tbuckley/cabot-search huggingface dataset:
Activity of cabozantinib in metastatic uveal melanoma: Updated results from a phase II randomized discontinuation trial (RDT).
Authors: Adil Daud, Harriet M. Kluger, Gerald Edelman, Michael S. Gordon, Frauke Schimmoller, Aaron Weitzman, Thomas A. Samuel, Ali H. Moussa, Keith Flaherty, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2013)

9094 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis, and upregulation of MET as a consequence of GNAQ/GNA11 mutation has been implicated in uveal melanoma. Historical rates of median overall survival (OS) in patients (pts) with metastatic uveal melanoma range from 6-9 months (mos). A RDT evaluated activity and safety of cabozantinib, a MET and VEGFR2 inhibitor, in 9 tumor types including a metastatic melanoma cohort where 55% and 5% of pts experienced objective tumor regression and confirmed partial response, respectively (J. Clin. Oncol. 30, 2012 (suppl; abstr. 8531)). Here we report on the longer term followup of metastatic uveal melanoma pts enrolled to this cohort. Methods: Eligible pts were required to have progressive measurable disease per RECIST. Pts received cabozantinib at 100 mg po qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabozantinib, pts with SD were randomized to cabozantinib vs placebo, and pts with PD discontinued. Pts were followed for overall survival. Results: 23 of 77 pts enrolled in the melanoma cohort had the uveal subtype. Median age was 65 yrs; median prior regimens was 1 (range 0-5). Tumor mutation status was determined for 10/23 pts. 9/10 harbored either a GNAQ or GNA11 mutation, while GNA11 status was unknown for one pt. Pts had substantial tumor burden; median sum of the longest diameter of target lesions was 11.9 cm (range, 2-37.2). Median follow-up was 26.5 mos. (range 21.7-33.8). Median PFS from Study Day 1 was 4.8 mos. The estimate of PFS at month 6 (PFS6) was 41% and median OS was 12.6 mos. Most common Grade 3/4 AEs were HTN (13%), abdominal pain (9%), hypokalaemia (9%), hyperbilirubinaemia (9%) and increased lipase (9%). Conclusions: Cabozantinib is active in pts with metastatic uveal melanoma. Treatment with cabozantinib is associated with encouraging progression-free and overall survival. The safety profile of cabozantinib was comparable to that of other VEGFR TKIs. A randomized Phase 2 study is planned comparing cabozantinib to temozolomide plus dacarbazine in pts with uveal melanoma. Clinical trial information: NCT00940225.
Late-Onset Hemorrhagic Cystitis in Children After Hematopoietic Stem Cell Transplantation (HSCT) for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir (CDV).
Authors: Javid Gaziev, Guido Lucarelli, Stefano Germani, Pierpaolo Paba, Carlo Federico Perno, Roberto Miano, Pierluigi Bove, Pietro Sodani, Antonella Isgro, Marco Marziali, Paola Polchi, Aldo Montuoro, Katia Paciaroni, Cristiano Gallucci, Maria Domenica Simone, Andrea Roveda, Gioia De Angelis, Cecilia Alfieri
Journal: Blood (2009)
The PML/RARα-Regulated MiR-181a/b-Cluster Targets the Tumor Suppressor RASSF1A in Acute Promyelocytic Leukemia
Authors: Daniela Braeuer-Hartmann, Jens-Uwe Hartmann, Dennis Gerloff, Christiane Katzerke, Alexander Arthur Wurm, Maria Vittoria Verga Falzacappa, Pier Guiseppe Pelicci, Carsten Müller-Tidow, Daniel G. Tenen, Dietger Niederwieser, Gerhard Behre
Journal: Blood (2014)
Results From a Phase 1 Multicenter Trial of Alisertib (MLN8237)–An Investigational Aurora A Kinase Inhibitor–in Patients with Advanced Hematologic Malignancies
Authors: Kevin R. Kelly, Swaminathan Padmanabhan, André Goy, Jesus G. Berdeja, Craig B. Reeder, Kevin T. McDonagh, Xiaofei Zhou, Hadi Danaee, Hugh Xiao, Ely Benaim, Thomas C. Shea
