keyword
https://read.qxmd.com/read/38520909/ex-vivo-drug-testing-of-patient-derived-lung-organoids-to-predict-treatment-responses-for-personalized-medicine
#21
REVIEW
Josephine A Taverna, Chia-Nung Hung, Madison Williams, Ryan Williams, Meizhen Chen, Samaneh Kamali, Vaishnavi Sambandam, Cheryl Hsiang-Ling Chiu, Pawel A Osmulski, Maria E Gaczynska, Daniel T DeArmond, Christine Gaspard, Maria Mancini, Meena Kusi, Abhishek N Pandya, Lina Song, Lingtao Jin, Paolo Schiavini, Chun-Liang Chen
Lung cancer is the leading cause of global cancer-related mortality resulting in ∼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models...
March 14, 2024: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/38520026/prognostic-pet-11-c-acetate-uptake-is-associated-with-hypoxia-gene-expression-in-patients-with-late-stage-hepatocellular-carcinoma-a-bench-to-bed-study
#22
JOURNAL ARTICLE
Keith Wan Hang Chiu, Kel Vin Tan, Xinxiang Yang, Xiaoqiang Zhu, Jingjing Shi, Chi-Leung Chiang, Lawrence Chan, Yuan Hui, Pek-Lan Khong, Kwan Man, Jason Wing Hon Wong
BACKGROUND: Positron Emission Tomography (PET) with combined [18 F]-FDG and [11 C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS: Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo...
March 22, 2024: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://read.qxmd.com/read/38520004/cdkl1-potentiates-the-antitumor-efficacy-of-radioimmunotherapy-by-binding-to-transcription-factor-ybx1-and-blocking-pd-l1-expression-in-lung-cancer
#23
JOURNAL ARTICLE
Zixuan Li, Huichan Xue, Jinsong Li, Zhikun Zheng, Zhiwei Liu, Xiaorong Dong, Hongbo Wang, Jing Chen, Shuangbing Xu
BACKGROUND: The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation of PD-L1 expression and the response to radioimmunotherapy in lung cancer...
March 22, 2024: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/38519641/colorectal-cancer-cells-secreting-dkk4-transform-fibroblasts-to-promote-tumour-metastasis
#24
JOURNAL ARTICLE
Xue Li, Yulin Chen, Ran Lu, Min Hu, Lei Gu, Qiaorong Huang, Wentong Meng, Hongyan Zhu, Chuanwen Fan, Zongguang Zhou, Xianming Mo
Wnt/β-catenin signalling is aberrantly activated in most colorectal cancer (CRC) and is one key driver involved in the initiation and progression of CRC. However, mutations of APC gene in CRC patients retain certain activity of APC protein with decreased β-catenin signalling and DKK4 expression significantly upregulates and represses Wnt/β-catenin signalling in human CRC tissues, suggesting that a precisely modulated activation of the Wnt/β-catenin pathway is essential for CRC formation and progression...
March 22, 2024: Oncogene
https://read.qxmd.com/read/38518726/a-novel-sik2-inhibitor-sic-19-exhibits-synthetic-lethality-with-parp-inhibitors-in-ovarian-cancer
#25
JOURNAL ARTICLE
Fang Wang, Xuejiao Yu, Jun Qian, Yumin Cao, Shunli Dong, Shenghua Zhan, Zhen Lu, Robert C Bast, Qingxia Song, Youguo Chen, Yi Zhang, Jinhua Zhou
PURPOSE: Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer. METHODS: The SIK2 protein was modeled using a Molecular Operating Environment (MOE), and the most favorable model was selected based on a GBVI/WSA dG scoring function...
March 6, 2024: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/38518121/discovery-of-novel-5-6-dihydro-4-h-pyrido-2-3-4-de-quinazoline-irreversible-inhibitors-targeting-both-wild-type-and-a775_g776insyvma-mutated-her2-kinases
#26
JOURNAL ARTICLE
Leifu Yang, Yaxin Li, Yunling Du, Yan Guo, Zhenke Guo, Baoxiu Liu, Jianglin Liu, Yanfei Liu, Hongdan Niu, Yueming Sun, Henglin Yan, Yajuan Yang, Shannan Yu, Yifan Zhang, Yuan Zhang, Kun Zheng, Nanqiao Zheng, Xiaoqing Zhang, Qiang Zhang, Liming Hu
HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4- de ]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4- de ]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib...
March 22, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38518105/the-il-7r-antagonist-lusvertikimab-reduces-leukemic-burden-in-xenograft-all-via-antibody-dependent-cellular-phagocytosis
#27
JOURNAL ARTICLE
Lennart Lenk, Irène Baccelli, Anna Laqua, Julia Heymann, Claas Reimer, Anna Dietterle, Dorothee Winterberg, Caroline Mary, Frédérique Corallo, Julien Taurelle, Emma Narbeburu, Stéphanie Lara Neyton, Mylène Déramé, Sabrina Pengam, Fotini Vogiatzi, Beat Bornhauser, Jean-Pierre Bourquin, Simon Raffel, Vladyslava Dovhan, Thomas Schüler, Gabriele Escherich, Monique L den Boer, Judith M Boer, Wiebke Wessels, Matthias Peipp, Julia Alten, Željko Antić, Anke Katharina Bergmann, Martin Schrappe, Gunnar Cario, Monika Brüggemann, Nicolas Poirier, Denis M Schewe
Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of precursor B or T cells (BCP- or T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (r/r) disease, high-risk leukemias and T-ALL, where immunotherapy approaches remain scarce. While the Interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL...
