8 results on '"Bruce J. Dezube"'
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2. Author Correction: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer
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Anniina Färkkilä, Doga C. Gulhan, Julia Casado, Connor A. Jacobson, Huy Nguyen, Bose Kochupurakkal, Zoltan Maliga, Clarence Yapp, Yu-An Chen, Denis Schapiro, Yinghui Zhou, Julie R. Graham, Bruce J. Dezube, Pamela Munster, Sandro Santagata, Elizabeth Garcia, Scott Rodig, Ana Lako, Dipanjan Chowdhury, Geoffrey I. Shapiro, Ursula A. Matulonis, Peter J. Park, Sampsa Hautaniemi, Peter K. Sorger, Elizabeth M. Swisher, Alan D. D’Andrea, and Panagiotis A. Konstantinopoulos
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Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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3. IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin–paclitaxel, with or without bevacizumab in patients with advanced cancer
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Wei Guo, Manish R Patel, Nashat Gabrail, Jordi Rodon, Erika Hamilton, Timothy A Yap, Meghan Duncan, Alberto Bessudo, Jasgit Sachdev, Lena Evilevitch, Sujatha Kumar, Sharon Lu, and Bruce J Dezube
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Doublet combination therapies targeting immune checkpoints have shown promising efficacy in patients with advanced solid tumors, but it is unknown if rational triplet combinations will be well tolerated and associated with improved antitumor activity. The objective of this trial was to determine the recommended phase 2 doses (RP2Ds) and to assess the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor dostarlimab in combination with (1) the poly(ADP-ribose) polymerase inhibitor niraparib with or without vascular endothelial growth factor inhibitor bevacizumab or (2) carboplatin–paclitaxel chemotherapy with or without bevacizumab, in patients with advanced cancer.Methods IOLite is a multicenter, open-label, multi-arm clinical trial. Patients with advanced solid tumors were enrolled. Patients received dostarlimab in combination with niraparib with or without bevacizumab or in combination with carboplatin–paclitaxel with or without bevacizumab until disease progression, unacceptable toxicity, or withdrawal from the study. Prespecified endpoints in all parts were to evaluate the dose-limiting toxicities (DLTs), RP2Ds, pharmacokinetics (PKs), and preliminary efficacy for each combination.Results A total of 55 patients were enrolled; patients received dostarlimab and: (1) niraparib in part A (n=22); (2) carboplatin–paclitaxel in part B (n=14); (3) niraparib plus bevacizumab in part C (n=13); (4) carboplatin–paclitaxel plus bevacizumab in part D (n=6). The RP2Ds of all combinations were determined. All combinations were safe and tolerable, with no new safety signals observed. DLTs were reported in 2, 1, 2, and 0 patients, in parts A–D, respectively. Preliminary antitumor activity was observed, with confirmed Response Evaluation Criteria in Solid Tumors v1.1 complete/partial responses reported in 4 of 22 patients (18.2%), 6 of 14 patients (42.9%), 4 of 13 patients (30.8%), and 3 of 6 (50.0%) patients, in parts A–D, respectively. Disease control rates were 40.9%, 57.1%, 84.6%, and 83.3%, in parts A–D, respectively. Dostarlimab PK was unaffected by any combinations tested. Coadministration of bevacizumab showed no impact on niraparib PKs. The overall mean PD-1 receptor occupancy was 99.0%.Conclusions Dostarlimab was well tolerated in both doublet and triplet regimens tested, with promising antitumor activity observed with all combinations. We observed higher disease control rates in the triplet regimens than in doublet regimens.Trial registration number NCT03307785.
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- 2022
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4. Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.
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John C Morris, Antoinette R Tan, Thomas E Olencki, Geoffrey I Shapiro, Bruce J Dezube, Michael Reiss, Frank J Hsu, Jay A Berzofsky, and Donald P Lawrence
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Medicine ,Science - Abstract
In advanced cancers, transforming growth factor-beta (TGFβ) promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients) and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks).GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.Clinicaltrials.gov NCT00356460.
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- 2014
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5. Kaposi sarcoma of the musculoskeletal system: A review of 66 patients.
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Gabriel Caponetti, Bruce J. Dezube, Carlos S. Restrepo, and Liron Pantanowitz
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KAPOSI'S sarcoma , *MUSCULOSKELETAL system , *AIDS patients , *SPINAL cord , *BONES , *PATHOLOGY - Abstract
Kaposi sarcoma (KS) of bone and skeletal muscle is unusual. In this report, the authors review 66 published patients with KS who had involvement of the musculoskeletal system reported from 1925 to 2006. In only 3 patients was acquired immunodeficiency syndrome (AIDS)‐related KS identified within skeletal muscle. Osseous KS lesions were more frequent and occurred with African, classic, and AIDS‐related KS and occurred rarely in transplantation‐associated KS. Patients seldom were asymptomatic. They usually had bone pain with limited mobility or infrequently developed serious sequelae like spinal cord compression. Locally aggressive African and classic KS lesions typically involved the peripheral skeleton; whereas, in patients with AIDS, the axial (vertebrae, ribs, sternum, and pelvis) and/or maxillofacial bones more commonly were involved. Almost all patients had concomitant nonosseous KS lesions. Joint involvement was exceptional, and pathologic fractures were not observed. Computed tomography scans and magnetic resonance images were better at detecting osseous KS lesions, which frequently went undetected on plain x‐ray films or bone scans. Pathologic diagnosis was important to exclude similar lesions like bacillary angiomatosis. Treatment options, including surgery and, in more recent patients, radiation and/or chemotherapy, had limited success. Cancer 2007 © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2007
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6. New therapies for the treatment of AIDS-related Kaposi sarcoma.
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Bruce J. Dezube
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- 2000
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7. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.
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Andrea J O'Hara, Pauline Chugh, Ling Wang, Eduardo M Netto, Estrella Luz, William J Harrington, Bruce J Dezube, Blossom Damania, and Dirk P Dittmer
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.
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- 2009
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8. Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042.
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Koon HB, Krown SE, Lee JY, Honda K, Rapisuwon S, Wang Z, Aboulafia D, Reid EG, Rudek MA, Dezube BJ, and Noy A
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- AIDS-Related Opportunistic Infections blood, AIDS-Related Opportunistic Infections enzymology, AIDS-Related Opportunistic Infections genetics, AIDS-Related Opportunistic Infections pathology, Adult, Aged, Anti-HIV Agents therapeutic use, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Benzamides adverse effects, Benzamides pharmacokinetics, Cytokines blood, Disease Progression, Female, Humans, Imatinib Mesylate, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Pilot Projects, Piperazines adverse effects, Piperazines pharmacokinetics, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors pharmacokinetics, Proto-Oncogene Proteins c-kit antagonists & inhibitors, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Pyrimidines adverse effects, Pyrimidines pharmacokinetics, Receptor, Platelet-Derived Growth Factor beta antagonists & inhibitors, Receptor, Platelet-Derived Growth Factor beta genetics, Receptor, Platelet-Derived Growth Factor beta metabolism, Sarcoma, Kaposi blood, Sarcoma, Kaposi enzymology, Sarcoma, Kaposi genetics, Sarcoma, Kaposi pathology, Time Factors, Treatment Outcome, United States, AIDS-Related Opportunistic Infections drug therapy, Antineoplastic Agents therapeutic use, Benzamides therapeutic use, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Sarcoma, Kaposi drug therapy
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Purpose: Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients., Patients and Methods: This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable., Results: Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines., Conclusion: Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.
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- 2014
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