tbuckley/cabot-search huggingface dataset:
Comparison of Outcomes After Related and Unrelated Hematopoietic Cell Transplantation in Adults with Myelodysplastic Syndromes: A Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)
Authors: Wael Saber, Corey Cutler, Ryotaro Nakamura, Mei-Jie Zhang, Ehab Atallah, J. Douglas Rizzo, Richard T. Maziarz, Jorge E. Cortes, Matt Kalaycio, Mary M. Horowitz
Journal: Blood (2012)
Abstract 15335: Sex-Specific Cardiomyocyte Death in Heart Failure due to Sex-Specific Calcium Remodeling
Authors: Georgios Kararigas, Cristina E Molina, Holger Summer, Istvan Baczko, Stefan Golz, Vera Regitz-Zagrosek
Journal: Circulation (2014)

L-type calcium (Ca2+) channels (LTCCs) play a key role in mitochondrial Ca2+ uptake, which may result in mitochondrial depolarization and metabolic collapse. Both apoptosis and necrosis occur in a sex-specific manner in heart failure (HF). However, the underlying mechanisms are unknown. We hypothesized significant sex differences in the cardiac transcriptome of end-stage non-ischemic dilated cardiomyopathy (DCM) patients. We compared left ventricular (LV) samples of age- and medication-matched male ( n = 5) and female ( n = 5) DCM patients with male ( n = 10) and female ( n = 8) controls by genome-wide expression profiling. Single gene differential analysis identified 4273 transcript clusters regulated in male, 1344 in female and 2817 in both male and female LVs (adjusted P &lt; 0.01). Pathway analysis (adjusted P &lt; 0.05) revealed induction of ECM-receptor interaction and several inflammatory pathways in male LVs, while oxidative phosphorylation and proteasome pathways were repressed. In female LVs, the Wnt and Hedgehog signaling pathways were induced, while the mTOR signaling pathway was repressed. Ca2+ signaling pathway was induced in both sexes. However, male LVs had a significantly higher induction of ca. 30% of genes encoding ion channels, accessory beta subunits and regulatory proteins than female LVs. Next, we isolated ventricular myocytes (VMs) from DCM patients and measured sarcoplasmic reticulum (SR) Ca2+ load and L-type Ca2+ current (ICa,L) by patch-clamp. While there were no sex differences in SR Ca2+ load, there was a 2-fold increase in ICa,L density in male vs. female VMs ( n = 6-8 cells/group; each cell originated from a different individual; P &lt; 0.05). The cytosolic release of cytochrome c was significantly higher in male than female LVs ( P &lt; 0.05). In view of that the anti-apoptotic protein BCL2 is involved in reducing recruitment of LTCCs, which in turn prevents mitochondrial Ca2+ overload, we found significantly higher BCL2 protein levels in female than male LVs ( P &lt; 0.05). Ca2+-mediated dephosphorylation of pyruvate dehydrogenase was higher in male than female LVs ( P &lt; 0.01) indicating more Ca2+ present in male mitochondria. We conclude that sex-specific regulation of Ca2+ homeostasis may account for sex differences in apoptosis and necrosis in HF.
P0814 : Hepatic improvement in response to ledipasvir/sofosbuvir/ribavirin as measured by the hepquant® (HQ)-shunt test in liver transplant (LT) recipients with allograft fibrosis or cirrhosis and non-LT patients with decompensated cirrhosis
Authors: J.R. Burton, J.G. O’Leary, S. Helmke, A. Herman, M. Cookson, S. Lauriski, J.F. Trotter, J. Denning, P. Pang, J. McHutchison, M.P. Curry, G.T. Everson
Journal: Journal of Hepatology (2015)
PTU-056 Efficacy of combination therapy for chronic hepatitis C: the Leeds experience
Authors: A C Ford, S A Sheridan, C M Wigglesworth, J Rehman, M A Aldersley, M H Davies, C E Millson, R L Jones
Journal: Gut (2010)

