Article
Multidisciplinary Sciences
Min-Sik Lee, Courtney Dennis, Insia Naqvi, Lucas Dailey, Alireza Lorzadeh, George Ye, Tamara Zaytouni, Ashley Adler, Daniel S. Hitchcock, Lin Lin, Megan T. Hoffman, Aladdin M. Bhuiyan, Jaimie L. Barth, Miranda E. Machacek, Mari Mino-Kenudson, Stephanie K. Dougan, Unmesh Jadhav, Clary B. Clish, Nada Y. Kalaany
Summary: This study reveals the distinct dependence of pancreatic ductal adenocarcinoma (PDA) on de novo ornithine synthesis from glutamine, mediated by ornithine aminotransferase (OAT), which is required for tumor growth and polyamine synthesis. The reliance on OAT-mediated ornithine synthesis in PDA provides a potential therapeutic window for treating pancreatic cancer with minimal toxicity.
Article
Microbiology
Vincent Mastrodomenico, Natalie J. J. LoMascolo, Mason R. R. Firpo, Maria del Mar Villanueva Guzman, Adam Zaporowski, Bryan C. C. Mounce
Summary: This study investigated the persistent infection of Coxsackievirus B3 (CVB3) in pancreatic ductal cells and found that CVB3 can establish a long-term infection by adapting to the cells and altering cellular metabolism. Targeting viral adaptation and replication fidelity can reduce persistent CVB3 infection.
Article
Oncology
Zhiqin Wang, Bowen Wu, Guangjun Nie, Jingyan Wei, Yiye Li
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy characterized by insidious onset and early distal metastasis. Metabolic reprogramming, driven by abnormal genetic events and crosstalk between cancer and non-cancer cells in the desmoplastic microenvironment, plays a pivotal role in the rapid progression of PDAC. Despite challenges, such as poor drug delivery efficiency and off-target side effects, metabolic modification and intervention have emerged as promising strategies for PDAC therapy, facilitated by the rapid development of nanotechnology-based drug delivery strategies.
Review
Oncology
Cristian Andres Carmona-Carmona, Elisa Dalla Pozza, Giulia Ambrosini, Andrea Errico, Ilaria Dando
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly tumor due to late diagnosis and ineffective treatments. The study of metabolic changes in cancer cells has uncovered potential therapeutic strategies. Mitochondria, crucial for cell survival, reshape through fusion or fission, impacting cancer metabolism. Understanding mitochondrial dynamics in PDAC may offer insights into new treatment approaches targeting cancer cells at the core.
Article
Genetics & Heredity
Jannat Pervin, Mohammad Asad, Shaolong Cao, Gun Ho Jang, Nikta Feizi, Benjamin Haibe-Kains, Joanna M. Karasinska, Grainne M. O'Kane, Steven Gallinger, David F. Schaeffer, Daniel J. Renouf, George Zogopoulos, Oliver F. Bathe
Summary: This study identified two novel and clinically impactful metabolic subtypes of PDAC by focusing on features within the tumor compartment. The M2 subtype showed significantly worse survival, characterized by net glycogen catabolism, accelerated glycolysis, increased proliferation, and cellular migration. There is substantial intercellular heterogeneity in the metabolic features typifying this aggressive phenotype in PDAC.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehr, David Fenyo, Pei Wang, Alexey Nesvizhskii, D. R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Summary: This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Review
Biochemistry & Molecular Biology
Nausika Betriu, Juan Bertran-Mas, Anna Andreeva, Carlos E. Semino
Summary: Syndecans, a subfamily of proteoglycans, play critical roles in various physiological processes and have implications in disease progression. Their interactions with other macromolecules contribute to normal cellular functions and disease pathogenesis.
Review
Oncology
Ahmad Ali, Ugo Chianese, Chiara Papulino, Antonella Toraldo, Mawada Elmagboul Abdalla Abakar, Eugenia Passaro, Rosario Cennamo, Nunzio Del Gaudio, Lucia Altucci, Rosaria Benedetti
Summary: This article describes the metabolic features of pancreatic ductal adenocarcinoma and discusses how this could be exploited as a weakness for clinical interventions. Metabolism plays a crucial role in the development of PDAC, and interventions on bioenergetic circuits could potentially reduce its aggressiveness.
Review
Oncology
Eleonora Lai, Pina Ziranu, Dario Spanu, Marco Dubois, Andrea Pretta, Simona Tolu, Silvia Camera, Nicole Liscia, Stefano Mariani, Mara Persano, Marco Migliari, Clelia Donisi, Laura Demurtas, Valeria Pusceddu, Marco Puzzoni, Mario Scartozzi
Summary: Despite ongoing research, there is still insufficient data on BRCA1/2-mutant PDAC, and more understanding is needed on the specific landscape of PDAC with BRCA mutations.
