BACKGROUND:Colorectal cancer (CRC) ranks among the most prevalent malignancies affecting the gastrointestinal tract. The infiltration of CD8+ T cells significantly influences the prognosis and progression of tumor patients. METHODS:This study establishes a CRC immune risk model based on CD8+ T cell-related genes. CD8+ T cell-related genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), and the enriched gene sets were annotated via Gene Ontology (GO) and Reactome pathway analysis. Employing machine learning methods, including the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Random Forest (RF), we identified nine genes associated with CD8+ T-cell infiltration. The infiltration levels of immune cells in CRC tissues were assessed using the ssGSEA algorithm. RESULTS:These genes provide a foundation for constructing a prognostic model. The TCGA-CRC sample model's prediction scores were categorized, and the prediction models were validated through Cox regression analysis and Kaplan-Meier curve analysis. Notably, although CRC tissues with higher risk scores exhibited elevated levels of CD8+ T-cell infiltration, they also demonstrated heightened expression of immune checkpoint genes. Furthermore, comparison of microsatellite instability (MSI) and gene mutations across the immune subgroups revealed notable gene variations, particularly with APC, TP53, and TNNT1 showing higher mutation frequencies. Finally, the predictive model's efficacy was corroborated through the use of Tumor Immune Dysfunction and Exclusion (TIDE), Immune Profiling Score (IPS), and immune escape-related molecular markers. The predictive model was validated through an external cohort of CRC and the Bladder Cancer Immunotherapy Cohort. CLRN3 expression levels in tumor and adjacent normal tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Subsequent in vitro and in vivo experiments demonstrated that CLRN3 knockdown significantly attenuated the malignant biological behavior of CRC cells, while overexpression had the opposite effect. CONCLUSIONS:This study presents a novel prognostic model for CRC, providing a framework for enhancing the survival rates of CRC patients by targeting CD8+ T-cell infiltration.
Induced pluripotent stem cells (iPSCs) tailored to express tumor-specific antigens have emerged as a promising strategy for cancer immunoprevention. Despite the potential of this approach, a number of challenges remain to be addressed—such as ensuring that iPSCs are safely transported to immune-processing organs, mitigating the risk of oncogenesis, and increasing the degree of antitumor efficacy. To address these, we developed innovative vesicles that merge the antigenic repertoire of iPSCs with the lymph node homing and dendritic cell (DC)-targeting capabilities of DC-derived exosomes (DEXO), further boosted by the use of CpG oligodeoxynucleotides (CpG ODNs) as adjuvants. Our engineered vesicles are crafted to engage with immune system gatekeepers, streamlining the delivery of tumor antigens and priming T-cell responses. Laboratory analyses clarified their proficiency in terms of navigating to lymph nodes and initiating potent activation of both DCs and T-cells, thereby intensifying antitumor effects. Further tests in animal models corroborated their therapeutic potential, offering significant defense against tumor initiation, growth, spread, and recurrence, alongside significant enhancements in survival rates. Our findings indicate a promising pathway for innovative iPSC-based cancer vaccine therapies, laying a foundation for future clinical applications.
AbstractBackgroundLymph node (LN) metastasis is a significant prognostic factor for esophageal squamous cell carcinoma (ESCC), and there are no satisfactory methods for accurately predicting metastatic LNs. The present study aimed to assess the efficacy of 99mTc‐3PRGD2 single‐photon emission computed tomography (SPECT)/computed tomography (CT) for diagnosing metastatic LNs in ESCC.MethodsA total of 15 enrolled patients with ESCC underwent 99mTc‐3PRGD2 SPECT/CT and 18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG PET/CT) examinations preoperatively. High‐definition bone carving reconstruction technology (HD‐xSPECT Bone) was applied to quantitatively assess the LN's SUVmax via SPECT/CT. The two methods were compared for diagnosing metastatic LNs with pathology as the gold standard.ResultsAmong 15 patients, 23 metastatic lymph node stations (mLNSs) were predicted by SPECT/CT, with a mean SUVmax of 2.71 ± 1.34, of which 15 were pathologically confirmed; 32 mLNSs were predicted by PET/CT with a mean SUVmax of 4.41 ± 4.02, of which 17 were pathologically confirmed. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of SPECT/CT for diagnosing metastatic LNs were 62.50%, 91.30%, 85.34%, 65.22%, and 90.32%, respectively, and those of PET/CT were 70.83%, 83.70%, 81.03%, 53.13%, and 91.67%, respectively. There was no significant difference in sensitivity (p = 0.061) or specificity (p = 0.058) between the two methods. The AUCSPECT/CT was 0.816 and the SUVmax threshold was 2.5.Conclusion99mTc‐3PRGD2 SPECT/CT might be an effective method for diagnosing metastatic LNs in ESCC, especially in combination with HD‐xSPECT Bone. The diagnostic efficiency of this method was noninferior to that of 18F‐FDG PET/CT. The SUVmax threshold of 2.5 showed the highest agreement with the pathology findings.
