MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. In this study, we investigated the roles and mechanisms of miR-140 ...in human non-small cell lung cancer (NSCLC). We found that miR-140 is significantly downregulated in NSCLC tissues and cell lines. Both gain-of-function and loss-of-function studies demonstrated that miR-140 suppresses NSCLC cell proliferation, migration, and invasion in vitro. Importantly, overexpression of miR-140 effectively repressed tumor growth and metastasis in nude mouse models. Integrated analysis identified IGF1R as a direct and functional target of miR-140. Knockdown of IGF1R inhibited cell proliferation and invasion resembling that of miR-140 overexpression, while overexpression of IGF1R attenuated the function of miR-140 in NSCLC cells. Together, our results highlight the significance of miR-140 and IGF1R in the development and progression of NSCLC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Rationale
Circular RNAs (circRNAs) have been demonstrated to contribute to esophageal cancer progression. CircBCAR3 (hsa_circ_0007624) is predicted to be differentially expressed in ...esophageal cancer by bioinformatics analysis. We investigated the oncogenic roles and biogenesis of circBCAR3 in esophageal carcinogenesis.
Methods
Functions of circBCAR3 on cancer cell proliferation, migration, invasion, and ferroptosis were explored using the loss-of-function assays. A xenograft mouse model was used to reveal effects of circBCAR3 on xenograft growth and lung metastasis. The upstream and downstream mechanisms of circBCAR3 were investigated by bioinformatics analysis and confirmed by RNA immunoprecipitation and luciferase reporter assays. The dysregulated genes in hypoxia-induced esophageal cancer cells were identified using RNA-seq.
Results
CircBCAR3 was highly expressed in esophageal cancer tissues and cells and its expression was increased by hypoxia in vitro. Silencing of circBCAR3 repressed the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro, as well as inhibited the growth and metastasis of esophageal xenograft in mice in vivo. The hypoxia-induced promotive effects on esophageal cancer cell migration and ferroptosis were rescued by circBCAR3 knockdown. Mechanistically, circBCAR3 can interact with miR-27a-3p by the competitive endogenous RNA mechanism to upregulate transportin-1 (TNPO1). Furthermore, our investigation indicated that splicing factor quaking (QKI) is a positive regulator of circBCAR3 via targeting the introns flanking the hsa_circ_0007624-formed exons in BCAR3 pre-mRNA. Hypoxia upregulates E2F7 to transcriptionally activate QKI.
Conclusion
Our research demonstrated that splicing factor QKI promotes circBCAR3 biogenesis, which accelerates esophageal cancer tumorigenesis via binding with miR-27a-3p to upregulate TNPO1. These data suggested circBCAR3 as a potential target in the treatment of esophageal cancer.
Graphical Abstract
Hypoxia induces the upregulation of E2F7, which transcriptionally activates QKI in esophageal cancer cells. QKI increases the formation of circBCAR3 by juxtaposing the circularized exons. CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES
In this retrospective study, we aimed to compare single-port (SP) and multiport (MP) video-assisted thoracoscopic surgery (VATS) for the surgical resection of non-small-cell lung cancer ...(NSCLC).
METHODS
Between October 2013 and October 2014, a total of 411 consecutive NSCLC patients who underwent VATS lobectomy in the Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, were enrolled. Propensity-matched analysis, incorporating preoperative clinical features, was used to compare the perioperative outcomes and analyse the safety and efficacy between SP and MP VATS lobectomies for NSCLCs.
RESULTS
There were 115 patients in the SP group, and 296 patients in the MP group from October 2013 to October 2014. Propensity matching produced 100 pairs in this retrospective study. During the operation, the lobectomy took less time in the SP than in the MP (65.7 ± 14.8 vs 81.3 ± 13.6, P < 0.001) group, while the duration of lymphadenectomy was longer in the SP group (29.6 ± 16.7 vs 17.4 ± 13.3, P < 0.001). The total operation duration, the volume of estimated blood loss (55.1 ± 9.0 ml vs 58.7 ± 7.1 ml, P = 0.22) and the length of postoperative hospital stay (4.7 ± 1.2 days vs 5.3 ± 1.4 days, P = 0.05) were similar between the two groups. Postoperatively, SP and MP groups showed similar results in terms of morbidity and mortality.