<h3>Introduction</h3> Combination therapy, with pegylated interferon and ribavarin, is the mainstay of treatment for chronic hepatitis C (CHC), and has been shown to be effective in achieving clearance of the virus in randomised controlled trials. We report efficacy of combination therapy in normal clinical practice, using a large cohort of CHC patients treated in a single tertiary referral centre in Leeds, UK. <h3>Methods</h3> Data for all individuals receiving combination therapy for CHC were collected prospectively between February 2001 and May 2008. Patient age, gender, ethnicity, type of interferon used (α-2a or α-2b), route of acquisition, genotype, presence of cirrhosis, body mass index (BMI), alcohol use, and history of previous psychiatric illness were recorded prior to commencement of therapy. Data from individuals being re-treated for CHC were not analysed. We defined efficacious therapy as a sustained viral response (SVR) 6 months after end of treatment with an undetectable hepatitis C viral load by PCR. Individuals with no SVR data at 6 months after end of therapy were classed as treatment failures. <h3>Results</h3> Between February 2001 and May 2008 there were 394 individuals with CHC who commenced combination therapy (257 (65%) male, 137 female, mean age 42 years (range 21–74)). Mean BMI at commencement of therapy was 26.6 (range 17.3–57.8). Genotypes were as follows: 139 (35%) genotype 1, 30 (8%) genotype 2, 206 (52%) genotype 3, 15 (4%) genotype 4, and one patient had genotype 5. A definite route of acquisition was determined in 280 (71%) individuals: intravenous drug use in 184 (47%) individuals, blood transfusion in 55 (14%), injection/needlestick injury in 20 (5%), sexual in 15 (4%), tattooing in 6 (1.5%), and in the remaining 114 this issue was unclear. 301 (76%) individuals were White Caucasian and 84 (21%) South Asian. There were 99 (25%) individuals with biopsy-proven cirrhosis, 104 (26%) consumed alcohol, and 75 (19%) had a history of psychiatric illness. The majority of patients (76%) received pegylated interferon α-2b. The overall SVR rate was 61% (240 of 394 treated), and SVRs by genotype were as follows: 44% (61/139) for genotype 1, 73% (22/30) for genotype 2, 73% (151/206) for genotype 3, 27% (4/15) for genotype 4, and 100% (1/1) for genotype 5. <h3>Conclusion</h3> Data from this large cohort of patients with CHC treated with combination therapy demonstrate SVR rates comparable to those in the clinical trial literature, using strict criteria to define an SVR, emphasising that results from intervention studies can be extrapolated to patients encountered in usual clinical practice.
A Phase II Study of Valproic Acid and Lenalidomide Combination Therapy in Patients with Myelodysplastic Syndrome (MDS) and a Favorable Risk Proﬁle: Final Results of the Valena Trial
Authors: Andrea Kuendgen, Michael Lübbert, Richard F. Schlenk, Uwe Platzbecker, Detlef Haase, Torsten Haferlach, Susanne Schnittger, Aristoteles Giagounidis, Carolin Brings, Ulrich Germing, Rainer Haas, Norbert Gattermann
Journal: Blood (2014)
A Framework for Unrestricted Prenatal Whole-Genome Sequencing: Respecting and Enhancing the Autonomy of Prospective Parents
Authors: Stephanie C. Chen, David T. Wasserman
Journal: The American Journal of Bioethics (2016)

Noninvasive, prenatal whole genome sequencing (NIPW) may be a technological reality in the near future, making available a vast array of genetic information early in pregnancy at no risk to the fetus or mother. Many worry that the timing, safety, and ease of the test will lead to informational overload and reproductive consumerism. The prevailing response among commentators has been to restrict conditions eligible for testing based on medical severity, which imposes disputed value judgments and devalues those living with eligible conditions. To avoid these difficulties, we propose an unrestricted testing policy, under which prospective parents could obtain information on any variant of known significance after a careful informed consent process that uses an interactive decision aid to deliver a mandatory presentation on the purposes, techniques, and limitations of genomic testing, as well as optional resources for reflection and consultation. This process would encourage thoughtful, informed deliberation by prospective parents before deciding whether or how to use NIPW.
