tbuckley/cabot-search huggingface dataset:
RELATIONSHIP OF PLASMA DABIGATRAN CONCENTRATIONS AND ACTIVATED PARTIAL THROMBOPLASTIN TIME IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Yoshihisa Nakagawa, Daiki Shimomura, Hirokazu Kondo, Toshihiro Tamura, Naoaki Onishi, Yodo Tamaki, Makoto Miyake, Kazuaki Kaitani, Chisato Izumi
Journal: Journal of the American College of Cardiology (2015)
Antagonism by Suramin of the Growth-Inhibitory Effect of Hydroxytamoxifen and Doxorubicin in Human MCF-7 Breast Cancer Cells
Authors: Y. Berthois, X.-F. Dong, P.-M. Martin, E. Cvitkovic
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Antagonism by Suramin of the Growth-Inhibitory Effect of Hydroxytamoxifen and Doxorubicin in Human MCF-7 Breast Cancer Cells Get access Yolande Berthois, Yolande Berthois * Laboratoire de Cancérologie Expérmentale, Faculté de Médecine secteur Nord, Boulevard Pierre Dramard, Marseille, France *Correspondence to : Yolande Berthois, M.D., Laboratoire de Cancérologie Expérimentalc, Faculté de Médecine secteur Nord, Boulevard Pierre Dramard, 13326 Marseille Cedex 15, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar Xue-Fen Dong, Xue-Fen Dong Laboratoire de Cancérologie Expérmentale, Faculté de Médecine secteur Nord, Boulevard Pierre Dramard, Marseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Pierre-Marie Martin, Pierre-Marie Martin Laboratoire de Cancérologie Expérmentale, Faculté de Médecine secteur Nord, Boulevard Pierre Dramard, Marseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Esteban Cvitkovic Esteban Cvitkovic Institut Gustave-Roussy, Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 18, 16 September 1992, Pages 1438–1439, https://doi.org/10.1093/jnci/84.18.1438 Published: 16 September 1992 Article history Received: 07 May 1992 Accepted: 23 June 1992 Published: 16 September 1992
Preclinical antitumor activity of an Fc domain-optimized HER2 monoclonal antibody (mAb).
Authors: J. L. Nordstrom, L. Huang, Y. Yang, N. Tuaillon, J. B. Stavenhagen, S. Stewart, P. A. Moore, S. Johnson, S. Koenig, E. Bonvini
Journal: Journal of Clinical Oncology (2010)

