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With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m 2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m 2 , d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1-14, 29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7-27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0-21.9 months) and 20.5 months (95% CI 11.8-27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33-NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77-26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27-1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72-2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula., (© 2024. The Author(s).)

Background: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged., Methods: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria., Discussion: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI., (© 2024. The Author(s).)

Background : Ovarian cancer is the public health issue worldwide. Paclitaxel is a first-line chemotherapy drug for ovarian cancer, but paclitaxel resistance weakens the therapeutic effect. Metformin (Met) improved the paclitaxel sensitivity in a mouse model of ovarian cancer. However, the mechanism of Met on paclitaxel sensitivity is still unclear in ovarian cancer. Materials and Methods : Cell viability, apoptosis, migration, and invasion were measured by Cell Counting Kit-8 (CCK8), flow cytometry, and transwell assays severally. The expression of long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) and microRNA-3127-5p (miR-3127-5p) were detected by real-time quantitative polymerase chain reaction. The protein levels of poly (ADP-ribose) polymerase, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and Beclin 1 were examined by Western blot assay. RNA immunoprecipitation assay detected the relationship between SNHG7 and miR-3127-5p. Then, the binding correlation between SNHG7 and miR-3127-5p was predicted by starBase and verified by the dual-luciferase reporter. The effects of Met and SNHG7 on tumor growth were tested in ovarian cancer mice model. Results : Met inhibited cell viability, migration, invasion, SNHG7 level, and autophagy and promoted apoptosis in paclitaxel-resistant ovarian cancer cells. Moreover, Met partly reversed SNHG7-mediated paclitaxel sensitivity and autophagy in ovarian cancer cells. SNHG7 directly bound to miR-3127-5p. Met abolished the promoting effect of SNHG7 overexpression on tumor growth and autophagy in vivo . Conclusion : The authors' findings indicated that Met expedited paclitaxel sensitivity by regulating SNHG7/miR-3127-5p-mediated autophagy in ovarian cancer cells.

Aberrant gene expression caused by miRNAs disorders plays a relevant role in multiple steps of tumorigenesis. In this attempt, we studied the functional role of miR-125b-5p and TPD52 in breast cancer. TPD52 mRNA and miR-125b-5p levels were assessed via qRT-PCR, and TPD52 protein level was analyzed via western blot. By performing CCK-8, transwell invasion and wound healing assays, the phenotype changes in breast cancer cells were assessed. miR-125b-5p was proven as an upstream miRNA of TPD52 in breast cancer via TargetScan database, luciferase activity, and western blot. MiR-125b-5p was prominently decreased while TPD52 was dramatically increased in breast cancer cells. Functional assays exhibited that forced level of TPD52 facilitated cell proliferation, invasion and migration in breast cancer. In the end, the rescue assay proved that miR-125b-5p was a cancer repressor and modulated breast cancer progression by targeting TPD52. All above offer potential biomarkers for breast cancer treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established., Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability., Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression ( P < 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them., Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Wang, Shao, Dong, Wang, Wei, Li, Chen, Chen, Zheng, He, Zhao, Du, Sun, Wang, Wang, Zhou, Lai, Feng, Shen, Qiu, Ji, Chen, Jiang, Liu, Zeng, Wang, Zhao, Yang, Hu, Ma, Chen, Chen, Jiang and Xu.)

Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS , KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2 , and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors., Competing Interests: XH, YJ, SL, XX, YS, WT, QO, HB and XW are the shareholders or employees of Nanjing Geneseeq Technology Inc., China. Other authors have no conflicts of interest to declare., (Copyright © 2022 Yue Li et al.)