CONCLUSIONS
In comparison with conventional VATS, SP VATS lobectomy showed better safety and efficacy in the surgical resection of NSCLCs. Further studies based on larger populations and better methodology are required to determine its further benefits towards patients.
Background Minimally invasive esophagectomy (MIE) theoretically offers advantages compared with open esophagectomy (OE). However, the long-term outcomes have not been well studied, especially for ...esophageal squamous cell carcinoma. We retrospectively compared postoperative outcomes, quality of life (QOL), and survival in a matched population of patients undergoing MIE, with a control (OE) group. Methods From May 2004 to August 2013, MIE was performed for a group of 735 patients, which was compared with a group of 652 cases of OE. Eventually, 444 paired cases, matched using propensity-score matching, were selected for further statistical analysis. Results Compared with the OE group, the MIE group had shorter operation duration (191 ± 47 minutes vs 211 ± 44 minutes, P < .001); less blood loss (135 ± 74 ml vs 163 ± 84 ml, P < .001); similar lymph node harvest (24.1 ± 6.2 vs 24.3 ± 6.0, P = .607); shorter postoperative hospital stay (11 days range: 7-90 days vs 12 days range: 8-112 days, P < .001); fewer major complications (30.4% vs 36.9%, P = .039); a lower readmission rate to the intensive-care unit (5.6% vs 9.7%, P = .023); and similar perioperative mortality (1.1% vs 2.0%, P = .281). At a median follow-up of 27 months, the 2-year overall survival rates in the MIE and OE group were: (1) stage 0 and I: 92% versus 90% ( P = .864); (2) stage II: 83% versus 82% ( P = .725); (3) stage III: 59% versus 55% ( P = .592); (4) stage IV: 43% versus 43% ( P = .802). The generalized estimating equation analysis showed that MIE had an independently positive impact on patients' postoperative QOL. Conclusions In our experience, MIE is a safe and effective procedure for the treatment of esophageal squamous cell carcinoma. It may offer better perioperative outcomes, better postoperative QOL, and equal oncologic survival, compared with OE.
Background Minimally invasive esophagectomy (MIE) has been advantageous for lowering pulmonary complications compared with open approaches. However, pulmonary complications remain the most common ...morbidity after surgical resection of esophageal cancer.2,3 The aim of this prospective, randomized, controlled, clinical trial was designed to see whether low tidal volume (VT) could further minimize pulmonary complications after MIE. Methods Between June 2011 and July 2012, a total of 101 patients who underwent MIE received left-lung ventilation during thoracoscopic esophagectomy. All patients received left-lung ventilation during thoracoscopic esophagectomy. Patients were randomly assigned to a low VT (5 mL/kg + 5 cm H2 O positive end-expiratory pressure) preserved ventilation (PV) group (n = 53) and a conventional VT (8 mL/kg) controlled ventilation (CV) group (n = 48) in the thoracic stage. Alveolar lavage fluid was harvested from the ventilated lung at intubation and at 18 hours after surgery for analysis of interleukin (IL)-1ß, IL-6, and IL-8 levels. Clinical characteristics, including patient demographics, operation features, and changes in oxygenation index, were recorded and analyzed. Pulmonary complications were identified and statistically compared between the 2 groups. Results The clinical characteristics and operation features were comparable between the 2 groups. IL-1ß, IL-6, and IL-8 expressions in preoperative alveolar lavage fluid were similar between the 2 groups. Significantly lower IL expressions were observed in the PV group than those in the CV group at 18 hours after MIE (IL-1ß, 25.42 ± 31.01 vs 94.96 ± 118.24 pg/mL; IL-6, 30.86 ± 75.78 vs 92.99 ± 72.90 pg/mL; IL-8, 258.75 ± 188.24 vs 403.95 ± 151.44 pg/mL; all P < .05). The 18-hour postoperative oxygenation index was lower in the CV group than that in the PV group (292.85 ± 28.74 vs 326.35 ± 34.43; P = .046). Pulmonary complications were observed in 18 cases of our series, occurring more frequently on the ventilation side (right, 6 cases; and left, 12 cases). All patients were cured by conservative therapy without severe sequelae. The occurrence of pulmonary complications in the PV group was lower than that in the CV group (9.43% vs 27.08%; P = .021). Conclusions Lung injury due to intraoperative single-lung ventilation may contribute to pulmonary complications after MIE. Low VT ventilation could decrease ventilation-associated lung inflammation, thus minimizing pulmonary complications after MIE. Further studies, based on a larger volume of populations, are required to confirm these findings.
