tbuckley/cabot-search huggingface dataset:
EXTRACCIÓN DE COLEDOCOLITIASIS MEDIANTE BALON DE GRAN DIÁMETRO: EXPERIENCIA EN MÁS DE 200 PACIENTES
Authors: J Espinel, E Pinedo, R Diez, G Rascarachi, L Arias, E Maroto, A Miguel, AB Dominguez, F Muñoz, JL Olcoz
Journal: Endoscopy (2010)

Objetivo: Valorar la eficacia y seguridad de la dilatación hidrostática con balones de gran diámetro en el tratamiento de la colédocolitiasis en pacientes con factores que dificultan o hacen peligrosa la extracción, por las características de los cálculos o de la anatomía peripapilar.
Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes
Authors: Yisheng Yang, Lawrence Chan
Journal: Endocrine Reviews (2016)

To date, more than 30 genes have been linked to monogenic diabetes. Candidate gene and genome-wide association studies have identified > 50 susceptibility loci for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for type 2 diabetes (T2D). About 1–5% of all cases of diabetes result from single-gene mutations and are called monogenic diabetes. Here, we review the pathophysiological basis of the role of monogenic diabetes genes that have also been found to be associated with common T1D and/or T2D. Variants of approximately one-third of monogenic diabetes genes are associated with T2D, but not T1D. Two of the T2D-associated monogenic diabetes genes—potassium inward-rectifying channel, subfamily J, member 11 (KCNJ11), which controls glucose-stimulated insulin secretion in the β-cell; and peroxisome proliferator-activated receptor γ (PPARG), which impacts multiple tissue targets in relation to inflammation and insulin sensitivity—have been developed as major antidiabetic drug targets. Another monogenic diabetes gene, the preproinsulin gene (INS), is unique in that INS mutations can cause hyperinsulinemia, hyperproinsulinemia, neonatal diabetes mellitus, one type of maturity-onset diabetes of the young (MODY10), and autoantibody-negative T1D. Dominant heterozygous INS mutations are the second most common cause of permanent neonatal diabetes. Moreover, INS gene variants are strongly associated with common T1D (type 1a), but inconsistently with T2D. Variants of the monogenic diabetes gene Gli-similar 3 (GLIS3) are associated with both T1D and T2D. GLIS3 is a key transcription factor in insulin production and β-cell differentiation during embryonic development, which perturbation forms the basis of monogenic diabetes as well as its association with T1D. GLIS3 is also required for compensatory β-cell proliferation in adults; impairment of this function predisposes to T2D. Thus, monogenic forms of diabetes are invaluable "human models" that have contributed to our understanding of the pathophysiological basis of common T1D and T2D.
Decreased TGFβ signaling and increased COX2 expression in high risk women with increased mammographic breast density.
Authors: WT Yang, MT Lewis, H Wong, K Hess, A Tsimelzon, N Karadag, M Cairo, F Meric-Bernstam, A Sahin, JC Chang
Journal: Cancer Research (2009)