The benefit of local ablative therapy (LAT) for oligo-recurrence has been investigated and integrated into the treatment framework. In recent decades, stereotactic body radiation therapy (SBRT) has been increasingly used to eliminate metastasis owing to its high rate of local control and low toxicity. This study aimed to investigate the outcomes of SBRT for patients with lung oligo-recurrence of non-small cell lung cancer (NSCLC) from our therapeutic center. Patients with lung oligo-recurrence of NSCLC treated with SBRT between December 2011 and October 2018 at Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) were reviewed. The characteristics, treatment-related outcomes, and toxicities of the patients were analyzed. Univariable and multivariable Cox regression were performed to identify the factors associated with survival. A total of 50 patients with lung oligo-recurrence of NSCLC were enrolled. The median follow-up period was 23.6 months. The 3-year local progression-free survival (LPFS), progression-free survival (PFS) and overall survival (OS) after SBRT were 80.2%, 21.9% and 45.3%, respectively. Patients in the subgroup with LAT to all residual diseases showed significantly improved OS and PFS. No treatment-related death occurred after SBRT. SBRT is a feasible option to treat patients with lung oligo-recurrence of NSCLC, with high rates of local control and low toxicity. LAT to all residual diseases was associated with better survival outcomes. Future prospective randomized clinical trials should evaluate SBRT strategies for such patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Recent developments in adipose-derived stromal/stem cell (ADSC) biology provide new hopes for tissue engineering and regeneration medicine. Due to their pluripotent activity, paracrine activity, and immunomodulatory function, ADSCs have been widely administrated and exhibited significant therapeutic effects in the treatment for autoimmune disorders, neurodegenerative diseases, and ischemic conditions both in animals and human clinical trials. Cell-assisted lipotransfer (CAL) based on ADSCs has emerged as a promising cell therapy technology and significantly improved the fat graft retention. Initially applied for cosmetic breast and facial enhancement, CAL has found a potential use for breast reconstruction in breast cancer patients. However, more challenges emerge related to CAL including lack of a standardized surgical procedure, the controversy in the effectiveness of CAL, and the potential oncogenic risk of ADSCs in cancer patients. In this review, we summarized the latest research and intended to give an outline involving the biological characteristics of ADSCs as well as the preclinical and clinical application of ADSCs.

Background: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated., Methods: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa&#95;circRNA&#95;103809, miR-377-3p and 3' untranslated region (3'UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues., Results: Here we identified a novel hsa&#95;circRNA&#95;103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa&#95;circRNA&#95;103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa&#95;circRNA&#95;103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa&#95;circRNA&#95;103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa&#95;circRNA&#95;103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa&#95;circRNA&#95;103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo., Conclusions: Analysis of data suggested that targeting the hsa&#95;circRNA&#95;103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention.

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., (© 2020 The Author(s).)

