tbuckley/cabot-search huggingface dataset:
PWE-022 Single centre experience of emr of large and giant colonic polyps
Authors: K Kok, E Seward, S Bloom, R Vega
Journal: Gut (2015)

<h3>Introduction</h3> Large colonic polyps are increasingly managed by endoscopic mucosal resection (EMR), avoiding the significant morbidity and potential mortality associated with surgical resection. The aim of this study was to assess the success of EMR of large and giant polyps as well as recurrence rate, complications and need for surgery. <h3>Method</h3> Retrospective analysis of all EMRs of large (&gt;20 mm) and giant (&gt; 40 mm) polyps performed between October 2012 and October 2014 in one tertiary centre. <h3>Results</h3> Success 60 large and 13 giant polyps were identified in 66 patients. 1 patient had 4 and 3 patients had 2 large polyps. Mean polyp size was 29 mm (20–70 mm). 69/72 polyps were successfully removed by EMR. 3/72 polyps were removed by surgical resection due to non-lifting of the lesion (n = 1) or position at the dentate line (n = 2). 5/72 polyps contained adenocarcinoma. 2 patients went on the have surgical resection. All 5 patients are well with no recurrence to date (mean follow up 14 months, 5–28 months). Recurrence 50/55 EMR sites checked showed no recurrence at 12 week follow up endoscopy (including all EMR sites of polyps containing adenocarcinoma). 14/69 EMR sites were never checked due to having undergone surgical resection (n = 6), comorbidities (n = 4), non-attendance (n = 2) or because the examination is still due (n = 2). 5/55 sites checked did have recurrence. 2 patients are still undergoing surveillance/treatment, 3 patients are now polyp-free. Average polyp size, APC was used, and presence of high grade dysplasia did not differ between the recurrence versus no recurrence groups. Complications 4/63 patients undergoing EMR presented with post-procedural bleeding. Further endoscopy for the bleeding was undertaken in 2 patients and endoscopic treatment was required in one of them. 2/63 patients have died since undergoing EMR. 1 patient died due to a stroke, 5 months after EMR. 1 patient had undiagnosed cirrhosis and died of decompensated liver disease with bleeding. <h3>Conclusion</h3> This single- centre analysis shows that large and giant colonic polyps can successfully be removed by EMR, without the need for any surgical intervention in 67/72 (93%) of cases. Post EMR bleeding occurred in 4/63 (6%) of cases. Recurrence is low at 9% (5/55) and 53/55 (96%) of patients are now polyp-free. <h3>Disclosure of interest</h3> None Declared.
Percutaneous transhepatic biliary drainage after failed endoscopic approach in patients with pancreatic cancer and situs inversus totalis
Authors: Giuseppe Giordano, Stefania Bonomo, Giovanni Failla, Carmelo Luigiano, Simona Caloggero, Vincenzo Magnano San Lio
Journal: Endoscopy (2014)

Situs inversus totalis is a rare entity with complete transposition of all viscera, making endoscopic, radiological, and surgical procedures challenging and complicated. Endoscopic retrograde cholangiopancreatography (ERCP) is the main treatment modality in patients with extrahepatic malignant biliary obstruction [1] [2], but in patients with situs inversus totalis, this presents a technical challenge and often fails to achieve duct access [3]. In patients with extrahepatic malignant biliary obstruction, when ERCP fails, percutaneous transhepatic biliary drainage represents a good alternative to decompress the biliary system [4] [5].
Abstract 437: Longitudinal imaging of the pancreatic cancer tumor microenvironment
Authors: Masashi Momiyama, Atsushi Suetsugu, Yasunori Tome, Michael Bouvet, Takashi Chishima, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract In order to visualize the tumor microenvironment (TME) in pancreatic cancer, the MIA PaCa-2 human pancreatic cancer cell line, expressing red fluorescent protein (RFP), was orthotopically transplanted in nude mice or transgenic mice expressing nestin-GFP. In the nestin-GFP mouse, nascent blood vessels which vascularize the growing tumor are labeled with GFP. A peritoneal flap was made on the left flank of nude mice. The tail of the pancreas was fixed on the peritoneal flap in order to image tumors on the pancreas directly and repeatedly. Color-coded imaging was observed with the Olympus OV100 Small Animal Imaging System under high magnification. The growing tumor expressing RFP, nascent blood vessels expressing GFP, and the interaction between RFP cancer cells and GFP macrophages were observed in real time. Imaging could be carried out until the tumor exceeded the size of the flap which occurred at approximately 21 days after tumor implantation. This mouse model for imaging in the pancreas TME will enable a deeper understanding of tumor-host interaction pancreatic cancer and make it possible to study new therapeutics for pancreatic cancer. 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 437. doi:10.1158/1538-7445.AM2011-437
11HDL-induced cardioprotection is independent of the HDL receptor, scavenger receptor B1
Authors: M Frias, J Brinck, MC Brulhart-Meynet, M Van Eck, R James
Journal: Cardiovascular Research (2014)

