tbuckley/cabot-search huggingface dataset:
ATM Gene Alterations in CLL Patients Induce Gene Profile Clusters and Predict Disease Progression.
Authors: Anna Guarini, Marilisa Marinelli, Simona Tavolaro, Isabella Torrente, Emanuele Bellacchio, Monia Magliozzi, Simona Santangelo, Nadia Peragine, Maria Stefania De Propris, Mauro Nanni, Sabina Chiaretti, Francesca Romana Mauro, Ilaria Del Giudice, Bruno Dallapiccola, Robert Foa
Journal: Blood (2008)
Expression of V617F JAK2 in Mice Leads to MPD Mimicking Human ET, Idiopahtic Myelofibrosis, and PV.
Authors: Kotaro Shide, Haruko K. Shimoda, Takashi Kumano, Kennosuke Karube, Takuro Kameda, Seido Oku, Katsuto Takenaka, Keiko Suzuki, Youko Kubuki, Mine Harada, Kazuya Shimoda
Journal: Blood (2007)
Transfusion Complications in Thalassemia: A Report From the Centers for Disease Control and Prevention (CDC)
Authors: Elliott Vichinsky, Lynne Neumayr, Sean Trimble, Alexis A. Thompson, Patricia Giardina, Alan R. Cohen, Thomas D. Coates, Ellis J. Neufeld, Althea M Grant, Jeanne Boudreaux
Journal: Blood (2011)
288. Development of Cocal Glycoprotein Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T Cells
Authors: Olivier Humbert, Donald Gisch, Martin Wohlfahrt, Phil Greenberg, Tom Schmitt, Grant Trobridge, Hans-Peter Kiem
Journal: Molecular Therapy (2016)

Lentiviral vectors (LVs) are routinely used for stable gene transfer and have demonstrated great promise in hematopoietic stem cell gene therapy and also immunotherapy using genetically modified T cells. LVs are commonly pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G), which confers broad tropism to the vector and allows for vector concentration by centrifugation. However, the use of VSV-G has several limitations, such as susceptibility to inactivation by human serum complement making it unsuitable for in vivo delivery. Furthermore, VSV-G is toxic when constitutively expressed, which has impeded efforts to generate stable producer cell lines. In this study, we first validate the use of cocal vesiculovirus envelope to pseudotype LVs by demonstrating that cocal LVs transduce hematopoietic stem cells and CD4+ T cells more efficiently than VSV-G LVs. We also provide evidence that cocal and VSV-G envelopes use the same receptor for cell entry. We then describe the development of two high-titer, cocal-pseudotyped, LV producer cell lines for a GFP reporter and for a WT1 tumor-specific T cell receptor (TCR). The different 3rd generation lentiviral helper genes were sequentially introduced in HEK293T cells by co-transfection with plasmids encoding antibiotic resistance genes followed by selection to allow for stable protein expression. Cells expressing the cocal envelope produced over 10-times more infectious LV particles as compared to VSV-G expressing cells. High-titer cocal producer cells were isolated by screening for best single clones, which were capable of generating concentrated titers above 108 infectious units per mL. We found that these producer cells were stable after serial passages for over 3 months, with no drop in titer detected over time. The resulting GFP and WT1-TCR vectors performed at least as well as identical vectors made with our standard transient transfection protocol for the transduction of CD34+ and CD4+ T cells, respectively. Cocal LV producer cells were also adapted for growth in suspension, serum-free culture, which will facilitate efforts for the scaling up of vector production. In summary, we have successfully developed two independent LV producer cells lines with clinically usable titers. The broad applicability of our cocal packaging cell line offers a promising tool toward the generation of large-scale, clinical grade LV.
