tbuckley/cabot-search huggingface dataset:
Abstract P282: Dairy Fat and Risk of Cardiovascular Disease in 3 Cohorts of US Adults
Authors: Mu Chen, Qi Sun, An Pan, Yanping Li, JoAnn E Manson, Kathryn M Rexrode, Walter C Willett, Eric B Rimm, Frank B Hu
Journal: Circulation (2016)

Background: Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD). Objective: We aimed to evaluate the association between dairy fat and incident CVD in US adults. Design: We followed 41,852men in the Health Professionals Follow-Up Study (1986-2010), 70,636women in the Nurses’ Health Study (1980-2010), and 90,056 women in the Nurses’ Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 years by validated food-frequency questionnaires. Results: During 4,324,477 person-years of follow-up, we documented 10,834 incident CVD cases including 5,107coronary heart disease (nonfatal myocardial infarction or fatal coronary disease) and 5,843 stroke cases. In multivariate analyses, dairy fat intake was not significantly related to the risk of total cardiovascular disease (for a 5% increase in energy from dairy fat, the relative risk (RR) was 1.00, 95% CI: 0.95-1.04), or coronary heart disease [RR: 1.02; 95%CI: 0.95-1.09] or stroke [RR: 0.98; 95%CI: 0.92-1.05]. In models estimating the effects of exchanging different fat sources, compared with equivalent energy from dairy fat, a 5% replacement in energy intake of dairy fat with vegetable fat was associated with a 10% (95%CI: 8%-12%) reduction in the risk of CVD. Substitution of other animal fat with dairy fat was not significantly associated with CVD risk. Conclusion: These results suggest that replacing dairy fat with carbohydrates or other animal fat was not associated with CVD risk. However, replacing dairy fat with vegetable sources of fat was associated with a lower risk of CVD. Figure 1. RR and 95% CI for cardiovascular disease associated with isocaloric substitutions (5% of energy) of vegetable fat (A) polyunsaturated fat (B) and other animal fat (C) for dairy fat.
Both the Endoplasmic Reticulum and the Mitochondria Are Involved in Apoptosis of Erythroid Precursors in Low Grade Myelodysplastic Syndromes.
Authors: Emmanuel Gyan, Emilie Frisan, Jean-Christophe Deschemin, Clotilde Randriamamptita, Anne Dubart-Kupperschmitt, Odile Beyne-Rauzy, Francois Dreyfus, Martine Guesnu, Catherine Lacombe, Patrick Mayeux, Eric Solary, Michaela Fontenay
Journal: Blood (2006)
Thrombin Generation Profiles Are Qualitatively and Quantitatively Distinct in Microparticles Derived from Red Cells (RMP), Platelets (PMP), and Endothelia (EMP).
Authors: Wenche Jy, Loreta Bidot, Joaquin J. Jimenez, Lawrence L. Horstman, Jaehoon Bang, Andrew Lin, William Zambrano, Eugene Ahn, Yeon-Soong Ahn
Journal: Blood (2006)
Body Mass Index (BMI) e quality of life (QoL) in cancer patients – the ‘Tor Vergata’ Observational study in oNCOlogy– TV-ONCO study
Authors: M. Schirru, V. Formica, V. Massimiliani, R. Pellegrino, J. Lucchetti, F.R. Antonetti, S. Pellicori, S. Riondino, M. Roselli
Journal: Annals of Oncology (2015)
The landscape of new drugs in lymphoma
Authors: Anas Younes, Stephen Ansell, Nathan Fowler, Wyndham Wilson, Sven de Vos, John Seymour, Ranjana Advani, Andres Forero, Franck Morschhauser, Marie Jose Kersten, Kensei Tobinai, Pier Luigi Zinzani, Emanuele Zucca, Jeremy Abramson, Julie Vose
Journal: Nature Reviews Clinical Oncology (2016)
398. Site-Specific Introduction of Chimeric Antigen Receptors to Primary Human T Cells
Authors: Malika Hale, Alexandra Grier, Yuchi Honaker, Guillermo S. Romano Ibarra, Karen Sommer, Iram F. Khan, Nicholas Hasle, Jaya Sahni, Baeckseung Lee, Jordan Jarjour, Alexander Astrakhan, Andrew M. Scharenberg, David J. Rawlings
Journal: Molecular Therapy (2016)

