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Purpose: To estimate the effect of simvastatin gel in the osseointegration of dental implants using bone scintigraphy. Materials and Methods: A total of 20 participants with missing mandibular first molars and D2 type bone were assigned equally to two groups. Group A received 1.2% simvastatin and group B received placebo gels during the placement of implants. The participants were subjected to bone scintigraphy to determine the osteoblastic activity at baseline, 30 days, and 90 days after implant placement. Results: Group A had a significant increase in osteoblastic activity between baseline, day 30, and day 90 (P < .05), with a higher mean of 100.06% ± 21.644% on day 30. Group B had a significant increase in osteoblastic activity only between baseline and day 30 and between baseline and day 90 (P < .05). There was no difference between days 30 and 90 (P > .05), with a higher mean of 79.20% ± 18.255% on day 30. A bivariate analysis performed at different time periods revealed a significant difference between groups A and B on day 30. Conclusions: Implants placed with 1.2% simvastatin gel showed enhanced osteoblastic activity in the 4th week after implant placement, indicating that there was a faster rate of osseointegration at an early stage. [ABSTRACT FROM AUTHOR]

There is an unmet clinical need to develop novel strategies to overcome resistance to tyrosine kinase inhibitors (TKI) in patients with oncogene-driven lung adenocarcinoma (LUAD). The objective of this study was to determine whether simvastatin could overcome TKI resistance using the in vitro and in vivo LUAD models. Human LUAD cell lines, tumor cells, and patient-derived xenograft (PDX) models from TKI-resistant LUAD were treated with simvastatin, either alone or in combination with a matched TKI. Tumor growth inhibition was measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and expression of molecular targets was assessed by immunoblots. Tumors were assessed by histopathology, IHC stain, immunoblots, and RNA sequencing. We found that simvastatin had a potent antitumor effect in tested LUAD cell lines and PDX tumors, regardless of tumor genotypes. Simvastatin and TKI combination did not have antagonistic cytotoxicity in these LUAD models. In an osimertinib-resistant LUAD PDX model, simvastatin and osimertinib combination resulted in a greater reduction in tumor volume than simvastatin alone (P < 0.001). Immunoblots and IHC stain also confirmed that simvastatin inhibited TKI targets. In addition to inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, RNA sequencing and Western blots identified the proliferation, migration, and invasion-related genes (such as PI3K/Akt/mTOR, YAP/TAZ, focal adhesion, extracellular matrix receptor), proteasome-related genes, and integrin (α3β1, αvβ3) signaling pathways as the significantly downregulated targets in these PDX tumors treated with simvastatin and a TKI. The addition of simvastatin is a safe approach to overcome acquired resistance to TKIs in several oncogene-driven LUAD models, which deserve further investigation.