tbuckley/cabot-search huggingface dataset:
Implementation of An Alternative Donor Option Is Prerequisite for a Good Intention-to-Treat (ITT) In Patients In Need of Allogeneic Transplantation: Analysis of 410 Patients
Authors: Maria Teresa Lupo-Stanghellini, Barbara Forno, Magda Marcatti, Cinzia Bitetti, Milena Coppola, Andrea Assanelli, Raffaella Greco, Francesca Lunghi, Michela Tassara, Elena Guggiari, Matteo Carrabba, Francesca Matteazzi, Lionello Camba, Daniela Clerici, Simona Malato, Sarah Marktel, Chiara Bonini, Claudio Bordignon, Consuelo Corti, Massimo Bernardi, Jacopo Peccatori, Fabio Ciceri
Journal: Blood (2010)
Identification of Core Gene Signature Associated with Synergism Between ABT-869, a FLT3 Inhibitor and SAHA, a HDAC Inhibitor in AML with FLT3-ITD Mutation.
Authors: Jianbiao Zhou, Chonglei Bi, Shaw-Cheng Liu, Wee-Joo Chng, Kian-Ghee Tay, Hanry Yu, Keith Glaser, Daniel Albert, Steven K Davidsen, Chien-Shing Chen
Journal: Blood (2008)
442. Developing Polymeric Bio-Scaffolds That Increase the Efficacy of Stem Cell-Mediated Therapy for Brain Tumors
Authors: Juli Bago, Onyi Okolie, Mahsa Mohiti-Asli, Elizabeth Loboa, Shawn Hingtgen
Journal: Molecular Therapy (2016)

Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. In this study, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(L-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer.
Association Of Pre-Existing Left Ventricular Dysfunction With Initial Lactic Acid Levels And Outcomes In Patients With Severe Sepsis And Septic Shock
Authors: K. J. Pak, D. Moll, L. A. Bazzano, F. Winterbottom, L. Shum, A. Pavlov, T. Nash, E. Sundell, L. Seoane
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Phase II Study of the c-Met Inhibitor ARQ 197 (Tivantinib) in Patients with Relapsed Multiple Myeloma.
Authors: Stephan Joseph Dorkhom, Shadia Zaman, Sheeba K. Thomas, Raymond Alexanian, Jatin J. Shah, Donna M. Weber, Michael Wang, Martha L. Anderson, Veerabhadran Baladandayuthapani, Yan Heather Lin, Min Fu, Christine M. Stellrecht, Claudia Morales de Partovi, Varsha V. Gandhi, Robert Z. Orlowski
Journal: Blood (2012)
Abstract AS21: Ovarian carcinomaCDK12mutations misregulate DNA repair genes via deficient formation and function of the Cdk12/CycK complex
Authors: Kingsley M. Ekumi, Hana Paculova, Vendula Pospichalova, Christian A. Bosken, Vitezslav Bryja, Matthias Geyer, Dalibor Blazek, Matjaz Barboric
Journal: Clinical Cancer Research (2015)

