Fabrication strategies for chiral self-assembly surface.

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

Correction: Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

[This corrects the article DOI: 10.1371/journal.pgen.1007888.].

MiR-323a-3p acts as a tumor suppressor by suppressing FMR1 and predicts better esophageal squamous cell carcinoma outcome.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has unfavorable outcomes with the highest incidence seen in China. Accordingly, exploring effective molecular biomarkers is of great value. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and modulate numerous biological processes in tumors. Our study aimed to identify prognostic miRNAs and investigate their role in ESCC. METHODS: Prognosis-related plasma miRNAs were detected by miRNA microarray and qRT-PCR. Functional assays and molecular mechanism studies were used to investigate the role of miRNA in ESCC. RESULTS: Over-expression of miR-323a-3p was associated with a favorable prognosis. MiR-323a-3p negatively regulated proliferation, migration, and invasion. Through biological predictions, the fragile X mental retardation 1 (FMR1) was found to be a potential target of miR-323a-3p. Further investigation revealed that miR-323a-3p directly targeted and suppressed FMR1. MiR-323a-3p and FMR1 mRNA, as well as miR-323a-3p and the FMR1-encoded protein FMRP, showed negative correlations. Luciferase activity of FMR1-3'-UTR, but not mutant counterparts, was decreased by mimic compared with that of the control. The compromised cell proliferation, migration, and invasion induced by transfection with miR-323a-3p mimic were rescued by transfection with a FMR1 expression plasmid. Tumors induced by miR-323a-3p overexpressed ESCC cells grew significantly slower in vivo and resulted in smaller tumor masses. Metastatic lung colonization was also inhibited by miR-323a-3p overexpression. CONCLUSIONS: MiR-323a-3p was significantly associated with survival and acted as a tumor suppressor by inhibiting proliferation, migration, and invasion via the regulation of FMR1. MiR-323a-3p is a promising biomarker and may be a potential therapeutic target.

Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

Brain metastasis (BM) is a major complication of lung adenocarcinoma (LAD). An investigation of the pathogenic mechanisms of BM, as well as the identification of appropriate molecular markers, is necessary. The aim of this study was to determine the expression patterns of microRNAs (miRNAs) in LAD with BM, and to investigate the biological role of these miRNAs during tumorigenesis. miRNA array profiles were used to identify BM-associated miRNAs. These miRNAs were independently validated in 155 LAD patients. Several in vivo and in vitro assays were performed to verify the effects of miRNAs on BM. We identified six miRNAs differentially expressed in patients with BM as compared to patients with BM. Of these, miR-4270 and miR-423-3p were further investigated. miR-4270 and miR-423-3p directly targeted MMP19 and P21, respectively, to influence cell viability, migration, and colony formation in vitro. miR-4270 downregulation and miR-423-3p upregulation was associated with an increased risk of BM in LAD patients. Thus, our results suggested that miR-4270 and miR-423-3p might play an important role in BM pathogenesis in LAD patients, and that these miRNAs might be useful prognostic and clinical treatment targets.

Spatially resolved metabolomics to discover tumor-associated metabolic alterations.

Characterization of tumor metabolism with spatial information contributes to our understanding of complex cancer metabolic reprogramming, facilitating the discovery of potential metabolic vulnerabilities that might be targeted for tumor therapy. However, given the metabolic variability and flexibility of tumors, it is still challenging to characterize global metabolic alterations in heterogeneous cancer. Here, we propose a spatially resolved metabolomics approach to discover tumor-associated metabolites and metabolic enzymes directly in their native state. A variety of metabolites localized in different metabolic pathways were mapped by airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) in tissues from 256 esophageal cancer patients. In combination with in situ metabolomics analysis, this method provided clues into tumor-associated metabolic pathways, including proline biosynthesis, glutamine metabolism, uridine metabolism, histidine metabolism, fatty acid biosynthesis, and polyamine biosynthesis. Six abnormally expressed metabolic enzymes that are closely associated with the altered metabolic pathways were further discovered in esophageal squamous cell carcinoma (ESCC). Notably, pyrroline-5-carboxylate reductase 2 (PYCR2) and uridine phosphorylase 1 (UPase1) were found to be altered in ESCC. The spatially resolved metabolomics reveal what occurs in cancer at the molecular level, from metabolites to enzymes, and thus provide insights into the understanding of cancer metabolic reprogramming.

