tbuckley/cabot-search huggingface dataset:
AB0209 Retrospective analysis of rheumatoid arthritis patients complicated with mtx-related lymphoproliferative diseases
Authors: A. Okuyama, H. Nagasawa, T. Kondo, E. Nishi, H. Takei, R. Sakai, K. Chino, A. Shibata, K. Amano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Methotrexate (MTX) is the anchor drug in the management of rheumatoid arthritis (RA) in the world. In Japan, maximal dose of weekly MTX was increased up to 16 mg/week from 8 mg/week in 2011. Although RA disease activity has been controlled much better with higher dose and longer duration of MTX therapy, there are increasing reports of MTX-related lymphoproliferative diseases (MTX-LPD) especially in Japan. <h3>Objectives</h3> To evaluate the clinical characteristics of the RA patients who developed MTX-LPD. <h3>Methods</h3> A retrospective study was done to review the medical records of 39 patients (14 men and 25 women) with MTX-LPD in our institute. <h3>Results</h3> Baseline characteristics of 39 patients at the diagnosis of MTX-LPD were following (average); age 64.3, RA disease duration 11.4 years, serum CRP 7.5 mg/dL, serum MMP-3 value 314.5 ng/dL, MTX dose 7.8 mg/w, MTX treatment period 4.8 years. The pathological diagnosis; 17 diffuse large B cell,5 Hodgkin, and 3 follicular lymphoma. EBV was detected in 10 of 31 cases. MTX was stopped soon after the diagnosis of MTX-LPD in all but one patient who was very active RA and showed no aggravation of LPD. After MTX cessation, 16 patients needed chemotherapy for LPD. LPD resolved spontaneously in the other 22 patients, but DMARDs including biologics were prescribed later for RA flare and 11 developed LPD again. There were no significant difference of the prescription with or without LPD relapse. Among 8 patients who died, most of them received chemotherapy. <h3>Conclusions</h3> MTX-LPD in RA developed more frequently in male patients who had long MTX treatment period and high CRP and MMP-3. Some of them had grave prognosis despite chemotherapy after MTX was withdrawn. In patients taking MTX for a long time with longstanding active disease may have risk of MTX-LPD. <h3>References</h3> Hoshida Y, et al.: Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol. 2007 Feb;34(2):322-31Tokuhira M, et al.: Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma. 2012 Apr;53(4):616-23 <h3>Acknowledgements</h3> We are very thankful to Michihide Tokuhira, Associate Professor of hematology in our institute, for his terrific advice for histological and hematological investigation of LPD. <h3>Disclosure of Interest</h3> None Declared
Abstract 5018: Transcriptional and functional analysis of the CHD5 gene in Colorectal Cancer
Authors: Mehrnaz Fatemi, Hassan Brim, Krisham kumar, Hassan Ashktorab
Journal: Cancer Research (2010)

Abstract Background: CHD5 is a family member of chromatin remodeling factors that functions as a tumor suppressor in neuroblastoma and ovarian cancer. The transcriptional activity of CHD5 is silenced by hypermethylation. It has been found that CHD5 is a biomarker in colon carcinogenesis. In this study, we have investigated the transcriptional regulation and function of the CHD5 in CRC. Methods: The transcriptional activity of CHD5 was tested by reporter luciferase assay. The 1kb large fragment upstream of CHD5 transcription start site (TSS) showed luciferase activity; while the 400 bp subfragment upstream of TSS was inactive in both RKO (CHD5 endogenous non-expressing) and HCT116 (CHD5 endogenous expressing) cell lines. This suggests that the transcriptionally active sites of CHD5 are located within −400 to −1000. There are two consensus TCF binding sites in the 1 kb promoter region. In order to investigate whether Wnt pathway affects the CHD5 transcriptional activity, we treated the RKO and HCT116 cell lines with 6-bromoindirubin-3′oxime (BIO), the GSK-3a inhibitor, which activates the β-Catenin. We tested the Wnt pathway activity in RKO and HCT116 cell lines by using the TCF/LEF responsive luciferase construct. Methylation profiles of CHD5 in 51 CRC and 6 adenomas from African Americans analyzed by MSP. Microdeletion analysis of the CHD5 region (1p36) was performed by aCGH. Results: The activity of TCF/LEF responsive element increased by 17.5 folds in RKO cell line and by 7.3 in HCT116 cell line after BIO treatment. Interestingly, the luciferase activity of 1kb CHD5 promoter increased after treating with BIO, and no changes were observed in activity of the 400 bp fragment. This suggests that the TCF/LEF and β-Catenin might act as coactivators for CHD5 transcriptional regulation. We also analyzed the proliferation of the RKO cell line after stably transfecting with CHD5 expressing plasmid (pcDNA). The results showed that the exogenous expression of CHD5 reduces the proliferation of the RKO cell line by two folds compared to the wild type and the mock controls. CHD5 was hypermethylated in 78% of the tested patients samples and deleted in 36%. Conclusion: The function of CHD5 is not well understood in CRC. Here, we suggest that the wnt/β-catenin pathway may be involved in the transcriptional regulation of CHD5. In addition in vivo CHD5 microdeletion and methylation excrement suggest that CHD5 act as tumor suppressor in CRC. 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 5018.
Stat Bite U.S. Lung Cancer Incidence Trends
Authors: B. K. Edwards, L. A. G. Ries
Journal: JNCI Journal of the National Cancer Institute (1991)

