tbuckley/cabot-search huggingface dataset:
Treatment with a Bortezomib-Containing Regimen Is Associated with Better Therapeutic Outcomes in Patients with Waldenstrom's Macroglobulinemia Who Have Familial Disease Predisposition
Authors: Steven P Treon, Zachary Hunter, Christina Hanzis, Christina Tripsas, Leukothea Ioakimidis, Christopher Patterson, Robert Manning, Patricia Sheehy, Barry Turnbull
Journal: Blood (2011)
Novel Efficient Primary Human Peripheral Blood Progenitor Cell-Targeted Recombinant Adeno-Associated Viral Vectors.
Authors: Marlon R. Veldwijk, Leopold Sellner, Marius Stiefelhagen, Jürgen A. Kleinschmidt, Stephanie Laufs, Julian Topaly, Frederik Wenz, W. Jens Zeller, Stefan Fruehauf
Journal: Blood (2007)
Frequency and Prognostic Relevance of Gene Mutations in Pediatric AML Patients At First Relapse.
Authors: Costa Bachas, Gerrit Jan Schuurhuis, Dirk Reinhardt, Ursula Creutzig, Zinia J. Kwidama, C. Michel Zwaan, Marry M. van den Heuvel-Eibrink, Evelina S De Bont, Sara Elitzur, Carmelo Rizzari, Valérie de Haas, Martin Zimmermann, Jacqueline Cloos, Gertjan J.L. Kaspers
Journal: Blood (2012)
Elevated Chemokine Expression in the Bone Marrow of Patients with Myeloma and MGUS Is Associated with Marked Alterations in the Distribution of CD4+ and CD8+ T Cell Subsets within the Blood and Bone Marrow
Authors: Oliver Goodyear, Sarah Essex, Helen McGettrick, Supratik Basu, Seetharam Anandram, Christopher D Buckley, Andrew Filer, Rahela Khanum, Karen P Piper, Paul AH Moss, Guy Pratt
Journal: Blood (2011)
Correction to “Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions”
Journal: Pharmacological Reviews (2013)

In the above article [Schmidt M, Dekker FJ, and Maarsingh H (2013) Pharmacol Rev 65: [670-709][1]], the wording “to reduce” is incorrect on page 692, legend to Fig. 6, and on page 693, left column, line 5. The correct wording is “to increase.”

The corrections are as follows:

Page 692, Fig
Characterization of functional heparan sulfate motifs overexpressed on multiple myeloma cells using single chain antibody variable fragments generated by phage display
Authors: M. Delcommenne, H. Klingemann, H. C. Fung, S. A. Gregory
Journal: Journal of Clinical Oncology (2006)

13060 Background: Multiple myeloma (MM) is the most prevalent plasma cell neoplasm and is characterized by the infiltration of the bone marrow by terminally differentiated B lymphocytes. Although novel drugs have recently been introduced, the disease remains incurable. No therapeutic antibody is as yet available for treatment of MM. One of the key molecules involved in multiple myeloma (MM) tumor progression is syndecan-1, a cell surface heparan sulfate (HS) proteoglycan expressed on both MM cells and normal plasma cells. Syndecan-1 regulates cell interactions with soluble molecules and the extracellular matrix through its heparan sulfate chains. These chains allow it to bind multiple growth factors such as Fibroblast Growth Factor type 2 (FGF-2), WNT, Hepatocyte Growth Factor (HGF), midkine, all of which promote survival and metastasis of MM cells. In addition, syndecan-1 on MM cells binds and internalizes osteoprotegerin, the RANKL antagonist, through its HS chains and depletes it from the bone marrow milieu, which triggers osteoclastogenesis. Methods: Using the phage display technique, we have generated a panel of MM-specific human antibody variable fragments (scFvs) against the MM cell line RPMI-8226. These scFvs were tested against a variety of cell lines and primary normal bone marrow or myeloma cells. The biochemical identity of the targeted antigens was determined. Results: Two of the selected scFvs, D4A4 and D6B10, reacted against heparan sulfate motifs that were highly expressed in MM cell lines and patient MM cells but absent (scFv D6B10) or poorly expressed (scFv D4A4) in normal plasma cells. Binding of scFv D6B10 to MM heparan sulfate chains required NS sulfation, 6-O-sulfation and, to a lesser extent, 2-O-sulfation. Additional experiments indicated that FGF-2, midkine and osteoprotegerin competed with scFv D6B10 for binding to HS. Conclusions: This study indicates that the structure of syndecan-1-associated HS is altered in MM cells and may influence its capacity to bind to growth factors and promote tumor progression. Human therapeutic antibodies derived from scFvs D4A4 and D6B10 may be useful for immune targeting of MM cells and interfering with pro-survival signaling pathways. No significant financial relationships to disclose.
Synovial sarcoma of the extremities and trunk: A long lasting disease
Authors: O. Merimsky, V. Soyfer, A. Goffman, J. Issakov, J. Bickels, S. Dadia, Y. Kollender, I. Meller
Journal: Journal of Clinical Oncology (2007)

