LncRNA NEAT1 induces autophagy through the miR-128-3p/ADAM28 axis to suppress apoptosis of nonsmall-cell lung cancer.

This study aimed to identify the molecular mechanism underlying NEAT1 regulation of non-small-cell lung cancer (NSCLC) autophagy and apoptosis. The expression levels of NEAT1, miR-128-3p, and ADAM28 in NSCLC tissues and cells were examined using qRT-PCR. The relationships between NEAT1, miR-128-3p, and ADAM28 expression levels and prognosis of NSCLC patients were investigated using the Kaplan-Meier analysis method. The interactions between NEAT1, miR-128-3p, and ADAM28 were confirmed by dual-luciferase reporter assay or FISH assay. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry assays, respectively. Apoptosis and autophagy-related proteins Bax, cleaved caspase-3, cleaved caspase-9, Bcl-2, LC3, Beclin-1, and p62 were analyzed by western blotting. Finally, an in vivo NSCLC mouse xenograft model was established to confirm the in vitro data. We showed NEAT1 and ADAM28 expression levels were upregulated, while the miR-128-3p level was downregulated in NSCLC tissues and cells. NSCLC patients with high NEAT1 expression levels, low miR-128-3p levels, or high ADAM28 levels had significantly reduced overall survival times. Silencing of NEAT1 inhibited NSCLC cell autophagy and promoted apoptosis by sponging miR-128-3p. MiR-128-3p directly targeted ADAM28 and suppressed ADAM28 expression, which led to deactivation of the JAK2/STAT3 signaling pathway. Furthermore, ADAM28 overexpression attenuated miR-128-3p overexpression-induced apoptosis and autophagy inhibition in NSCLC by increasing the phosphorylation of JAK2 and STAT3. NEAT1 depletion or miR-128-3p overexpression inhibited autophagy and promoted apoptosis in vivo by suppressing ADAM28. In other word, silencing NEAT1 inhibited autophagy and then promoted NSCLC cell apoptosis by deactivating the JAK2/STAT3 signaling pathway through regulation of miR-128-3p/ADAM28 axis.

Uniportal versus multiportal thoracoscopic lobectomy: Ergonomic evaluation and perioperative outcomes from a randomized and controlled trial.

BACKGROUND: To compare perioperative outcomes and surgeon physical and mental stress when performing lobectomy through uniportal and multiportal video-assisted thoracoscopic surgery (VATS) on patients with non-small-cell lung cancer (NSCLC). METHODS: Patients aged 41 to 73 years with resectable NSCLC were randomly assigned via a computer-generated randomisation sequence to receive either uniportal VATS (UVATS) or multiportal VATS (MVATS) lobectomy and lymphadenectomy between December 2015 and October 2016. Overall, we randomly assigned 35 patients to the UVATS and 34 to the MVATS group. Patients and the investigators undertaking interventions, assessing short-term outcomes, performing ergonomic evaluations, and analyzing data were not masked to group assignment. RESULTS: Patient demographics of the 2 groups were comparable. The ergonomic evaluation considered eye blink rate and the NASA Task Load Index (NASA-TLX), better results were observed in UVATS than in MVATS. The operative time, number of lymph nodes harvested, chest tube duration, length of hospital stay, and lung function were not significantly different between the groups. Compared with MVATS lobectomy, UVATS lobectomy was associated with less intraoperative blood loss and less volume of total drainage in the 24 hours. No conversion, no reoperation, and no in-hospital mortality occurred in either group. CONCLUSIONS: UVATS lobectomy is a safe and programmable technique with some better perioperative outcomes and ergonomic results than MVATS. Further studies based on large numbers of patients and with long-term follow-up are required to confirm its benefits towards patients. TRIAL REGISTRATION: ClinicalTrials.gov ID:NCT02462356. Registered May 27, 2015.

Effect of erlotinib combined with cisplatin on IL-6 and IL-12 in mice with Lewis lung cancer.

