The relationship between circulating metabolites and prostate hyperplasia: a Mendelian randomization study.

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.

Toward large-scale, ordered and tunable Majorana-zero-modes lattice on iron-based superconductors.

Majorana excitations are the quasiparticle analog of Majorana fermions in solid materials. Typical examples are the Majorana zero modes (MZMs) and the dispersing Majorana modes. When probed by scanning tunneling spectroscopy, the former manifest as a pronounced conductance peak locating precisely at zero-energy, while the latter behaves as constant or slowly varying density of states. The MZMs obey non-abelian statistics and are believed to be building blocks for topological quantum computing, which is highly immune to the environmental noise. Existing MZM platforms include hybrid structures such as topological insulator, semiconducting nanowire or 1D atomic chains on top of a conventional superconductor, and single materials such as the iron-based superconductors (IBSs) and 4Hb-TaS2. Very recently, ordered and tunable MZM lattice has also been realized in IBS LiFeAs, providing a scalable and applicable platform for future topological quantum computation. In this review, we present an overview of the recent local probe studies on MZMs. Classified by the material platforms, we start with the MZMs in the iron-chalcogenide superconductors where FeTe0.55Se0.45and (Li0.84Fe0.16)OHFeSe will be discussed. We then review the Majorana research in the iron-pnictide superconductors as well as other platforms beyond the IBSs. We further review recent works on ordered and tunable MZM lattice, showing that strain is a feasible tool to tune the topological superconductivity. Finally, we give our summary and perspective on future Majorana research.

Nanoscale Manipulation of Wrinkle-Pinned Vortices in Iron-Based Superconductors.

The controlled manipulation of Abrikosov vortices is essential for both fundamental science and logical applications. However, achieving nanoscale manipulation of vortices while simultaneously measuring the local density of states within them remains challenging. Here, we demonstrate the manipulation of Abrikosov vortices by moving the pinning center, namely one-dimensional wrinkles, on the terminal layers of Fe(Te,Se) and LiFeAs, by utilizing low-temperature scanning tunneling microscopy/spectroscopy (STM/S). The wrinkles trap the Abrikosov vortices induced by the external magnetic field. In some of the wrinkle-pinned vortices, robust zero-bias conductance peaks are observed. We tailor the wrinkle into short pieces and manipulate the wrinkles by using an STM tip. Strikingly, we demonstrate that the pinned vortices move together with these wrinkles even at high magnetic field up to 6 T. Our results provide a universal and effective routine for manipulating wrinkle-pinned vortices and simultaneously measuring the local density of states on the iron-based superconductor surfaces.

Observation of magnetic adatom-induced Majorana vortex and its hybridization with field-induced Majorana vortex in an iron-based superconductor.

Braiding Majorana zero modes is essential for fault-tolerant topological quantum computing. Iron-based superconductors with nontrivial band topology have recently emerged as a surprisingly promising platform for creating distinct Majorana zero modes in magnetic vortices in a single material and at relatively high temperatures. The magnetic field-induced Abrikosov vortex lattice makes it difficult to braid a set of Majorana zero modes or to study the coupling of a Majorana doublet due to overlapping wave functions. Here we report the observation of the proposed quantum anomalous vortex with integer quantized vortex core states and the Majorana zero mode induced by magnetic Fe adatoms deposited on the surface. We observe its hybridization with a nearby field-induced Majorana vortex in iron-based superconductor FeTe0.55Se0.45. We also observe vortex-free Yu-Shiba-Rusinov bound states at the Fe adatoms with a weaker coupling to the substrate, and discover a reversible transition between Yu-Shiba-Rusinov states and Majorana zero mode by manipulating the exchange coupling strength. The dual origin of the Majorana zero modes, from magnetic adatoms and external magnetic field, provides a new single-material platform for studying their interactions and braiding in superconductors bearing topological band structures.

A comprehensive evaluation of single nucleotide polymorphisms associated with osteosarcoma risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with osteosarcoma (OS) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with OS. METHODS: Databases were searched to identify association studies of SNPs and OS published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with OS susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with OS susceptibility. REGISTRATION: INPLASY202040023.

Nearly quantized conductance plateau of vortex zero mode in an iron-based superconductor.

Majorana zero modes (MZMs) are spatially localized, zero-energy fractional quasiparticles with non-Abelian braiding statistics that hold promise for topological quantum computing. Owing to the particle-antiparticle equivalence, MZMs exhibit quantized conductance at low temperature. By using variable-tunnel-coupled scanning tunneling spectroscopy, we studied tunneling conductance of vortex bound states on FeTe0.55Se0.45 superconductors. We report observations of conductance plateaus as a function of tunnel coupling for zero-energy vortex bound states with values close to or even reaching the 2e 2/h quantum conductance (where e is the electron charge and h is Planck's constant). By contrast, no plateaus were observed on either finite energy vortex bound states or in the continuum of electronic states outside the superconducting gap. This behavior of the zero-mode conductance supports the existence of MZMs in FeTe0.55Se0.45.

Evidence for Majorana bound states in an iron-based superconductor.

