Article
Oncology
Huajun Han, Laurie A. Davidson, Martha Hensel, Grace Yoon, Kerstin Landrock, Clinton Allred, Arul Jayaraman, Ivan Ivanov, Stephen H. Safe, Robert S. Chapkin
Summary: The study reveals the protective role of AhR signaling in genetically induced colon tumorigenesis at least by suppressing Wnt signaling and provides rationale for the AhR as a therapeutic target for cancer prevention and treatment.
MOLECULAR CANCER RESEARCH
(2021)
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
Biology
Thanh Huong Nguyen Ho-Bouldoires, Kevin Sollier, Laura Zamfirov, Florence Broders-Bondon, Demosthene Mitrossilis, Sebastian Bermeo, Coralie L. Guerin, Anna Chipont, Gabriel Champenois, Renaud Leclere, Nicolas Andre, Laurent Ranno, Aude Michel, Christine Menager, Didier Meseure, Charlie Demene, Mickael Tanter, Maria Elena Fernandez-Sanchez, Emmanuel Farge
Summary: The study found that high frequency pulsatile mechanical stresses maintain the physiological level of mice colon stem cells through the mechanosensitive Ret kinase. However, when stimulated by permanent tumor growth pressure, the stem cell levels increase pathologically and undergo hyperproliferation and tumorigenic transformation. Additionally, Ret activation in human colon cancer tissue is associated with tumor grade.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Yuyang Dai, Jinsong Liu, Xuyan Li, Jianzhong Deng, Cheng Zeng, Wenbin Lu, Yongzhong Hou, Ying Sheng, Honglin Wu, Qian Liu
Summary: This research aims to investigate the regulatory network of NKD1 and miRNAs in colon cancer. The study identified let-7b-5p as a miRNA that can inhibit colon cancer cell proliferation, migration, and invasion by targeting NKD1. Further analysis revealed that NKD1 enhances colon cancer cell proliferation and migration by inhibiting APC expression.
Review
Biochemistry & Molecular Biology
Qiyun Xiao, Johannes Werner, Nachiyappan Venkatachalam, Kim E. Boonekamp, Matthias P. Ebert, Tianzuo Zhan
Summary: Targeting cancer hallmarks is crucial for improving anti-cancer treatment, but cross-talk between signaling pathways often leads to resistance. This article provides an overview of the molecular interactions between the p53 and Wnt pathways in cancer, including complex feedback loops and reciprocal transactivation, as well as the mutational landscape of genes associated with these pathways.
Article
Gastroenterology & Hepatology
Koelina Ganguly, Rakesh Bhatia, Sanchita Rauth, Andrew Kisling, Pranita Atri, Christopher Thompson, Raghupathy Vengoji, Shiv Ram Krishn, Dhananjay Shinde, Vinai Thomas, Sukhwinder Kaur, Kavita Mallya, Jesse L. Cox, Sushil Kumar, Surinder K. Batra
Summary: The study reveals that MUC5AC promotes gemcitabine resistance in pancreatic cancer cells by affecting glutamine metabolism and nucleotide biosynthesis. Depletion of MUC5AC and deprivation of glutamine can enhance sensitivity of pancreatic cancer cells to gemcitabine. Dual-targeting therapy against MUC5AC, beta-catenin, and glutamine metabolism can overcome gemcitabine resistance in pancreatic cancer.
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Valerie S. Meniel, Toby J. Phesse, Helen B. Pearson
Summary: Aberrant activation of the Wnt pathway is closely related to tumor formation, progression, and therapeutic resistance in prostate cancer. Targeting the Wnt pathway for prostate cancer treatment has shown potential efficacy. However, the functional consequences of activating the Wnt pathway during different stages of prostate cancer progression are still unclear. Preclinical research on targeting Wnt signaling in the treatment of prostate cancer is crucial for identifying effective treatment strategies and improving patient care.