Effect of erlotinib combined with cisplatin on tumor growth, interleukin-6 (IL-6) and interleukin-12 (IL-12) in mice with Lewis lung cancer (LLC) was investigated. Forty-four pure inbred SPF C57BL/6J mice were modeled for LLC and randomized into groups A, B, C and D (n=11 each group). Mice in group A were given normal saline, group B was given erlotinib, group C was given cisplatin injection and group D erlotinib combined with cisplatin. Tumor growth of the mice was observed and the tumor mass was measured. Serum IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) 40 days later. At different time-points after medication, tumor volume in group D was significantly lower than that in groups A, B and C (P<0.05), and that in groups B and C was significantly lower than that in group A (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Tumor mass in groups B, C and D was significantly lower than that in group A (P<0.05), and that in group D was significantly lower than that in groups B and C (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Compared with groups B and C, mice in group D had significantly lower IL-6 level (P<0.05), but significantly higher IL-12 level (P<0.05). There was no significant difference in IL-6 and IL-12 levels between groups B and C (P>0.05). In conclusion, erlotinib combined with cisplatin can inhibit the tumor growth of mice with LLC, and inhibition of IL-6 level and upregulation of IL-12 level may be one of its therapeutic mechanisms.

miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway.

It has been generally believed that cancer-associated fibroblasts (CAFs) have the ability to increase the process of tumor angiogenesis. However, the potential mechanisms by which cancer-derived exosomes in lung cancer (LC) remains to be investigated. LC-derived exosomes were administrated to NIH/3T3 cells. A variety of experiments were conducted to investigate the proangiogenic factors of CAFs, including Western blot, RT-PCR, colony formation assay, tube formation assay, Matrigel plug assay et al. In addition, the impact of JAK2/STAT3 signaling pathway were also explored. The role of hsa-miR-210 was identified with microarray profiling and validated in vitro and in vivo assays. The target of miR-210 was screened by RNA pull down, RNA-sequencing and then verified. It was shown that LC-derived exosomes could induce cell reprogramming, thus promoting the fibroblasts transferring into CAFs. In addition, the exosomes with overexpressed miR-210 could increase the level of angiogenesis and vice versa, which suggested the miR-210 secreted by the LC-derived exosomes may initiate the CAF proangiogenic switch. According to our analysis, the miR-210 had the ability of elevating the expression of some proangiogenic factors such as MMP9, FGF2 and vascular endothelial growth factor (VEGF) a (VEGFa) by activating the JAK2/STAT3 signaling pathway, ten-eleven translocation 2 (TET2) was identified as the target of miR-210 in CAFs which has been involved in proangiogenic switch. miR-210 was overexpressed in serum exosomes of untreated non-small cell LC (NSCLC) patients. We concluded that the promotion effect of exosomal miR-210 on proangiogenic switch of CAFs may be explained by the modulation of JAK2/STAT3 signaling pathway and TET2 in recipient fibroblasts.

Downregulation of SOX2 may be targeted by miR-590-5p and inhibits epithelial-to-mesenchymal transition in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is the leading type of cancer worldwide and sex determining region Y-box 2 (SOX2) has been implicated as an oncogene in various types of cancer. In the present study, SOX2 was positively associated with NSCLC stage and lymph node metastasis. Wound healing and Transwell assays demonstrated that knockdown of SOX2 inhibited A549 and H1299 cell migration. Furthermore, it was identified that knockdown of SOX2 inhibited epithelial-to-mesenchymal transition of NSCLC cells, which was demonstrated by increased expression of epithelial-cadherin and decreased expression of vimentin, zinc finger protein SNAI1 and zinc finger protein SNAI2. It was then demonstrated that SOX2 may be targeted by microRNA (miR)-590-5p, which indicated a potential therapeutic strategy for NSCLC focusing on the miR-590-5p/SOX2 axis.

Left upper lobectomy and systematic lymph nodes dissection in enlarged pulmonary hilar lymph nodes in primary lung cancer patient by uniportal video-assisted thoracic surgery.

Uniportal video-assisted thoracic surgery (VATS) anatomical pulmonary resection, with only one small incision for surgery instruments and camera insertion, requires higher operative skills, especially in the cases of the enlarged pulmonary hilar lymph nodes. With improved technology and increased experiences in VATS lobectomy, uniportal VATS lobectomy has been applied in major medical centers recently. A 67-year-old male patient with left upper peripheral lung cancer and enlarged hilar lymph nodes underwent unipotal VATS lobectomy and systemic mediastinal lymph node dissection. The patient recovered uneventfully.

