Article
Pharmacology & Pharmacy
Shan Wang, Hui-feng Hao, Yan-na Jiao, Jia-lei Fu, Zheng-wang Guo, Yang Guo, Yuan Yuan, Ping-ping Li, Shu-yan Han
Summary: This study investigated the potential regulatory mechanisms of dandelion extract against triple-negative breast cancer (TNBC) using network pharmacology and multi-omics techniques. The results showed that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism of TNBC by downregulating CHKA expression and inhibiting the PI3K/AKT/SREBP/FADS2 axis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Pablo Garcia-Molina, Alberto Sola-Leyva, Pilar M. Luque-Navarro, Alejandro Laso, Pablo Rios-Marco, Antonio Rios, Daniela Lanari, Archimede Torretta, Emilio Parisini, Luisa C. Lopez-Cara, Carmen Marco, Maria P. Carrasco-Jimenez
Summary: The overexpression of Choline Kinase alpha 1 (ChoK alpha 1) has been associated with cell proliferation, oncogenic transformation, and carcinogenesis, making it a potential target in cancer therapy. Additionally, the choline transporter CTL1 is highly expressed in tumor cell lines. Inhibition of both choline uptake and ChoK alpha 1 activity has been shown to correlate with reduced cell proliferation in cancer cell lines, suggesting both proteins as potential targets for cancer therapy.
Article
Oncology
Tina Jost, Lucie Heinzerling, Rainer Fietkau, Markus Hecht, Luitpold V. Distel
Summary: The CDK4/6 inhibitor palbociclib induces cell cycle arrest in the G0/G1 phase, with minimal impact on cell death. It enhances cellular growth arrest and senescence in cancer cells, and may downregulate FOXM1 to induce senescence. Combination therapy with palbociclib and radiotherapy shows an additive effect on cellular growth arrest and deserves further study in clinical trials.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Zhichao Fan, Jisheng Ma, Xuebo Pan, Liangcai Zhao, Yuying Wu, Hui Lin, Yidan Zhao, Haowei Jiang, Tingting Pan, Xiaokun Li, Fen Wang, Cong Wang
Summary: This study demonstrates that FGFR1 promotes proliferation and survival of prostate cancer cells by regulating choline metabolism through the formation of a complex with choline kinase alpha at the posttranslational level. The interaction between FGFR1 and choline metabolism could be a potential target for managing prostate cancer progression.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Hoon Sik Choi, Jin Hyun Kim, Si Jung Jang, Jeong Won Yun, Ki Mun Kang, Hojin Jeong, In Bong Ha, Bae Kwon Jeong
Summary: This study showed that alpha-lipoic acid (ALA) promoted apoptotic cell death and enhanced radiation-induced cellular senescence in MDA-MB-231 breast cancer cells. The synergistic effect of ALA on cell death and senescence provides a new treatment strategy for cancer cells resistant to radiotherapy.
CANCER RESEARCH AND TREATMENT
(2021)
Article
Biochemistry & Molecular Biology
Pei Yu, Xiong Zhu, Jia-Le Zhu, Yu-Bao Han, Hao Zhang, Xiang Zhou, Lei Yang, Yuan-Zheng Xia, Chao Zhang, Ling-Yi Kong
Summary: Chk2 is negatively correlated with VM formation in p53-mutated TNBC and reduces VM formation through metabolic regulation. Chk2 promotes VM suppression by interacting with PKM2 and phosphorylating PKM2.
Article
Chemistry, Multidisciplinary
N. Giri Lakshman, S. M. Esther Rubavathy, S. Priyankha, K. Palanisamy, M. Prakash
Summary: In this study, we investigated the effect of different anion mixtures in biodegradable ionic liquids (ILs) on the stability of insulin. Our findings suggest that ILs based on choline geranate [Cho][Ger] stabilize the insulin dimer structure, while the ternary complex [Cho][Ger][Tau] destabilizes insulin. This research provides valuable information for designing novel oral insulin formulations.
