Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials.

Bacterial infections can compromise the physical and biological functionalities of humans and pose a huge economical and psychological burden on infected patients. Nitric oxide (NO) is a broad-spectrum antimicrobial agent, whose mechanism of action is not affected by bacterial resistance. S-nitrosoglutathione (GSNO), an endogenous donor and carrier of NO, has gained increasing attention because of its potent antibacterial activity and efficient biocompatibility. Significant breakthroughs have been made in the application of GSNO in biomaterials. This review is based on the existing evidence that comprehensively summarizes the progress of antimicrobial GSNO applications focusing on their anti-infective performance, underlying antibacterial mechanisms, and application in anti-infective biomaterials. We provide an accurate overview of the roles and applications of GSNO in antibacterial biomaterials and shed new light on the avenues for future studies.

Macrophage derived miR-7219-3p-containing exosomes mediate fibroblast trans-differentiation by targeting SPRY1 in silicosis.

Silicosis is one of the most serious occupational diseases with the main feature of inflammatory cell infiltration, fibroblasts activation, and large deposition of extracellular matrix in the lung. Increasing evidence indicates that macrophage-derived exosomes may play an important role in the development of silicosis by transferring their loaded microRNAs (miRNAs). Hence we carried out high-throughput sequencing to identify the expression of exosomal miRNA from macrophages exposed to silica or not in the previous study. Then we verified that miR-7219-3p was significantly up-regulated in macrophages and their exosomes after silica-exposure, as well as in the silicotic mice model by qRT-PCR, subsequent experiments confirmed that the increase of miR-7219-3p facilitated fibroblast to myofibroblast trans-differentiation (FMT), as well as cell proliferation and migration. Spouty1 (SPRY1), which served as a negative modulator of the Ras/ERK/MAPK signaling pathway, was verified as the target gene of miR-7219-3p, the knockdown or over-expression of SPRY1 apparently promoted or inhibited FMT via the Ras/ERK/MAPK signaling pathway. Furthermore, the inhibition of exosomal miR-7219-3p partially suppressed FMT and silica-induced pulmonary fibrosis in vitro and in vivo. In brief, our results demonstrated that exosomal miR-7219-3p played an important role in FMT and might be a novel therapeutic target of silicosis.

Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma: A SEER population-based study.

ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.

A Novel Risk Model Based on Lipid Metabolism-Associated Genes Predicts Prognosis and Indicates Immune Microenvironment in Breast Cancer.

BACKGROUND: Breast cancer (BRCA) is the most common tumor in women, and lipid metabolism involvement has been demonstrated in its tumorigenesis and development. However, the role of lipid metabolism-associated genes (LMAGs) in the immune microenvironment and prognosis of BRCA remains unclear. METHODS: A total of 1076 patients with BRCA were extracted from The Cancer Genome Atlas database and randomly assigned to the training cohort (n = 760) or validation cohort (n = 316). Kaplan-Meier analysis was used to assess differences in survival. Consensus clustering was performed to categorize the patients with BRCA into subtypes. Using multivariate Cox regression analysis, an LMAG-based prognostic risk model was constructed from the training cohort and validated using the validation cohort. The immune microenvironment was evaluated using the ESTIMATE and tumor immune estimation resource algorithms, CIBERSORT, and single sample gene set enrichment analyses. RESULTS: Consensus clustering classified the patients with BRCA into two subgroups with significantly different overall survival rates and immune microenvironments. Better prognosis was associated with high immune infiltration. The prognostic risk model, based on four LMAGs (MED10, PLA2G2D, CYP4F11, and GPS2), successfully stratified the patients into high- and low-risk groups in both the training and validation sets. High risk scores predicted poor prognosis and indicated low immune status. Subgroup analysis suggested that the risk model was an independent predictor of prognosis in BRCA. CONCLUSION: This study demonstrated, for the first time, that LMAG expression plays a crucial role in BRCA. The LMAG-based risk model successfully predicted the prognosis and indicated the immune microenvironment of patients with BRCA. Our study may provide inspiration for further research on BRCA pathomechanisms.

Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram.

BACKGROUND: We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival. METHODS: Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit. RESULTS: All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1-35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514-6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246-7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013-1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000-1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963-0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63-0.85) and the clinical usefulness of the model. CONCLUSIONS: SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.

TGF­ß1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review).

