BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. Circular RNAs (circRNAs) are recently identified as important gene regulators with critical roles in cancer biology. In this study, we focus on the effect of circ_0000376 targeting miR-384 on malignant phenotypes of NSCLC cells. METHODS: Circ_0000376 and miR-384 expression in NSCLC tissue samples were measured using qRT-PCR. The association between pathological parameters and the circ_0000376 expression was analyzed as well. Human NSCLC cell lines A549 and NCI-H460 were used as cell models. CCK-8 and BrdU assay were used to assess the effect of circ_0000376 on NSCLC cell line proliferation and drug sensitivity. Transwell assay was conducted to detect the effect of circ_0000376 on migration and invasion. Further, luciferase reporter assay was employed to validate the targeting of miR-384 by circ_0000376. RESULTS: Circ_0000376 expression in NSCLC clinical samples was up-regulated and this was linked to unfavorable pathological parameters. Circ_0000376 markedly accelerated the proliferation and metastasis, and enhanced chemoresistance of NSCLC cells. Mechanically, circ_0000376 overexpression could bind with miR-384 and repress its expression. CONCLUSIONS: Circ_0000376 is a newly discovered oncogenic circRNA in NSCLC, and can be potentially regarded as a diagnostic biomarker and therapy target.

Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.

Background The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8–11 months in the West and 13–17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. Methods/Design This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). Discussion This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. Trial Registration ChiCTR.gov.cn: ChiCTR2000034109.

This study aimed to investigate the effect and mechanism of long non-coding RNA FLVCR1-AS1 on proliferation, invasion and migration of colorectal cancer. QRT-PCR was used to detect the expression of FLVCR1-AS1 in colorectal cancer. The target genes of FLVCR1-AS1 were predicted using the StarBase and Luciferase assay. The biological function of miR-493-3p through a series of in vitro experiments. We examined the expression of FLVCR1-AS1 in colorectal cancer cell lines was remarkably increased. Interference with FLVCR1-AS1 inhibits proliferation, invasion and migration of colorectal cancer cell lines. MiR-493-3p is a targeted miRNA of lncRNA FLVCR1-AS1, and overexpression of miR-493-3p inhibits proliferation of colorectal cancer cells, invasion and migration of colorectal cancer cells, and it can be reversed by lncRNA FLVCR1-AS1. LncRNA FLVCR1-AS1 acts as miR-493-3p sponge to modulate cancer cell proliferation, invasion and migration in colorectal cancer.

4951 Objective To investigate the relevance of Inducing apoptosis and reversal effect of nilotinib in combination with Tet on multidrug reststahoe of K562/A02 cell line and its mechanism. Methods Methyl-thiazol tetrazolium(MTT) assay is employed to examine the pharmacological effect of Nilotinib or Tet alone on K562/A02 cell line, to calculate the inhibitor concerntration 50(IC50) of daunorubicin(DNR) in K562/A02 cell line and the resistance multiple of DNR to K562/A02 cell line. Flow cytometry(FCM) was employed to comple the effect on the inducing apoptosis of K562/A02. The expression of bax/survivin mRNA was determined by RT-PCR, and the expression of bax/survivin protein was assessed by Western blot. Results After 48 h 5 nmol/L nilotinib or 1.0μmoL/L Tet treatment, IC50 of DNR to K562/A02 was 5.71mg/L or 6.52 mg/L respectively;While on combinative treatment, its IC50 decreased to 3.12 mg/L. Nilotinib or Tet alone was able to increase the DNR induced apoptosis rate of K562/A02 cell (P<0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmoL/L nilotinib or 1.0μmoL/L Tet treatment alone, gray—scale vaule of bax mRNA Was 2.90±0.31 or 3.6±0.46, respectively Gwhile on combinative treatment the value increased to 5.9±0.98. The bax protein expression level in K562/A02 cells was 2.1±0.07 or 2.90±0.09 when treated with 5 nmoL/L nilotinib or 1.0μmoL/L Tet alone for 48 h, but on combination treatment, the level increased to 4.8±0.31. After 48 h 5 nmoL/L nilotinib or 1.0μmoL/L Tet treatment alone, gray—scale vaule of survivin mRNA was 0.70±0.01 or 0.55±0.02, respectively;while on combinative treatment the value decreased to 0.35±0.08. The survivin protein expression level in K562/A02 cells was 0.74±0.03or 0.61±0.04 when treated with 5 nmoL/L nilotinib or 1.0μmoL/L Tet alone for 48 h, but on combination treatment, the level decreased to 0.42±0.06. Conclusion Nilotinib or Tet alone can pattially reverse drug resistance of K562/A02 cells. There is resistance phenomena of DNR to K562/A02 cells, and Nilotinib or Tet alone alone is able to reserve the resistance of DNR and enhance the inducing apoptasis effect of DNR. The mechanism may be associated with the increase of bax mRNA and protein expression and decrease of survivin mRNA and protein expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination. Disclosures: No relevant conflicts of interest to declare.