Journal: Blood (2011)
GW26-e4395 Collaboration of HIF-2α and Oct4 Promotes Survival and Myocardia Repair of Human Very Small Embryonic-like Mesenchymal Stem Cells In Myocardial Infarction
Authors: Shaoheng Zhang, Lan Zhao, Feng Su, Jiahong Wang, Nannan Chen, Jinhui Tang, Jian Yan, Jianyi Zhang, Junbo Ge
Journal: Journal of the American College of Cardiology (2015)
GW26-e1038 MicroRNA-20a/b Regulates Cholesterol Efflux through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1 in THP-1 macrophage/RAW 264.7-derived foam cells
Authors: Bin Liang, Xin Wang, Rui Bai, Huiyu Yang, Yaoxia Han, Zhiming Yang, Yunfei Bian, Chuanshi Xiao
Journal: Journal of the American College of Cardiology (2015)
Auto-Reactive Glycosyl-Phosphatidyl-Inositol (GPI) Specific T Cells Are Present in Most Patients with Idiopathic Aplastic Anemia (IAA)
Authors: Lucia Gargiulo, Yoshitaka Zaimoku, Barbara Scappini, Hiroyuki Maruyama, Rie Ohumi, Lucio Luzzatto, Shinji Nakao, Rosario Notaro
Journal: Blood (2015)
Relationship Between Presence Of Osteolytic Lesions, Cytogenetic Features and Bone Marrow Levels Of Cytokines and Chemokines In Multiple Myeloma Patients: Role Of Chemokine (C-C motif) Ligand 20
Authors: Nicola Giuliani, Benedetta Dalla Palma, Daniela Guasco, Mario Pedrazzoni, Marina Bolzoni, Gabriella Sammarelli, Paola Storti, Angelica Spolzino, Luisa Craviotto, Massimo De Filippo, Livia Ruffini, Franco Aversa
Journal: Blood (2013)
Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation
Authors: C. Arden Pope, Aruni Bhatnagar, James P. McCracken, Wesley Abplanalp, Daniel J. Conklin, Timothy O’Toole
Journal: Circulation Research (2016)

Epidemiological evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking.To examine whether acute exposure to PM2.5 is associated with endothelial injury and systemic inflammation.Blood was collected from healthy, nonsmoking, young adults during 3 study periods that included episodes of elevated PM2.5 levels. Microparticles and immune cells in blood were measured by flow cytometry, and plasma cytokine/growth factors were measured using multiplexing laser beads. PM2.5 exposure was associated with the elevated levels of endothelial microparticles (annexin V+/CD41-/CD31+), including subtypes expressing arterial-, venous-, and lung-specific markers, but not microparticles expressing CD62+. These changes were accompanied by suppressed circulating levels of proangiogenic growth factors (EGF [epidermal growth factor], sCD40L [soluble CD40 ligand], PDGF [platelet-derived growth factor], RANTES [regulated on activation, normal T-cell-expressed and secreted], GROα [growth-regulated protein α], and VEGF [vascular endothelial growth factor]), and an increase in the levels of antiangiogenic (TNFα [tumor necrosis factor α], IP-10 [interferon γ-induced protein 10]), and proinflammatory cytokines (MCP-1 [monocyte chemoattractant protein 1], MIP-1α/β [macrophage inflammatory protein 1α/β], IL-6 [interleukin 6], and IL-1β [interleukin 1β]), and markers of endothelial adhesion (sICAM-1 [soluble intercellular adhesion molecule 1] and sVCAM-1 [soluble vascular cellular adhesion molecule 1]). PM2.5 exposure was also associated with an inflammatory response characterized by elevated levels of circulating CD14+, CD16+, CD4+, and CD8+, but not CD19+ cells.Episodic PM2.5 exposures are associated with increased endothelial cell apoptosis, an antiangiogenic plasma profile, and elevated levels of circulating monocytes and T, but not B, lymphocytes. These changes could contribute to the pathogenic sequelae of atherogenesis and acute coronary events.