Article
Nanoscience & Nanotechnology
Xiao-Min Liu, Wen-Ting Zhu, Meng-Lei Jia, Yu-Ting Li, Ye Hong, Zhong-Qiu Liu, Peng-Ke Yan
Summary: The study demonstrated that the combination of Rapa/Lps and 5-FU effectively suppressed colorectal tumor formation by inhibiting angiogenesis and proliferation.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Oncology
Rahui Park, Seungmin Lee, Hyunjung Chin, Anh Thai-Quynh Nguyen, Daekee Lee
Summary: In this study, the researchers found that GNA14 promotes the progression of colorectal cancer (CRC) through the ERK and beta-catenin pathways. Knockdown of GNA14 inhibits the proliferation of CRC cells and suppresses malignant tumor progression in the intestine. These findings suggest that GNA14 may be a potential therapeutic target for CRC.
Article
Nutrition & Dietetics
Jun Chen, Zhiguang Duan, Yannan Liu, Rongzhan Fu, Chenhui Zhu
Summary: This study found that ginsenoside Rh4 inhibits the metastasis of esophageal squamous cell carcinoma (ESCC) by regulating the Wnt/beta-catenin signaling pathway and the level of c-Myc. In vitro and in vivo experiments confirmed the inhibitory effect of Rh4 on ESCC metastasis.
Article
Oncology
Jiong Ning, Qi Sun, Zijie Su, Lifeng Tan, Yun Tang, Sapna Sayed, Huan Li, Vivian Weiwen Xue, Shanshan Liu, Xianxiong Chen, Desheng Lu
Summary: CK1 delta/epsilon enhance beta-catenin-mediated transcription by regulating beta-catenin acetylation. CK1 delta/epsilon interact with Tip60 and facilitate its recruitment to the beta-catenin complex, leading to increased beta-catenin acetylation at K49. Furthermore, this study discovers that a complex consisting of CK1 delta/CK1 epsilon/beta-catenin/Tip60 is present in colon cancer cells, and this complex plays an important role in beta-catenin acetylation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Seong-Ho Lee, Hee-Seop Lee, Jihye Lee, Darshika Amarakoon, Zhiyuan Lou, Leela E. Noronha, Thomas J. Herald, Ramasamy Perumal, Dmitriy Smolensky
Summary: High-phenolic sorghum bran extracts have been found to inhibit proliferation and induce apoptosis in colorectal cancer cell lines. They can repress NF-kappa B and PI3K/AKT pathways while activating AMPK and autophagy, which significantly suppress tumor formation in colorectal cancer mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Wibke Groenewald, Anders H. H. Lund, David Michael Gay
Summary: It is well known that mutations in the WNT-signalling pathway are significant in cancer development. Understanding the role and occurrence of these mutations within the pathway is crucial for developing effective therapeutic strategies. Some cancers have mutations at the receptor level of the pathway, while others have mutations in the cytoplasmic segment, leading to ligand-dependent or ligand-independent pathway activation, respectively. This review explores the driving mutations in cancer and the available therapeutic interventions for each type of mutation, and also discusses a potential new therapeutic avenue targeting the translational apparatus downstream from WNT signalling.
Article
Hematology
Yue Sheng, Rui Ma, Chunjie Yu, Qiong Wu, Steven Zhang, Kimberly Paulsen, Jiwang Zhang, Hongyu Ni, Yong Huang, Yi Zheng, Zhijian Qian
Summary: This study investigated the dosage effect of c-Myc on hematopoiesis and its role in the Wnt/beta-catenin pathway in HSC and bone marrow niche cells. The results demonstrated the critical role of Nr4a1, Nr4a2, and Jmjd3 as downstream targets of c-Myc in HSCs. Additionally, the study provided evidence of c-Myc-mediated Apc loss inducing IL6 secretion in endothelial cells and its impact on erythroid cell differentiation.
Article
Oncology
Kathleen A. O'Leary, Debra E. Rugowski, Michael P. Shea, Ruth Sullivan, Amy R. Moser, Linda A. Schuler
Summary: Prolactin (PRL) collaborates with Apc(Min/+) to increase tumor incidence and modulate cancer stem cell activity through Notch-driven signals, shedding light on mechanisms whereby PRL elevates risk of breast cancer.
