tbuckley/cabot-search huggingface dataset:
PTH-050 The Impact Of A Dedicated Inpatient Bleeders Endoscopy List In The Timely Management Of Acute Upper Gastrointestinal Bleeds: Abstract PTH-050 Table 1
Authors: M Harrington, S Subramaniam, V Mathew, S Gupta
Journal: Gut (2014)

<h3>Introduction</h3> Acute upper gastrointestinal bleeding (AUGIB) is still a medical emergency with a hospital mortality rate of 10%<sup>[1]</sup>. NICE guidelines recommend that endoscopy is offered to all patients presenting with AUGIB within 24 h<sup>[1]</sup>. In order to improve our waiting times, a week day dedicated Inpatient Bleeders (IB) list was introduced from October 2012 and its impact on time to endoscopy and length of hospital stay monitored through audit. <h3>Methods</h3> A retrospective audit of all AUGIB in Princess Alexandra Hospital (a district general hospital in Essex) was conducted from April-September 2012 (prior to the introduction of the IB list) and from January-April 2013 (once IB list established). The IB list set aside 3 slots every Monday-Friday from 8–9 am for inpatient AUGIB. Each week a designated consultant gastroenterologist was responsible for performing endoscopies on the IB list. AUGIB cases were identified from endoscopy indications being ‘haematemesis’ and/or ‘melaena’. Patients who developed AUGIB after admission were excluded. For each patient, the endoscopy date, admission and discharge dates were collected from electronic discharge summaries and patient records. The time (in days) to endoscopy (from admission) and length of hospital stay (LOS) was calculated for all cases. <h3>Results</h3> The longest wait to OGD was for patients admitted on a weekend (Friday-Sunday) with a mean waiting time of 3.04 days pre IB list though this figure reduced to 1.88 days with the introduction of the IB list. <h3>Conclusion</h3> The introduction of the 5 day IB list enabled our gastroenterology service to improve compliance with the NICE guidelines for AUGIB as the mean number of days to OGD decreased from 2.15 to 1.78, with over 50% of patients having an OGD within 24 h under the new system. The median LOS was also reduced from 5 to 4 days with the IB list. We expect that an extension of the IB list from a 5 to 7 day service would further reduce waiting times to OGD and LOS. The use of a dedicated ‘bleeders’ list prior to the start of elective endoscopy lists is an efficient and safe method of meeting targets in AUGIB and we would recommend its use particularly in a district general hospital setting with limited access to a 24/7 emergency AUGIB endoscopy service. <h3>Reference</h3> 1Acute upper gastrointestinal bleeding: management’; Issued June 2012; NICE clinical guidance 141; guidance.nice.org.uk/cg141 <h3>Disclosure of Interest</h3> None Declared.
Does Hiatus Hernia Affect Competence of the Gastroesophageal Sphincter?
Authors: Sidney Cohen, Lauran D. Harris
Journal: New England Journal of Medicine (1971)

To measure the effect of a sliding (concentric) hiatus hernia on gastroesophageal sphincter competence, 75 patients were studied: 25 patients without esophageal symptoms and without hiatus hernia (Group A); 25 patients without esophageal symptoms but with hiatus hernia (Group B); and 25 patients with symptoms of severe gastroesophageal reflux, with or without a hiatus hernia (Group C). In Group C, 12 patients had a hiatus hernia, and 13 did not. Symptomatic patients were readily separated from asymptomatic ones both by a weaker base-line sphincter strength and by decreased sphincteric response to the stimulus of an increase in intraabdominal pressure. However, in neither the asymptomatic nor the symptomatic groups of patients could any effect of hiatus hernia be found. A hiatus hernia apparently has no effect on gastroesophageal sphincter competence. The rationale for surgical repair of hiatus hernia in patients with gastroesophageal reflux must therefore be questioned.
Abstract LB-174: A DNA hypermethylation module for the stem/progenitor cell signature of cancer
Authors: Hariharan Easwaran, Sarah E. Johnstone, Leander Van Neste, Joyce E. Ohm, Tim Mosbruger, Martin Aryee, Srinivasan Yegnasubramanian, William Matsui, Stephen B. Baylin
Journal: Cancer Research (2011)