Immune checkpoint blockade treatments bring remarkable clinical benefits to fighting several solid malignancies. However, the efficacy of immune checkpoint blockade in breast cancer remains controversial. Several clinical trials of immune checkpoint blockades focused on the effect of CTLA4 and PD1/PDL1 checkpoint inhibitors on breast cancer. Only a small portion of patients benefited from these therapies. Here we systematically investigated the expression of 50 immune checkpoint genes, including ADORA2A, LAG-3, TIM-3, PD1, PDL1, PDL2, CTLA-4, IDO1, B7-H3, B7-H4, CD244, BTLA, TIGIT, CD80, CD86, VISTA, CD28, ICOS, ICOSLG, HVEM, CD160, LIGHT, CD137, CD137L, OX40, CD70, CD27, CD40, CD40LG, LGALS9, GITRL, CEACAM1, CD47, SIRPA, DNAM1, CD155, 2B4, CD48, TMIGD2, HHLA2, BTN2A1, DC-SIGN, BTN2A2, BTN3A1, BTNL3, BTNL9, CD96, TDO, CD200 and CD200R, in different subtypes of breast cancer and assessed their prognostic value. The results showed that the expression patterns of these 50 immune checkpoint genes were distinct in breast cancer. High expression of B7-H3 mRNA was significantly associated with worse overall survival (OS), especially in patients with luminal A and luminal B breast cancer. The mRNA expression levels of TIM-3, ADORA2A, LAG3, CD86, CD80, PD1 and IDO1 had no relationship with OS in breast cancer. High expression levels of CTLA-4 and TIGIT were correlated with favorable prognosis in breast cancer. Interestingly, we observed that B7-H3 expression was negatively correlated with the efficacy of cyclophosphamide (CTX). In summary, our study suggested that B7-H3 has potential prognostic value in breast cancer and is a promising target for immune therapy., (© 2020 The Author(s).)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-19-975). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Myopia is the most common form of refractive eye disease, and the prevalence is increasing rapidly worldwide. However, the key metabolic alterations in individuals with high myopia are not understood clearly, and serum biomarkers remain to be determined. The objectives of this study were to identify serum biomarkers and investigate the metabolic alterations of myopia. The serum metabolomics profiling was investigated on 30 high myopia cases and 30 controls (without myopia) using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), and an independent additional cohort including 20 cases and 19 controls were investigated to validate potential metabolite candidates for biomarkers. According to the metabolic differences, the myopia patients and controls could be divided into different clusters and nine metabolites were found to be closely correlated with myopia. In the cohort of validation, eight metabolites were confirmed. Metabolic pathway analyses of these metabolites of high myopia involved abnormal phospholipid, diacylglycerol, amino acid, and vitamin metabolism, which were closely correlated with oxidative stress and inflammation. Multiple logistic regression analyses showed that γ-glutamyltyrosine and 12-oxo-20-trihydroxy-leukotriene B4 were potential biomarkers of myopia with a combined high sensitivity (97%), specificity (90%), and area under the curve value (0.983). These findings may contribute to an understanding of the pathophysiological changes and pathogenesis of myopia, and provide novel insight into the early prevention and control of high myopia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Lobectomy is the standard treatment for patients with stage I non-small cell lung cancer (NSCLC). Recent studies have shown promising results of stereotactic body radiation therapy (SBRT) in these patients. We retrospectively compared the outcomes of lobectomy and SBRT in these patients from our therapeutic center., Methods: Patients who underwent lobectomy or SBRT for clinical T1-2a (T size≤5 cm), N0 M0, NSCLC between December 2011 and August 2016 were reviewed. Patient characteristics, treatment-related outcomes and toxicities were analyzed. Propensity score matching (PSM) was performed to improve comparability between the two groups., Results: Median follow-up period in the lobectomy (n = 246) and SBRT (n = 70) group was 31.4 months and 24.9 months, respectively. Three-year local recurrence-free survival (LRFS) was comparable in the two groups (97% vs. 91.7%, respectively; P = 0.768). Recurrence-free survival (RFS) at 3-year in the lobectomy and SBRT groups was 85.4 and 69.5%, respectively (P = 0.014). Three-year overall survival (OS) after lobectomy and SBRT was 88.2 and 79.7%, respectively (P = 0.027), while 3-year cancer-specific survival (CSS) was 91.3 and 82.5% (P = 0.022). After PSM (45 matched patients in each group), there was no significant between-group difference with respect to 3-year LRFS (89.6% vs. 87.5%, P = 0.635), RFS (77.6% vs. 67.3%, P = 0.446), OS (78.5% vs. 79.5%, P = 0.915) or CSS (86.4 and 79.5%, P = 0.551). In matched subgroup, 30-day mortality after lobectomy was 2.2%, and no treatment-related death occurred after SBRT., Conclusions: Treatment-related outcomes of SBRT and lobectomy were comparable. SBRT was well tolerated and had a very low toxicity profile in our study. SBRT is a promising alternative treatment option for stage I NSCLC patients. This study indicates that matching these disparate cohorts of patients is challenging. Clinical trials are essential to define the indications and relative efficacy of lobectomy and SBRT in a selected population.

Cisplatin (CDDP) is a commonly used drug for gallbladder cancer (GBC) chemotherapy. However, resistance to CDDP treatment results in relapse. Therefore, there is a need for the development of more effective treatment strategies to overcome chemoresistance. Dual-specificity phosphatase 1 (DUSP1) was reported to be involved in the resistance of a number of chemotherapeutic agents and was revealed to be highly expressed in CDDP-resistant GBC cells and CDDP-treated tumor types compared with normal cells or tissues in the present study. DUSP1 was revealed to inhibit the cytotoxicity of CDDP in two GBC cell lines, SGC996 and GBC-SD. P38 mitogen-activated protein kinases may be involved in the mechanism of chemoresistance. Furthermore, the number of DNA double-strand breaks in SGC996 OE cells was reduced compared with SGC996 vector cells indicating DUSP1 may attenuate the chemotherapeutic efficiency. Due to its potency against CDDP treatment, DUSP1 may be a promising target to overcome chemoresistance in GBC therapy.