e13135 Background: Response to trastuzumab in metastatic breast cancer correlates with expression of the high affinity allele of the activating Fcγ receptor IIIA (CD16A). We engineered MGAH22, a HER2 mAb with specificity and affinity similar to trastuzumab, to have an optimized Fc domain that confers increased binding to both alleles of CD16A and decreased binding to CD32B (the inhibitory FcγRIIB). Methods: MGAH22 was compared to RES120, an identical mAb except for a wild type Fc domain. Antibody-dependent cell cytotoxicity (ADCC) assays were performed with HER2-expressing cancer cells and human PBMC or purified NK cells. Xenograft studies were conducted in mice with wild-type murine FcγRs; mice lacking murine CD16; or mice lacking mCD16 but transgenic for human CD16A-158F, the low-binding variant. The latter model reproduces the differential binding between wild type and Fc-optimized mAbs for human CD16A. JIMT-1 breast tumor cells were from a patient that progressed on trastuzumab therapy. Results: Compared to RES120, MGAH22 exhibited greater ADCC against HER2-expressing cancer cells with lower EC50. Increased maximal lysis was seen against cells expressing low HER2 levels. With JIMT-1 cells as targets and NK cells as effectors, MGAH22 was more potent than RES120, but an increase in maximal cytotoxicity was only observed with NK cells from CD16-158F carriers. In mouse xenograft models, MGAH22 was active against HER2 expressing breast, ovarian or pancreatic tumors in a manner similar to RES120. MGAH22, however, showed enhanced activity against JIMT-1 xenografts in mCD16-/- hCD16A+ transgenic mouse lines, but not in wild type or mCD16-/- mouse lines. Conclusions: The optimized Fc domain confers enhanced activity against HER2-positive tumor cells, including cells expressing low HER2 levels or resistant to trastuzumab anti-proliferative activity, and enhanced activity against HER2-expressing tumors in hCD16A-158F transgenic mice. MGAH22 may have utility in patients with low HER2 expressing tumors, irrespective of the patient's CD16A genotype. A phase I dose- escalation study to assess the safety and PK of MGAH22 in patients with refractory HER2-positive cancers for whom no standard therapy is available is planned for 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MacroGenics, Inc. MacroGenics, Inc.
Agreement to Develop Taxotere Expected in April
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Agreement to Develop Taxotere Expected in April Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 9, 6 May 1992, Page 673, https://doi.org/10.1093/jnci/84.9.673 Published: 06 May 1992
OP0027 A single nucleotide polymorphism in the MED29 gene is associated with the clinical outcome of a TNF-blocker and B-cell directed therapy in RA patients
Authors: S. Drynda, M. Gloetzner, D. Leesch, J. Kekow
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Due to the wide range of highly specific and effective biologicals for the treatment of RA it has become of great importance to identify biomarkers for the prediction of therapy outcome, supporting an individualized therapy. Most studies in this field analysed potential markers for a single biological or substance group, respectively. <h3>Objectives</h3> In this study we analysed the association of the single nucleotide polymorphism (SNP) rs10414216 in the MED29 gene with the outcome of two different therapeutic approaches. <h3>Methods</h3> We studied 275 RA patients treated first with the TNF-blocker etanercept (ETN) and a subgroup of 61 patients treated later in the course of the disease with rituximab (RTX), directed against B-cells. The frequency of the MED29 C/T polymorphism was analysed using a validated TaqMan™ genotyping assay. Disease activity and therapy response were assessed according to the EULAR improvement criteria (http://www.das-score.nl). The primary response of the ETN therapy was assessed 3-4 months after initiation of therapy, the outcome of rituximab after 4-6 months after the first infusion of RTX. <h3>Results</h3> The genotype distribution of the SNP MED29 C/T in 275 investigated RA patients was similar compared to healthy controls. There were no differences in the genotype frequencies in association to CCP-antibody positivity. The disease activity at baseline before start of ETN or RTX treatment was comparable for all genotypes. After 3-4 months of ETN treatment the DAS28 decreased by 1.670±1.377, 2.083±1.348 and 2.382±1.286 (mean±SD) for the C/C, C/T and T/T genotypes, respectively. The improvement of the DAS28 was significantly better for the T/T genotype compared to C/C (p=0.003). 58% of T/T carriers but only 27.2% of the C/C carriers were identified as good responders to ETN. However, in RTX treated patients the carriage of the C/C genotype was identified as a predictor for a better response, after 4-6 months the DAS28 decreased by 2.277±1.558 for the C/C genotype compared to 1.310±1.347 for the C/T genotype (p=0,025). 46.2% of C/C and only 27.3% of C/T carriers were good responders to RTX. The T/T carriers were underrepresented in the RTX subgroup, probably as a result of a better outcome of the TNF-blocker therapy in these patients. <h3>Conclusions</h3> Our data clearly indicate that a single SNP has the potential to predict the outcome to different therapeutic approaches. The functional importance of this genetic variation has not yet been characterized. However, this SNP is located in the gene region of MED29, a subunit of the mediator complex which plays a substantial role in the regulation of gene expression. Further analysis of this SNP and the respective gene locus could provide further insight into the mechanisms which determine the outcome of different targeted therapies. <h3>Disclosure of Interest</h3> None Declared
PTU-171 Recurrence After Successful Radiofrequency Ablation For Barrett’s Related Neoplasia Is More Likely In Males: Data From The United Kingdom Patient Registry
Authors: RJ Haidry, M Banks, A Gupta, M Butt, G Fullarton, H Smart, J Morris, R Willert, R Narayanasamy, M Rodriguez-Justo, M Novelli, L Lovat
Journal: Gut (2014)