Abstract 637: Preclinical activity of hLL2-PBD, a novel anti-CD22 antibody-pyrrolobenzodiazepine (PBD) conjugate in models of non-Hodgkin lymphoma
Authors: Francesca Zammarchi, David Williams, Karin Havenith, Francois D'Hooge, Philip W. Howard, John A. Hartley, Patrick van Berkel
Journal: Cancer Research (2015)

Abstract CD22 is a type I transmembrane sialoglycoprotein, which expression is restricted to the B-cell lineage. CD22 is also found highly expressed on most malignant mature B cells, including follicular non-Hodgkin lymphoma (NHL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL). The differential and favorable expression profile of CD22 in normal and tumor tissues, together with its rapid internalization upon binding with a ligand or antibody, make CD22 an attractive target for an antibody drug conjugate (ADC) mediated treatment of B-cell malignancies. hLL2-PBD is an ADC composed of the humanized monoclonal antibody epratuzumab (hLL2) against human CD22 stochastically conjugated via a valine-alanine cleavable, maleimide linker to a PBD dimer. PBD dimers represent a novel class of payloads, which bind in the DNA minor groove and form highly cytotoxic DNA interstrand cross-links. The average drug to antibody ratio (DAR) of hLL2-PBD is 2. In vitro, hLL2-PBD showed potent and specific cytotoxicity, as assessed by the MTS assay, in the CD22-positive human Burkitt's lymphoma-derived cell lines Ramos and Daudi and the human diffuse large B-cell lymphoma-derived cell line WSU-DLCL2. In vivo, hLL2-PBD demonstrated potent anti-tumor efficacy in subcutaneously (s.c.) implanted Daudi and Ramos xenograft models. In the Daudi model, hLL2-PBD, administered as a single dose at either 0.1 or 0.3 mg/kg, achieved dose-dependent anti-tumor activity, resulting in significant increase in survival. At 0.3 mg/kg, hLL2-PBD induced complete tumor regression in all treated animals. In the Ramos xenograft model, a single dose of 1 mg/kg of hLL2-PBD achieved strong tumor regression. Moreover, hLL2-PBD achieved a superior anti-tumor activity compared to Hu10F4-vcMMAE, a CD22-targeting ADC with the auristatin payload vcMMAE and a DAR of 4 (Genentech Inc.), when tested at 1 mg/kg, single dose. Pharmacokinetic (PK) analysis of hLL2-PBD in CB.17 SCID mice showed a favorable PK profile, with a half-life of approximately 12 days. In conclusion, these data demonstrate the potent in vitro and in vivo anti-tumor activity of hLL2-PBD against CD22-positive hematological tumors and warrant further development of this ADC into the clinic. Citation Format: Francesca Zammarchi, David Williams, Karin Havenith, Francois D'Hooge, Philip W. Howard, John A. Hartley, Patrick van Berkel. Preclinical activity of hLL2-PBD, a novel anti-CD22 antibody-pyrrolobenzodiazepine (PBD) conjugate in models of non-Hodgkin lymphoma. [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 637. doi:10.1158/1538-7445.AM2015-637
Abstract LB-084: A role of long interspersed nuclear element-1 (LINE-1) for telomere maintenance in cells with alternative lengthening of telomeres
Authors: Thomas Aschacher, Brigitte Wolf, Philip Kienzl, Florian Enzmann, Barbara Messner, Klaus Holzmann, Michael M. Bergmann
Journal: Cancer Research (2015)

Abstract LINE-1 elements (L1s, long interspersed nuclear elements-1) are abundant retrotransposons in the eukaryotic genome that are primarily known for facilitating aberrant recombination. Here we show the involvement of L1 in telomere maintenance in cells using the less characterized alternative lengthening of telomeres (ALT) mechanism. Interestingly, ALT cells show significantly higher expression levels of L1 when compared to TA cells. Knock-down (KD) of L1 in ALT cell lines was associated with reduced length of telomeres, an increase in telomere dysfunction foci, a reduced expression of ALT characteristics such as c-circles and ALT associated PML bodies, and a decreased growth. On the other hand, overexpression of L1 in ALT cell lines lead to a higher rate of c-circles and increased length of telomeres. LINE-1 not only bound to the C-strand of telomeric DNA but also to telomere-repeat-containing RNA (TERRA), a multifunctional component of human telomeres that is highly expressed in ALT cells and has been described to be involved in telomere stabilization. Whereas L1-KD decreased overall TERRA, L1 overexpression increased this RNA. Moreover, L1 KD abrogated the nuclear retention of TERRA. Moreover, the L1-ribonucleoprotein can use the polyadenylated form of TERRA as a template to generate telomere-specific DNA. Thus, L1 appears to contribute to telomere maintenance by a mechanism involving TERRA, either by ensuring its nuclear localization or by using this RNA as a template for the generation of telomere-specific DNA. Our findings now render L1 proteins a promising target in cancer therapy by interfering with telomere lengthening in ALT cells. Citation Format: Thomas Aschacher, Brigitte Wolf, Philip Kienzl, Florian Enzmann, Barbara Messner, Klaus Holzmann, Michael M. Bergmann. A role of long interspersed nuclear element-1 (LINE-1) for telomere maintenance in cells with alternative lengthening of telomeres. [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 LB-084. doi:10.1158/1538-7445.AM2015-LB-084
Guideline adherence rates and costs of chemotherapy treatment for NSCLC patients treated in U.S. community oncology practices.
