Janina‐Miriam Noy, Hongxu Lu, Philip J. Hogg, Jialin Yang, Martina H. Stenzel,
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine ... of polymeric micelles based on the anticancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid ... resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt % of PENAO MA. The different block copolymers self-assembled into ... and cellular uptake compared to the free drug PENAO (IC50 (PENAO) = 2.7 ± 0.3 μM; IC50 ( ...
Tópico(s): Metal complexes synthesis and properties
2018 - American Chemical Society | Bioconjugate Chemistry
Han Shen, S. Decollogne, Pierre J. Dilda, Eric Hau, Sylvia A. Chung, Peter P. Luk, Philip J. Hogg, Kerrie L. McDonald,
... with 4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid (PENAO), an in-house designed novel arsenic-based mitochondrial ... flux assay and mass spectrometry.As monotherapies, both PENAO and DCA induced proliferation arrest in a panel of GBM cell lines and primary isolates. PENAO inhibited oxygen consumption, induced oxidative stress and depolarized ... activated mitochondria-mediated apoptosis. By combining DCA with PENAO, the two drugs worked synergistically to inhibit cell ... in the mechanism by which the combination of PENAO and DCA induces cell death. Additionally, PENAO-induced ...
Tópico(s): Mitochondrial Function and Pathology
2015 - BioMed Central | Journal of Experimental & Clinical Cancer Research
S. Decollogne, Swapna Joshi, Sylvia A. Chung, Peter P. Luk, Reichelle X. Yeo, Sheri Nixdorf, André Fedier, Viola Heinzelmann‐Schwarz, Philip J. Hogg, Pierre J. Dilda,
... The purpose of this study was to test PENAO, a promising new organoarsenical that is in phase ... Methods Proliferation arrest and cell death induced by PENAO in serous (OVCAR-3), endometrioid (SKOV-3, TOV112D), ... mitochondrial depolarisation, oxygen consumption and acid production. Results PENAO demonstrated promising anti-proliferative activity on the most ... cells were, however, shown to be resistant to PENAO in vitro and in a xenograft mouse model. ... was due to an ability to cope with PENAO-induced oxidative stress, notably through heme oxygenase-1 ...
Tópico(s): Metabolism and Genetic Disorders
2015 - Elsevier BV | Gynecologic Oncology
Bevan P. Gang, Pierre J. Dilda, Philip J. Hogg, Anneke C. Blackburn,
... PDK) inhibitor that can reverse the Warburg effect. PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) is ... using DCA to promote mitochondrial activity combined with PENAO to inhibit mitochondrial activity, in breast and other carcinoma cell lines. PENAO was effective at low uM concentrations in luminal ( ... cells, in normoxia and hypoxia. The cytotoxicity of PENAO was enhanced by DCA by a mechanism involving ... all cancer cell lines tested toward apoptosis of PENAO. DCA and PENAO are both currently in clinical ...
Tópico(s): Mitochondrial Function and Pathology
2014 - Taylor & Francis | Cancer Biology & Therapy
Bevan P. Gang, Pierre J. Dilda, Philip J. Hogg, Anneke C. Blackburn,
... by 4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid (PENAO), a novel anti-mitochondrial agent. At 5 mM ... ability of DCA to enhance apoptosis induced by PENAO was also examined. The IC50 for PENAO (48 hr) was 3-13 µM for MDA- ... combined with 5 mM DCA, the IC50 of PENAO for all cancer cell lines decreased by 15- ... hr with 5 mM DCA and 5 µM PENAO doubled the proportion of apoptotic cells compared to PENAO alone on T-47D and MDA-MB-231 ...
Tópico(s): ATP Synthase and ATPases Research
2012 - American Association for Cancer Research | Cancer Research
Janina‐Miriam Noy, Fan Chen, Dewan Taslima Akhter, Zachary H. Houston, Nicholas L. Fletcher, Kristofer J. Thurecht, Martina H. Stenzel,
... and 4-(N-(S-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was reported. The anticancer drug 4-(N-(S-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was conjugated to the shell-forming block. Interactions ... assessed using in vitro experiment (with PEG-co- PENAO-coated micelles showing slightly higher cytotoxicity and better ... of injection, the majority of the MPC-co-PENAO-coated nanoparticles were found to accumulate in the ...
Tópico(s): Advanced Drug Delivery Systems
2020 - American Chemical Society | Biomacromolecules
Danielle Park, Joyce Chiu, Gabriel G. Perrone, Pierre J. Dilda, Philip J. Hogg,
... 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) and PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) are ... tumours. The trivalent arsenical moiety of GSAO and PENAO reacts with two matrix facing cysteine residues of ... interaction with the arsenical moiety of GSAO and PENAO. The arsenic atom of both compounds cross-links ...