Abstract The Cdk12/CycK complex promotes gene expression by phosphorylating the C-terminal domain of RNA polymerase II. In previous work we found that CDK12/CycK complex maintains genomic stability via regulation of expression of several key DNA damage response genes such as BRCA1, ATR, FANCD2 or FANCI. CDK12 is among only nine genes with recurrent somatic mutations in high-grade serous ovarian carcinoma. However, the influence of these mutations on the Cdk12/CycK complex and their link to cancerogenesis remain ill-defined. Here, we show that most mutations interfere with the Cdk12/CycK complex formation, rendering the kinase inactive. By examining the mutations within the Cdk12/CycK structure, we find that they likely provoke structural rearrangements detrimental to Cdk12 activation. Our mRNA expression analysis of the patient samples containing the CDK12 mutations identifies coordinated down-regulation of key DNA damage response genes. Accordingly, we observed that the mutant Cdk12 proteins fail to promote the repair of DNA double strand breaks via homologous recombination. Together, we provide the molecular basis of how mutated CDK12 ceases to function in ovarian carcinoma. We propose that CDK12 is a tumor suppressor of which the loss-of-function mutations may elicit defects in multiple DNA repair pathways, leading to genomic instability that underlies the genesis of the cancer.. Citation Format: Kingsley M. Ekumi, Hana Paculova,Vendula Pospichalova, Christian A. Bosken,Vitezslav Bryja, Matthias Geyer, Dalibor Blazek, Matjaz Barboric. Ovarian carcinoma CDK12 mutations misregulate DNA repair genes via deficient formation and function of the Cdk12/CycK complex [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS21.
Transplantation of Haplo-Identical Bone Marrow-Derived Mesenchymal Stem Cells Together with Hematopoietic Stem Cells To Promote Engraftment in Children. A Phase I/II Multicenter Study.
Authors: Lynne Margaret van Velzen-Ball, Katarina Le Blanc, Arjen C. Lankester, Helene Roelofs, Maarten Egeler, Francesco Frassoni, Olle Ringdén, Willem E. Fibbe
Journal: Blood (2005)
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse
Authors: Marco Demaria, Monique N. O'Leary, Jianhui Chang, Lijian Shao, Su Liu, Fatouma Alimirah, Kristin Koenig, Catherine Le, Natalia Mitin, Allison M. Deal, Shani Alston, Emmeline C. Academia, Sumner Kilmarx, Alexis Valdovinos, Boshi Wang, Alain de Bruin, Brian K. Kennedy, Simon Melov, Daohong Zhou, Norman E. Sharpless, Hyman Muss, Judith Campisi
Journal: Cancer Discovery (2016)

Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells nonspecifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence, and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anticancer treatments.Many genotoxic chemotherapies have debilitating side effects and also induce cellular senescence in normal tissues. The senescent cells remain chronically present where they can promote local and systemic inflammation that causes or exacerbates many side effects of the chemotherapy. Cancer Discov; 7(2); 165-76. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115.
Lenalidomide (CC-5013) Treatment for Anemia Associated with Myelofibrosis with Myeloid Metaplasia.
Authors: Ayalew Tefferi, Ruben A. Mesa, William J. Hogan, Trudy A. Shaw, Gayle E. Reyes, Jacob B. Allred, Cynthia X. Ma, Grace K. Dy, Alexandra P. Wolanskyj, Mark L. Litzow, David P. Steensma, Timothy G. Call, Rebecca F. McClure
Journal: Blood (2005)
319. Improving the Odds of Adenovirus-Mediated Gene Therapy By Upregulation of the Coxsackievirus and Adenovirus Receptor
Authors: Katherine J.D.A. Excoffon, Poornima L.N. Kotha, Abimbola O. Kolawole, Ran Yan, Mahmoud S. Alghamri, Brockman L. Brockman, Julian Gomez-Cambronero, Priyanka Sharma
Journal: Molecular Therapy (2015)

Adenovirus-mediated gene therapy has been limited by the fact that the primary receptor for most adenovirus serotypes, the Coxsackievirus and adenovirus receptor (CAR), is inaccessible or not expressed on many cell types of interest. Few mechanisms have been discovered that regulate CAR expression and tissue specific localization. In the airway, CAR is mostly considered a cell-cell adhesion protein localized at the basolateral surface of polarized epithelia. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that upregulation of cellular mechanisms that facilitate endogenous CAREx8 protein expression at the apical surface would enhance adenovirus gene transfer. Using polarized model epithelial cell lines and primary human airway epithelia, we found that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. IL-8- mediated upregulation of CAREx8 increased AdV5-β-Gal entry and transduction by approximately 5-fold. Moreover, we found that infiltrating neutrophils bind CAREx8 at the apical surface of a polarized epithelium and, surprisingly, neutrophils enhance AdV5-β-Gal entry into the epithelium by 2-3 fold. The effect of IL-8 and neutrophils on AdV infection could be blocked by fiber-knob from AdV5 but not AdV3, a non-CAR binding serotype, indicating the importance of CAR. These findings suggest that acute inflammation may enhance adenovirus infection. Moreover, therapeutics that stimulate the AKT/S6K pathway or inhibit GSK3β may be able to augment adenovirus-mediated gene therapy.
Randomized Study of Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults with Untreated High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) at High Risk of Treatment-Related Mortality
Authors: Roland B. Walter, Kaysey F. Orlowski, Morgan A. Powell, Pamela S. Becker, Paul C. Hendrie, Fabiana Ostronoff, Elizabeth M. Ranker, Megan Othus, Arthur C. Louie, Elihu H. Estey
Journal: Blood (2014)
Gene Expression and Transcription Factor (TF) Activation Profiling Identifies Suppression of Multiple Myeloma (MM) Cell Survival and Chemoresistance Pathways By Inhibition of XPO1/CRM1-Dependent Nuclear Export with Selinexor
Authors: Shaun Rosebeck, Mattina Alonge, Jagoda Jasielec, Anoop Mayampurath, Samuel L. Volchenboum, Sharon Shacham, Michael Kauffman, Andrzej Jakubowiak
Journal: Blood (2014)
Abstract 4477: A 5-nitrobenzoate-derived compound elicits anti-cancer metastatic activity by inhibition of poloplanin-stimulated tumor cell-induced platelet aggregation
Authors: Yao-Wen Chang, Pei-Wen Hsieh, Kowit-Yu Chong, Ching-Ping Tseng
Journal: Cancer Research (2015)