Stat Bite U.S. Lung Cancer Incidence Trends Get access Brenda K. Edwards, Ph.D., Brenda K. Edwards, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn A. G. Ries Lynn A. G. Ries Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 13, 3 July 1991, Page 901, https://doi.org/10.1093/jnci/83.13.901 Published: 03 July 1991
A1.6 IDO Pathway in RA Patients Responding to Biologic Treatments
Authors: G Falgarone, S Rullé, X Guillot, L Semerano, C Laroche, E Assier, MC Boissier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in immune tolerance, which is thought to be defective in Rheumatoid Arthritis (RA). It is expressed in mononuclear cells including dendritic cells (DC), and could play a role in DC-regulatory T cells crosstalk. Our aim was to study IDO expression in peripheral blood of patients with RA compared to controls. Effect of biotherapies on IDO was also evaluated under anti-rheumatic biotherapies. <h3>Methods</h3> Human PBMC were purified by density gradient centrifugation and IDO gene expression was assessed by qRT-PCR. In parallel, the dosage of kynurenine was performed in plasma to evaluate IDO activity. For some patients, PBMC were cultured for 24 hours with LPS, IFNγ or both before IDO assays. <h3>Results</h3> We included 40 patients with RA and 30 controls including 15 spondylarthropathies (SpA), 10 osteoarthritis (OA) and 5 osteoporosis (OP). Our results showed that IDO was over-expressed and more active in RA than in non inflammatory diseases. Interestingly, in RA patients, before treatment with biotherapies, kynurenine plasmatic levels were negatively correlated with the DAS28 activity score (r = –0.552; p &lt; 0.016), and IDO mRNA ratio with ESR (r = –0.536; p &lt; 0.003). After 3 months of biologics (independently of treatments), kynurenine levels significantly decreased in responders, while they remained unchanged in non responders. In anti-TNFα-treated RA patients (n = 10), IDO mRNA was significantly decreased after 3 months whereas in tocilizumab (IL-6 receptor-inhibitor, n = 17) or abatacept (CTLA4-Ig; n = 10) treated patients, IDO levels did not change significantly. <h3>Conclusions</h3> IDO was up-regulated and more functional in patients with RA. It was negatively correlated with systemic inflammation and disease activity. IDO gene expression was also more inducible in this group of patients. So, in RA, IDO could contribute to decrease systemic inflammation and disease activity in a counter-regulation loop (which needs to be confirmed in further experiments). Tocilizumab and abatacept exerted an IDO-independent protection, whereas after an anti-TNFα treatment, IDO expression and inductibility decreased. This could help in treatment strategies in RA.
Abstract 1780: <i>Synthesis and antitumor activity of proximicins A, B and C</i>
Authors: Federico Brucoli, Antonino Natoli, Preethi Marimuthu, Andreas Schätzlein
Journal: Cancer Research (2012)