OBJECTIVES: Uniportal video-assisted thoracoscopic surgery (UniVATS) is widely used as a minimally invasive thoracic operation. The goal of our study was to analyse the effect of long-term experience with the UniVATS lobectomy on the learning curve. METHODS: The learning curves were quantitatively evaluated by the unadjusted cumulative sum, and they were segmented using join-point linear regression analysis. The variables were compared between subgroups using trend analysis, and linear regression analysis was applied to correlate clinical characteristics at different stages of the learning curve with the duration of the operation. RESULTS: The learning curve for the UniVATS lobectomy can be divided into 3 phases of proficiency at similar to 200-300 procedures, with a fourth phase as the number of procedures increases. The 1st-52nd, 52nd-156th, 156th-244th and 244th-538th procedures comprised the preliminary learning stage, preliminary proficiency stage, proficiency stage and advanced proficiency stage, respectively. Surgical outcomes and their variability between stages improved with increasing case numbers, with the most significant addition of an auxiliary operating port and conversions. In multivariable analysis, as stages progressed, influences other than surgical experience increased the operative time, with male and extensive pleural adhesions in the preliminary proficiency stage; male and incomplete pulmonary fissures in the proficiency stage; and male, extensive pleural adhesions and incomplete pulmonary fissures in the advanced proficiency stage. CONCLUSIONS: As the number of procedures increases, there may be 4 different proficiency stages in the UniVATS lobectomy learning curve. The surgeon enters the fourth stage at approximately the 244th procedure. Moreover, at stage 4, the perioperative indicators tend to stabilize, and influences other than surgical experience become more significant.
Abstract Background Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma. Methods First, FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β (IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting. Results Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples (6.70 ± 1.79 vs. 16.32 ± 2.40, P = 0.0184; 11.20 ± 2.11 vs. 21.00 ± 3.00, P = 0.033, respectively) and HDM-induced asthmatic mouse lung lysates (1.00 ± 0.15 vs. 5.14 ± 0.42, P < 0.001). Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model (R 2 = 0.857 and 0.783, P = 0.0008 and 0.0043, respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration (2.45 ± 0.09 vs. 2.88 ± 0.14, P = 0.0288) and recruited more subepithelial neutrophils after HDM challenge [(110.20 ± 29.43) cells/mm2 vs. (238.10 ± 42.77) cells/mm2, P = 0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels (up to 1.41 ± 0.12- or 1.44 ± 0.14-fold change vs. IL-1β alone groups, P = 0.001 or 0.0344, respectively). The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Conclusion Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.
Abstract Objectives: This study aims to investigate the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as adjuvant therapy for resected non-small cell lung cancer (NSCLC) patients harboring EGFR mutations compared with adjuvant chemotherapy or placebo, including the latest updated data.Methods: A comprehensively systematic search for relevant randomized controlled trials (RCTs) was performed. Hazard ratios (HRs) and 95% confidence intervals (CI) were used to analyse disease-free survival (DFS) and overall survival (OS). For dichotomous data, risk ratio (RR) of severe adverse events and relapse patterns was calculated as effect measures. Results: Nine RCTs involving 1,835 completely resected patients with NSCLC with EGFR mutations were included in the meta-analysis. The use of EGFR-TKIs resulted in a significant improvement in DFS when compared to non-EGFR-TKIs based treatment (HR:0.45; 95% CI=0.29–0.71, P < 0.0005), but no OS benefit was shown (HR:0.79; 95%CI=0.54–1.16, P =0.23). In subgroup analyses, adjuvant EGFR-TKIs elevated DFS significantly compared to single-agent chemotherapy (HR: 0.50; 95%CI = 0.30–0.82, P = 0.006). Adjuvant EGFR-TKIs following chemotherapy also improved DFS significantly compared with single-agent chemotherapy (HR:0.34; 95%CI=0.16–0.69, P=0.003). No differences were found in DFS between adjuvant EGFR-TKIs versus placebo (HR:0.51; 95% CI=0.18 –1.47, P=0.21). Patients with a median treatment time over 12 months (HR:0.42; 95% CI=0.20–0.86; P =0.02) or diagnosed with stage III non-small cell lung cancer NSCLC (HR:0.42;95% CI = 0.20–0.86; P =0.02) induced better DFS. Elevated DFS from adjuvant EGFR-TKIs was still observed regardless of EGFR Mutation Status. Nevertheless, in subgroup analysis, neither subgroup analysis of therapeutic strategies nor median treatment duration observed any benefit from adjuvant EGFR-TKIs in OS. Moreover, adjuvant EGFR-TKIs decreased the risk of lung recurrence (RR: 0.63 ;95%CI=0.44 –0.89). Rash (RR:15.28; 95% CI = 4.71–49.55), Diarrhea (RR:3.08; 95% CI = 1.26–7.52) and ALT or AST increase (RR:8.85; 95% CI = 4.14–18.90) were several common grades 3 or higher adverse events (AEs) of EGFR-TKIs treatment.Conclusions: EGFR-TKIs treatment exhibited significant improvement in DFS with fewer manageable toxicities for NSCLC patients with EGFR mutations completely resection compared with non-EGFR-TKIs treatment. However, prolonged DFS did not produce any benefits for the OS.
Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.
Background Single-port inflatable mediastinoscopy with simultaneous laparoscopic-assisted surgery for radical esophagectomy is a promising surgical method with high technical requirements and needs team cooperation. Therefore, it is necessary to define a learning curve to guide personnel training and improve the safety of these surgical techniques. Method This study prospectively analyzed the data of 79 consecutive patients, who underwent the surgery in the Fifth Affiliated Hospital of Sun Yat-sen University from October 2016 to May 2018. All of these patients were treated by the same surgical team with extensive experience in thoracotomy, laparotomy, thoracoscopic surgery and laparoscopic surgery. The learning curve was analyzed by cumulative summation (CUSUM) analysis, with the assessment of operative time, estimated blood loss, and postoperative complications. Result By analyzing these data, The scatter diagram of every measure showing a declining situation. The learning curve decreased beginning at 25 th operation. All patients were chronologically divided into two groups, the group 1(the first 25 patients) and the group 2 (the last 54 patients). The median estimated blood loss of group 2 was lower than group 1(200 vs 100ml, p <0.05). No other clinic or pathologic characteristics were observed as significantly different. Conclusion For a surgical team with extensive experience in thoracotomy, laparotomy, thoracoscopic surgery and laparoscopic surgery, 25 cases are needed before becoming proficient in this surgery.
Background Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2), as a m6A “reader”, is known to be an oncogene, and its expression is elevated in multiple tumors. However, the role of IGF2PB2 in esophageal squamous cell carcinoma (ESCC) is still unclear. Methods This study aims to investigate the role of IGF2PB2 expression in ESCC proliferation, invasion and migration as well as the possible mechanism. IGF2BP2 expression was found to be elevated in ESCC tissues by qRT-PCR, western blotting, and immunohistochemical (IHC) staining. Results Knocking down IGF2BP2 expression prevented the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of KYSE450 and TE1 cells . Knocking out IGF2BP2 reduced tumorigenesis in vivo. Overexpression of IGF2BP2 was performed, and it was proven that IGF2BP2 had an oncogenic effect in KYSE450 and TE1 cells. Moreover, LY294002, a highly selective inhibitor of PI3K, reversed the effect of IGF2BP2 overexpression on EMT processes. All these results show that the effects of IGF2BP2 on oncogenesis and EMT were clearly exerted via the PI3K/AKT signaling pathway. Conclusions In conclusion, this study demonstrates that the oncogenic function of IGF2BP2 is mediated by the PI3K/AKT signaling pathway and is related to EMT in ESCC. In addition, IGF2BP2 can serve as a diagnostic and oncotherapeutic marker in further studies.
