keyword
https://read.qxmd.com/read/38520334/detection-of-single-nucleotide-polymorphisms-of-circulating-tumor-dna-by-strand-displacement-amplification-coupled-with-liquid-chromatography
#21
JOURNAL ARTICLE
Ziyu Ma, Junjie Xu, Weilin Hou, Zi Lei, Tingting Li, Wei Shen, Hui Yu, Chang Liu, Jinghui Zhang, Sheng Tang
The detection of multiple single nucleotide polymorphisms (SNPs) of circulating tumor DNA (ctDNA) is still a great challenge. In this study, we designed enzyme-assisted nucleic acid strand displacement amplification combined with high-performance liquid chromatography (HPLC) for the simultaneous detection of three ctDNA SNPs. First, the trace ctDNA could be hybridized to the specially designed template strand, which initiated the strand displacement nucleic acid amplification process under the synergistic action of DNA polymerase and restriction endonuclease...
March 23, 2024: Analytical Chemistry
https://read.qxmd.com/read/38520037/multi-institutional-study-of-osimertinib-dose-optimization-in-non-small-cell-lung-cancer-patients-with-egfr-activating-mutation-aged-70%C3%A2-years-or-older-money-trial
#22
JOURNAL ARTICLE
Yoko Tsukita, Masataka Taguri, Yasushi Goto, Yukio Hosomi, Tomonori Mizutani, Kageaki Watanabe, Kiyotaka Yoh, Satoshi Takahashi, Kaoru Kubota, Hideo Kunitoh
Osimertinib is the standard of care for patients with epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer. Dose-toxicity has been previously reported, but no dose-response data within the range of 20-240 mg daily (mg/d). Thus, the current 80 mg/d dosing might be too high for elderly Japanese patients with an average body weight of only 50 kg, resulting in excessive toxicity and cost. We therefore initiated a study to investigate whether osimertinib at 40 mg/d is non-inferior to 80 mg/d in patients with advanced or recurrent epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer aged ≥70 years, using a regression discontinuity design...
March 22, 2024: Japanese Journal of Clinical Oncology
https://read.qxmd.com/read/38517388/evaluation-of-the-clinical-significance-of-long-non-coding-rna-malat1-genetic-variants-in-human-lung-adenocarcinoma
#23
JOURNAL ARTICLE
Shu-Hui Lin, Jeng-Wei Lu, Wang-Ting Hsieh, Ying-Erh Chou, Tzu-Cheng Su, Tun-Jen Tsai, Yun-Jung Tsai, Po-Jen Yang, Shun-Fa Yang
Lung adenocarcinoma (LUAD) is the most frequent histological subtype of lung cancer, which is the most common malignant tumor and the main cause of cancer-related mortality globally. Recent reports revealed that long non-coding RNA (lncRNA) of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in tumorigenesis and metastasis development in lung cancer. However, the contribution of MALAT1 genetic variants to the development of LUAD is unclear, especially in epidermal growth factor receptor (EGFR) mutation status...
March 21, 2024: Aging
https://read.qxmd.com/read/38516754/all-in-one-oscidrop-digital-pcr-system-for-automated-and-highly-multiplexed-molecular-diagnostics
#24
JOURNAL ARTICLE
Caiming Li, Nan Kang, Shun Ye, Weihang Huang, Xia Wang, Cheng Wang, Yuchen Li, Yan-Fei Liu, Ying Lan, Liang Ma, Yuhang Zhao, Yong Han, Jun Fu, Danhua Shen, Lianhua Dong, Wenbin Du
Digital PCR (dPCR) holds immense potential for precisely detecting nucleic acid markers essential for personalized medicine. However, its broader application is hindered by high consumable costs, complex procedures, and restricted multiplexing capabilities. To address these challenges, an all-in-one dPCR system is introduced that eliminates the need for microfabricated chips, offering fully automated operations and enhanced multiplexing capabilities. Using this innovative oscillation-induced droplet generation technique, OsciDrop, this system supports a comprehensive dPCR workflow, including precise liquid handling, pipette-based droplet printing, in situ thermocycling, multicolor fluorescence imaging, and machine learning-driven analysis...