Editorial Material
Oncology
Michael Flood, Robert Ramsay, Alexander Heriot
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Mahmoud A. Bassal, Saumya E. Samaraweera, Kelly Lim, Brooks A. Bernard, Sheree Bailey, Satinder Kaur, Paul Leo, John Toubia, Chloe Thompson-Peach, Tran Nguyen, Kyaw Ze Ya Maung, Debora A. Casolari, Diana G. Iarossi, Ilaria S. Pagani, Jason Powell, Stuart Pitson, Siria Natera, Ute Roessner, Ian D. Lewis, Anna L. Brown, Daniel G. Tenen, Nirmal Robinson, David M. Ross, Ravindra Majeti, Thomas J. Gonda, Daniel Thomas, Richard J. D'Andrea
Summary: This study reveals the mutual exclusivity between germline mutations in mitochondrial complex I and somatic mutations in the metabolic enzyme IDH1 in patients with acute myeloid leukemia (AML), and finds that IDH1 mutant cells have increased sensitivity to complex I inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Atara Posner, Owen Wj Prall, Tharani Sivakumaran, Dariush Etemadamoghadam, Niko Thio, Andrew Pattison, Shiva Balachander, Krista Fisher, Samantha Webb, Colin Wood, Anna DeFazio, Nicholas Wilcken, Bo Gao, Christos S. Karapetis, Madhu Singh, Ian M. Collins, Gary Richardson, Christopher Steer, Mark Warren, Narayan Karanth, Gavin Wright, Scott Williams, Joshy George, Rodney J. Hicks, Alex Boussioutas, Anthony J. Gill, Benjamin J. Solomon, Huiling Xu, Andrew Fellowes, Stephen B. Fox, Penelope Schofield, David Bowtell, Linda Mileshkin, Richard W. Tothill
Summary: This study compared the diagnostic utility of RNA and DNA tests in 215 CUP patients, and found that DNA mutation profiling was more diagnostically informative, especially for cases unresolved by clinicopathology assessment alone.
JOURNAL OF PATHOLOGY
(2023)
Article
Cell Biology
Dylan Jones, Clarissa A. Whitehead, Marija Dinevska, Samuel S. Widodo, Liam M. Furst, Andrew P. Morokoff, Andrew H. Kaye, Katharine J. Drummond, Theo Mantamadiotis, Stanley S. Stylli
Summary: Glioblastoma is a highly invasive and destructive brain tumor, and current standard treatments often fail to effectively eliminate it. In this study, we investigate the effects of several FDA-approved drugs on the invasion and viability of GBM cells. We found that these drugs can reduce cell invasion and viability, suggesting their potential as therapeutic options for GBM.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Economics
Louisa G. Gordon, C. Wood, R. W. Tothill, P. M. Webb, P. Schofield, L. Mileshkin
Summary: This study aimed to describe and quantify healthcare resource usage and costs for patients with cancer of unknown primary (CUP) in Australia, and compare them with patients with ovarian cancer. The study found that pre-diagnosis costs for CUP patients were nearly triple those for ovarian cancer patients. Six months after diagnosis, healthcare costs remained higher for CUP patients than for ovarian cancer patients.
PHARMACOECONOMICS-OPEN
(2023)
Article
Oncology
Robert Ramsay, Shienny Sampurno, Michael P. Flood, Andrew C. Lynch
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Kamil Wolyniec, Clare O'Callaghan, Krista Fisher, Sharp Jessica, Richard W. W. Tothill, David Bowtell, Mileshkin Linda, Penelope Schofield
Summary: Patients with Cancer of Unknown Primary (CUP) often have poor understanding of their illness and high levels of psychological distress. This study aimed to understand patients' experiences of communication with doctors, their understanding of diagnosis, and the role of genomic testing, as well as their information needs. Semi-structured interviews were conducted with CUP patients, and qualitative analysis was performed. Results showed varied perceptions of communication, different levels of information needs, and limited understanding of genomic testing among patients.