In current clinical trials, delivery of an anti-cancer chimeric antigen receptor (CAR) to patient T cells is accomplished using randomly integrating retroviruses. Designer nucleases and AAV donor templates allow an alternative delivery method that introduces the CAR gene cassette at a target locus via homologous recombination, with concomitant disruption of the endogenous gene. Here we show high-efficiency introduction of anti-CD19 and anti-BCMA CAR expression cassettes in primary human T cells at two clinically relevant loci: CCR5 and TCRa. These gene-targeted CAR+ cells (tCARs) exhibit equivalent activity in vitro against CD19+ and BCMA+ cell lines compared to lentiviral-delivered CARs, and effectively clear tumor in a murine xenograft model. Advantages over lentiviral delivery include utilization of a defined integration site for the CAR construct linked with endogenous gene disruption. The use of specific nucleases and AAV for CAR delivery expands the possibilities for a precisely engineered cell therapy product in the clinic. For example, a CCR5-tCAR may be clinically useful in HIV+ patients, where traditional delivery methods leave therapeutic cells vulnerable to HIV infection and elimination. Moreover, a TCRa-tCAR could allow for off-the-shelf CAR therapy, potentially removing limitations to current approaches. Finally, the approach described here is broadly applicable for targeted delivery of alternative therapeutic cassettes at translationally relevant sites across the human genome.
FLT3-ITD As a Target for Minimal Residual Disease Monitoring in Early T-Cell Precursor (ETP) Acute Lymphoblastic Leukemia
Authors: Nellina Andriano, Barbara Buldini, Daniela Silvestri, Tiziana Villa, Franco Locatelli, Rosanna Parasole, Elena Barisone, Anna Maria Testi, Andrea Biondi, Maria Grazia Valsecchi, Valentino Conter, Giuseppe Basso, Luca Lo Nigro, Giovanni Cazzaniga
Journal: Blood (2014)
315. Highly Efficient Targeted Addition of Large XIST Transgenes in a Population of Somatic Cells
Authors: Jun Jiang, Jeanne Lawrence
Journal: Molecular Therapy (2016)

Recent advances in genome editing technologies enable precise and corrective genome modification to treat genetic diseases in a targeted way. High efficiency of genome editing can be achieved through error-prone NHEJ pathway, however, the absolute rate of precise genome editing through homology-directed repair (HDR) pathway remains relatively low, especially for targeted addition of large DNA sequences. Although it is sufficient for the generation of cell lines derived from single targeted clones when coupled with drug selection, poor rates of homologous recombination greatly limit the practical application of targeted gene integration in somatic tissue. XIST encodes a large long non-coding RNA (19 kb) that plays an essential role in X chromosome inactivation in mammalian females. Recently, we have shown that XIST can be inserted to chromosome 21 and silence the extra copy of entire chromosome in Down syndrome stem cells derived from a single-targeted clones. Successful trisomy silencing in vitro holds promise for potential development of 'chromosome therapy" in patients with Down syndrome. Here, using Zinc finger nuclease (ZFN) technology, we tested the feasibility of targeted addition of large XIST transgenes into different loci of human genome in a population of transformed cells, as well as primary fibroblasts. Our results demonstrate ZFNs enable highly efficient targeted addition of several large XIST transgenes (up to 21 kb) into multiple selected loci of human genome, which are the largest sequences for targeted addition to date. Surprisingly, the frequency of targeted integration is independent of the size of transgenes but possibly depends on ZFN cleavage activity. Highly efficient targeted addition of large XIST transgenes allows to directly compare silencing of XIST transgenes that contain different functional domains in a pool of many independent integrants. This study provides a powerful tool to test functional mini-XIST transgenes that can be packaged in a viral vector, and has particularly important applications in potential development of in vivo delivery of XIST transgenes into an organ of patients with trisomic chromosomal abnormalities.
