Editorial Material
Oncology
Yuqing Zhang, Rolf A. Brekken
Summary: The study challenges the functional significance of Tie2-expressing macrophages in tumor angiogenesis and relapse after chemotherapy, highlighting the need for reconsideration of Tie2 as a therapeutic target or prognostic indicator.
Article
Medicine, Research & Experimental
Ana Garcia-del Rio, Endika Prieto-Fernandez, Leire Egia-Mendikute, Asier Antonana-Vildosola, Borja Jimenez-Lasheras, So Young Lee, Adrian Barreira-Manrique, Samanta Romina Zanetti, Ander de Blas, Paloma Velasco-Beltran, Alexandre Bosch, Ana M. Aransay, Asis Palazon
Summary: Factor-inhibiting HIF (FIH) is an asparagine hydroxylase expressed in tumors, and its deletion may lead to increased metabolism, decreased proliferation, and increased immune infiltration in cancer cells.
Review
Biochemistry & Molecular Biology
Ping Song, Fan Yang, Hongchuan Jin, Xian Wang
Summary: In addition to gene regulation and post-translational modifications, abnormal translation from mRNAs to proteins is essential in cancer pathogenesis. Targeting mRNA translation presents a potential strategy for cancer treatment. Modulation of protein translation involves factors such as initiation factors, RNA-binding proteins, mRNA modifications like m(6)A, and noncoding RNAs like microRNAs and long noncoding RNAs. This review highlights the interplay between mRNA modifications and ncRNAs in regulating protein translation, offering insights for precision therapy in human cancers.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Multidisciplinary Sciences
Xin-qi Zhong, Tao-fang Hao, Qi-jiong Zhu, Jing Zheng, Mao-fei Zheng, Xiu-hong Li, Li-hua Luo, Chang-shun Xia, Yu-wei Fan, Jian Gu, Tao Liu, Dun-jin Chen
Summary: Bronchopulmonary dysplasia (BPD) is a lung disorder characterized by abnormal development of blood vessels and alveoli, primarily occurring in premature infants. Exosomes (EXO) from very preterm infants (VPI) with BPD (BPD-EXO) were found to impair angiogenic activities in endothelial cells and worsen lung injury in a mouse model of BPD. BPD-EXO affected gene expression in the lungs, particularly in the MAPK pathway, which is crucial for angiogenesis and vascular remodeling. These findings suggest that BPD-EXO could serve as potential targets for predicting and treating BPD.
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Emma Minnee, William James Faller
Summary: Protein synthesis is crucial in all kingdoms of life, and dysregulation can drive cancer development, as seen in colorectal cancer with translational reprogramming. Multiple signaling pathways impact the translation initiation machinery, playing a critical role in regulating gene expression differentially.
Article
Biochemistry & Molecular Biology
Evrim Fer, Kaitlyn M. McGrath, Lionel Guy, Adam J. Hockenberry, Betul Kacar
Summary: Protein translation is a fundamental process in all living cells. A study on the evolutionary history of translation machinery factors suggests that the ancestors of these factors may have had similar functions and structures to their modern counterparts. By reconstructing the ancestral sequences and studying the changes in residues and structures, the researchers propose an evolutionary scenario for the origins and diversification of essential translation factors EF-Tu and IF2. Understanding the early evolution of the translation machinery is crucial for characterizing universal constraints and capabilities of cellular evolution.
Article
Chemistry, Medicinal
Xintao Gao, Yonglong Jin, Wenyong Zhu, Xiaochen Wu, Jing Wang, Chuanlong Guo
Summary: eIF4E is a central regulator in cancer cell growth, but there are currently no clinically available eIF4E inhibitors. Interfering with eIF4E/eIF4G interactions may provide a new strategy for designing eIF4E inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shulei Gong, Yu Li, Ling Lv, Wanfu Men
Summary: MiR-519a enhances radiosensitivity of NSCLC by inhibiting EphA2 expression, indicating its potential as a therapeutic target for NSCLC.
Article
Multidisciplinary Sciences
Alexandra J. Dickinson, Jingyuan Zhang, Michael Luciano, Guy Wachsman, Evan Sandoval, Martin Schnermann, Jose R. Dinneny, Philip N. Benfey
Summary: Research has shown that retinal binding occurs before lateral root formation and helps to promote root clock oscillations. The Arabidopsis protein TIL oscillates in the region of retinal binding, shares homology with vertebrate retinoid-binding proteins, and plays a role in lateral root organogenesis.