Abstract 1139: Tumor-associated fibroblasts facilitate head and neck cancer metabolism
Authors: Dhruv Kumar, Partha Kasturi, Bennett Van Houten, Sufi Thomas
Journal: Cancer Research (2015)

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy affecting 40,000 cases in the USA annually, associated with poor prognosis and significant morbidity. HNSCC tumors are dysplastic with up to 80% fibroblasts. We reported that tumor associated fibroblasts (TAFs) facilitate HNSCC progression. However, the molecular mechanisms that facilitate TAF-mediated tumor growth and metastasis remain unknown. Unlike normal cells, malignant cells often display increased glycolysis, even in the presence of oxygen; a phenomenon known as the Warburg effect. As a consequence, there is an increase in lactic acid (LA) production. It has been reported that HNSCC tumors have high LA levels that correlate with reduced survival. The mechanisms whereby HNSCC tumors survive in highly acidic conditions remain unknown. We reported that activation of the receptor tyrosine kinase, c-Met, by TAF-secreted hepatocyte growth factor (HGF) contributes to HNSCC progression. The role of TAFs-secreted HGF in HNSCC metabolism remains unknown. In addition, we were unable to detect HGF secretion by HNSCC indicating paracrine activation of c-Met. In nasopharyngeal carcinoma, c-Met inhibition down regulates the TP53-induced glycolysis and apoptosis regulator (TIGAR) and NADPH production. We hypothesized that TAF-secreted HGF regulates HNSCC glycolysis via c-Met. Further, HNSCC cells regulate metabolism in TAFs. We found that PF2341066, a c-Met inhibitor significantly decreased glycolysis (p = 0.0023) and hexokinase-II levels in HNSCC cells. These data demonstrate that c-Met regulate glycolysis in HNSCC through modulation of hexokinase-II. In admixed cultures, HNSCC and TAFs demonstrate higher expression of the bi-directional lactate transporter monocarboxylate transporter 1 (MCT-1). Our data demonstrate that TAFs have a higher capacity to proliferate than HNSCC in the presence of LA. Others have reported that NFκB increases MCT-1 levels in tumor associated stroma under high LA conditions. In ongoing studies, we will determine the role of HNSCC in regulating MCT-1 levels in TAFs. Further, the role of c-Met in regulating expression of MCT-1 in HNSCC will be elucidated. Based on the cumulative data we conclude that TAF-secreted HGF regulates HNSCC metabolism and TAFs utilize LA as a carbon source making the microenvironment more conducive to tumor progression. Keywords : HNSCC, TAFs, HGF, Glycolysis, OXPHOS Citation Format: Dhruv Kumar, Partha Kasturi, Bennett Van Houten, Sufi Thomas. Tumor-associated fibroblasts facilitate head and neck cancer metabolism. [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 1139. doi:10.1158/1538-7445.AM2015-1139
Late-breaking abstract: COPD healthcare research: Multicentre study on COPD out-patient healthcare in Germany (ORCAS)
Authors: Christian Witt, Melissa Jehn, Uta Liebers, Robert Ehrlich, Ilka Krohn, Schremmer Dieter
Journal: European Respiratory Journal (2014)

Background: In accordance with current guidelines for COPD management, there is a need to investigate daily clinical practice for guiding therapy in COPD.  Objectives: The purpose of this nationwide German study is to characterise COPD patients in order to identify predictors that determine the necessity for therapeutic adjustments to be made.  Methods: In order to evaluate COPD out-patient healthcare, a total of 1,807 study sites representing 9,383 patients were enrolled in this multicentre cross-sectional study. General practitioners were asked to document clinical patient data by means of a comprehensive medical questionnaire. Data acquisition lasted from January until July 2013.  Results: In our study cohort, 27 % of patients were classified as GOLD I, 53 % as GOLD II, 16 % as GOLD III and 3 % as GOLD IV. 80.4 % of patients suffered from exacerbation of COPD during the last 12 months, with a frequency of 2.4 ± 1.9 exacerbations per year. Worsening symptoms were stated by 60 % of COPD patients during the day, of whom 40.2 % experienced them mostly in the morning, and 17 % at night. 68% of patients reported sleep disturbances, triggered particularly by coughing (60.1 %) and breathlessness (37.9 %). Overall, disease progression (51.3 %) and exacerbation of COPD (32.6 %) was the most frequent cause given for changing current medication. The addition of long-acting muscarinic antagonists (LAMAs) dominated among doctors with prescription increasing from 38.7% to 85.2%.  Conclusion: COPD progression, including exacerbation, is highly prevalent in the out-patient setting. Long-acting muscarinic antagonists (LAMAs) are the most popular choice when prescribing therapy change in COPD.