March 22, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38515096/clinical-characteristics-and-mri-based-radiomics-nomograms-can-predict-ipfs-and-short-term-efficacy-of-third-generation-egfr-tki-in-egfr-mutated-lung-adenocarcinoma-with-brain-metastases
#25
JOURNAL ARTICLE
Haoran Qi, Yichen Hou, Zhonghang Zheng, Mei Zheng, Qiang Qiao, Zihao Wang, Xiaorong Sun, Ligang Xing
BACKGROUND: Predicting short-term efficacy and intracranial progression-free survival (iPFS) in epidermal growth factor receptor gene mutated (EGFR-mutated) lung adenocarcinoma patients with brain metastases who receive third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy was of great significance for individualized treatment. We aimed to construct and validate nomograms based on clinical characteristics and magnetic resonance imaging (MRI) radiomics for predicting short-term efficacy and intracranial progression free survival (iPFS) of third-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma patients with brain metastases...
March 21, 2024: BMC Cancer
https://read.qxmd.com/read/38514012/clinical-significance-of-the-cystic-phenotype-in-alport-syndrome
#26
JOURNAL ARTICLE
Letizia Zeni, Federica Mescia, Diego Toso, Chiara Dordoni, Cinzia Mazza, Gianfranco Savoldi, Laura Econimo, Roberta Cortinovis, Simona Fisogni, Federico Alberici, Francesco Scolari, Claudia Izzi
RATIONALE & OBJECTIVE: Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. STUDY DESIGN: Retrospective cohort study. SETTING: & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN)...
March 19, 2024: American Journal of Kidney Diseases
https://read.qxmd.com/read/38513538/the-impact-of-pre-treatment-smoking-status-on-survival-after-chemoradiotherapy-for-locally-advanced-non-small-cell-lung-cancer
#27
JOURNAL ARTICLE
Neil D Wallace, Marliese Alexander, Jing Xie, David Ball, Fiona Hegi-Johnson, Nikki Plumridge, Shankar Siva, Mark Shaw, Susan Harden, Tom John, Ben Solomon, Ann Officer, Michael MacManus
INTRODUCTION: Smoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). METHODS: All patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database...
March 11, 2024: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/38513197/furmonertinib-and-intrathecal-pemetrexed-chemotherapy-rechallenges-osimertinib-refractory-leptomeningeal-metastasis-in-a-non-small-cell-lung-cancer-patient-harboring-egfr20-r776s-c797s-and-egfr21-l858r-compound-egfr-mutations-a-case-report
#28
JOURNAL ARTICLE
Guoxia Jia, Shoaib Bashir, Minting Ye, Yin Li, Mingyao Lai, Linbo Cai, Meng Xu
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, due to the rarity of cases, the response of EGFR-TKIs in patients harboring uncommon compound EGFR mutations still needs to be determined. Here, we demonstrated the case of a 47-year-old smoker diagnosed with leptomeningeal metastasis from NSCLC and had EGFR20 R776S, C797S, and EGFR21 L858R compound mutations...
March 15, 2024: Anti-cancer Drugs
https://read.qxmd.com/read/38513159/egfr-exon-18-dele709_t710insd-mutated-stage-iv-non-small-cell-lung-cancer-treated-with-osimertinib-a-case-report
#29
JOURNAL ARTICLE
Sena Valcárcel, Noemi Villanueva, Carlos Álvarez, Emilio Esteban
Mutations in tyrosine kinase domain of epidermal growth factor receptor (EGFR) are observed in approximately 15% of non-small cell lung cancer adenocarcinoma. Exon 19 deletions or exon 21 L858R mutations are predominant in frequency and show high sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Exon 18 mutations are extremely rare and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation. This specific mutation in exon 18 seems to respond to certain EGFR TKIs such as afatinib...
March 15, 2024: Anti-cancer Drugs
https://read.qxmd.com/read/38512449/molecular-characterization-of-chinese-patients-with-small-bowel-adenocarcinoma
#30
JOURNAL ARTICLE
Bryan Jin, Bin Lv, Zhengqing Yan, Wenshuai Li, Huan Song, Haoshu Cui, Yao Liu, Bin Zhong, Xin Shen, Xiao Li, Bei Zhang, Shiqing Chen, Wanwei Zheng, Jie Liu, Feifei Luo, Zhongguang Luo
PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS...
