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101. Allogeneic and Syngeneic Marrow Transplantation for Aplastic Anemia: Overview of Seattle

Author

Storb, Rainer, primary, Doney, Kristine, additional, Thomas, E. Donnall, additional, Anasetti, Claudio, additional, Appelbaum, Frederick R., additional, Beatty, Patrick, additional, Bensinger, William, additional, Buckner, C. Dean, additional, Clift, Reginald, additional, Fefer, Alexander, additional, Hansen, John, additional, Hill, Roger, additional, Martin, Paul, additional, McGuffin, Robert, additional, Sanders, Jean E., additional, Singer, Jack, additional, Stewart, Patricia, additional, Sullivan, Keith, additional, and Witherspoon, Robert, additional

Published
1988
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102. Chronic Graft-versus-Host Disease: Pathogenesis, Diagnosis, Treatment, and Prognostic Factors

Author

Sullivan, Keith, primary, Witherspoon, Robert, additional, Storb, Rainer, additional, Appelbaum, Frederick R., additional, Beatty, Patrick, additional, Bensinger, William, additional, Bigelow, Carolyn, additional, Buckner, C. Dean, additional, Cheever, Martin, additional, Clift, Reginald A., additional, Doney, Kristine, additional, Fefer, Alexander, additional, Greenberg, Philip, additional, Hansen, John, additional, Martin, Paul, additional, Matthews, Dana, additional, McDonald, George, additional, Meyers, Joel, additional, Petersen, Finn Bo, additional, Sanders, Jean, additional, Shulman, Howard, additional, Singer, Jack, additional, Stewart, Patricia, additional, and Thomas, E. Donnall, additional

Published
1988
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103. Urology in Childhood

Author

Williams, D. Innes, primary, Barratt, T. Martin, additional, Eckstein, Herbert B., additional, Kohlinsky, Sheila M., additional, Newns, George H., additional, Polani, Paul E., additional, and Singer, Jack D., additional

Published
1974
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104. Phospholipase C δ-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells

Author

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

Subjects
MAP Kinase Signaling System, Breast Neoplasms, Cell Growth Processes, lcsh:RC254-282, Culture Media, Serum-Free, Gene Expression Regulation, Enzymologic, Hydrogel, Polyethylene Glycol Dimethacrylate, Spheroids, Cellular, Tumor Cells, Cultured, Humans, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Protein Kinase C, Cell Proliferation, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Research, Genes, erbB-1, Genes, erbB-2, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Up-Regulation, Enzyme Activation, Isoenzymes, Agar, Type C Phospholipases, Phospholipase C delta
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

105. A Randomized Phase II Study of Tosedostat in Combination with Either Cytarabine or Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Author

Mawad, Raya, primary, Becker, Pamela S., additional, Hendrie, Paul C., additional, Scott, Bart L, additional, Wood, Brent L., additional, Dean, Carol, additional, Sandhu, Vicky, additional, Deeg, H. Joachim, additional, Walter, Roland B., additional, Wang, Lixia, additional, Singer, Jack, additional, Estey, Elihu H., additional, and Pagel, John, additional

Published
2014
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108. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms

Author

Sullivan, Keith M., Storb, Rainer, Buckner, C. Dean, Fefer, Alexander, Fisher, Lloyd, Weiden, Paul L., Witherspoon, Robert P., Appelbaum, Frederick R., Banaji, Meera, Hansen, John, Martin, Paul, Sanders, Jean E., Singer, Jack, and Thomas, E. Donnall

Subjects
Graft versus host reaction -- Physiological aspects, Bone marrow -- Transplantation, Immunosuppressive agents -- Dosage and administration, Leukemia -- Physiological aspects, Immunotherapy -- Research, Methotrexate -- Dosage and administration
Abstract

Graft-versus-host-disease (GVHD) can occur after allogenic transplantation (donor is usually a close relative) of bone marrow to a host (patient) in the treatment of leukemia. It is thought that GVHD may actually decrease the likelihood that the patient will have a recurrence of disease. This effect is known as "adoptive immunotherapy"; cells from the bone marrow of the donor recognize and destroy malignant cancer cells in the host, resulting in a "graft-versus-leukemia" effect. A study was conducted to determine whether the antileukemic effect of GVHD could be enhanced to improve long-term survival among patients with advanced leukemia. The patients selected had received allogenic bone marrow transplants, were under 30 years of age (less likely to develop severe GVHD) and had a high risk of cancer recurrence. Three different types of treatment regimens to suppress the immune system (i.e., drugs given to prevent graft rejection) were administered: methotrexate for 102 days (Group I); methotrexate for 11 days (Group II); and methotrexate plus buffy-coat cells (white blood cells and platelets from centrifuged donor blood samples) for 102 days (Group III). GVHD occurred in 25 percent of the patients in Group I, 59 percent of Group II, and 82 percent of Group III. The incidence of chronic GVHD and the five-year probability of survival did not differ among the three groups. Non-cancer related deaths were due to infections complicated by GVHD. Researchers conclude that shortening the period of methotrexate administration or infusing buffy-coat cells increased the incidence of GVHD and related mortality, but did not effect the incidence of chronic GVHD or cancer recurrence. It is speculated that chronic GVHD accompanied by clinical symptoms may be required for a graft-versus-leukemia effect.

