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Prospective serial proteomic analysis uncovers mechanistic pathways of chemotherapy resistance in advanced non-small cell lung cancer

Thu, 01 Jan 2026 00:00:00 GMT

標題: Prospective serial proteomic analysis uncovers mechanistic pathways of chemotherapy resistance in advanced non-small cell lung cancer 作者: Kuo, Wei-Ke; Chu, Hsin-Yu; Ko, Yen-Kun; Hsu, Pang-Hung 摘要: Predicting chemotherapy response in advanced non-small cell lung cancer (NSCLC) remains a clinical challenge, as baseline profiles often fail to capture dynamic molecular adaptations under treatment. This prospective study employed serial plasma proteomics to identify mechanistic pathways associated with chemotherapy resistance in 44 patients with stage IV NSCLC receiving platinum-based doublet chemotherapy. By analyzing blood samples collected immediately before the first and second cycles using liquid chromatography-tandem mass spectrometry, we demonstrated that a ratio-based proteomic model (early-treatment/pre-treatment) yielded superior separation between controlled and uncontrolled disease (UCD) compared to baseline-only assessment. Among 159 quantified proteins, 13 showed significant differential abundance, with UCD patients exhibiting marked upregulation of tetranectin, coagulation factor XIII A chain, and complement factor H-related protein 2. Ingenuity Pathway Analysis revealed that therapeutic resistance was characterized by three dominant axes: the activation of complement-coagulation-acute-phase signaling, the induction of lipid-nuclear receptor activity (LXR/RXR and DHCR24 signaling), and the relative attenuation of immune-regulatory pathways such as IL-12 signaling. These findings highlight the potential of serial proteomic profiling to uncover treatment-induced molecular adaptations, providing insights for therapeutic monitoring and hypothesis generation in precision oncology. Significance: This study demonstrates the added value of prospective serial plasma proteomic profiling, compared with baseline-only approaches, for capturing early treatment-associated molecular adaptations in advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. By quantifying proteomic changes between pretreatment and early-treatment time points, we identified coordinated alterations involving the complement-coagulation-acute-phase axis and lipid-nuclear receptor signaling programs, including LXR/RXR and DHCR24, alongside relative attenuation of immune-regulatory pathways. Rather than reflecting isolated protein effects, these findings highlight interconnected host-tumor response programs that emerge under therapeutic pressure and may contribute to early adaptive resistance. Importantly, this work moves beyond static baseline markers by emphasizing dynamic, pathway-level changes and provides a hypothesis-generating framework for longitudinal therapeutic monitoring. Candidate proteins such as tetranectin and coagulation factor XIII A chain are proposed as molecular features associated with treatment response, warranting further validation in larger, prospective cohorts before translational application.

Zerovalent Fe Atom-Enriched Fe₃C@C Electrocatalysts for Selective Heavy Metals Sensing

Wed, 01 Jan 2025 00:00:00 GMT

標題: Zerovalent Fe Atom-Enriched Fe₃C@C Electrocatalysts for Selective Heavy Metals Sensing 作者: Karuppusamy, Naveen; Manavalan, Shaktivel; Chen, Shen Ming; Lou, Bih-Show; Jung, Sung Mi; Nga, Ta Thi Thuy; Mannu, Pandian; Dong, Chung Li; Li, Ying; Wang, Chih-Min; Duann, Yeh-Fang; Chen, Chi-Liang; Lee, Jyh-Wei 摘要: This study addresses emerging concerns regarding the toxicity of heavy metals in daily consumption and their severe health implications. Hence, there is a critical need to develop an accurate monitoring tool for heavy metals in environmental sources. Herein, we report zerovalent iron-enriched Fe3C@C (Fe(0)/Fe3C@C) obtained from carbonization of materiaux l'institut lavoisier-88A (MIL-88A), a member of the metal-organic framework (MOF) as a superior electrocatalyst for the simultaneous detection of various heavy metals. The morphology and properties of Fe(0)/Fe3C@C are controllable at different temperature conditions so that the maximum carbon-confined zerovalent iron (ZVI) atoms are achieved at higher temperature pyrolysis (900 degrees C) of MIL-88A. As a result, it shows the best performance in the electrochemical detection of heavy metals owing to its reduction capability, higher affinity, strong adsorption capacity, abundant active sites, and ionic conductivity. The X-ray absorption spectroscopy (XAS) performed under different conditions indicates that the additional charges from modified Fe clusters significantly enhance the electrochemical performance. The simultaneous and individual electrochemical sensing performance based on Fe(0)/Fe3C@C-900 demonstrated an excellent sensitivity with a lower limit of detection (LOD) of 0.29 nM, 0.54 nM, 0.68 nM, and 0.92 nM for simultaneous sensing and 3.20 nM, 1.69 nM, 7.96 nM, and 2.04 nM for individual sensing of cadmium ion (Cd2+), lead ion (Pb2+), copper ion (Cu2+), and mercury ion (Hg2+), respectively, over concentrations ranges from 15 mu M to 75 mu M using the differential pulse voltammetry (DPV) technique. Furthermore, real-time analysis in water samples for the electrochemical detection of proposed heavy metals is demonstrated. Overall, this study aims to highlight the importance of controlling pyrolysis and electrode characterization and enabling simultaneous electrochemical detection of heavy metal for further commercial applications.

