Article
Oncology
Sami Shoucair, Joseph R. Habib, Ning Pu, Benedict Kinny-Koster, A. Floortje van Ooston, Ammar A. Javed, Kelly J. Lafaro, Jin He, Christopher L. Wolfgang, Jun Yu
Summary: The study revealed that combinations of mutations in the four driver genes are associated with prognosis in resected PDAC patients. Patients with combined mtKRAS and mtTP53 had a better overall survival and recurrence-free survival when the KRAS p.G12D variant was present.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Luiz Henrique Araujo, Bianca Mendes Souza, Laura Rabelo Leite, Sabrina A. F. Parma, Natalia P. Lopes, Frederico S. V. Malta, Maira C. M. Freire
Summary: KRAS G12C mutation frequency is higher than other driver mutations in colorectal and non-small cell lung cancer, suggesting KRAS testing should be considered for all patients regardless of clinical or demographic characteristics.
Article
Multidisciplinary Sciences
Madiha Naseem, Shu Cao, Dongyun Yang, Joshua Millstein, Alberto Puccini, Fotios Loupakis, Sebastian Stintzing, Chiara Cremolini, Ryuma Tokunaga, Francesca Battaglin, Shivani Soni, Martin D. Berger, Afsaneh Barzi, Wu Zhang, Alfredo Falcone, Volker Heinemann, Heinz-Josef Lenz
Summary: In this study, the random survival forests (RSF) method was used to identify predictive markers of overall survival (OS) and progression-free survival (PFS) in mCRC patients treated with FOLFIRI/bevacizumab. The results show that SNPs in the Wnt/β-catenin and tumor associated macrophage pathways are strong predictors of OS and PFS in mCRC patients, regardless of KRAS status, while a SNP in the sex-differentiation pathway gene DMRT1 is strongly predictive of OS and PFS in KRAS mutant mCRC patients. RSF is highlighted as a useful method for identifying predictive SNPs in multiple pathways.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Sanne M. van Neerven, Nina E. de Groot, Lisanne E. Nijman, Brendon P. Scicluna, Milou S. van Driel, Maria C. Lecca, Daniel O. Warmerdam, Vaishali Kakkar, Leandro F. Moreno, Felipe A. Vieira Braga, Delano R. Sanches, Prashanthi Ramesh, Sanne ten Hoorn, Arthur S. Aelvoet, Marouska F. van Boxel, Lianne Koens, Przemek M. Krawczyk, Jan Koster, Evelien Dekker, Jan Paul Medema, Douglas J. Winton, Maarten F. Bijlsma, Edward Morrissey, Nicolas Leveille, Louis Vermeulen
Summary: In the ISC niche, the delicate balance of WNT agonists and antagonists is crucial for maintaining the ISC compartment and preventing unrestrained activation of the WNT pathway. Apc-mutant ISCs function as supercompetitors by secreting WNT antagonists to induce differentiation of neighboring wild-type ISCs. Lithium chloride prevents the expansion of Apc-mutant clones and adenoma formation by rendering wild-type ISCs insensitive to WNT antagonists through downstream activation of WNT by inhibiting GSK3 beta. Boosting the fitness of healthy cells may be a powerful strategy to limit the formation of cancers in high-risk individuals.
Article
Multidisciplinary Sciences
Lillian J. Eichner, Stephanie D. Curtis, Sonja N. Brun, Caroline K. McGuire, Irena Gushterova, Joshua T. Baumgart, Elijah Trefts, Debbie S. Ross, Tammy J. Rymoff, Reuben J. Shaw
Summary: HDAC3 plays a critical role in Kras-mutant lung cancer, promoting tumor growth and mediating the expression of target genes, including FGFR1. Inhibition of HDAC3 with entinostat can reverse resistance to the MEK inhibitor trametinib. Combination treatment of entinostat and trametinib shows therapeutic benefit in Kras/LKB1 GEMM.
Article
Oncology
Isidoro Cobo, Mar Iglesias, Marta Flandez, Caroline Verbeke, Natalia del Pozo, Miriam Llorente, Rita Lawlor, Claudio Luchini, Borislav Rusev, Aldo Scarpa, Francisco X. Real
Summary: Pancreatic cystic neoplasms are a growing public health concern, with some progressing to cancer. The gene NR5A2 may play a role in pancreatic diseases, with its effects being time- and cell context-dependent. These findings suggest potential new models for studying pancreatic lesions and their progression, with implications for patient treatment.