Abstract Proximicins A, B and C are a family of three novel aminofuran antibiotics isolated from marine actinomycetes of the genus Verrucosispora. The distinctive features of these compounds are (a) the structural similarity to the DNA-binding agents distamycin (4) and netropsin (5), and (b) the presence in their molecular framework of an unusual α-aminoacid, 4-aminofuran-2-carboxylic acid. Preliminary in vitro biological evaluation of proximicins A - C against selected carcinoma cell lines has shown that all compounds have a significantly higher cytotoxicity than netropsin and distamycin. In addition, proximicins can activate cell-cycle regulatory proteins involved in the transition of cells from G1 to S phase, and proximicin C, in contrast to distamycin, can induce up-regulation of p53 and p21 in gastric adenocarcinoma cells. The total synthesis of the proximicins A, B and C was successfully carried out starting from methyl 4-Boc-aminofuran-2-carboxylate and sufficient quantities of each compound were prepared for extensive in vitro evaluation. The anticancer activity of proximicins was investigated using cellular methods. The compounds induced apoptotic cell death in L1236 (Hodgkin's Lymphoma) and Jurkat 16 (T-cell leukemia) cells as confirmed by flow cytometric DNA fragmentation analysis. Proximicin B exhibited a strong lethal effect in both L1236 and Jurkat 16 cell lines and apoptosis induction was shown to be dose-dependent after 48 h treatment. Proximicin C induced apoptosis only in Jurkat 16 cells, with L1236 showing higher resistance to the drug. In addition, the proximicins cytotoxicity was determined against selected cancer cell lines different from those previously reported. Proximicin C exhibited significantly higher cytotoxicity against U-87 MG (glioblastoma) and MDA-MD-231 (breast carcinoma) cells compared to proximicin B. Further biological experiments are currently underway to elucidate the mechanism of action of these furan-based oligopeptides. In conclusion, given their interesting molecular framework and their significant anticancer activity, proximicins represent an attractive synthetic target and could be potentially developed into anticancer drugs of broad utility. 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 1780. doi:1538-7445.AM2012-1780
P5-03-04: Circadian Modulation of Estrogen Receptor alpha Promoter Activity.
Authors: LM Villa, CS Santos, S Cousins, CV Finkielstein
Journal: Cancer Research (2011)

Abstract The circadian clock is a molecular mechanism that synchronizes environment variations with physiological changes. Disruption of the circadian clock has been linked to increased risk in diseases and a number of disorders (e.g. jet lag, insomnia, coronary heart disease and cancer). Period 2 (PER2), a circadian protein, is at the center of the clock's function. The complete loss of per2 has been shown to be common in several types of cancer including breast and ovarian. Epidemiological studies established a correlation between circadian disruption and the development of estrogen dependent tumors. The expression of estrogen receptor alpha (ERa) mRNA oscillates in a 24-hour period and, unlike PER2, ERa peaks during the light phase of the day. Because up regulation of ER relates to tumor development, defining the mechanisms of ERa expression will contribute to our comprehension of cellular proliferation and regulation of normal developmental processes. The overall goal of this project is to investigate the molecular basis for circadian control of estrogen receptor alpha (ERa) transcription. Transcriptional activation of ERa was measured using a reporter system in Chinese Hamster Ovary and MCF-7 cell lines. Data show that PER2 influence ERa transcription through a non-canonical mechanism independent of its circadian counterparts. Promoter analysis using the Alibaba 2.0 suite revealed the presence of various putative novel partners. Among them, OCT-1 was found to directly interact with Per2, in vitro, and with corresponding response element within the ERa promoter. The predicted binding site of OCT-1 is 267 bps upstream of the promoter. Pull-down assays were used to map direct interaction of various PER2 recombinant proteins and the DNA-binding domain of OCT-1. Radiolabeled OCT-1 was found to bind to the C-terminal end of PER2. Electrophoretic mobility shift assays were used to determine direct binding of OCT-1 to the promoter. ChIP assay confirmed the recruitment of PER2 to the estrogen promoter by OCT-1. Fluorescence anisotropy and surface plasmon resonance were employed to establish the binding affinity of OCT-1 to the ERa promoter and PER2. OCT-1 was found to have a high affinity for the ERa promoter (∼10 nM). Furthermore, OCT-1 recruits PER2 to the estrogen promoter. Preliminary data suggests that the transcription factor PER2 might play a role in the regulation of the estrogen promoter. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-03-04.
P4-17-12: Analysis of Predictive and Prognostic Factors for Metastatic Breast Cancer Patients with Brain Metastasis Treated by Whole Brain Radiotherapy.
Authors: IH Park, KS Lee, KH Shin, J Ro
Journal: Cancer Research (2011)

