Full Text Journal Articles by
Author Donald Durden

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Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma.

Venugopal Gunda, Anup S Pathania, Srinivas Chava, Philip Prathipati, Nagendra K Chaturvedi, Don W Coulter, Manoj K Pandey, Donald L Durden, Kishore B Challagundla,

Neuroblastoma are pediatric, extracranial malignancies showing alarming survival prognosis outcomes due to their resilience to current aggressive treatment regimens, including chemotherapies with cisplatin (CDDP) provided in the first line of therapy regimens. Metabolic deregulation supports tumor cell survival in drug-treated conditions. However, metabolic pathways underlying cisplatin-resistance are least studied in ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(9):]

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A triple action CDK4/6-PI3K-BET inhibitor with augmented cancer cell cytotoxicity.

Adam M Burgoyne, Kendra R Vann, Shweta Joshi, Guillermo A Morales, Francisco M Vega, Alok Singh, Dhananjaya Pal, Aran B Merati, Tatiana G Kutateladze, Donald L Durden,

Cell Discov (Cell discovery)
[2020, 6:49]

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Design of thienopyranone-based BET inhibitors that bind multiple synthetic lethality targets.

Kendra R Vann, Dhananjaya Pal, Guillermo A Morales, Adam M Burgoyne, Donald L Durden, Tatiana G Kutateladze,

Development of small molecule compounds that target several cancer drivers has shown great therapeutic potential. Here, we developed a new generation of highly potent thienopyranone (TP)-based inhibitors for the BET bromodomains (BDs) of the transcriptional regulator BRD4 that have the ability to simultaneously bind to phosphatidylinositol-3 kinase (PI3K) and/or cyclin-dependent ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):12027]

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Macrophage Syk-PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk-PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression.

Shweta Joshi, Kevin X Liu, Muamera Zulcic, Alok R Singh, Dylan Skola, Christopher K Glass, P Dominick Sanders, Andrew B Sharabi, Timothy V Pham, Pablo Tamayo, Daniel Shiang, Huy Q Dinh, Catherine C Hedrick, Guillermo A Morales, Joseph R Garlich, Donald L Durden,

Macrophages (MΦ) play a critical role in tumor growth, immunosuppression, and inhibition of adaptive immune responses in cancer. Hence, targeting signaling pathways in MΦs that promote tumor immunosuppression will provide therapeutic benefit. PI3Kγ has been recently established by our group and others as a novel immuno-oncology target. Herein, we report ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2020, 19(3):755-764]

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Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma.

Kirti Kandhwal Chahal, Jie Li, Irina Kufareva, Milind Parle, Donald L Durden, Robert J Wechsler-Reya, Clark C Chen, Ruben Abagyan,

Dysregulation of the seven-transmembrane (7TM) receptor Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway contributes to the development of cancers including basal cell carcinoma (BCC) and medulloblastoma (MB). However, SMO-specific antagonists produced mixed results in clinical trials, marked by limited efficacy and high rate of acquired resistance ... Read more >>

PLoS ONE (PloS one)
[2019, 14(9):e0214901]

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Hypoxia-induced PIM kinase and laminin-activated integrin α6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC.

Rachel K Toth, Jack D Tran, Michelle T Muldong, Eric A Nollet, Veronique V Schulz, Corbin C Jensen, Lori A Hazlehurst, Eva Corey, Donald Durden, Christina Jamieson, Cindy K Miranti, Noel A Warfel,

Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical trials. ... Read more >>

Am J Clin Exp Urol (American journal of clinical and experimental urology)
[2019, 7(4):297-312]

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Hypoxia-Induced PIM Kinase and Laminin-Activated Integrin α6 Mediate Resistance to PI3K Inhibitors in Bone-Metastatic CRPC

Rachel Toth, Jack Tran, Michelle Muldong, Eric Nollet, Veronique Schulz, Corbin Jensen, Lori Hazelhurst, Eva Corey, Donald Durden, Christina Jamieson, Cindy Miranti, Noel Warfel,

ABSTRACT Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical ... Read more >>

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SF2523: Dual PI3K/BRD4 Inhibitor Blocks Tumor Immunosuppression and Promotes Adaptive Immune Responses in Cancer.