<h3>Introduction</h3> Barrett’s oesophagus (BE) can lead to oesophageal adenocarcinoma (OAC). BE is more prevalent in males. Endoscopic mucosal resection (EMR) for visible lesions followed by Radiofrequency ablation (RFA) have become first line treatment for patients with BE related neoplasia. Recurrence after treatment can occur in up to 25% of patients. Risk factors for recurrence are unclear. <h3>Methods</h3> We examine prospective data from United Kingdom (UK) registry of patients undergoing RFA/EMR over past 5 years. We examine if recurrence after treatment is influenced by gender, baseline histology, BE length and prior EMR. Before RFA, visible lesions were removed by EMR. Thereafter patients underwent RFA 3 monthly. Biopsies were taken at 12 months and outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) were assessed. After successful treatment patients were followed up 3 monthly for the first year, 6 monthly for second year and annually thereafter. Biopsies were taken from 1cm below neo z-line and previously treated BE segment. <h3>Results</h3> A total of 412 males and 95 females have been treated with no statistical difference in baseline BE length, histology or prior EMR in both groups. CR-D in Males was 84% and CR-IM 80%. In females CR-D was 86% and CR-IM 64% and not significantly different (p = 0.61 and p = 0.22, respectively). Progression to cancer was 3% in both cohorts at 12 months. There were 21 patients from both groups with recurrent dysplasia on follow up biopsy after successful treatment. Median time to recurrence in these after successful RFA was 380 days (IQR 177–615). Twenty recurrences were in males compared to one in female group which was statistically significant (p = 0.04). There were 11 recurrences of IM alone in patients who had confirmed CR-IM at 12 months. All were in male patients (median time to recurrence of 626 days, IQR 237–822). Baseline BE length, histology, prior EMR did not influence risk of recurrence of dysplasia or IM. <h3>Conclusion</h3> RFA for BE related neoplasia is equally effective in both males and females. Recurrence of neoplasia after successful eradication although uncommon overall is more common in males. The much lower recurrence rate in women raises the possibility that they could be discharged from follow up after successful treatment or have prolonged surveillance intervals compared to men. This could reduce the burden of surveillance endoscopy on overstretched services. <i>All collaborators of UK RFA registry are acknowledged for their contributions to this work.</i> <h3>Disclosure of Interest</h3> None Declared.
Primary chronic lymphocytic leukemia (CLL) cells survival support from NLC and SDF-1a (CXCL-12) in vitro and the effect of lenalidomide (LEN)
Authors: D. F. James, M. Y. Choi, M. Betty, R. Mosadeghi, T. J. Kipps
Journal: Journal of Clinical Oncology (2008)

7070 Background: LEN is approved for treatment of del 5q myelodysplastic syndromes and treated multiple myeloma. LEN has potential therapeutic activity in early trials of relapsed CLL. The mechanism(s) whereby this drug is active in CLL is unknown. LEN is not directly cytotoxic to CLL cells in vitro that has stimulated speculation that the activity of LEN might be through modulation of the CLL microenvironment. Cells in the CLL microenvironment, such as Nurse-like cells (NLCs), protect CLL cells from spontaneous and drug mediated apoptosis in vitro and presumably in-vivo. NLCs support CLL survival via multiple mechanisms, including elaboration of SDF-1a and TNF family members BAFF and APRIL. [Burger 2000, Nishio 2005]. Methods: We evaluated the effects of LEN on CLL survival when the CLL cells from different patients were cultured alone, with recombinant SDF-1 or BAFF, or with NLC generated as previously described [Tsukada 2002]. Results: When cultured with NLC, the survival of CLL cells was higher than that of CLL cells cultured alone. LEN at concentrations of 0.1uM and greater to co-cultures of NLC and CLL cells caused specific reductions in CLL cell survival to levels similar to or lower than that of CLL cells cultured without NLC. In the presence of NLC, LEN at 1uM reduced CLL cell viability compared to control (42% vs. 56% ±4% p [<] 0.0005 n=13). CLL B cells from different patients (N=11) were cultured alone or with recombinant cytokines know to be secreted by NLC, all in duplicate in a series of 3 experiments. Both NLC and SDF-1a protected CLL cell viability and it was significantly mitigated in the presence of LEN 0.1–10uM. Under the same conditions, LEN had no significant effect on the survival support provided by rhBAFF at. Subsequent experiments evaluated suprapharmacologic LEN 100uM at days 3–6 and found LEN significantly decreased viability of CLL cells supported by SDF-1, but not recombinant BAFF. CXCR4, the receptor for SDF-1a was downmodulated in 7/8 patients in the presence of lenalidomide versus vehicle control at day 7 (p=0.03 for MFI). Conclusions: LEN might abrogate the protective influence of NLC and SDF-1a on CLL cell survival an effect that was not seen on the survival support provided by rhBAFF. No significant financial relationships to disclose.
Diagnostic yield and safety of sequential endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in pancreatobiliary disorders
Authors: C Ortiz-Moyano, FJ Pellicer-Bautista, V Lería-Yébenes, R Romero-Castro, JM Herrerías-Gutiérrez
Journal: Endoscopy (2006)

