Combined targeted therapy and immunotherapy in anaplastic thyroid carcinoma with distant metastasis: A case report.

BACKGROUND: Anaplastic thyroid carcinoma (ATC), also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers[1]. It has poor prognosis, and is the leading cause of death from malignant thyroid tumors. The one-year survival rate is 20%, with a median overall survival (OS) of only 5 mo[2]. The aim of this report is to provide our experience in the diagnosis and treatment of ATC. CASE SUMMARY: A patient with a thyroid mass underwent surgical treatment after developing symptoms of hoarseness. The resected tumor was pathologically diagnosed as ATC. Imaging examination revealed organ and lymph node metastasis. After multiple cycles of chemotherapy and local radiotherapy, the metastases were not relieved and gradually increased in size and new metastases appeared. The patient immediately received immunotherapy combined with targeted therapy. During treatment, immune-related adverse reactions occurred, which were improved after symptomatic treatment, and tolerated by the patient. The OS of the patient was more than 30 mo after immunotherapy combined with targeted therapy. CONCLUSION: For metastatic ATC, surgical treatment, radiotherapy and chemotherapy have no significant effect on remission of the disease. However, immunotherapy has made a breakthrough in the treatment of ATC.

Mutational landscape of nasopharyngeal carcinoma based on targeted next-generation sequencing: implications for predicting clinical outcomes.

BACKGROUND: The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). METHODS: A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests. RESULTS: The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. CONCLUSIONS: In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.

Efficient Multi-Material Structured Thin Film Transfer to Elastomers for Stretchable Electronic Devices.

Stretchable electronic devices must conform to curved surfaces and display highly reproducible and predictable performance over a range of mechanical deformations. Mechanical resilience in stretchable devices arises from the inherent robustness and stretchability of each component, as well as from good adhesive contact between functional and structural components. In this work, we combine bench-top thin film structuring with solvent assisted lift-off transfer to produce flexible and stretchable multi-material thin film devices. Patterned wrinkled thin films made of gold (Au), silicon dioxide (SiO2), or indium tin oxide (ITO) were produced through thermal shrinking of pre-stressed polystyrene (PS) substrates. The wrinkled films were then transferred from the PS to poly(dimethylsiloxane) (PDMS) substrates through covalent bonding and solvent-assisted dissolution of the PS. Using this approach, different materials and hybrid structures could be lifted off simultaneously from the PS, simplifying the fabrication of multi-material stretchable thin film devices. As proof-of-concept, we used this structuring and transfer method to fabricate flexible and stretchable thin film heaters. Their characterization at a variety of applied voltages and under cyclic tensile strain showed highly reproducible heating performance. We anticipate this fabrication method can aid in the development of flexible and stretchable electronic devices.

Graft-Then-Shrink: Simultaneous Generation of Antifouling Polymeric Interfaces and Localized Surface Plasmon Resonance Biosensors.

Antifouling polymer coatings that are simple to manufacture are crucial for the performance of medical devices such as biosensors. "Grafting-to", a simple technique where presynthesized polymers are immobilized onto surfaces, is commonly employed but suffers from nonideal polymer packing leading to increased biofouling. Herein, we present a material prepared via the grafting-to method with improved antifouling surface properties and intrinsic localized surface plasmon resonance (LSPR) sensor capabilities. A new substrate shrinking fabrication method, Graft-then-Shrink, improved the antifouling properties of polymer-coated Au surfaces by altering graft-to polymer packing while simultaneously generating wrinkled Au structures for LSPR biosensing. Thiol-terminated, antifouling, hydrophilic polymers were grafted to Au-coated prestressed polystyrene (PS) followed by shrinking upon heating above the PS glass transition temperature. Interestingly, the polymer molecular weight and hydration influenced Au wrinkling patterns. Compared to Shrink-then-Graft controls, where polymers are immobilized post shrinking, Graft-then-Shrink increased the polymer content by 76% in defined footprints and improved the antifouling properties as demonstrated by 84 and 72% reduction in macrophage adhesion and protein adsorption, respectively. Wrinkled Au LSPR sensors had sensitivities of ∼200-1000 Δλ/ΔRIU, comparing favorably to commercial LSPR sensors, and detected biotin-avidin and desthiobiotin-avidin complexation in a concentration-dependent manner using a standard plate reader and a 96-well format.

Radiotranscriptomics signature-based predictive nomograms for radiotherapy response in patients with nonsmall cell lung cancer: Combination and association of CT features and serum miRNAs levels.