Shweta Joshi, Alok R Singh, Kevin X Liu, Timothy V Pham, Muamera Zulcic, Dylan Skola, Hyun Bae Chun, Christopher K Glass, Guillermo A Morales, Joseph R Garlich, Donald L Durden,

Macrophages (MΘs) are key immune infiltrates in solid tumors and serve as major drivers behind tumor growth, immune suppression, and inhibition of adaptive immune responses in the tumor microenvironment (TME). Bromodomain and extraterminal (BET) protein, BRD4, which binds to acetylated lysine on histone tails, has recently been reported to promote ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2019, 18(6):1036-1044]

Cited: 2 times

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Nilotinib, an approved leukemia drug, inhibits Smoothened signaling in Hedgehog-dependent medulloblastoma

Kirti Chahal, Jie Li, Irina Kufareva, Milind Parle, Donald Durden, Robert Wechsler-Reya, Clark Chen, Ruben Abagyan,

Abstract Dysregulation of the seven-transmembrane (7TM) receptor Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway contributes to the development of cancers including basal cell carcinoma (BCC) and medulloblastoma (MB). However, SMO-specific antagonists produced mixed results in clinical trials, marked by limited efficacy and high rate of acquired ... Read more >>

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Combinatorial Approach to Improve Cancer Immunotherapy: Rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System.

Shweta Joshi, Donald L Durden,

Cancer immunotherapy, including immune checkpoint blockade and adoptive CAR T-cell therapy, has clearly established itself as an important modality to treat melanoma and other malignancies. Despite the tremendous clinical success of immunotherapy over other cancer treatments, this approach has shown substantial benefit to only some of the patients while the ... Read more >>

J Oncol (Journal of oncology)
[2019, 2019:5245034]

Cited: 9 times

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PDCT-03. A PHASE II TRIAL OF POLY-ICLC IN THE MANAGEMENT OF RECURRENT OR PROGRESSIVE PEDIATRIC LOW GRADE GLIOMAS. RESULTS FOR THE NEUROFIBROMATOSIS 1 GROUP. (NCT01188096).

Dolly Aguilera, Tobey MacDonald, Robert Castellino, Anna Janss, Claire Mazewski, Nadja Kadom, Minya Pu, Karen Messer, John Crawford, Erin Connelly, Rachel Gray, Andres Salazar, Donald Durden,

AbstractBACKGROUNDPolyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) is a double stranded RNA that acts as a ligand for the Toll Receptor 3 (TLR3) and results in a broad host defense stimulation, including T-cell and natural killer cell activation and cytokine release (interferons alpha, beta, and gamma, interleukins, corticosteroids, and ... Read more >>

Neuro-oncology (Neuro-oncology)
[2018, 20(Suppl 6):vi201-vi201]

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Erratum to: Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

Esther J Cooke, Jenny Y Zhou, Tine Wyseure, Shweta Joshi, Vikas Bhat, Donald L Durden, Laurent O Mosnier, Annette von Drygalski,

Thromb. Haemost. (Thrombosis and haemostasis)
[2019, 119(9):1546]

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LGG-58. A PHASE II TRIAL OF POLY-ICLC IN THE MANAGEMENT OF RECURRENT OR PROGRESSIVE PEDIATRIC LOW GRADE GLIOMAS (NCT01188096): PRELIMINARY ANALYSIS.

Dolly Aguilera, Tobey MacDonald, John Crawford, Nadja Kadom, Anna Janss, Claire Mazewski, Robert Craig Castellino, Rachael Gray, Minya Pu, Erin Connelly, Andres Salazar, Donald L Durden,

AbstractLow dose Poly-ICLC (Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose) has a direct immune enhancing action independent of interferon, including increased antibody response to antigen, and NK cell, T-cell, macrophage and cytokine activation.METHODSWe conducted an immunotherapy trial to evaluate the effect of Poly-ICLC in the children with recurrent or progressive ... Read more >>

Neuro-oncology (Neuro-oncology)
[2018, 20(Suppl 2):i116-i117]

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Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

Esther J Cooke, Jenny Y Zhou, Tine Wyseure, Shweta Joshi, Vikas Bhat, Donald L Durden, Laurent O Mosnier, Annette von Drygalski,

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty ... Read more >>

Thromb. Haemost. (Thrombosis and haemostasis)
[2018, 118(6):1036-1047]

Cited: 8 times

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Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype.

Shweta Joshi, Alok R Singh, Simon S Wong, Muamera Zulcic, Min Jiang, Annie Pardo, Moises Selman, James S Hagood, Donald L Durden,

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present ... Read more >>

PLoS ONE (PloS one)
[2017, 12(8):e0182851]

Cited: 6 times

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Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis.