Tópico(s): Cancer, Hypoxia, and Metabolism
2012 - BioMed Central | Cancer Cell International
Janith A. Seneviratne, Daniel R. Carter, Rituparna Mittra, Andrew J. Gifford, Patrick Y. Kim, Jie‐Si Luo, Chelsea Mayoh, Alice Salib, Aldwin Suryo Rahmanto, Jayne Murray, Ngan Ching Cheng, Zsuzsanna Nagy, Qian Wang, Ane Kleynhans, Owen Tan, Selina K. Sutton, Chengyuan Xue, Sylvia A. Chung, Yizhuo Zhang, Chengtao Sun, Li Zhang, Michelle Haber, Murray D. Norris, Jamie I. Fletcher, Tao Liu, Pierre J. Dilda, Philip J. Hogg, Belamy B. Cheung, Glenn M. Marshall,
... in pre-clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma ... use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in ... cells independent of TP53-status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre- ...
Tópico(s): Histone Deacetylase Inhibitors Research
2022 - Wiley | International Journal of Cancer
Janina‐Miriam Noy, Cheng Cao, Martina H. Stenzel,
... the synthesis of poly(2-methacryloyloxyethyl phosphorycholine-co-PENAO)-block-poly(methyl methacrylate) core-shell nanoparticles which ... reactivity and cytotoxicity of the organoarsenical anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid). More ... scattering (SANS) experiments were conducted, evidencing that having PENAO located in the hydrophilic building block indeed influences ...
Tópico(s): Nanoparticle-Based Drug Delivery
2018 - American Chemical Society | ACS Macro Letters
Ben Tran, Anne Hamilton, Lisa G. Horvath, Michael Lam, Peter Savas, Peter Grimison, James R. Whittle, James Kuo, Nicole Signal, David J. Edmonds, Philip J. Hogg, Danny Rischin, Jayesh Desai,
e14025 Background: PENAO is an organic arsenical with anti-mitochondrial activity mediated by covalent inhibition of adenine nucleotide translocase (ANT). In ... activity of continuous drug exposure at 1-10µM PENAO (or equivalent arsenic (As) atoms), most evident in ... warranted exploration of more convenient dosing schedules. Conclusions: PENAO can be given safely as an uninterrupted CIVI ...
Tópico(s): Drug-Induced Ocular Toxicity
2016 - Lippincott Williams & Wilkins | Journal of Clinical Oncology
Sylvia A. Chung, S. Decollogne, Peter P. Luk, Han Shen, Wendy Ha, Bryan W. Day, Brett W. Stringer, Philip J. Hogg, Pierre J. Dilda, Kerrie L. McDonald,
PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a promising new treatment for glioblastoma patients and is currently in Phase-I clinical trial testing. PENAO selectively targets cancer-specific mitochondrial metabolism by binding ... and reactive oxygen species (ROS)-related cell death. PENAO, as a monotherapy, has shown potent efficacy however we have recently found significant synergism with PENAO and the blocking of glutathione. In a panel ... derived lines (from both primary and recurrent tumours), PENAO demonstrated marked anti-proliferative activity with IC50 values ...
Tópico(s): Cancer, Lipids, and Metabolism
2014 - Oxford University Press | Neuro-Oncology
Janina‐Miriam Noy, Fan Chen, Martina H. Stenzel,
... methyl ether methacrylate) (pPEGMA) and the anticancer drug PENAO (4-( N -( S -penicillaminylacetyl)amino)phenylarsenonous acid) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and PENAO were reported. Both PISA particles were reacted with ...
Tópico(s): Lanthanide and Transition Metal Complexes
2021 - Beilstein Institute for the Advancement of Chemical Sciences | Beilstein Journal of Organic Chemistry
Maria Tsoli, Jie Liu, Laura Franshaw, Han Shen, Cecilia Y. Cheng, MoonSun Jung, Swapna Joshi, Anahid Ehteda, Aaminah Khan, Angel Montero-Carcabosso, Pierre J. Dilda, Philip J. Hogg, David S. Ziegler,
... a key organelle that facilitates these critical processes. PENAO is a novel anti-cancer compound that targets ... protein and are sensitive to the mitochondrial inhibitor PENAO through oxidative stress, while its apoptotic effects were ...
Tópico(s): Mitochondrial Function and Pathology
2018 - Impact Journals LLC | Oncotarget
Pierre J. Dilda, S. Decollogne, Lakmini Weerakoon, Murray D. Norris, Michelle Haber, John Allen, Philip J. Hogg,
... A cysteine mimetic analogue of GSAO was made, PENAO, which accumulates in cells 85 times faster than ... MRP1/2. The faster rate of accumulation of PENAO corresponds to a 44-fold increase in antiproliferative ...