10073 Background: Synovial sarcoma (SS) of an extremity or trunk is a relatively rare type of soft tissue sarcoma. SS most commonly affects adolescents and young adults. SS usually originates at an extremity, carries a t(X;18)(p11;q11) translocation, and approached by limb sparing surgery, radiation therapy, and chemotherapy. Methods: A retrospective analysis of clinical and histopathological data of 73 patients with proven SS, treated at the National Unit of Orthopedic Oncology, from January 1991 through December 2004 was performed. Results: At a median follow-up time of 6 years, a local-recurrence was observed in 17.8% of the patients, while systemic recurrence in 35.6% (local-only in 6.8 %, systemic-only in 24.6 %, and combined in 11%). Accumulation of events of local and systemic recurrence following a limb sparing approach, did not reach a plateau even after 192 months from diagnosis. The 10-year local recurrence free survival (LRFS), the 10-year systemic recurrence-free survival (SRFS), and the 10-year overall survival (OS) were 78%, 68%, and 61%, respectively. The median SRFS time was 180 months, while the median LRFS and OS have not been reached yet. LRFS was significantly better for ILP treated patients; SRFS was influenced by a shorter delay in diagnosis. Conclusions: The practical aspects of our observations are the need for long-term follow-up for diagnosis of recurrence, the fact that not all local or distant recurrences are necessarily associated with shortening of overall survival, and the important role of induction ILP with TNF in cases of extremity SS. No significant financial relationships to disclose.
The prevalence of diagnosed α<sub>1</sub>-antitrypsin deficiency and its comorbidities: results from a large population-based database
Authors: Timm Greulich, Christoph Nell, David Hohmann, Marco Grebe, Sabina Janciauskiene, Andreas Rembert Koczulla, Claus Franz Vogelmeier
Journal: European Respiratory Journal (2016)

α 1 -Antitrypsin deficiency (AATD) is a genetically determined disorder that is associated with different clinical manifestations. We aimed to assess the prevalence of diagnosed AATD and its comorbidities using a large healthcare database. In this retrospective longitudinal observational study, we analysed data from 4 million insurants. Using International Classification of Diseases revision 10 (ICD-10) codes, we assessed the prevalence, comorbidities and healthcare utilisation of AATD patients (E88.0 repeatedly coded) relative to non-AATD patients with chronic obstructive pulmonary disease (COPD), emphysema or asthma. In our study population, we identified 673 AATD patients (590 aged ≥30 years), corresponding to a prevalence of 23.73 per 100 000 in all age groups and 29.36 per 100 000 in those ≥30 years. Based on the number of AATD cases detected in the sample size (673 out of 2 836 585), we extrapolated that there were 19 162 AATD cases in Germany during the years studied. AATD patients had a higher prevalence of arterial hypertension, chronic kidney disease and diabetes relative to non-AATD asthma or emphysema patients. When compared to non-AATD COPD patients, AATD patients had significantly more consultations and more frequent and longer hospitalisations. Our data strengthen the assumption that AATD is associated with a variety of other diseases. Healthcare utilisation appears to be higher among AATD patients as compared to patients with non-AATD-related obstructive lung diseases.
Pegylated liposomal doxorubicin (PLD) with cyclophosphamide (C) as 1st-line chemotherapy for metastatic breast cancer (MBC) patients previously treated with adjuvant anthracyclines
Authors: T. A. Vandenberg, M. Trudeau, L. Provencher, L. C. Panasci, L. Yelle, D. Rayson, J. Latreille, M. Clemons, M. Giroux, J. Pouliot
Journal: Journal of Clinical Oncology (2006)