Abstract It has been firmly established that cancer gene expression partly mimics the gene expression signature in embryonic stem cells (ESC). Since most cancers arise in adult stem or progenitor cells, rather than ESC, we now compare cancer chromatin to both embryonic and adult cell renewal systems to understand the relationships between DNA hypermethylation, gene expression, and chromatin states. DNA hypermethylation at CpG island promoters of hundreds of genes, including classic tumor suppressors, is a major modulator of gene expression in human cancers. Past studies suggest ∼ 50% of these are frequently marked by polycomb complex (PcG) transcriptional repressors, but not DNA methylation, in embryonic stem cells (ESC). In ESC, PcG occupancy is predominantly in the context of “bivalent chromatin”, wherein the active transcription mark H3K4me3 and the repressive PcG mark H3K27me3 are simultaneously present. Genes so marked are in a low, but poised, transcription state important for stemness and self-renewal, characteristics shared with tumor cells. Using whole genome ChIP-seq and DNA methylation arrays, we find between 70 to 80% of genes with DNA hypermethylation in cancer have bivalent chromatin not only in ESC, but also in adult stem cells. For these genes, there appears to be an epigenetic switch in cancer wherein bivalent chromatin is replaced by DNA hypermethylation resulting in tighter repression of gene expression. Many of these DNA methylated cancer genes are constituents of the recently proposed “PRC module” of the “ESC cancer signature.” Our data suggest a “DNA methylation module” that recapitulates the “stem cell signature” and that DNA hypermethylation may be a key mechanism that confers cell-renewal and stemness to tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-174. doi:10.1158/1538-7445.AM2011-LB-174
Marrow Visualization on an Abdominal Blood Pool Scan
Authors: SANJAY M. GANDHI, ALEX AZBEL, KHALID SALEEMI, LEONARD M. FREEMAN
Journal: Clinical Nuclear Medicine (1997)

A Tc-99m RBC gastrointestinal bleeding study was performed on a 65-year-old woman with acute promyelocytic leukemia who had thrombocytopenia and anemia due to chemotherapy. Striking visualization of the lumbar vertebral bodies and iliac bones were apparent throughout the entire 90 minutes that the study was initially performed. A delayed 20-hour image showed sacroiliac activity. At approximately 50 minutes into the study, a new focus of activity appeared over a right iliac vessel, which may represent a site of intramural bleeding. The osseous visualization likely represents enhanced bone marrow circulation and uptake secondary to the blood dyscrasia. This finding previously has been described on renal perfusion studies, but not on delayed blood pool images.
Abstract 2151: Characterization of a novel anti-apoptotic signaling pathway downstream of FGFR4 in rhabdomyosarcoma
Authors: Marco Wachtel, Beat Schaefer
Journal: Cancer Research (2011)

Abstract FGFR4 is highly overexpressed in Rhabdomyosarcoma tumors and contains activating mutations in eight percent of the cases. These data strongly suggest that FGFR4 plays an important role in the tumorigenesis of this cancer type. However, the molecular mechanisms behind the benefit of active FGFR4 for Rhabdomyosarcoma cells are largely unknown. Here, we describe a survival pathway activated by FGFR4 in Rhabdomyosarcoma cells. Active FGFR4 is able to block apoptosis induced by inhibition of other central signaling pathways with small molecule inhibitors, such as the IGF1R pathway with AEW541 and PI3K-controlled pathways with BEZ235. Using different biochemical and genetic approaches, we could locate the apoptotic block upstream of the pro-apoptotic BH3-only proteins bmf and bim. To further elucidate the mechanism of this prosurvival signaling, we then performed proteomic studies to define the complete interactome of FGFR4 in Rhabdomyosarcoma cells. These analyses revealed a strong interaction of FGFR4 with PLCγ, linking FGFR signaling to PKCs. Indeed, activation of PKCs strongly inhibits AEW541/BEZ253-induced apoptosis, suggesting that PKCs are central for FGFR4-activated survival signaling. In contrast, the classical survival pathways via Akt and Erk are not or only marginally involved in the rescue mechanism. Treatment approaches targeting the IGF1R/PI3K axis in Rhabdomyosarcoma are under intensive investigation. Our data suggest that rescue mechanisms via FGFR4 and PKCs should be taken into account when applying such treatment strategies. A combination of IGF1R- and FGFR4/PKC-inhibitors therefore might be superior compared to single treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2151. doi:10.1158/1538-7445.AM2011-2151
F-18 FDG Versus Ga-67 for Detecting Splenic Involvement in Hodgkin’s Disease
Authors: Josephine N Rini, Evelyn Y Manalili, Mark A Hoffman, Gungor Karayalcin, Bhoomi Mehrotra, Maria B Tomas, Christopher J Palestro
Journal: Clinical Nuclear Medicine (2002)