Abstract A22: In situ image-based monitoring of extracellular matrix mechanics in 3D pancreatic tumor-stroma co-culture models to inform therapeutic development
Authors: Dustin P. Jones, William Hanna, Gwendolyn M. Cramer, Hamid El-Hamidi, Jonathan P. Celli
Journal: Cancer Research (2016)

Abstract A number of compelling studies have shown that the mechanical landscape of the tumor microenvironment contributes significantly to regulation of growth behavior, phenotype, and therapeutic response. These findings could be particularly relevant to pancreatic tumors, which are associated with a profound desmolastic reaction. The exceptional abundance of rigid, fibrotic stroma encasing these lethal malignancies has been implicated in obstructing drug delivery and playing multiple tumor-promoting roles. In this context, we use in vitro 3D tumor models with customized stromal composition, combined with in situ quantitative measurements of extracellular matrix (ECM) rigidity via optical microrheology, as a platform for evaluation of therapeutics targeting biomechanical interactions with the microenvironment. Using ECM formulations of calibrated rheological properties (rigidity) in conjunction with optical measurements that provide readouts of dynamic changes provides a window into both sides of a mechanoregulatory dialogue, in which ECM rigidity influences tumor growth and, in turn, cancer cells and stromal fibroblasts remodel their mechanical environment. Here we examine differential therapeutic response to selected chemotherapy agents and photodynamic therapy (PDT) in culture conditions that lead to fibrosis (increasing mechanical strength) as well invasive behavior (local breakdown of ECM). The methodology used here could be more broadly applied to directly quantify impact of stromal depletion therapies and altered ECM remodeling concomitant with therapy. Citation Format: Dustin P. Jones, William Hanna, Gwendolyn M. Cramer, Hamid El-Hamidi, Jonathan P. Celli. In situ image-based monitoring of extracellular matrix mechanics in 3D pancreatic tumor-stroma co-culture models to inform therapeutic development. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A22.
Empirical second-line antimicrobial therapy in febrile neutropenic cancer patients
Authors: W. Dong, L. Liu, Y. Li, X. Ren, C. Cheng, S. Liu
Journal: Journal of Clinical Oncology (2004)

8199 Background:The treatment of infectious complications in cancer patients has evolved as a consequence of the developments in the chemotherapy of cancer patients. Monotherapy with the carbapenems (imipenem/cilastatin and meropenem) represents realistic options for risk-based treatment of febrile neutropenic patients. In the past years, imipenem-cilastatin was the most appropriate choices in our institution. The objective of this trial was to evaluate the potential advantages of the combination of quinolones and vancomycin as second-line antimicrobial therapy. Methods:From January 1999 to November 2001, 114 episodes of fever and neutropenia (neutrophils less than 500/mm3) occurring in 67 patients with cancer received treatment with imipenem/cilastatin and glycosylated G-CSF. Target therapy is mandatory if the culture data become available. If infection continued 72 hours later, patients were randomized to receive vancomycin or vancomycin plus quinolones, and if infection had not disappeared 7 days after starting antibiotics, fluconazole was started. Results:In our study group, the success rate with initial empirical imipenem/cilastatin was 72.8%, while other 31 episodes of 23 patients were enrolled the test. Of 27 evaluable episodes, 16 were treated with vancomycin and 11 were treated with vancomycin plus quinolones. 43.8% (7 of 16) of vancomycin treated patients and 63.6% ( 7 of 11) of vancomycin plus quinolones treated patients responded to treatment, respectively. 4 patients needed fluconazole to become afebril. 74% of episodes were culture-positive: gram-positive pathogens accounted for 62% of the isolates. Staphylococcus aureus, enterococcus, stenotrophomonas maltophilia and candida were the commonly isolated organisms. Bacteremia, and respiratory tract was the most frequent site of infection. Conclusions: This study demonstrated that the combination therapy of vancomycin plus quinolones were effective empirical therapy for febrile neutropenic cancer patients. Empiric antifungal therapy with intravenous fluconazole is beneficial for second-line treatment. No significant financial relationships to disclose.