Identifying the lymphatic drainage pathway is important for accurate lymph node (LN) dissection in esophageal cancer (EC). This study aimed to assess lymphatic drainage mapping in thoracic EC using near-infrared fluorescent (NIRF) imaging with indocyanine green (ICG) and identify its feasibility for intraoperative LN drainage visualization and dissection. From November 2019 to August 2020, esophagectomy was performed using intraoperative NIRF navigation with ICG injected into the esophageal submucosa by endoscopy. All LNs were divided into four groups according to the NIRF status and presence of metastasis: NIRF+LN+, NIRF+LN−, NIRF−LN+, and NIRF−LN−. Regional LNs were detected in all 84 enrolled patients with thoracic EC. A total of 2164 LNs were removed, and the mean number of dissected LNs was 25.68 ± 12.00. NIRF+ LNs were observed in all patients and distributed at 19 LN stations, which formed lymphatic drainage maps. The top five LN stations of NIRF+ probability in upper thoracic EC were No. 7, 106ecR, 107, 1, and 106recL; in middle thoracic EC, they were No. 107, 7, 110, 1, and 105; and in lower thoracic EC, they were No. 107, 7, 110, 106recR, and 1. There were no cases of ICG-related adverse events or chylothorax. The 30-day mortality rate was 0%. Major complications included anastomotic fistula (7.14%), pneumonia (4.76%), pleural effusion (13.10%), atelectasis (3.75%), hoarseness (8.33%), and arrhythmia (4.76%). Regional LN mapping of thoracic EC was performed using ICG/NIRF imaging, which showed different preferred LN drainage stations in various anatomical locations of the thoracic esophagus. ICG/NIRF imaging is feasible for intraoperative LN drainage visualization and dissection. The clinical trial registration number is NCT04173676 ( http://www.clinicaltrials.gov/ ).
Primary tumor (PT) and metastatic lymph node (MLN) status have a great influence on diagnosis and treatment of lung cancer. Our main purpose was to investigate the imaging characteristics of PT or MLN by applying the 18F-FDG PET dynamic modeling approach for non-small cell lung cancer (NSCLC). Dynamic 18F-FDG PET scans were performed for 76 lung cancer patients, and 62 NSCLC cases were finally included in this study: 37 with newly diagnosed early and locally advanced lung cancer without distant metastases (group M0) and 25 metastatic lung cancer (group M1). Patlak graphic analysis (Ki calculation) based on the dynamic modeling and SUV analysis from conventional static data were performed. For PT, both KiPT (0.050 ± 0.005 vs 0.026 ± 0.004 min−1, p < 0.001) and SUVPT (8.41 ± 0.64 vs 5.23 ± 0.73, p < 0.01) showed significant higher values in group M1 than M0. For MLN, KiMLN showed significant higher values in M1 than M0 (0.033 ± 0.005 vs 0.016 ± 0.003 min−1, p < 0.01), while no significant differences were found for SUVMLN between M0 and M1 (4.22 ± 0.49 vs 5.57 ± 0.59, p > 0.05). Both SUV PT and KiPT showed significant high values in squamous cell carcinoma than adenocarcinoma, but neither SUVPT nor KiPT showed significant differences between EGFR mutants versus wild types. The overall Spearman analysis for SUV and Ki from different groups showed variable correlation (r = 0.46–0.94). The dynamic modeling for MLN (KiMLN) showed more sensitive than the static analysis (SUV) to detect metastatic lymph nodes in NSCLC, although both methods were sensitive for PT. This methodology of non-invasive imaging may become an important tool to evaluate MLN and PT status for patients who cannot undergo histological examination. The clinical trial registration number is NCT03679936 (http://www.clinicaltrials.gov/).
An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
It has been described as a new non-transthoracic esophagectomy that the single-port inflatable mediastinoscopy and laparoscopic surgery is safe and effective for the radical esophagectomy of esophageal cancer. This report describes the whole procedure in detail. The patient lies in the supine position with the legs apart. The procedure is performed under general anesthesia with a single lumen endotracheal tube. For upper mediastinal operation, a lateral incision of the clavicle was made about 3 cm; for laparoscopic operation, the incisions of 5 ports for the laparoscopic operation. CO2 insufflation is performed into the mediastinum with 10 mmHg to make artificial mediastinal emphysema. The Maryland forceps is used to perform separation before dissection. In the non-transthoracic esophagectomy, it is essential to expose the recurrent laryngeal nerve and the azygos vein. The lymph nodes around the esophagus were removed in en bloc. Maintaining double lung ventilation during surgery can significantly reduce carbon dioxide accumulation, especially for those with reduced lung function or severe pleural adhesion. Furthermore, it saves much time that upper mediastinal operation and laparoscopic operation are undergone simultaneously. It is a perfect surgical technique that is worth to promote.