Abstract Tumor cells dissemination and survival within the vascular system play an important role in cancer metastasis and is a clinical challenge for post-surgical cancer management. Podoplanin (PDPN) is one of the frequently over-expressed proteins in squamous cell carcinoma. By binding to platelet C-type lectin-like receptor 2 (CLEC-2), PDPN stimulates tumor cell-induced platelet aggregation (TCIPA) and facilitates cancer cell metastasis. In this study, a series of 5-nitrobenzoate-derived compounds were synthesized to screen for anti-cancer metastasis compounds that elicit functional blockage of PDPN-stimulated CLEC-2 activation and TCIPA. Platelet aggregation assays indicate that the small molecule compound 2CP selectively inhibited PDPN-induced platelet aggregation and the TCIPA of C6/Lung and osteosarcoma cells which expressed high levels of PDPN protein. Mouse tail bleeding time assay revealed that 2CP did not cause deleterious effects on normal blood hemostasis. In xenograft experimental metastasis model, 2CP possessed in vivo anti-cancer metastatic activity and augments the therapeutic efficacy of cisplatin; both the formation of pulmonary tumor foci and the body weight loss associated with the increased tumor burden were attenuated by combined treatment of 2CP and cisplatin. In conclusion, we present a novel and non-cytotoxic small molecule compound 2CP that elicits specific inhibitory effects on tumor cells-platelet interaction through intervening PDPN/CLEC-2 interaction and PDPN-mediated TCIPA. The findings are valuable for future application of 2CP in the prevention and treatment of cancer metastasis. Citation Format: Yao-Wen Chang, Pei-Wen Hsieh, Kowit-Yu Chong, Ching-Ping Tseng. A 5-nitrobenzoate-derived compound elicits anti-cancer metastatic activity by inhibition of poloplanin-stimulated tumor cell-induced platelet aggregation. [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 4477. doi:10.1158/1538-7445.AM2015-4477
Effectiveness of FIr-B/FOx and liver metastasectomies in liver-only metastatic colorectal cancer (MCRC).
Authors: G. Bruera, K. Cannita, P. Lanfiuti Baldi, A. Santomaggio, P. Marchetti, G. Nuzzo, A. Antonucci, C. Ficorella, E. Ricevuto
Journal: Journal of Clinical Oncology (2011)

