has improved desired duct cannulation and drainage success within our endoscopy unit. This advantage of anaesthetist-led sedation has not been previously demonstrated. The mechanism of improved success is likely to be multi-factorial in origin. Although agitation and sedation failure were cited in only a minority of procedural failures, we believe the increased control and safety afforded allows the endoscopist to successfully perform more challenging interventions. These data may support the wider introduction of anaesthetist-led sedation/general anaesthesia for ERCP. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Bo LL<i></i><i>et al.</i> Propofol vs traditional sedative agents for endoscopic retrograde cholangiopancreatography: a meta-analysis.<i> World J Gastroentero</i>l. 2011 Aug 14; 17(30):3538–43. Garewal D <i>et al.</i> Sedative techniques for endoscopic retrograde cholangiopancreatography. <i>Cochrane Database Syst Rev</i>. 2012 Jun 13; 6:CD007274.
Abstract P2-14-10: Self Reported Cognitive Function in Breast Cancer Survivors: A 12 Month Longitudinal Descriptive Study
Authors: D Barton, K Burger, P Novotny, J. Sloan
Journal: Cancer Research (2010)

Abstract Background: Changes in cognitive function are commonly reported in breast cancer (BC) survivors. Longitudinal studies have only recently been completed and are few. In particular, long term studies are lacking. The purpose of this abstract is to describe self-reported cognitive changes in women before the start, or after the first cycle of chemotherapy, through 12 months. Methods: The data for this analysis were collected as part of a placebo-controlled randomized trial evaluating ginkgo biloba for the prevention of cognitive decline during adjuvant chemotherapy for BC. As there was no evidence that gingko biloba impacted cognitive function in any way, the sample was combined. Descriptive statistics were calculated to obtain the percent of women reporting worse perceived functioning or changes in their cognitive function at the start of chemotherapy, at the completion of treatment, and at 6, 12 and 24 months later (24 month data still being analyzed). 210 women, mostly white and mostly beginning anthracycline based chemotherapy, completed self report measures of cognition throughout the study. Women rated 10 areas of functioning by choosing a number from 1, signifying “functioning extremely less than normal”, to 7, signifying “extremely better than normal”. A score of 4 represented functioning perceived as “normal” for the respondent. Results: At baseline and after chemotherapy, the means for all 10 self reported cognitive items indicated “less than normal” functioning. Areas with the worst functioning included memory, ability to think clearly, staying focused, and planning ahead. At 6 and 12 months after chemotherapy, a percentage of participants reported worse functioning compared to baseline in every area. Changes in functioning are in the table below. Table 1 At 12 months, the mean for only 4 items indicated these areas were at “normal” functioning. These were the ability to learn, solve problems, react quickly and balance a checkbook. Discussion: For a subgroup of women, cognitive changes continue to worsen throughout 12 months and for many, perceived deficits remain. Areas most negatively impacted relate to attention, memory and executive function. Future research should focus on identifying predictors of worse functioning and continued research is needed to elucidate targets for intervention research to prevent unwanted cognitive changes. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-10.
Cancer Program Praised And Criticized As Plans Are Forged For the 21st Century
Authors: Susan Jenks
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Cancer Program Praised And Criticized As Plans Are Forged For the 21st Century Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 20, 20 October 1993, Pages 1631–1632, https://doi.org/10.1093/jnci/85.20.1631 Published: 20 October 1993
NC-12 * DEPRESSION AND EXECUTIVE FUNCTIONING IN RELATION TO SURVIVAL AMONG PATIENTS WITH GLIOBLASTOMA
Authors: K. Noll, A. Garbarino, C. Turner, A. M. S. Verhaak, J. Wefel
Journal: Neuro-Oncology (2014)

OBJECTIVE: Depression and neurocognitive function (NCF), particularly executive functioning (EF), have been associated with overall survival (OS) in patients with glioblastoma (GBM). However, the combined effect of depression and impaired EF has not been reported. METHODS: Patients with GBM (n = 102) completed neuropsychological assessment postoperatively (mean = 23.5 days post surgery) including the Beck Depression Inventory-Second Edition (BDI-II) and the Trail Making Test Part B (TMTB). Median splits were used to determine cut-points indicating the presence of elevated depressive symptoms on the BDI-II (BDI-II > 8) and executive impairment on TMTB (demographically-adjusted z-score < -1.7). Patients were stratified into 4 groups: no depression/no EF impairment (-Dep/-Imp; n = 23), depression/no EF impairment (+Dep/-Imp; n = 28), no depression/EF impairment (-Dep/ + Imp; n = 28), and depression/EF impairment (+Dep/ + Imp; n = 23). The Kaplan-Meier method, log-rank test, and cox regression were used to examine differences in survival between groups. RESULTS: Relative to -Dep/-Imp patients (median OS = 22.8 months), median OS in all other patient groups patients was shorter (+Dep/-Imp OS= 16.6, HR 1.71, CI = 0.91 to 3.22; -Dep/ + Imp OS = 14.8, HR 2.13, CI = 1.14 to 3.99; +Dep/ + Imp OS = 10.8 months, HR 4.15, CI = 2.12 to 8.10). The groups did not differ in terms of distribution of RPA class, extent of resection, initial therapy, salvage therapy with bevacizumab, tumor location, history of depression, and psychotropic medication use. While groups differed in percent of patients with KPS = 70-80 and age > 50, neither KPS nor age modified the independent effect of BDI-II and TMTB on OS in cox regression models. CONCLUSION: The presence of depressive symptoms and impaired EF are independently associated with shorter survival in patients with GBM. This retrospective analysis was unable to determine if these factors were independent of tumor molecular markers. Routine neuropsychological assessment of mood and cognition can help refine prognosis and facilitate initiation of psychological and cognitive interventions, which are likely to improve patient quality of life and may extend survival time.
Case 9-1998
Authors: Michael F. Greene, Drucilla J. Roberts, Eugene J. Mark
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 38-year-old woman (gravida 5, para 1) was admitted to another hospital in spontaneous labor.The patient's first pregnancy, six years earlier, had ended successfully at 36 weeks' gestation. A low transverse cesarean section was performed because of a breech presentation, and a uterine leiomyoma was resected. Subsequently, the patient had three spontaneous abortions in the first trimester. The most recent abortion occurred a year before admission, at six weeks' gestation. An ultrasonographic examination showed a nonviable fetus and a leiomyoma, 5 cm in diameter, adjacent to the gestational sac. A suction dilation and curettage was performed . . .
T-Cell Function and Migration — Two Sides of the Same Coin
Authors: Ulrich H. von Andrian, Charles R. Mackay
Journal: New England Journal of Medicine (2000)