Abstract 3960: The role and therapeutic potential of miRNAs in colorectal liver metastasis
Authors: Smiti Snigdha Sahu, Sarah Nabinger, Jiang Guanglong, Allison Bates, Sangbin Lee, Tanaka Hiromi, Yunlong Liu, Janaiah Kota
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Liver metastasis occurs in 60% of CRC patients and usually responds poorly to treatment - contributing to mortality rate. MicroRNAs (miRNAs) are highly conserved, endogenously encoded small, non-coding RNA molecules regulating global gene expression. Their role in cancer pathogenesis, including CRC, has been well documented. Detailed miRNA expression analysis on a large cohort of CRC tumors is needed to identify clinically relevant miRNAs and explore their potential to target liver metastases. We analyzed miRNA expression data of 406 CRC tumors from publically available CRC genome sequencing project and identified 58 miRNAs, which were significantly downregulated. Using miRNA target prediction analysis, 10 miRNAs were selected for further studies as they were either known to target genes in cellular pathways associated with CRC liver metastases, or located within a chromosomal loci commonly lost in colorectal liver metastases. qPCR analysis of these 10 selected miRNAs in primary and colorectal liver metastasis tissues and in CRC cell lines demonstrated four miRNAs; miR-132, miR-378f, miR-605, and miR-1976 that are significantly down-regulated with &amp;lt;2 fold change (p&amp;gt;0.05). To investigate the anti-tumorigenic and metastatic properties of miR-132, -378f, -605, and -1976, we transfected 3 different CRC cell lines (SW620, HCT-116, and CT-26) with miR-mimics and subjected them to cell proliferation, apoptosis, soft agar, invasion, and migration assays. Ectopic expression of miR-378f, -605, and -1976 suppressed CRC cell proliferation, anchorage independent growth, migration, and invasion and increased apoptosis. Interestingly, CRC patients with high miR-378f and miR-1976 had better survival compared to low expressing patients (p&amp;lt;0.044). In conclusion, our in vitro findings suggest anti-tumorigenic/metastatic properties of miR-378f, -605, and -1976 in CRC. A further understanding of their function and in vivo therapeutic evaluation may help in developing novel therapeutic strategies for this malignancy. Citation Format: Smiti Snigdha Sahu, Sarah Nabinger, Jiang Guanglong, Allison Bates, Sangbin Lee, Tanaka Hiromi, Yunlong Liu, Janaiah Kota. The role and therapeutic potential of miRNAs in colorectal liver metastasis. [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 3960. doi:10.1158/1538-7445.AM2015-3960
A phase II study of paclitaxel poliglumex (PPX), temozolamide (TMZ), and radiation (RT) for newly diagnosed high-grade gliomas.
Authors: S. A. Jeyapalan, M. Goldmann, J. Donahue, H. Elinzano, D. L. Evans, B. M. O'Connor, M. A. Puthawala, A. Oyelese, D. Cielo, M. Blitstein, M. Dargush, A. Santaniello, M. Constantinou, T. Dipetrillo, H. Safran
Journal: Journal of Clinical Oncology (2011)

2036 Background: PPX is a drug conjugate that links paclitaxel to a polyglutamic acid polymer yielding a radiosensitization index of 4-8 as compared to 1.5-2 for paclitaxel. Phase I/II studies of PPX in esophageal cancer established that 50 mg/m2/week of PPX can be safely administered with concurrent chemo/RT. The primary objective of this study is to determine the safety of PPX with standard TMZ and RT for high-grade gliomas. Methods: Patients received weekly PPX 50 mg/ m2 and daily TMZ 75 mg/m2 for 6 weeks with concomitant RT (60 Gy). Adjuvant chemotherapy with TMZ (200 mg/m2/d x 5 d), every 28 days, was started 1 month after completion of chemoradiation. Results: This study completed planned accrual of 25 patients (median age, 60 years; 48% male; 60% GBMs). Grade 4 hematologic toxicity occurred in 6 of 25 patients, starting 4-6 weeks after initiating PPX/TMZ/RT and lasting up to 5 months. Median follow-up is 13 months (range, 1-24). 6- and 12- month PFS were 76% (19/25 patients) and 52% (13/25). The 6-month PFS of GBM patients was 66.7% (10/15). Median PFS is 12.5 months. Pseudoprogression (PsdP) was prominent. 16 patients had post-PPX enhancement, 5 were classified with progressive disease (mean time to progression = 4.6 months; rCBV at progression ranged from 2.66 to 6.25, mean = 4.1) and 11 remain on trial. For cases of PsdP, rCBV at time of initial progressive enhancement ranged from 0.63 to 5.28 (mean 2.55), but subsequently stabilized or monotonically decreased, with no statistically significant increased rCBV compared with initial post-PPX baseline. rCBV in progressive disease was not found to be significantly larger than rCBV at initial progressive enhancement in PsdP (p=0.16, unpaired t-test). 5 patients with apparent progression by MRI had resection (2) or biopsy (3). Pathologic specimens showed gliotic edematous brain and all had Ki-67 < 5%. Conclusions: PPX is a promising radiation enhancer in high grade gliomas. Stable or decreasing rCBV on longitudinal follow-up exams may be a better indicator of PsdP than individual absolute rCBV values. Hematologic toxicity may be due to interaction between PPX and TMZ. A randomized study of PPX/RT versus TMZ/RT for with non-methylated MGMTpatients is planned.
