Efficacy of apatinib combined with tegafur gimeracil and oteracil potassium in the second-line treatment of advanced gastric cancer.

PURPOSE: To investigate the clinical efficacy and safety of apatinib combined with tegafur-gimeracil-oteracil potassium (S-1) in the second-line treatment of advanced gastric cancer. METHODS: A total of 126 patients with advanced gastric cancer admitted to our hospital from January 2017 to September 2018 were enrolled as the research objects, none of whom underwent surgery. For these patients, second-line treatment was recommended due to the failure of first-line treatment. According to the different therapeutic options, patients were categorized into S-1 group (n=63) and Apatinib group (S-1 combined with apatinib, n=63), and drugs were administered orally. The clinical efficacy, serological indicators, adverse reactions and immune function were compared between the two groups. Besides, the survival status of patients was recorded through follow-up. RESULTS: In S-1 group and Apatinib group, the objective response rate (ORR) was 30.2% (19/63) vs. 50.8% (32/63) and the disease control rate (DCR) was 54.0% (34/63) vs. 74.6% (47/63), respectively. The results indicated that Apatinib group was superior to S-1 group in terms of ORR and DCR, suggesting statistically significant differences (p=0.018, p=0.016). Compared with those before treatment, the serum levels of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor supplied group of factors (TSGF) in the two groups of patients were prominently reduced after treatment (p<0.05). After treatment, CA19-9 and TSGF levels were remarkably lower in Apatinib group than those in S-1 group (p=0.008, p=0.023), and there was no statistically significant difference in the CEA level between the two groups (p=0.057). After treatment, the quality of life of patients was improved notably in Apatinib group compared with that in S-1 group (p=0.002). Adverse reactions mainly involved hematological toxicity, nausea and vomiting, abnormal renal function, impairment of hepatic function, neurotoxicity, hypertension and hand-foot syndrome, most of which were in grade I-II and relieved after symptomatic treatment and could be tolerated for continued treatment. Serious adverse reactions in grade III-IV occurred rarely. No statistically significant difference was found in the incidence rate of adverse reactions between the two groups of patients (p>0.05). Besides, according to the follow-up results, median overall survival (OS) was 8.1 months vs. 10.7 months and median progression-free survival (PFS) was 4.2 months vs. 5.3 months, respectively, in S-1 group and Apatinib group. The results of log-rank test demonstrated that Apatinib group was superior to S-1 group with respect to OS, showing a statistically significant difference (p=0.028), and no statistically significant difference was found in PFS between the two groups of patients (p=0.159). CONCLUSION: In the second-line treatment of advanced gastric cancer, apatinib combined with S-1 is superior to S-1 alone in term of clinical efficacy, and its adverse reactions can be tolerated. Apatinib combined with S-1 can prominently improve the quality of life, reduce the serum tumor marker levels and prolong the OS of patients, but it cannot extend the PFS.

Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis.

BACKGROUND: Circular RNAs (circRNAs) have been disclosed to exert important roles in human cancers, including gastric cancer (GC). CircRNA hsa_circ_0000144 was identified as an oncogene in GC development. The aim of our study was to explore the role of hsa_circ_0000144 in oxaliplatin (OXA) resistance of GC. METHODS: Expression levels of hsa_circ_0000144, microRNA-502-5p (miR-502-5p) and A disintegrin and metalloproteinase 9 (ADAM9) were examined by quantitative real-time PCR (RT-qPCR) or Western blot assay. The OXA resistance of GC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed to assess the colony formation capacity. Cell apoptosis was determined by flow cytometry and caspase 3 activity. And cell migration and invasion were detected by Transwell assay. Target association between miR-502-5p and hsa_circ_0000144 or ADAM9 was demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Moreover, role of hsa_circ_0000144 in vivo was analyzed by xenograft tumor assay. RESULTS: Hsa_circ_0000144 and ADAM9 were highly expressed, while miR-502-5p was downregulated in OXA-resistant GC tissues and cells. Depletion of hsa_circ_0000144 could inhibit OXA resistance, proliferation and metastasis in OXA-resistant GC cells, which was attenuated by miR-502-5p inhibition. Hsa_circ_0000144 sponged miR-502-5p to positively regulate ADAM9 expression. MiR-502-5p suppressed OXA resistance, proliferation and metastasis in OXA-resistant GC cells by targeting ADAM9. Hsa_circ_0000144 knockdown could hamper tumor growth in vivo. CONCLUSION: Hsa_circ_0000144 exerted inhibitory effects on OXA resistance, proliferation and metastasis of OXA-resistant GC cells by regulating miR-502-5p/ADAM9 axis, at least in part.

Dynamic Changes in Cognitive Function in Patients With Radiation-Induced Temporal Lobe Necrosis After IMRT for Nasopharyngeal Cancer.

Purpose: Radiation-induced temporal lobe necrosis (TLN) was once regarded as a progressive and irreversible disease in the era of two-dimensional radiotherapy. However, in the era of intensity-modulated radiotherapy (IMRT), the long-term development process of TLN remains unknown. We performed a prospective study to evaluate the dynamic changes in cognitive function in patients with TLN after definitive IMRT for nasopharyngeal carcinoma (NPC). Methods: The enrollment criteria were as follows: (1) patients must have had confirmed NPC and must have received only one course of definitive IMRT; (2) patients radiologically diagnosed with TLN during follow-up; (3) patients with TLN who had not undergone surgical resection; and (4) patients with TLN with a follow-up period of more than 2 years. Cognitive function was measured with the mini-mental state examination (MMSE) at an interval of every 3 months. Changes in the size of the necrotic mass in the temporal lobe were evaluated by magnetic resonance imaging. The treatment interventions included the wait-and-see policy or the administration of nerve growth factor (NGF) combined with pulsed steroids. Results: From January 2008 to December 2017, 86 patients with TLN entered this study. With a median follow-up of 32 months (26-50 months), 60 patients (70%) showed normal cognitive function as quantified by MMSE scores (≥27). Twenty-six patients (30%) demonstrated obvious cognitive impairment (MMSE scores ≤ 26) during follow-up. However, after receiving NGF combined with pulsed steroids, cognitive function improved significantly, and 21 of 26 patients demonstrated recovery to normal levels. Magnetic resonance imaging studies demonstrated that 10 patients had a complete response (CR), 13 had a partial response, and 3 had stable disease. Conclusions: In the IMRT era, TLN is not always a progressive disease. Most patients remain stable both in their cognitive function and in the size of the necrotic mass. For patients with progressive TLN, active intervention with the administration of NGF and pulsed steroids not only can improve cognitive function but also can decrease the size of the necrotic mass.