Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer
- 作者列表："Muhammad, Tahir","Sakhawat, Ali","Khan, Aamir Ali","Huang, Hua","Khan, Haroon Rashid","Huang, Yinghui","Wang, Juan
Purpose Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and ranked top in terms of incidence and mortality in men and women. Recently, improvements in treatment approaches for NSCLC have reported, but still, there is a need to devise innovative treatment strategies, especially to manage the advanced and metastatic stage of NSCLC. Aloperine (ALO), an herbal alkaloid, has exerted anti-cancer effects in many cancers. However, the use of any chemotherapeutic agents is dose limited due to possible adverse effects and drug-resistance issues. Therefore, a combination of chemotherapy with viral-based targeted gene therapy may provide a novel treatment strategy for NSCLC. Methods/results In this study, the results of the MTT and flow cytometry-based assays showed that Aloperine–Adbic (adenoviral vector expressing p14 ^ ARF /p53 ) combined treatment on NSCLC cells synergistically produced anti-proliferative effects, induced apoptosis, and arrested cell cycle at the G1 phase. Furthermore, the expression analysis suggested that the p53 / p21 pathway might contribute to achieving aforesaid cytotoxic effects. The ALO–Adbic combined treatment prolonged the percent survival of NSCLC xenograft models. Conclusion In conclusion, ALO–Adbic combination can produce synergistic anti-cancer effects at low doses, and may offer a more effective and less toxic new treatment strategy for NSCLC.
目的非小细胞肺癌 (Non-small cell lung cancer，NSCLC) 是最常见的肺癌类型，在男性和女性中的发病率和死亡率均居首位。最近，NSCLC 治疗方法的改进已经报道，但是仍然需要设计创新的治疗策略，特别是管理 NSCLC 的晚期和转移性阶段。苦豆碱 (ALO) 是一种草药生物碱，在许多癌症中发挥了抗癌作用。然而，由于可能的不良反应和耐药性问题，任何化疗药物的使用都是有限的。因此，联合化疗和基于病毒的靶向基因治疗可能为 NSCLC 提供一种新的治疗策略。方法/结果在本研究中，基于 MTT 和流式细胞术的检测结果显示，Aloperine-Adbic (表达 p14 ^ ARF/p53 的腺病毒载体) 联合治疗 NSCLC 细胞协同产生抗增殖作用，诱导细胞凋亡，并将细胞周期阻滞在 G1 期。此外，表达分析表明 p53/p21 通路可能有助于实现上述细胞毒作用。ALO-Adbic 联合治疗可延长 NSCLC 异种移植模型的生存率百分比。结论阿洛-阿多比联合用药可在低剂量下产生协同抗癌作用，可能为 NSCLC 提供一种更有效、毒性更小的新治疗策略。
METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.
METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.
METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.