Review
Oncology
Aamir Salam Teeli, Kamila Luczynska, Effi Haque, Mohmmad Abrar Gayas, Dawid Winiarczyk, Hiroaki Taniguchi
Summary: Liver cancer is a deadly disease with hotspot mutations in HNF4 alpha and HNF1 alpha. These transcription factors play crucial roles in maintaining tissue homeostasis and have been identified as important therapeutic targets in liver cancer treatment. Their dysregulation can lead to tumorigenesis and personalized medicine approaches are being developed to target them for liver cancer therapy.
Article
Pharmacology & Pharmacy
Bastian Haberkorn, Dennis Loewen, Lukas Meier, Martin F. F. Fromm, Joerg Koenig
Summary: Due to alternative splicing, the SLCO1B3 gene encodes two protein variants, Lt-OATP1B3 and Ct-OATP1B3, expressed in different tissues. The transcriptional regulation and transcription factors controlling the expression of these variants are not well understood. In this study, we cloned DNA fragments from the promoter regions of the Lt-SLCO1B3 and Ct-SLCO1B3 genes and investigated their activity in different cell lines. We identified potential binding sites for transcription factors and found that ZKSCAN3 and SOX9 are important for the cell type-specific regulation of the Ct-SLCO1B3 gene.
Review
Endocrinology & Metabolism
Qinying Zhao, Li Ding, Ying Yang, Jinhong Sun, Min Wang, Xin Li, Ming Liu
Summary: This study investigated the clinical characteristics of patients with HNF1-alpha MODY and found that the clinical manifestations differed based on geographical regions, HNF1-alpha mutations, and islet autoantibody status.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Leila E. Zyla, Rocio Cano, Silvina Gomez, Alexa Escudero, Lara Rey, Flavia E. Santiano, Flavia A. Bruna, Virginia Pistone Creydt, Ruben W. Caron, Constanza Lopez Fontana
Summary: Hypothyroidism is a protective factor against breast cancer, but overdoses of thyroid replacement therapy with thyroxine (T-4) may increase breast cancer risk. The study found that T-4 can regulate mammary carcinogenesis by mainly activating its non-genomic signaling pathway and interacting with other hormone or growth factor pathways, potentially increasing the risk of breast cancer.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Cell Biology
Kang Zheng, Fengjie Hao, Sandra Medrano-Garcia, Chaobo Chen, Feifei Guo, Laura Moran-Blanco, Sandra Rodriguez-Perales, Raul Torres-Ruiz, Maria Isabel Peligros, Javier Vaquero, Rafael Banares, Manuel Gomez del Moral, Jose R. Regueiro, Eduardo Martinez-Naves, Mohamed Ramadan Mohamed, Rocio Gallego-Duran, Douglas Maya, Javier Ampuero, Manuel Romero-Gomez, Albert Gilbert-Ramos, Sergi Guixe-Muntet, Anabel Fernandez-Iglesias, Jordi Gracia-Sancho, Mar Coll, Isabel Graupera, Pere Gines, Andreea Ciudin, Jesus Rivera-Esteban, Juan M. Pericas, Maria Dolores Frutos, Bruno Ramos Molina, Jose Maria Herranz, Matias A. Avila, Yulia A. Nevzorova, Edgar Fernandez-Malave, Francisco Javier Cubero
Summary: Progressive hepatic damage and fibrosis in chronic liver diseases can be controlled by N-RAS through downregulation of signaling pathways leading to hepatocyte necroptosis. This study suggests that N-RAS may have potential as a prognostic biomarker and therapeutic target for chronic liver diseases.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
German Belenguer, Gianmarco Mastrogiovanni, Clare Pacini, Zoe Hall, Anna M. Dowbaj, Robert Arnes-Benito, Aleksandra Sljukic, Nicole Prior, Sofia Kakava, Charles R. Bradshaw, Susan Davies, Michele Vacca, Kourosh Saeb-Parsy, Bon-Kyoung Koo, Meritxell Huch
Summary: RNF43/ZNRF3 alterations contribute to liver disease and liver cancer by affecting differentiation and lipid metabolism of hepatocytes. The loss of these genes leads to steatohepatitis and an increase in unsaturated lipids. Deletion of Rnf43/Znrf3 results in defective hepatocyte regeneration and liver cancer, causing an imbalance between differentiation and proliferation. Interestingly, ZNRF3 mutant liver cancer patients have a poorer prognosis and exhibit altered hepatic lipid metabolism and steatohepatitis/NASH signatures.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Markus A. Brown, Thomas Ried
Summary: The major signaling pathways in colon cancer are WNT, RAS, and TGF-beta. Mutations in these pathways reflect the behavior of intestinal stem cells and play a role in the progression of colon cancer. Understanding the intersection and interaction between these pathways can provide insights into the regulation of cell proliferation and the development of colon cancer.
