The Kaohsiung journal of medical sciences最新文献

A direct strategy to achieve specific treatments and reduce side effects is through cell type-specific drug delivery. Exosomes (Exos) can be modified with folic acid (FA) to prepare drug delivery systems targeting tumor cells that highly express FA receptors. This study aimed to produce an exo drug delivery system with FA decoration and temozolomide (TMZ) loading to improve the sustained TMZ release and targeting. We used DSPE-PEG₂₀₀₀-FA to modify exos derived from astrocyte U-87 to prepare FA-modified exos (Astro-exo-FA). TMZ was encapsulated into Astro-exo-FA or Astro-exo through electroporation to produce TMZ@Astro-exo and TMZ@Astro-exo-FA. In vitro drug release was examined using the dialysis bag method. Through cell experiments in vitro and mouse glioma models in vivo, the effect of TMZ@Astro-exo-FA on U-87 cells was determined. Exo properties were not affected by FA modification and TMZ loading. The drug release rate of TMZ@Astro-exo-FA was slower. TMZ@Astro-exo-FA uptake by U-87 cells was higher compared to TMZ@Astro-exo, indicating that TMZ@Astro-exo-FA has a stronger targeting toward U-87 cells. TMZ@Astro-exo-FA remarkably reduced U-87 cell proliferation, migration, and invasion compared with TMZ@Astro-exo and free TMZ. Treatment with TMZ@Astro-exo-FA reduced the side effects of TMZ (minimal change in body weight), prolonged survival, and inhibited tumor growth in mouse glioma models, and its efficacy was stronger than that of TMZ@Astro-exo and free TMZ. TMZ@Astro-exo-FA could enhance the effect of TMZ against glioma, providing novel ideas for drug targeting delivery and exploring exos as drug carriers against glioma.

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.