Abstract Abstract #1107 Background&amp;#x2028; High mammographic density is associated with up to a 6-fold increased risk of breast cancer. Pathways responsible for this increased density are unknown. We hypothesize that specific molecular pathways exist that are associated with increased mammographic density and breast cancer risk, and may therefore be used to identify potential targets for chemoprevention.&amp;#x2028; Methods&amp;#x2028; Histologically confirmed normal breast tissue was collected from women undergoing breast surgery who had available demographic data and mammograms for review. Breast parenchymal density was classified according to the American College of Radiology's Breast Imaging – Reporting and Data System reporting system. Quantitative classification of mammographic parenchyma was performed using thresholding method and percent density. Women with low (less than 50%) versus high (greater than 50%) breast density were compared. Double-stranded cDNA was synthesized from the normal breast tissue using an oligo-dT primer containing a T7 RNA polymerase promoter, followed by in vitro transcription with biotinylated ribonucleotides. The labeled cRNA was hybridized to Affymetrix HG U133Plus2 chips which comprise ∼28,600 genes to determine gene expression patterns. Immunohistochemical analysis (IHC) of estrogen receptor, progesterone receptor, proliferation (Ki67) and COX2 expression was performed.&amp;#x2028; Results&amp;#x2028; Sixty-two women were identified, 26 (42%) had high, and 36 (58%) had low mammographic density. Neither age, menopausal nor hormone receptor status influenced the gene expression pattern. Seventy-three genes had differential expression between normal breast tissue with high and low mammographic density (p&amp;lt;0.001, fold change&amp;gt;1.5) and had a low false discovery rate (&amp;lt;10%). Of these 73 differentially expressed genes, network and canonical pathway analysis demonstrate decreased TGFβ signaling (TGFBR2, SOS, SMAD3 and CD44 expression) in dense breast relative to non-dense breast. By IHC, Ki67 (stroma) and COX2 expression were significantly higher in dense breasts (p&amp;lt;0.05) on univariate analysis, and only COX2 expression in the stroma was statistically significant at (p&amp;lt;0.01) on multivariate analysis.&amp;#x2028; Conclusion&amp;#x2028; TGFβ ligands are currently the only growth factors known to prevent mammary epithelial cell proliferation. TGFβ has been reported to influence COX-2 expression, and these molecules are highly differentially expressed in individuals at high risk of developing breast cancer. These results suggest that COX2 inhibition should be further investigated for breast cancer prevention despite possible increase in cardiovascular risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1107.
Safe recovery of a fully fractured basket in the bile duct using endoscopic papillary large balloon dilation
Authors: Takao Nishikawa, Toshio Tsuyuguchi, Yuji Sakai, Osamu Yokosuka
Journal: Endoscopy (2014)

Traction wires are occasionally fractured while endoscopic mechanical lithotripsy is being performed for bile duct stones. Various methods have been used to crush the bile stones during the rescue of an impacted basket including a transoral endotripter [1], laser or electrohydraulic lithotripsy under cholangioscopy guidance [2] [3], or extracorporeal shock wave lithotripsy [4]. In most cases, fractured wires are recovered by pulling their distal ends outside of the bile duct after the impacted basket has been released. However, if all the wires have fractured in the proximal portion of the bile duct, what then is a suitable method? We describe the successful recovery from the bile duct of a fully fractured basket using endoscopic techniques.
Acute colonic intramural hematoma: a rare complication of colonoscopy
Authors: Masaki Katsurahara, Noriyuki Horiki, Takashi Kitade, Yasuhiko Hamada, Kyosuke Tanaka, Hiroyuki Inoue, Norihiko Yamamoto, Yoshiyuki Takei
Journal: Endoscopy (2014)

A 74-year-old man with a medical history of chronic renal failure and congestive heart failure underwent diagnostic colonoscopy following a positive fecal occult blood test. He was given oral antiplatelet medications including aspirin (100 mg/day) and sarpogrelate hydrochloride (100 mg/day), which were stopped 5 days before colonoscopy. During the procedure, difficulty was encountered in reaching the ileocecal valve because of a redundant tortuous sigmoid colon, and the procedure took approximately 1 hour. On withdrawal of the colonoscope, a bright-red, hyperemic, elevated mass with some oozing blood was identified in the sigmoid colon, although no abnormalities had been detected on insertion. The colonic lumen was occupied by the mass, the surface of which was smooth and covered with normal colonic mucosa ([Fig. 1]). Urgent abdominal computed tomography (CT) showed a soft tissue mass of the sigmoid colon with a density suggesting blood ([Fig. 2]). There was no evidence of free air. On the basis of these findings, a diagnosis of colonic intramural hematoma was made. As the patient's condition was stable, he was treated conservatively with observation. Three days later, follow-up colonoscopy showed that the hematoma had ruptured and disappeared, having reverted spontaneously back to flat mucosa ([Fig. 3]). The patient was discharged home 5 days later free of symptoms.
BI-03 * GLIOBLASTOMA-SPECIFIC AND GLIOBLASTOMA STEM CELL SUBTYPE-SPECIFIC SIGNATURES OF LONG, NON-CODING RNAs
Authors: A. Bronisz, M. Mineo, K. Ansari, A. Rooj, I. Nakano, E. Antonio Chiocca, J. Godlewski
Journal: Neuro-Oncology (2014)

