tbuckley/cabot-search huggingface dataset:
Thinking out of theGut: a case of obscure lower GI bleeding
Authors: Frederick H Koh, Hian-Li Chan, Fredrik Petersson, Choon-Seng Chong
Journal: Gut (2016)

A middle-aged man was admitted for episodes of fresh per-rectal bleeding, which were not associated with defecation. He was recently investigated for macrocytic anaemia in the outpatient haematology clinic. Examination of the perineum revealed grade 1 internal haemorrhoids with no signs of bleeding.Initial laboratory tests revealed macrocytic anaemia (haemoglobin 10.5 g/dL, normal 12.9-17.0 g/dL; mean corpuscular haemoglobin 95.3 fL, normal 80.0-95.0 fL). Peripheral blood film showing blasts, dysplastic neutrophils, nucleated red blood cells and hypogranular platelets.The patient underwent a sigmoidoscopy and rubber band ligation of the internal haemorrhoids after persistent fresh per-rectal bleeding. The bleeding persisted with the development of hypotension and a significant drop of haemoglobin to 4.8 g/dL requiring blood transfusions and intensive care monitoring. Repeated endoscopy, including intubation of the terminal ileum, revealed uncomplicated right-sided diverticulosis. CT mesenteric angiography performed during an episode of significant bleeding revealed extravasation of contrast in the ileum, but mesenteric angiography was unsuccessful, possibly due to a temporary cessation of bleeding. Bleeding subsequently recurred and in light of the persistent bleeding with no clear source and with a total of 12 units of packed cell transfused, exploratory laparotomy, on-table enteroscopy (figure 1) with small bowel resection was performed. Histopathological examination of the specimen was performed (figures 2-4).gutjnl;66/12/2068/GUTJNL2016313252F1F1GUTJNL2016313252F1Figure 1Multiple ileal lesions with stigmata of recent bleed.gutjnl;66/12/2068/GUTJNL2016313252F2F2GUTJNL2016313252F2Figure 2Area of ulceration associated with atypical mononuclear infiltrate.gutjnl;66/12/2068/GUTJNL2016313252F3F3GUTJNL2016313252F3Figure 3Atypical mononuclear infiltrate composed of cells with enlarged, irregular nuclei containing variably prominent nucleoli.gutjnl;66/12/2068/GUTJNL2016313252F4F4GUTJNL2016313252F4Figure 4Atypical cells displayed cytoplasmic expression of myeloperoxidase.What is the diagnosis?
Abstract 2131: The Arkadia-ESRP2 axis suppresses tumor progression: Analyses in clear cell renal cell carcinoma
Authors: Anna Mizutani, Daizo Koinuma, Hiroyuki Seimiya, Kohei Miyazono
Journal: Cancer Research (2015)

Abstract Tumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC), a major subtype of kidney cancer accounting for 70-80% of all kidney cancer patients. Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC, while ESRP1 is decreased in most of the ccRCC as previously reported. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons, including ENAH exon 11a, ITGA6 exon 27, and SLK exon 13, correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia, a RING-type E3 ligase, that is known to enhance TGF-β signaling activities, physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC. Citation Format: Anna Mizutani, Daizo Koinuma, Hiroyuki Seimiya, Kohei Miyazono. The Arkadia-ESRP2 axis suppresses tumor progression: Analyses in clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2131. doi:10.1158/1538-7445.AM2015-2131
Polyclonal Secondary <i>FGFR2</i> Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion–Positive Cholangiocarcinoma
Authors: Lipika Goyal, Supriya K. Saha, Leah Y. Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G. Ahronian, Jochen K. Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E. Van Seventer, Joseph M. Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P. Ryan, James R. Stone, A. John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B. Corcoran, Nabeel Bardeesy, Andrew X. Zhu
Journal: Cancer Discovery (2016)

Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases. Serial analysis of cfDNA demonstrated multiple recurrent point mutations in the
Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation
Authors: Pushkar Malakar, Asaf Shilo, Adi Mogilevsky, Ilan Stein, Eli Pikarsky, Yuval Nevo, Hadar Benyamini, Sharona Elgavish, Xinying Zong, Kannanganattu V. Prasanth, Rotem Karni
Journal: Cancer Research (2016)

Abstract Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis are still emerging. Here we report that the lncRNA MALAT1 is upregulated in hepatocellular carcinoma and acts as a proto-oncogene through Wnt pathway activation and induction of the oncogenic splicing factor SRSF1. Induction of SRSF1 by MALAT1 modulates SRSF1 splicing targets, enhancing the production of antiapoptotic splicing isoforms and activating the mTOR pathway by modulating the alternative splicing of S6K1. Inhibition of SRSF1 expression or mTOR activity abolishes the oncogenic properties of MALAT1, suggesting that SRSF1 induction and mTOR activation are essential for MALAT1-induced transformation. Our results reveal a mechanism by which lncRNA MALAT1 acts as a proto-oncogene in hepatocellular carcinoma, modulating oncogenic alternative splicing through SRSF1 upregulation. Cancer Res; 77(5); 1155–67. ©2016 AACR.
Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer?
Authors: S. M. Domchek, T. Friebel, S. L. Neuhausen, H. T. Lynch, C. F. Singer, R. A. Eeles, C. Isaacs, N. M. Tung, P. A. Ganz, F. J. Couch, J. N. Weitzel, O. I. Olopade, W. S. Rubinstein, G. E. Tomlinson, G. C. Pichert, M. B. Daly, E. T. Matloff, D. G. Evans, J. E. Garber, T. R. Rebbeck
Journal: Journal of Clinical Oncology (2011)

1501 Background: Women with B1 and B2 mutation are at increased risk of breast and ovarian cancer, which is significantly reduced by RRSO. The reduction in breast cancer risk may be greatest prior to age 40; however, such early menopause can lead to significant menopausal symptoms and other health problems. Two small prior studies have suggested that HRT following RRSO does not increase the risk of breast cancer, but further data are needed. Methods: From the PROSE consortium, 1,299 B1 (n= 795) and B2 (n=504) mutation carriers who underwent RRSO following study ascertainment and in whom HRT status was known were followed prospectively. Data were collected on HRT use and subsequent breast cancer diagnosis. Results: In both B1 and B2 mutation carriers with ever use of HRT following RRSO, no increased risk of breast cancer was observed compared to those with no RRSO. In B1 carriers, HRT use both with (HR 0.52) and without (HR 0.29) RRSO was associated with a decreased risk of breast cancer. No increased risk of breast cancer was seen with either combination HRT or estrogen-only HRT. Conclusions: In this prospective study of 1,299 B1 and B2 mutation carriers, HRT following RRSO was not associated with an increased risk of breast cancer. HRT use Never Ever Never Post-RRSO RRSO: No No Yes Yes Controls Mean age at RRSO – – 45.0 (20.5-79.0) 40.8 (29.4-63.4) Mean age in controls 34.4 (18.1-90.4) 45.6 (18.7-90.0) – – Mean follow-up to BC 4.8 (0.5-17.6) 7.4 (0.9-20.6) 2.7 (0.5-6.0) 4.9 (0.8-20.2) Mean follow-up to censoring 5.1 (0.5-27.8) 5.9 (0.5-27.7) 3.6 (0.5-18.8) 5.4 (0.6-27.4) Total sample (N) 867 111 177 144 BC in follow-up 194 (22%) 19 (17%) 22 (12%) 20 (14%) HR (95% CI) [1] 0.51 (0.32-0.80) 0.62 (0.38-1.01) 0.46 (0.28-0.76) BRCA1 (N) 520 55 115 105 BC in follow-up 118 (23%) 5 (9%) 16 (14%) 17 (16%) HR (95% CI) [1] 0.29 (0.13-0.69) 0.63 (0.35-1.14) 0.52 (0.30-0.92) BRCA2 (N) 347 56 62 39 BC in follow-up 76 (22%) 14 (25%) 6 (10%) 3 (8%) HR (95% CI) [1] 0.73 (0.42-1.27) 0.52 (0.21-1.27) 0.24 (0.05-1.03)
Next-Generation Sequencing and Real-Time Quantitative PCR for Minimal Residual Disease (MRD) Detection Using the Immunoglobulin Heavy Chain Variable Region: A Methodical Comparison in Acute Lymphoblastic Leukemia (ALL), Mantle Cell Lymphoma (MCL) and Multiple Myeloma (MM)
Authors: Marco Ladetto, Monika Bruggemann, Simone Ferrero, Francois Pepin, Daniela Drandi, Luigia Monitillo, Antonio Palumbo, Roberto Passera, Mario Boccadoro, Victoria Carlton, Heiko Trautmann, Malek Faham, Christiane Pott
Journal: Blood (2012)
Abstract 3065: MicroRNA-137 confers chemoresistance by suppressing CASP3 in lung cancer cells
Authors: Te-Jen Shu, Sung-Liang Yu, Jeremy J.W. Chen
Journal: Cancer Research (2015)