Purpose: High-density lipoproteins (HDL) are atheroprotective. New evidence shows that HDL has widespread actions, including protection against cardiac ischemia reperfusion injury (IRI). This cardioprotective role has been attributed to several constituents of the HDL particle, including apolipoprotein A1 (apoA1) the major protein constituent and sphingosine-1-phosphate (S1P). However, the exact mechanisms of HDL-induced cardioprotection are still unknown and are under intensive investigation. A particular unresolved question remains the specific role of the HDL receptor, Scavenger Receptor BI (SR-BI), in the heart. The latter mediates many of the intracellular effects of HDL. The aim of this study was to evaluate the specific role of SR-BI in the protective impact of HDL on the heart. Methods and Results: The effects of HDL on the heart was evaluated in vitro using rat cultured neonatal cardiomyocytes and ex vivo in mice using the isolated heart Langendorff model of IRI (global no flow ischemia 35min, reperfusion 60min). In this model, HDL (400μg/mL) was injected during the first 7min of reperfusion and infarct size was assessed by triphenyltetrazolium chloride (TTC) staining. The specific role of SR-BI was investigated in vitro using specific siRNA facilitated knockdown and ex vivo using SR-BI knockout (SR-BI KO) mice. We confirmed that SR-BI is expressed in the cardiomyocytes and that HDL binds specifically to these cells. Treatment of cardiomyocytes with HDL induced the activation of several prosurvival signalling proteins, including Akt, STAT3 and ERK1/2 and protected the cells against oxidative stress induced by doxorubicin. Although specific binding of HDL was significantly reduced in SR-BI knockdown cardiomyocytes, activation of the prosurvival pathways was not affected. Similarly, SR-BI knockdown did not reduce the in vitro protective influence of HDL against oxidative stress induced by doxorubicin. Ex vivo, IRI induced an infarct size of 17.3±0.6% in isolated hearts of wildtype mice. HDL treatment during the first phase of reperfusion significantly reduced the infarct size by approximately 35% (p<0.05). This protective effect induced by HDL is maintained in SR-BI KO mice (40% of infarct size reduction (p<0.05) compared to non-treated SR-BI-KO mice). Conclusion: This is the first time that the specific role of SR-BI in the impact of HDL on the heart is investigated. Our results do not support a role for the HDL receptor SR-BI in the protective influence of HDL. Further investigations will be required to elucidate the exact mechanisms of HDL-induced cardioprotection.
Abstract 3960: MicroRNA-23b targeting urokinase-type plasminogen activator facilitates human papillomavirus type 16 E6 induction of cervical cancer cell migration
Authors: Chi Lam Au Yeung, Tsun Yee Tsang, Pak Lun Yau, Tim Tak Kwok
Journal: Cancer Research (2011)

Abstract Aberrant expression of microRNA in human cervical cancer is associated frequently with human papillomavirus (HPV) integration. MicroRNA-23b (miR-23b) is often down-regulated in HPV-associated cervical cancer. Also, urokinase-type plasminogen activator (uPA), a target of miR-23b, is reported to be over-expressed in cervical cancer. Thus, in the present study, the functional role of miR-23b in HPV-16 E6 associated cervical cancer development was investigated. Knockdown of oncoprotein E6 by E6 siRNA in HPV-16 positive human cervical carcinoma SiHa cells and CaSki cells led to an increase in the expression of miR-23b and a decrease in the expression of uPA as assessed by quantitative RT-PCR and Western blot analyses. Besides, uPA is confirmed to be the target of miR-23b as transient transfection of SiHa cells with miR-23b precursor vector repressed uPA expression and also the activity of luciferase reporter carrying the 3’UTR of uPA mRNA. uPA is known to be involved in cell migration and cell invasion. By wound healing assay, the cell migration rate of SiHa cells was reduced upon E6 as well as uPA knockdown. Moreover, the effect of E6 siRNA on cell migration was offset upon transfection with anti-miR-23b inhibitor. The results indicate that HPV-16 E6 may regulate cell migration through miR-23b/uPA pathway. Furthermore, p53 is a well-known gene target of HPV-16 E6. Knockdown of p53 by p53 siRNA decreased the miR-23b expression and increased the uPA expression. This shows that p53 may mediate the E6 effect on miR-23b/uPA expressions and thus cell migration of human cervical cancer. 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 3960. doi:10.1158/1538-7445.AM2011-3960
Designer and Catalytic Antibodies
Authors: Jane F. Desforges, Ruth D. Mayforth, José Quintáns
Journal: New England Journal of Medicine (1990)