为了探讨采用单孔充气式纵隔镜同步联合腹腔镜,进行不开胸食管癌根治术的可行性,收集2016年3月至2017年3月,采用单孔充气式纵隔镜联合腹腔镜完成42例食管癌根治术患者的临床资料.男27例,女15例;年龄38~ 76岁,中位年龄57岁.肿瘤部位包括:食管胸上段10例,胸中段23例,胸下段9例.肿瘤分期(第七版TNM分期)包括:0期2例,Ⅰ期18例,ⅡA期15例,ⅢA期7例.41例肺功能正常,1例合并Ⅰ型呼吸功能衰竭.全组手术顺利,42例均顺利完成纵隔镜手术,1例结肠癌术后患者因腹腔粘连严重中转开腹.全组中位手术时间226 min,术中中位出血量250 ml,清扫淋巴结中位数21个.1例Ⅰ型呼吸功能衰竭者住ICU 24 h后转普通病房.全组无手术死亡,术后食管吻合口瘘3例,喉返神经损伤导致声音嘶哑3例,饮水呛咳1例,胸腔积液3例.单孔充气式纵隔镜联合腹腔镜作为一种不开胸食管癌根治术近期疗效满意,并发症少,术中能完成食管全系膜切除和满足淋巴结清扫要求,是有效、可行的微创食管外科技术.
•Adjuvant EGFR-TKIs improved the DFS for resected EGFR-mutant NSCLC.•Adjuvant EGFR-TKIs did not improve the DFS for EGFR wild type resected NSCLC.•Adjuvant EGFR-TKIs did not improve the DFS for unselected resected NSCLC.•Adjuvant EGFR-TKIs resulted in more adverse events than placebo.•Adjuvant EGFR-TKIs experienced fewer adverse events than adjuvant chemotherapy.
BACKGROUND:Gastric cancer (GC) is one of the most common digestive tract tumors, and a serious threat to human health. Long non-coding RNA (lncRNA) are involved in many cancers. However, the biological functions of most lncRNAs are unclear. In this study, we investigated the mechanisms by which FLVCR1-AS1 regulated GC progression.METHODS:FLVCR1-AS1 expression in GC tissues and 3 GC cell lines were measured by quantitative real-time PCR (qRT-PCR). Invasion, proliferation, and apoptosis profiles were analyzed by commercial assays to determine the biological functions of FLVCR1-AS1 in GC cells. The binding sites of micro RNA-155 (miR-155) on FLVCR1-AS1 were predicted using the miRDB program. Luciferase reporter assay was used to validate direct targeting of FLVCR1-AS1 by miR-155. The effects of FLVCR1-AS1 on expressions of c-Myc and p21 were assessed by western blotting. In vivo experiments were performed to analyze the effects of FLVCR1-AS1 on GC tumor growth.RESULTS:High expression of FLVCR1-AS1 correlated with poor clinical outcomes and prognosis in patients with GC. FLVCR1-AS1 promoted proliferation and invasion of GC cells by acting as a ceRNA to sponge miR-155.CONCLUSION:FLVCR1-AS1 acted as an oncogene in GC via FLVCR1-AS1-miR-155-c-Myc signaling and may serve as a novel therapeutic target for treatment of patients with GC.
Insufficient blood supply in the gastric tube is considered as a risk factor for postoperative anastomotic strictures in patients receiving esophagectomy, but the direct evidence is lacking. We aimed to investigate the correlation between perioperative blood supply in the anastomotic area of the gastric tube and the formation of anastomotic strictures in the patients undergoing esophagectomy. This prospective study included 60 patients with esophageal squamous cell carcinoma undergoing Ivor Lewis esophagectomy between March 2014 and February 2016, which were divided into stricture group (n = 13) and non-stricture group (n = 47) based on their severity of anastomotic strictures at 3 months post-operation. The perioperative anastomotic blood supply was measured using a laser Doppler flowmetry. The gastric intramucosal pH (pHi) was measured by a gastric tonometer within 72 h post-operation. The perfusion index and gastric pHi were compared between groups. The stricture group had a significantly lower blood flow index (P < 0.001) and gastric pHi values from day 1 to day 3 post-operation than the non-stricture group (all P < 0.001). In addition, Pearson correlation analysis showed that both the perfusion index and gastric pHi were significantly correlated with stricture size and stricture scores, respectively (r = 0.65 − 0.32, all P < 0.05). Furthermore, the multivariate logistic regression analysis showed that perfusion index was an influential factor associated with postoperative anastomotic strictures (OR 0.84. 95% CI 0.72–0.98, P = 0.026). These results suggested that poor blood supply in the anastomotic area of the gastric tube in the perioperative period was a risk factor for postoperative anastomotic strictures.
We previously developed a novel non-trans thoracic esophagectomy, the single-port inflatable mediastinoscopy combined with laparoscopy for the radical esophagectomy of esophageal cancer. The purpose of this study was to report its therapeutic efficacy and safety.
Objective To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients. Methods The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group. Results The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05). Conclusion The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.