BRITISH JOURNAL OF CANCER
(2021)
Article
Microbiology
Stephen E. Noell, Gregory E. Barrell, Christopher Suffridge, Jeff Morre, Kevin P. Gable, Jason R. Graff, Brian J. VerWey, Ferdi L. Hellweger, Stephen J. Giovannoni
Summary: The SAR11 bacteria can uptake and metabolize multiple polyamine compounds, serving as sources of carbon and nitrogen. These polyamines can meet their nitrogen requirements, but cannot fully substitute for the need for glycine or pyruvate. The findings support the hypothesis that enzyme multifunctionality enables streamlined cells in planktonic ecosystems to increase the range of DOM compounds they metabolize.
Article
Biochemistry & Molecular Biology
Divya Murthy, Kuldeep S. Attri
Summary: Metabolic reprogramming is an important factor in multiple cancers, including pancreatic cancer. Prostaglandin metabolites play a critical role in inflammation and tumorigenesis. This study investigated the relationship between PTGES expression and the pathogenesis and regulation of pancreatic cancer. The findings suggest that PTGES may have an oncogenic function and is associated with metabolic pathways, immune pathways, and DNA methylation-dependent epigenetic mechanisms in pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
George Sharbeen, Joshua A. McCarroll, Anouschka Akerman, Chantal Kopecky, Janet Youkhana, John Kokkinos, Jeff Holst, Cyrille Boyer, Mert Erkan, David Goldstein, Paul Timpson, Thomas R. Cox, Brooke A. Pereira, Jessica L. Chitty, Sigrid K. Fey, Arafath K. Najumudeen, Andrew D. Campbell, Owen J. Sansom, Rosa Mistica C. Ignacio, Stephanie Naim, Jie Liu, Nelson Russia, Julia Lee, Angela Chou, Amber Johns, Anthony J. Gill, Estrella Gonzales-Aloy, Val Gebski, Yi Fang Guan, Marina Pajic, Nigel Turner, Minoti Apte, Thomas P. Davis, Jennifer P. Morton, Koroush S. Haghighi, Jorjina Kasparian, Benjamin J. McLean, Yordanos F. Setargew, Phoebe A. Phillips
Summary: High expression of SLC7A11 in human PDAC tumor stroma, independently prognostic of poorer overall survival. The study demonstrates that PDAC-derived CAFs are highly dependent on SLC7A11 for cystine uptake and glutathione synthesis. Inhibition of SLC7A11 decreases CAF proliferation, reduces their resistance to oxidative stress, and inhibits their ability to support PDAC cell growth.
Review
Oncology
Zhao Liu, Hiromitsu Hayashi, Kazuki Matsumura, Norio Uemura, Yuta Shiraishi, Hiroki Sato, Hideo Baba
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type with high metastatic properties and difficulty in early diagnosis. Most PDAC patients have glucose metabolism disorders, which are closely related to the initiation, development, invasion, and metastasis of PDAC. This review provides valuable insights into the clinical and molecular impacts of glycolysis on PDAC research and treatment.
Review
Oncology
Hannah Pook, Siim Pauklin
Summary: Pancreatic cancer is highly deadly, with current treatments facing various challenges such as late diagnosis, immunologically cold phenotype, and difficulty in distinguishing beneficial drug targets. Recent progress includes identifying mFOLFIRINOX as a standard-of-care adjuvant therapy and discovering KRAS(G12C) mutant inhibitors, with promising new approaches targeting the tumor microenvironment, enhancing immunotherapies, epigenetic modulation, and destruction of CSCs.
Article
Oncology
Parmanand Malvi, Vipin Rawat, Romi Gupta, Narendra Wajapeyee
Summary: Metabolic reprogramming, characterized by the overexpression of metabolic enzymes, is a key feature of cancer cells. This study focuses on lactate dehydrogenase (LDHA) as an overexpressed enzyme in various cancer types, including pancreatic ductal adenocarcinoma (PDAC), and its role in promoting cancer growth. The study models the adaptation of cancer cells to LDHA inhibition, specifically using the competitive LDHA inhibitor sodium oxamate. Through various molecular analyses, the study identifies significant differences in mRNA expression, chromatin accessibility, and metabolite levels between oxamate-resistant PDAC cells and parental cells. Furthermore, integrated analysis reveals changes in metabolic enzymes that contribute to the observed alterations in metabolites. This study provides insights into the transcriptional, chromatin, and metabolic landscapes of LDHA inhibitor resistance in PDAC cells, and highlights the need for further functional studies to understand the mechanisms underlying this resistance and optimize the use of LDHA inhibitors in cancer therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Chantal Reigada, Otto Phanstiel, Mariana R. Miranda, Claudio A. Pereira
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Medicine, Research & Experimental
Sarah B. Gitto, Veethika Pandey, Jeremiah L. Oyer, Alicja J. Copik, Frederick C. Hogan, Otto Phanstiel, Deborah A. Altomare
MOLECULAR PHARMACEUTICS
(2018)
Article
Chemistry, Medicinal