Monte Carlo study of TG-43 dosimetry parameters of GammaMed Plus high dose rate 192 Ir brachytherapy source using TOPAS.

PURPOSE: To develop a simulation model for GammaMed Plus high dose rate 192 Ir brachytherapy source in TOPAS Monte Carlo software and validate it by calculating the TG-43 dosimetry parameters and comparing them with published data. METHODS: We built a model for GammaMed Plus high dose rate brachytherapy source in TOPAS. The TG-43 dosimetry parameters including air-kerma strength SK , dose-rate constant Λ, radial dose function gL (r), and 2D anisotropy function F(r,θ) were calculated using Monte Carlo simulation with Geant4 physics models and NNDC 192 Ir spectrum. Calculations using an old 192 Ir spectrum were also carried out to evaluate the impact of incident spectrum and cross sections. The results were compared with published data. RESULTS: For calculations using the NNDC spectrum, the air-kerma strength per unit source activity SK /A and Λ were 1.0139 × 10-7 U/Bq and 1.1101 cGy.h-1 .U-1 , which were 3.56% higher and 0.62% lower than the reference values, respectively. The gL (r) agreed with reference values within 1% for radial distances from 2 mm to 20 cm. For radial distances of 1, 3, 5, and 10 cm, the agreements between F(r,θ) from this work and the reference data were within 1.5% for 15° < Î¸ < 165°, and within 4% for all θ values. The discrepancies were attributed to the updated source spectrum and cross sections. They caused deviations of the SK /A of 2.90% and 0.64%, respectively. As for gL (r), they caused average deviations of -0.22% and 0.48%, respectively. Their impact on F(r,θ) was not quantified for the relatively high statistical uncertainties, but basically they did not result in significant discrepancies. CONCLUSION: A model for GammaMed Plus high dose rate 192 Ir brachytherapy source was developed in TOPAS and validated following TG-43 protocols, which can be used for future studies. The impact of updated incident spectrum and cross sections on the dosimetry parameters was quantified.

Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients: A phase II clinical trial.

OBJECTIVE: To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma (EC). METHODS: Eligible patients were aged 70 years or older and had treatment-naïve, histologically proven inoperable locally advanced EC. Enrolled patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions, concurrent with weekly infusion of nimotuzumab. The primary end point was the rate of more than grade 3 toxicities. RESULTS: From June 2011 to July 2016, 46 patients with stage II-IV EC with a median age of 76.5 years were enrolled. There were 10, 28 and 8 patients with stage II, III and IV disease, respectively. The common acute toxicities included esophagitis (grade 1-2, 75.4%; grade 3, 8.7%), pneumonitis (grade 1, 4.3%; grade 2, 6.5%; grade 3, 2.2%), leukopenia (grade 1-2, 60.9%; grade 3-4, 4.4%), gastrointestinal reaction (grade 1-2, 17.3%; grade 3, 2.2%), thrombocytopenia (grade 1-2, 21.7%; grade 3, 2.2%), and radiothermitis (grade 1-2, 39.2%). The incidence of grade 3-4 adverse effects was 17.4%. No grade 5 toxicities were observed. Clinical complete response, partial response, stable disease, and progressive disease were observed in 1 (2.2%), 31 (67.4%), 12 (26.1%), and 2 (4.3%) patients, respectively. The median overall survival (OS) and progression-free survival (PFS) were 17 and 10 months, respectively. The 2-, 3-, and 5-year OS and PFS rates were 30.4%, 21.7%, 19.6%, and 26.1%, 19.6%, 19.6%, respectively. CONCLUSIONS: Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical candidates. Further studies are warranted to confirm its therapeutic effects in elderly EC patients.

Efficacy and safety of concurrent chemoradiotherapy in ECOG 2 patients with locally advanced non-small-cell lung cancer: a subgroup analysis of a randomized phase III trial.