Purpose The objectives of this investigation were to characterize splenic uptake patterns of F-18 fluorodeoxyglucose (FDG) and Ga-67 in newly diagnosed Hodgkin’s disease, to correlate these uptake patterns with the presence or absence of splenic disease, and to compare the accuracy of these two studies for detecting splenic disease. Methods FDG positron emission tomography and Ga-67 whole-body and SPECT imaging were performed in 32 patients with previously untreated Hodgkin’s disease. Two readers, blinded to clinical information and final diagnoses, independently reviewed the study results. For both FDG and Ga-67, the intensity of splenic uptake was compared with the intensity of hepatic uptake and graded as follows: 0, less than liver uptake; 1, equal to liver uptake; and 2, greater than liver uptake. Differences in interpretation were resolved by consensus. Results Twelve (38%) of 32 patients had splenic disease. Using splenic uptake greater than hepatic uptake as the criterion for a positive study, the sensitivity, specificity, and accuracy of FDG were 92%, 100%, and 97%, respectively. Using splenic uptake at least as intense as hepatic uptake as the criterion for a positive study, the sensitivity specificity, and accuracy of Ga-67 were 50%, 95%, and 78%, respectively. The differences in sensitivity and accuracy of FDG and Ga-67 were significant (P = 0.04, and 0.03, respectively). Conclusion In newly diagnosed Hodgkin’s disease, FDG accurately diagnoses splenic involvement and is significantly more sensitive and accurate than Ga-67 for this purpose.
Abstract LB-431: Randomized trial of oral melatonin supplementation in breast cancer survivors
Authors: Eva S. Schernhammer, Anita Giobbie-Hurder, Kathryn Gantman, Jennifer Savoie, Rochelle Scheib, Wendy Chen
Journal: Cancer Research (2010)

Abstract Background: Night shift work has been classified by the International Agency for Research and Cancer and the World Health Organization as a probable carcinogen, presumably due to its effect on the melatonin pathway. Extensive laboratory and some human data also support that melatonin may influence breast cancer risk, although the mechanism is not clear. Both pharmacologic and physiologic doses of melatonin inhibit the growth of malignant cells of the breast in vitro and in animal models. Study Design: 95 postmenopausal women with a prior history of Stage 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were recruited to a double-blind randomized trial of 4 months of 3 mg melatonin daily compared to placebo. Endpoints included changes in breast cancer biomarkers, sleep, hot flashes, and mood. Results: 5 subjects on melatonin and 4 on placebo withdrew from the study or did not complete the 4 month assessment leaving 86 women (43 on placebo and 43 on melatonin) with evaluable data. Melatonin was well-tolerated without any grade 3/4 toxicity. At baseline, there was no statistical difference between the two arms for any of the endpoints or standard demographic characteristics. Mean age was 59 years (range 38-71) with mean 8 years since diagnosis. At 4 months, there were no statistically significant differences between the two groups for the biomarker endpoints (estradiol, IGF-1, IGFBP-3, or IGF-1/IGFBP-3 ratios), depressive symptoms, or hot flashes. However, subjects taking melatonin had significantly improved sleep quality, sleep duration, and total sleep scores compared with subjects taking placebo. Conclusions: Among postmenopausal women with a prior history of breast cancer, a 4 month course of 3 mg melatonin daily did not influence IGF-1, IGFBP-3 or estradiol levels. Effects of longer courses of melatonin and among premenopausal women are unknown. However, melatonin was effective in improving sleep quality among breast cancer survivors without any significant adverse effects. 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 LB-431.
End-of-life care for hospitalized patients with metastatic melanoma in France: a nationwide, register-based study
Authors: I. Gallais Sérézal, Y. Beaussant, P. Rochigneux, C. Tournigand, R. Aubry, B. Lindelöf, L. Morin
Journal: British Journal of Dermatology (2016)

