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413 results on '"Singer, Jack W."'

1. Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy

Author

Singer, Jack W, Fleischman, Angela, Al-Fayoumi, Suliman, Mascarenhas, John O, Yu, Qiang, and Agarwal, Anupriya

Subjects
Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Inflammatory and immune system, MyD88, cancer, inflammatory diseases, interleukin-1 receptor associated kinase, pacritinib, Oncology and Carcinogenesis
Abstract

Interleukin-1 receptor-associated kinases (IRAK1, IRAK2, IRAK3 [IRAK-M], and IRAK4) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways, through which they regulate innate immunity and inflammation. Evidence exists that IRAKs play key roles in the pathophysiologies of cancers, and metabolic and inflammatory diseases, and that IRAK inhibition has potential therapeutic benefits. Molecules capable of selectively interfering with IRAK function and expression have been reported, paving the way for the clinical evaluation of IRAK inhibition. Herein, we focus on IRAK1, review its structure and physiological roles, and summarize emerging data for IRAK1 inhibitors in preclinical and clinical studies.

Published
2018

2. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial

Author

Mesa, Ruben A, Vannucchi, Alessandro M, Mead, Adam, Egyed, Miklos, Szoke, Anita, Suvorov, Aleksandr, Jakucs, Janos, Perkins, Andrew, Prasad, Ritam, Mayer, Jiri, Demeter, Judit, Ganly, Peter, Singer, Jack W, Zhou, Huafeng, Dean, James P, te Boekhorst, Peter A, Nangalia, Jyoti, Kiladjian, Jean-Jacques, and Harrison, Claire N

Published
2017
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7. Supplementary Materials, Figures 1-4, Tables 1-2 from Antileukemic Activity of Lysophosphatidic Acid Acyltransferase-β Inhibitor CT32228 in Chronic Myelogenous Leukemia Sensitive and Resistant to Imatinib

Author

La Rosée, Paul, primary, Jia, Taiping, primary, Demehri, Shadmer, primary, Härtel, Nicolai, primary, de Vries, Peter, primary, Bonham, Lynn, primary, Hollenback, David, primary, Singer, Jack W., primary, Melo, Junia V., primary, Druker, Brian J., primary, and Deininger, Michael W., primary

Published
2023
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14. Poly-l-Glutamic Acid Anti-cancer Drug Conjugates

Author

Singer, Jack W., McKennon, Marc, Pezzoni, Gabriella, Giovine, Stefano di, Cassin, Mara, de Feudis, Paola, Allievi, Cecilia, Angiuli, Patrizia, Natangelo, Marco, Vezzali, Enrico, Fazioni, Stefano, Reddy, L. Harivardhan, editor, and Couvreur, Patrick, editor

Published
2010
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16. Poly-(L)-Glutamic Acid-Paclitaxel (CT-2103) [XYOTAX™], a Biodegradable Polymeric Drug Conjugate : Characterization, Preclinical Pharmacology, and Preliminary Clinical Data

Author

Singer, Jack W., Baker, Brian, de Vries, Peter, Kumar, Anil, Shaffer, Scott, Vawter, Ed, Bolton, Mary, Garzone, Pamela, Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Maeda, Hiroshi, editor, Kabanov, Alexander, editor, Kataoka, Kazunori, editor, and Okano, Teruo, editor

Published
2003
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18. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial

Author

Pettengell, Ruth, Coiffier, Bertrand, Narayanan, Geetha, de Mendoza, Fernando Hurtado, Digumarti, Raghunadharao, Gomez, Henry, Zinzani, Pier Luigi, Schiller, Gary, Rizzieri, David, Boland, Giles, Cernohous, Paul, Wang, Lixia, Kuepfer, Christine, Gorbatchevsky, Igor, and Singer, Jack W

Published
2012
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25. Randomized Phase III Trial Comparing Single-Agent Paclitaxel Poliglumex (CT-2103, PPX) with Single-Agent Gemcitabine or Vinorelbine for the Treatment of PS 2 Patients with Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer

Author

O'Brien, Mary E.R., Socinski, Mark A., Popovich, Alexander Y., Bondarenko, Igor N., Tomova, Antoaneta, Bilynsky˘ı, Borys T., Hotko, Yevhen S., Ganul, Valentin L., Kostinsky, Ippolit Y., Eisenfeld, Amy J., Sandalic, Larissa, Oldham, Fred B., Bandstra, Bruce, Sandler, Alan B., and Singer, Jack W.