A HUMAN being possesses on the order of 1 trillion (1012) B cells, capable of making more than 10 million different antibodies. Tapping this vast resource for clinical purposes is an important but technically challenging endeavor. The production of hybridomas makes it feasible to manufacture large quantities of monoclonal antibodies, and in principle that method appeared to provide the ideal way to produce a large repertoire of human antibodies. Unfortunately, only mouse and rat myeloma cell lines have turned out to be reliable fusion partners for the production of stable hybridomas. Rodent monoclonal antibodies have provided many new reagents . . .
621 IMPROVING RISK PREDICTION IN ACUTE VARICEAL BLEEDING WITH OBJECTIVE VARIABLES: THE ROLE OF MELD
Authors: E. Reverter, F. Turon, S. Casu, S. Seijo, E. Llop, A. Berzigotti, J. Bosch, J.C. García-Pagán, J.G. Abraldes
Journal: Journal of Hepatology (2013)
Abstract 1219: Identification of synthetic lethal interactions with the BRAF oncogene in colorectal cancer.
Authors: Loredana Vecchione, Valentina Gambino, Giovanni D'Ario, Tian Sun, Iris Simon, Vlad Popovici, Mauro Delorenzi, Rene’ Bernards, Sabine Tejpar
Journal: Cancer Research (2013)

Abstract Background Approximately 8-15% of colorectal (CRC) patients carry an activating mutation in BRAF. This CRC subtype is associated with poor outcome and with resistance, both to chemotherapeutic treatments and to tailored drugs. We recently showed that BRAF (V600E) colon cancers (CCs) have a characteristic gene expression signature (1, 2) which is found also in subsets of KRAS mutant and KRAS-BRAF wild type (WT2) tumors. Tumors having this gene signature, referred as “BRAF-like," have a similar poor prognosis irrespective of the presence of the BRAF (V600E) mutation. By using a shRNA-based genetic screen in BRAF mutant CC cell lines we aimed to identify genes and pathways necessary for survival and growth of BRAF mutant CC. Such studies may reveal additional targets for therapy and potentially provide new biomarkers for patient stratification. Method We identified 363 genes that are selectively overexpressed in BRAF mutant tumors as compared to WT2 type tumors, based on gene expression profiles of the PETACC3 (1) and Agendia (1) datasets. The TRC human genome-wide shRNA collection (TRC-Hs1.0) was used to generate a 1815 hairpins sub-library targeting those identified genes (BRAF library). BRAF(V600E) CC cell lines were infected with the BRAF library and screened for shRNAs that cause lethality. LIM1215 CC cell line (WT2) was used as a control. Cells stably expressing the shRNA library were cultured for 13 days, after which shRNAs were recovered by PCR. Deep sequencing was applied to determine the specific depletion of shRNA in BRAF(V600E) cells as compared to LIM1215 cells. Results Candidate genes were identified by using following filtering criteria: depletion in BRAF(V600E) cells by at least 50% and depletion in BRAF(V600E) cells 1,5-fold higher than in control cells with the corresponding p-value to be ≤ 0.1. A total of 34 genes met our criteria of which 6 genes were presented with more than one hairpin and were concordant across the cell lines selected for validation. Conclusion We identified candidate synthetic lethal genes in BRAF mutant CC cell lines. Functional analysis is ongoing. Data will be presented. Citation Format: Loredana Vecchione, Valentina Gambino, Giovanni D'Ario, Tian Sun, Iris Simon, Vlad Popovici, Mauro Delorenzi, Rene’ Bernards, Sabine Tejpar. Identification of synthetic lethal interactions with the BRAF oncogene in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1219. doi:10.1158/1538-7445.AM2013-1219
Abstract 2027: Proteomic analysis identifies pathways regulated by miR-34a
Authors: Qing-Rong Chen, Li-Rong Yu, Adam Cheuk, Young Song, Jun Wei, Joon-Yong Chung, Stephen Hewitt, Timothy D. Veenstra, Javed Khan
Journal: Cancer Research (2010)