Safety and feasibility of uniportal video-assisted thoracoscopic surgery for locally advanced non-small cell lung cancer.

BACKGROUND: Conventional video-assisted thoracoscopic surgery (VATS) lobectomy for locally advanced non-small cell lung cancer (NSCLC) is a feasible and safe surgery in high-volume centers with significant VATS experience. Uniportal VATS lobectomy has been recently been reported to be a promising, less invasive approach. The purpose of this study is to explore the safety and feasibility of uniportal video-assisted thoracoscopic surgery (U-VATS) for the treatment of patients with locally advanced NSCLC. METHODS: From January 2013 to September 2015, a total of 132 patients with locally advanced NSCLC underwent U-VATS or open thoracotomy major pulmonary resections and standard mediastinal lymph node dissection. Patients were divided into two groups: (I) locally advanced NSCLC underwent U-VATS (U-VATS); (II) locally advanced NSCLC underwent open thoracotomy (open). A descriptive and retrospective study was performed, including the operative time, operative blood loss, postoperative chest tube duration, postoperative hospital stay, lymph node dissection, postoperative complications and postoperative recovery. RESULTS: A total of 132 patients with locally advanced NSCLC were included in this study: 64 (U-VATS) vs. 68 (open) patients. The patient demographic data was similar in both groups. Median operative time (157.0 vs. 160.6) and median number of lymph nodes (35.5 vs. 32.5) were similar in both groups. Chest tube duration and hospital of stay were statistically shorter in U-VATS group while rate of complications were higher in open thoracotomy group. One patient died on the 55th postoperative day because of tumor metastasis and bronchopleural fistula. A higher percentage of patients who underwent UVATS resections were able to receive adjuvant therapy timely compared to the open group. CONCLUSIONS: Uniportal VATS major pulmonary resections and mediastinal lymph node dissection is a safe and feasible procedure for the treatment of locally advanced NSCLC. Particularly it is suitable for the frail patients with locally advanced NSCLC who require comprehensive treatment.

Left lower sleeve lobectomy and systematic lymph node dissection by single-incision video-assisted thoracic surgery.

Sleeve lobectomy for selected cases of intratracheal tumor has better parenchyma preservation compared to pneumonectomy. And the left lower sleeve lobectomy is considered one of the most complex resections. Thanks to the advancement of equipment and accumulation of skills, video-assisted thoracic surgery (VATS) sleeve lobectomy has become safe and feasible. Typically, 3-4 ports are used, but the surgery can also be completed through one incision. A 51-year-old male patient with left lower central lung cancer underwent sleeve lobectomy and systematic mediastinal lymphadenectomy by single-incision VATS and recovered uneventfully. Sleeve lobectomy by single-incision video-assisted thoracic surgery is feasible and safe.

Left lower sleeve lobectomy and systematic lymph node dissection by complete video-assisted thoracic surgery.

Sleeve lobectomy for selected cases of central lung cancer has better functional outcomes comparing to pneumonectomy. With improved technology and increased experiences in complete video-assisted thoracic surgery (VATS) lobectomy, complete VATS sleeve lobectomy has been applied in major medical centers recently. A 64-year-old male patient with left lower central lung cancer underwent thoracoscopic sleeve lobectomy and systemic mediastinal lymph node dissection. The major incision, of four incisions in total, was a 4 cm mini-incision in the 4th intercostal space of anterior axillary line. The patient had recovered uneventfully after the surgery.

Video-assisted thoracoscopic superior segmentectomy of the right lower lobe.

Sublobar resections are still controversial for lung cancer, but for patients who can't tolerate lobectomy, such as those suffering from cardiopulmonary comorbidities and aged people, sublobar resections are better choices. Lobectomy and sublobar resections have similar surgical effect on patients with tumors ≤2 cm. A 64-year-old patient with chronic obstructive pulmonary disease (COPD) and poor pulmonary function on pre-operation evaluation underwent thoracoscopic superior segementectomy with systemic mediastinal lymph node dissection. Three holes were adopted, the major operation hole was a 3 cm mini-incision in the 4(th) intercostal space of anterior axillary line. The patient has recovered well after the surgery.