Small cell lung cancer (SCLC) is an aggressive tumor with poor prognosis due to early metastatic spread and development of chemoresistance. Playing a key role in tumor-stroma interactions the CXCL12-CXCR4 axis may be involved in both processes and thus represent a promising therapeutic target in SCLC treatment. In this study we investigated the effect of CXCR4 inhibition on metastasis formation and chemoresistance using an orthotopic xenograft mouse model. This model demonstrates regional spread and spontaneous distant metastases closely reflecting the clinical situation in extensive SCLC. Tumor engraftment, growth, metabolism, and metastatic spread were monitored using different imaging techniques: Magnetic Resonance Imaging (MRI), Bioluminescence Imaging (BLI) and Positron Emission Tomography (PET). Treatment of mice bearing chemoresistant primary tumors with the specific CXCR4 inhibitor AMD3100 reduced the growth of the primary tumor by 61% (P<0.05) and additionally suppressed metastasis formation by 43%. In comparison to CXCR4 inhibition as a monotherapy, standard chemotherapy composed of cisplatin and etoposide reduced the growth of the primary tumor by 71% (P<0.01) but completely failed to suppress metastasis formation. Combination of chemotherapy and the CXCR4 inhibitor integrated the highest of both effects. The growth of the primary tumor was reduced to a similar extent as with chemotherapy alone and metastasis formation was reduced to a similar extent as with CXCR4 inhibitor alone. In conclusion, we demonstrate in this orthotopic mouse model that the addition of a CXCR4 inhibitor to chemotherapy significantly reduces metastasis formation. Thus, it might improve the overall therapy response and consequently the outcome of SCLC patients.
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http://dx.doi.org/10.18632/oncotarget.13238 | DOI Listing |
Curr Oncol Rep
January 2025
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC, 20007, USA.
Purpose Of Review: Neuregulin 1 (NRG1) fusions are rare but actionable oncogenic drivers that occur in a variety of tumor types, including non-small cell lung cancer (NSCLC). These fusions lead to pathophysiologic activation of HER signaling pathways, promoting tumor growth, invasion, and metastasis. Current evidence suggests that NRG1 fusion-positive NSCLC does not respond well to conventional treatments such as immunotherapy and chemotherapy.
View Article and Find Full Text PDFWorld J Microbiol Biotechnol
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School of Biotechnology, Dublin City University, Dublin, D9, Ireland.
Exopolysaccharides (EPS) produced by lactic acid bacteria with immunomodulatory potential are promising natural food additives. This study employs small-scale, 250 mL bioreactors combined with a central composite design to optimise two important bioprocess parameters, namely temperature and airflow, to achieve high yields of biomass and EPS from Lacticaseibacillus rhamnosus LRH30 (L. rhamnosus LRH30).
View Article and Find Full Text PDFMol Neurobiol
January 2025
Department of Orthopedics, The Fourth Medical Center, Chinese PLA General Hospital, Beijing, 100048, China.
Spinal cord injury (SCI) is a severe central nervous system injury without effective therapies. PANoptosis is involved in the development of many diseases, including brain and spinal cord injuries. However, the biological functions and molecular mechanisms of PANoptosis-related genes in spinal cord injury remain unclear.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
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Non-small cell lung cancer (NSCLC) is a widespread highly malignant type of lung cancer. Conventional chemotherapeutic drugs may be accompanied by both drug resistance and serious side effects in patients. Therefore, safer and more effective medications are urgently needed for the treatment of NSCLC.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Zhejiang Laboratory, Hangzhou 311100, Zhejiang, China.
Deoxyribonucleic acid (DNA) serves as a repository of genetic information in cells and is a critical molecular target for various antibiotics and anticancer drugs. A profound understanding of small molecule interaction with DNA is crucial for the rational design of DNA-targeted therapies. While the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics/generalized Born surface area (MM/GBSA) approaches have been well established for predicting protein-ligand binding, their application to DNA-ligand interactions has been less explored.
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