Although the aggressiveness of end‐of‐life cancer care has come under great scrutiny over the past two decades, little is known about the intensity of care and treatments in the last months of life of patients with metastatic melanoma. To measure the prevalence of aggressive cancer care use, and to assess the frequency of palliative care referral over the course of the last 3 months of life of hospitalized patients who died from metastatic melanoma. A nationwide register‐based study in France was carried out, including all hospitalized adults aged ≥ 20 years who died from metastatic melanoma in metropolitan France between 2010 and 2013. Of 3889 patients who died from metastatic melanoma, 51·9% received chemotherapy in the last 3 months before death, 25·9% in the last month, 12·9% in the last 2 weeks and 7·6% in the last week. On average, patients were hospitalized for 31·7 days over the course of their last 3 months of life. During the final month before death, 12·0% of patients received radiation therapy, 14·0% received blood transfusion, 12·1% were transferred into an intensive care unit and 19·7% remained hospitalized continuously. Palliative care needs were identified in 78·4% of patients, with variations according to the type of facility. In total 17% of all patients died in palliative care inpatient units. Treatment intensity near the end of life of patients with metastatic melanoma raises concerns for the quality of care. There is a need for clinical guidelines and adequate support to facilitate patient–physician communication and to improve access to palliative care services.
Abstract 731: Nuclear factor-κB activation and cetuximab-resistance in HNSCC cell lines
Authors: Hiromitsu Hatakeyama, Kimberly Brown Dahlman, Zengliu Su, Slebos Robbert, William Pao, Christine H. Chung
Journal: Cancer Research (2011)

Abstract Background: Cetuximab, a monoclonal antibody targeting EGFR, has been shown to increase survival in patients with head and neck squamous cell carcinoma (HNSCC). However, only selective patients gain therapeutic benefit. To determine a mechanism of primary resistance to cetuximab, we characterized a primary keratinocyte cell line and 34 HNSCC cell lines for somatic mutations and gene expression alterations. Experimental design: Thirty-five cell lines were assessed by 1) multiplex SNaPshot genotyping to detect 38 somatic mutations in the EGFR and its related pathways, 2) DNA sequencing of the tyrosine kinase domains of MET and FGFR3 to detect mutations, 3) qRT-PCR to quantify EGFR, MET and FGFR1 gene copy number (CN), 4) microarray analyses for gene expression profiles, and 5) matrigel colony formation assays to determine sensitivity to cetuximab. Gene mutations and CN changes were examined for potential association with cetuximab sensitivity. Differentially expressed genes between the cetuximab-resistant and -sensitive cell lines were assessed by GeneSpring and Ingenuity Pathways Analysis (IPA). To confirm the expression array data, seven representative cell lines were treated with BAY-11-7082, an IKB kinase inhibitor, to inhibit NF-kB activity. Results: Three of 35 cell lines had mutations in PIK3CA (E542K, E545Q and H1047R). The cell line with E542K mutation was resistant to cetuximab while the cell lines with E545Q and H1047R were sensitive to cetuximab. No mutations were found in MET or FGFR3. CN gains were detected in EGFR and FGFR1 (20 cell lines with EGFR CN 4-10, 10 with EGFR CN &amp;gt;10, and 9 with FGFR1 CN 4-10), but not in MET. Interestingly, many of the cell lines with EGFR CN gains also had FGFR1 CN gains (Spearman rank test, r=0.48, p=0.0032). However, there was no correlation with the CN gains and cetuximab sensitivity. IPA showed genes involved in epithelial-to-mesenchymal transition (EMT) and NF-kB activation to be associated with cetuximab resistance. Cetuximab-resistant cell lines had higher expression of vimentin and lower expression of E-cadherin. BAY-11-7082 inhibited cellular proliferation of four cetuximab-resistant cell lines, but not three sensitive cell lines. Conclusion: Mutations commonly seen in non-HNSCC cancers are rare, but EGFR and FGFR1 CN gains are common in HNSCC cell lines. The EMT phenotype and NF-kB activation may have an important role in cetuximab resistance and in novel therapeutic development in HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 731. doi:10.1158/1538-7445.AM2011-731
Abstract 3113: Effects of an up-regulated ATR-CHEK1 pathway in head and neck squamous cell carcinomas
Authors: Rahul A. Parikh, Dale W. Lewis, Susanne M. Gollin
Journal: Cancer Research (2012)