Background: The aim of this study is to assess the survival benefits of additional induction chemotherapy before concurrent chemotherapy, intensity-modulated radiotherapy and nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Clinical data from 1104 nonmetastatic nasopharyngeal carcinoma patients diagnosed between May 2008 and April 2014 were retrospectively reviewed. All patients received addition of induction chemotherapy to concurrent chemoradiotherapy with or without nimotuzumab. A propensity score matched method was used to identify paired patients according to various covariates. Results: In total, 120 pairs were selected by propensity score matched method. At a median follow-up time of 56 months (10-99 months), the 5-year locoregional relapse-free survival, distant metastases-free survival, progression-free survival and overall survival rates in patients treated with nimotuzumab vs. without nimotuzumab were 91.6% vs. 91.1% (P= 0.957), 95.8% vs. 83.9% (P= 0.007), 87.4% vs. 81.3% (P= 0.225), 94.5% vs. 85.6% (P= 0.058), respectively. Multivariate analysis revealed that nimotuzumab was an independent prognosticator of OS and DMFS. Conclusions: Nimotuzumab is an effective treatment option for locoregionally advanced nasopharyngeal carcinoma, and the addition of induction chemotherapy to concurrent chemoradiotherapy and nimotuzumab could obtain the best survival benefits., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The apparent diffuse coefficient (ADC) may correlate with the treatment response to chemotherapy/radiotherapy in solid tumors. Our aim was to determine the inter- and intra-observer reproducibility of ADC measurements in primary esophageal squamous cell carcinoma (ESCC). ADCs were blindly measured in 31 patients diagnosed with ESCC by two observers before treatment (pre-ADC) and after 5 th fraction radiotherapy (intra-ADC) twice with a 2-week interval. The mean pre-ADC of primary tumors was 1.25±0.22 and 1.27±0.23 (in 10 -3 mm 2 /s) from observer A for measurements 1 and 2, respectively, and the intra-observer measurements were -0.02 bias vs. -0.13-0.09 limits of agreement. From observer B, the mean pre-ADC varied between 1.25±0.23 and 1.27±0.23 (in 10 -3 mm 2 /s) for measurements 1 and 2, respectively, and intra-observer measurements were -0.02 bias vs. -0.17∼0.16 limits of agreement. The mean pre-ADC of primary tumors was 1.26±0.24 (in 10 -3 mm 2 /s) from observers A and B, and inter-observer measurements were 0.01 bias vs. -0.09-0.09 limits of agreement, revealing a low inter-observer variance. Similar measurements of the intra-SD parameters showed that the pre- and intra-ADC of primary tumors differed significantly. Thus ADC measurements may have sufficient inter-observer and intra-observer reproducibility to measure primary tumor responses to treatment, and the ADCs before and during treatment differed., Competing Interests: CONFLICTS OF INTEREST On behalf of all authors of this paper, I declare that this study will not lead to any financial or other kinds of conflicts of interest.

Purpose: To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in patients with esophageal squamous cell carcinoma (ESCC) in Chinese population., Patients and Methods: Patients with ESCC, who received SIB-IMRT from September 2011 to January 2013 were retrospectively analyzed. The SIB-IMRT plans were designed to deliver primary gross tumor volume at 60-64.4 Gy in 28-30 fractions, and planning target volume at 50.4-56 Gy in 28-30 fractions. Treatment-related toxicities were estimated based on Common Terminology Criteria for Adverse Events version 4.0, and tumor response after the treatment was estimated according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS), locoregional progression-free survival (LPFS), and progression-free survival (PFS) were estimated with Kaplan-Meier., Results: All patients completed definitive radiotherapy, 54 (78.3%) received combined chemotherapy, of which 31 (44.9%) were concurrent chemoradiotherapy and 23 (33.3%) were sequential chemotherapy. The objective response rate is 82.6% (56/69), with complete response 11 (15.9%), partial response 45 (65.2%), stable disease 8 (11.6%), and progressive disease 5 (7.2%). The 1-, 2- and 3-year LPFS was 74.4%, 57.8%, and 55.6%, respectively. The 1-, 2- and 3-year PFS was 62.3%, 41.0%, and 34.2%, respectively, and the 1-, 2-, and 3-year OS was 73.8%, 57.4%, and 41.0%, respectively, with a median OS of 27.1 months (4.5-54.9 m). For those who received concurrent chemotherapy, the 1-, 2-, and 3-year OS was 75.9%, 69.0%, and 55.2%, respectively, better than those who had sequential chemotherapy or radiotherapy alone (χ2 = 3.115, P = 0.078). Radiation esophagitis occurred in 63.8% and 14.5% with Grade 2 and 3, respectively. No patients occurred ≥ Grade 3 radiation pneumonia., Conclusions: It is safe and effective using SIB-IMRT technology to treat patients with ESCC. More prospective clinical studies should be needed.