Article
Oncology
Marija Dinevska, Samuel S. Widodo, Liam Furst, Lucero Cuzcano, Yitong Fang, Stefano Mangiola, Paul J. Neeson, Phillip K. Darcy, Robert G. Ramsay, Ryan Hutchinson, Fabienne MacKay, Michael Christie, Stanley S. Stylli, Theo Mantamadiotis
Summary: Tumor microenvironment in malignant astrocytoma undergoes changes in cell composition, cell signaling activation, and extracellular matrix deposition during disease progression. Targeting the extracellular matrix and cell signaling activation will be critical in designing personalized therapy.
Review
Oncology
Padmashree Rao, Liam Furst, Deborah Meyran, Chelsea Mayoh, Paul J. Neeson, Rachael Terry, Dong-Anh Khuong-Quang, Theo Mantamadiotis, Paul G. Ekert
Summary: Pediatric brain tumors are the most common solid tumor in children, and current treatments include surgery, chemotherapy, and radiotherapy. Immunotherapy, especially CAR T cell therapy, may provide new avenues for improved outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Editorial Material
Hematology
Thomas J. Gonda
Summary: Clarke et al(1) demonstrate in this study that loss of 1 allele of Myb in mice leads to increased myeloproliferation and development of myeloid neoplasms, including AML, during aging. This is surprising given the established role of MYB in normal hematopoiesis and leukemogenesis. These findings suggest that even partial loss of MYB activity can predispose individuals to myeloid neoplasms.
Article
Oncology
Sarah A. Cain, Bernard Pope, Stefano Mangiola, Theo Mantamadiotis, Katharine J. Drummond
Summary: This study aimed to identify somatic mutations and copy number alterations associated with grade progression in meningiomas. Through targeted next-generation sequencing, mutations and CNAs associated with different grade progression were found. NF2 mutations played an important role in grade progression.
Review
Cell Biology
Robert G. Ramsay, Vicki Whitehall, Michael P. Flood
Summary: Adoption of organoid/tumoroid propagation of normal and malignant intestinal epithelia has provided unprecedented opportunities to compare cell growth factor and signaling dependencies. These 3D structures mimic tumors in terms of gene expression and offer deeper insights into the tumor microenvironment (TME). Manipulation of TME elements and evaluation of different therapies can be done using patient-derived tumor models.
Article
Oncology
Clarissa A. Whitehead, Haoyun Fang, Huaqi Su, Andrew P. Morokoff, Andrew H. Kaye, Eric Hanssen, Cameron J. Nowell, Katharine J. Drummond, David W. Greening, Laura J. Vella, Theo Mantamadiotis, Stanley S. Stylli
Summary: In this study, it was found that glioblastoma cells promote invadopodia activity by secreting small extracellular vesicles (sEVs) containing matrix metalloproteinase MMP-2. Additionally, the invasiveness of cells and sEV secretion were increased after radiotherapy/temozolomide treatment. These findings reveal a relationship between sEVs and invadopodia, providing important insights into the functional capacity of sEVs in promoting glioblastoma cell invasion.
Article
Developmental Biology
Tom C. Karagiannis, Christian Orlowski, Katherine Ververis, Eleni Pitsillou, Gulcan Sarila, Samuel T. Keating, Laura J. Foong, Stefanie Fabris, Christina Ngo-Nguyen, Neha Malik, Jun Okabe, Andrew Hung, Theo Mantamadiotis, Assam El-Osta
Summary: This study investigates the role of phosphorylated histone H2AX (gamma H2AX) as a marker of DNA double-strand breaks (DSBs) and its implication in stem cell differentiation. The research establishes a mouse embryonic stem cell (mESC) differentiation model and examines the dynamics of gamma H2AX foci during the process. The findings reveal that gamma H2AX serves as a versatile marker of DSBs and may have a role as a biomarker in stem cell differentiation.
CELLS & DEVELOPMENT
(2024)