Published
1989

111. Stress busters: surefire strategies for success over stress

Author

Singer, Jack N.

Subjects
Stress management, General interest
Abstract

Sarah has been suffering a series of medical conditions, which her doctors have not been able to diagnose or treat effectively. On and off pain in her stomach, achiness in [...]

Published
2011

112. Procoagulant inhibitory properties of paclitaxel poliglumex

Author

Nemunaitis,John, Senzer,Neil, Cooper,Barry, Nemunaitis,Michael, Bedell,Cynthia, Singer,Jack W, Oldham,Fred B, Nemunaitis,John, Senzer,Neil, Cooper,Barry, Nemunaitis,Michael, Bedell,Cynthia, Singer,Jack W, and Oldham,Fred B

Abstract

John Nemunaitis1,2,3, Neil Senzer1,2,3, Barry Cooper2,3, Michael Nemunaitis1, Cynthia Bedell1, Jack W Singer4, Fred B Oldham41Mary Crowley Cancer Research Centers, Dallas, TX, USA; 2Baylor Sammons Cancer Center, Dallas, TX, USA; 3Texas Oncology, Dallas, TX, USA; 4Cell Therapeutics, Inc., Seattle, WA, USABackground: In Phase I evaluation of CT-2103 (paclitaxel poliglumex), prolongation of prothrombin time (PT) and activated thromboplastin time (aPTT) was observed, without clinical consequence, with doses 1.3–1.5 times higher than the current clinical dose of 175 mg/m2. This Phase I, open-label, nonrandomized pilot study was performed to study the effect of the standard dose regimen on blood coagulation.Methods: Seven previously treated solid tumor patients received CT-2103 175 mg/m2 intravenously on day 1 of 21-day cycles for a mean of 5.4 cycles (median 4, range 2–14). Plasma samples were collected for cycle 1 predose and at hours 1, 24, 48, and 72 after the end of administration for drug levels, and for PT and aPTT assays.Results: No coagulopathy-related adverse events were documented. Bleeding time remained normal in the six patients tested, with transient increases in PT and aPTT noted but resolving within 72 hours. Titration studies at 100 µg/mL of CT-2103 (corresponding to the standard clinical dose) prolonged PT and aPTT clotting times, produced a modest dose-dependent reduction of thrombin and factor Xa, and no significant changes in factors IXa, XIa, or XIIa. Two patients achieved stable disease for ≥10 cycles.Conclusion: CT-2103 is associated with transient prolongation of PT and aPTT without clinical sequelae.Keywords: CT-2103, paclitaxel, poliglumex, cancer

Published
2010

113. 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-naive advanced non-small cell lung cancer

Author

Langer, Corey, O'Byrne, Kenneth, Socinski, Mark, Mikhailov, Sergei, Lesniewski-Kmak, Krzysztof, Smakal, Martin, Ciuleanu, Tudor, Orlov, Sergey, Dediu, Mircea, Heigener, David, Eisenfeld, Amy, Sandalic, Larissa, Oldham, Fred, Singer, Jack, Ross, Helen, Langer, Corey, O'Byrne, Kenneth, Socinski, Mark, Mikhailov, Sergei, Lesniewski-Kmak, Krzysztof, Smakal, Martin, Ciuleanu, Tudor, Orlov, Sergey, Dediu, Mircea, Heigener, David, Eisenfeld, Amy, Sandalic, Larissa, Oldham, Fred, Singer, Jack, and Ross, Helen

Abstract

Free to read at publisher's site. INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

Published
2008

114. A Phase II Study Of Tosedostat (TST) In Combination With Either Cytarabine Or Decitabine In Newly Diagnosed Older Patients With Acute Myeloid Leukemia (AML) Or High-Risk Myelodysplastic Syndrome (MDS)

Author

Mawad, Raya, primary, Becker, Pamela S., additional, Hendrie, Paul C., additional, Scott, Bart L, additional, Wood, Brent L., additional, Dean, Carol, additional, Sandhu, Ravinder K, additional, Deeg, H. Joachim, additional, Walter, Roland B., additional, Appelbaum, Frederick R., additional, Wang, Lixia, additional, Myint, Han, additional, Singer, Jack, additional, Estey, Elihu H., additional, and Pagel, John M., additional