Idiopathic pulmonary fibrosis (IPF) is a worldwide disease characterized by the chronic and irreversible decline of lung function. Currently, there is no drug to successfully treat the disease except for lung transplantation. Numerous studies have been devoted to the study of the fibrotic process of IPF and findings showed that transforming growth factor­ß1 (TGF­ß1) plays a central role in the development of IPF. TGF­ß1 promotes the fibrotic process of IPF through various signaling pathways, including the Smad, MAPK, and ERK signaling pathways. There are intersections between these signaling pathways, which provide new targets for researchers to study new drugs. In addition, TGF­ß1 can affect the fibrosis process of IPF by affecting oxidative stress, epigenetics and other aspects. Most of the processes involved in TGF­ß1 promote IPF, but TGF­ß1 can also inhibit it. This review discusses the role of TGF­ß1 in IPF.

MiR-34a reverses radiation resistance on ECA-109 cells by inhibiting PI3K/AKT/mTOR signal pathway through downregulating the expression of SIRT1.

BACKGROUND: Radiotherapy is an effective treatment for esophageal squamous cell carcinoma (ESCC). However, many ESCC patients relapsed after receiving radiotherapy due to the inherent resistance. The function of miR-34a and SIRT1, as well as the correlation between miR-34a and SIRT1 has been widely claimed in multiple types of malignant tumors. This study aimed to investigate the effects of miR-34a on radiation resistance against ESCC and the underlying mechanism. METHODS: In this study, CCK8, flow cytometry, wounding healing assays, and cell clone formation assay were used to determine the in vitro anti-tumor effects of radiation on radiation-resistant ESCC cell line (rECA-109). The luciferase activity and Western Blot assays were used to investigate the relationship among miR-34a, SIRT1, and the anti-radiation resistant effects. The xenograft experiments were used to verify the important function of miR-34a and SIRT1 in radiation resistance against ESCC. The apoptosis state of tumor tissues was evaluated by TUNEL assay. RESULTS: The introduction of miR-34a significantly induced the cell death and apoptosis of rECA-109 and inhibit the migration of rECA-109 treated by radiation. The anti-tumor effect was accompanied by the downregulation of SIRT1 and the inhibition of PI3K/AKT/mTOR signal pathway. The radiation resistance on rECA-109 cells was reversed by silencing SIRT1, accompanied by the PI3K/AKT/mTOR signal pathway inhibited. In vivo experiments revealed that the radiation resistance on ESCC was reversed by the introduction of miR-34a, the effect of which was promoted by the activation of SIRT1. CONCLUSION: Our results showed that miR-34a could reverse the radiation resistance on rECA-109 cells by downregulating the expression of SIRT1through inhibiting the PI3K-AKT-mTOR signal pathway.

Is two-incision approach superior to the mini-posterior approach in total hip arthroplasty?: a meta-analysis.

BACKGROUND: Whether there is any clinical superiority for the two-incision total hip arthroplasty (THA) over the mini-posterior THA remains controversial. The present meta-analysis aimed to comprehensively compare the clinical outcomes between the two mini-invasive THAs. METHODS: Two authors searched the database of Web of Science, PubMed, EMBASE and Cochrane Library to screen eligible studies individually. The quality evaluation of included studies was performed according to the principle of risk-of-bias of the Cochrane Library. The pooled results were analysed by Review Manager 5.3 software. RESULTS: A total of seven prospective studies (including five randomized controlled trials) with 423 hips were finally included for meta-analysis. The pooled results revealed that the mini-posterior THA outperformed the two-incision THA in shortening operative times, reducing blood loss and postoperative fracture risks, while no significant difference was found between the two surgery methods with respect to HSS scoring, SF-12 scoring, postoperative function recovery and other postoperative complications. CONCLUSION: Based on the pooled results, we suggested the mini-posterior THA as a preferable choice for patients suffering from severe advanced hip diseases.

Pretreatment MRI-Derived Radiomics May Evaluate the Response of Different Induction Chemotherapy Regimens in Locally advanced Nasopharyngeal Carcinoma.