Long-non coding RNAs (lncRNAs) are large and heterogeneous group of non-protein coding RNAs larger than 200nt. They regulate the expression of their target genes by multiple mechanisms including regulation of transcription, splicing, translation and epigenetic regulation. There is growing evidence of important role of lncRNAs in carcinogenesis, including glioblastoma multiforme (GBM). To profile lncRNAs in GBM patient samples and cells, we designed a platform using NanoString system to detect 73 lncRNAs that has been implicated in cancer pathophysiology. We used our collection of matched samples (i.e. from the same patient) of GBM tumors and adjacent brain tissue. We showed that 27-lncRNA signature (10 GBM-low and 17 GBM-high) clustered these samples. Glioblastoma stem cells (GSCs) are highly tumorigenic and therapy-resistant sub-population of glioblastoma. We characterized our large collection of patient-derived GSCs maintained in serum-free culture. Based on 10-gene signature we ascribed them to either proneural (PN), mesenchymal (MES) subtype. We demonstrated that 28-lncRNA signature (7 PN-low and 21 PN-high) clustered PN and MES GSCs. Testing the functionality of lncRNAs, we showed that PN-MES subtype switch achieved by de-regulation of important regulator of GSC self-renewal - miR-128, was concurrent with the shift in lncRNA signature. Finally, based on 29-lncRNA signature, we were able to establish that, irradiated PN GSCs acquired more mesenchymal characteristics. Our results thus suggest broad involvement of lncRNAs in the regulation of pathophysiological processes in GBM/GSC cells.
Abstract 3578: New Angiochem-modified doxorubicin with increased brain penetration and efficacy against brain tumors
Authors: Michel Demeule, Anthony Régina, Goagiang Yang, Christian Ché, Richard Béliveau, Jean-Paul Castaigne
Journal: Cancer Research (2010)

Abstract The blood-brain barrier (BBB) is mainly formed by brain capillary endothelial cells which are closely sealed by tight junctions and express high levels of active efflux transport proteins, including P-glycoprotein (Pgp). As a result, the overwhelming majority of small molecules, proteins and peptides do not cross the BBB. Angiochem's engineered peptide compounds (EPiC) provides a non-invasive and flexible platform for small and large molecules to treat brain diseases. Based on these properties, we have created a portfolio of new drug entities composed of siRNA, peptides and mAbs, the most advanced of which is ANG1005 formed by chemical conjugation of our peptide to three molecules of paclitaxel. ANG1005 demonstrated safety and efficacy in two phase ½ clinical trials for the treatment of primary and secondary brain tumors in humans. In the present study, we have investigated the brain uptake of a new chemical entity formed by conjugation of the peptide Angiopep-2 (An2) with 3 molecules of the anti-cancer drug doxorubicin. Despite the clinical effectiveness of doxorubicin in the treatment of many malignant tumors, clinical trials involving systemic administration have demonstrated very limited efficacy in the treatment of gliomas. This limited efficacy can be explained by the poor penetration of the drug thru the BBB and by the effect of the multidrug resistance pump, P-gp. Here, we show by mice in-situ brain perfusion that the ANG-doxorubicin (ANG1007) is transported very efficiently across the BBB. The transport rate is higher than that of unconjugated doxorubicin by at least 10-fold. In vitro, ANG1007 inhibits cancer cell proliferation, with highly cytotoxic activities against various tumor cell lines. In addition, brain perfusion studies performed with P-gp knock-out mice showed that ANG1007 bypasses the drug efflux pump P-gp at the BBB. Furthermore, ANG1007 inhibits growth of glioblastoma s.c. tumors and increases survival of mice implanted with brain tumors. In conclusion, these data confirm that conjugation of chemotherapeutic drugs such as doxorubicin to the peptide Angiopep-2 significantly enhances their entry into the brain and further validate the use of Angiochem's technology for new brain tumor therapies. 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 3578.
FRACTURES OF HIP WITH MANUALLY CONTROLLED BRIEF STIMULUS ECT
Authors: D. H. KRANS
Journal: American Journal of Psychiatry (1954)

