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JOURNAL ARTICLE
Kaili Guo, Yu Jiang, Wei Qiao, Panpan Yuan, Miao Xue, Jiping Liu, Hao Wei, Bin Wang, Xingmei Zhu
The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P...
April 15, 2024: Heliyon
#22
JOURNAL ARTICLE
Ambritha Balasundaram, George Priya C Doss
Targeted therapy revolutionizes the treatment of non-small-cell lung cancer (NSCLC), harboring molecular change. Epidermal growth factor receptor (EGFR) mutations play a crucial role in the development of NSCLC, serving as a pivotal factor in its pathogenesis. We elucidated the mechanisms of resistance and potential therapeutic strategies in NSCLC resistant to the EGFR-tyrosine kinase inhibitor (EGFR-TKI). This is achieved by identifying rare missense variants through whole exome sequencing (WES). The goal is to enhance our understanding, identify biomarkers, and lay the groundwork for targeted interventions, thereby offering hope for an improved NSCLC treatment landscape...
April 9, 2024: ACS Omega
#23
Harrison T Muturi, Hilda E Ghadieh, Suman Asalla, Sumona G Lester, Stefaan Verhulst, Hannah L Stankus, Sobia Zaidi, Raziyeh Abdolahipour, Getachew D Belew, Leo A van Grunsven, Scott L Friedman, Robert F Schwabe, Terry D Hinds, Sonia M Najjar
OBJECTIVES: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with MASH. Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARγ on CEACAM1 transcriptoin and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation...
April 3, 2024: bioRxiv
#24
Arba Karcini, Nicole R Mercier, Iulia M Lazar
Modern cancer treatment approaches aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eliminate the cancer cells. To overcome a relatively short-lived response due to the development of resistance to the administered drugs, combination therapies have been pursued, as well. To expand the outlook of combination therapies, the objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the response of HER2+ breast cancer cells to a mixture of two kinase inhibitors that has not been adopted yet as a standard treatment regime...
April 3, 2024: bioRxiv
#25
JOURNAL ARTICLE
Atta Ullah, Saeed Ullah, Muhammad Waqas, Majid Khan, Najeeb Ur Rehman, Asaad Khalid, Afnan Jan, Shahkar Aziz, Muhammad Naeem, Sobia Halim, Ajmal Khan, Ahmed Al-Harrasi
BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)...
April 9, 2024: Current Medicinal Chemistry
#26
JOURNAL ARTICLE
Purva H Rumde, Timothy F Burns
Residual cancer cells persist even after targeted therapies, serving as a reservoir for the subsequent acquisition of genetic alterations that lead to acquired drug resistance and tumor relapse. These initial drug-tolerant persisters (DTP) are phenotypically heterogenous with transient phenotypes attributed to epigenetic, metabolic, and cell-cycle changes. DTPs are responsible for the inevitable relapse seen in EGFR-mutant non-small cell lung cancer (NSCLC) despite high initial response to tyrosine kinase inhibitor (TKI) treatment...
April 15, 2024: Cancer Research
#27
JOURNAL ARTICLE
Naoya Nishioka, Hisao Imai, Masahiro Endo, Akifumi Notsu, Kosei Doshita, Satoshi Igawa, Hiroshi Yokouchi, Takashi Ninomiya, Takaaki Tokito, Sayo Soda, Takasato Fujiwara, Tetsuhiko Asao, Shinji Nakamichi, Takahisa Kawamura, Minehiko Inomata, Kazuhisa Nakashima, Kentaro Ito, Yasuhiro Goto, Yukihiro Umeda, Soichi Hirai, Ryota Ushio, Keiki Yokoo, Takayuki Takeda, Tomoya Fukui, Masashi Ishihara, Takashi Osaki, Sousuke Kubo, Takumi Fujiwara, Chie Yamamoto, Takeshi Tsuda, Nobumasa Tamura, Shinobu Hosokawa, Yusuke Chihara, Satoshi Ikeda, Naoki Furuya, Yoshiro Nakahara, Satoru Miura, Hiroaki Okamoto
BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis...