582 Background: Effectiveness of liver metastasectomies was evaluated in liver-MCRC patients treated with FIr-B/FOx association in a previous phase II study (Bruera et al, submitted 2010). Methods: Treatment schedule: 12h-timed-flat-infusion/5-Fluorouracil 900 mg/m 2 days 1-2, 8-9, 15-16, 22-23; Irinotecan 160 mg/m 2 , Bevacizumab 5 mg/kg days 1, 15; Oxaliplatin 80 mg/m 2 days 8, 22; every 4 weeks. Resection rate, activity, efficacy were analysed and compared in liver-only versus multiple metastatic sites and single versus multiple liver metastases. Results: Liver-MCRC were 33: liver-only 22 patients (67%); multiple metastatic sites 11 patients (33%). Liver metastasectomies were performed in 13 patients (11 R0, 84.6%): 26% of 50 MCRC patients enrolled in the FIr-B/FOx phase II study; 39% of liver-MCRC patients; 54% of liver-only, 6 of 9 (67%) single and 6 of 13 (46%) multiple liver metastases; one liver and lung metastasectomy. Pathologic complete responses (CRs) were 2 (15%); downsizing with modification of surgical resectability, 9 patients (41%); conversion rate of unresectable liver metastases, 83%. Overall activity, including 3 clinical CR, in liver-only patients, 68%. ORR, PFS, OS, respectively: in liver-MCRC patients, 84%, 11 and 23 months; in liver-only metastases, 86%, 17 and 44 months; in liver metastasectomies, 100%, 21 months (PFS from liver surgery 10 months) and 47 months. Significantly increased efficacy: PFS and OS in liver-only versus multiple metastatic sites (p 0.006 and 0.011, respectively) and single versus multiple liver metastasis (p 0.026 and 0.022, respectively). Conclusions: FIr-B/FOx chemotherapy increases resection rate of liver metastases, thus significantly improving efficacy of liver-only MCRC patients. No significant financial relationships to disclose.
Long-Term Outcome of Methotrexate-Free GVHD Prophylaxis Using Sirolimus and Tacrolimus in Matched Related (MRD) and Unrelated Donor (URD) Peripheral Blood Stem Cell Transplantation (PBSCT).
Authors: Corey Cutler, Shuli Li, Vincent Ho, John Koreth, Edwin Alyea, Robert J. Soiffer, Joseph H. Antin
Journal: Blood (2006)
Abstract 5439: Development of a robust reporter-based T-cell activation assay for bispecific therapeutic antibodies in immunotherapy
Authors: Pete Stecha, Jamison Grailer, Zhi-jie Jey Cheng, Jim Hartnett, Frank Fan, Mei Cong
Journal: Cancer Research (2015)

Abstract Bispecific T-cell Engager (BiTE), which simultaneously targets CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, has emerged as a promising immunotherapy approach to treat cancer. Current methods for bispecific antibody potency determination measure T-cell proliferation or cytokine release using primary peripheral blood mononuclear cells. They can be complex and highly variable. Here we report the development of a reporter-based T cell activation assay using two Jurkat cell lines stably expressing luciferase reporter driven by IL-2 promoter or NFAT-response element. Both Jurkat reporter cell lines showed robust reporter signal upon stimulation of crossed-linked CD3 antibody. These cell lines were developed in Thaw-and-Use format and showed similar assay performance as that from the cells fresh-from-culture. When tested with bispecific therapeutic antibody catumaxomab, we showed specific reporter response by co-culturing Jurkat reporter cells with cancer target cells endogenously expressing EpCAM, such as MDB-MA-231 and SK-BR-3 cells. No signal was observed without target cells or with EpCAM negative Raji cells. The assay can measure the relative potency for catumaxomab with good precision. It also can detect changes in biological activity for catumaxomab in stressed stability study, and therefore has appropriate stability-indicating property. In summary, the reporter-based T cell activation assay provides a simple and robust approach to quantitatively measure antibody potency for bispecific antibody. It can potentially serve as a potency bioassay for bispecific therapeutic antibodies during drug development and manufacture. Citation Format: Pete Stecha, Jamison Grailer, Zhi-jie Jey Cheng, Jim Hartnett, Frank Fan, Mei Cong. Development of a robust reporter-based T-cell activation assay for bispecific therapeutic antibodies in immunotherapy. [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 5439. doi:10.1158/1538-7445.AM2015-5439
Abstract 4874: OASIS: A centralized portal for cancer omics data analysis
Authors: Julio Fernandez-Banet, Anthony Esposito, Scott Coffin, Sabine Schefzick, Ying Ding, Keith Ching, Istvan Horvath, Peter Roberts, Paul Rejto, Zhengyan Kan
Journal: Cancer Research (2015)