RATIONALE AND OBJECTIVES: To evaluate and compare the performance of radiomics in predicting induction chemotherapy response treated with two different regimens in patients with advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: A total of 265 patients with pathologically confirmed locally advanced nasopharyngeal carcinoma (stage II-IV), including 115 treated with gemcitabine plus cisplatin (GP group) and 150 treated with docetaxel plus cisplatin (TP group) were retrospectively enrolled. Radiomics features were extracted from the volume of interest delineated in multi-MR sequences on a 3T scanner. After random stratified grouping (training and validation cohorts) and logistic regression based on selected features, the association between the radiomics signature and the early response to induction chemotherapy were established for GP and TP regiments, respectively. RESULTS: Clinical factors showed no significant difference between the response and non-response groups for the GP and TP regiments (all p > 0.05). The accuracy of the radiomics signature consisting of selected features from the joint T1, T2, and T1C in the GP group (0.852 in the training cohort vs. 0.853 in the validation cohort) was significantly higher than that in the TP group (0.774 vs 0.727). The overall performance of the GP model was steady, with efficiency to distinguish responders from nonresponders with an AUC reaching 0.907 (95% confidence interval [CI] [0.843-0.970]) in the training cohort and 0.886 (95% CI [0.772-0.998]) in the validation cohort, while leveling at 0.800 (95% CI [0.712-0.888]) in the training cohort and 0.863 (95% CI [0.758-0.967]) in the validation cohort in the TP group. CONCLUSION: Pretreatment MR radiomics signature can better predict the early response to IC in the GP regimen than the TP regimen, which may be helpful to guide IC management.

Different Risk Target Volumes for Nasopharyngeal Carcinoma Treated with Simultaneous Integrated Boost Intensity-Modulated Radiotherapy.

Background and Objectives: Although intensity-modulated radiotherapy (IMRT) provides promising survival advantages and fewer late complications in patients with nasopharyngeal cancer (NPC), appropriated target volumes and prescribed doses are still being explored. This study aimed to propose different risk target volumes and corresponding prescribed doses in our center and to evaluate the physical basis and efficacy of this protocol based on the long-term survival of NPC patients. Methods and Materials: We retrospectively assessed patients with histology-proven non-metastatic NPC treated with definitive IMRT using our protocol of different risk target volumes and corresponding prescribed doses based on the orderly stepwise pattern of tumor spread. We described the delineation for different risk target volumes and the design of IMRT planning for an NPC case. Additionally, we compared the dosimetric distributions between the China protocol and our protocol through two NPC cases. The patterns of failure and locoregional control were the primary endpoints. All survival outcomes were calculated using the Kaplan-Meier method. Results: From January 2013 to December 2014, a total of 335 patients were treated; the median follow-up for patients who survived was 70 months. All patients completed IMRT using our protocol. Twenty-five patients developed locoregional recurrence, and all recurrences occurred within the high-dose target volumes. The rates of locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival, and overall survival at 5 years were 92.2%, 92.1%, 85.9%, and 86.3%, respectively. The biological effective doses of the prescribed doses in our protocol were similar to those of the China and 0615 protocols. Moreover, our protocol offered a reduction in D1 and D2 in the primary gross tumor volume (GTV), while V30 and V40 in normal tissues were lower. Conclusion: Our protocol of different risk target volume delineations and corresponding prescribed doses based on the stepwise pattern of tumor spread resulted in favorable locoregional control with no relapse outside the GTV.

Therapeutic patterns and outcomes in older patients (aged ≥65 years) with stage II-IVB Nasopharyngeal Carcinoma: an investigational study from SEER database.

Purpose: Currently, the optimal treatment regimens for older nasopharyngeal carcinoma (NPC) patients remained unclear. The aim of this retrospective study is to investigate therapeutic patterns and survival outcomes for a cohort of older NPC patients receiving radiation therapy (RT) with or without chemotherapy (CT). Methods: The clinical data of 529 patients with aged ≥65 years and NPC, who were identified within the Surveillance, Epidemiology, and End Results (SEER) registry (years 2004-2015), were collected and retrospectively reviewed. Among these patients, 74 patients treated with RT alone and 455 cases were administrated for RT plus CT. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The differences in OS and CSS were compared using Log-rank test. Results: The estimated OS and CSS rates at 5 years were 48.9% and 59.6%, respectively. Univariate analysis indicated that age, histology, T stage, and clinical stage were independent prognosticators of OS and CSS, while treatment option was only associated with OS. Multivariate analysis demonstrated that age, T stage, histology, and therapeutic strategy were correlated with OS, while age, T stage and histology were independent prognostic factors of CSS. Subgroup analyses showed that the combination of RT and CT yielded better OS and CSS in patients with stage T3 or N2 or III. Conclusion: Among these NPC patients with aged ≥65 years reported in the SEER database, treatment with RT plus CT provided longer OS than those treated with radiation therapy alone. Moreover, the combination of RT and CT obtained favorable OS and CSS in NPC patient stage T3 or N2 or III.