Abstract Lung cancer is the leading cause of cancer-related death. Although molecular targeting therapy (MTT) could benefit patients with EGFR activating mutations, chemotherapy still is the first choice of EGFR wild type patients, MTT failed ones and patients of developing countries without regarding their EGFR status. However most of these chemotherapy-treated patients will develop drug resistance eventually. Here, we identified miR-137 might contribute to chemo-resistance in lung cancer in part. Our previous study identified 5 miRNAs (let-7a, miR-182*, miR-372, miR-137 and miR-221) whose expression can be an independent marker to predict the outcome of non-small cell lung cancer (NSCLC) patients. Among them, miR-137 acts as a risky miRNA. Caspase-3 (CASP3) was predicted as one of miR-137 potential targets. CASP3 is a critical effector caspase that promotes programmed cell-death when activated in the apoptotic cells both by extrinsic and intrinsic pathways that are highly conserved and related to drug resistance. We found miR-137 could regulate CASP3 through binding to its 3′UTR. Endogenous CASP3 can be up-regulated by over-expressing miR 137 in CL1-5, H1437 and A549 cells and down-regulated by silencing miR-137 in H1299, CL1-0 and A549 cells. Suppression of CASP3 by miR-137 providing lung cancer cells with ability of anti-apoptosis under UV-induced cell death. MiR-137 also increase IC50 of CL1-5, H1437, A549 and H1975 cells under cisplatin treatment to at least 2 folds. Restoration of CASP3 could reverse the effect. Our IHC data also shows the CASP3 protein expression is negative correlated with miR-137 level. In summary, manipulation of miR-137 might provide a potential treatment for EGFR wild-type and MTT failed NSCLC. patients in the future. Citation Format: Te-Jen Shu, Sung-Liang Yu, Jeremy J.W. Chen. MicroRNA-137 confers chemoresistance by suppressing CASP3 in lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3065. doi:10.1158/1538-7445.AM2015-3065
Relationships Between Late Viral Infections and Immune Reconstitution after Hematopoietic Stem Cell Transplantation.
Authors: Yuki Asano-Mori, Yoshinobu Kanda, Kumi Oshima, Yasuhito Nanya, Keiki Kumano, Takashi Asai, Akira Hangaishi, Tsuyoshi Takahashi, Yoichi Imai, Mineo Kurokawa
Journal: Blood (2008)
Effect of increased expression of C-terminal binding protein-2 in epithelial ovarian carcinoma on DNA repair pathways and tumor response to histone deacetylase inhibitors.
Authors: T. May, L. M. Barroilhet, J. Yang, M. Singh, W. R. Welch, S. P. Sugrue, R. S. Berkowitz, S. Ng
Journal: Journal of Clinical Oncology (2011)