JOURNAL OF PATHOLOGY
(2021)
Review
Oncology
Molly L. Parrish, Russell R. Broaddus, Andrew B. Gladden
Summary: Endometrial carcinoma is the most diagnosed gynecological malignancy in Western countries, with rising incidence and mortality rates. Mutations in exon 3 of the CTNNB1 gene may lead to decreased progression-free survival in a subset of patients with endometrioid EC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yan-Long Han, Dan Luo, Kakeng Habaxi, Julaiti Tayierjiang, Wei Zhao, Wei Wang, Wumaierjiang Aikebaier, Li Wang
Summary: In this study, we identified COL5A2 as a prognostic gene for osteosarcoma through bioinformatics analysis, and showed that COL5A2 inhibits invasion and metastasis of osteosarcoma by suppressing the TGF-beta and Wnt/β-Catenin signaling pathways.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Hao Zhang, Chuanchuan Zheng, Wei Chen, Xiaoqiang Li, Jinshu Wang, Taikun Wang, Qi Zhao, Hao Huang, Yiting Li, Chengliang Yang, Kegong Xie, Shengcai Pan, Binghao Wang, Chong Wang, Yujin Tang, Kai Li, Jia Liu, Liqiang Wang
Summary: Our study demonstrates that targeting Src with PP2 can inhibit Wnt/beta-catenin signaling and activate TGF-beta/Smad signaling, thus protecting against cartilage destruction in OA. This provides a potential therapeutic target for OA treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Physiology
Qian Zhang, Xinhua Xiao, Jia Zheng, Ming Li, Miao Yu, Fan Ping, Tong Wang, Xiaojing Wang
Summary: The study reveals that Qishen Yiqi dripping pill exerts renal-protective function by inhibiting the Wnt/beta-catenin and TGF-beta/Smad2 signaling pathways in diabetic rats, as evidenced by reduced levels of serum markers and improved kidney histology and fibrosis.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Oncology
Pariyada Tanjak, Amphun Chaiboonchoe, Tharathorn Suwatthanarak, Onchira Acharayothin, Kullanist Thanormjit, Jantappapa Chanthercrob, Thanawat Suwatthanarak, Bundit Wannasuphaphol, Kemmapon Chumchuen, Bhoom Suktitipat, Somponnat Sampattavanich, Krittiya Korphaisarn, Ananya Pongpaibul, Naravat Poungvarin, Harald Grove, Woramin Riansuwan, Atthaphorn Trakarnsanga, Asada Methasate, Manop Pithukpakorn, Vitoon Chinswangwatanakul
Summary: This study investigates the transcriptomic impact of KRAS mutations in colorectal cancers, focusing on the tumor microenvironment and pathways beyond metabolic deregulation. It is found that CRC patients with KRAS mutations are mainly enriched in CMS3 and exhibit specific immune gene signatures in an immunosuppressive TME, leading to worse overall survival. Activation of TGF beta signaling by KRAS mutations is associated with reduced pro-inflammatory and cytokine gene signatures, suppressing immune infiltration. Spatially resolved gene expression profiling suggests up-regulated immune suppression genes in the TME of KRAS-mutated CMS3-classified tissues. This study provides important insights into the complex transcriptomic profile of KRAS mutations in an immunosuppressive TME.
Article
Neurosciences
Yu Zhan, Yong Wen, Fan Zheng, Li-juan Du, Tai-yu Chen, Xu-long Shen, Rong Wu, Xue-gui Tang
Summary: This study revealed that miR-26b-3p promotes intestinal dysmotility by targeting FZD10 to induce apoptosis in EGCs. This finding provides a new research direction for the treatment and intervention of intestinal dysmotility.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoshuang Wang, Mei Feng, Tengfei Xiao, Baosen Guo, Danyang Liu, Chenglong Liu, Jinpeng Pei, Qiaofeng Liu, Yi Xiao, Rina Rosin-Arbesfeld, Ying Shi, Yang Zhou, Mengxuan Yang, Yu-Xiong Feng, Yizhou Jiang, Zhimin Shao, Ker Yu, Di Zhu
Summary: The expression of BCL9 and BCL9L is correlated with malignancy in TNBC patient tumors, and they promote tumor cell growth, migration, and metastasis. Inhibition of BCL9/BCL9L and TGF-beta suppresses Treg activity, while TGF-beta signaling increases tumor infiltration of cytotoxic CD8 (+) T cells. Inhibiting BCL9/BCL9L synergizes with PD-1/L1 antibodies to inhibit tumor growth.
Article
Immunology
Shengyun Zhu, Kairen Xu, Shuyao Li, Xiangru Yu, Yahui Liu, Qigang Zhang, Lingyu Zeng, Kailin Xu, Chunling Fu
Summary: This study investigates the impact of the MPLW515L mutation on intestinal homeostasis in a mutated MPN mice model. The mutation aggravates inflammation, decreases the levels of tight junction proteins and receptors for bacteria metabolites, and increases the activation of the caspase1/IL-1 beta signaling pathway. Additionally, the mutation leads to upexpression of anti-microbial genes in the intestinal tract.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Mustafa Karabicici, Yagmur Azbazdar, Gunes Ozhan, Serif Senturk, Zeynep Firtina Karagonlar, Esra Erdal
Summary: In this study, it was found that regorafenib treatment activated Wnt/beta-catenin signaling only in hepatoblast-like HCC cell lines and induced enrichment of markers associated with hepatic stem/progenitor cells. On the other hand, regorafenib resistant cells demonstrated diminished Wnt/beta-catenin signaling activity and enhanced TGF-beta signaling activity. The inhibition of TGF-beta pathway in combination with regorafenib administration might increase regorafenib-induced cell death in HCC tumors with aberrant activation in the Wnt/beta-catenin pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)