Publications by authors named "Junqiang Fan"

17 Publications

  • Page 1 of 1

Lepidic component identifies a subgroup of lung adenocarcinoma with a distinctive prognosis: a multicenter propensity-matched analysis.

Ther Adv Med Oncol 2020 23;12:1758835920982845. Epub 2020 Dec 23.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Zhengmin Road 507, Shanghai 200443, China.

Background: Our aim was to investigate the prognostic impact of the lepidic component on T stage in patients with lung adenocarcinoma (LUAD).

Methods: A retrospective data set including 863 cases of LUAD with lepidic component and 856 cases without lepidic component was used to identify matched lepidic-positive and lepidic-negative cohorts ( = 376 patients per group) using a propensity-score matching. Primary outcome variables included recurrence-free survival (RFS) and overall survival (OS). Prognostic factors were assessed by Cox regression analysis and Kaplan-Meier estimates.

Results: Multivariate analysis revealed that lepidic component presence was an independent prognostic factor for prolonged RFS ( < 0.001) and OS ( < 0.001). Furthermore, lepidic ratio (LR) >25% or ⩽25% were confirmed to be independent prolonged survival predictors. No survival differences were observed between patients with LUAD with LR >25% or ⩽25% (RFS  = 0.333; OS  = 0.078). The 5-year OS rates of patients with LUAD with a lepidic component were 90% regardless of the T stage, and these survival rates were significantly better than those of patients with LUAD without a lepidic component in the corresponding T stage. Multivariate analysis confirmed that T stage was associated with survival only in patients with LUAD without a lepidic component.

Conclusions: Lepidic component presence identifies a LUAD subgroup with an excellent prognosis independent of the LR, pathological T classification. Considering the lepidic component presence may improve prognostic predictions for patients with LUAD.
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http://dx.doi.org/10.1177/1758835920982845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768877PMC
December 2020

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

Medicine (Baltimore) 2020 Oct;99(42):e22719

Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.

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.
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http://dx.doi.org/10.1097/MD.0000000000022719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571977PMC
October 2020

Prognostic impact of micropapillary component in patients with node-negative subcentimeter lung adenocarcinoma: A Chinese cohort study.

Thorac Cancer 2020 Dec 15;11(12):3566-3575. Epub 2020 Oct 15.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: In this study, we investigated the prognostic significance of a micropapillary (MP) component in patients with subcentimeter lung adenocarcinoma.

Methods: A total of 311 patients with subcentimeter lung adenocarcinoma who underwent surgical resection between January 2009 to December 2012 from seven medical centers were included. Recurrence-free survival (RFS) and overall survival (OS) were analyzed.

Results: The five-year RFS was 79.8% in 97 (97/311, 31%) cases of adenocarcinoma with a MP component and 93.5% in the 214 (214/311, 69%) cases without. In multivariate analysis, MP was an independent risk factor for worse RFS (hazard ratio [HR], 3.73; 95% confidence interval [CI]: 1.87-7.42; P < 0.001) and OS (HR, 5.84; 95% CI: 2.20-15.49; P < 0.001). There was no significant difference among wedge resection, segmentectomy and lobectomy on RFS (P = 0.256) and OS (P = 0.103) in patients without MP. Regarding patients with a MP component, lobectomy achieved equivalent prognosis than segmentectomy, and both were better than wedge resection (P = 0.001).

Conclusions: A MP component still suggest a poor prognosis in subcentimeter lung adenocarcinoma. Patients with subcentimeter lung adenocarcinoma with a MP component of 5% or greater treated with wedge resection were at higher risk of recurrence than patients treated with anatomical resection.
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http://dx.doi.org/10.1111/1759-7714.13702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705621PMC
December 2020

Uniportal video-assisted thoracic surgery for the treatment of lung cancer: a consensus report from Chinese Society for Thoracic and Cardiovascular Surgery (CSTCVS) and Chinese Association of Thoracic Surgeons (CATS).