Abstract 2120: Not all ribosomes are created equal: How cancer abuses the translational machinery
Authors: Ari L. Landon, Parameswary Muniandy, Ronald B. Gartenhaus
Journal: Cancer Research (2015)

Abstract Translational Dysregulation is emerging as a prominent mechanism leading to the malignant phenotype. These changes in protein levels can lead to cancer initiation, maintenance and progression. Cap-dependent translation is the primary mechanism of mRNA translation in eukaryotic cells. Cap-dependent translation is initiated by eIF4E1 binding to the 7-methyl-guanosine-cap (cap). The conventional translation initiation complex eIF4F consists of eIF4A, eIF4G and eIF4E. eIF4E binds the cap structure in the mRNA functioning as a bridge between mRNA and the ribosome. MNK kinases are responsible for phosphorylating eIF4E1. We observed that knocking down MNK kinases translationally represses total eIF4E1 expression. Interestingly, MNK down regulating total eIF4E1 occurs specifically in B-cells. This novel impact on total eIF4E1 demonstrates the potential for MNK1 and MNK2 to directly impact a large subset of oncogenes in a B-cell specific manner. Inhibiting MNK kinase activity and subsequent eIF4E1 phosphorylation results in an increase in eIF4E3 protein expression. eIF4E3 is another member of the eIF4E family that has been shown to bind the cap by an atypical mechanism. We explored the biological function of eIF4E3 in a diffuse large B-cell lymphoma model. The increase in total eIF4E3 competes with eIF4E1 for binding to the cap. We found that eIF4E3 also physically associates with eIF4A and eIF4G forming a novel eIF4F complex. We interrogated the functional aspects of eIF4E3-mediated translation by analyzing the translatome and transcriptome of eIF4E3 expressing cells. eIF4E3 and eIF4E1 mutually regulate a high fraction of total mRNA transcripts while both family members exclusively modulate translation of select messages. We identified selective motif enrichments in the 5′UTR that may facilitate transcript selection by eIF4E1 or eIF4E3. These findings imply alternative ribosomal complexes that are able to selectively translate mRNA via transcript recognition. The dual roles of MNK proteins for both eIF4E1 phosphorylation and total expression highlight MNK as a powerful oncogenic translation switch. Citation Format: Ari L. Landon, Parameswary Muniandy, Ronald B. Gartenhaus. Not all ribosomes are created equal: How cancer abuses the translational machinery. [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 2120. doi:10.1158/1538-7445.AM2015-2120
P0328 : Incidence, characteristics and determinants of primary liver cancer occurring during surveillance of compensated HCV cirrhosis according to sustained virological response (ANRS CO12 CirVir)
Authors: P. Nahon, V. Bourcier, R. Layese, N. Talmat, S. Allam, P. Marcellin, D. Guyader, S. Pol, D. Larrey, F. Zoulim, D. Roulot, V. de Lédinghen, D. Ouzan, J.-P. Zarski, J.-C. Trinchet, F. Roudot-Thoraval
Journal: Journal of Hepatology (2015)
Abstract 1313: Characterization and isolation of antigen-responding T cells in Sipuleucel-T treated patients
Authors: Jeff Pufnock, Tuyen Vu, James Trager, Nadeem Sheikh
Journal: Cancer Research (2015)