Article
Chemistry, Multidisciplinary
Fengzhi Zhao, Wei Huang, Lizhen He, Shiqing Nie, Zhiting Sun, Tianfeng Chen, Haiyan Yin, Jianfu Zhao
Summary: Tolerance to radiotherapy is a major problem in lung cancer treatment, and this study developed a novel EGFR/mitochondrial dual-targeting radiosensitizer to overcome radioresistance. The nanosystem successfully targeted the mitochondria, leading to increased accumulation and penetration of the radiotherapy agent in lung cancer cells and enhanced sensitivity to X-rays. Moreover, the combined treatment reshaped the tumor immune microenvironment. These findings offer a facile design strategy for nanoradiosensitizers in reversing radiation resistance and provide insights into their application in cancer medicine theranostics.
Review
Genetics & Heredity
Prakash Amruth Raj Chukka, Stacey D. Wetmore, Nehal Thakor
Summary: Translational control plays a crucial role in dictating gene expression and altering physiological processes in eukaryotic cells. eIF5B plays a significant role in this process, especially in the survival and drug resistance of cancer cells.
FRONTIERS IN GENETICS
(2021)
Article
Biochemical Research Methods
Ping Zhao, Xiao Liu, Xing Zhang, Li Wang, Haoran Su, Liyi Wang, Ningxiang He, Dongrui Zhang, Zhengxing Li, Hongyan Kang, Anqiang Sun, Zengsheng Chen, Li Zhou, Min Wang, Yinghui Zhang, Xiaoyan Deng, Yubo Fan
Summary: The study reveals that luminal shear stress inhibits endothelial cell sprouting and tube formation in a dose-dependent manner, while a high concentration of VEGF increases EC sprouting with little additional impact from VEGF gradients. HSPGs act as mechanosensors to sense changes in fluid shear stress, modulate multiple EC gene expressions, and therefore influence neovascularization. Changes in shear stress magnitude and forms play a critical role in the initiation of neovascularization.
Article
Biochemistry & Molecular Biology
Francesco Pantano, Martine Croset, Keltouma Driouch, Natalia Bednarz-Knoll, Michele Iuliani, Giulia Ribelli, Edith Bonnelye, Harriet Wikman, Sandra Geraci, Florian Bonin, Sonia Simonetti, Bruno Vincenzi, Saw See Hong, Sofia Sousa, Klaus Pantel, Giuseppe Tonini, Daniele Santini, Philippe Clezardin
Summary: This study identified ITGA5 as a mediator of breast-to-bone metastasis, with high expression correlating with poor bone metastasis-free survival. Silencing ITGA5 impaired tumor cell functions and bone metastasis, while inhibition with M200 showed similar effects.
Article
Cell Biology
Pengcheng Cai, Rui Ni, Mengzhu Lv, Huijuan Liu, Jieqiong Zhao, Jianbo He, Lingfei Luo
Summary: This study reveals the crucial role of VEGF signaling in initiating BEC-to-hepatocyte transdifferentiation, mediated by the activation of the PI3K-mTORC1 axis. Modulation of VEGF signaling in BECs could be a potential therapeutic approach for patients with end-stage liver diseases.
