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Featured researches published by Nadiya Sydorenko.


Oncogene | 2018

BMI1 is a therapeutic target in recurrent medulloblastoma

David Bakhshinyan; Chitra Venugopal; Ashley Adile; Neha Garg; Branavan Manoranjan; Robin M. Hallett; Xin Wang; Sujeivan Mahendram; Parvez Vora; Thusyanth Vijayakumar; Minomi Subapanditha; Mohini Singh; Michelle Kameda-Smith; Maleeha Qazi; Nicole McFarlane; Aneet Mann; Olufemi Ajani; Blake Yarascavitch; Vijay Ramaswamy; Hamza Farooq; Sorana Morrissy; Liangxian Cao; Nadiya Sydorenko; Ramil Baiazitov; Wu Du; Josephine Sheedy; Marla Weetall; Young-Choon Moon; Chang-Sun Lee; Jacek M. Kwiecien

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor, representing 20% of newly diagnosed childhood central nervous system malignancies. Although advances in multimodal therapy yielded a 5-year survivorship of 80%, MB still accounts for the leading cause of childhood cancer mortality. In this work, we describe the epigenetic regulator BMI1 as a novel therapeutic target for the treatment of recurrent human Group 3 MB, a childhood brain tumor for which there is virtually no treatment option beyond palliation. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naive tumors will provide limited clinical benefit since recurrent metastatic MBs are highly genetically divergent from their primary tumor. Using a small molecule inhibitor against BMI1, PTC-028, we were able to demonstrate complete ablation of self-renewal of MB stem cells in vitro. When administered to mice xenografted with patient tumors, we observed significant reduction in tumor burden in both local and metastatic compartments and subsequent increased survival, without neurotoxicity. Strikingly, serial in vivo re-transplantation assays demonstrated a marked reduction in tumor initiation ability of recurrent MB cells upon re-transplantation of PTC-028-treated cells into secondary recipient mouse brains. As Group 3 MB is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious targeted agent would be rapidly transitioned to clinical trials.


Molecular Cancer Therapeutics | 2018

Evaluating the mechanism and therapeutic potential of PTC-028, a novel inhibitor of BMI-1 function in ovarian cancer

Anindya Dey; Xunhao Xiong; A.K. Crim; Shailendra Kumar Dhar Dwivedi; Soumyajit Banerjee Mustafi; Priyabrata Mukherjee; Liangxian Cao; Nadiya Sydorenko; Ramil Baiazitov; Young Choon Moon; Melissa Dumble; Thomas P. Davis; Resham Bhattacharya

BMI-1, also known as a stem cell factor, is frequently upregulated in several malignancies. Elevated expression of BMI-1 correlates with poor prognosis and is therefore considered a viable therapeutic target in a number of malignancies including ovarian cancer. Realizing the immense pathologic significance of BMI-1, small-molecule inhibitors against BMI-1 are recently being developed. In this study, we functionally characterize PTC-028, an orally bioavailable compound that decreases BMI-1 levels by posttranslational modification. We report that PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays, whereas normal cells remain unaffected. Mechanistically, hyperphosphorylation-mediated depletion of cellular BMI-1 by PTC-028 coupled with a concurrent temporal decrease in ATP and a compromised mitochondrial redox balance potentiates caspase-dependent apoptosis. In vivo, orally administered PTC-028, as a single agent, exhibits significant antitumor activity comparable with the standard cisplatin/paclitaxel therapy in an orthotopic mouse model of ovarian cancer. Thus, PTC-028 has the potential to be used as an effective therapeutic agent in patients with epithelial ovarian cancer, where treatment options are limited. Mol Cancer Ther; 17(1); 39–49. ©2017 AACR.


Journal of Organic Chemistry | 2017

Unexpected Observation of the Dimroth Rearrangement in the Ribosylation of 4-Aminopyrimidines

Ramil Baiazitov; Nadiya Sydorenko; Hongyu Ren; Young-Choon Moon

A method for the preparation of 1-(N-ribofuranosyl)-6-imino-1,6-dihydropyrimidin-4-amines 3 or 4-(N-ribofuranosyl)-6-aminopyrimidines 4 via glycosylation of 4-aminopyrimidines 2 or 5 is described. Silylated 4-aminopyrimidines 2 or 5 upon ribosylation with 1 provide products 3. When intermediates 3 contain a strongly electron-withdrawing group, such as C(4)-Cl or C(5)-NO2, they rearrange to products 4 in the presence of aqueous ammonia. A mechanism is proposed that involves a ring-opening/ring-closing (Dimroth) rearrangement.


European Journal of Organic Chemistry | 2005

A Formal [3 + 3] Cycloaddition Approach to Natural‐Product Synthesis

Richard P. Hsung; Aleksey V. Kurdyumov; Nadiya Sydorenko


Journal of Organic Chemistry | 2005

A Formal [3 + 3] Cycloaddition Reaction. 5. An Enantioselective Intramolecular Formal Aza-[3 + 3] Cycloaddition Reaction Promoted by Chiral Amine Salts

Aleksey I. Gerasyuto; Richard P. Hsung; Nadiya Sydorenko; Brian W. Slafer


Organic Letters | 2006

Torquoselective 6pi-electron electrocyclic ring closure of 1-azatrienes containing acyclic chirality at the C-terminus.

Nadiya Sydorenko; Richard P. Hsung; Eymi L. Vera


Organic Letters | 2006

A Lewis Acid-Catalyzed Formal [3 + 3] Cycloaddition of α,β-Unsaturated Aldehydes with 4-Hydroxy-2-Pyrone, Diketones, and Vinylogous Esters

Aleksey V. Kurdyumov; Nan Lin; Richard P. Hsung; Glen C. Gullickson; Kevin P. Cole; Nadiya Sydorenko; Jacob J. Swidorski


Journal of Organic Chemistry | 2004

Tetronamides as Latent Acyclic Vinylogous Amides in Formal Aza-[3 + 3] Cycloaddition Reactions with α,β-Unsaturated Iminium Salts. An Unexpected Rearrangement and an Approach to Synthesis of Substituted Piperidines

Nadiya Sydorenko; Richard P. Hsung; Ossama Saleh Darwish; Juliet M. Hahn; Jia Liu


Organic and Biomolecular Chemistry | 2005

Total syntheses of enantiomerically enriched R-(+)- and S-(−)-deplancheine

Nadiya Sydorenko; Craig A. Zificsak; Aleksey I. Gerasyuto; Richard P. Hsung


Archive | 2009

BMI-1 PROTEIN EXPRESSION MODULATORS

Young-Choon Moon; Nadiya Sydorenko; Thomas W. Davis; Liangxian Cao; Daniel Medina; Marites A. Rafanan

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Richard P. Hsung

University of Wisconsin-Madison

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Thomas W. Davis

University of Wisconsin-Madison

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Marites A. Rafanan

University of Medicine and Dentistry of New Jersey

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Jia Liu

University of Wisconsin-Madison

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Aleksey V. Kurdyumov

University of Wisconsin-Madison

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