10627 Background: Anthracyclines (A) are key elements in adjuvant and metastatic chemotherapy regimens for breast cancer. Pre-exposure limits the utilization of A in advanced disease due to cumulative cardiotoxicity. PLD (Caelyx/Doxil) has equivalent activity to conventional doxorubicin in MBC. However PLD has reduced toxicity, including significantly less cardiotoxicity. Combinations of A+C are the backbone of many adjuvant therapies, thus C represents a logical drug to combine with PLD. Methods: MBC patients with measurable disease who completed anthracycline containing adjuvant therapy &gt; 12 months ago were entered in a multi-center single arm phase II trial. They received PLD 35mg/m 2 + cyclophosphamide 600 mg/m 2 every 3 weeks. This study was powered to demonstrate an objective response rate &gt; 25%. Results: Seventy three patients were enrolled. Prior adjuvant therapy included: AC (37%), CEF/FEC (28%), AC-T (15%), AT (7%), EC (7%). The median cumulative dose of prior A were 240mg/m 2 and 580mg/m 2 for doxorubicin or epirubicin, respectively. Median time since adjuvant chemotherapy was 4.4 years (1–14). Patients received a median of 6 cycles (2–10) of PLD + C. Major toxicities were; grade 3/4 neutropenia (7.5%), asymptomatic &gt; 10% declines in LVEF (9%) (reversible upon discontinuation of PLD), grade 3/4 hand foot syndrome (6%). Other toxicities were uncommon and usually did not require discontinuation. The objective response rate (ORR) was 38% (4% CR and 34% PR), with an additional 32% having stable disease &gt; 6 months for a clinical benefit of 70% (CB). ORR was similar for patients who had received adjuvant taxanes. Kaplan-Meyer estimated median time to progression was 31.5 weeks (23% progression free). Conclusions: The combination of PLD + C every 3 weeks in patients who have completed adjuvant anthracycline chemotherapy after more than one year prior is well tolerated and has a clinical benefit rate of 70%. This finding is similar to other commonly employed chemotherapeutic regimens for MBC and suggests that re-treatment with a non-cardiotoxic anthracycline following previous anthracycline therapy may be a reasonable therapeutic option for some patients. [Table: see text]
Impact of Mutations in the Spliceosome Machinery and Ring Sideroblasts in Patients with Myeloid Malignancies Who Received Conventional Chemotherapy or Allogeneic Hematopoietic Cell Transplantation
Authors: Betty K. Hamilton, Ali Tabarroki, Valeria Visconte, Edy Hasrouni, Hideki Makishima, Shawnda Tench, Matt Kalaycio, Mikkael A. Sekeres, Ronald Sobecks, Hien K. Duong, Brian T. Hill, Jaroslaw P. Maciejewski, Brian J. Bolwell, Edward A. Copelan, Ramon V. Tiu
Journal: Blood (2012)
Co-Inheritance of Delta Thalassemia Might Contribute to the High Fetal Hemoglobin in Sickle Cell Anemia Patients with the Saudi-Indian Haplotype
Authors: Abdulrahman Alsultan, Duyen A. Ngo, John J. Farrell, Hazem Ghabbour, Idowu Akinsheye, Amein Al-Ali, Ahmed Alsuliman, Muneer Al-Baghshi, Waleed Albuali, Mohammed Alabdulaali, Paola Sebastiani, Clinton T. Baldwin, David H.K. Chui, Martin H. Steinberg
Journal: Blood (2011)
Deletion of the Tumor Suppressor Gene NF1 Is An Alternative Mechanism for Aberrant Activation of the RAS Pathway and Is Found in 11% of Acute Myeloid Leukemia.
Authors: Claudia Haferlach, Alexander Kohlmann, Sonja Schindela, Wolfgang Kern, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2009)
CTDGFinder: A Novel Homology-Based Algorithm for Identifying Closely Spaced Clusters of Tandemly Duplicated Genes
Authors: Juan F. Ortiz, Antonis Rokas
Journal: Molecular Biology and Evolution (2016)