Abstract MicroRNA 34a (miR-34a) is an important tumor suppressor gene and has been identified as a miRNA component of the p53 network. To better understand the biological pathways involved in miR-34a action, we performed parallel global protein and mRNA expression profiling on miR-34a treated neuroblastoma cells (IMR32 cells) using isotope-coded affinity tags (ICAT) and Affymetrix U133plus2 microarray respectively. Global profile suggests a mild overall mRNA expression changes in miR-34a treated cells, but systematic protein level changes have been detected. A total of 1495 proteins represented by 2 or more peptides were identified from the quantitative ICAT analysis, of which 143 and 192 proteins are significantly up- or down-regulated in miR-34a treated cells. Several of these down-regulated proteins contain seed sequences for miR-34a. Pathway analysis of the differentially expressed proteins shows the enrichment of apoptosis and cell death in up-regulated proteins, and DNA replication and cell cycle processes in the down-regulated proteins in miR-34a treated cells. Biological network analysis of direct interaction between differentially expressed proteins suggests that YY1 as well as its downstream proteins are significantly inhibited by miR-34a. Western blotting confirmed the suppression of YY1 protein expression by miR-34a. MiR-34a might target YY1 through miR-34a-binding site in the 3’ UTR of YY1. YY1 is a ubiquitous transcription factor and it is a negative regulator of p53. YY1 has been associated with cell proliferation, anti-apoptosis, tumorigenesis and metastatic potential. Therefore the elucidation of the role of YY1 may shed important light on tumor suppressive function of miRNA-34a. 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 2027.
Phase I Trial of Granulocyte-Macrophage Colony-Stimulating Factor With High-Dose Cisplatin and Etoposide for Treatment of Small-Cell Lung Cancer: A Study of the National Cancer Institute of Canada Clinical Trials Group
Authors: Frances A. Shepherd, Paul E. Goss, James Rusthoven, Elizabeth A. Eisenhauer
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Phase I Trial of Granulocyte-Macrophage Colony-Stimulating Factor With High-Dose Cisplatin and Etoposide for Treatment of Small-Cell Lung Cancer: A Study of the National Cancer Institute of Canada Clinical Trials Group Get access FRANCES A. SHEPHERD, FRANCES A. SHEPHERD Search for other works by this author on: Oxford Academic PubMed Google Scholar PAUL E. GOSS, PAUL E. GOSS Search for other works by this author on: Oxford Academic PubMed Google Scholar JAMES RUSTHOVEN, JAMES RUSTHOVEN Search for other works by this author on: Oxford Academic PubMed Google Scholar ELIZABETH A. EISENHAUER ELIZABETH A. EISENHAUER Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 59–60, https://doi.org/10.1093/jnci/84.1.59 Published: 01 January 1992
Abstract 4005: Active SHP2 mutant induces lung hyperproliferative lesions and adenoma in transgenic mice
Authors: Valentina Schneeberger, Noreen Luetteke, Alex S. Lopez, Liwei Chen, Derek Radisky, Domenico Coppola, Jie Wu
Journal: Cancer Research (2012)

Abstract SHP2 is a protein tyrosine phosphatase encoded by the PTPN11 gene. SHP2 is normally auto-inhibited by its regulatory N-SH2 domain. It is activated by several receptor tyrosine kinases and positively regulates the RAS/ERK and other signaling pathways by mechanisms that remain incompletely defined. Furthermore, gain-of-function activating SHP2 mutants have been found in human hematologic malignancies and solid tumors, including lung, colon, and prostate cancer. Previous studies have demonstrated the oncogenic activity of gain-of-function SHP2 mutants in the hematopoietic system. To investigate the biological functions of mutant SHP2 in vivo, we generated transgenic mice harboring a tetO-SHP2E76K transgene for tetracycline-inducible expression of the constitutively active SHP2E76K mutant. This allows us to examine the roles of the cancer-associated, Glu-76 mutant SHP2 in various tissues in bitransgenic mice. tetO-SHP2E76K mice were crossed with CCSP-rtTA or SPC-rtTA mice for inducible expression of SHP2E76K in the lung type II pneumocytes. Elevated levels of active Erk1/2 and Src were detected in the lungs of bitransgenic mice induced with doxycycline. Focal hyperplasia of bronchioloalveolar epithelial cells was observed within one month of doxycycline induction in bitransgenic mice, which progressed to more extensive atypical adenomous hyperplasia and adenoma after six months. These results suggest that Shp2 is a proto-oncogene of lung carcinoma. 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 4005. doi:1538-7445.AM2012-4005
Abstract 1225: Regulation of ARE-mediated mRNA decay during colorectal tumorigenesis
Authors: Fernando F. Blanco, Sandhya Sanduja, Lisa Young, Dan Dixon
Journal: Cancer Research (2010)