Purpose: To retrospectively compare taxane-based with fluorouracil-based chemoradiotherapy in terms of toxicity profiles, efficacy and survival in patients with inoperable esophageal cancer., Methods and Materials: We analyzed retrospectively 179 consecutive patients who were unresectable or medically unfit for surgery between March 2009 and November 2014. Eight-three patients were included in the taxane group and 96 cases were in the fluorouracil group., Results: The overall response rate (ORR) in the taxane group was higher than fluorouracil group, but was not significantly different (71.6% vs. 63.5%, respectively, P=0.255). In total, 53.0% (44/83) of the patients in the taxane group had progressive disease versus 54.2% (52/96) in the fluorouracil group (not significantly different (P=0.758)). There was no significant difference in overall response rate, progression free survival and overall survival, as well as treatment-related death. In terms of non-hematological toxicity, patients in the taxane group experienced a lower incidence of ≥ grade 3 esophageal perforation or fistula (4.8% vs. 13.5%, P=0.047) and pneumonia (4.8% vs. 9.7%, P=0.242). Regarding hematological toxicity, thrombocytopenia in the taxane group was significantly lower (4.8% vs. 13.5%, P=0.047), but there was a trend towards a higher rate of ≥ grade 3 leukopenia (34.9% vs.26.0%, P=0.196)., Conclusions: Chemoradiation with taxane-based regimens is well tolerated, with potentially promising efficacy, and could become a good alternative treatment in a first line setting for patients with inoperable esophageal squamous cell carcinoma.

MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNA's expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Dose escalation of thoracic radiation can improve the local tumor control and surivival, and is in the meantime limited by the occurrence of radiation-induced lung injury (RILI). This study investigated the clinical and dosimetric factors influencing RILI in lung-cancer patients receiving chemoradiotherapy for better radiation planning., Methods and Materials: A retrospective analysis was carried out on 161 patients with non-small-cell or small-cell lung cancer (NSCLC and SCLC, respectively), who underwent chemoradiotherapy between April 2010 and May 2011 with a median follow-up time of 545 days (range: 39-1453). Chemotherapy regimens were based on the histological type (squamous cell carcinoma, adenocarcinoma, or SCLC), and radiotherapy was delivered in 1.8-3.0 Gy (median, 2.0 Gy) fractions, once daily, to a total of 39-66 Gy (median, 60 Gy). Univariate analysis was performed to analyze clinical and dosimetric factors associated with RILI. Multivariate analysis using logistic regression identified independent risk factors correlated to RILI., Results: The incidence of symptomatic RILI (≥grade 2) was 31.7%. Univariate analysis showed that V5, V20, and mean lung dose (MLD) were significantly associated with RILI incidence (P=0.029, 0.048, and 0.041, respectively). The association was not statistically significant for histological type (NSCLC vs. SCLC, P = 0.092) or radiation technology (IMRT vs. 3D-CRT, P = 0.095). Multivariate analysis identified MLD as an independent risk factor for symptomatic RILI (OR=1.249, 95%CI=1.055-1.48, P= 0.01). The incidence of bilateral RILI in cases where the tumor was located unilaterally was 22.7% (32/141) and all dosimetric-parameter values were not significantly different (P>0.05) for bilateral versus ipsilateral injury, except grade-1 (low) RILI (P < 0.05). The RILI grade was higher in cases of ipsilateral lung injury than in bilateral cases (Mann-Whitney U test, z=8.216, P< 0.001)., Conclusion: The dosimetric parameter, MLD, was found to be an independent predictive factor for RILI. Additional contralateral injury does not seem to be correlated with increased RILI grade under the condition of conventional radiotherapy treatment planning.

Purpose: The relationship between plasma D-dimer level and the prognosis of advanced non-small-cell lung cancer (NSCLC) is not well studied. This study investigated the role of plasma D-dimer as a prognostic factor in advanced NSCLC., Methods: The plasma D-dimer was measured in 1,931 newly diagnosed advanced NSCLC patients by enzyme-linked immunosorbent assay. Correlations between plasma D-dimer levels and other clinical parameters were analyzed. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis., Results: Plasma D-dimer concentrations were within the normal range in 1,393 patients (72.1%) and elevated in 538 patients (27.9%). The median overall survival was 11.5 and 8.8 months in the normal and high plasma D-dimer group, respectively (P<0.001). The progression-free survival of first-line chemotherapy was 5.0 months and 4.4 months in the groups with normal and high levels of plasma D-dimer, respectively, (P<0.001). By multivariate analyses, the elevated plasma D-dimer level was found to be an independent prognostic factor for poor survival (hazard ratio =1.245; P<0.001)., Conclusion: Plasma D-dimer is an independent determinant of poor prognosis in advanced NSCLC.

The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.