Two cases of fracture of the neck of the femur are reported in healthy schizophrenics under 30 while using a technique of electrotherapy with a manually controlled square wave brief stimulus current, raised at intervals during the convulsion. These cases occurred in a group of 35 patients, representing an incidence of 5.7% or 0.3% of treatments, which is in marked contrast to 2 such fractures in the same hospital during the many years of standard ECT. It is suspected that the alterations in current level superimpose muscular contractions on the convulsive movements, which in certain phases of the convulsion might be particularly hazardous to the hip joint.
Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss
Authors: Tara E. Tracy, Peter Dongmin Sohn, S. Sakura Minami, Chao Wang, Sang-Won Min, Yaqiao Li, Yungui Zhou, David Le, Iris Lo, Ravikumar Ponnusamy, Xin Cong, Birgit Schilling, Lisa M. Ellerby, Richard L. Huganir, Li Gan
Journal: Neuron (2016)
AB0842 Anti-ku antibodies: Clinical and serological evaluation of 12 patients
Authors: T.L. Santiago, J. Rovisco, M. Santiago, J. Silva, J. da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-Ku antibody is a DNA-binding protein, initially described in the 80's. Although, reported in a large variety of connective tissue diseases, they are a serologic marker of overlap syndromes, namely those that included myositis. The prevalence of antibodies against Ku protein is variable ranging from 2% to 55%. The discrepancy is due to the different detection methods, the disease type, the geographic clustering and the genetic background. In the meantime, several studies have been performed in order to assess the prevalence and the clinical significance of these antibodies in connective tissue diseases. <h3>Objectives</h3> To describe clinical and serological associations of anti-Ku antibodies. <h3>Methods</h3> Twelve patients with anti-Ku antibody detected by immunoblot were retrospectively evaluated. <h3>Results</h3> Patients (7 women, 5men) had a mean age of 64.4 (range 29-83). Three had overlap syndromes: two polymyositis (PM)/scleroderma (SSc) and one arthritis rheumatoid (RA)/PM. Four additional patients had undifferentiated connective tissue disease, two RA, one PM, one SSc. Moreover, one patient had a monoclonal gammopathy. In the patients with connective tissue disease the clinical manifestations most frequently recorded were arthralgias (58%), myositis (42%) and Raynaud's phenomenon (42%). Three patients had esophageal dysmotility, while 2 showed interstitial pulmonary fibrosis (one with reduced DLCO). One case of pulmonary hypertension was observed. The majority of the patients had favorable prognosis. Hence, 33% were not receiving treatment with immunosuppressors or immunomoduladors. Ongoing treatment included corticosteroids (40%), antimalaric drugs (30%), and methotrexate (20%). All patients had very high titer of ANA with speckled and nucleolar pattern. Three sera contained additional antibody specificities: anti-SSA, anti-Jo1 and anti-Pl7 in one each case. <h3>Conclusions</h3> Anti-Ku antibody is reported in various connective tissue diseases including overlap syndromes and myositis. Raynaud's phenomenon, muscular and joint involvement are the most frequent clinical manifestations associated with anti-Ku antibodies. Anti-Ku antibodies detection in myositis is associated with a favorable prognosis. <h3>Disclosure of Interest</h3> None Declared
Abstract 280: Met (the HGF receptor) localizes to the nucleus in wound healing
Authors: Jennifer Bordeaux, Jason A. Hanna, Seema Agarwal, David L. Rimm
Journal: Cancer Research (2010)