Article
Biochemistry & Molecular Biology
Lotte E. E. Tholen, Heidi Schigt, Sanne G. E. Kleuskens, Caro Bos, Cornelia G. G. Spruijt, Brigith Willemsen, Michiel Vermeulen, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: We identified BAIAP2L2 as a novel transcriptional target of HNF1 beta, which plays a role in maintaining epithelial cell integrity in the kidney.
Article
Reproductive Biology
Rebecca M. Borneman, Elaine Gavin, Alla Musiyenko, Wito Richter, Kevin J. Lee, David K. Crossman, Joel F. Andrews, Annelise M. Wilhite, Steven McClellan, Ileana Aragon, Antonio B. Ward, Xi Chen, Adam B. Keeton, Kristy Berry, Gary A. Piazza, Jennifer M. Scalici, Luciana Madeira da Silva
Summary: A leading theory suggests that inflammation from constant ovulation is a driving factor for ovarian carcinogenesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown potential in chemoprevention of ovarian cancer, although their long-term use is associated with toxicity. PDE10A, a novel therapeutic target, has been identified as a potential treatment for ovarian cancer, as its inhibition can reduce cancer cell growth and induce apoptosis.
JOURNAL OF OVARIAN RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Nianshuang Li, Xinbo Xu, Yuan Zhan, Xiao Fei, Yaobin Ouyang, Pan Zheng, Yanan Zhou, Cong He, Chuan Xie, Yi Hu, Junbo Hong, Nonghua Lu, Zhongming Ge, Yin Zhu
Summary: This study investigates the crosstalk between the Yes-associated protein 1 (YAP) and beta-catenin pathways in H. pylori-associated gastric tumorigenesis. The findings suggest that YAP and beta-catenin synergistically promote H. pylori-induced gastric carcinogenesis through their physical interaction, and identify CDX2, LGR5, and RUVBL1 as downstream genes shared by both pathways.
Review
Oncology
Matthias Christgen, Gabor Cserni, Giuseppe Floris, Caterina Marchio, Lounes Djerroudi, Hans Kreipe, Patrick W. B. Derksen, Anne Vincent-Salomon
Summary: This review summarizes the development of microscopic assessment of invasive lobular breast cancer (ILC) from 1941 until today, discussing various concepts and implications, providing an overview of ILC variants, and highlighting recent advances contributing to a better understanding of the special histologic spectrum of ILC.
Article
Endocrinology & Metabolism
Chiara Verdelli, Giulia Stefania Tavanti, Irene Forno, Valentina Vaira, Riccardo Maggiore, Leonardo Vicentini, Paolo Dalino Ciaramella, Francesca Perticone, Giovanni Lombardi, Sabrina Corbetta
Summary: This study found that osteocalcin (OC), a bone matrix protein, can modulate the function of parathyroid tumor cells by activating the calcium sensing receptor (CASR). OC reduces the activity of pERK/ERK and increases the levels of active beta-catenin through CASR activation. It also affects the expression of related genes to influence the physiological functions of parathyroid tumor cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pathology
Baris Boyraz, Arnaud da Cruz Paula, Kelly A. Deveraux, Ivy Tran, Edaise M. da Silva, Robert H. Young, Matija Snuderl, Britta Weigelt, Esther Oliva
Summary: We report three rare cases of endometrial/endometrioid stromal tumors with unique histologic and molecular features. These tumors exhibit specific morphologic characteristics associated with CTNNB1 translocation. This study expands the morphologic and molecular spectrum of these tumors.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eleonora Vecchio, Nancy Nistico, Gaetanina Golino, Enrico Iaccino, Domenico Maisano, Selena Mimmi, Annamaria Aloisio, Maurizio Renna, Angelica Avagliano, Alessandro Arcucci, Giuseppe Fiume, Ileana Quinto
Summary: The IBTK gene encodes the IBtk alpha protein, which plays a role in the regulation of MYC-dependent B-lymphomagenesis. Mechanistically, IBtk alpha indirectly activates the beta-catenin-dependent transcription of the MYC gene by modulating GSK3 beta. Silencing IBtk alpha leads to downregulation of MYC expression and increased apoptosis in Burkitt's lymphoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Wallace M. de Araujo, Marcelo N. Tanaka, Pedro H. S. Lima, Cassio F. de Moraes, Fernanda Leve, Lilian G. Bastos, Murilo R. Rocha, Bruno K. Robbs, Joao P. B. Viola, Jose A. Morgado-Diaz
Summary: TGF-beta plays a dual role in colorectal cancer, acting as both a tumor suppressor and a promoter. Research demonstrates that TGF-beta can regulate COX-2 and Ras oncogene through different pathways, influencing the development of colorectal cancer.