Transl Lung Cancer Res 2020 Aug;9(4):971-987

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Uniportal video-assisted thoracoscopic surgery (UniVATS) has been widely adopted in China, where several ultra-high volume thoracic surgical and training centers are located. The objective of this consensus from Chinese experts was to summarize the current application and give reference for the future development of UniVATS in the treatment of lung cancer. A panel of 41 experts from 21 Chinese hospitals was invited to join this project. The Delphi method was used in this consensus consisting of two rounds of voting. The questionnaire was based on the current clinical evidence. Forty (97.6%) experts completed the 2 rounds of questionnaires. The experts' experience was relatively similar. We defined the UniVATS as monitor-dependent surgery, no use of rib-spreading and single incision less than 4 cm. Tumor with stage of T1-T3 and N0-N2 is considered amenable to UniVATS. Other consensus was reached on several points outlining the safety and feasibility, surgical skills, learning curve, short-term and long-term outcomes for lung cancer, and current application of subxiphoid and nonintubated UniVATS approach. This consensus statement represents a collective agreement among Chinese experts to suggest that UniVATS is an effective alternative to multi-portal approach, although high-level evidence is expected in the future. Some agreements can be referred in the training of young surgeons.
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http://dx.doi.org/10.21037/tlcr-20-576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481589PMC
August 2020

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

Clin Sci (Lond) 2020 04;134(7):807-825

Thoracic Surgery Department, The Second Affiliated of Zhejiang University, School of Medicine, Hangzhou, China.

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.
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http://dx.doi.org/10.1042/CS20200039DOI Listing
April 2020

Postoperative analgesic effect of hydromorphone in patients undergoing single-port video-assisted thoracoscopic surgery: a randomized controlled trial.

J Pain Res 2019 27;12:1091-1101. Epub 2019 Mar 27.

Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, People's Republic of China.

To study the general efficacy of hydromorphone as a systemic analgesic in postoperative pain management following single-port video-assisted thoracoscopic surgery (VATS) and to explore the optimal administration regimen. A prospective, randomized, double-blind study was designed and conducted in a tertiary hospital. In total, 157 valid patients undergoing single-port VATS were randomly allocated into three groups. A total of 53 patients received morphine bolus only for postoperative analgesia (Group Mb); 51 patients received a hydromorphone background infusion plus bolus (Group Hb + i), and 53 patients received a hydromorphone bolus only (Group Hb). The primary outcomes were patient-reported static and dynamic pain levels; the secondary outcomes included side effects, sleep quality, and recovery indexes. Patients in Group Hb + i experienced lower pain intensity (approximately 10 out of 100 on the visual analog scale) in both static pain and dynamic pain in the days following surgery (<0.01), better sleep quality during the first night only (=0.002), and a higher satisfaction level than those in the other two groups (=0.006). A comparison of these variables in Group Mb and Group Hb resulted in no significant differences. Lastly, side effects and recovery indexes remained the same among bolus-only groups and bolus-plus-background-infusion groups. There is no advantage to administering hydromorphone over morphine using bolus only mode. Within 24 h after surgery, a background infusion should be considered as a part of a standard protocol for patient-controlled intravenous analgesia. At 24 h after surgery, the background infusion should be adjusted in accordance with patient preferences and pain intensity.
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http://dx.doi.org/10.2147/JPR.S194541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497863PMC
March 2019

Does chronic obstructive pulmonary disease relate to poor prognosis in patients with lung cancer?: A meta-analysis.

Medicine (Baltimore) 2019 Mar;98(11):e14837

The Second Affiliated Hospital, School of Medicine.

Background: Nowadays, there is growing recognition that chronic obstructive pulmonary disease (COPD) may have influence on lung cancer. However, coexisted COPD related to prognosis of lung cancer is still elusive. We conducted this meta-analysis to examine the association between COPD and 5-year overall survival (OS) and postoperative pulmonary complications of patients with lung cancer.

Methods: A comprehensive computer-based online search was conducted using PubMed, Embase, Medline, and the Cochrane Library for articles published before September 30, 2017. We identified 29 eligible studies, which included 70,111 patients in the related literature.

Results: Twenty-two of the 29 studies provided hazard ratio for OS (1.18, 95% confidence interval: 1.11-1.25; P < .001), it suggested that the presence of COPD indicated poor survival for the patients with lung cancer. In subgroup analysis, the relationship between COPD and OS occurrence remained statistically prominent in the subgroups stratified by study designs, COPD diagnosis timing, lung cancer surgery, cancer stage, and origins of patients. The presence of COPD increased the risk of bronchopleural fistula, pneumonia, prolonged air leakage, and prolonged mechanical ventilation.

