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The preparation of cell-containing microbubble scaffolds to mimic alveoli structure as 3D drug screening system for lung cancer.

制备模拟肺泡结构的含细胞微泡支架作为肺癌 3D 药物筛选系统。

  • 影响因子:7.71
  • DOI:10.1088/1758-5090/ab78ee
  • 作者列表:"Sun YJ","Hsu CH","Ling TY","Liu L","Lin TC","Jakfar S","Young IC","Lin FH
  • 发表时间:2020-02-21
Abstract

:Cancer is the leading cause of mortality worldwide, and lung cancer is the most malignant. However, the high failure rate in oncology drug development from in vitro studies to in vivo preclinical models indicates that the modern methods of evaluating drug efficacies in vitro are not reliable. Traditional 2-dimensional (2D) cell culture has been proved inadequate to mimic real physiological conditions. Current 3-dimensional (3D) cell culture methods do not represent the delicate structure of lung alveoli. To mimic lung alveoli structure, a cell containing enzyme-cross-linked gelatin microbubble scaffold was produced by mixing surfactant-containing gelatin solution with microbial transglutaminase (mTGase)-mixed A549 cell suspension in a four-channel flow focusing microfluidic device. With uniform pore size of about 100 μm in diameter, this gelatin microbubble scaffold resembled the lung alveoli in structure and in mechanical properties with good biocompatibility. Effective gemcitabine concentration required to induce cell death in microbubble scaffolds was significantly higher than in 2D culture together with a longer treatment time. Cell death mechanisms were confirmed to be gemcitabine-induced cell apoptosis through Western blotting and real-time PCR. H&E staining and TUNEL assay showed rounded cells with DNA damage in drug-treated scaffolds. Taken together, the cell-containing microbubble scaffolds successfully mimicked lung alveoli in structure and cellular responses after gemcitabine treatment were similar to clinical regimen of treating lung carcinoma. The microbubble scaffold is promising to facilitate anticancer drug discovery by providing more accurate preclinical predictions.

摘要

: 癌症是全球死亡的主要原因,而肺癌是最恶性的。然而,从体外研究到体内临床前模型的肿瘤学药物开发的高失败率表明,体外评价药物疗效的现代方法并不可靠。传统的二维 (2D) 细胞培养已被证明不足以模拟真实的生理条件。目前的三维 (3D) 细胞培养方法并不代表肺泡的精细结构。为了模拟肺泡结构,将含表面活性剂的明胶溶液与微生物转谷氨酰胺酶 (mTGase) 混合,制成含酶交联明胶微泡支架。 -四通道流动聚焦微流控装置中的混合 A549 细胞悬液。该明胶微泡支架孔径均匀,直径约 100 μ m,结构和力学性能与肺泡相似,具有良好的生物相容性。微泡支架诱导细胞死亡所需的有效吉西他滨浓度显著高于 2D 培养,同时处理时间更长。通过 Western blotting 和 real-time PCR 证实细胞死亡机制为吉西他滨诱导细胞凋亡。H & E 染色和 TUNEL 检测显示药物处理支架中圆形细胞 DNA 损伤。总之,含细胞微泡支架在结构上成功模拟了肺泡,吉西他滨治疗后的细胞反应与临床治疗肺癌的方案相似。微泡支架有望通过提供更准确的临床前预测来促进抗癌药物的发现。

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作者列表:["Esme H","Can A","Şehitogullari A"]

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.

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

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.

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影响因子:8.44
发表时间:2020-02-01
DOI:10.1016/j.annonc.2019.10.022
作者列表:["Mazieres J","Cropet C","Montané L","Barlesi F","Souquet PJ","Quantin X","Dubos-Arvis C","Otto J","Favier L","Avrillon V","Cadranel J","Moro-Sibilot D","Monnet I","Westeel V","Le Treut J","Brain E","Trédaniel J","Jaffro M","Collot S","Ferretti GR","Tiffon C","Mahier-Ait Oukhatar C","Blay JY"]

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