Abstract Background: The hepatocyte growth factor (HGF)/Met signaling pathway has been shown to be important for stimulating cell proliferation, motility, invasion and metastasis. Recent work from our lab has also demonstrated patients with high levels of nuclear Met have a worse prognosis even in lymph node negative breast cancer and has also identified a 60 kDa fragment from the carboxy-terminal domain of Met that localizes to the nucleus. Methods: We developed a method for quantification of in vitro wounding of epithelial cellular monolayers that we have utilized to further characterize nuclear Met. Nuclear Met was identified by immunofluorescence with the carboxy-terminal Met specific antibody CVD13 (Invitrogen) in H1650, A431 and Caco2 cells. The Met ligand (HGF) was used to stimulate wound healing and the Pfizer Met kinase inhibitor PHA-665752 (PHA) was used to determine the dependence of activated Met for nuclear localization. Results: As previously observed, stimulating cells with HGF (50 ng/mL) increases overall wound healing and inhibition of Met kinase activity with PHA reduces overall wound healing. Using immunofluorescence we have determined nuclear Met is present at the wound edge of lung (H1650), colon (CaCo2), and skin (A431) cancer cell lines. Additionally, nuclear localization of Met is also observed in H1650 cells by immunofluorescence with a phospho-Met antibody (CST). Nuclear localization of Met is inhibited when cells are pretreated with PHA even in the presence of HGF. However, HGF stimulation alone is not sufficient to induce nuclear Met in the A549 lung cancer cell line. Finally, the 60 kDa Met fragment is absent by Western blot when H1650 cells are grown in serum-starved conditions. Conclusion: Nuclear Met is observed during the wound healing of cellular monolayers and can be inhibited with Met specific kinase inhibitors. Nuclear Met, as defined by the presence of the 60 kDa fragment, is lost in serum-starved growth conditions. Since, several pharmaceutical companies are currently developing Met-based therapies, the role of Met the nucleus may be important in future targeted cancer therapy. 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 280.
Abstract 3380: Comparison proteome analysis of scirrhous gastric carcinoma stem cell-like SP and hypoxia-resistant cell lines
Authors: Tamami Morisaki, Masakazu Yashiro, Anna Kakehashi, Yoshihiro Okita, Tatsunari Fukuoka, Naoki Aomatsu, Mami Yoshii, Tsuyoshi Hasegawa, Junko Matsuoka, Hisashi Nagahara, Kenjiro Kimura, Eiji Noda, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Nobuya Yamada, Kiyoshi Maeda, Bunzo Nakata, Masaichi Ohira, Hideki Wanibuchi, Kosei Hirakawa
Journal: Cancer Research (2012)

Abstract Intro Cancer stem cells (CSCs) are considered to be responsible for cancer metastasis, and hypoxia is supposed to be an important regulator of CSCs differentiation. Furthermore, tumor hypoxia was reported to be associated with more aggressive tumor phenotypes such as high metastatic ability and resistance to various anti-cancer therapies which may lead to a poorer prognosis. This raises the question of whether there might be proteins representing similar alterations which are responsible for the correlation between hypoxic and CSCs phenotypes. We have established a diffuse-type of gastric carcinoma cell line (OCUM-12), and a hypoxia-resistant cancer cell line (OCUM-12/Hypo) cloned from parent OCUM-12 cells by continuous exposure to 1% oxygen. The side population (SP), as evaluated by a flow cytometric analysis using Hoechst 33342, has been known as CSC-rich population. To investigate and compare the proteomes of the hypoxic (OCUM-12/Hypo), stem cell (OCUM-12SP) and parent OCUM-12 diffuse-type gastric carcinoma cell lines, protein lysates from those cell lines were analyzed using QSTAR Elite LC MS/MS. Method Triplicate pooled samples (10 ug protein each) from stomach cancer cell lines were prepared and labeled with iTRAQ reagents. MS/MS data were searched against the Swiss Protein database (HUMAN) using ProteinPilot™ 2.0 software (AB Sciex). The Ingenuity Pathway analysis program was utilized, to assign biological significance, and to identify networks of interacting differentially expressed proteins, functional groups and pathways. Result In both OCUM-12SP and OCUM-12/Hypo cells, significant overexpression of Wnt signaling pathway was obvious. Furthermore, elevation of MTHFD1, a protein controlling histidine and purine nucleotide metabolism, cytokeratins 18 (CK18), and 19 (CK19) regulating cell cycle, apoptosis and angiogenesis, transcriptional regulator ANP32A, and cellular chaperones heat shock proteins A9 and STIP was observed as compared to the parent OCUM-12 cell line. Furthermore, anterior gradient homolog 2 (AGR2)was down-regulated in both cell lines. Conclusion Wnt signal, MTHFD1, CK18, CK19, ANP32A, HSPA9 and STIP, AGR2 might be responsible for the stem-like phenotype, hypoxia resistance and higher invasiveness of gastric cancer. 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 3380. doi:1538-7445.AM2012-3380