March 22, 2024: Blood
https://read.qxmd.com/read/38517886/evolution-of-chromosome-arm-aberrations-in-breast-cancer-through-genetic-network-rewiring
#28
JOURNAL ARTICLE
Elena Kuzmin, Toby M Baker, Tom Lesluyes, Jean Monlong, Kento T Abe, Paula P Coelho, Michael Schwartz, Joseph Del Corpo, Dongmei Zou, Genevieve Morin, Alain Pacis, Yang Yang, Constanza Martinez, Jarrett Barber, Hellen Kuasne, Rui Li, Mathieu Bourgey, Anne-Marie Fortier, Peter G Davison, Atilla Omeroglu, Marie-Christine Guiot, Quaid Morris, Claudia L Kleinman, Sidong Huang, Anne-Claude Gingras, Jiannis Ragoussis, Guillaume Bourque, Peter Van Loo, Morag Park
The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation...
March 21, 2024: Cell Reports
https://read.qxmd.com/read/38516781/sesn1-functions-as-a-new-tumor-suppressor-gene-via-toll-like-receptor-signaling-pathway-in-neuroblastoma
#29
JOURNAL ARTICLE
Zhongyan Hua, Bo Chen, Baocheng Gong, Meizhen Lin, Yifan Ma, Zhijie Li
AIMS: Neuroblastoma (NB) is the most common extracranial solid tumor in children, with a 5-year survival rate of <50% in high-risk patients. MYCN amplification is an important factor that influences the survival rate of high-risk patients. Our results indicated MYCN regulates the expression of SESN1. Therefore, this study aimed to investigate the role and mechanisms of SESN1 in NB. METHODS: siRNAs or overexpression plasmids were used to change MYCN, SESN1, or MyD88's expression...
March 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38516703/integrated-network-pharmacology-and-experimental-verification-to-explore-the-potential-mechanism-of-san-ying-decoction-for-treating-triple-negative-breast-cancer
#30
JOURNAL ARTICLE
Xiaojuan Yang, Feifei Li, Youyang Shi, Yuanyuan Wu, Rui Yang, Xiaofei Liu, Yang Zhang, Guangtao Zhang, Mei Ma, Zhanyang Luo, Xianghui Han, Ying Xie, Sheng Liu
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database...
March 21, 2024: Acta Biochimica et Biophysica Sinica
https://read.qxmd.com/read/38515951/erlotinib-combination-with-a-mitochondria-targeted-ubiquinone-effectively-suppresses-pancreatic-cancer-cell-survival
#31
JOURNAL ARTICLE
Pui-Yin Leung, Wenjing Chen, Anissa N Sari, Poojitha Sitaram, Pui-Kei Wu, Susan Tsai, Jong-In Park
BACKGROUND: Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity of the epidermal growth factor receptor (EGFR) is often observed in pancreatic cancer, and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration. Nevertheless, erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm ), facilitate tumor cell uptake of Δψm -sensitive agents, disrupt mitochondrial homeostasis, and subsequently trigger tumor cell death...
February 21, 2024: World Journal of Gastroenterology: WJG
https://read.qxmd.com/read/38515278/prom2-overexpression-induces-metastatic-potential-through-epithelial-to-mesenchymal-transition-and-ferroptosis-resistance-in-human-cancers
#32
JOURNAL ARTICLE
Justine Paris, Claire Wilhelm, Celeste Lebbé, Mohammed Elmallah, Frédéric Pamoukdjian, Audrey Héraud, Guillaume Gapihan, Aurore Van De Walle, Van Nhan Tran, Diaddin Hamdan, Clara Allayous, Maxime Battistella, Emmanuel Van Glabeke, Kah Wai Lim, Christophe Leboeuf, Sébastien Roger, Géraldine Falgarone, Anh Tuan Phan, Guilhem Bousquet
INTRODUCTION: Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. METHODS AND RESULTS: Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance...
March 2024: Clinical and Translational Medicine
https://read.qxmd.com/read/38515149/circhas2-activates-ccne2-to-promote-cell-proliferation-and-sensitizes-the-response-of-colorectal-cancer-to-anlotinib
#33
JOURNAL ARTICLE
Haosheng Li, Haoran Feng, Tao Zhang, Junwei Wu, Xiaonan Shen, Shuiyu Xu, Lianghui Xu, Shaodong Wang, Yaqi Zhang, Wenqing Jia, Xiaopin Ji, Xi Cheng, Ren Zhao
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure...
March 21, 2024: Molecular Cancer
https://read.qxmd.com/read/38515112/aurkb-promotes-bladder-cancer-progression-by-deregulating-the-p53-dna-damage-response-pathway-via-mad2l2
#34
JOURNAL ARTICLE
Linzhi Li, Pengcheng Jiang, Weimin Hu, Fan Zou, Ming Li, Ting Rao, Yuan Ruan, Weimin Yu, Jinzhuo Ning, Fan Cheng
BACKGROUND: Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer...
