Background: Isolated lung perfusion (ILuP) proved to be superior for the treatment of lung metastases compared with intravenous (i.v.) injection. However its invasive character limits repetitive treatment. Blood flow occlusion (BFO) as a regional therapy with gemcitabine (GCB) was evaluated in a rat model. Lung levels of GCB were examined with different exposure times and flow rates and compared with ILuP and i.v.. Cell kill was studied in vitro.
Methods: In vitro survival of CC531 adenocarcinoma cells was determined after 10, 20, and 40 minutes of exposure to GCB. In vivo 48 Wag/Rij rats underwent BFO with GCB at a rate of 0.2 mL/min and 0.5 mL/min during 10, 20, 30, and 40 minutes. Statistical analysis was performed using Student's t test.
Results: In vitro, the dose of GCB resulting in 50% growth inhibition was 9.1 microg/mL, 7.2 microg/mL, and 2.2 microg/mL after 10, 20, and 40 minutes exposure respectively. In vivo, no significant difference in lung levels of GCB was observed between a flow rate of 0.2 mL/min compared with 0.5 mL/min at any exposure time point (p < 0.05). Lung tissue was saturated after 20 minutes. Blood flow occlusion resulted in a lower plasma levels and higher lung levels of GCB compared with i.v. injection of the maximal tolerated dose of 40 mg.
Conclusions: Growth inhibition of CC531 cells in vitro increased with exposure time while lung tissue was saturated after 20 minutes of BFO. No difference in GCB lung levels were seen after BFO compared with ILuP. Systemic exposure after i.v. injection was higher compared with BFO but did not result in higher lung levels.
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http://dx.doi.org/10.1016/s0003-4975(03)00839-7 | DOI Listing |
Virol J
January 2025
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections.
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January 2025
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Medical Research Building (MRB) II, Ghent University Hospital, 2 Floor, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
Introduction: Diesel exhaust particles (DEP) have been proven to aggravate asthma pathogenesis. We previously demonstrated that concurrent exposure to house dust mite (HDM) and DEP in mice increases both eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) and also results in higher levels of neutrophil-recruiting chemokines and neutrophil extracellular trap (NET) formation compared to sole HDM, sole DEP or saline exposure. We aimed to evaluate whether treatment with anti-IL-5 can alleviate the asthmatic features in this mixed granulocytic asthma model.
View Article and Find Full Text PDFNat Comput Sci
January 2025
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
How complex phenotypes emerge from intricate gene expression patterns is a fundamental question in biology. Integrating high-content genotyping approaches such as single-cell RNA sequencing and advanced learning methods such as language models offers an opportunity for dissecting this complex relationship. Here we present a computational integrated genetics framework designed to analyze and interpret the high-dimensional landscape of genotypes and their associated phenotypes simultaneously.
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January 2025
Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Growing evidences have suggested the airway microbiota may participate in lung cancer progression. However, little was known about the relationship between airway microbiota and lung cancer associated systemic inflammation. Here we aimed to explore the association between sputum microbiota and systemic inflammation in lung cancer.
View Article and Find Full Text PDFCell Death Discov
January 2025
Laboratory of Genome Stress Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan.
DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.
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