Closely spaced clusters of tandemly duplicated genes (CTDGs) contribute to the diversity of many phenotypes, including chemosensation, snake venom, and animal body plans. CTDGs have traditionally been identified subjectively as genomic neighborhoods containing several gene duplicates in close proximity; however, CTDGs are often highly variable with respect to gene number, intergenic distance, and synteny. This lack of formal definition hampers the study of CTDG evolutionary dynamics and the discovery of novel CTDGs in the exponentially growing body of genomic data. To address this gap, we developed a novel homology-based algorithm, CTDGFinder, which formalizes and automates the identification of CTDGs by examining the physical distribution of individual members of families of duplicated genes across chromosomes. Application of CTDGFinder accurately identified CTDGs for many well-known gene clusters (e.g., Hox and beta-globin gene clusters) in the human, mouse and 20 other mammalian genomes. Differences between previously annotated gene clusters and our inferred CTDGs were due to the exclusion of nonhomologs that have historically been considered parts of specific gene clusters, the inclusion or absence of genes between the CTDGs and their corresponding gene clusters, and the splitting of certain gene clusters into distinct CTDGs. Examination of human genes showing tissue-specific enhancement of their expression by CTDGFinder identified members of several well-known gene clusters (e.g., cytochrome P450s and olfactory receptors) and revealed that they were unequally distributed across tissues. By formalizing and automating CTDG identification, CTDGFinder will facilitate understanding of CTDG evolutionary dynamics, their functional implications, and how they are associated with phenotypic diversity.
Bevacizumab in patients (pts) with advanced hepatocellular carcinoma (HCC): Preliminary results of a phase II study with circulating endothelial cell (CEC) monitoring
Authors: D. Malka, C. Dromain, F. Farace, S. Horn, J. Pignon, M. Ducreux, V. Boige
Journal: Journal of Clinical Oncology (2007)

4570 Background: Effective therapy for pts with advanced HCC is still lacking. This phase II trial was designed to define efficacy of bevacizumab in HCC pts. Methods: Pts with unresectable HCC received bevacizumab at 5–10 mg/kg bimonthly. Prior treatment for HCC was allowed. Main ineligibility criteria included Child-Pugh score &gt; 7; CLIP score &gt; 3; recent (&lt; 6 months) thromboembolic event; and anticoagulation or anti-platelet therapy. Propranolol had to be prescribed in case of large esogastric varices. CEC, identified by a CD45- CD31+CD146+7AAD- phenotype by four-color flow cytometry, were measured at day (D) 1,3,15 and 46 after start of treatment. Results: Overall, 30 pts (27 men; median age, 65.5 years [range, 23–84]; histologically proven cirrhosis, 20 pts [Child-Pugh A5/A6/B7: 12/15/3; CLIP 0/1/2/3/4: 1/6/14/6/3] received a median of 6 cycles (range, 2–25; total, 234). As progressive disease (PD) was observed within 16 weeks in 12 pts after inclusion of the first 23 pts treated at 5mg/kg, subsequent pts (n=7) were treated at 10 mg/kg as planned by the protocol design. Of the 30 pts treated at either dose, 6 (20%) discontinued bevacizumab because of variceal hemorrhage (variceal banding successful in every case) (n=3); grade 3 transient ischemic attack (n=1); grade 3 hemorrhagic ascites (n=1); and grade 3 proteinuria (n=1). Grade 1–2 toxicities included fatigue, epistaxis, hypertension, and proteinuria. Among the 24 pts evaluable for efficacy, 3 (12.5%) had partial response (PR), and 13 (54%) had stable disease (SD) (&gt; 16 weeks in 7 pts) (disease control rate (DCR), 67%). Median baseline CEC level (n=21) was 14/ml (range, 0- 71), as compared to 5.5/ml (range, 0–15) in healthy subjects (n=20) and 16/ml (range, 0–179) in pts with various metastatic cancers (n=80). CEC levels increased more than two-fold at D3 in 11 (52%) among 21 pts; a dramatic drop was observed in all PR pts, as well as in a fraction (25%) of SD pts. Conclusions: Bevacizumab is relatively safe and provides an encouraging DCR in patients with HCC and compensated cirrhosis. Accrual is ongoing at the dose of 10 mg/kg. The predictive value of CEC will be presented at the meeting. [Table: see text]
Role of cytokine-induced plasticity in melanoma on invasive, therapy-resistant cells that express EMT-related genes and pathways.
Authors: Jonathan S. Cebon, Matthew Anaka, Christopher Hudson, Pu-Han Lo, Ian D. Davis, Laura J Vella, Aparna Jayachandran, Andreas Behren
Journal: Journal of Clinical Oncology (2012)