Abstract Sipuleucel-T is an FDA-approved autologous cellular therapy for men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate (mCRPC). Sipuleucel-T is manufactured from peripheral blood mononuclear cells (PBMCs) cultured with PA2024, a fusion antigen composed of prostatic acid phosphatase (PAP) fused to granulocyte macrophage-colony stimulating factor (GM-CSF). We have demonstrated that following three infusions this therapy results in T cell antigen specific responses directed against both PA2024 and PAP in treated patients. In this study we utilized the cellular dye Carboxyfluorescein succinimidyl ester (CSFE) and flow cytometric analysis to further characterize antigen responding T cells in Sipuleucel-T treated patients. We observed that CD4+ T cells predominate the antigen-responding T cell population following treatment, confirming our previous studies. Importantly, this approach has allowed us to also visualize a previously undetected population of antigen responding CD8+ T cells. The frequency of both of these populations is enhanced following treatment relative to baseline responses and the responding T cells display increased surface expression of the prototypical T cell activation markers CD134 and CD137 relative to non-proliferating T cells. Additionally, we are exploiting the increased surface expression of these activation markers on antigen-responding T cells to isolate these cells in an HLA and epitope-independent manner. Using this methodology we have demonstrated Sipuleucel-T is capable of inducing both CD4+ and CD8+ antigen-specific T cell responses in treated patients, and that we are capable of isolating these antigen-responding T cells specifically and with minimal manipulation. Citation Format: Jeff Pufnock, Tuyen Vu, James Trager, Nadeem Sheikh. Characterization and isolation of antigen-responding T cells in Sipuleucel-T treated patients. [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 1313. doi:10.1158/1538-7445.AM2015-1313
Short Course of Levofloxacin During Neutropenia Prevents Early and Late Bacteremia Episodes After Allogeneic Blood and Marrow Transplantation (alloBMT)
Authors: Sophia Francis, Theresa Hahn, Yali Zhang, Nikolaos Almyroudis, George L. Chen, Hong Liu, Maureen Ross, Brahm H Segal, Philip L. McCarthy
Journal: Blood (2012)
Switching from Deferoxamine (Desferal®, DFO) to Deferasirox (Exjade®) Maintains Effective Control of Iron Levels in Patients with Thalassemia Major (TM)
Authors: Maria Domenica Cappellini, Antonis Kattamis, Christos Kattamis, John B Porter, John M Ford, Martha Rodriguez, Lisa Rojkjaer, Antonio Piga
Journal: Blood (2008)
Array Comparative Genomic Hybridization: A Better Alternative for Genomic Profiling and Prognosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Authors: Annette Leon, Deborah Sevilla, Joseph M Marino, Kenneth D Moreno, Rev Obrera, PoShing Lee, Donjiu Ye, Jotica Talwar, Rajendra Persad, Cesar Villamil, Melissa Maya, Nirav Mehta, Yelena Kemel, James Weisberger
Journal: Blood (2012)
Abstract 5257: Immunohistochemical analysis and comprehensive hormone receptor profiling of uterine adenosarcomas at a single institution
Authors: Jenna R. Zechmeister, Gloria S. Huang, Rouzan Karabakhtsian, Melissa Schwartz, Eric R. Prossnitz, Gary L. Goldberg, Merieme Klobocista
Journal: Cancer Research (2015)

Abstract Uterine adenosarcomas (AS) are rare uterine tumors with benign epithelium and a sarcomatous component which is typically low-grade. Those displaying sarcomatous overgrowth (AS+SO) behave in a more aggressive fashion and are associated with worse clinical outcomes. Immunohistochemistry performed on AS and AS+SO have shown a greater preponderance for estrogen receptor alpha (ERα) and progesterone receptor (PR) positivity in those with a low-grade sarcomatous component. Further studies showed an increased proliferative index (Ki-67) in AS+SO and confirmed loss of expression in ER/PR in addition to loss of CD10. Expression of estrogen receptor beta (ERβ), a classic estrogen receptor as well as G protein-coupled estrogen receptor (GPER), a receptor that interacts with estrogen independently of the classic receptors, has been reported in uterine carcinosarcomas and they are associated with advanced stage disease. We conducted this study to analyze the receptor