Since the pioneering work of Gowans and colleagues in the 1960s,1,2 much progress has been made in understanding the pivotal role of cell migration in immunity. We now have considerable knowledge of the way in which specialized leukocytes are channeled to distinct target tissues in immune responses and inflammation (Figure 1). This review will concentrate on the migration of T cells, which are at the heart of most adaptive immune responses.Since T cells respond to pathogens only on direct contact with pathogen-derived antigen, they must migrate to sites where antigen is found. The T-cell receptor recognizes a peptide . . .
Cerebral Arterial Spasm – A Controlled Trial of Nimodipine in Patients with Subarachnoid Hemorrhage
Authors: George S. Allen, Hyo S. Ahn, Thomas J. Preziosi, Roy Battye, Stephen C. Boone, Shelley N. Chou, David L. Kelly, Bryce K. Weir, Ruth A. Crabbe, Paula J. Lavik, Shelley B. Rosenbloom, Frank C. Dorsey, Charles R. Ingram, David E. Mellits, Linda A. Bertsch, Donald P. J. Boisvert, Mary B. Hundley, Rayetta K. Johnson, Jo A. Strom, Carole R. Transou
Journal: New England Journal of Medicine (1983)

We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm. (N Engl J Med. 1983; 308:619–24.)
Abstract 1636: Anticancer drug-induced Jak2/Stat3 activation confers a survival advantage in lung cancer cells
Authors: Wen-Pin Su, Ya-Chin Lo, Chien-Chung Lin, Helen H.W. Chen, Wu-Wei Lai, Wu-Chou Su
Journal: Cancer Research (2010)

Abstract Chemotherapy may trigger survival signaling in cancer cells and the cells may change the response to chemotherapy. Here we found chemotherapeutics-induced Jak2/Stat3 signaling activation, by which cancer cells escape from death in human lung cancer PC14PE6AS2 (AS2) and H157 cells with constitutively activated Stat3 protein. Cisplatin, paclitaxel and epirubicin are important agents in lung cancer treatment and they are reactive oxygen species (ROS)-producing agents. In AS2 and H157 cells, we found that during the paclitaxel treatment, early Jak2 activation occurred and then Stat3 tyrosine phosphorylation upregulated early. But Stat3 serine phosphorylation was not significantly increased. When AS2 and H157 cells were treated with cisplatin and epirubicin, the Jak2/Stat3 activation was also observed, which can be blocked by AG490. It is indicated that chemotherapy, such as paclitaxel, cisplatin and epirubicin, may activate Jak2/Stat3 pathway. In AS2 cells, chemotherapeutics generated ROS, and the chemotherapy-induced Jak2/Stat3 activation was only effectively inhibited by mitochondrial ROS scavengers as rotenone and antimycin. The similar finding was also observed in H157 cells. It is said that “mild” mitochondrial uncoupling provides a survival benefit in cancer cells. In AS2 and H157 cells, pretreatment with the mitochondrial uncoupler carbonylcyanide-4-trifluoromethoxy-phenylhydrazone (FCCP) inhibited paclitaxel-induced mitochondrial ROS generation, abolished paclitaxel-induced Stat3 activation in AS2 and H157 cells, and augmented paclitaxel-induced mitochondrial membrane potential decrease. Thereafter, we classified AS2 and H157 cells as “FCCP-responsive” or “less mitochondrial uncoupling” cancer cells. So that mitochondrial coupling-mediated oxidative stress modulated paclitaxel-induced Jak2/Stat3 activation in AS2 and H157 cells. Subsequently, Stat3 activation by chemotherapeutics enhanced survivin expression in AS2 and H157 cells. Pretreatment with AG490, FCCP and rotenone blocked paclitaxel-induced survivin expression in a dose-dependent manner. Pretreatment with FCCP and rotenone also made AS2 and H157 cells more sensitive to the drug. Conclusively, anti-cancer drugs-induced Jak2/Stat3 activation confers a survival advantage in lung cancer AS2 and H157 cells via mitochondrial-coupling mediated ROS generation. This is a new phenomenon of cellular response to chemotherapeutics, by which cancer cells escape from drug-induced death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1636.