16S pan-bacterial PCR can accurately identify patients with ventilator-associated pneumonia
Authors: Andrew Conway Morris, Naomi Gadsby, James P McKenna, Thomas P Hellyer, Paul Dark, Suveer Singh, Timothy S Walsh, Danny F McAuley, Kate Templeton, A John Simpson, Ronan McMullan
Journal: Thorax (2016)

Ventilator-associated pneumonia (VAP) remains a challenge to intensive care units, with secure diagnosis relying on microbiological cultures that take up to 72 hours to provide a result. We sought to derive and validate a novel, real-time 16S rRNA gene PCR for rapid exclusion of VAP. Bronchoalveolar lavage (BAL) was obtained from two independent cohorts of patients with suspected VAP. Patients were recruited in a 2-centre derivation cohort and a 12-centre confirmation cohort. Confirmed VAP was defined as growth of &gt;10<sup>4</sup> colony forming units/ml on semiquantitative culture and compared with a 16S PCR assay. Samples were tested from 67 patients in the derivation cohort, 10 (15%) of whom had confirmed VAP. Using cycles to cross threshold (C<sub>t</sub>) values as the result of the 16S PCR test, the area under the receiver operating characteristic (ROC) curve (AUROC) was 0.94 (95% CI 0.86 to 1.0, p&lt;0.0001). Samples from 92 patients were available from the confirmation cohort, 26 (28%) of whom had confirmed VAP. The AUROC for C<sub>t</sub> in this cohort was 0.89 (95% CI 0.83 to 0.95, p&lt;0.0001). This study has derived and assessed the diagnostic accuracy of a novel application for 16S PCR. This suggests that 16S PCR in BAL could be used as a rapid test in suspected VAP and may allow better stewardship of antibiotics. <h3>Trial registration number</h3> VAPRAPID trial ref NCT01972425.
Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) in Children with Acute Leukemia: Risks and Benefits of Umbilical Cord Blood (CB) Versus HLA A, B, C, DRB1 Allele-Matched Bone Marrow (BM).
Authors: Mary Eapen, Pablo Rubinstein, Mei-Jie Zhang, Cladd Stevens, Joanne Kurtzberg, Andromachi Scaradavou, Mary M. Horowitz, John E. Wagner
Journal: Blood (2006)
Abstract 988: Triple negative breast cancer cells have higher dependence on mitophagy for their survival as compared to hormone positive breast cancer cells
Authors: Bhawana Dikshit, Aakansha Rai, Soumya Sinha Roy
Journal: Cancer Research (2015)

Abstract Autophagy is a key pathway utilised by the cells to clear the dysfunctional cellular components and maintain homeostasis. However cancer cells having defective apoptosis, deploy autophagy as a survival mechanism by limiting tumor necrosis and metabolic stress. Autophagy has been reported to be upregulated in triple negative breast cancers which are categorized as the most aggressive breast cancers with poor prognosis. Nevertheless the exact mechanism of autophagic upregulation in TNBC is still elusive. Therefore analyzing pathways specifically altered in these tumors might provide better targets for therapeutic intervention. Results: In the present study we observed higher basal autophagy in TNBC cell line MDA MB 231 as compared to triple positive MCF7 cells as analyzed by the presence of higher number of GFP-LC3 puncta in the former. Treatment with 20μM of autophagy inhibitor chloroquine for 48 hrs led to significant cell death in TNBC cell line as compared to MCF7 whereas treatment with 20μM of PI3K inhibitor wortamannin did not significantly affected the survival of TNBC and MCF7 cells. Further the analysis of autophagy markers revealed higher LC3B and Beclin1 levels as compared to ATG5 and ATG7 levels in MDA MB 231 cells both at mRNA and protein levels as analyzed by qPCR and western blot. Also the knockdown of ATG7 by ATG7 shRNA did not significantly affected the survival of TNBC cells. Conclusion: Thus in this study we aim to highlight the difference in the expression of autophagy markers and the effect of autophagy inhibitors wherein only late phase of autophagy seems to significantly upregulated in TNBC. The difference can be attributed to the dependence of TNBC cells upon ‘late phase autophagy’ or particularly ‘mitophagy’ that is crucial for rapid clearance of misfolded proteins and dysfunctional mitochondria as has been reported in TNBCs. Further study to dissect the mechanism of selective upregulation of ‘late phase autophagy’or ‘mitophagy’ in TNBC might provide novel targets for treatment strategies in these breast cancers. Citation Format: Bhawana Dikshit, Aakansha Rai, Soumya Sinha Roy. Triple negative breast cancer cells have higher dependence on mitophagy for their survival as compared to hormone positive breast 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 988. doi:10.1158/1538-7445.AM2015-988