NEW JOURNAL OF CHEMISTRY
(2023)
Review
Oncology
Alakananda Basu, Christoffer Briggs Lambring
Summary: This article discusses the importance of breast cancer in women in the United States and the role of Akt isoforms in the development of breast cancer. While Akt isoforms share similar structures, they exhibit redundant, distinct, and opposite functions in breast cancer. Understanding the isoform-specific function of Akt is critical for effectively targeting the Akt signaling pathway in cancer therapy.
Article
Cell Biology
Margherita Boieri, Emanuela Marchese, Quan Minh Pham, Marjan Azin, Lauren E. Steidl, Anna Malishkevich, Shadmehr Demehri
Summary: Research shows that TSLP-activated CD4(+) T cells have antitumor effects in advanced breast cancer by inducing cancer cells into a senescent-like state. Inflammatory CD4(+) T cells release interferon-gamma and tumor necrosis factor-alpha, which directly affects cancer cell receptors, driving them into senescence.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Natalia Rubtsova, Michael C. Hart, Alejandro D. Arroyo, Sofya A. Osharovich, Benjamin K. Liebov, Joann Miller, Min Yuan, Jeffrey M. Cochran, Sanghoon Chong, Arjun G. Yodh, Theresa M. Busch, E. James Delikatny, Nadia Anikeeva, Anatoliy Popov
Summary: A novel nanocomposite NIR fluorescent imaging probe was introduced and tested for its potency as a photosensitizing agent against triple-negative breast cancer cells by targeting abnormal choline metabolism. The probe was shown to have higher activation levels in cancer cells compared to normal cells in vitro, suggesting its potential as a theranostic agent. Additionally, the ability of the nanocomposite to function as a sensitizer in PDT experiments implies promising applications in cancer therapy.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Melina Beykou, Mar Arias-Garcia, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Nicolas Moser, Pantelis Georgiou, Chris Bakal
Summary: Palbociclib treatment can induce a senescence-like cell state in TNBC cells, providing insights for the future use of CDK4/6 inhibitors and the development of combination therapies in TNBC subtypes.
Article
Oncology
Dana C. Borcherding, Eric R. Hugo, Sejal R. Fox, Eric M. Jacobson, Brian G. Hunt, Edward J. Merino, Nira Ben-Jonathan
Summary: This study describes the use of high throughput screening to identify novel small molecules that block the prolactin receptor and suppress breast cancer cell growth, demonstrating their potential as effective therapeutics for breast cancer patients.
Article
Biochemistry & Molecular Biology
Amani Odeh, Hossam Eddini, Lujain Shawasha, Anastasia Chaban, Aaron Avivi, Imad Shams, Irena Manov
Summary: Subterranean blind mole rat, Spalax, has developed strategies to withstand cancer by maintaining genome stability and suppressing the inflammatory response. Conditioned medium from senescent Spalax fibroblasts can induce senescence in cancer cells without inducing an inflammatory response, thereby suppressing malignant behavior.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Manni Wang, Siyuan Chen, Yuquan Wei, Xiawei Wei
Summary: The study identified that the DNA-PK inhibitor M3814 enhanced the anti-tumor effect of chemotherapy in NSCLC cell lines, providing a theoretical basis for its potential use in clinical practice to optimize NSCLC treatment.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Pharmacology & Pharmacy
Noa Rotem-Dai, Amitha Muraleedharan, Etta Livneh
Summary: Autophagy is one of the mechanisms that promote chemoresistance in cancer cells, and PKC eta facilitates the transition from autophagy to senescence induced by ER and oxidative stress. PKC eta is proposed as a target for therapeutic intervention in breast cancer, and its combination with autophagy-inducing drugs can overcome resistance and enhance cell death.
Article
Medical Laboratory Technology
Elena Porcu, Francesca Maule, Lorenzo Manfreda, Elena Mariotto, Silvia Bresolin, Alice Cani, Roberta Bortolozzi, Alessandro Della Puppa, Diana Corallo, Giampietro Viola, Elena Rampazzo, Luca Persano
Summary: We found that ANXA2 is a key mediator of the pro-oncogenic features of GBM tumors, involved in stemness, proliferation and invasion, thus affecting patient prognosis. Using the QUADrATiC bioinformatic tool, we identified Homoharringtonine (HHT) as a potent inhibitor of GBM cell motility and proliferation. HHT inhibits a transcriptional program involved in cell migration and invasion by impairing PDGFRα-dependent signaling through STAT3 and RhoA axes. This suggests that HHT could be an effective treatment option for GBM by targeting its hallmarks.