Abstract Background We addressed the progression free survival of brain metastasis (PFS_BM) in metastatic breast cancer (MBC) patients treated by whole brain radiotherapy (WBRT) for brain metastasis (BM). In addition, we investigated predictive and prognostic factors for the PFS_BM and OS_BM. Patients and methods A total of 212 patients with BM, treated by WBRT at the National Cancer Center between January 2000 and December 2010 were reviewed. The PFS_BM was defined as the time interval from the date of start of WBRT to the date of a progression of metastatic lesions in the brain or death or last follow-up. Results The median age of patients was 45 years (range, 22–72 years) and the median time to brain metastasis was 12.7 months (range, 0.0−72.8 months). Of all patients, 50 (23.6%) patients were hormone receptor (HR) positive and 104 (49.1%) HER2 positive. Six patients received a surgery or a focal radiotherapy for metastatic lesions prior to WBRT. Seventy one (33.4%) patients had well controlled extracranial systemic disease (CR+PR+SD) when brain metastasis was diagnosed. The median survival after BM (OS_BM) was 5.4 months (95% CI, 4.4−6.4 months) and approximately 14.6% of patients died mainly of progressive brain metastasis. The PFS_BM was significantly affected by poor performance status (PS ≥3) (P&amp;lt;0.001), uncontrolled systemic disease status (P=0.029), disease free interval (DFI) &amp;lt; 2 years (P=0.011), no chemotherapy after BM (P&amp;lt;0.001), and HER2 positivity (P=0.002). Of those, poor PS, no chemotherapy after BM, and uncontrolled systemic disease status were remained important factors on a multivariate analysis. In terms of OS_BM, poor PS (P&amp;lt;0.001), older age (P=0.005), number of systemic metastatic sites &amp;gt;3 (P&amp;lt;0.001), uncontrolled systemic disease status (P&amp;lt;0.001), disease free interval (DFI) &amp;lt; 2 years (P=0.014), no chemotherapy after BM (P&amp;lt;0.001), and visceral involvement (P=0.009) were significant factors. Of those, poor PS (P&amp;lt;0.001), uncontrolled systemic disease status (P&amp;lt;0.001), and no chemotherapy after BM (P&amp;lt;0.001) were important factors for shorter OS_BM when adjusted with other factors. Conclusions Uncontrolled extracranial systemic disease status, no chemotherapy after BM, and poor PS were significant factors for shorter PFS_BM and overall survival after brain metastasis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-12.
Bone Marrow–Allograft Rejection by T Lymphocytes Recognizing a Single Amino Acid Difference in HLA-B44
Authors: Katharina Fleischhauer, Nancy A. Kernan, Richard J. O'Reilly, Bo Dupont, Soo Young Yang
Journal: New England Journal of Medicine (1990)

BONE marrow from unrelated donors is increasingly being transplanted for the treatment of patients with leukemia, aplastic anemia, and lethal congenital disorders of hematopoiesis and immunologic function. National and international registries of HLA-typed volunteer donors have been developed to optimize HLA matching between unrelated donors and recipients.1 , 2 The fate of marrow grafts depends on many factors, including conditioning regimens, the composition of the cells in the graft, immunosuppression after transplantation, and the degree of histocompatibility between donor and recipient. Clinically serious graft-versus-host disease occurs in 20 to 50 percent of patients receiving marrow grafts from HLA-identical siblings, and some measure . . .
President Signs 1993 Appropriations Bill
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article President Signs 1993 Appropriations Bill Get access Dorothy A. Tisevich Dorothy A. Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 21, 4 November 1992, Page 1622, https://doi.org/10.1093/jnci/84.21.1622 Published: 04 November 1992
A “tuft” procedure
Authors: Michael Sey, John DeWitt
Journal: Endoscopy (2013)

A 53-year-old man presented with dysphagia for solid food. He had a history of esophageal atresia that had required repair with a colonic interposition as a child. In 2008, he had presented with dysphagia, dyspnea, and a bulge in his neck. Computed tomography (CT) scanning showed herniation of the colonic conduit into his neck with ischemic changes. He had undergone emergency resection of the conduit and esophagogastric reconstruction, which was complicated by a tight anastomotic stricture that had been managed with esophageal dilation and stenting for 3 years. Unfortunately, a large anterior esophagocutaneous fistula had developed in his chest wall, which required repair in 2012 with a pectoralis major musculocutaneous skin flap to reconstruct his cervical esophagus. He was subsequently referred for endoscopy because of recurrence of his dysphagia.
Case 1-1967
Authors: Sydney S. Gellis, Wallace A. Jones
Journal: New England Journal of Medicine (1967)