Abstract Colon cancer is mediated through various genetic alterations that promote the initiation and progression of tumorigenesis. As a consequence of these defects, overexpression of many oncogenic factors promoting enhanced cell growth and inflammation are observed. In the normal intestinal epithelium, oncogenic factor gene expression is controlled through AU-rich mRNA elements (AREs) that target mRNA for rapid decay. However, ARE-mRNA turnover is compromised during colon tumorigenesis resulting in a 3- to 4-fold enrichment in ARE-containing genes. To better understand how loss of ARE-mRNA decay contributes to colon tumorigenesis, the role of the mRNA decay factor tristetraprolin (TTP) in normal and tumor cells was examined. The RNA-binding protein TTP binds ARE motifs and promotes rapid mRNA decay by sequestering the mRNA to cytoplasmic sites known as processing bodies (P-bodies). Here, we demonstrate that treatment of non-transformed intestinal epithelial cells with TGF-B inhibited ARE-mRNA expression. This effect of TGF-B occurred through a Smad-dependent induction of TTP expression and this led to a 2-fold increase in cytoplasmic P-body assembly. These findings indicate that induction of post-transcriptional regulation is a novel growth-inhibitory feature of TGF-B in normal cells. Colon cancer progression is frequently characterized by the presence of activating mutations in the RAS proto-oncogene, and, in this context, the tumor-promoting effects of TGF-B signaling are observed. Using an intestinal epithelial cell model stably transfected with an inducible oncogenic Ras cDNA, we determined the impact of oncogenic cellular transformation on TTP expression. In cells expressing oncogenic Ras, the expression of TTP was decreased and these cells were rendered refractory to TGF-B-mediated TTP induction. The functional significance of this loss of TTP expression in transformed cells is observed with a 2-fold decrease in P-body formation. Consistent with this, colon cancer cells and tumor tissue show decreased TTP expression compared to normal tissue and a respective loss of P-body formation. Taken together, these results demonstrate that loss of the mRNA decay factor TTP occurs during colon tumorigenesis, thereby compromising ARE-mRNA decay and resulting in stabilization of various cancer-associated mRNAs. Through its ability to modulate expression of a majority of oncogenic factors, these findings define a role for TTP in tumor-suppressor capacity in the context of colon cancer. 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 1225.
Neutrophil Recruitment by Interleukin-17 into Rat Airways <i>In Vivo</i>
Authors: HIROSHI HOSHINO, JAN LÖTVALL, BENGT-ERIC SKOOGH, ANDERS LINDÉN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We determined whether neutrophil recruitment induced by the T-lymphocyte cytokine, interleukin-17 (IL-17) is modulated by tachykinins in airways in vivo. Cell recruitment into airways was induced by either human (h) IL-17 (1 μ g) or rat (r) IL-1 β (2.5 ng), instilled intratracheally in rats (n = 5 to 7). Six hours after instillation, hIL-17 (3.1 ± 1.2 × 106 cells/ml) and rIL-1 β (4.1 ± 0.5 × 106 cells/ml), respectively, induced a significant and selective increase in neutrophil count in bronchoalveolar lavage fluid (BAL) when compared with vehicle (0.6 ± 0.2 × 106 cells/ml). For hIL-17, this effect was dose-dependent. Inhalation of peptidase inhibitors (phosphoramidon plus captopril) potentiated the effect of both hIL-17 and rIL-1 β . Inhalation of a neutral endopeptidase inhibitor (phosphoramidon) alone also increased the neutrophil count for hIL-17, whereas an angiotensin-converting enzyme inhibitor (captopril) alone did not. A selective neurokinin (NK)-1 receptor antagonist (SR 140333) reduced the neutrophil count, both with and without phosphoramidon pretreatment. In conclusion, IL-17 selectively recruits neutrophils into rat airways in vivo and this effect is modulated by endogenous tachykinins acting via NK-1 receptors.