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38 results on '"Savage, Jason E."'

3. A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer

Author

Zhen, David B, Griffith, Kent A, Ruch, Joshua M, Camphausen, Kevin, Savage, Jason E, Kim, Edward J, Sahai, Vaibhav, Simeone, Diane M, and Zalupski, Mark M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Clinical Trials and Supportive Activities, Rare Diseases, Cancer, Clinical Research, Orphan Drug, Pancreatic Cancer, 6.2 Cellular and gene therapies, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adenocarcinoma, Adult, Aged, Anilides, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Deoxycytidine, Female, Follow-Up Studies, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms, Prognosis, Pyridines, Survival Rate, Gemcitabine, Cabozantinib, XL-184, Pancreatic cancer, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis, Pharmacology and pharmaceutical sciences
Abstract

Background Cabozantinib and gemcitabine improve tumor control in pancreatic ductal adenocarcinoma (PDAC) in preclinical models through c-Met inhibition. We sought to determine the maximum tolerated dose (MTD) of this combination in patients with advanced PDAC. Methods Patients with ≤1 prior treatment and adequate performance status were eligible. Cabozantinib was given orally once daily, beginning day (-)7 and continued with gemcitabine given intravenously on days 1, 8, and 15 every 28 days. Dose level was assigned using Time to Event Continual Reassessment Method (TITE-CRM). Primary endpoint was MTD, defined as the highest dose level at which ≤25 % of patients incurred a dose-limiting toxicity (DLT). Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS) and urinary biomarker assessment. Results Twelve patients were enrolled and treated with 10 patients evaluable for DLT. The probability of DLT was >25 % for all dose levels tested, and thus an MTD was not determined. DLTs included grade 3 ALT/AST elevations and thrombocytopenia. Three patients had partial responses, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95 % CI: 1.4-9.7) and 10.1 months (95 % CI: 3.6-20.6). Exploratory biomarker analysis showed correlation of c-Met and VEGF levels with response. Conclusions An MTD for the combination was not established. Cabozantinib and gemcitabine appear impractical for further development due to DLT at low doses and continuing toxicities with ongoing therapy. Acknowledging the small sample size, responses were seen suggesting further investigation of c-Met inhibition in PDAC may be warranted.

Published
2016

8. Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer

Author

Simone, Brittany A., primary, Dan, Tu, additional, Palagani, Ajay, additional, Jin, Lianjin, additional, Han, Sunny Y., additional, Wright, Christopher, additional, Savage, Jason E., additional, Gitman, Robert, additional, Lim, Meng Kieng, additional, Palazzo, Juan, additional, Mehta, Minesh P., additional, and Simone, Nicole L., additional

Published
2016
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10. Caloric restriction augments radiation efficacy in breast cancer.

Author

Saleh, Anthony D, Simone, Brittany A, Palazzo, Juan, Savage, Jason E, Sano, Yuri, Dan, Tu, Jin, Lianjin, Champ, Colin E, Zhao, Shuping, Lim, Meng, Sotgia, Frederica, Camphausen, Kevin, Pestell, Richard G, Mitchell, James B, Lisanti, Michael P, Simone, Nicole L, Saleh, Anthony D, Simone, Brittany A, Palazzo, Juan, Savage, Jason E, Sano, Yuri, Dan, Tu, Jin, Lianjin, Champ, Colin E, Zhao, Shuping, Lim, Meng, Sotgia, Frederica, Camphausen, Kevin, Pestell, Richard G, Mitchell, James B, Lisanti, Michael P, and Simone, Nicole L

Abstract

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC.

Published
2013

11. Caloric restriction augments radiation efficacy in breast cancer

Author

Saleh, Anthony, primary, Simone, Brittany, additional, Palazzo, Juan, additional, Savage, Jason E., additional, Sano, Yuri, additional, Dan, Tu, additional, Jin, Lianjin, additional, Champ, Colin, additional, Zhao, Shuping, additional, Lim, Meng, additional, Sotgia, Frederica, additional, Camphausen, Kevin, additional, Pestell, Richard, additional, Mitchell, James, additional, Lisanti, Michael, additional, and Simone, Nicole L., additional

Published
2013
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18. Abstract 1328: p53 represses microRNAs let-7a and let-7b in response to ionizing radiation

Author

Saleh, Anthony D., primary, Savage, Jason E., additional, Ly, David, additional, Nguyen, Phuongmai, additional, Cao, Lui, additional, Soule, Benjamin P., additional, Dan, Tu D., additional, DeGraff, William, additional, Finkel, Toren, additional, Harris, Curtis C., additional, Mitchel, James B., additional, Gius, David, additional, and Simone, Nicole L., additional

Published
2010
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27. N1-(Benzenesulfonyl)tryptamines as novel 5-HT6 antagonists

Author

Tsai, Yuching, primary, Dukat, Malgorzata, additional, Slassi, Abdelmalik, additional, MacLean, Neil, additional, Demchyshyn, Lidia, additional, Savage, Jason E., additional, Roth, Bryan L., additional, Hufesein, Sandy, additional, Lee, Mase, additional, and Glennon, Richard A., additional

Published
2000
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36. ChemInform Abstract: Synthesis of Potent and Selective Dopamine D4Antagonists as Candidate Radioligands.

Author

Huang, Yiyun, Kegeles, Lawrence S., Bae, Sung‐A, Hwang, Dah‐ren, Roth, Bryan L., Savage, Jason E., and Laruelle, Marc

Abstract

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Published
2001
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37. ChemInform Abstract: 2‐Substituted Tryptamines: Agents with Selectivity for 5‐HT6Serotonin Receptors.

Author

Glennon, Richard A., Lee, Mase, Rangisetty, Jagadeesh B., Dukat, Malgorzata, Roth, Bryan L., Savage, Jason E., McBride, Ace, Rauser, Laura, Hufeisen, Sandy, and Lee, David K. H.

Abstract

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Published
2000
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38. Geometry-affinity relationships of the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene.

Author

Runyon SP, Peddi S, Savage JE, Roth BL, Glennon RA, and Westkaemper RB

Subjects
3T3 Cells, Animals, Anthracenes chemistry, Anthracenes metabolism, Mice, Models, Molecular, Molecular Conformation, Radioligand Assay, Receptor, Serotonin, 5-HT2A, Structure-Activity Relationship, Transfection, Anthracenes chemical synthesis, Receptors, Serotonin metabolism
Abstract

With the exception of its two aromatic rings and basic nitrogen atom, 9-(aminomethyl)-9,10-dihydroanthracene (AMDA; 1) is remarkably devoid of the pharmacophore features usually associated with high-affinity receptor ligands such as the heteroatom hydrogen bonding features of the endogenous ligand serotonin. AMDA does contain a phenylethylamine skeleton within a tricyclic ring system, and the presence of the second aromatic group is necessary for optimal receptor affinity. The structural requirements for the binding of AMDA at 5-HT(2A) receptors were investigated with respect to the geometric relationship between the two aromatic rings. It appears that the geometry of the AMDA parent is in the optimal range for fold angle between aromatic moieties. Evaluation of conformationally constrained derivatives of AMDA suggests that a chain extended trans, gauche form is most likely responsible for high affinity.

Published
2002
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