April 13, 2024: Targeted Oncology
#28
JOURNAL ARTICLE
Oliver Illini, Felix Carl Saalfeld, Petros Christopoulos, Michaël Duruisseaux, Anders Vikström, Nir Peled, Ingel Demedts, Elizabeth Dudnik, Anna Eisert, Sayed M S Hashemi, Urska Janzic, Waleed Kian, Katja Mohorcic, Saara Mohammed, Maria Silvoniemi, Sacha I Rothschild, Christian Schulz, Claas Wesseler, Alfredo Addeo, Karin Armster, Malinda Itchins, Marija Ivanović, Diego Kauffmann-Guerrero, Jussi Koivunen, Jonas Kuon, Nick Pavlakis, Berber Piet, Martin Sebastian, Janna-Lisa Velthaus-Rusik, Luciano Wannesson, Marcel Wiesweg, Robert Wurm, Corinna Albers-Leischner, Daniela E Aust, Melanie Janning, Hannah Fabikan, Sylvia Herold, Anna Klimova, Sonja Loges, Yana Sharapova, Maret Schütz, Christoph Weinlinger, Arschang Valipour, Tobias Raphael Overbeck, Frank Griesinger, Marko Jakopovic, Maximilian J Hochmair, Martin Wermke
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab...
April 3, 2024: International Journal of Molecular Sciences
#29
JOURNAL ARTICLE
Valentina Fustaino, Giuliana Papoff, Francesca Ruberti, Giovina Ruberti
We investigated mRNA-lncRNA co-expression patterns in a cellular model system of non-small cell lung cancer (NSCLC) sensitive and resistant to the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib/gefitinib. The aim of this study was to unveil insights into the complex mechanisms of NSCLC targeted therapy resistance and epithelial-to-mesenchymal transition (EMT). Genome-wide RNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs and lncRNAs...
March 29, 2024: International Journal of Molecular Sciences
#30
REVIEW
Ya-Tao Wang, Peng-Cheng Yang, Jing-Yi Zhang, Jin-Feng Sun
The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic...
March 23, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#31
JOURNAL ARTICLE
Rossella Bruno, Anello Marcello Poma, Martina Panozzi, Alessandra Lenzini, Gianmarco Elia, Carmelina Cristina Zirafa, Vittorio Aprile, Marcello Carlo Ambrogi, Editta Baldini, Marco Lucchi, Franca Melfi, Antonio Chella, Andrea Sbrana, Greta Alì
Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort...
April 3, 2024: Cancers
#32
JOURNAL ARTICLE
Xianping Xu, Yu Liu, Qiang Gong, Le Ma, Wei Wei, Linqiong Zhao, Zhibin Luo
PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer...
April 12, 2024: Cancer Chemotherapy and Pharmacology
#33
JOURNAL ARTICLE
Priyanka Kanth, Mark W Hazel, John C Schell, Jared Rutter, Ruoxin Yao, Alyssa P Mills, Don A Delker
Serrated polyposis syndrome (SPS) presents with multiple sessile serrated lesions (SSL) in the large intestine and confers increased colorectal cancer (CRC) risk. However, the etiology of SPS is not known. SSL-derived organoids have not been previously studied but may help provide insights into SPS pathogenesis and identify novel biomarkers and chemopreventive strategies. This study examined effects of EGFR and COX pathway inhibition in organoid cultures derived from uninvolved colon and polyps of SPS patients...
April 12, 2024: Familial Cancer
#34
JOURNAL ARTICLE
Yujing Xu, Jinrong Yang, Xiaoyu Han, Chunchun Gan, Xiaopeng Wei
In this paper, our objective was to investigate the potential mechanisms of Actinidia chinensis Planch (ACP) for breast cancer treatment with the application of network pharmacology, molecular docking, and molecular dynamics. "Mihoutaogen" was used as a key word to query the Traditional Chinese Medicine Systems Pharmacology database for putative ingredients of ACP and its related targets. DrugBank, GeneCards, Online Mendelian Inheritance in Man, and therapeutic target databases were used to search for genes associated with "breast cancer...