TRANSLATIONAL RESEARCH
(2023)
Article
Hematology
Alice Cani, Caterina Tretti Parenzan, Chiara Frasson, Elena Rampazzo, Pamela Scarparo, Samuela Francescato, Federico Caicci, Vito Barbieri, Antonio Rosato, Simone Cesaro, Marco Zecca, Concetta Micalizzi, Laura Sainati, Martina Pigazzi, Alessandra Biff, Barbara Buldini, Franco Locatelli, Luca Persano, Riccardo Masetti, Geertruijte Kronnie, Silvia Bresolin
Summary: This study reports the development of a novel patient-derived three-dimensional (3D) in vitro model for studying juvenile myelomonocytic leukemia (JMML). The model, called patient-derived JMML Atypical Organoid (pd-JAO), can sustain the long-term proliferation of JMML cells with stem cell features and patient-specific hallmarks. Microenvironmental conditions in the 3D model enhance the proliferative and survival advantages of JMML cells, and specific metabolic energy pathways are activated. The model also exhibits migratory, propagation, and self-renewal capacities, making it a promising tool for studying JMML disease and therapeutic interventions.
Article
Chemistry, Medicinal
Pilar M. Luque-Navarro, M. Paz Carrasco-Jimenez, Laura Goracci, Jose M. Paredes, Laura Espinar-Barranco, Javier Valverde-Pozo, Archimede Torretta, Emilio Parisini, Elena Mariotto, Chiara Marchioro, Alejandro Laso, Carmen Marco, Giampietro Viola, Daniela Lanari, Luisa Carlota Lopez Cara
Summary: We propose a series of bioisosteric inhibitors based on the introduction of sulphur, which are effective in inhibiting human choline kinase and reducing phosphatidylcholine biosynthesis. PL 48, PL 55, and PL 69 are identified as the most active compounds in the series. These compounds induce apoptosis through the mitochondrial pathway and significantly reduce the expression of anti-apoptotic protein Mcl-1.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Materials Science, Biomaterials
Ramin Nasehi, Jana Schieren, Caroline Grannemann, Alena L. Palkowitz, Aaron Babendreyer, Nicole Schwarz, Sanja Aveic, Andreas Ludwig, Rudolf E. Leube, Horst Fischer
Summary: The modality of hydrostatic pressure during nozzle-based bioprinting affects the biological response of processed cells differently. Pulsatile hydrostatic pressure leads to an immediate increase of intracellular ATP in both endothelial and epithelial cells. Bioprinting-associated hydrostatic pressure triggers a pro-inflammatory response in endothelial cells but not in epithelial cells.
BIOMATERIALS ADVANCES
(2023)
Article
Cell Biology
Caterina Vianello, Federica Dal Bello, Sang Hun Shin, Sara Schiavon, Camilla Bean, Ana Paula Magalhaes Rebelo, Tomas Knedlik, Emad Norouzi Esfahani, Veronica Costiniti, Rodrigo S. Lacruz, Giuseppina Covello, Fabio Munari, Tommaso Scolaro, Antonella Viola, Elena Rampazzo, Luca Persano, Sara Zumerle, Luca Scorrano, Alessio Gianelle, Marta Giacomello
Summary: Recent studies have found a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms, and the function of these organelles needs to be validated. However, a method for high-throughput quantification of mitochondrial membrane potential has not been established yet. In this study, we present a methodology for unbiased quantification of mitochondrial membrane potential in vitro, suitable for various cell models. Our method successfully analyzed mitochondrial membrane potential in different cell types and allowed discrimination between cell subpopulations using automated image analysis and machine learning.