Presentation of CaseA six-year-old boy was admitted to the hospital in an unresponsive state.His birth weight was 7 pounds, 2 ounces; he had always been small for his age. A staphylococcal infection of the skin at birth had been treated at another hospital. He was admitted to a second hospital at the age of four months because of bronchitis and diarrhea and was readmitted at the age of eleven months because of bronchitis. Otherwise, he had been healthy and active.For several weeks before admission chicken pox developed among his classmates. Four days before entry he complained of . . .
556 PREVALENCE OF HEPATITIS E IN NEW YORK AMONG HIV NEGATIVE CHRONIC LIVER DISEASE POPULATION “IS IT AN INNOCENT BYSTANDER”
Authors: P.P. Basu, T. Nair, M. Jafri, S. Farhat, S. Faustin, L. Ang, K. Mittimani, N. James Shah
Journal: Journal of Hepatology (2012)
Mass distribution of albendazole for hookworm control in women smallholder famers, Democratic Republic of Congo: a double blind randomised controlled trial
Authors: Maurice Masoda, Margaret Salmon, Christian Salmon, Jean Maurice Salumu, Carmine Bozzi, Rene Zaidi, Lisa Marie Harrison, Debbie Humphries, Clinton Trout, Naomi Awaca Uvon, Sarah K Wendel, Michael Cappello
Journal: The Lancet Global Health (2016)

Background An estimated 4·7 billion people worldwide live in regions with high potential for exposure to soil transmitted helminths, a group of intestinal parasites that include Ascaris lumbricoides, Trichuris trichiura and hookworms (Necator americanus and Ancylostoma spp), each of which can affect the health and nutritional status of women smallholder farmers. The two aims of this double blind, prospective, randomised trial were to determine the prevalence and intensity of hookworm infection in this population and to test whether treatment with albendazole affects women's work capacity, as measured by aerobic fitness.
Abstract 1330: Low dose irradiation reverts chemoresistance towards fluorouracil in human pancreatic adenocarcinoma cells by upregulation of thymidine phosphorylase
Authors: Hendrik Seeliger, Ying Xin, Peter Camaj, Ivan Ischenko, Moshe Schaffer, Karl-Walter Jauch, Christiane J. Bruns
Journal: Cancer Research (2010)

Abstract Background: Resistance towards cytotoxic drugs and ionizing radiation (IR) accounts for poor therapy response in pancreatic cancer. The radiosensitizing effects of fluorouracil (FU) are well characterized, however, it is not known whether IR itself exerts sensitizing effects towards cytotoxic chemotherapy. Here, we hypothesize that IR induced upregulation of thymidine phosphorylase (TP) results in a reversal of resistance towards FU. Methods: An FU resistant variant of the human pancreatic adenocarcinoma cell line AsPC-1 was developed by long term in vitro FU exposure. Proliferation of AsPC-1 and AsPC-1FUres cells was determined by an MTT proliferation assay after previous low dose (0.05 Gy) exposure of IR. To antagonize a possible effect mediated by TP upregulation, anti-TP siRNA was added in the same setting. TP expression in AsPC-1 cells before and after IR was determined by Western blotting. Results: FU resistant AsPC-1 cells showed a 7.5-fold increase of the IC50 after FU exposure, compared to non-resistant cells. When challenging both cell lines with FU after low dose IR, no significant difference of proliferation was observed in AsPC-1 cells and their FU resistant variant, suggesting a reversal of chemoresistance by IR. This chemosensitizing effect was abrogated when blocking TP by anti-TP siRNA before IR. In cell lysates harvested from AsPC-1 cells, an increase of TP expression was seen after exposure of low dose IR (0.05 Gy) as well as high dose IR (2.0 Gy). Conclusion: Our results suggest a TP mediated reversal of chemoresistance towards FU that is triggered by low dose IR in vitro. These results have to be confirmed in an in vivo model. In conclusion, induction of TP expression by low dose irradiation may be an interesting concept to overcome chemotherapy resistance in pancreatic cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1330.