Authors: Z. Wang, I. Aksamit, L. Tuscher, B. S. Tom, C. B. Del Buono, U. Campbell, S. Shields, T. Lam, K. B. Whitlock, M. Mayo, J. Huang, A. M. Christman, K. A. Bergstrom
Journal: Journal of Clinical Oncology (2011)

7538 Background: Adherence to national treatment guidelines (TG) is a key step to improving the quality and outcomes of cancer treatment in the U.S. This study examined guideline adherence rates and cost of chemotherapy treatment for NSCLC patients treated in the adjuvant (Adj) and first-line metastatic (Met) settings in U.S. community oncology practices. Methods: Using a large U.S. medical oncology clinical database derived from web-based drug dispensing technology, adult patients (Pat) with NSCLC treated with Adj and Met chemotherapy were identified from 7/1/09-06/30/10. Regimens (Reg) utilized were compared to national guideline recommendations. Costs based on Medicare (MC) reimbursement were compared. Results: A total of 811 Adj and 2,761 Met regs were administered by 333 practices across 41 states. Median patient age was 68 and 67 yrs in the Adj and Met groups respectively. National guidelines recommend 26 and 67 regs (TG-Reg) for Adj or Met treatment, respectively. The rate of guideline adherence was significantly higher in the Met group than the Adj group. Carboplatin (Carbo)-containing regs were administered (Adm) significantly more than Cisplatin (Cis)-containing regs in both groups. Reg costs based on MC national reimbursement rates (including antineoplastic and supportive care drugs, CPT and some lab codes) for the top 5 regs in the Adj and Met settings varied. A standard course of therapy in the Adj group ranged from $2,803 [Carbo(AUC5)D1-Eto(100)D1-3 q21d] to $7,362 [Carbo(AUC2)D1,8,15-Pac(75)D1,8,15 q28d]. Reg costs in the Met group ranged from $3,297 [Carbo(6)D1-Pac(200)D1 q21d] to $29,322 [Carbo(AUC6)D1-Pac(200)D1-Bev(15)D1 q21d] based on 3 months of therapy. Conclusions: The rate of guideline adherence was significantly higher in the Met group than in the Adj group. Carbo-containing regs were administered more than Cis-containing regs. There were a large number of unique regimens administered in the Met group. Costs for the top 5 regs vary considerably. TG adherence. TG-Reg (N) Pat (N) Unique Reg adm (N) TG-Reg Adm (N) Pat treated by TG-Reg (N) Pat treated by top 5 Reg (%) TG-Reg in top 10 Reg (N) TG adherence (%) Adj 26 811 45 15 427 69.9 6 52.6 Met 67 2,761 138 45 2,009 37.3 9 72.8* * P < 0.0001 by X2 test.
Next-Generation STAT3 Inhibitors As Targeted Therapeutics in Chronic Myeloid Leukemia.
Authors: Ira L Kraft, Anna M. Eiring, Brent DG Page, Clinton C Mason, Zhimin Gu, Jamshid S Khorashad, David J Anderson, Anthony D Pomicter, Kimberly R Reynolds, Johanna Estrada, Matthew S Zabriskie, Patrick T Gunning, Thomas O'Hare, Michael W Deininger
Journal: Blood (2012)
Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT).
Authors: A. Jain, M. J. Brames, D. J. Vaughn, L. H. Einhorn
Journal: Journal of Clinical Oncology (2011)

4579 Background: Salvage chemotherapy with Ifosfamide based regimen or high dose chemotherapy (HDCT) has curative potential in GCTs. We still need novel therapies for patients where cure is not possible. Oxaliplatin has single agent activity in refractory GCTs. Bevacizumab in combination with chemotherapy has activity in many solid tumors but has not been studied in GCTs. This is the first study of bevacizumab in refractory GCT patients. Methods: Patients with serologically or histologically proven metastatic GCT who have failed cisplatin based combination chemotherapy and progressed on salvage therapy were eligible. Prior HDCT and paclitaxel plus gemcitabine were required unless late relapse or primary mediastinal non-seminomatous GCT (NSGCT). Oxaliplatin was given 85 mg/m2 and bevacizumab 10 mg/kg every 2 weeks with a maximum of 14 cycles. Results: 25 total patients have been enrolled with 24 evaluable and 1 too early to evaluate. 9 were late relapses and 5 with primary mediastinal NSGCT. Median number of previous chemotherapies was 4 including 13 with prior HDCT. Median number of cycles administered was 5. There were 7 (29%) objective responders. Median duration of response was 6 months (range 4 to 22 months). Of these 7 patients 3 had normalization of HCG and/or AFP. One additional patient had serologic response (>1 log reduction in HCG) for 5 months with stable radiographic lesions. Median survival was 8 months (range 2 to 40 months). Four patients had Grade 3 adverse events (peripheral neuropathy, hypertension, seizures and DVT). Conclusions: Oxaliplatin plus bevacizumab has promising activity in heavily pretreated GCTs with manageable toxicity.