8542 Background: The acquisition of new mutations can explain resistance to targeted therapies; however resistance also develops without demonstrable new mutations. To better understand potential mechanisms for treatment failure we studied subpopulations of chemo-resistant cells that can be identified in early passage cell lines and the cellular plasticity that yields these. Methods: Melanoma subpopulations were identified and sorted on the basis of functional assays. Gene expression was evaluated with Illumina HT12 arrays and qPCR to identify potential mechanisms and targets. Sorted cells were evaluated in vitro for the induction of phenotype switching and effects of target inhibition. Results: A subset of slow proliferating label-retaining cells (LRC) was identified using a membrane dye. Direct isolation of LRC from a pt showed these were not an in vitro artefact. LRC isolated from multiple cell lines comprised the majority of cells that resisted cytotoxic drugs and could invade through an artificial extracellular membrane. Gene expression profiling identified a network of over-expressed genes related to epithelial-to-mesenchymal transition (EMT) notable for the expression of Thrombospondin-1 (TSP-1), Transforming-Growth Factor, Beta Induced, (TGFBI) and other extracellular matrix molecules. Initial studies show that LRC shared gene expression characteristics with PLX4032-resistant cells. Although interrogating LRC by qPCR showed up-regulation of the putative melanoma stem cell marker ABCB5 and the lysine specific demethylase Jarid1B, cell sorting and serial re-labelling experiments revealed a dynamic and interchangeable phenotype for these cells, challenging the hierarchical stem cell model for melanoma. The observed slow-cycling and chemo-resistant phenotype could be induced in vitro through TGF beta-mediated phenotype switching and cellular invasion was blocked using an antibody against TSP-1. Conclusions: Cytokine-induced plasticity in melanoma yields invasive, therapy-resistant cells which express EMT-related genes and pathways. We hypothesize that these cells are a source of treatment resistance in vivo and blocking their emergence may prevent treatment failure.
GW26-e0087 Therapeutic Value of Extracorporeal Membrane Oxygenation in Acute Fulminant Myocarditis: An Observational Study
Authors: Changzhi Liu, Jingcheng Lin, Mao Liu, Dezhu Chen, Ruiqiu Zhu, Jianhai Lu, Yunzhao Hu, Zuo Liuer
Journal: Journal of the American College of Cardiology (2015)
GW26-e1477 Effect of the JNK signal pathway on the differentiation of bone marrow mesenchymal stem cells into cardiomyocytes induced by the active principle regions of Yangxin Tongmai Decoction
Authors: Jinghui Zheng, Jian Liang, Shuang Luo, Weixiong Jian, Guilan Ning, Fasheng Wu, Zuling Jiang, Xia Chen, Xiaocong Ma, Mingdong Xu, Tiehua Wang
Journal: Journal of the American College of Cardiology (2015)
Spontaneous Mutation Accumulation in<i>Daphnia pulex</i>in Selection-Free vs. Competitive Environments
Authors: Jullien M. Flynn, Frédéric J.J. Chain, Daniel J. Schoen, Melania E. Cristescu
Journal: Molecular Biology and Evolution (2016)