status of ERβ and GPER in cases of uterine AS. An H-score was calculated as the product of intensity and the percentage of cells staining positive (0-100%), higher scores indicate increased intensity and a greater number of positive cells. Unpaired t-test was used to compare the mean H-scores of receptor expression between low-grade AS (LG-AS) and high-grade AS (HG-AS). Mean age of diagnosis was 59.4 ± 11.9 years, mean BMI of 34.2 ± 8.5, and median disease free survival was 18 months (range 2-113 months). There were 7 cases of LG-AS and 3 cases of HG-AS, 2 cases displayed SO. Seven cases were stage IA, two were IB and one stage IV. There was a significant difference (p = 0.01) between the mean H-score for ERα between LG-AS (203) and HG-AS (1.7), There was also a significant difference (p = 0.04) in mean H-score for PR between LG-AS (188.6) and HG-AS (18.3). ERβ and GPER expression were retained in the HG-AS at similar levels as in the LG-AS, thus there was no difference in mean H-scores. In one patient with HG-AS and recurrent disease after 2 years, the recurrent tumor remained negative for ERα and PR, and showed somewhat decreased ERβ expression. Although the sample size is small, this is the first report of comprehensive estrogen receptor profiling in this uncommon uterine tumor. Citation Format: Jenna R. Zechmeister, Gloria S. Huang, Rouzan Karabakhtsian, Melissa Schwartz, Eric R. Prossnitz, Gary L. Goldberg, Merieme Klobocista. Immunohistochemical analysis and comprehensive hormone receptor profiling of uterine adenosarcomas at a single institution. [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 5257. doi:10.1158/1538-7445.AM2015-5257
Abstract 4126: CSF-1R inhibition blocks rhabdomyoscarcoma metastasis by polarizing macrophage differentiation
Authors: Justin Evans, Amber Giles, Caitlin Reid, Rosandra Kaplan
Journal: Cancer Research (2015)

Abstract Colony Stimulating Factor 1 (CSF-1) is overexpressed by many tumors and predicts poor clinical outcome. CSF-1 expression results in the recruitment of CSF-1R (Fms)-expressing cells, which have been shown to suppress tumor immunity, thereby promoting cancer progression. PLX3397 is a novel, orally active small molecule inhibitor that selectively targets CSF-1R, KIT, and oncogenic FIT3. CSF-1R and KIT regulate the tumor, tumor microenvironment, and the pre-metastatic niche. However, it is unknown if targeting the myeloid CSF-1R expressing component of the tumor microenvironment regulates metastasis of pediatric tumors, such as rhabdomyosarcoma. Using the M3-9-M murine syngeneic orthotopic rhabdomyosarcoma model, we evaluated the effects of PLX3397 on primary tumor growth and metastatic progression. This highly metastatic rhabdomyosarcoma model has high infiltration of CSF-1R-expressing bone marrow-derived cells, which includes inflammatory monocytes, M2 macrophages, and myeloid-derived suppressor cells. Therefore, we hypothesized PLX3397 would have a direct effect on CSF-1R expressing M2 macrophages and inflammatory monocytes, resulting in decreased metastasis. Using both in vitro and in vivo models, we found that PLX3397 treatment decreased tumor-infiltrating M2 macrophages and skewed the differentiation of inflammatory monocytes toward M1 macrophages and development of immunocompetent mature dendritic cells. This resulted in impairment of spontaneous M3-9-M metastasis to secondary sites. In addition, we have found that the polarization of inflammatory monocytes reversed the T cell suppressive capability of tumor-derived myeloid cells. In conclusion, CSF-1R blockage with PLX3397 inhibited metastatic progression by decreasing the infiltration of M2 macrophages in the primary tumor and pre-metastatic niche. The polarization of inflammatory monocytes to dendritic