Forest H Andrews, Alok R Singh, Shweta Joshi, Cassandra A Smith, Guillermo A Morales, Joseph R Garlich, Donald L Durden, Tatiana G Kutateladze,

MYC is a major cancer driver but is documented to be a difficult therapeutic target itself. Here, we report on the biological activity, the structural basis, and therapeutic effects of the family of multitargeted compounds that simultaneously disrupt functions of two critical MYC-mediating factors through inhibiting the acetyllysine binding of ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2017, 114(7):E1072-E1080]

Cited: 29 times

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The differential ability of asparagine and glutamine in promoting the closed/active enzyme conformation rationalizes the Wolinella succinogenes L-asparaginase substrate specificity.

Hien Anh Nguyen, Donald L Durden, Arnon Lavie,

Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase ... Read more >>

Sci Rep (Scientific reports)
[2017, 7:41643]

Cited: 3 times

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Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126.

Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden,

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but ... Read more >>

Oncotarget (Oncotarget)
[2016, :]

Cited: 1 time

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Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126.

Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden,

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(32):52193-52210]

Cited: 4 times

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PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma.

Alok R Singh, Shweta Joshi, Muamera Zulcic, Michael Alcaraz, Joseph R Garlich, Guillermo A Morales, Yoon J Cho, Lei Bao, Michael L Levy, Robert Newbury, Denise Malicki, Karen Messer, John Crawford, Donald L Durden,

Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and ... Read more >>

PLoS ONE (PloS one)
[2016, 11(3):e0150836]

Cited: 12 times

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Vascular remodeling underlies rebleeding in hemophilic arthropathy.

Vikas Bhat, Merissa Olmer, Shweta Joshi, Donald L Durden, Thomas J Cramer, Richard Fw Barnes, Scott T Ball, Tudor H Hughes, Mauricio Silva, James V Luck, Randy E Moore, Laurent O Mosnier, Annette von Drygalski,

Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We ... Read more >>

Am. J. Hematol. (American journal of hematology)
[2015, 90(11):1027-1035]

Cited: 27 times

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Knockout Serum Replacement Promotes Cell Survival by Preventing BIM from Inducing Mitochondrial Cytochrome C Release.

Yuki Ishii, May Keu Nhiayi, Edison Tse, Jonathan Cheng, Michele Massimino, Donald L Durden, Paolo Vigneri, Jean Y J Wang,

Knockout serum replacement (KOSR) is a nutrient supplement commonly used to replace serum for culturing stem cells. We show here that KOSR has pro-survival activity in chronic myelogenous leukemia (CML) cells transformed by the BCR-ABL oncogene. Inhibitors of BCR-ABL tyrosine kinase kill CML cells by stimulating pro-apoptotic BIM and inhibiting ... Read more >>

PLoS ONE (PloS one)
[2015, 10(10):e0140585]

Cited: 6 times

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Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma.

Shweta Joshi, Alok R Singh, Donald L Durden,

SF1126 is a vascular-targeted pan-PI-3K inhibitor prodrug with antitumor and antiangiogenic activity and has completed phase I clinical trial in solid tumors and B-cell malignancies. In this study, we investigated the effect of SF1126 on hypoxic HIF-1α/HIF-2α stability as well as on antitumor and/or antiangiogenic activity in renal cell carcinoma ... Read more >>

Cancer Chemother. Pharmacol. (Cancer chemotherapy and pharmacology)
[2015, 75(3):595-608]

Cited: 11 times

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Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model.

Alok R Singh, Shweta Joshi, Elizabeth George, Donald L Durden,

Growth factor mediated activation of RAS-MAP-kinase and PI3-kinase-AKT pathways are critical for the pathogenesis of glioblastoma. The attenuation of PI3-kinase/AKT signaling will be effective in regulating the tumorigenic phenotypes of the glioma cells.Glioma cells derived from the brain of the (12) V-Ha-Ras transgenic mice were used to study the effect of ... Read more >>

Cancer Cell Int. (Cancer cell international)
[2014, 14(1):105]

Cited: 11 times

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Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors.

Lisa L R Hartman, John R Crawford, Milan T Makale, Mehrzad Milburn, Shweta Joshi, Andres M Salazar, Beth Hasenauer, Scott R VandenBerg, Tobey J MacDonald, Donald L Durden,

Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded ... Read more >>

J. Pediatr. Hematol. Oncol. (Journal of pediatric hematology/oncology)
[2014, 36(6):451-457]

Cited: 16 times

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