CELL BIOLOGY INTERNATIONAL
(2021)
Article
Environmental Sciences
Nan-Hung Hsieh, Zunwei Chen, Ivan Rusyn, Weihsueh A. Chiu
Summary: The study evaluated the validity of traditional mixture risk assessment paradigms IA and CA with NAMs data. Results showed that CA is more accurate in predicting mixture effects compared to IA, but in some cases, mixture bioactivity appeared to be greater than that of individual components.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2021)
Letter
Environmental Sciences
Skylar W. Marvel, John S. House, Matthew Wheeler, Kuncheng Song, Yi-Hui Zhou, Fred A. Wright, Weihsueh A. Chiu, Ivan Rusyn, Alison Motsinger-Reif, David M. Reif
ENVIRONMENTAL HEALTH PERSPECTIVES
(2021)
Article
Environmental Sciences
Alina T. Roman-Hubers, Thomas J. McDonald, Erin S. Baker, Weihsueh A. Chiu, Ivan Rusyn
Summary: This study examined the potential of IMS-MS as a high-throughput method for the chemical characterization of crude oils, finding it to be either equal or better than GC-MS in classifying the origins of crude oils and greatly increasing sample analysis throughput. The study demonstrated the utility of IMS-MS for rapid fingerprinting of complex samples and showed its advantages over traditional GC-MS-based analyses in emergency decision-making situations.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Courtney Sakolish, Celeste E. Reese, Yu-Syuan Luo, Alan Valdiviezo, Mark E. Schurdak, Albert Gough, D. Lansing Taylor, Weihsueh A. Chiu, Lawrence A. Vernetti, Ivan Rusyn
Summary: The human microfluidic liver acinus microphysiology system (LAMPS) was evaluated for drug pharmacokinetics and toxicology, showing robustness and reproducibility when seeded with primary human hepatocytes or iPSC-derived hepatocytes, and demonstrating more physiologically and clinically relevant effects compared to 2D cultures.
Article
Food Science & Technology
Yu-Syuan Luo, Zunwei Chen, Alexander D. Blanchette, Yi-Hui Zhou, Fred A. Wright, Erin S. Baker, Weihsueh A. Chiu, Ivan Rusyn
Summary: This study characterized the chemical profiles and effects of energy drinks and their ingredients on human induced pluripotent stem cell-derived cardiomyocytes, identifying potential active ingredients contributing to adverse effects. The analysis revealed that some ingredients in energy drinks, such as theophylline, adenine, and azelate, may be responsible for QT prolongation in cardiomyocytes. Additionally, adverse effects on cardiomyocytes were observed, including increased beat rate and QT prolongation, particularly at lower concentrations.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Editorial Material
Pharmacology & Pharmacy
Ivan Rusyn, Adrian Roth
Article
Engineering, Environmental
Meichen Wang, Zunwei Chen, Ivan Rusyn, Timothy D. Phillips
Summary: This study demonstrated that broad-acting sorbents can effectively prevent toxic effects of various chemical mixtures, with activated carbon showing the highest efficacy in mitigating pesticides, plasticizers, PAHs, and mycotoxins.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Chemistry, Medicinal
Sarah D. Burnett, Alexander D. Blanchette, Weihsueh A. Chiu, Ivan Rusyn
Summary: This study used iPSC-derived cardiomyocytes from 5 donors to conduct concentration-response testing of 1029 chemicals, finding that many environmental chemicals pose a hazard to human cardiomyocytes in vitro. However, most of the tested environmental chemicals had wide margins of exposure and do not appear to pose a significant human health risk in a general population.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Environmental Sciences
Sarah D. Burnett, Moumita Karmakar, William J. Murphy, Weihsueh A. Chiu, Ivan Rusyn
Summary: Inter-species and inter-individual variability contribute to sensitivity differences in cell death, with the magnitude of these differences being chemical-dependent. This study suggests a shift in risk assessment towards higher-throughput in vitro or alternative methods to replace default adjustment factors and address toxicodynamic inter-individual and inter-species variability through experimental characterization.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2021)