Background
It is known that ypN0 status after induction treatment can be divided into “natural” N0 (cN0/ypN0) and “downstaged” N0 (cN+/ypN0). Whether natural N0 patients and downstaged N0 patients ...with esophageal squamous cell carcinoma (ESCC) after neoadjvant chemoradiotherapy (nCRT) have similar prognosis is unknown.
Methods
An institutional database was reviewed to identify ESCC patients after nCRT, whose CT scans were retrieved and reviewed to reclassify nodal status. The patients were divided into 3 groups based on node status: natural N0, downstaged N0, and ypN+. Impact of nodal status on survival and associations with survival were analyzed.
Results
We identified 110 patients, and 25 had natural N0 disease, 52 had downstaged N0 disease, and 33 had ypN+ disease. The 3-year OS was 76.7%, 79.5%, and 49% in natural N0, downstaged N0 and ypN+ group, respectively, and, correspondingly, the 3-year DFS was 77%, 73.9%, and 36.3%. In multivariable analysis, OS (
P
= 0.794) and DFS (
P
= 0.957) did not differ between natural N0 and downstaged N0 groups, but it was significantly shorter in ypN+ group (OS,
P
= 0.032; DFS,
P
= 0.021). In subgroups with “poor response” of primary tumor, the prognosis of natural N0 and downstaged N0 paitents was poor almost identical to ypN+ in both OS (
P
= 0.721;
P
= 0.252) and DFS (
P
= 0.694;
P
= 0.114).
Conclusions
The ypN0 status is an important hallmark demonstrating the effectiveness of nCRT for ESCC, regardless of cN status. Additionally, the survival of natural N0 and downstaged N0 patients with bad response at primary site may be poor, similar to ypN+ patients.
In this paper, Changji, Xinjiang, northwest China, was selected as the study area, and platinum group elements (PGEs) in PM
2.5
were quantified by ICP-MS using microwave digestion. The results ...indicated that the average concentrations (and range) of Rh, Pd, and Pt in PM
2.5
were 0.21 (n.d. −1.41) ng/m
3
, 8.09 (n.d. −59.50) ng/m
3
, and 0.12 (n.d. −0.83) ng/m
3
, respectively
.
The concentration of Pd was significantly higher than Rh and Pt. Moreover, the seasonal variations of Rh and Pd were the same: highest in summer and lower in other seasons. However, the seasonal variation of Pt was opposite to that of Rh and Pd: highest in winter and lower in other seasons. Seasonal differences in emission sources of PGEs and the climatic characteristics of arid regions played important roles in the seasonal changes of PGEs. Rh and Pd had a common source and similar diurnal variation. The major influencing factors were traffic volume and meteorological conditions. The diurnal variation regularity of Pt was different from Rh and Pd. The superimposed effect of vehicle exhaust emissions and coal-fired emissions was the main reason why the diurnal variation of Pt was more complicated than those of Rh and Pd. The diurnal concentration of Pt varied with the seasons. It is caused by seasonal coal combustion and meteorological conditions.
•We leveraged 10 machine learning algorithms and identified an optimal programmed cell death signature (CDS).•The CDS had a stable and powerful performance in predicting the clinical outcome of LUAD ...and served as an independent risk factor in TCGA and 8 GEO datasets.•LUAD patients with low CDS score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, indicating a better immunotherapy response low CDI score indicated a higher TME score, higher abundance of immune cells, higher immunophenoscore, and lower TIDE score.•Single cell analysis revealed a strong and frequent communication between epithelial cells and cancer-related fibroblasts by specific ligand-receptor pairs, including COL1A2-SDC4 and COL1A2-SDC1.•SLC7A5 was upregulated in LUAD and knockdown of SLC7A5 obviously suppressed tumor cell proliferation.
Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis. Programmed cell death (PCD) plays a crucial function in tumor progression and immunotherapy response in lung adenocarcinoma (LUAD).
Integrative machine learning procedure including 10 methods was performed to develop a prognostic cell death signature (CDS) using TCGA, GSE30129, GSE31210, GSE37745, GSE42127, GSE50081, GSE68467, GSE68571, and GSE72094 dataset. The correlation between CDS and tumor immune microenvironment was evaluated using various methods and single cell analysis. qRT-PCR and CCK-8 assay were conducted to explore the biological functions of hub gene.
The prognostic CDS developed by Lasso + survivalSVM method was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting the clinical outcome of LUAD and served as an independent risk factor in TCGA and 8 GEO datasets. The C-index of CDS was higher than that of clinical stage and many developed signatures for LUAD. LUAD patients with low CDS score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, indicating a better immunotherapy benefit. Single cell analysis revealed a strong and frequent communication between epithelial cells and cancer-related fibroblasts by specific ligand-receptor pairs, including COL1A2-SDC4 and COL1A2-SDC1. Vitro experiment showed that SLC7A5 was upregulated in LUAD and knockdown of SLC7A5 obviously suppressed tumor cell proliferation.
Our study developed a novel CDS for LUAD. The CDS served as an indicator for predicting the prognosis and immunotherapy benefits of LAUD patients.
Heavy metals and PGEs are accumulating in the environment, due to industrial activities and car emissions. In this research, we chose the heavy industrial city (Changji, China) as a study area, and ...used ICP-MS to examine concentrations of some platinum group elements (PGEs) platinum (Pt), palladium (Pd), and rhodium (Rh) and heavy metals in total suspended particulate (TSP) in arid urban environment. We also investigated seasonal variation and distribution of size-fractionated atmospheric particulate matter for PGEs and heavy metals in TSP. The results indicated that PGEs and heavy metal concentrations in TSP followed the same seasonal trend: winter > autumn > spring > summer; this may be attributed to seasonal variation in pollution sources in Changji. However, there was a difference between PGEs and heavy metal distributions in size-fractionated atmospheric particulate matter in TSP. The highest concentrations of PGEs were not observed in the smallest size fraction of atmospheric particulate matter, while the concentrations of heavy metals increased as particulate matter size decreased. The emission mechanism of PGEs may lead to this special distribution of size fractionated.
Background The prone position (PP) and decubitus position (DP) have both been used for thoracoscopic esophagectomy. However, which of these positions is ergonomically better for the operating surgeon ...is unknown. In this randomized controlled trial ( NCT01144325 ), we aimed to assess the surgeon’s physical and mental stress in operating on patients in the PP compared with that in the DP. Methods From October 2012 to June 2013, 67 consecutive patients who underwent a three-stage minimally invasive esophagectomy were randomly assigned to the DP or the PP during the thoracic stage. The same senior surgeon performed all operations. Objectively, the surgeon’s spontaneous eye blink rate was recorded during thoracoscopic esophagectomy. Subjectively, the physician’s musculoskeletal symptoms were rated on a scale ranging from 1 (uninfluenced) to 10 (maximum fatigue). Clinical characteristics, including patient demographics and operative features of the two patient groups, were statistically compared. Results There were 35 patients in the PP group and 32 in the DP group. The two groups were comparable in patient demographics. The thoracic stage of the operation was longer in the DP group than in the PP group (87 ± 24 minutes vs 68 ± 22 minutes, p < 0.001), and the volume of blood loss was higher (89 ± 18 mL vs 67 ± 16 mL, p < 0.001). The surgeon’s eye blink rate at the end of thoracic stage decreased more from baseline in the DP group than in the PP group (3.0 ± 1.4 blinks/min vs 1.2 ± 0.9 blinks/min, p < 0.001), and the surgeon’s symptom scale score was higher after operation with the patient in the DP than in the PP (6.29 ± 1.54 vs 3.13 ± 2.82, p < 0.001). No conversion to open thoracotomy was recorded in either group. Conclusions Thoracoscopic esophagectomy in the PP provided less workload and better ergonomic results than the DP. Further study based on a larger number of patients is required to confirm these findings.
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