March 21, 2024: Clinical & Translational Oncology
https://read.qxmd.com/read/38511563/mobocertinib-mechanism-of-action-clinical-and-translational-science
#31
REVIEW
Michael J Hanley, D Ross Camidge, Robert J Fram, Neeraj Gupta
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations represent ~6%-12% of all EGFR-mutated non-small cell lung cancer (NSCLC) cases. First-, second-, and third-generation tyrosine kinase inhibitors (TKIs) have limited clinical activity against EGFR ex20ins mutations. Mobocertinib is a first-in-class oral EGFR TKI that selectively targets in-frame EGFR ex20ins mutations in NSCLC; accelerated approval in the United States was granted for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations whose disease has progressed on or after platinum-based chemotherapy...
March 2024: Clinical and Translational Science
https://read.qxmd.com/read/38510242/antibody-dependent-cellular-cytotoxicity-inducing-anti-egfr-antibodies-as-effective-therapeutic-option-for-cutaneous-melanoma-resistant-to-braf-inhibitors
#32
JOURNAL ARTICLE
Elena Muraro, Barbara Montico, Benedict Lum, Francesca Colizzi, Giorgio Giurato, Annamaria Salvati, Roberto Guerrieri, Aurora Rizzo, Elisa Comaro, Vincenzo Canzonieri, Andrea Anichini, Michele Del Vecchio, Roberta Mortarini, Massimo Milione, Alessandro Weisz, Maria Antonietta Pizzichetta, Fiona Simpson, Riccardo Dolcetti, Elisabetta Fratta, Luca Sigalotti
INTRODUCTION: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR)...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38509711/epidermal-growth-factor-receptor-inhibition-leads-to-cellular-phenotype-correction-of-dsp-mutated-keratinocytes
#33
JOURNAL ARTICLE
Daniela Andrei, Jeroen Bremer, Duco Kramer, Albertine M Nijenhuis, Marije van der Molen, Gilles F H Diercks, Peter C van den Akker, Mathilde C S C Vermeer, Peter van der Meer, Maria C Bolling
Desmoplakin (DSP) is a desmosomal component expressed in skin and heart, essential for desmosome stability and intermediate filament connection. Pathogenic variants in the DSP gene encoding DSP, lead to heterogeneous skin, adnexa and heart-related phenotypes, including skin fragility, woolly hair (WH), palmoplantar keratoderma (PPK) and arrhythmogenic/dilated cardiomyopathy (ACM/DCM). The ambiguity of computer-based prediction analysis of pathogenicity and effect of DSP variants, indicates a necessity for functional analysis...
March 2024: Experimental Dermatology
https://read.qxmd.com/read/38509647/genomic-testing-and-targeted-therapy-of-non-small-cell-lung-cancer-in-china-a-nationwide-survey-of-physicians-and-clinical-pathologists
#34
JOURNAL ARTICLE
Jie Wang, Jianming Ying, Zhijie Wang, Xiao Meng, Meiling Wu, Cui Qian
BACKGROUND: Genomic diagnostic testing is necessary to guide optimal treatment for non-small cell lung cancer (NSCLC) patients. The proportion of NSCLC patients whose treatment was selected based on genomic testing is still unknown in many countries or needs further improvement. This survey aimed to assess perception of genomic testing and targeted therapy for NSCLC in clinical pathologists and physicians across China. METHODS: The web-based survey was conducted with 150 clinical pathologists and 450 physicians from oncology, respiratory and thoracic surgery departments from May to September 2020, across 135 cities in China...
March 15, 2024: Annals of Palliative Medicine
https://read.qxmd.com/read/38509433/clinical-management-of-patients-with-non-small-cell-lung-cancer-brain-metastases-and-actionable-genomic-alterations-a-systematic-literature-review
#35
REVIEW
Mustafa Khasraw, Priyanka Yalamanchili, Anu Santhanagopal, Chuntao Wu, Maribel Salas, Jie Meng, Maha Karnoub, Stephen Esker, Enriqueta Felip
INTRODUCTION: Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During the disease course, 25-50% of patients will develop BrMs. Despite available treatments, survival rates for patients with NSCLC and BrMs remain low, and their overall prognosis is poor. Even with newer agents for NSCLC, options for treating BrMs can be limited by their ineffective transport across the blood-brain barrier (BBB) and the unique brain tumor microenvironment...