Who Participates in an Adult Cooperative Group Trial for Adolescent and Young Adults (AYAs)? Baseline Demographic and Psychosocial Characteristics of AYAs Enrolled On Intergroup Trial C10403 for Acute Lymphoblastic Leukemia (ALL)
Authors: Lori S. Muffly, Wendy Stock, Kate Breitenbach, Flora Mulkey, Selina Luger, Anjali Advani, Edy Parker, Matthew C Foster, Michaela Liedtke, Reynaldo Garcia, Kristin Coffan, Joselene Sipin-Sayno, Jennifer McNeer, Martin S Tallman, Frederick R. Appelbaum, Richard M. Stone, Richard A. Larson
Journal: Blood (2012)
Abstract 3200: Acidic microenvironment activates endoplasmic reticulum stress pathways through GPR4 in human vascular endothelial cells
Authors: Lixue Dong, Elizabeth A. Krewson, Li V. Yang
Journal: Cancer Research (2015)

Abstract The tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (“Warburg effect”), and defective vasculature that is inefficient to deliver oxygen and nutrients and to remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4, a member of the proton-sensing G protein-coupled receptors, has high expression in endothelial cells. We have previously reported that acidosis induces a broad inflammatory response in human vascular endothelial cells through the GPR4 receptor. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress genes such as CHOP and ATF3. In the current study, we have thoroughly examined acidosis/GPR4-induced ER stress pathways in human umbilical vein endothelial cells (HUVEC). All three arms of the ER stress/unfolded protein response (UPR) pathways are activated by acidosis in HUVEC, as we observed an increased expression of phosphorylated eIF2α, phosphorylated IRE1α, and cleaved ATF6 upon acidic pH treatment. In addition, the expression of other downstream mediators of the UPR, such as ATF4, ATF3, CHOP and spliced XBP1, were also induced by acidosis at the mRNA and/or protein levels. Through genetic modifications and a small molecule inhibitor to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis stimulation. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in endothelial cells may regulate angiogenesis and inflammatory response in the acidic tumor microenvironment. Citation Format: Lixue Dong, Elizabeth A. Krewson, Li V. Yang. Acidic microenvironment activates endoplasmic reticulum stress pathways through GPR4 in human vascular endothelial 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 3200. doi:10.1158/1538-7445.AM2015-3200
Impact of Pretransplant Cytogenetics and Marrow Remission Status on Outcome of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Stem Cell Transplantation Conditioned with Busulfan and Fludarabine
Authors: Ebru Koca, Rima M Saliba, Marcos De Lima, Uday Popat, Partow Kebriaei, Gabriela Rondon, Sergio Giralt, Borje S Andersson, Richard E Champlin
Journal: Blood (2008)
Docosahexaenoic Acid and Eicosapentaenoic Acid Are Keyplayers of the Cytotoxicity of a Parenteral Fish Oil Emulsion in Acute Myeloid Leukemia Cell Lines and Primary Blasts and This Effect Is Additive with Chemotherapy in Vitro
Authors: Emmanuel Gyan, Christelle Debeissat, Elfi Ducrocq, Jorge Domenech, Olivier Herault
Journal: Blood (2011)
Efficacy of Frontline Nilotinib Therapy in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myeloid Leukemia in Early Chronic Phase (CML-CP)
Authors: Alfonso Quintás-Cardama, Hagop M Kantarjian, Rajyalakshmi Luthra, Susan o'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Stefan Faderl, Marina Konopleva, William G. Wierda, Elizabeth Burton, Jorge E. Cortes
Journal: Blood (2011)