Article
Chemistry, Medicinal
Luke Erber, Samantha Goodman, Fred A. Wright, Weihsueh A. Chiu, Natalia Y. Tretyakova, Ivan Rusyn
Summary: The study focused on examining the variability of urinary N7-(1-hydroxy-3-buten-2-yl)guanine (EB-GII) DNA adduct, a biomarker of exposure to 1,3-butadiene, in mice, rats, and humans. Variability in EB-GII levels in mice was influenced by sex and strain, with metabolic saturation possibly contributing to modest variability. In humans, despite larger variability, urinary EB-GII levels were consistent with estimates for other chemicals based on non-cancer endpoints data.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Samantha Goodman, Grace Chappell, Kathryn Z. Guyton, Igor P. Pogribny, Ivan Rusyn
Summary: This study systematically reviewed the epigenetic alterations induced by occupational and environmental human carcinogens. The evidence of epigenetic effects varied across different agents, with DNA methylation being the most studied area and histone modifications/chromatin state alterations being less investigated. Future studies should consider comprehensive study designs and investigate the persistence of effects following cessation of exposure.
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
(2022)
Article
Environmental Sciences
Alan Valdiviezo, Noor A. Aly, Yu-Syuan Luo, Alexandra Cordova, Gaston Casillas, MaKayla Foster, Erin S. Baker, Ivan Rusyn
Summary: PFAS are widely present in water and require analytical methods for rapid comprehensive assessment and fingerprinting. After a fire incident, PFAS-containing firefighting foams were released into water, raising concerns about the contamination level. Untargeted LC-IMS-MS analysis revealed additional PFAS in the water samples, improving our understanding of PFAS presence in complex environmental samples.
JOURNAL OF ENVIRONMENTAL SCIENCES
(2022)
Article
Engineering, Environmental
Oladayo Oladeji, Mariana Saitas, Toriq Mustapha, Natalie M. M. Johnson, Weihsueh A. A. Chiu, Ivan Rusyn, Allen L. L. Robinson, Albert A. A. Presto
Summary: On February 3, 2023, a train carrying hazardous chemicals derailed in East Palestine, OH, leading to temporary evacuation and controlled burn of some of the hazardous cargo. Residents reported health symptoms, and initial data from air monitoring indicated potential concern for air toxics. Mobile air monitoring conducted later showed that the levels of some chemicals were below risk levels, but acrolein levels were high and additional unique compounds were found, suggesting the need for further monitoring to characterize long-term exposure and risk levels.
ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS
(2023)
Article
Toxicology
Zunwei Chen, Dillon Lloyd, Yi-Hui Zhou, Weihsueh A. Chiu, Fred A. Wright, Ivan Rusyn
Summary: This study analyzed surface soil samples in a residential area in Texas inundated with PAH contaminants using in vitro bioactivity measurements. The results showed significant spatial correlation between PAH contaminants and cell-based phenotypes, demonstrating the predictive capability of cell-based bioactivity data for environmental concentrations of PAH and cancer risk.
TOXICOLOGICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
John S. House, Fabian A. Grimm, William D. Klaren, Abigail Dalzell, Srikeerthana Kuchi, Shu-Dong Zhang, Klaus Lenz, Peter J. Boogaard, Hans B. Ketelslegers, Timothy W. Gant, Fred A. Wright, Ivan Rusyn
Summary: This study demonstrates that NAMs can be used to inform groupings of UVCBs, showing that bioactivity data-based groupings of petroleum substances were generally consistent with manufacturing class-based categories. In vitro data, especially bioactivity from human iPSC-derived and primary cells, can be used to rank substances based on their expected in vivo hazard potential.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2021)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