BACKGROUND: There is no consensus on the therapeutic approach to ECOG 2 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), despite the sizable percentage of these patients in clinical practice. This study focused on the efficacy, toxicity and the optimal chemotherapy regimen of CCRT in ECOG 2 patients in a phase III trial. METHODS: Patients capable of all self-care with bed rest for less than 50% of daytime were classified as ECOG 2 subgroup. A subgroup analysis was performed for ECOG 2 patients recruited in the phase III trial receiving concurrent EP (etoposide + cisplatin)/PC (paclitaxel + carboplatin) chemotherapy with intensity-modulated radiation therapy (IMRT) or three-dimensional conformal external beam radiation therapy (3D-CRT). RESULTS: A total of 71 ECOG 2 patients were enrolled into the study. Forty-six (64.8%) patients were treated with IMRT technique. The median overall survival (OS) and progression free survival (PFS) for ECOG 2 patients were 16.4 months and 9 months, respectively. No difference was observed in treatment compliance and toxicities between ECOG 2 patients and ECOG 0-1 patients. Within the ECOG 2 group (31 in the EP arm and 40 in the PC arm), median OS and 3-year OS were 15.7 months and 37.5% for the EP arm, and 16.8 months and 7.5% for the PC arm, respectively (p = 0.243). The incidence of grade ≥ 3 radiation pneumonitis was higher in the PC arm (17.5% vs. 0.0%, p = 0.014) with 5 radiation pneumonitis related deaths, while the incidence of grade 3 esophagitis was numerically higher in the EP arm (25.8% vs. 10.0%, p = 0.078). CONCLUSIONS: CCRT provided ECOG 2 patients promising outcome with acceptable toxicities. EP might be superior to PC in terms of safety profile in the setting of CCRT for ECOG 2 patients. Prospective randomized studies based on IMRT technique are warranted to validate our findings. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01494558. (Registered 19 December 2011).

Debulking Surgery Plus Radiation: Treatment Choice for Unresectable Stage III Thymic Carcinoma.

BACKGROUND: Total resection may not be achieved in patients with thymic carcinoma, particularly those with Masaoka stage III disease. Debulking surgery plus postoperative radiotherapy and radiation alone are treatment options for such patients. We aimed to compare the overall survival (OS) between patients with thymic carcinoma who underwent debulking surgery plus postoperative radiotherapy and those who underwent radiation alone. METHODS: This was a single-center retrospective study of patients histologically diagnosed as having Masaoka stage III thymic carcinoma between January 1980 and January 2010. Patients were classified into the following groups according to treatments received: debulking surgery plus radiotherapy (group A) and radiotherapy alone (group B). Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected. Survival time was calculated and compared between the groups using the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Of the 47 enrolled patients, 26 and 21 patients were categorized into groups A and B, respectively. There are no significant differences in the Eastern Cooperative Oncology Group performance status score, histological type, great vessel invasion, and chemotherapy proportion between the groups. The median radiation dose was 60 Gy in both groups. The 5-year OS rates were 54.4 and 0% in groups A and B, respectively (p = 0.019). No operation-induced mortality was recorded. CONCLUSION: For patients with unresectable Masaoka stage III disease, debulking surgery with radiotherapy is preferred, as this was proven to be more efficient than the radiation-alone procedure.

Stable and Active Oxidation Catalysis by Cooperative Lattice Oxygen Redox on SmMn2O5 Mullite Surface.

The correlation between lattice oxygen (O) binding energy and O oxidation activity imposes a fundamental limit in developing oxide catalysts, simultaneously meeting the stringent thermal stability and catalytic activity standards for complete oxidation reactions under harsh conditions. Typically, strong O binding indicates a stable surface structure, but low O oxidation activity, and vice versa. Using nitric oxide (NO) catalytic oxidation as a model reaction, we demonstrate that this conflicting correlation can be avoided by cooperative lattice oxygen redox on SmMn2O5 mullite oxides, leading to stable and active oxide surface structures. The strongly bound neighboring lattice oxygen pair cooperates in NO oxidation to form bridging nitrate (NO3-) intermediates, which can facilely transform into monodentate NO3- by a concerted rotation with simultaneous O2 adsorption onto the resulting oxygen vacancy. Subsequently, monodentate NO3- species decompose to NO2 to restore one of the lattice oxygen atoms that act as a reversible redox center, and the vacancy can easily activate O2 to replenish the consumed one. This discovery not only provides insights into the cooperative reaction mechanism but also aids the design of oxidation catalysts with the strong O binding region, offering strong activation of O2, high O activity, and high thermal stability in harsh conditions.

Postoperative radiotherapy is effective in improving survival of patients with stage pIII-N2 non-small-cell lung Cancer after pneumonectomy.