Published
2013
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122. Marrow Transplantation for the Treatment of Chronic Myelogenous Leukemia

Author

THOMAS, DONNALL E., CLIFT, REGINALD A., FEFER, ALEXANDER, APPELBAUM, FREDERICK R., BEATTY, PATRICK, BENSINGER, WILLIAM I., BUCKNER, DEAN C., CHEEVER, MARTIN A., DEEG, JOACHIM H., DONEY, KRISTINE, FLOURNOY, NANCY, GREENBERG, PHILIP, HANSEN, JOHN A., MARTIN, PAUL, McGUFFIN, ROBERT, RAMBERG, ROBERT, SANDERS, JEAN E., SINGER, JACK, STEWART, PATRICIA, STORB, RAINER, SULLIVAN, KEITH, WEIDEN, PAUL L., and WITHERSPOON, ROBERT

Published
1986
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125. Phase 3 Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (EXTEND): End of Study Results.

Author

Pettengell, Ruth, primary, Zinzani, Pier Luigi, additional, Narayanan, Geetha, additional, de Mendoza, Fernando Hurtado, additional, Digumarti, Raghunadharao, additional, Gomez, Henry, additional, Coiffier, Bertrand, additional, Schiller, Gary, additional, Rizzieri, David A., additional, Cernohous, Paul, additional, Wang, Lixia, additional, and Singer, Jack, additional

Published
2010
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129. Phase III Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin's Lymphoma (EXTEND): Results From the Treatment and Follow-up Periods.

Author

Pettengell, Ruth, primary, Coiffier, Bertrand, additional, Narayanan, Geetha, additional, de Mendoza, Fernando Hurtado, additional, Digumarti, Raghunadharao, additional, Gomez, Henry, additional, Zinzani, Pier Luigi, additional, Schiller, Gary J, additional, Rizzieri, David A, additional, Cernohous, Paul, additional, Wang, Lixia, additional, and Singer, Jack W., additional

Published
2009
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131. Novel Bis-platinum Complexes Endowed with an Improved Pharmacological Profile

Author

Gatti, Laura, primary, Perego, Paola, additional, Leone, Roberto, additional, Apostoli, Piero, additional, Carenini, Nives, additional, Corna, Elisabetta, additional, Allievi, Cecilia, additional, Bastrup, Ulla, additional, De Munari, Sergio, additional, Di Giovine, Stefano, additional, Nicoli, Paola, additional, Grugni, Mario, additional, Natangelo, Marco, additional, Pardi, Gianluca, additional, Pezzoni, Gabriella, additional, Singer, Jack W., additional, and Zunino, Franco, additional

Published
2009
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140. 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, additional, Demehri, Shadmer, additional, Härtel, Nicolai, additional, de Vries, Peter, additional, Bonham, Lynn, additional, Hollenback, David, additional, Singer, Jack W., additional, Melo, Junia V., additional, Druker, Brian J., additional, and Deininger, Michael W., additional

Published
2006
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147. Lysophosphatidic Acid Acyltransferase-β Is a Prognostic Marker and Therapeutic Target in Gynecologic Malignancies

Author

Springett, Gregory M., primary, Bonham, Lynn, additional, Hummer, Amanda, additional, Linkov, Irina, additional, Misra, Dipika, additional, Ma, Chia, additional, Pezzoni, Gabriella, additional, Di Giovine, Stefano, additional, Singer, Jack, additional, Kawasaki, Hiroaki, additional, Spriggs, David, additional, Soslow, Robert, additional, and Dupont, Jakob, additional

Published
2005
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148. Induction of Apoptosis Using Inhibitors of Lysophosphatidic Acid Acyltransferase-β and Anti-CD20 Monoclonal Antibodies for Treatment of Human Non-Hodgkin's Lymphomas

Author

Pagel, John M., primary, Laugen, Christian, additional, Bonham, Lynn, additional, Hackman, Robert C., additional, Hockenbery, David M., additional, Bhatt, Rama, additional, Hollenback, David, additional, Carew, Heather, additional, Singer, Jack W., additional, and Press, Oliver W., additional

Published
2005
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150. Molecular Characterization of PS-341 (bortezomib) Resistance: Implications for Overcoming Resistance Using Lysophosphatidic Acid Acyltransferase (LPAAT)-β Inhibitors.

Author

Hideshima, Teru, primary, Chauhan, Dharminder, primary, Ishitsuka, Kenji, primary, Raje, Noopur, primary, Kumar, Shaji, primary, Podar, Klaus, primary, Mitsiades, Constantine, primary, Hideshima, Hiromasa, primary, Bonham, Lynn, primary, Munshi, Nikhil C., primary, Richardson, Paul G., primary, Singer, Jack W., primary, and Anderson, Kenneth C., primary

Published
2004
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