April 12, 2024: Medicine (Baltimore)
#35
JOURNAL ARTICLE
Seung-Jin Park, Shinyeong Ju, Sung-Ho Goh, Byoung-Ha Yoon, Jong-Lyul Park, Jeong-Hwan Kim, Seonjeong Lee, Sang-Jin Lee, Yumi Kwon, Wonyeop Lee, Kyung Chan Park, Geon Kook Lee, Seog Yun Park, Sunshin Kim, Seon-Young Kim, Ji-Youn Han, Cheolju Lee
UNLABELLED: Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA), we selected 141 NSLA tissues and performed proteogenomic characterization, including whole genome sequencing (WGS), transcriptomic, methylation EPIC array, total proteomic, and phosphoproteomic analyses...
April 12, 2024: Cancer Research
#36
REVIEW
Ramesh Kumar, Wanjin Hong
Originally identified in Drosophila melanogaster in 1995, the Hippo signaling pathway plays a pivotal role in organ size control and tumor suppression by inhibiting proliferation and promoting apoptosis. Large tumor suppressors 1 and 2 (LATS1/2) directly phosphorylate the Yki orthologs YAP (yes-associated protein) and its paralog TAZ (also known as WW domain-containing transcription regulator 1 [WWTR1]), thereby inhibiting their nuclear localization and pairing with transcriptional coactivators TEAD1-4. Earnest efforts from many research laboratories have established the role of mis-regulated Hippo signaling in tumorigenesis, epithelial mesenchymal transition (EMT), oncogenic stemness, and, more recently, development of drug resistances...
March 22, 2024: Cells
#37
Min Deng, Xiaoqing Li, Honghao Mu, Man Wei, Lan Sun
BACKGROUND: Lung adenocarcinoma with esophageal squamous cell carcinoma is rare and the prognosis is poor, therefore there is an urgent need to improve this situation. The objective of this study was to explore the effect of first-generation tyrosine kinase inhibitors (TKIs) in the patient of the double primary malignant tumors. CASE REPORT: We report a case of lung adenocarcinoma with esophageal squamous cell carcinoma treated by icotininb after five-year follow-up...
2024: Frontiers in Medicine
#38
JOURNAL ARTICLE
Isabelle Senechal, Nikolaos Vogiatzakis, Maria Sol Andres, Jieli Tong, Sivatharshini Ramalingam, Stuart D Rosen, Alexander R Lyon, Muhummad Sohaib Nazir
Panitumumab is a human immunoglobulin monoclonal antibody designed to target the epidermal growth factor receptor (EGFR) which is used in the treatment of metastatic colorectal cancer alone or in combination with chemotherapy. In this report, we present a case of new onset heart failure with reduced ejection fraction in a patient following panitumumab therapy. A 73-year-old gentleman with metastatic rectal adenocarcinoma presented to his local hospital with increased shortness of breath, two months after his first and only dose of panitumumab...
April 11, 2024: Cardio-Oncology
#39
JOURNAL ARTICLE
Simona Pellecchia, Melania Franchini, Gaetano Viscido, Riccardo Arnese, Gennaro Gambardella
BACKGROUND: Most primary Triple Negative Breast Cancers (TNBCs) show amplification of the Epidermal Growth Factor Receptor (EGFR) gene, leading to increased protein expression. However, unlike other EGFR-driven cancers, targeting this receptor in TNBC yields inconsistent therapeutic responses. METHODS: To elucidate the underlying mechanisms of this variability, we employ cellular barcoding and single-cell transcriptomics to reconstruct the subclonal dynamics of EGFR-amplified TNBC cells in response to afatinib, a tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR...
April 11, 2024: Genome Medicine
#40
JOURNAL ARTICLE
Payal Kamboj, Anjali, Khalid Imtiyaz, Moshahid A Rizvi, Virendra Nath, Vipin Kumar, Asif Husain, Mohd Amir
A new series of imidazothiazole derivatives bearing thiazolidinone moiety (4a-g and 5a-d) were designed, synthesized and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer and anti-inflammatory activity, cardiomyopathy toxicity and hepatotoxicity. Compound 4c inhibited EGFR kinase at a concentration of 18.35 ± 1.25 µM, whereas standard drug erlotinib showed IC50 value of 06.12 ± 0.92 µM. The molecular docking, dynamics simulation and MM-GBSA binding energy calculations revealed strong interaction of compound 4c with binding site of EGFR...
April 11, 2024: Scientific Reports
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