BACKGROUND: There were few reports of postoperative radiotherapy (PORT) in stage pIII-N2 Non-small-cell Lung Cancer (NSCLC) patients receiving pneumonectomy followed by adjuvant chemotherapy. This study aims to evaluate safety and efficacy of PORT among these patients. METHODS: Between Jan. 2004 and Dec. 2015, stage pIII-N2 NSCLC patients receiving pneumonectomy and adjuvant chemotherapy with or without PORT in our institution were retrospectively reviewed. RESULTS: Totally 119 patients were included, 32 patients receiving adjuvant chemotherapy and PORT (PORT group) and 87 receiving adjuvant chemotherapy alone (Control group). There were more patients with non-R0 resection in PORT group than Control group (25% vs. 8%, p = 0.031). In PORT group, ≥Grade 2 radiation-induced pneumonitis was 2/32. No severe radiation-related heart injury was observed. There was no PORT-related death. Of all patients, median follow-up time was 25 months. Median overall survival time (mOS) and median disease-free survival time (mDFS) were 46 months and 15 months, respectively. The PORT group had significantly better OS (not reached vs. 34 months, p = 0.003), DFS (19 months vs. 13 months, p = 0.024), local recurrence free survival (LRFS, p = 0.012), and distant metastasis free survival (DMFS, p = 0.047) than the Control group. As for failure pattern, PORT significantly reduced local regional failure rate (39.1% vs. 15.6%, p = 0.016). In subgroup analysis, patients with R0 resection (n = 104), OS and LRFS in PORT group were significantly longer, and PORT tended to increase DFS and DMFS. CONCLUSION: For patients with stage pIII-N2 NSCLC after pneumonectomy and adjuvant chemotherapy, PORT can improve OS, DFS, LRFS and DMFS with tolerable toxicity.

Pulmonary transit time derived from pulmonary angiography for the diagnosis of hepatopulmonary syndrome.

BACKGROUND & AIMS: Pulmonary transit time (PTT) is the transit time of blood from the right side of the heart to the left side of the heart. The aim of the present study was to evaluate the role of the PTT derived from pulmonary angiography in the diagnosis of hepatopulmonary syndrome (HPS). METHODS: From December 2014 to September 2015, all patients with chronic liver disease and/or portal hypertension undergoing a venous interventional radiologic procedure at our institution were eligible for inclusion in this prospective study. Pulmonary angiography was performed in all patients, and the PTT, which was defined as the time between opacification of the pulmonary trunk and the right border of the left atrium, was determined. RESULTS: A total of 53 patients were included, 20 of whom had a positive contrast-enhanced echocardiography result and an elevated alveolar-arterial oxygen gradient were considered to have HPS. PTT was significantly shorter in patients with HPS than in those without [median, 3.34 (interquartile range, 3.01-3.67) seconds vs 4.0 (interquartile range, 3.67-4.17) seconds; P < .001]. The area under the receiver operating characteristic curve of PTT for diagnosing HPS was 0.83 (95% confidence interval, 0.70-0.92). The optimal cut-off value of PTT for diagnosing HPS, based on Youden's index, was 3.55 seconds. The sensitivity, specificity and accuracy of PTT < 3.55 seconds for diagnosing HPS were 70%, 85% and 79% respectively. CONCLUSIONS: Pulmonary transit time derived from pulmonary angiography is useful for diagnosing HPS, especially for patients with intracardiac shunts and inadequate echocardiographic windows.

MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAD) is considered to be a highly aggressive disease with heterogeneous prognosis and the molecular mechanisms underlying tumor progression remain elusive. Growing evidence demonstrates that the dysregulation of microRNAs (miRNAs) plays an important role in various tumor processes. The aim of this study is to discover prognostic miRNA and investigate its role involved in progression of LAD. METHODS: Prognosis related miRNA was detected by miRNA microarray using formalin-fixed paraffin-embedded (FFPE) specimens from 87 patients with IIIA-N2 LAD. The cell proliferation was evaluated by Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS), and the migration/invasion was evaluated by transwell assay. The bioinformatics methods and luciferase reporter assay were applied to detect the relationship between miRNA and its target. The mRNA and protein levels of miRNA target were determined by quantitative real time polymerase chain reaction (qRT-PCR) analysis, western blot and enzyme-linked immunosorbent assay (ELISA). Changes of angiogenesis induced by miRNA was evaluated by human umbilical vein endothelial cell (HUVEC) tube formation assay. Immunohistochemistry (IHC) analysis was performed in FFPE specimens of patients to evaluate the correlation between miR-29c with microvessel density (MVD) and vascular endothelial growth factor A (VEGFA) expression. RESULTS: MiR-29c expression downregulation was significantly associated with unfavorable prognosis in IIIA-N2 LAD. MiR-29c inhibited cell proliferation, migration and invasion in cell lines. Integrated analysis revealed that VEGFA was a direct target of miR-29c. MiR-29c reduced the capability of tumor cells to promote HUVEC tube formation. The compromised cell proliferation, migration/invasion and angiogenesis induced by miR-29c mimic transfection were reversed by transfection of VEGFA expression plasmid. Furthermore, the correlation of miR-29c with MVD and VEGFA was confirmed in patients' samples. CONCLUSIONS: MiR-29c acts as a tumor suppressor by targeting VEGFA and may represent a promising prognostic biomarker as well as a potential therapeutic target for LAD.

Intensity-Modulated Radiation Therapy May Improve Local-Regional Tumor Control for Locally Advanced Non-Small Cell Lung Cancer Compared With Three-Dimensional Conformal Radiation Therapy.

BACKGROUND: Consistent results are lacking as regards the comparative effectiveness of intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Patients treated with definitive radiotherapy (RT) between 2002 and 2010 were retrospectively reviewed. Overall survival (OS), local-regional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were compared among patients irradiated with different techniques. The association between RT technique and survival indexes was assessed in a Cox proportional hazard regression model. Propensity score matching (PSM) was used to balance known confounding factors. RESULTS: A total of 652 patients were eligible for analysis, including 206 with 3DCRT and 446 with IMRT. The median OS of the 3DCRT and IMRT groups were 19.4 and 23.3 months, with the 5-year rate of 13% and 19%, respectively (p = .043). Multivariate analysis identified IMRT as an independent favorable factor associated with LRPFS and DMFS. PSM analysis further verified the beneficial effect of IMRT on LRPFS. No difference in OS or PFS was observed between the two techniques. Subgroup analysis revealed that IMRT might be differentially more effective in both OS and LRPFS among patients who were female, nonsmokers, with adenocarcinoma, or without weight loss. There was a significant reduction of lung toxicity and similar esophagus toxicity in the IMRT group when compared with the 3DCRT group. CONCLUSION: IMRT may confer superior LRPFS and comparable OS than can be achieved with 3DCRT in LA-NSCLC, along with the reduction of pulmonary toxicity. IMPLICATIONS FOR PRACTICE: Based on the largest number of patients from a single institution, the present study demonstrated that intensity-modulated radiotherapy (IMRT) could provide superior local-regional progression-free survival and similar overall survival compared with the traditional three-dimensional conformal radiotherapy (3DCRT) for stage III non-small cell lung cancer (NSCLC). IMRT was also found to be associated with the significantly decreased incidence of pulmonary toxicity. These results suggest that IMRT should be considered a surrogate for 3DCRT in locally advanced NSCLC and might be the preferred option for a female nonsmoker with adenocarcinoma and a potentially high risk of pulmonary toxicity from radiotherapy.

Further understanding of an uncommon disease of combined small cell lung cancer: clinical features and prognostic factors of 114 cases.

OBJECTIVE: Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of small cell lung cancer (SCLC) and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment. METHODS: Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors. RESULTS: One hundred and fourteen patients were enrolled, with a median age of 59 (range: 20-79) years old. The most common combined component was squamous cell carcinoma (52.6%). Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients (70.2%) received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival (OS) was 26.2 months. On univariate analysis, smoking (P=0.029), Karnofsky performance score (KPS) <80 (P=0.000), advanced TNM stage (P=0.000), no surgery (P=0.010), positive resection margin (P=0.000), positive lymph nodes ≥4 (P=0.000), positive lymph node ratio >10% (P=0.000) and non-multimodality treatment (P=0.004) were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio >10% were poor prognostic features. CONCLUSIONS: C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio >10% are poor prognostic factors.

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy--retrospective analysis of 203 cases.