EUS and ERCP are complementary procedures in pancreatobiliary processes (PBD). Our aim was to evaluate the diagnostic yield and safety of both procedures performed in the same endoscopic session.
Abstract 1410: TIP-1 regulates Glioma invasion through small GTPases
Authors: Hailun Wang, Miaojun Han, Dennis E. Hallahan, Zhaozhong Han
Journal: Cancer Research (2011)

Abstract Therapy resistance and invasion are two common features of malignant glioma. Our previous studies showed that TIP-1 regulates sensitivity of glioma cells to ionizing radiation. It was also found that TIP-1 protein level was elevated in human malignant glioma compared to the normal brain tissue counterparts, and correlated with the malignancy of gliomas. This observation was supported with a survival study within animal models, in which TIP-1 knockdown within glioma cell lines significantly retarded progression of the intracranially implanted tumors and extended survival time of the mice. In vitro and in vivo studies indicated that it is the reduced migration and invasion capability, but not the cell proliferation rate, that contributed to the retarded tumor progression of gliomas with TIP-1 knockdown. The glioma cells with TIP-1 knockdown also showed morphological changes with reorganized cytoskeleton and reduced efficiency of reorientation in directional migration. TIP-1 was reported to associate to beta-catenin and Rhotekin, two proteins that are involved in the cell skeleton reorganization and cell migration. Their interactions are through the single PDZ domain within TIP-1 and the classic Type I PDZ-binding motifs located at the carboxyl terminus of beta-catenin and Rhotekin respectively. It was found that TIP-1 knockdown altered intracellular location of Rhotekin. Mislocalization of Rhotekin at the cell migration leading edge resulted in irregular activation of RhoA, which generally regulates cell rear body retraction. Further, we identified that beta-PIX shares a similar PDZ-binding motif and associates to TIP-1 in vitro and in vivo. Beta-PIX is recruited to the leading edge by Scribble for Rac1 or Cdc42 activation and thus regulates cell front protrusion. Knockdown of TIP-1 within the invasive glioma cells disrupted the association of beta-PIX and Scribble, resulted in mislocalization of beta-PIX and reduced Rac1 activation. Taken together, these data illustrated that TIP-1 is one critical modulator in migration of the invasive glioma through regulating two small GTPases (RhoA and Rac1), and targeting TIP-1 might represent one novel approach to treat the highly invasive and mortal glioma tumors. 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 1410. doi:10.1158/1538-7445.AM2011-1410
The Limit of Viability -- Neonatal Outcome of Infants Born at 22 to 25 Weeks' Gestation
Authors: Marilee C. Allen, Pamela K. Donohue, Amy E. Dusman
Journal: New England Journal of Medicine (1993)

With improved survival of preterm infants, questions have been raised about the limit of viability. To provide better information and counseling for parents of infants about to be delivered after 22 to 25 weeks' gestation, we evaluated the mortality and neonatal morbidity of preterm infants born at these gestational ages.
Chikungunya at the Door — Déjà Vu All Over Again?
Authors: David M. Morens, Anthony S. Fauci
Journal: New England Journal of Medicine (2014)