Methodology of dose calculation for external beam radiation combined with high dose rate brachytherapy in the era of 3-dimensional treatment planning system.

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.

Bioinformatics-based analysis of the lncRNA-miRNA-mRNA and TF regulatory networks reveals functional genes in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a 5-year survival rate unsatisfied malignancies. The study aimed to identify the novel diagnostic and prognostic targets for ESCC. Expression profiling (GSE89102, GSE97051, and GSE59973) data were downloaded from the GEO database. Then, differentially expressed (DE) lncRNAs, DEmiRNAs, and genes (DEGs) with P-values < 0.05, and |log2FC| ≥ 2, were identified using GEO2R. Functional enrichment analysis of miRNA-related mRNAs and lncRNA co-expressed mRNA was performed. LncRNA-miRNA-mRNA, protein-protein interaction of miRNA-related mRNAs and DEGs, co-expression, and transcription factors-hub genes network were constructed. The transcriptional data, the diagnostic and prognostic value of hub genes were estimated with ONCOMINE, receiver operating characteristic (ROC) analyses, and Kaplan-Meier plotter, respectively. Also, the expressions of hub genes were assessed through qPCR and Western blot assays. The CDK1, VEGFA, PRDM10, RUNX1, CDK6, HSP90AA1, MYC, EGR1, and SOX2 used as hub genes. And among them, PRDM10, RUNX1, and CDK6 predicted worse overall survival (OS) in ESCC patients. Our results showed that the hub genes were significantly up-regulated in ESCA primary tumor tissues and cell lines, and exhibited excellent diagnostic efficiency. These results suggest that the hub genes may server as potential targets for the diagnosis and treatment of ESCC.

Influence of concurrent chemotherapy on locoregionally advanced nasopharyngeal carcinoma treated with neoadjuvant chemotherapy plus intensity-modulated radiotherapy: A retrospective matched analysis.

Neoadjuvant chemotherapy (NAC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) will be the new standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) patients. However, many patients fail to receive CC for multiple reasons. We aimed to investigate long-term survival outcomes and toxicities in these patients with NPC treated with additional NAC plus concurrent chemoradiotherapy (CCRT) or IMRT alone. In total, 1,378 previously untreated, newly diagnosed locoregionally advanced NPC patients receiving NAC plus IMRT with or without CC were retrospectively reviewed. We used a propensity score-matched (PSM) method with 1:1 matching to identify paired patients according to various covariates. Survival outcomes and toxicities were compared between the two groups. In total, 288 pairs were identified. With a median follow-up of 86 (range: 8-110) months, the estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates in patients treated with NAC plus CCRT vs. NAC plus IMRT alone were 96.1% vs. 94.7% (P = 0.201), 93.7% vs. 89.8% (P = 0.129), 91.3% vs. 85.1% (P = 0.024), and 93.0% vs. 90.6% (P = 0.362), respectively. Multivariate analysis showed that CC omission was a prognostic factor for worse PFS. In a subgroup analysis, PFS did not differ significantly between two groups of female patients or aged <60 years or stage T1-2 or stage N0-1 disease. However, fewer acute complications were observed in the NAC plus IMRT alone group. NAC with IMRT alone confers similar survival rates and less acute toxicities. Specifically, NAC plus IMRT alone may be enough for female patients <60 years with stage T1-2 or stage N0-1. However, a prospective randomised trial is needed to validate these results.

A nanomicelle with miR-34a and doxorubicin reverses the drug resistance of cisplatin in esophageal carcinoma cells by inhibiting SIRT1 signal pathway.

BACKGROUND: Esophageal carcinoma (EC) is one of the most deadly malignant tumors in the world. Surgery, combined with chemotherapy or radiotherapy, is the traditional strategy for the treatment of EC. Cisplatin (CDDP) is a common chemotherapy drug widely used to treat EC due to its powerful anti-tumor effect. However, CDDP is subject to intrinsic or acquired resistance in EC cells, which badly hinders the efficacy of chemotherapy. The resistance phenomenon is mostly caused by the p53 mutant in the EC and the low efficiency of the drug delivery system. METHODS: In this study, a specially designed nanomicelle was used to promote the anti-tumor effect of chemotherapy drugs against the CDDP-resistant EC cells. The nanomicelle consisted of miR-34a, doxorubicin (DOX), polyethylene glycol (PEG), and other excipients in an appropriate ratio. RESULTS: The results showed that the nanomicelle could exert significant cell proliferation inhibition and apoptosis-inducing effects in the CDDP-resistant EC cells. The endogenous expression of miR-34a in the CDDP-resistant EC cells was promoted by the incubation with the nanomicelle. After incubation with the nanomicelle, the expression of protein SIRT1 was inhibited, and the expression of caspase3 was promoted significantly in the CDDP-resistant EC cells. CONCLUSIONS: Our results indicate that the specially designed nanomicelle can exert promising anti-tumor effects by introducing miR-34a to inhibit SIRT1 signaling pathway and enhance the efficiency of the drug delivery system.