Article
Multidisciplinary Sciences
Kotaro Tokuda, Yoshiaki Yamanaka, Yosuke Mano, Manabu Tsukamoto, Takafumi Tajima, Hitoshi Suzuki, Makoto Kawasaki, Soshi Uchida, Eiichiro Nakamura, Ke-Yong Wang, Akinori Sakai
Summary: This study demonstrated that metformin treatment can effectively suppress joint capsular fibrosis, with the most effective time for administration being early after joint immobilization; a delay of more than 2 weeks of administration will result in reduced effectiveness.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Sungyong You, Minhyung Kim, Steven Widen, Alexander Yu, Gloria C. Galvan, Yunhee Choi-Kuaea, Eduardo J. Eyzaguirre, Lars Dyrskjot, David J. McConkey, Woonyoung Choi, Dan Theodorescu, Keith S. Chan, Yong Shan, Douglas S. Tyler, Amanda M. De Hoedt, Stephen J. Freedland, Stephen B. Williams
Summary: This study aimed to compare the subtype distribution and differentially expressed genes between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC). The results showed differences in gene expression between AAs and EAs, suggesting potential race-based etiologies for muscle invasion, response to treatments, and transcriptome pathway regulations.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2022)
Article
Multidisciplinary Sciences
Fotis Nikolos, Kazukuni Hayashi, Xen Ping Hoi, Mark Ellie Alonzo, Qianxing Mo, Armine Kasabyan, Hideki Furuya, Jane Trepel, Dolores Di Vizio, Jlenia Guarnerio, Dan Theodorescu, Charles Rosser, Andrea Apolo, Matthew Galsky, Keith Syson Chan
Summary: Chemoimmunotherapy has shown limited clinical benefit in bladder cancer patients and the reasons for this are not well understood. This study reveals that platinum-based chemotherapy hinders the infiltration and activity of CD8+ T cells in mouse models of muscle-invasive bladder cancer. The release of prostaglandin E-2 (PGE(2)) from dying cancer cells is identified as a mechanism that inhibits dendritic cell maturation. By blocking PGE(2) release, CD8+ T cells regain their tumoricidal activity and infiltrate the tumor site. Blocking PGE(2) release synergizes with chemotherapy and enhances the response to immune checkpoint inhibitor therapy. These findings highlight the potential of targeting the COX-2/PGE2 axis in chemoimmunotherapy for bladder cancer.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Yang Zhang, Fan Huo, Qiang Cao, Ru Jia, Qiju Huang, Zhu A. Wang, Dan Theodorescu, Qiang Lv, Pengchao Li, Chao Yan
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Sungyong You, Minhyung Kim, Xen Ping Hoi, Yu Cheng Lee, Li Wang, David Spetzler, Jim Abraham, Dan Magee, Prerna Jain, Matthew D. Galsky, Keith Syson Chan, Dan Theodorescu
Summary: The study found that gene signature scores driven by DDR1 and DDR2 can predict the response to anti-PD-1 therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Review
Urology & Nephrology
Yu-Cheng Lee, Hung-Ming Lam, Charles Rosser, Dan Theodorescu, William C. Parks, Keith Syson Chan
Summary: Bladder cancer is a prevalent but currently understudied cancer type. Current research focuses on the genetic and epigenetic alterations of the bladder, while the role of the stromal compartment receives less attention. The bladder tumor microenvironment and the metastatic tumor microenvironment are important but unexploited niches.
NATURE REVIEWS UROLOGY
(2022)
Review
Multidisciplinary Sciences
Johanna M. Schafer, Tong Xiao, Hyunwoo Kwon, Katharine Collier, Yuzhou Chang, Hany Abdel-Hafiz, Chelsea Bolyard, Dongjun Chung, Yuanquan Yang, Debasish Sundi, Qin Ma, Dan Theodorescu, Xue Li, Zihai Li
Summary: This article explains the reasons behind higher incidence and mortality rates for males in non-reproductive system cancers, focusing on the role of sex chromosomes and sex hormones in driving differential adaptive immunity. The article highlights the involvement of cell-intrinsic androgen receptors in CD8(+) T cell dysfunction or exhaustion in the tumor microenvironment, and summarizes ongoing clinical efforts to investigate the impact of androgen blockade on cancer immunotherapy. It emphasizes the importance of a comprehensive research approach to understanding sex dimorphisms in cancer and advocating for considering sex as a crucial factor in guiding treatment decisions in the future.
Review
Urology & Nephrology
Michael Nazmifar, Cheyenne Williams, Aurash Naser-Tavakolian, John Heard, Charles Rosser, Dan Theodorescu, Michael Ahdoot
Summary: The purpose of this study is to evaluate the efficacy of various therapeutic agents for high-grade nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guerin treatment. A systematic review of available clinical trials was conducted, and a total of 70 studies evaluating 27 treatment options were analyzed. Intravesical chemotherapy and hyperthermia paired with chemotherapy demonstrated high complete response rates, while immunotherapy and novel agents also showed promising results. The treatments had low toxicity profiles and complication rates.