cells restored the immune recognition and decreased metastasis. This data supports our rationale for testing PLX3397 in patients with high M2 infiltration and suggests value in this agent as an adjuvant setting for metastasis prevention in high-risk patients. Note: This abstract was not presented at the meeting. Citation Format: Justin Evans, Amber Giles, Caitlin Reid, Rosandra Kaplan. CSF-1R inhibition blocks rhabdomyoscarcoma metastasis by polarizing macrophage differentiation. [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 4126. doi:10.1158/1538-7445.AM2015-4126
Outcomes of hormone-responsive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC) patients (P) according to their starting first-line (1st) treatment (T): chemotherapy (CT) or hormonal therapy (HT)
Authors: C. Bighin, F. Poggio, B. Dozin, M. Ceppi, P. Bruzzi, A. D'Alonzo, S. Giraudi, A. Levaggi, M. Lambertini, L. Miglietta, M. Vaglica, V. Fontana, G. Iacono, P. Pronzato, L. Del Mastro
Journal: Annals of Oncology (2015)
A Phase 2 Study of Birinapant in Combination with 5-Azacitadine in Patients with Myelodysplastic Syndrome Who Are Naïve to 5-Azacitadine: A Preliminary Analysis of Phase 2a
Authors: Ellen K. Ritchie, Apurv Agrawal, Kashyap B Patel, Seth Rosen, Amy Law, Jeffrey M Skolnik, Ashkan Lashkari
Journal: Blood (2015)
Gastric Visualization in Dacryoscintigraphy
Authors: Hamed Shayegani, Somayeh Khosravi, Toktam Masoudi, Ghasemali Divband, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2016)

We reported a 6-year-old girl with a history of left-eye epiphora since 2 years ago who was referred to our nuclear medicine center for dacryoscintigraphy imaging. The scan showed obstruction in the proximal portion of the nasolacrimal duct in the left eye. Imaging also showed patent nasolacrimal duct of the right eye. Tc pertechnetate activity was seen in the esophagus and stomach owing to swallowing of the excreted tracer in the nasal cavity. This was an unequivocal sign of patent lacrimal apparatus.
Fourteen cases of ADL and cognitive function during high-dose methotrexate treatment for malignant primary CNS lymphoma
Authors: Takuro Sakurai, Toshihisa Nakashima, Mayumi Horikawa, Yoichi Shimizu, Noriko Watanabe, Moonhwa Park, Aiko Matsuoka, Yasuji Miyakita, Yoshitaka Narita, Akira Kawai
Journal: Annals of Oncology (2015)
Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation
Authors: Eliane Gluckman, Barbara Cappelli, Francoise Bernaudin, Myriam Labopin, Fernanda Volt, Jeanette Carreras, Belinda Pinto Simões, Alina Ferster, Sophie Dupont, Josu de la Fuente, Jean-Hugues Dalle, Marco Zecca, Mark C. Walters, Lakshmanan Krishnamurti, Monica Bhatia, Kathryn Leung, Gregory Yanik, Joanne Kurtzberg, Nathalie Dhedin, Mathieu Kuentz, Gerard Michel, Jane Apperley, Patrick Lutz, Bénédicte Neven, Yves Bertrand, Jean Pierre Vannier, Mouhab Ayas, Marina Cavazzana, Susanne Matthes-Martin, Vanderson Rocha, Hanadi Elayoubi, Chantal Kenzey, Peter Bader, Franco Locatelli, Annalisa Ruggeri, Mary Eapen
Journal: Blood (2016)
Multiple Variants of <i>Klebsiella pneumoniae</i> Producing Carbapenemase in One Patient
Authors: Michael R Mulvey, Louis-Patrick Haraoui, Yves Longtin
Journal: New England Journal of Medicine (2016)

Determinants of antimicrobial resistance can be highly mobile. In this report, the diversity of carbapenem-resistant bacteria in a single patient over several years is investigated.
Once Daily Intravenous Busulphan Plus Fludarabine As New Reduced Toxicity Myeloablative Conditioning for Acute Myeloid Leukemia and MDS Allogeneic Transplantation
Authors: Donatella Baronciani, Cristina Depau, Clara Targhetta, Anna Angela Di Tucci, Daniele Derudas, Fabio Culurgioni, Donatella Pulisci, Igor Tandurella, Emanuele Angelucci
Journal: Blood (2014)