Published
2008
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26. Phase III Trial Comparing Paclitaxel Poliglumex (CT-2103, PPX) in Combination with Carboplatin Versus Standard Paclitaxel and Carboplatin in the Treatment of PS 2 Patients with Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer

Author

Langer, Corey J., O’Byrne, Kenneth J., Socinski, Mark A., Mikhailov, Sergei M., Leśniewski-Kmak, Krzysztof, Smakal, Martin, Ciuleanu, Tudor E., Orlov, Sergey V., Dediu, Mircea, Heigener, David, Eisenfeld, Amy J., Sandalic, Larissa, Oldham, Fred B., Singer, Jack W., and Ross, Helen J.

Published
2008
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32. Poly-l-Glutamic Acid Anti-cancer Drug Conjugates

Author

Singer, Jack W., primary, McKennon, Marc, additional, Pezzoni, Gabriella, additional, Giovine, Stefano di, additional, Cassin, Mara, additional, de Feudis, Paola, additional, Allievi, Cecilia, additional, Angiuli, Patrizia, additional, Natangelo, Marco, additional, Vezzali, Enrico, additional, and Fazioni, Stefano, additional

Published
2009
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36. Randomized Phase III Trial Comparing Single-Agent Paclitaxel Poliglumex (CT-2103, PPX) with Single-Agent Gemcitabine or Vinorelbine for the Treatment of PS 2 Patients with Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer

Author

O’Brien, Mary E. R., Socinski, Mark A., Popovich, Alexander Y., Bondarenko, Igor N., Tomova, Antoaneta, Bilynsky, Borys T., Hotko, Yevhen S., Ganul, Valentin L., Kostinsky, Ippolit Y., Eisenfeld, Amy J., Sandalic, Larissa, Oldham, Fred B., Bandstra, Bruce, Sandler, Alan B., and Singer, Jack W.

Published
2008
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40. Modulating phosphatidic acid metabolism decreases oxidative injury in rat lungs

Author

Guidot, David M., Bursten, Stuart L., Rice, Glenn C., Chaney, Robert B., Singer, Jack W., Repine, Alexander J., Hybertson, Brooks M., and Repine, John E.

Subjects
Lungs -- Injuries, Rats -- Physiological aspects, Acute respiratory distress syndrome -- Development and progression, Neutrophils -- Physiological aspects, Acids -- Physiological aspects, Biological sciences
Abstract

The ability of lisofylline, an inhibitor of oleate- and linoleate-containing phosphatidic acid formation, to mediate capillary leak and oxidative injury in lungs stimulated by interleukin-8 was investigated. Adult male Sprague-Dawley rats were used as experimental models to examine the effects of lisofylline on neutrophil metabolism and responsiveness in vitro. Results showed that lisofylline did not prevent interleukin-8-induced neutrophil calcium mobilization or chemotaxis. Moreover, neutrophils pretreated with lisofylline were unable to prevent capillary leak in rat lungs.

Published
1997

42. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer

Author

Neumunaitis, John, Rabinowe, Susan N., Singer, Jack W., Bierman, Philip J., Vose, Julie M., Freedman, Arnold S., Onetto, Nicole, Gillis, Steven, Oette, Dagmar, Gold, Morris, Buckner, C. Dean, Hansen, John A., Ritz, Jerome, Appelbaum, Frederick R., Armitage, James O., and Nadler, Lee M.

Subjects
Granulocyte-macrophage colony stimulating factor -- Evaluation, Lymphomas -- Care and treatment, Granulocyte-macrophage colony stimulating factor -- Health aspects, Bone marrow -- Transplantation
Abstract

