Journal: Science Advances

Article Title: CASTOR1 functional inactivation drives KRAS -mutant NSCLC and therapy resistance by a noncanonical mechanism of tumor suppression

doi: 10.1126/sciadv.aeb9836

Figure Lengend Snippet: ( A and B ) mTORC1 inhibitor rapamycin and dual PI3K/mTOR inhibitor BGT226 sensitized KRAS G12D ;C1 WT and KRAS G12D ;C1 KO organoids to MRTX1133. Representative pictures of organoids treated with mono- or combined therapy of MRTX1133 and rapamycin (A) or BGT226 (B). Representative organoid images are shown (top panels) and results were quantified (bottom panels). ( C to E ) Dual PI3K/mTOR inhibitor BGT226 sensitized KRAS G12D ;C1 WT and KRAS G12D ;C1 KO tumors to MRTX1133. Mice were intranasally inoculated with Adeno-Cre for 4 weeks and then treated with vehicle, MRTX1133, BGT226 or a combination of both for 4 weeks. Representative H&E images of lungs collected from KRAS G12D ;C1 WT or KRAS G12D ;C1 KO mice (C). Tumor size (D) and burden (tumor area/total lung area × 100) (E) were quantified. Results presented as mean and SD. Statistical analysis was performed by nested ANOVA, followed by Tukey’s post hoc test for multiple comparisons. * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001.

Article Snippet: For drug treatment assays, organoids were treated with the following drug concentrations: 10 nM MRTX1133 (ChemGood, catalog no. C1420), 20 nM rapamycin (MCE, catalog no. HY10219), and 10 nM BGT226 (MCE, catalog no. 13334).

Techniques: Organoids, Analysis

Journal: Science Advances

Article Title: CASTOR1 functional inactivation drives KRAS -mutant NSCLC and therapy resistance by a noncanonical mechanism of tumor suppression

doi: 10.1126/sciadv.aeb9836

Figure Lengend Snippet: ( A ) Knockdown of CASTOR1 enhanced cell proliferation of human lung cancer cell lines. Clonogenic assay and immunoblotting of human lung cancer cell lines following siRNA knockdown of CASTOR1 . ( B ) Overexpression of CASTOR1 inhibited cell proliferation of human lung cancer cell lines. Clonogenic assay and immunoblotting of human lung cancer cell lines following the overexpression of CASTOR1 . ( C ) Knockdown of CASTOR1 enhanced resistance to mTORC1 inhibitor Torin1 in human lung cancer cell lines. Clonogenic assay and immunoblotting of human lung cancer cell lines treated with Torin1 following siRNA knockdown of CASTOR1 . ( D ) Overexpression of CASTOR1 sensitized human lung cancer cell lines to mTORC1 inhibitors Torin1 and rapamycin. Clonogenic assay and immunoblotting of human lung cancer cell lines with mTOR inhibitors Torin1 and rapamycin following the overexpression of CASTOR1 . Rapamycin was used at 20 nM, while Torin1 was used at 0.2 μM.

Article Snippet: For drug treatment assays, organoids were treated with the following drug concentrations: 10 nM MRTX1133 (ChemGood, catalog no. C1420), 20 nM rapamycin (MCE, catalog no. HY10219), and 10 nM BGT226 (MCE, catalog no. 13334).

Techniques: Knockdown, Clonogenic Assay, Western Blot, Over Expression

Journal: Transboundary and Emerging Diseases

Article Title: All‐Trans Retinoic Acid Inhibits Canine Influenza Virus Replication Through Keratin 27–Mediated Autophagy Modulation

doi: 10.1155/tbed/2088414

Figure Lengend Snippet: ATRA enhanced the autophagy by facilitating the production of autophagosomes. (A, B) Quantitative analysis of ATRA‐induced autophagy in MDCK cells through the IFA assay. Scale bar: 10 μm. The statistical significance of differences was evaluated with the one‐way ANOVA. ∗ p < 0.05, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. ns, no significance.

Article Snippet: The reagents ATRA, rapamycin, chloroquine, and CCK‐8 kit were purchased from Topscience (China).

Techniques: Analysis