JOURNAL OF UROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Soehngen, David J. Thomas, Margaretha A. Skowron, Felix Bremmer, Markus Eckstein, Anja Stefanski, Marc D. Driessen, Gamal A. Wakileh, Kai Stuehler, Peter Altevogt, Dan Theodorescu, Ruediger Klapdor, Axel Schambach, Daniel Nettersheim
Summary: This study aimed to understand the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of NK cell CAR against CD24 in urological tumor cells. The results showed that CD24 interacts with proteins involved in cell adhesion, ATP binding, phosphoprotein binding, and post-translational modifications. Treatment with NK-CD24-CAR cells significantly decreased cell viability and induced apoptosis specifically in CD24(+) tumor cells. This study provides a promising novel target for immune therapeutic approaches against urological malignancies.
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Johanna M. Schafer, Xingyu Chen, Tong Xiao, Timothy D. Gauntner, Zihai Li, Dan Theodorescu
Summary: Loss of the Y chromosome (LOY) correlates with poor prognoses in bladder cancer patients. LOY mutations alter T cell function, promoting T cell exhaustion and sensitizing them to PD-1-targeted immunotherapy.
Article
Cell Biology
Florus C. de Jong, Teemu D. Laajala, Robert F. Hoedemaeker, Kimberley R. Jordan, Angelique C. J. van der Made, Egbert R. Boeve, Deric K. E. van der Schoot, Bart Nieuwkamer, Emiel A. M. Janssen, Tokameh Mahmoudi, Joost L. Boormans, Dan Theodorescu, James C. Costello, Tahlita C. M. Zuiverloon
Summary: The recommended treatment for high-risk non-muscle-invasive bladder cancer patients is tumor resection followed by adjuvant Bacillus Calmette-Guerin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. Identifying tumors unlikely to respond to BCG can lead to alternative treatments for these patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Peris R. Castaneda, Dan Theodorescu, Charles J. Rosser, Michael Ahdoot
Summary: Bladder cancer is a complex disease with variable prognosis, and recent studies have identified frequent genetic alterations and molecular subtypes. Personalized treatment strategies and the development of biomarkers to predict response and guide therapy in bladder cancer have become a focus of research. In this review, we summarize the latest studies on novel biomarkers in bladder cancer, specifically those intended to improve risk stratification and treatment selection, based on a search of recently published PubMed articles using relevant keywords.
FRONTIERS IN ONCOLOGY
(2023)
Article
Urology & Nephrology
Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David James McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson Jr, Seth P. Lerner
Summary: This article mainly evaluated the predictive role of the COXEN gene expression model in neoadjuvant chemotherapy for bladder cancer, and conducted a secondary analysis of the association between COXEN scores and event-free survival and overall survival.
Review
Medicine, General & Internal
Lars Dyrskjot, Donna E. Hansel, Jason A. Efstathiou, Margaret A. Knowles, Matthew D. Galsky, Jeremy Teoh, Dan Theodorescu
Summary: Bladder cancer is a global health issue with distinct molecular subtypes and pathogenic pathways. Early detection and diagnosis are crucial for improving patient outcomes. Treatment options vary depending on the invasion level and include surgery and immunotherapy. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Saravana Kumar Kailasam Mani, Wesley Huang, I. I. I. Kenneth H. Gouin, Yuzhou Chang, Tong Xiao, Qin Ma, Zihai Li, Simon R. V. Knott, Dan Theodorescu
Summary: In this study, single-cell RNA sequencing was used to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. Proportional and gene expression differences were found in epithelial and non-epithelial subpopulations between male and female tumors. Several genes were found to predict sex-specific survival in human BLCA datasets. Novel and clinically relevant sex-specific transcriptional signatures were identified, including immune cells in the tumor microenvironment. It validated the relevance of the BBN model for studying sex differences in human BLCA.
Review
Urology & Nephrology
Jun Gong, Daniel M. Kim, Michael R. Freeman, Hyung Kim, Leigh Ellis, Bethany Smith, Dan Theodorescu, Edwin Posadas, Robert Figlin, Neil Bhowmick, Stephen J. Freedland
Summary: Black men with prostate cancer have biologically distinct cancers compared to white men, including genetic alterations, protein differences, and tumor microenvironment. Socioeconomic status partially explains the disparities, but not completely. Further research on these biological differences can guide efforts to improve treatment outcomes for Black men.
NATURE REVIEWS UROLOGY
(2023)