Abstract Advances in cancer research and sequencing technologies have contributed to the proliferation of large-scale cancer omics data sets from both public consortia and privately funded collaborations. There are increasing demands for broadly accessible tools that enable scientists to perform ad hoc analyses of cancer omics data. Here we present OASIS (http://oasis.pfizer.com), an open-access web portal that enables complex analytical queries across somatic mutations, copy number changes (CNV) and gene expression data from public domain and Pfizer funded omics studies. OASIS was designed to perform multidimensional data integration, allowing users to analyze correlations among multiple data types, as well as visualize and compare alterations across different cancers. Users can browse alteration summary reports at the gene and sample level and perform analyses using interactive visualizations. These include the Pan-Cancer Report, a unique tool that provides a high-level overview of genetic variation across multiple cancer types. Through the use of the interactive visualizations researchers can explore differentially expressed genes, identify tumor samples for over expression, investigate the correlation between CNV and expression or survey alteration patterns for a list of genes. Users can explore molecular profiles from the Cancer Cell Line Encyclopedia (CCLE) and the Catalog of Somatic Mutations in Cancer (COSMIC), to identify cell line models of interest. Researchers can also construct complex queries through a user-friendly web interface supported by the Biomart query engine. Programmatic access is also available through web services. OASIS is a powerful tool that enables cancer researchers to perform integrative analyses of large-scale cancer omics data sets, thereby facilitating key steps in oncology drug discovery ranging from target identification to model selection. Citation Format: Julio Fernandez-Banet, Anthony Esposito, Scott Coffin, Sabine Schefzick, Ying Ding, Keith Ching, Istvan Horvath, Peter Roberts, Paul Rejto, Zhengyan Kan. OASIS: A centralized portal for cancer omics data analysis. [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 4874. doi:10.1158/1538-7445.AM2015-4874
Abstract 2264: Dual effects of podoplanin on the regulation of cancer cell gene expression and platelet CLEC-2 signaling during cancer metastasis
Authors: Ching-Ping Tseng, Yao-Wen Chang, Pei-Wen Hsieh, Ju-Chien Cheng
Journal: Cancer Research (2015)

Abstract Podoplanin (PDPN) is frequently up-regulated in squamous cell carcinoma and is a marker for poor prognosis. PDPN facilitates cancer metastasis and tumor cell-induced platelet aggregation (TCIPA) by modulating cancer cell cytoskeleton reorganization and platelet C-type lectin-like receptor 2 (CLEC-2) activation. In this study, the effects of PDPN on the regulation of cancer cell gene expression and platelet CLEC-2 signaling are investigated. Using xenograft injection of the C6 glioma cells into nude mice as a metastatic model, the cells that colonized at lung tissue were isolated to establish a subline C6-Lung that was found to express high levels of PDPN. Knockdown of PDPN expression in C6-Lung resulted in the abrogation of TCIPA, indicating that PDPN plays a key role in platelet activation and TCIPA. Microarray analyses revealed differential gene expression signatures between low and high PDPN-expressed cells. Several genes were up-regulated (Sncg, Timp1, Mmp3 and Pla1a) and down-regulated (Calcb, Filip1, Agrn and Itga4) significantly in high PDPN-expressed C6-Lung cells. On the other hand, distinct platelet protein tyrosine phosphorylation profiles were revealed when platelets were treated with different CLEC-2 agonists including PDPN, aggretin and fucoidan. In addition to the activation of common CLEC-2 signaling proteins such as Src family kinase, Syk, and phospholipase Cγ2, Akt1/PDK1 and PKCμ were identified as the two novel signaling pathways activated by PDPN, indicating the presence of SFK-independent pathway downstream of CLEC-2. Our data together provide a definitive evidence for the presence of a unique network for PDPN-regulated cancer cell gene expression and platelet CLEC-2 signaling that shed a new insight for the functional roles of PDPN in cancer metastasis. Citation Format: Ching-Ping Tseng, Yao-Wen Chang, Pei-Wen Hsieh, Ju-Chien Cheng. Dual effects of podoplanin on the regulation of cancer cell gene expression and platelet CLEC-2 signaling during cancer 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 2264. doi:10.1158/1538-7445.AM2015-2264
mTOR Inhibition for Relapsed or Refractory Hodgkin Lymphoma: Promising Single Agent Activity with Everolimus (RAD001).
Authors: Patrick B. Johnston, Steven M. Ansell, Joseph P. Colgan, Thomas M. Habermann, David J. Inwards, Ivana N.M. Micallef, Luis F. Porrata, Craig B. Reeder, Vivek Roy, Betsy R. LaPlant, Thomas E. Witzig
Journal: Blood (2007)