Lipid-like Carbon-Dot Liposomes for Enhanced Drug Delivery and Membrane Fluidity Modulation in the Treatment of Metastatic Triple-Negative Breast Cancer

Wed, 01 Jan 2025 00:00:00 GMT

標題: Lipid-like Carbon-Dot Liposomes for Enhanced Drug Delivery and Membrane Fluidity Modulation in the Treatment of Metastatic Triple-Negative Breast Cancer 作者: Lin, Yu-Feng; Wu, Ren-Siang; Lin, Yu-Syuan; Chan, Kai-Min; Chen, Pei-Feng; Huang, Tzu-Yun; Huang, Chih-Ching; Wang, Robert Y. -L.; Chou, Hsu-Huan; Huang, Yu-Fen; Chang, Huan-Tsung 摘要: Cancer metastasis remains a major clinical challenge, leading to discouraging treatment outcomes and over 90% of cancer-related mortality. In this study, lipid-like carbon dots (LCDs) are designed to self-assemble into liposome-like structures, namely carbon-dot liposomes (CDsomes), serving as a multifunctional drug carrier for anticancer and anti-metastasis therapy in highly invasive triple-negative breast cancer (TNBC). The amphiphilic nature of CDsomes enables efficient fusion with TNBC cell membranes, facilitating drug delivery while reducing membrane fluidity. This modulation significantly suppresses TNBC cell invasion, migration, and metastasis both in vitro and in vivo. The unilamellar structure of CDsomes allows efficient encapsulation of anticancer drugs with varying polarities, including doxorubicin (Dox), carfilzomib, docetaxel, gemcitabine, and cisplatin. CDsomes also promote tumor penetration and Dox accumulation through the enhanced permeability and retention effect, along with their inherent elastic and lipophilic properties. Consequently, Dox-loaded CDsomes (Dox@CDsomes) exhibit superior antitumor and anti-metastatic efficacy and improved survival rates compared to free Dox in an orthotopic TNBC model while ameliorating systemic toxicity. Notably, Dox@CDsomes achieve therapeutic outcomes comparable to commercial liposomal Dox (Doxil) while extending survival rates by 20%. These findings highlight CDsomes-mediated membrane fluidity modulation as a promising therapeutic strategy for metastasis suppression, offering new avenues in multimodal cancer therapies.

A novel Klebsiella pneumoniae diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and in vivo virulence by gastrointestinal infection

Wed, 01 Jan 2025 00:00:00 GMT

標題: A novel Klebsiella pneumoniae diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and in vivo virulence by gastrointestinal infection 作者: Hsu, Chun-Ru; Huang, Ya-Ling; Hsu, Pang-Hung; Huang, Chen-Hsiu; Huang, Yu-Chieh; Kao, Ming-Ti; Ye, You-Wei 摘要: Klebsiella pneumoniae is responsible for various infections such as bacteremia, urinary tract infections, pneumonia, and liver abscesses. Multidrug-resistant K. pneumoniae infections pose a critical public health threat, often associated with high mortality rates. The emergence of hypervirulent K. pneumoniae has also raised global health concerns due to its invasive disease potential. Clinical studies suggest intestinal colonization by K. pneumoniae as a risk factor for subsequent infections, but the underlying mechanisms remain unclear. Cyclic di-GMP (c-di-GMP), a bacterial signaling molecule synthesized by diguanylate cyclases (DGCs), controls various cellular processes and is absent in higher organisms, making it an attractive target for antimicrobial development. In this study, we identified a novel DGC, designated as DgcG, in K. pneumoniae, which plays a pivotal role in gastrointestinal colonization and pathogenesis. Using genetic deletion and complementation analyses in a bacteremia and liver abscesses-inducing strain Ca0437, we observed that DgcG promoted intestinal adherence, biofilm formation, iron utilization, and in vivo virulence. RT-qPCR showed that DgcG regulated genes involved in type 3 fimbrial expression and iron transport. In a gastrointestinal infection model of female BALB/cByl mice, dgcG deletion significantly reduced host mortality and bacterial load in the liver, spleen, and intestines, underscoring its role in enhancing bacterial survival and dissemination. Additionally, dgcG gene was found highly conserved and prevalent among diverse K. pneumoniae isolates. These findings provide new insights into c-di-GMP-mediated virulence regulation in K. pneumoniae and highlight DgcG as a potential therapeutic target for controlling K. pneumoniae infections, especially amidst the growing global antimicrobial resistance crisis.

DSpace 集合:

Prospective serial proteomic analysis uncovers mechanistic pathways of chemotherapy resistance in advanced non-small cell lung cancer

Zerovalent Fe Atom-Enriched Fe3C@C Electrocatalysts for Selective Heavy Metals Sensing

Lipid-like Carbon-Dot Liposomes for Enhanced Drug Delivery and Membrane Fluidity Modulation in the Treatment of Metastatic Triple-Negative Breast Cancer

A novel Klebsiella pneumoniae diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and in vivo virulence by gastrointestinal infection

Zerovalent Fe Atom-Enriched Fe₃C@C Electrocatalysts for Selective Heavy Metals Sensing