Understanding the rates, spectra, and fitness effects of spontaneous mutations is fundamental to answering key questions in evolution, molecular biology, disease genetics, and conservation biology. To estimate mutation rates and evaluate the effect of selection on new mutations, we propagated mutation accumulation (MA) lines of Daphnia pulex for more than 82 generations and maintained a non-MA population under conditions where selection could act. Both experiments were started with the same obligate asexual progenitor clone. By sequencing 30 genomes and implementing a series of validation steps that informed the bioinformatic analyses, we identified a total of 477 single nucleotide mutations (SNMs) in the MA lines, corresponding to a mutation rate of 2.30 × 10-9 (95% CI 1.90-2.70 × 10-9) per nucleotide per generation. The high overall rate of loss of heterozygosity (LOH) of 4.82 × 10-5 per site per generation was due to a large ameiotic recombination event spanning an entire arm of a chromosome (∼6 Mb) and several hemizygous deletion events spanning ∼2 kb each. In the non-MA population, we found significantly fewer mutations than expected based on the rate derived from the MA experiment, indicating purifying selection was likely acting to remove new deleterious mutations. We observed a surprisingly high level of genetic variability in the non-MA population, which we propose to be driven by balancing selection. Our findings suggest that both positive and negative selection on new mutations is powerful and effective in a strictly clonal population.
Nuclear expression of aryl hydrocarbon receptor and prognosis for non-small lung cancer.
Authors: H. Chang
Journal: Journal of Clinical Oncology (2010)

10595 Background: Lung cancer is the leading cause of cancer death in many countries including Taiwan. Aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, which translocates from the cytoplasm to the nucleus after activation. Our previous studies showed the positive association between cytoplasmic AhR expression and the expression of cytochrome P450 1B1 (CYP1B1) and p53 in non-small cell carcinomas. In this study, we further investigated the association between nuclear expression (nuclear translocation) of AhR and the expression of p53 and/or CYP1B1 when the presence of nuclear translocation of AhR. We also studied the prognostic value of AhR, CYP1B1 and p53. Methods: Immunohistochemistry for AhR, CYP1B1, and p53 expression was performed on tissue microarrays containing 138 non-small cell carcinoma specimens. Results: Nuclear AhR immunohistochemical expression was detected in 29% of non-small cell carcinomas. Expression of nuclear, but not cytoplasmic, AhR, CYP1B1, and p53 was associated with advanced stage diseases. Nuclear AhR expression was associated with expression of CYP1B1 or p53 in adenocarcinomas. Univariate analysis showed that nuclear AhR- expressing tumors, p53-expressing tumors, smoking and advanced stage diseases had a negative effect on survival. Patients with nuclear AhR-positive tumors had the shortest median survival time (266 days), as compared to patients with both cytoplasmic and nuclear AhR-negative tumors who had the longest (532 days, p < 0.001). Nuclear AhR expression was also associated with poor prognosis in adenocarcinomas. When adjusted for covariates, nuclear AhR expression was independently associated with cancer death in stage III diseases. Conclusions: Nuclear AhR expression not only was associated with the expression of CYP1B1 and p53 in adenocarcinomas, but also was a negative factor for survival in adenocarcinoma patients. No significant financial relationships to disclose.
Interferon Alpha Treated Patients with Chronic Myeloid Leukemia (CML) In Prolonged Complete Remission Have Increased Numbers of NK-Cells and Clonal Gamma-Delta T-Cells, and a Distinct Plasma Cytokine Profile.
Authors: Anna Kreutzman, Peter Rohon, Edgar Faber, Karel Indrak, Vesa Juvonen, Veli Kairisto, Jaroslava Voglova, Marjatta Sinisalo, Emilia Flochova, Petteri Arstila, Kimmo Porkka, Satu Mustjoki
Journal: Blood (2010)