Background: Circulating tumor cells (CTCs) are detectable in peripheral blood of metastatic lung cancer patients. In this article, we evaluate a new CTC separation method based on a combination of anti-EpCAM and immunomagnetic beads with the aim to detect CTCs more conveniently and specifically.
Methods: Lung cancer cells were magnetically labeled by anti-EpCAM magnetic beads, and subsequently captured by magnetic separation using our novel device. Isolated lung cancer cells were identified by pathomorphological by hematoxylin-eosin staining protocol. The system was used to detect CTCs in 2 ml blood. Blood samples of healthy donors spiked with lung cancer cell line A549 cells were used to determine the sensitivity and specificity of the method. Prevalence of CTCs was examined in samples from 56 patients with lung cancer.
Results: Regression analysis of number of recovered versus spiked A549 cells yielded a coefficient of determination of R(2) = 0.996 (P < 0.001). The average recovery was 68% or more at each spiking level. The coefficient of variation increased as the number of spiked cells decreased, ranging from 6.4% (1,000-cell spike) to 18.4% (50-cell spike). Forty-nine of the fifty-six patients (87.5%) were found to have CTCs in peripheral blood. None of the 2 ml peripheral blood samples of the 20 healthy subjects analyzed were found to have CTCs.
Conclusions: This novel turbulence device provides a new tool allowing for feasible and specific detection of CTCs in lung cancer patients. It is likely clinically useful in diagnosis and monitoring of lung cancer and may have a role in clinical decision making.
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http://dx.doi.org/10.1002/jcla.21918 | DOI Listing |
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFMol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Istituti Fisioterapici Ospitalieri, Italy.
Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.
Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.
Discov Nano
January 2025
Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany.
Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
Purpose: Liver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC).
Methods: In this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development.
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