The search for Majorana bound states (MBSs) has been fueled by the prospect of using their non-Abelian statistics for robust quantum computation. Two-dimensional superconducting topological materials have been predicted to host MBSs as zero-energy modes in vortex cores. By using scanning tunneling spectroscopy on the superconducting Dirac surface state of the iron-based superconductor FeTe0.55Se0.45, we observed a sharp zero-bias peak inside a vortex core that does not split when moving away from the vortex center. The evolution of the peak under varying magnetic field, temperature, and tunneling barrier is consistent with the tunneling to a nearly pure MBS, separated from nontopological bound states. This observation offers a potential platform for realizing and manipulating MBSs at a relatively high temperature.

Serum peptide expression and treatment responses in patients with advanced non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation.

ALK-rearrangement in non-small-cell lung cancer (NSCLC).

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large-cell lymphoma. Since then, ALK has been associated with other types of cancers, including non-small-cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK-rearrangement (ALK-R), and the ALK-tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung cancer and predictors of response to crizotinib therapy.

Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s rRNA as the most stable endogenous control gene using geNorm and NormFinder algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK-negative NSCLC patients (n = 32) were quantified using real-time reverse transcriptase quantitative polymerase chain reaction. The expression levels of miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%, respectively. Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362-5p were significantly associated with progression-free survival (p = 0.015). Thus, in this preliminary investigation, we identified a potential panel of 3 microRNAs for distinguishing between patients with ALK-positive and ALK-negative NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.

Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report.

A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator.

Serum CEA level change and its significance before and after Gefitinib therapy on patients with advanced non-small cell lung cancer.

OBJECTIVE: The aim of this study was to explore change and significance of serum carcino-embryonic antigen (CEA) before and after gefitinib therapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Forty patients with advanced NSCLCs in III~IV stages were selected as study objects given gefitinib therapy combined with routine local radiotherapy until tumor progression or intolerable toxicity. After treatment, all patients were divided into control and non-control groups according to the results of evaluation based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors in 2009). Peripheral fasting blood from all patients was collected in the early morning and serum CEA was assessed by electro-chemiluminescence immunoassay (ECLIA) before and after treatment. Before treatment, patients were divided into high CEA group (CEA level > 50 ng/mL) and low CEA group (CEA level ≤ 50 ng/mL). Adverse reactions were noted and progression-free survival (PFS) in both groups was recorded after long-term follow-up that ended in December, 2012. RESULTS: There was no difference between control and non-control groups in CEA level before treatment (P>0.05), whereas serum CEA decreased more markedly lower in the control group after treatment (P<0.01). All patients were divided into high CEA group (26) and low CEA group (14) according to serum CEA level. There was no statistically significant difference between two groups in adverse reactions (P>0.05) but the rate in former group was lower. Additionally, survival rates at 9 and 12 months in high CEA group were clearly higher than in the low CEA group (P<0.01). CONCLUSIONS: Serum CEA level can serve as a biochemical index to evaluate the prognosis with gefitinib treatment for NSCLC.

Whole brain radiotherapy plus chemotherapy in the treatment of brain metastases from lung cancer: a meta-analysis of 19 randomized controlled trails.

OBJECTIVE: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis based on randomized controlled trials (RCTs). METHODS: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012. After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software, with funnel plot evaluation of publication bias. RESULTS: 19 RCTs involving 1,343 patients were included. The meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective with regard to the objective response rate (OR = 2.30, 95% CI = 1.79-2.98; P < 0.001); however, the incidences of gastrointestinal reactions (RR = 3.82, 95% CI = 2.33-6.28, P <0.001), bone marrow suppression (RR = 5.49, 95% CI = 3.65-8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39-86.59; P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77-5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61-4.68; P < 0.001) in patients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obvious publication bias detected. CONCLUSION: WBRT plus chemotherapy can obviously improve total efficacy rate, but also increases the incidence of adverse reactions compared to WBRT alone. From the limitations of this study, more large-scale, high-quality RCTs are suggested for further verification.

Identification and expression of a tumor-associated antigen in esophageal squamous cell carcinoma.

OBJECTIVE: To search for novel tumor associated antigens (TAA) in esophageal squamous cell carcinoma (ESCC). METHODS: The proteins extracted from tissues of ESCC were separated by two dimensional polyacrylamide gel electrophoresis and transferred to PVDF membrane. Sera from ESCC patients and healthy individuals were used for primary antibodies for Western blot analysis. The differential spots were excised for trypsin hydrolysis and the tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The identified TAA of ESCC was validated by immunohistochemical staining (IHC). RESULTS: Sera from ESCC patients yielded multiple positive spots, and one 28 800 Da protein that exhibited positive reactivity with 60% (12/20) sera of ESCC patients and only 5% (1/20) sera of healthy controls (P<0.01). The 28 800 Da protein was identified as phosphoglycerate mutase 1 (PGAM1) by MALDI-TOF-MS. Immunohistochemical analysis showed that PGAM1 was located in both cytoplasm and nucleus, and had a higher expression in cancer tissues. CONCLUSION: PGAM1 maybe a candidate of ESCC.

