The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the blood-brain barrier (BBB) to the brain cancer cells. A cyclic arginine-glycine-aspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TF-LP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TF-LP provided the highest brain distribution. As a result, the paclitaxel-loaded RGD/TF-LP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TF-LP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

Long noncoding RNAs have an essential role in the tumorigenesis of breast cancer (BC). Nonetheless, the consequences of long intergenic noncoding RNA 00641 (LINC00641) in BC remain unidentified. This study shows that LINC00641 expression level was decreased in BC tissues. LINC00641 expression level was negatively related to tumor size, lymphnode metastasis, as well as clinical stage. LINC00641 overexpression inhibited cell proliferation, migration, and invasion but stimulated apoptosis in BC cells. LINC00641 overexpression also remarkably reduced BC growth and metastasis in vivo. LINC00641 acts as a competitive endogenous RNA to sponge miR-194-5p. miR-194-5p level was higher in BC tissues and cells compared with normal-adjacent tissues and normal breast epithelial cell. miR-194-5p expression was negatively correlated with LINC00641 expression in BC tissues. miR-194-5p overexpression reversed the effects of LINC00641 on cell proliferation, cycle, apoptosis, migration, as well as invasion. In conclusion, LINC00641 inhibits BC cell proliferation, migration, as well as invasion by sponging miR-194-5p. K E Y W O R D S breast cancer, LINC00641, lncRNA, metastasis, proliferation

Background: This study aimed to compare the real-world efficacy and safety of the TCbHP regimen (docetaxel, carboplatin, trastuzumab and pertuzumab) and the THP regimen (docetaxel, trastuzumab and pertuzumab) as neoadjuvant therapy for Chinese patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: We compared efficacy and safety outcomes from 72 Chinese patients with HER2-positive breast cancer who underwent neoadjuvant dual HER2 blockade plus TCb or T chemotherapy and surgery between March 2019 and June 2020. Results: All 72 patients were women (32-76 years old) and the overall pathological complete response (pCR) rate was 70.8% (51/72). The pCR rates were 76.1% (35/46) for the TCbHP regimen and 61.5% (16/26) for the THP regimen (P=0.28). Univariate analyses revealed that pCR was associated with clinical T classification (P=0.024), AJCC stage (P=0.042), estrogen receptor (ER) status (P=0.002), progesterone receptor (PR) status (P=0.035), Ki-67 index (P<0.001), and immunohistochemical HER2 status (P<0.001).Multivariate analyses revealed that pCR was independently predicted by ER status (OR: 0.227, 95% CI: 0.053-0.852; P=0.032) and immunohistochemical HER2 status (OR: 43.673, 95% CI: 6.801-875.86; P<0.001). The common adverse events for both regimens included neutropenia, anemia, thrombocytopenia, nausea, and diarrhea. Relative to the THP group, the TCbHP group had higher frequencies of grade 3-4 thrombocytopenia (17% vs. 0%, P=0.044) and grade 3-4 diarrhea (15% vs. 0%, P=0.044). Both regimens had very good cardiac safety.Conclusions: These results suggest that both TCbHP and THP regimens may be useful neoadjuvant treatments for high-risk early or locally advanced HER2-positive breast cancer. Both regimens had generally good safety outcomes, although clinicians should be aware of the risks of grade 3-4 thrombocytopenia and diarrhea during TCbHP treatment. Elderly patients who require neoadjuvant therapy may benefit from 6 cycles of THP treatment, based on its good efficacy and mild adverse events.