5075 Background: Ovarian cancer continues to be the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. Our group recently demonstrated that C-terminal binding protein 2 (CtBP2) is overexpressed in epithelial ovarian carcinoma and alters their response to histone deacetylase (HDAC) inhibitors. We designed a study aimed at examining the differential gene expression between wild-type and CtBP2-knockdown cancer cell lines to identify key pathways regulated by CtBP2. Methods: Gene expression profiling was performed on CtBP2 wild type and knockdown cell lines. RNA was extracted, labeled and hybridized to Affymetrix Gene 1.0 ST Microarray. Differentially expressed genes were identified using D-Chip and SAM, validated using qRT-PCR and integrated into the Ingenuity Protein Analysis system. Key protein interactions were verified by co-immunoprecipitation assays and immunofluorescence microscopy. Protein expression levels were examined using immunohistochemistry (IHC) on 64 ovarian tissues and Western blot on 15 ovarian cancer cell lines. Results: Analyses of gene expression profiling resulted in 89 gene signatures largely involved in DNA repair. A significant number of differentially expressed genes were down-regulated in the knockdown cell lines, which is unexpected when CtBP2 is considered as a co-repressor. The nuclear protein Pinin was found to co-precipitate and co-localize with CtBP2 in the nucleus. IHC and Western blot studies showed significant overexpression of Pinin in carcinoma specimens compared to benign specimens (P<0.001). Conclusions: We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression by modulating HDAC activity and DNA repair. Specific nuclear interaction between CtBP2 and the co-regulator protein Pinin was discovered suggesting that Pinin may modify the co-repressor function of CtBP2 in ovarian carcinoma. Given that overexpression of CtBP2 decreases sensitivity of ovarian cancer cells to HDAC inhibitors, concurrent CtBP2 targeted therapy may enhance response of epithelial ovarian carcinoma to HDAC inhibitor therapy.
Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults
Authors: J. Gottlieb, S. Ingen-Housz-Oro, M. Alexandre, S. Grootenboer-Mignot, F. Aucouturier, E. Sbidian, E. Tancrede, P. Schneider, E. Regnier, C. Picard-Dahan, E. Begon, C. Pauwels, K. Cury, S. Hüe, C. Bernardeschi, N. Ortonne, F. Caux, P. Wolkenstein, O. Chosidow, C. Prost-Squarcioni
Journal: British Journal of Dermatology (2016)

Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described.To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD.This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses.Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified.Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.
Phase I/II Study of the P-Glycoprotein (Pgp) Inhibitor Zosuquidar Administered by Continuous Infusion (CIV) with Daunorubicin (DNR) and Cytarabine (ARA-C) as Primary Therapy in Older Patients with Pgp-Positive Acute Myeloid Leukemia (AML).
Authors: Jeffrey E. Lancet, Jason Gotlib, Meir Wetzler, Selina Luger, Larry D. Cripe, Martin S. Tallman, Ivana Gojo, Deborah Mulford, Maria R. Baer, Alan F. List, Pratik S. Multani, Branimir I. Sikic
Journal: Blood (2007)
Second Stem Cell Transplantation (SCT) for Relapsed Leukemia Provides Only Modest Prolongation of Survival
Authors: Zachariah A. McIver, Thomas Hughes, Sawa Ito, Minoo Battiwalla, Eleftheria K. Koklanaris, Janice Haggerty, Nancy F. Hensel, A. John Barrett
Journal: Blood (2011)
The Legality of Biometric Screening of Professional Athletes
Authors: Jessica L. Roberts, I. Glenn Cohen, Christopher R. Deubert, Holly Fernandez Lynch
Journal: The American Journal of Bioethics (2016)