Robotic radiosurgery of liver metastases of solid tumors
Authors: S. Stintzing, R. T. Hoffmann, V. Heinemann, M. Kufeld, A. Muacevic
Journal: Journal of Clinical Oncology (2009)

e15049 Background: The number of patients (pts) suffering from isolated liver metastases is growing. Although surgical excision is the treatment of choice many pts do not qualify for surgery. So local ablative techniques like radiofrequency ablation, laser induced thermal ablation therapy, brachytherapy and different external beam radiation therapies have been employed. We here report the therapeutic efficacy of a robotic radiosurgery device for local control of liver metastases of solid tumors. Methods: Patients with liver metastases not qualifying for surgery were treated with single session radiosurgery (24 Gy) using robotic image-guided real-time tumor tracking. In a prospective analysis, follow-up was done by MRI scanning at two months after the treatment, and subsequently at 3-month intervals to evaluate local control. For inclusion into the radiosurgery treatment protocol, tumor volumes had to be smaller than 80cc. Results: 27 pts (median age 62 years) with a total of 43 target lesions were evaluated. 17 pts were treated with single, 10 pts with multiple targets. Metastases (n=27) originated from: colon (12), rectum (2), pancreas (2), lung (1), bladder (2), malignant melanoma (1), stomach (1), cholangiocellular carcinoma (2), breast (1), ovary (1), appendix (1) and endometrium (1). Median tumor volume was 21cc (range 2.2–79.3). Median KPS was 100% (range 80–100). The median follow up was 12 months. 23 pts (85%) reached local control of the disease, 4 pts (15%) had local recurrence. Grade 2–4 adverse events due to cyberknife treatment were not observed. Conclusions: Robotic radiosurgery with image-guided real-time tumor tracking of liver metastases is a new and promising treatment approach for pts not eligible for surgical resection and might enhance the possibilities of multidisciplinary oncological treatment concepts. No significant financial relationships to disclose.
P0626 : The analysis of the expression of A2M, COL1A1, MMP2 and CHI3L identifies significant fibrosis in patients with chronic hepatitis B
Authors: E. Estrabaud, R. Carvalho-Filho, O. Lada, C. Laouenan, A.C. Ferreira Netto Cardoso, M. Martinot-Peignoux, I. Bieche, M. Lapalus, M. Vidaud, T. Asselah, P. Marcellin
Journal: Journal of Hepatology (2015)
Early Relapses in Primary CNS Lymphoma (PCNSL) without Intraventricular Treatment.
Authors: Ingo G.H. Schmidt-Wolf, Hendrick Pels, Annika Jurgens, Axel Glasmacher, Holger Schulz, Andreas Engert, Michael Linnebank, Gabriele Schackert, Heinz Reichmann, Frank Kroschinsky, Marlies Vogt-Schaden, Gertlinde Egerer, Carlo Schaller, Monika Lamprecht, Ulrich Bogdahn, Martina Deckert, Rolf Fimmers, Christoph Bangard, Uwe Schlegel
Journal: Blood (2007)
Interferon-alpha-2b induced signal transduction and gene regulation in patient immune cells is not enhanced by a dose increase from 5 MU/m<sup>2</sup> to 10 MU/m<sup>2</sup>
Authors: J. M. Zimmerer, A. Lehman, A. Ruppert, T. Olencki, K. Kendra, M. J. Walker, W. E. Carson
Journal: Journal of Clinical Oncology (2007)

3026 Background: High dose interferon-alpha-2b (IFN-a) is employed as an adjuvant in melanoma patients who have had surgery for high-risk lesions. It mediates its anti-tumor effects via activation of the transcription factor STAT1 (signal transducer and activator of transcription) within host immune cells. We hypothesized that intermediate doses of IFN-a would be just as effective as higher doses in stimulating the activation of STAT1 and gene transcription in immune cells. Methods: Samples for analysis were obtained from patients with metastatic melanoma who were enrolled in a clinical trial of bevacizumab in combination with escalating doses of IFN-a (5 MU/m^2 and then 10 MU/m^2). Peripheral blood mononuclear cells (PBMCs) were procured before and 1 hour after the administration of IFN-a and analyzed for the presence of phosphorylated STAT1 (P-STAT1) and P-STAT2 by intracellular flow cytometric analysis and the induction of interferon stimulated gene (ISG) transcripts by Real Time PCR. Results: P-STAT1 in response to 5 MU/m^2 IFN-a was higher than that for the 10 MU/m^2 dose (p = 0.0617). The 5 MU/m^2 dose also led to a greater activation of STAT2 (p = 0.0388). The induction of interferon stimulated genes (ISGs; IFIT1, IFIT2, OAS3) within PBMCs was not enhanced following the increase in IFN-a dose to 10 MU/m^2 at 2 weeks although inhibitors of IFN-a-signaling (SOCS1 and SOCS3) were activated to a greater degree. In addition, microarray analysis was performed on 4 patients and revealed that only one of 36 interferon regulated genes was expressed to a greater extent following treatment with 10 MU/m^2 IFN-a as compared to 5 MU/m^2. Conclusions: These results suggest that 5 MU/m^2 of IFN-a are as effective as higher doses with respect to the induction of STAT signal transduction and ISGs within immune effector cells. No significant financial relationships to disclose.