Abstract Background: The ATR-CHEK1 pathway is upregulated in a subset of head and neck squamous cell carcinoma (HNSCC) cell lines with loss of the G1 cell cycle checkpoint. We hypothesized that the upregulated ATR-CHEK1 pathway protects HNSCC from mitotic catastrophe (cell death) by enhancing the G2M phase checkpoint and that inhibition of this pathway may sensitize HNSCC to DNA damaging agents. Methods and Results: In HNSCC, we observed gain, amplification or translocation of the ATR gene in 8 of 20 cell lines studied; whereas the CHEK1 gene is partially lost in 12 of 20 cell lines. ATR and CHEK1 FISH in paraffin sections of primary head and neck squamous cell carcinomas confirmed our findings in HNSCC cell lines. We observed that both ATR and CHEK1 are overexpressed by quantitative PCR in five of eight HNSCC cell lines with loss of the G1 cell cycle checkpoint. Inhibition of ATR and CHEK1 with caffeine or specific inhibition with the respective siRNAs results in increased susceptibility of HNSCC to ionizing radiation by clonogenic cell survival assay. siRNA-mediated ATR or CHEK1 knockdown leads to loss of G2M checkpoint accumulation and increased sub-G0 apoptotic population by flow cytometric analysis. The mechanism of cell death after ATR and CHEK1 knockdown is by mitotic catastrophe, as evidenced by increased premature chromatin condensation. Conclusions: The ATR-CHEK1 pathway is up-regulated in a subset of HNSCC with loss of G1 phase cell cycle checkpoint. The up-regulated ATR-CHEK1 pathway protects these HNSCC from mitotic catastrophe by enhancing the G2M phase cell cycle checkpoints and inhibition of ATR and/or CHEK1 increase the sensitivity of the HNSCC to ionizing radiation. We conclude that inhibition of the up-regulated ATR-CHEK1 pathway in HNSCC may potentiate or increase the efficacy of the current therapeutic modalities for HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3113. doi:1538-7445.AM2012-3113
NRF2 Intensifies Host Defense Systems to Prevent Lung Carcinogenesis, but After Tumor Initiation Accelerates Malignant Cell Growth
Authors: Hironori Satoh, Takashi Moriguchi, Daisuke Saigusa, Liam Baird, Lei Yu, Hirofumi Rokutan, Keiko Igarashi, Masahito Ebina, Tatsuhiro Shibata, Masayuki Yamamoto
Journal: Cancer Research (2016)

Abstract Nrf2 activation promotes resistance to chemical carcinogenesis in animal models, but activating mutations in Nrf2 also confer malignant characters to human cells by activating antioxidative/detoxifying enzymes and metabolic reprogramming. In this study, we examined how these contradictory activities of Nrf2, cancer chemoprevention and cancer cell growth enhancement, can be reconciled in an established mouse model of urethane-induced lung carcinogenesis. Using Keap1-knockdown (kd) mice, which express high levels of Nrf2, we found that urethane was rapidly excreted into the urine, consistent with an upregulation in the expression of urethane detoxification genes. Consequently, urethane-induced tumors were significantly smaller and less frequent in Keap1-kd mice than in wild-type mice. In contrast, tumor cells derived from Keap1-kd mice and transplanted into nude mice exhibited higher tumorigenicity compared with cells derived from wild-type mice. To identify the factors contributing to the tumor growth phenotype in the transplantation model, we performed a microarray analysis and found that many antioxidative stress genes were upregulated in the Keap1-kd–derived tumors. Therefore, we suggest that Nrf2 activation in cancer cells enhances their tumorigenicity, but global Nrf2 activation, as in Keap1-kd mice, simultaneously enhances anticancer immunity, thereby suppressing the growth potential of Keap1-kd tumors. Our findings provide relevant insight into the dual role of Nrf2 in cancer and warrant further studies of Nrf2 function during different stages of carcinogenesis. Cancer Res; 76(10); 3088–96. ©2016 AACR.