In their thoughtful article, “Tracking U.S. Professional Athletes: The Ethics of Biometric Technologies,” Katrina Karkazis and Jennifer Fishman do an excellent job of outlining the concerns associa...
Preclinical Studies of the IAP Antagonist Debio 1143 in Combination with Cytarabine or Doxorubicin in a Mouse Model of AML
Authors: Ambrose Campbell, Ezhilarasi Chendamarai, Matthew Holt, Julie Prior, Linda Eissenberg, Michael P. Rettig, Gregoire Vuagniaux, Claudio Zanna, John F. DiPersio
Journal: Blood (2014)
Positron Emission Tomography Combined with Computed Tomography (PET-CT) Should Substitute Classical CT in the Initial Staging of Hodgkin Lymphoma (HL).
Authors: Ewa Bednaruk-Mlynski, Joanna Pienkowska, Waldemar Kulikowski, Edyta Subocz, Justyna Dzietczenia, Bogdan Malkowski, Marta Zalewska, Adam Skorzak, Krzysztof Lesniewski-Kmak, Tomasz Wrobel, Jan M Zaucha
Journal: Blood (2012)
High CD45 (PTPRC) Expression Is Associated with An Overall Poor Outcome in Childhood Acute Lymphoblastic Leukemia Treated on the ALL-BFM 2000 Protocol and Exerts An Especially Pronounced Effect in Intermediate Risk Patients
Authors: Gunnar Cario, Rita Mitlohner, Martin Zimmermann, Renja Romey, Peter Rhein, André Schrauder, Anja Moericke, Jean-Pierre Bourquin, Wolf-Dieter Ludwig, Richard Ratei, Martin Schrappe, Leonid Karawajew, Martin Stanulla
Journal: Blood (2011)
Genetic and Chemical Inhibition of Sphingosine 1-Phosphate Lyase Results in Peripheral Lymphopenia and Alleviates Disease Development in Animal Models of Inflammation and Autoimmunity.
Authors: Tamas Oravecz, Michael S. Donoviel, Stephen J. Anderson, Kenneth Carson, Weimei Sun, Jonathan Swaffield, Qingyun Liu, S. David Kimball, James R. Piggott, Alan J. Main, Brian P. Zambrowicz, Arthur T. Sands, C. Alexander Turner, David J. Augeri
Journal: Blood (2007)
Diagnosing Mania in the Age of DSM-5
Authors: Joseph R. Calabrese, Keming Gao, Gary Sachs
Journal: American Journal of Psychiatry (2017)

DSM-5 describes the primary criterion of mania as being "a distinct period of abnormally and persistently elevated, expansive, or irritable mood" and "abnormally and persistently increased goal-directed activity or energy."One of our forefathers of psychiatric phenomenology, Emil Kraepelin, referred to this phenomenon a century ago, suggesting that "increased busyness" was the most striking feature of mania (1).He elegantly described it as follows:The patient feels the need to get out of himself, to be on more intimate terms with his surroundings, to play a part.As he is a stranger to fatigue, his activity goes on day and night; work becomes very easy to him; ideas flow to him.He cannot stay long in bed; early in the morning, even at four o'clock he gets up, he clears out lumber rooms, discharges business that was in arrears, undertakes morning walks, excursions.He begins to take part in social entertainments, to write many long letters, to keep a diary, to go in a great deal for music and authorship.Especially the tendency of rhyming … is usually very conspicuous.… His pressure of activity causes the patient to change about his furniture, to visit distant acquaintances, to take himself up with all possible things and circumstances, which formerly he never thought about (1, pp.57-58).
SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
Authors: Yumiko Oishi, Nathanael J. Spann, Verena M. Link, Evan D. Muse, Tobias Strid, Chantle Edillor, Matthew J. Kolar, Takashi Matsuzaka, Sumio Hayakawa, Jenhan Tao, Minna U. Kaikkonen, Aaron F. Carlin, Michael T. Lam, Ichiro Manabe, Hitoshi Shimano, Alan Saghatelian, Christopher K. Glass
Journal: Cell Metabolism (2016)