Hana Douafer, Veronique Andrieu, Otto Phanstiel, Jean Michel Brunel
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Correction
Chemistry, Medicinal
Hana Douafer, Veronique Andrieu, Otto Phanstiel, Jean Michel Brunel
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Chelsea Massaro, Jenna Thomas, Houssine Ikhlef, Sharifa Dinara, Sara Cronk, Holly Moots, Otto Phanstiel
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Eric T. Alexander, Kelsey Mariner, Julia Donnelly, Otto Phanstiel, Susan K. Gilmour
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Biochemistry & Molecular Biology
Aiste Dobrovolskaite, Meenu Madan, Veethika Pandey, Deborah A. Altomare, Otto Phanstiel
Summary: Polyamines play a critical role in cancer cell growth, and inhibiting their synthesis is important for anticancer strategies. The novel non-polyamine-based polyamine transport inhibitor GW5074 has been identified, which effectively inhibits the growth of human pancreatic cancer cells and reduces tumor growth in a murine pancreatic cancer model. The combination of GW5074 with DFMO shows potential to enhance anticancer activity in pancreatic cancers.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christian J. Malpica-Nieves, Yomarie Rivera, David E. Rivera-Aponte, Otto Phanstiel, Ruediger W. Veh, Misty J. Eaton, Serguei N. Skatchkov
Summary: This study investigated the impact of HIV-Tat on the uptake and release of N-acetylated spermine in astrocytes, showing that Cx43 hemichannels are not the main pathway. The preliminary findings suggest that polyamine uptake may proceed through other channels such as organic cation transporter.
Article
Biochemistry & Molecular Biology
Sai Preethi Nakkina, Sarah B. Gitto, Jordan M. Beardsley, Veethika Pandey, Michael W. Rohr, Jignesh G. Parikh, Otto Phanstiel, Deborah A. Altomare
Summary: This study focuses on addressing the challenges of treating pancreatic ductal adenocarcinoma by targeting KRAS and MYC. The use of DFMO and GW5074 showed significant reduction in PDAC cell viability in vitro and inhibition of PDAC growth in vivo. DFMO was more effective in reducing tumor size, increasing survival, and modulating the tumor microenvironment compared to GW5074.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Mukund P. Tantak, Vandana Sekhar, Xianzun Tao, R. Grace Zhai, Otto Phanstiel
Summary: A spermine prodrug was developed in this study, which successfully increased intracellular spermine levels in SRS fibroblasts. Administering the prodrug in a Drosophila SRS model showed significant beneficial effects, providing a lead compound for future spermine replacement therapy experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Aiste Dobrovolskaite, Richard Andrew Gardner, Jean-Guy Delcros, Otto Phanstiel
Summary: In this study, polyamine lassos were synthesized by attaching nine- and twelve-membered triaza-macrocycles to homospermidine. These compounds were found to be potent polyamine transport inhibitors in pancreatic ductal adenocarcinoma cells with high polyamine transport activity. The smaller lasso showed superior inhibition of polyamine uptake and reduced intracellular polyamine levels.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Oncology
Sai Preethi Nakkina, Sarah B. Gitto, Veethika Pandey, Jignesh G. Parikh, Dirk Geerts, Hans Carlo Maurer, Kenneth P. Olive, Otto Phanstiel, Deborah A. Altomare
Summary: Pancreatic cancer has a low survival rate and is the fourth leading cause of cancer death in the United States. Targeting polyamine metabolism in the tumor microenvironment may be a potential strategy to inhibit pancreatic tumor progression. Studies have shown that polyamine blockade therapy can increase survival and modulate the tumor microenvironment in pancreatic cancer.
Review
Plant Sciences
Ewelina Stolarska, Ewelina Paluch-Lubawa, Magda Grabsztunowicz, Umesh Kumar Tanwar, Magdalena Arasimowicz-Jelonek, Otto Phanstiel, Autar K. Mattoo, Ewa Sobieszczuk-Nowicka
Summary: Polyamines (PAs) are crucial molecules that control cell lifespan and viability. Supplementation with spermidine has been found to reduce age-related diseases and increase lifespan in various organisms, including humans. PAs also play a role in preventing plant senescence. This review aims to provide a comprehensive understanding of PA metabolism regulation and its impact on cell homeostasis.
CRITICAL REVIEWS IN PLANT SCIENCES
(2023)
Article
Medicine, Research & Experimental
Aya G. Elmarsafawi, Rebecca S. Hesterberg, Mario R. Fernandez, Chunying Yang, Lancia N. F. Darville, Min Liu, John M. Koomen, Otto Phanstiel, Reginald Atkins, John E. Mullinax, Shari A. Pilon-Thomas, Frederick L. Locke, Pearlie K. Epling-Burnette, John L. Cleveland
Summary: Glutaminolysis is a characteristic of T cell activation and metabolic reprogramming, and the polyamine-hypusine axis can be modulated to regulate the development of tissue-resident memory T cells and enhance therapeutic outcomes.