Tópico(s): Cancer therapeutics and mechanisms
2009 - American Chemical Society | Journal of Medicinal Chemistry
Jerry Kang, Mahzarin R. Banaji,
... Justice Ginsburg, dissenting in Adarand Constructors, Inc. v. PenaÔ ne thing I have leamed in a long ...
Tópico(s): Psychology of Moral and Emotional Judgment
2006 - UC Berkeley School of Law | California Law Review
... 58, No. 2Alterations in the mitochondrial responses to PENAO as a mechanism of resistance in ovarian cancer ...
Tópico(s): Thermal Regulation in Medicine
2004 - Mary Ann Liebert, Inc. | Antioxidants and Redox Signaling
Xiaochun Wang, Reichelle X. Yeo, Philip J. Hogg, David Goldstein, Philip Crowe, Pierre J. Dilda, Jialin Yang,
... epidermal growth factor receptor (EGFR) inhibitor gefitinib monotherapy. PENAO, an anti-tumour metabolic compound created in our ... and mechanisms of combination therapy using gefitinib and PENAO in sarcoma cell lines in vitro and in vivo. PENAO monotherapy reduced proliferation in 12 sarcoma cell lines. Combining gefitinib and PENAO resulted in synergistic inhibition in both a time- ... perturbed mitochondrial function. In vivo combination therapy with PENAO and gefitinib was non-toxic to mice and ... difference across and between groups. The combination of PENAO and gefitinib in vitro and in vivo, shows ...
Tópico(s): Protein Degradation and Inhibitors
2020 - Impact Journals LLC | Oncotarget
T. J. Jue, Sylvia A. Chung, Robert W. Rapkins, Pierre J. Dilda, Philip J. Hogg, Kerrie L. McDonald,
... the mitochondrial activity with an organic arsenide compound, PENAO, has been previously shown to decrease oxidative phosphorylation ... been shown to interfere with glycolysis. We combined PENAO and temsirolimus to determine if the drugs act ... and cell proliferation. Methods: In vitro experimentation of PENAO and temsirolimus as single agents, and in combination, ... into different treatment arms: (i) untreated control; (ii) PENAO alone (3 mg/kg/day); (iii) low dose ... dose temsirolimus alone (5mg/kg/day); (v) combined PENAO and low dose temsirolimus; and (vi) combined PENAO ...
Tópico(s): Glioma Diagnosis and Treatment
2017 - Oxford University Press | Neuro-Oncology
Han Shen, Peter P. Luk, Sylvia A. Chung, S. Decollogne, Pierre J. Dilda, Philip J. Hogg, Kerrie L. McDonald,
... related death. New therapeutic strategies are urgently needed. PENAO, (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) is ... ANT) located on the inner-membrane of mitochondria. PENAO blocks ANT delivery of ATP to mitochondrial-bound ... death. In vitro, we tested the efficacy of PENAO on a panel of glioblastoma cell lines including ... and primary glioblastoma neural stem (GNS) cell lines. PENAO demonstrated potent anti-proliferative activity in all cells. The half-maximal inhibitory concentration (IC50) values for PENAO were in the range of 0.3-6 ...
Tópico(s): Metabolism and Genetic Disorders
2013 - American Association for Cancer Research | Cancer Research
Pierre J. Dilda, Wimali Weerakoon, Amanda Philp, John Allen, Richard B. Lock, Philip J. Hogg,
... acts. Phenylarsenoxide was conjugated to penicillamine to produce PENAO (4-(N-(S-penicillamine acetyl)amino)-phenylarsenoxide). PENAO is a mitochondrial poison. It cross-links closely ... mitochondrial permeability transition pore. Inactivation of ANT by PENAO triggers mitochondrial permeability transition which results in proliferation arrest and apoptosis of cultured cells. PENAO cellular levels are controlled by export via the ... dependent multidrug resistance-associated proteins 1 and 2. PENAO was tested for anti-proliferative and cytotoxic activity ...
Tópico(s): Biotin and Related Studies
2007 - American Association for Cancer Research | Cancer Research
Sylvia A. Chung, Pierre J. Dilda, Emma E. Ramsay, Charlie Teo, Philip J. Hogg, Kerrie L. McDonald,
... of new potential anti-tumorigenic drugs is needed. PENAO, (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is ... and tumor-supporting cells. The cytostatic efficacy of PENAO was tested on a panel of five commercial ... in tumorigenicity, drug resistance, invasion and DNA repair. PENAO demonstrated an impressive anti-proliferative activity compared to ... The half maximal inhibitory concentration (IC50) values for PENAO were all in the low micromolar range. The increase in anti-proliferative activity for PENAO compared to carboplatin ranged from 6 to 200- ...