Patients with recurrent lymphoma (a malignancy that affects lymphoid tissue, such as lymph nodes) often undergo autologous bone marrow transplantation after total-body irradiation or chemotherapy, in which their own bone marrow (removed before radiation therapy) is re-infused to establish a supply of functioning bone marrow tissue. However, this treatment approach carries the risk of serious side effects, with death ensuing in as many as 15 percent of cases due to the dramatic reduction in the number of blood cells, particularly neutrophils (a type of white blood cell), that takes place. The effectiveness of a growth factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), was evaluated for its ability to promote the development and survival of myeloid cells (cells present in bone marrow) in patients undergoing bone marrow transplantation. One hundred twenty-eight patients at three research centers who had lymphoma (both Hodgkin's and non-Hodgkin's) received their regular treatments plus either rhGM-CSF (65 patients) or a placebo infusion (63), begun within four hours after the infusion of autologous bone marrow and ending 21 days later. The patients' levels of blood cells were closely monitored and infections or other complications were noted. Results showed that neutrophils in patients who received rhGM-CSF were replenished faster than in those who received the placebo: 59 percent and 39 percent of rhGM-CSF patients reached two criterion levels of neutrophils within 21 days, compared with 32 and 11 percent of the placebo patients. The rhGM-CSF group developed fewer infections and needed fewer days of antibiotic treatment compared with the placebo group. Their initial stay in the hospital was six days shorter. Although rhGM-CSF did not appear to affect relapse, survival, or the stability of the grafts during the first 100 days after marrow infusion, the drug was associated with less illness. Survival during this time was no different between the two groups. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

43. Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)

Author

Pettengell, Ruth, primary, Długosz‐Danecka, Monika, additional, Andorsky, David, additional, Belada, David, additional, Georgiev, Pencho, additional, Quick, Donald, additional, Singer, Jack W., additional, Singh, Simran B., additional, Pallis, Athanasios, additional, Egorov, Anton, additional, and Salles, Gilles, additional

Published
2019
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45. Phospholipase C δ-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells

Author

Morris Valerie, Coon Mike, Ball Alexey, Brewer Jim, Tompkins Chris, Leung David W, Waggoner David, and Singer Jack W

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The expression of the rodent phosphoinositide-specific phospholipase C δ-4 (PLCδ4) has been found to be elevated upon mitogenic stimulation and expression analysis have linked the upregulation of PLCδ4 expression with rapid proliferation in certain rat transformed cell lines. The human homologue of PLCδ4 has not been extensively characterized. Accordingly, we investigate the effects of overexpression of human PLCδ4 on cell signaling and proliferation in this study. Results The cDNA for human PLCδ4 has been isolated and expressed ectopically in breast cancer MCF-7 cells. Overexpression of PLCδ4 selectively activates protein kinase C-φ and upregulates the expression of epidermal growth factor receptors EGFR/erbB1 and HER2/erbB2, leading to constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in MCF-7 cells. MCF-7 cells stably expressing PLCδ4 demonstrates several phenotypes of transformation, such as rapid proliferation in low serum, formation of colonies in soft agar, and capacity to form densely packed spheroids in low-attachment plates. The growth signaling responses induced by PLCδ4 are not reversible by siRNA. Conclusion Overexpression or dysregulated expression of PLCδ4 may initiate oncogenesis in certain tissues through upregulation of ErbB expression and activation of ERK pathway. Since the growth responses induced by PLCδ4 are not reversible, PLCδ4 itself is not a suitable drug target, but enzymes in pathways activated by PLCδ4 are potential therapeutic targets for oncogenic intervention.

Published
2004
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46. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma : post‐hoc analyses from a phase III trial

Author

Pettengell, Ruth, Sebban, Catherine, Zinzani, Pier Luigi, Derigs, Hans-Günter, Kravchenko, Sergey, Singer, Jack W., Theocharous, Panteli, Wang, Lixia, Pavlyuk, Mariya, Makhlouf, Kahina M., and Coiffier, Bertrand

Subjects
ddc:610
Abstract

This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28-d cycles of 85 mg/m2 pixantrone dimaleate (equivalent to 50 mg/m2 in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2–6) with pixantrone and 3 (2–6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression-free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26–1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B-cell NHL in the 3rd or 4th line setting, independently of previous rituximab.

Published
2017

50. Results of a Phase 3 Randomised Multicenter Study Comparing Pixantrone + Rituximab with Gemcitabine + Rituximab in Patients with Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma Not Eligible for Stem Cell Transplantation

Author

Salles, Gilles Andre, primary, Jurczak, Wojciech, additional, Andorsky, David J., additional, Quick, Donald P., additional, Singer, Jack W., additional, Bedi Singh, Simran, additional, Wang, Lixia, additional, Egorov, Anton, additional, Gabarroca, Christine, additional, and Pettengell, Ruth, additional

Published
2018
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