A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved. METHOD: In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The EGFR mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively. RESULTS: As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma. CONCLUSIONS: When using body fluids for EGFR mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.

Graphene nanosheets-polypyrrole hybrid material as a highly active catalyst support for formic acid electro-oxidation.

A novel electrode material based on graphene oxide (GO)-polypyrrole (PPy) composites was synthesized by in situ chemical oxidation polymerization. Palladium nanoparticles (NPs) with a diameter of 4.0 nm were loaded on the reduced graphene oxide(RGO)-PPy composites by a microwave-assisted polyol process. Microstructure analysis showed that a layer of coated PPy film with monodisperse Pd NPs is present on the RGO surface. The Pd/RGO-PPy catalysts exhibit excellent catalytic activity and stability for formic acid electro-oxidation when the weight feed ratio of GO to pyrrole monomer is 2:1. The superior performance of Pd/RGO-PPy catalysts may arise from utilization of heterogeneous nucleation sites for NPs and the greatly increased electronic conductivity of the supports.

[Erlotinib in the treatment of advanced non-small-cell lung cancer (NSCLC)].

OBJECTIVE: Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement of survival in non-small-cell lung cancer (NSCLC) after the failure of front-line chemotherapy. The aim of this study was to evaluate the antitumor efficacy and toxicity of Erlotinib in the treatment of advanced NSCLC patients. METHODS: A total of 104 patients with advanced NSCLC admitted in our department during December 2006 to November 2008 were enrolled in this study. Eligible patients received oral Erlotinib 150 mg/d until disease progression or intolerable toxicity. Best clinical response was determined using RECIST criteria, the adverse events were evaluated according to the NCI criteria. RESULTS: The total effective rate was 27.9% (29/104) and the clinical benefit was 76.0% (79/104). The median progression-free survival was 5.1 months (95%CI 4.0 - 8.0). The median survival time was 13.1 months (95%CI 10.0 - 15.7). The 1-year survival rate was 61.5%. Significant survival benefit from erlobinib therapy was observed for patients with good personal status (HR 0.56, P = 0.006), adenocarcinoma (HR 0.43, P = 0.004) and skin rash (HR 0.46, P = 0.005). But patients with smoking (HR 2.75, P < 0.001) and liver metastasis (HR 2.91, P = 0.002) add the risk of death. The adverse events were mild (grade < or = 2), most common toxicities were skin rash in 73.1% (76/104) and diarrhea in 41.3% (43/104). Only 6.7% (7/104) patients got adverse events of grade > or = 3. CONCLUSION: Erlotinib is an effective and well-tolerated treatment option for advanced NSCLC and could offer an alternative for patients after the failure of first-line chemotherapy, unsuitable for or not wishing to receive chemotherapy.

[Inhibitory effects of a combination of rmhTRAIL and gemcitabine on human non-small cell lung cancer cell line NCI-H460 cells in vitro and in vivo].

OBJECTIVE: To evaluate the inhibitory effects of recombinant mutant tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) combined with chemotherapeutic agent gemcitabine (GEM) on human lung cancer cell line NCI-H460 cells in vitro and in vivo. METHODS: MTT was used to evaluate the cytotoxic effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI-H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor-bearing nude mice were randomly divided into 6 groups (n = 6): negative control group (to be injected intraperitoneally with normal saline); rmhTRAIL group; GEM group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP group. The tumor size was measured every 3 - 4 days. Twenty one days after the administration of different drugs the mice were killed and the tumors were taken out and weighed. RESULTS: The growth inhibition of NCI-H460 cells was dose-dependent after exposure to rmhTRAIL, GEM alone or together. The combination of rmhTRAIL and GEM showed a synergistic inhibitory effect at different concentrations. The relative tumor volume of rmhTRAIL group, rmhTRAIL plus GEM group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 +/- 3.04, 2.53 +/- 1.25, 4.52 +/- 2.87, and 1.69 +/- 0.97, respectively, all significantly smaller than that of the negative control group (8.82 +/- 5.62, P < 0.05 or P < 0.01). The tumor weight of these four groups were (2.23 +/- 0.29) g, (1.12 +/- 0.77) g, (2.51 +/- 0.87) g, and 0.60 +/- 0.18 g, respectively, all significantly less then that of the negative control group (4.71 g +/- 0.97 g, all P < 0.01). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were significantly smaller than those of either rmhTRAIL group or GEM group (P < 0.05 and P < 0.01, respectively). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM and DDP group were significantly smaller than those of either rmhTRAIL group or GEM plus DDP group (P < 0.05 and P < 0.01, respectively). CONCLUSION: The combination of rmhTRAIL and GEM has a synergistic inhibitory effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.

[Circulating endothelial cells in the peripheral blood of advanced NSCLC patients].

OBJECTIVE: To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient. METHODS: Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry. RESULTS: The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004). CONCLUSION: Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment.

[Effect of hypoxic radiosensitizer sodium glycididazole on long-term result of radiotherapy for nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma. METHODS: Between May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis. RESULTS: The clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy. CONCLUSION: Sodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.