Tópico(s): Cancer, Hypoxia, and Metabolism
2011 - American Association for Cancer Research | Cancer Research
Pierre J. Dilda, S. Decollogne, Lakmini Weerakoon, Philip J. Hogg,
... developed a novel covalent inhibitor of ANT called PENAO, (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) (1). ... resulting in proliferation arrest and apoptotic cell death. PENAO rapidly enters the cell via an organic ion ... of proliferation of the cell and then apoptosis. PENAO targets both proliferating endothelial and tumor cells. It ... tumor models when administered either subcutaneously or intravenously. PENAO is the most potent anti-tumor compound of ...
Tópico(s): ATP Synthase and ATPases Research
2011 - American Association for Cancer Research | Cancer Research
Tópico(s): Glioma Diagnosis and Treatment
2021 - Springer Science+Business Media | Investigational New Drugs
Sunit Sarkar, Ben Tran, Lisa G. Horvath, Michael Lam, Peter Savas, Peter Grimison, James R. Whittle, James Kuo, Nicole Signal, David J. Edmonds, Philip J. Hogg, Danny Rischin, Jayesh Desai, Anne Hamilton,
Tópico(s): Drug-Induced Ocular Toxicity
2021 - Springer Science+Business Media | Cancer Chemotherapy and Pharmacology
André Fedier, Saruar Alam, K Winkelbach, Rebecca Köhler, Viola Heinzelmann‐Schwarz, Francis Jacob,
Introduction/Aim: We investigate the yet unknown function of neolacto-glycosphingolipids GSLs (P1 and nLc4) on drug sensitivity and response to hypoxia, two major obstacles in cancer management. We used parental IGROV1 ovarian cancer cells and our previously generated knockout subline disrupted in B3GNT5 gene (B3GNT5-ko). B3GNT5 is the key enzyme in P1 and nLc4 biosynthesis. GSLs are located on the cell membranes and considered to be critically implicated in the pathogenesis of various diseases and ...
Tópico(s): Microtubule and mitosis dynamics
2016 - Thieme Medical Publishers (Germany) | Geburtshilfe und Frauenheilkunde
Resumen en: Mayra Santos-Febress first novel was received immediately upon publication as a crucial text within Puerto Rican literature. This novel can be read in...
Tópico(s): Cuban History and Society
2003 - University of North Carolina Press | Centro journal
Sylvia A. Chung, S. Decollogne, Wendy Ha, Pierre J. Dilda, Philip J. Hogg, Kerrie L. McDonald,
PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a mitochondrial metabolism inhibitor that is currently in ... patients with solid tumors refractory to standard therapy. PENAO is a cysteine mimetic trivalent arsenical that enters ... proliferation arrest and ultimately apoptosis of the cell. PENAO only reacts with ANT when cells are proliferating ... in growth quiescent cells, and so unreactive towards PENAO. PENAO inhibited the proliferation of a panel of 13 ... respectively, indicating selectivity for glioblastoma cells. Administration of PENAO (3 mg/kg/day) to mice bearing subcutaneous ...
Tópico(s): Retinoids in leukemia and cellular processes
2015 - Oxford University Press | Neuro-Oncology
Toni Rose Jue, Sylvia A. Chung, Robert W. Rapkins, Pierre J. Dilda, Philip J. Hogg, Kerrie L. McDonald,
PENAO is a potent mitochondrial inhibitor, currently in a Phase 1 clinical trial in Australia as a ... aim of this study is to combine both PENAO and temsirolimus, both potent inhibitors of mitochondrial metabolism, ... particularly in patients with an unmethylated MGMT promoter. PENAO and temsirolimus were tested in vitro as single ... were implanted with the PDCL RN1, we combined PENAO (3 mg/kg/day) and temsirolimus (1 mg/ ... panel of PDCLs showed promising synergistic effects with PENAO and temsirolimus. IC50 dose of PENAO and temsirolimus ...
Tópico(s): Mitochondrial Function and Pathology
2016 - Oxford University Press | Neuro-Oncology
Peter P. Luk, Sylvia A. Chung, Han Shen, S. Decollogne, Pierre J. Dilda, Kerrie L. McDonald, Philip J. Hogg,
... this hypothesis using a novel water-soluble organoarsenical, PENAO, to inactivate ANT (1). Treatment of glioblastoma cell lines and primary glioma initiating cells with PENAO inhibited acid (lactate) production, a measure of cancer ... for mitochondrial integrity and low micromolar concentrations of PENAO increased the cytosolic levels of superoxide, disrupted the ... O2 utilization in glioblastoma cells. Blocking ANT with PENAO resulted in inhibition of glioblastoma cell migration at ... µM and mitochondrial-mediated apoptotic cell death at PENAO concentrations of 0.3-5 µM. These effects ...
Tópico(s): Metabolism and Genetic Disorders
2012 - American Association for Cancer Research | Cancer Research
... extática! ¿Es el alma el centro de mi penao la pena el centro de mi alma? [End ...
Tópico(s): Comparative Literary Analysis and Criticism
2008 - Johns Hopkins University Press | Sirena