BACKGROUND: For patients with locally advanced non-small-cell lung cancer (LA-NSCLC), the role of consolidation chemotherapy (CCT) following concurrent chemoradiotherapy (CRT) is partially defined. The aim of this study was to evaluate the efficacy and toxicity of CCT. METHODS: The characteristics of LA-NSCLC patients treated with curative concurrent CRT from 2001 to 2010 were retrospectively reviewed. RESULTS: Among 203 patients, 113 (55.7 %) patients received CCT. The median number of delivered CCT was 3 and 89.4 % patients completed ≥2 cycles. The OS was significantly better for patients in the CCT group compared with that in the non-CCT group (median OS, 27 months vs. 16 months; 5-year OS, 30.4 % vs. 22.5 %; p = 0.012). The median PFS were 12 months in the CCT group and 9 months in the non-CCT group (p = 0.291). The survival advantages of CCT were significant for males (HR: 0.63; 95 % CI, 0.44 - 0.90), patients with age < 60 years (HR: 0.63; 95 % CI, 0.42 - 0.95), non-squamous histology (HR: 0.44; 95 % CI, 0.25 - 0.76), pretreatment KPS ≥ 80 (HR: 0.67; 95 % CI, 0.48 - 0.93), stage IIIb (HR: 0.64; 95 % CI, 0.43 - 0.95), stable disease (HR: 0.31; 95 % CI, 0.14 - 0.65) and radiotherapy dose ≥ 60 Gy (HR: 0.69; 95 % CI, 0.48 - 1.00). There was no significant difference between the CCT group and the non-CCT group regarding treatment-related toxicities. CONCLUSIONS: CCT might further prolong survival compared with CRT alone for LA-NSCLC without increasing treatment-related toxicities, especially for males, patients with age < 60 years, non-squamous histology, pretreatment KPS ≥ 80, stage IIIb, stable disease and radiotherapy dose ≥ 60 Gy. Large size prospective investigations that incorporate patient characteristics and treatment response are warranted to validate our findings.

Global and targeted metabolomics of esophageal squamous cell carcinoma discovers potential diagnostic and therapeutic biomarkers.

Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.

[Prognostic value of AJCC TNM Staging 7th edition in limited-stage small cell lung cancer: validation in 437 patients].

OBJECTIVE: To explore the impact of AJCC TNM Staging 7th edition on survival outcome of limited stage small cell lung cancer (SCLC). METHODS: Four hundred and thirty-seven SCLC patients with completed diagnosis and treatment data treated in our department between January 1996 and December 2006 were reclassified according to the AJCC TNM Staging 7th edition. The patients of stages IA, IB, IIA, IIB, IIIA, IIIB were 8, 44, 7, 64, 192 cases, respectively. Kaplan-Meier method was used for survival analysis and log-rank test was used to identify the prognostic factors. The survival rate was determined using chi-square test. RESULTS: The median follow-up time was 64 months. The median survival time was 26.2 months and median progression free survival time was 13.7 months. The 1-, 2- and 5-year overall survival rates were 86.0%, 52.7%, and 29.7%, respectively. The log-rank test showed that TNM stage is a statistically significant prognostic factor for OS in LS-SCLC (P<0.001). TNM staging system generally allowed a good separation in pairwise comparison for OS between successive stages except there was no significant difference between stages I and II (P=0.061). The 5-year progression free survival rates of patients of stage I, II, IIIA and IIIB were 53.2%, 43.2%, 16.8%, and 10.9%, respectively. TNM stage also was a statistically significant prognostic factor for PFS in LS-SCLC (P<0.001), but there was no significant difference between successive stages (P>0.05 for all). The T staging confirmed significant influence on OS (P<0.001) with no significant difference between successive stages (P>0.05 for all), while T stage was not a significant prognostic factor for PFS in the LS-SCLC patients (P=0.194). N stage also had a significant influence on OS (P<0.001), but with no significant differences between successive stages except N1 and N2 (P=0.001). N staging also showed significant influence on PFS (P=0.001), but with no significant difference between successive stages (P>0.05) except that between the 5-year survival rates of N2 and N3 cases (P=0.013). The cumulative brain metastasis rates of stages I, II, IIIA, and stage IIIB were 17.3%, 28.6%, 33.3%, and 35.8%, respectively(P=0.072), and were 12.8% and 30.8% for pathological stage I and clinical stage I (P=0.203). CONCLUSION: AJCC TNM Staging 7th edition criteria for LS-SCLC patients have a high prognostic impact and therefore are preferable in clinical practice and future therapeutic trials.