Conclusions: The present meta-analysis suggested that coexisting COPD is associated with poor survival outcomes in patients with lung cancer and higher rates of postoperative pulmonary complications.
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http://dx.doi.org/10.1097/MD.0000000000014837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426564PMC
March 2019

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

J Thorac Dis 2016 Dec;8(12):3543-3550

Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China.

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) . 68 (open) patients. The patient demographic data was similar in both groups. Median operative time (157.0 . 160.6) and median number of lymph nodes (35.5 . 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 55 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.
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http://dx.doi.org/10.21037/jtd.2016.12.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227252PMC
December 2016

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

J Thorac Dis 2015 Oct;7(10):1865-9

Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 31009, China.

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.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2015.10.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635291PMC
October 2015

Bilateral video-assisted thoracoscopic thymectomy for Masaoka stage IIIA thymomas.

Thorac Cardiovasc Surg 2015 Apr 2;63(3):206-11. Epub 2014 Dec 2.

Department of Thoracic Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Larger invasive thymomas are generally resected via an open approach with thoracotomy or sternotomy. Following accumulation of experience and modifications to the technique, certain invasive tumors can be safely resected by video-assisted thoracic surgery (VATS) without resorting to sternotomy.

Patients And Methods: Thirteen consecutive patients with large invasive thymomas, who underwent bilateral VATS thymectomy, were analyzed retrospectively.

Results: All patients underwent radical en bloc resection of the tumor and the involved structures, without breaching the tumor capsule or tumor seeding. In one patient, difficulties in removal of the tumors from the left brachiocephalic vein necessitated conversion to an open approach with minithoracotomy. No procedure-related hemorrhage occurred. The average operation time, including the case requiring conversion, was 132 minutes. The mean postoperative hospital stay was 4.7 days. There were no perioperative deaths. All patients completed follow up, with a mean duration of 17.4 months. Follow-up chest computed tomography showed no cases of recurrence.

Conclusion: With proper patient selection, preoperative planning, and a standardized approach to the operative method, we believe that bilateral VATS thymectomy can be a safe and effective procedure, and may provide an attractive alternative approach to median sternotomy.
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http://dx.doi.org/10.1055/s-0034-1395389DOI Listing
April 2015

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

J Thorac Dis 2013 Aug;5 Suppl 3:S287-8

Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.

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.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2013.07.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771586PMC
August 2013

Effects of polyphyllin I on growth inhibition of human non-small lung cancer cells and in xenograft.

Acta Biochim Biophys Sin (Shanghai) 2010 Nov;42(11):827-33

Department of Cardiothoracic Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, China.

Polyphyllin I (PPI), a small molecular monomer extracted from Rhizoma of Paris polyphyllin, shows strong anticancer effects in previous study. Human lung adenocarcinoma A549 cells, human lung squamous cell carcinoma SK-MES-1 cells, and human lung large cell carcinoma H460 cells were cultured and then treated with PPI. Cell proliferation and apoptosis were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot analysis, and DNA ladder. Athymic nude mice bearing tumors were injected with PPI, and tumor growth was recorded. Our results showed that PPI significantly inhibited the proliferation of three non-small cell lung cancer (NSCLC) cell lines, with the inhibitory concentrations (IC50) of 1.24, 2.40, and 2.33 μg/ml for A549, H460, and SK-MES-1 cells, respectively. After being treated with 2.5 µg/ml of PPI for 24 h, the apoptotic rate of A549 cells was 39.68%, which was remarkably higher than that of the control. Tumor growth was significantly inhibited in the PPI-treated group compared with the group treated with cisplatin (DDP) or PBS in the nude mice. PPI exhibits antitumor ability in NSCLC cells in vitro and in vivo, which might be related to the apoptosis induced by PPI.
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http://dx.doi.org/10.1093/abbs/gmq091DOI Listing
November 2010

[The significance of erythrocyte fragment count to predicting hemolysis in roller pumps].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2008 Jun;25(3):632-6

Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Hemolysis in blood pumps has been measured by various in vitro tests, in which normalized index of hemolysis (NIH) was established. As NIH is complicated and difficult to calculate, erythrocyte fragment count (EFC) is proposed in the present study to predict hemolysis in roller pumps. Five paired in vitro tests were conducted using the POLYSTAN pediatric pump (group A) and COBE pump (group B). Ten whole blood samples (400ml) were circled in the roller pump for 16 hours. Erythrocyte fragments count and plasma-free hemoglobin (FHb) were measured before pumping and every 2 hours through circulation after 4 hours pumping. The morphological changes of erythrocyte were observed by scanning electron microscope. Simple linear regression analysis showed the two groups' EFC and FHb levels increased linearly during a long period of pumping, and the coefficient of determination (R2) was 0.64. These data suggested that Erythrocyte fragments count could be used as an index in evaluating the in vitro hemolytic properties of blood pumps.
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June 2008

Does sleeve lobectomy concomitant with or without pulmonary artery reconstruction (double sleeve) have favorable results for non-small cell lung cancer compared with pneumonectomy? A meta-analysis.

Eur J Cardiothorac Surg 2007 Jul 17;32(1):20-8. Epub 2007 Apr 17.

Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

It has been reported that sleeve lobectomy (SL) concomitant with or without pulmonary artery reconstruction (PAR) might be an alternative procedure for pneumonectomy (PN) in non-small cell lung cancer (NSCLC). The aim of this study was to assess whether SL or PN offers a low morbidity and mortality and better long-term survival. We performed a meta-analysis of studies published in English between 1996 and 2006 to comprehensively compare the postoperative mortality, morbidity, locoregional recurrences, and time-to-event outcomes of SL and PN in NSCLC, and reviewed the recent literatures on PAR in the corresponding period as well. Twelve studies met the defined criteria including a total of 2984 subjects, and five studies for PAR. The odds ratio for postoperative mortality (SL vs PN) was 0.65 (95% confidence interval (CI): 0.42-1.01), 1.01 (95% CI: 0.70-1.44) for postoperative complications, and 0.91 (95% CI: 0.45-1.82) for locoregional recurrences. The weighted mean operative mortality for PAR was 3.3%, and 32.4% for complications. The estimated combined hazard ratio for overall survival in 10 studies was 0.70 (95% CI: 0.62-0.79) in favor of SL group. The median overall survival was 60 months for the SL group, 26 months for the PN group, and 30 months for PAR group. Survival difference in patients with pN0 or pN1 at 1 year demonstrated a pooled risk difference (SL vs PN) of 0.03 (95% CI: -0.08-0.13), 0.13 (95% CI: 0.00-0.25) in patients with pN2 at 1 year, 0.21 (95% CI: 0.07-0.36) in patients with pN0 or pN1 at 5 years, and 0.06 (95% CI: -0.10-0.21) in patients with pN2 at 5 years. Our results suggests that SL with or without PAR can be accomplished safely in selected patients without increasing the morbidity and mortality as compared to PN, that SL even with PAR offers better long-term survival than does PN, and that a more radical operation such as PN is not a more appropriate procedure, even in higher stage tumors.
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http://dx.doi.org/10.1016/j.ejcts.2007.03.018DOI Listing
July 2007

Suppression of type 1 Insulin-like growth factor receptor expression by small interfering RNA inhibits A549 human lung cancer cell invasion in vitro and metastasis in xenograft nude mice.

Acta Biochim Biophys Sin (Shanghai) 2007 Feb;39(2):137-47

Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Cancer invasion and metastasis, involving a variety of pathological processes and cytophysiological changes, contribute to the high mortality of lung cancer. The type 1 insulin-like growth factor receptor (IGF-1R), associated with cancer progression and invasion, is a potential anti-invasion and anti-metastasis target in lung cancer. To inhibit the invasive properties of lung cancer cells, we successfully down-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA) technology, and evaluated its effects on invasion-related gene expression, tumor cell in vitro invasion, and metastasis in xenograft nude mice. A549 cells transfected with a plasmid expressing hairpin siRNA for IGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the protein level. In biological assays, transfected A549 cells showed a significant reduction of cell-matrix adhesion, migration and invasion. Consistent with these results, we found that down-regulation of IGR-1R concomitantly accompanied by a large reduction in invasion-related gene expressions, including MMP-2, MMP-9, u-PA, and IGF-1R specific downstream p-Akt. Direct tail vein injections of plasmid expressing hairpin siRNA for IGF-1R significantly inhibited the formation of lung metastases in nude mice. Our results showed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasion and metastasis.
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http://dx.doi.org/10.1111/j.1745-7270.2007.00257.xDOI Listing
February 2007