March 21, 2024: Advances in Therapy
https://read.qxmd.com/read/38507464/egfr-amplification-and-egfrviii-predict-and-participate-in-tat-cx43266-283-antitumor-response-in-preclinical-glioblastoma-models
#36
JOURNAL ARTICLE
Andrea Álvarez-Vázquez, Laura San-Segundo, Pilar Cerveró-García, Raquel Flores-Hernández, Claudia Ollauri-Ibáñez, Berta Segura-Collar, C G Hubert, Gillian Morrison, Steven M Pollard, Justin D Lathia, Pilar Sánchez-Gómez, Arantxa Tabernero
BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ) and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo...
March 20, 2024: Neuro-oncology
https://read.qxmd.com/read/38506620/comprehensive-molecular-and-clinical-insights-into-non-small-cell-lung-cancer-transformation-to-small-cell-lung-cancer-with-an-illustrative-case-report
#37
REVIEW
Kreso Tomic, Kristina Krpina, Lara Baticic, Miroslav Samarzija, Semir Vranic
Histologic transformation to small cell lung cancer (tSCLC) is a rare but increasingly recognized mechanism of acquired resistance to tyrosine kinase inhibitors (TKI) in patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). Beyond its acknowledged role in TKI resistance, histologic transformation to SCLC might be an important, yet under-recognized, mechanism of resistance in NSCLC treated with immunotherapy. Our review identified 32 studies that investigated tSCLC development in patients with EGFR -mutated NSCLC treated with TKI therapy and 16 case reports of patients treated with immunotherapy...
March 20, 2024: Journal of Drug Targeting
https://read.qxmd.com/read/38505064/negative-impact-of-ratio-of-the-microvascular-area-to-tumor-area-on-the-response-to-egfr-tki-in-non-small-cell-lung-cancer-with-an-egfr-mutation
#38
JOURNAL ARTICLE
Moriyasu Anai, Koichi Saruwatari, Kosuke Imamura, Kosuke Fujino, Takayuki Jodai, Shinya Sakata, Shinji Iyama, Yusuke Tomita, Sho Saeki, Hidenori Ichiyasu, Koei Ikeda, Makoto Suzuki, Takuro Sakagami
BACKGROUND: The clinical impact of tumor microvessels on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) is unclear. Thus, the aim of this study was to investigate whether a tumor microenvironment, abundant in microvessels, affects EGFR-TKI efficacy in patients with NSCLC and EGFR mutations. METHODS: We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital from January 2010 to February 2021...
February 29, 2024: Journal of Thoracic Disease
https://read.qxmd.com/read/38503739/drug-resistant-egfr-mutations-promote-lung-cancer-by-stabilizing-interfaces-in-ligand-free-kinase-active-egfr-oligomers
#39
JOURNAL ARTICLE
R Sumanth Iyer, Sarah R Needham, Ioannis Galdadas, Benjamin M Davis, Selene K Roberts, Rico C H Man, Laura C Zanetti-Domingues, David T Clarke, Gilbert O Fruhwirth, Peter J Parker, Daniel J Rolfe, Francesco L Gervasio, Marisa L Martin-Fernandez
The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation...
March 19, 2024: Nature Communications
https://read.qxmd.com/read/38503018/dynamic-ctdna-based-analysis-of-drug-resistant-gene-alterations-at-ras-braf-wild-type-metastatic-colorectal-cancer-patients-after-cetuximab-plus-chemotherapy-as-the-first-line-treatment
#40
JOURNAL ARTICLE
Yu-Wen Zhou, Xin Zhao, Lu Ni, Peng Cao, Wei-Bing Leng, Qing Zhu, Hong-Feng Gou, Jiao Zhang, Xiao-Fen Li, Meng Qiu
BACKGROUND: The purpose of this study was to explore the dynamic changes of genomic mutations and their correlations with the efficacy in metastatic colorectal cancer (mCRC) patients treated with cetuximab plus mFOLFOX as the first-line treatment. METHODS: We included mCRC patients from January 2018 to October 2020 as a studied cohort which were treated with cetuximab plus mFOLFOX as first line therapy. Blood samples were collected for circulating tumor DNA (ctDNA) test at three timepoints: before the first-line therapy(baseline), at the time of first-line progression and at the time of second-line progression...
March 18, 2024: International Immunopharmacology
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