March 21, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38515107/factors-associated-with-engraftment-success-of-patient-derived-xenografts-of-breast-cancer
#35
JOURNAL ARTICLE
Jongwon Lee, GunHee Lee, Hye Seon Park, Byung-Kwan Jeong, Gyungyub Gong, Jae Ho Jeong, Hee Jin Lee
BACKGROUND: Patient-derived xenograft (PDX) models serve as a valuable tool for the preclinical evaluation of novel therapies. They closely replicate the genetic, phenotypic, and histopathological characteristics of primary breast tumors. Despite their promise, the rate of successful PDX engraftment is various in the literature. This study aimed to identify the key factors associated with successful PDX engraftment of primary breast cancer. METHODS: We integrated clinicopathological data with morphological attributes quantified using a trained artificial intelligence (AI) model to identify the principal factors affecting PDX engraftment...
March 21, 2024: Breast Cancer Research: BCR
https://read.qxmd.com/read/38514720/the-immune-regulation-and-therapeutic-potential-of-the-smad-gene-family-in-breast-cancer
#36
JOURNAL ARTICLE
Zhuo Chen, Yu Wang, Xiaodi Lu, Hong Chen, Yiran Kong, Liwei Rong, Guonian Wang
Breast cancer is a serious threat to human health. The transforming growth factor-β signaling pathway is an important pathway involved in the occurrence and development of cancer. The SMAD family genes are responsible for the TGF-β signaling pathway. However, the mechanism by which genes of the SMAD family are involved in breast cancer is still unclear. Therefore, it is necessary to investigate the biological roles of the SMAD family genes in breast cancer. We downloaded the gene expression data, gene mutation data, and clinical pathological data of breast cancer patients from the UCSC Xena database...
March 21, 2024: Scientific Reports
https://read.qxmd.com/read/38514606/the-eif3h-hax1-axis-increases-raf-mek-erk-signaling-activity-to-promote-colorectal-cancer-progression
#37
JOURNAL ARTICLE
Huilin Jin, Xiaoling Huang, Qihao Pan, Ning Ma, Xiaoshan Xie, Yue Wei, Fenghai Yu, Weijie Wen, Boyu Zhang, Peng Zhang, Xijie Chen, Jie Wang, Ran-Yi Liu, Junzhong Lin, Xiangqi Meng, Mong-Hong Lee
Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing βTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2...
March 21, 2024: Nature Communications
https://read.qxmd.com/read/38514083/preclinical-characterization-of-dpi-4452-a-68-ga-177-lu-theranostic-ligand-for-carbonic-anhydrase-ix
#38
JOURNAL ARTICLE
Frédéric Massière, Norbert Wiedemann, Inês Borrego, Aileen Hoehne, Frank Osterkamp, Matthias Paschke, Dirk Zboralski, Anne Schumann, Anne Bredenbeck, Franck Brichory, Antoine Attinger
The membrane protein carbonic anhydrase IX (CAIX) is highly expressed in many hypoxic or von Hippel-Lindau tumor suppressor-mutated tumor types. Its restricted expression in healthy tissues makes CAIX an attractive diagnostic and therapeutic target. DPI-4452 is a CAIX-targeting cyclic peptide with a DOTA cage, allowing radionuclide chelation for theranostic purposes. Here, we report CAIX expression in multiple tumor types and provide in vitro and in vivo evaluations of 68 Ga-labeled DPI-4452 ([68 Ga]Ga-DPI-4452) and 177 Lu-labeled DPI-4452 ([177 Lu]Lu-DPI-4452)...
March 21, 2024: Journal of Nuclear Medicine
https://read.qxmd.com/read/38514057/elevated-mmp1-expression-in-carcinoma-associated-fibroblasts-of-breast-cancer-contributes-to-tumor-progression-and-unfavorable-prognosis
#39
JOURNAL ARTICLE
Chunfang Xi, Zhendi Song, Qingyu Cui, Ye Zhao, Kaifu Li, Hua Kang
OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors...
January 2024: Annals of Clinical and Laboratory Science
https://read.qxmd.com/read/38513058/eif4a3-bound-hsa_circ_0006847-exerts-a-tumor-suppressive-role-in-gastric-cancer
#40
JOURNAL ARTICLE
Chunli Cao, Xinxin Wu, Zhe Li, Yaoyao Xie, Shiyi Xu, Junming Guo, Weiliang Sun
Numerous studies have shown that circular RNAs are associated with the occurrence and development of various cancers, but the biological functions and mechanisms of hsa_circ_0006847 (circASPHD1) in gastric cancer (GC) remain unclear. The expression of hsa_circ_0006847 in GC cell lines, tissue, and plasma from GC patients was assayed by quantitative real-time reverse transcription-polymerase chain reaction. Hsa_circ_0006847 expression in cells was downregulated or upregulated by transfected small interfering RNA (siRNA) or overexpression plasmid...
March 22, 2024: DNA and Cell Biology
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