A chikungunya fever outbreak that appeared in the Caribbean in December has spread to the Americas, where populations were not previously exposed to alphaviruses. The potential for chikungunya to become established in the Western Hemisphere must be considered.
Blood-Borne and Sexual Transmission of Human Herpesvirus 8 in Women with or at Risk for Human Immunodeficiency Virus Infection
Authors: Michael J. Cannon, Sheila C. Dollard, Dawn K. Smith, Robert S. Klein, Paula Schuman, Josiah D. Rich, David Vlahov, Philip E. Pellett
Journal: New England Journal of Medicine (2001)

Human herpesvirus 8 (HHV-8), the causal agent of Kaposi's sarcoma, is transmitted sexually among homosexual men, but little is known of its transmission among women. Although HHV-8 has been detected in blood, there has been no clear evidence of blood-borne transmission.
Lysosomal Acid Lipase Deficiency — A New Therapy for a Genetic Lipid Disease
Authors: Daniel J. Rader
Journal: New England Journal of Medicine (2015)

There are more than 50 different lysosomal storage diseases, genetic disorders characterized by lysosomal accumulation of substrate.1 Phenotypes vary widely, depending on the specific cell types affected. Enzyme-replacement therapy has been transformational in the treatment of some lysosomal storage diseases2; however, enzyme-replacement therapy is currently approved and commercially available for only 7 lysosomal storage diseases.The principle of enzyme-replacement therapy is that after administration of a recombinant enzyme, it is taken up by target cells and directed to lysosomes, where it can hydrolyze its substrate.2 In Gaucher's disease, the recombinant enzyme is taken up by target macrophages by means . . .
Increased DNA Synthesis and Repair-Enzyme Expression in Lymphocytes From Patients With Chronic Lymphocytic Leukemia Resistant to Nitrogen Mustards
Authors: R. Geleziunas, A. McQuillan, A. Malapetsa, M. Hutchinson, D. Kopriva, M. A. Wainberg, J. Hiscott, J. Bramson, L. Panasci
Journal: JNCI Journal of the National Cancer Institute (1991)

Resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia (CLL) correlates with an enhanced removal of melphalan-induced DNA interstrand cross-links. This finding suggests that DNA repair enzymes may be involved in this process. The activity of 3-methyladenine-DNA glycosylase, which can release altered bases, including adducts at the N-7 position of guanine, was increased significantly in lymphocytes from patients with resistant CLL compared with those from untreated CLL patients. Since glycosylase activity varies with cell proliferation, the amount of [ 3 H]thymidine incorporated into DNA was determined and found to be elevated almost threefold in lymphocytes from patients with resistant CLL. The ratio of glycosylase activity to level of thymidine incorporation did not differ between these two groups of patients. Northern blot analysis of ERCC1 gene (a putative DNA repair enzyme involved in nucleotide excision repair) expression in lymphocytes from patients with CLL revealed multiple gene transcripts (1.1, 3.4, and 3.8 kilobases). In addition, analysis of two samples revealed the presence of a 2.6-kilobase transcript. The 2.6-kilobase transcript was recognized by specific RNA probes that hybridize to antisense ERCC1 transcripts. Levels of expression of the 1.1-kilobase protein encoding transcript in lymphocytes from patients with resistant CLL were increased twofold to threefold above those of untreated patients with CLL. These results indicate that increased expression of ERCC1 and increased activity of 3-methyladenine-DNA glycosylase occur with the development of resistance to the nitrogen mustards in patients with CLL, suggesting a role for enhanced DNA repair in this process. [J Natl Cancer Inst 83:557–564, 1991]
Studies on the Absorption of Orally Administered Iron from Sustained-Release Preparations
Authors: E. J. Middleton, E. Nagy, A. B. Morrison
Journal: New England Journal of Medicine (1966)

SUSTAINED-release products have been designed to contain in one dosage form the equivalent of several single doses of a drug, which is released to the body over an extended period. This slow release allows the drug to have prolonged therapeutic effects, and thus eliminates the need for repeated dosage. Various types of sustained-release products are now on the commercial market. Some of them have been tested clinically and found to have sustained-release properties whereas others are relatively unavailable and do not show the sustained effect as measured by blood levels and urinary excretion rates of the drug.In studies with . . .