Biweekly docetaxel and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (NSCLC)
Authors: E. Gaspar, J. Firvida, M. Amenedo, D. Orts, M. Salgado, C. LLorca, M. Ramos, E. Perez, J. Cervera, J. Abal
Journal: Journal of Clinical Oncology (2007)

18147 Background: The activity and tolerability of third-generation agents led many investigators to evaluate doublet combinations in the hope that platinum analogues could be eliminated from the treatment of advanced NSCLC. To improve the therapeutic index of this combination, we performed a study with biweekly gemcitabine and docetaxel. Primary objective was determination of objective response rate (ORR). Secondary objectives were time to progression, tolerability and overall survival. Methods: Patients histologically confirmed of non-small cell lung cancer, aged ≥ 18, ECOG PS 0–2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function were included. Prior chemotherapy was not allowed. Patients received treatment with a combination of Docetaxel 50 mg/m 2 and gemcitabine 20,00 mg/m 2 each 15 days for a maximum of 8 cycles. Results: Fifty patients were included between July 2005 and October 2006.Now we present the results of the first 32 patients: 88% were male, median age was 62.7 years old, 69% had ECOG 0–1 and 81% of patients had stage IV. Histology was squamous cell carcinoma (53%) adenocarcinoma (31%) and large cell carcinoma (16%). A total 221 cycles were administrated . Over 30 patients evaluable for response, none achieved CR, 11 PR (36%), 7 SD (23%) and 12 PD, with an overall response rate of 36%. Median follow up of patients is 16 months, with a median overall survival of 9 months. Grade 3–4 toxicity per patient was: neutropenia (6%).Grade 1–2 toxicity per patient asthenia (75%), and nauseas (30%). Conclusions: These results suggest that biweekly schedule of gemcitabine / docetaxel is a safe and active regimen in first line advanced NSCLC patients.Updated results will be presented. No significant financial relationships to disclose.
Glutaminolysis: A Hallmark of Cancer Metabolism
Authors: Lifeng Yang, Sriram Venneti, Deepak Nagrath
Journal: Annual Review of Biomedical Engineering (2017)

Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines, pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells. In this article, we review oncogene-, tumor suppressor-, and tumor microenvironment-mediated regulation of glutamine metabolism in cancer cells. We describe the mechanism of glutamine's regulation of tumor proliferation, metastasis, and global methylation. Furthermore, we highlight the therapeutic potential of glutamine metabolism and emphasize that clinical application of in vivo assessment of glutamine metabolism is critical for identifying new ways to treat patients through glutamine-based metabolic therapy.
Biomarker for Benzopyrene Exposure Is Mitochondrial Mass and Mitochondrial DNA Copy in Blood Cells and Hematopoietic Tissues
Authors: Myung-Geun Shin, Hye-Ran Kim, Hyun-Jung Choi, Hwan-Young Kim, Dong-Kyun Han, Hee-Jo Baek, Jai Dong Moon, Hoon Kook, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang
Journal: Blood (2011)
Inhibition of Nuclear Factor Kappa B (NFkB)/Interferon Regulatory Factor 4 (IRF4) Signaling Pathway in Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) By Combining MLN4924, a Novel NEDD8 Activating Enzyme Inhibitor (NAE) and Ibrutinib
Authors: Pallawi Torka, Francisco J. Hernandez-Ilizaliturri, Sarah Belliotti, Cory Mavis, Juan Gu, Myron S. Czuczman
Journal: Blood (2014)
Phase 1, Multicenter, Open-Label, Combination Study (NPI-0052-107; NCT02103335) of Pomalidomide (POM), Marizomib (MRZ, NPI-0052), and Low-Dose Dexamethasone (LD-DEX) in Patients with Relapsed and Refractory Multiple Myeloma
Authors: Andrew Spencer, Jacob P. Laubach, Jeffrey A Zonder, Ashraf Z Badros, Simon Harrison, Amit Khot, Dharminder Chauhan, Kenneth C. Anderson, Steven D Reich, Mohit Trikha, Paul G. Richardson
Journal: Blood (2015)