ADC correlation with Sirtuin1 to assess early chemoradiotherapy response of locally advanced esophageal carcinoma patients.

AIMS: To determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT). METHODS: A total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1~2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and ΔADC, ADCratio were calculated. Pearson's correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman's rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT. RESULTS: The findings of this study showed different correlations between ADC values and the levels of SIRT1 (ΔADC: r = - 0.943, P = 0.002; ADCratio: r = - 0.911, P = 0.000; intra-ADC: r = - 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between ΔADC and early response to treatment (ρ = 0.615, P = 0.023), and multivariable logistic regression revealed that ΔADC was significantly associated with short-term response of CRT in esophageal carcinoma patients. CONCLUSIONS: In summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.

Identification of candidate genes of nasopharyngeal carcinoma by bioinformatical analysis.

OBJECTIVE: This study aimed to identify candidate genes as potential biomarkers in nasopharyngeal carcinoma (NPC) by bioinformatical analysis. METHODS: Three microarray datasets: GSE32906, GSE15170, GSE53819 were download from public database and analyzed to identify the differentially expressed genes (DEGs) between NPC and normal samples. Functional and pathway enrichment analysis of the DEGs were performed. Protein-protein interaction network and gene-transcription factor regulatory network of DEGs were constructed. And the expression of hub genes in NPC was also validated based on the public database. RESULTS: A total of 16 up-regulated and 27 down-regulated genes were screened out from the microarray datasets. Functional and pathway enrichment analysis showed that DEGs were mostly enriched in positive regulation of angiogenesis, mesenchymal cell proliferation, cell surface and DNA binding, ECM-receptor interaction pathway, PI3K-Akt signaling pathway, and pathways in cancer. Five hub genes JUN, VEGFA, FOXM1, MYB, and WNT5A were identified from the protein-protein interaction network. Subsequently, the hub gene-transcription factor regulatory network revealed that STAT3, MYC, SOX2, RUNX2 present key relations with hub genes. The expression of these five hub genes were also validated to be differentially expressed among NPC and normal samples. CONCLUSIONS: The current study indicated that the hub DEGs JUN, VEGFA, FOXM1, MYB, and WNT5A we identified might be potential therapeutic biomarkers of NPC.

Quantitative Multiparametric MRI May Augment the Response to Radiotherapy in Mid-Treatment Assessment of Patients with Esophageal Carcinoma.

OBJECTIVE: The purpose of this study was to assess the mid-treatment response to radiotherapy (RT) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with esophageal cancer (EC). METHODS: 42 patients with squamous EC were prepared for DCE-MRI and DWI scans both before treatment (NRT) and after the fifth radiotherapy (5th RT). The patients were classified into two groups (complete response [CR] and partial response [PR]) according to tumor regression after treatment. The quantitative parameters of DCE-MRI (Ktrans, Kep, Ve, and ADC) were measured. A receiver operating characteristic curve (ROC) was used to detect the efficiency of the above parameters. RESULTS: After 1 month of RT, 29 patients were classified as CR and 11 patients were classified as PR. In the NRT group, the p values of Ktrans, Kep, Ve, and ADC were 0.004, 0.078, 0.0008, and <0.0001, respectively. After the 5th RT, the p values of the above parameters were <0.001, 0.005, 0.108, and 0.365, respectively. In the NRT group, the areas under the ROC curves of Ktrans, Ve, and ADC were 0.790, 0.617, and 0.737; the sensitivity values were 89.3, 92.5, and 90.0%; the specificity values were 69.4, 27.5, and 50.0%. In the 5th RT group, the areas under the ROC curves of Ktrans and Kep were 0.816 and 0.804; the sensitivity values were 71.2 and 95.0%; the specificity values were 81.6 and 50.0%. CONCLUSION: DCE-MRI combined with DWI is effective in the early prediction of radiotherapeutic response of EC after the 5th RT other than after the traditional final treatment.