Review
Biology
Lorenzo Manfreda, Elena Rampazzo, Luca Persano
Summary: The involvement of Wnt signaling in normal tissue homeostasis and disease, particularly in neoplastic malignancies, has been summarized. The impact of aberrant Wnt pathway activation on brain tumorigenesis and tumor aggressiveness, as well as the interdependency between Wnt signaling components and the brain tumor microenvironment, has been emphasized. Furthermore, the latest therapeutic approaches targeting Wnt signaling in cancer treatment have been extensively reviewed and discussed. This review provides evidence that Wnt signaling could be a relevant target in brain tumors, but requires further investigation and overcoming potential concerns for clinical application.
Article
Engineering, Biomedical
Ramin Nasehi, Ali T. Abdallah, Marcella Pantile, Carlo Zanon, Michael Vogt, Stephan Ruetten, Horst Fischer, Sanja Aveic
Summary: The lack of in vitro cell models is a challenge for discovering new molecular targets and therapeutics for pediatric bone metastatic disease. Using a beta-tricalcium phosphate (β-TCP) multicellular 3D in vitro bone microtissue model, the study successfully reconstitutes key phenotypic and transcriptional patterns of native metastatic tumor cells and enhances their stemness and proinvasive features. The geometry and chemical impact of β-TCP reveals a prometastatic landscape of the tumor microenvironment, providing insights for further analysis of the disease and preclinical target validations.
MATERIALS TODAY BIO
(2023)
Article
Pharmacology & Pharmacy
Diana Corallo, Marco Dalla Vecchia, Daria Lazic, Sabine Taschner-Mandl, Alessandra Biffi, Sanja Aveic
Summary: Cell motility is a crucial process in multicellular organisms and is essential for tissue formation and regeneration, but uncontrolled cell motility can lead to various diseases including neoplasms. This review focuses on the regulatory mechanisms of metastatic neuroblastoma, a solid pediatric tumor originating from migratory cells in the neural crest. Targeting intracellular and extracellular processes involved in the highly motile phenotype of metastatic neuroblastoma cells could improve treatment for high-risk patients. The development of migration-inhibiting compounds and standardized preclinical approaches for selecting anti-metastatic drugs in neuroblastoma is also discussed.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matilde Cescon, Elena Rampazzo, Silvia Bresolin, Francesco Da Ros, Lorenzo Manfreda, Alice Cani, Alessandro Della Puppa, Paola Braghetta, Paolo Bonaldo, Luca Persano
Summary: Collagen VI has a distinct distribution within GBM tumors and is strongly correlated with aggressive and phenotypically immature cells. It sustains the stem-like properties of GBM cells and promotes cancer cell proliferation and survival. Collagen VI plays a pivotal role in GBM tumor biology, affecting phenotypic identity, gene transcription, and response to treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maike Sahle, Mattis Wachendoerfer, Alena L. Palkowitz, Ramin Nasehi, Sanja Aveic, Horst Fischer
Summary: Fibrin-based hydrogel blends can increase the long-term stability of in vitro gingival models, mimicking the histology of native gingiva and providing a new perspective for evaluating specific biological or pathological conditions of artificial gingival tissue.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Ghazi Ben Messaoud, Sanja Aveic, Mattis Wachendoerfer, Horst Fischer, Walter Richtering
Summary: Porous hydrogels derived from aqueous two-phase systems (ATPS) are an interesting alternative to overcome the restricted porosity of most hydrogels in vitro. By tuning the phase behavior and concentration, ATPS hydrogels with three distinct microstructures, including bicontinuous hydrogels with interconnected pores, can be formed. These ATPS hydrogels show cytocompatibility and can sustain their unique porous structure when processed by inkjet and microextrusion techniques.
Letter
Oncology
Igor Fijalkowski, Jin Wang, Qi Jin, Jolien Van Laere, Valentina Serafin, John D. Crispino, Panagiotis Ntziachristos
Article
Chemistry, Medicinal
Federica Budassi, Chiara Marchioro, Martina Canton, Annagiulia Favaro, Mattia Sturlese, Chiara Urbinati, Marco Rusnati, Romeo Romagnoli, Giampietro Viola, Elena Mariotto
Summary: A new compound FB49 with high affinity to BAG3 protein has been discovered, which exhibits antiproliferative activity in various human tumor cell lines without toxicity to healthy cells. Moreover, FB49 can block cell cycle and induce apoptosis and autophagy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)