Clonal Architecture of Relapsed MLL-AF9 Acute Myeloid Leukemia in a Child
Authors: Hélène Boutroux, Pierre Hirsch, Chrystele Bilhou-Nabera, Ruoping Tang, Fanny Fava, Hélène Lapillonne, Guy Leverger, Luc Douay, Francois Delhommeau
Journal: Blood (2014)
Mutational Status of TET2, JAK2, and MPL in Refractory Anemia with Ringed Sideroblasts Associated with Marked Thrombocytosis.
Authors: Luca Malcovati, Angela Brisci, Daniela Pietra, Matteo G Della Porta, Anna Gallífi, Francesca Bruno, Erica Travaglino, Sabrina Boggi, Elisa Rumi, Francesco Passamonti, Maurizio Ferrari, Rosangela Invernizzi, Laura Cremonesi, Mario Cazzola
Journal: Blood (2009)
Nanoparticles for radiooncology: Mission, vision, challenges
Authors: Leoni A. Kunz-Schughart, Anna Dubrovska, Claudia Peitzsch, Alexander Ewe, Achim Aigner, Samuel Schellenburg, Michael H. Muders, Silke Hampel, Giuseppe Cirillo, Francesca Iemma, Rainer Tietze, Christoph Alexiou, Holger Stephan, Kristof Zarschler, Orazio Vittorio, Maria Kavallaris, Wolfgang J. Parak, Lutz Mädler, Suman Pokhrel
Journal: Biomaterials (2016)
Association Between Presence of a Cardiac Intensivist and Mortality in an Adult Cardiac Care Unit
Authors: Soo Jin Na, Chi Ryang Chung, Kyeongman Jeon, Chi-Min Park, Gee Young Suh, Joong Hyun Ahn, Keumhee C. Carriere, Young Bin Song, Jin-Oh Choi, Joo-Yong Hahn, Jin-Ho Choi, Seung-Hyuk Choi, Young Keun On, Hyeon-Cheol Gwon, Eun-Seok Jeon, Duk-Kyung Kim, Jeong Hoon Yang
Journal: Journal of the American College of Cardiology (2016)
Abstract 3094: Sprouty and cell proliferation in colorectal cancer
Authors: Qiong Zhang, Katherine Shim, Kevin Wright, Alexander Jurkevich, Sharad Khare
Journal: Cancer Research (2015)

Abstract BACKGROUND &amp; AIMS: Sprouty (SPRY) proteins are evolutionarily conserved modulators of mitogen-activated protein kinase pathway. SPRY2 appears to function as a tumor suppressor in other cancers, whereas we reported that SPRY2 functions as an oncogene in colorectal cancer (CRC). To further understand the oncogenic potential of SPRY1 and SPRY2 in CRC, we investigated the mechanisms by which these proteins regulate cell proliferation in CRC. MATERIALS &amp; METHODS: Human CRC cDNA arrays were employed to assess mRNA levels of SPRY1, SPRY2 and p21. SPRY1 and SPRY2 were knocked-down in CaCo2 colon cancer cells by siRNA. Effects of SPRY were assessed by immunoblotting, real time PCR, luciferase reporter assay, and confocal microscopy. Mouse embryonic fibroblasts (MEFs) derived from SPRY mutant mice were utilized to dissect SPRY functions in mesenchymal cells. RESULTS: In this study, surprisingly, we present evidence to suggest that concomitant activation of ERK, p-38 and AKT signaling cascades is insufficient to drive cancer cell proliferation in SPRY modulated cells. Suppression of SPRY in colon cancer cells upregulates p21, a cell cycle inhibitor. SPRY2 dependent p21 promoter activation may account for upregulation of p21 expression and inhibition of cancer cell proliferation. Underscoring the biological relevance of these findings, recombination of floxed SPRY1 and SPRY2 alleles in mouse embryonic fibroblasts (MEFs) resulted in increased expression of p21. Finally, in a human CRC cDNA array we established an inverse correlation of SPRY1 and SPRY2 with p21 mRNA expression. CONCLUSIONS: Together, this study indicates that SPRY is a target of therapeutic intervention in CRC. Citation Format: Qiong Zhang, Katherine Shim, Kevin Wright, Alexander Jurkevich, Sharad Khare. Sprouty and cell proliferation in colorectal cancer. [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 3094. doi:10.1158/1538-7445.AM2015-3094