PURPOSE: We aimed to establish radiotranscriptomics signatures based on serum miRNA levels and computed tomography (CT) texture features and develop nomogram models for predicting radiotherapy response in patients with nonsmall cell lung cancer (NSCLC). METHODS: We first used established radioresistant NSCLC cell lines for miRNA selection. At the same time, patients (103 for training set and 71 for validation set) with NSCLC were enrolled. Their pretreatment contrast-enhanced CT texture features were extracted and their serum miRNA levels were obtained. Then, radiotranscriptomics feature selection was implemented with the least absolute shrinkage and selection operator (LASSO), and signatures were generated by logistic or Cox regression for objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Afterward, radiotranscriptomics signature-based nomograms were constructed and assessed for clinical use. RESULTS: Four miRNAs and 22 reproducible contrast-enhanced CT features were used for radiotranscriptomics feature selection and we generated ORR-, OS-, and PFS- related radiotranscriptomics signatures. In patients with NSCLC who received radiotherapy, the radiotranscriptomics signatures were independently associated with ORR, OS, and PFS in both the training (OR: 2.94, P < .001; HR: 2.90, P < .001; HR: 3.58, P = .001) and validation set (OR: 2.94, P = .026; HR: 2.14, P = .004; HR: 2.64, P = .016). We also obtained a satisfactory nomogram for ORR. The C-index values for the ORR nomogram were 0.86 [95% confidence interval (CI), 0.75 to 0.92] in the training set and 0.81 (95% CI, 0.69 to 0.89) in the validation set. The calibration-in-the-large and calibration slope performed well. Decision curve analysis indicated a satisfactory net benefit. CONCLUSIONS: The radiotranscriptomics signature could be an independent biomarker for evaluating radiotherapeutic responses in patients with NSCLC. The radiotranscriptomics signature-based nomogram could be used to predict patients' ORR, which would represent progress in individualized medicine.

Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target.

Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients' radiosensitivity and prognosis. Overall, our study fully investigated the effect of miR-1246 on radiosensitivity and comprehensively investigated the potential of miR-1246 as a prognostic biomarker and radiotherapy sensitization target.

Dendritic fibrous nano-silica & titania (DFNST) spheres as novel cataluminescence sensing materials for the detection of diethyl ether.

Selective and controllable cataluminescence (CTL) sensors for volatile organic compounds (VOCs) are significant for chemical safety, environmental monitoring, health effects on human beings, and so forth. Most of the exploited CTL-based sensors suffer relatively low response and poor selectivity because of their high sensitivities to interferential substances. In this investigation, dendritic fibrous nano-silica & titania (DFNST) spheres have been synthesized as novel sensing materials and the corresponding DFNST-based CTL sensor has been fabricated to detect diethyl ether with high selectivity via a method of utilizing one 440 nm bandpass filter. The as-prepared DFNST hybrids not only keep the excellent dendritic fibrous morphology but also bear ca. 21 wt% catalytic titanium oxide of anatase crystalline structure. The DFNST-based sensor exhibits extremely strong CTL emission at 440 nm toward diethyl ether against other VOCs like acetone, ethyl acetate, butanol, and so forth. The high response can be attributed to the unique architectural texture of DFNST. Under the optimum parameters, ether could be easily detected in a wide range from 2.0 to 40.0 mM with a fine detection limit of 1.55 mM (S/N = 3). Furthermore, the working life of this CTL sensor is satisfactory with outstanding stability and durability, far from damaging the morphology and activity of the DFNST sensing material. In conclusion, it is expected that this novel sensing material, the relevant CTL sensor, and the approach of employing the bandpass filter will be significant for the detection of diethyl ether in actual applications.

Coronin3 Promotes Nasopharyngeal Carcinoma Migration And Invasion By Induction Of Epithelial-To-Mesenchymal Transition.

PURPOSE: Coronin3 is a cytoskeletal protein that has been implicated in metastasis in many cancer types. Here, we demonstrate its effect in nasopharyngeal carcinoma (NPC) and propose a new probable mechanism of CORO1C-mediated cell migration and invasion by regulation of epithelial-to-mesenchymal transition (EMT) and CDH11. PATIENTS AND METHODS: First, we measured the differential expression of CORO1C between NPC and non-NPC cells in both cell lines and clinical specimens, using public datasets. Then, we investigated its relationship with clinicopathological factors and its potential as a biomarker to predict the prognosis of NPC patients. We also explored its influence on the cell behaviors of migration and invasion by upregulating and downregulating the expression of CORO1C and attempted to determine the underlying mechanism. RESULTS: The results verified our original hypothesis. CORO1C was overexpressed in both NPC cell lines and clinical specimens, in both public datasets and our own samples. NPC patients with lower CORO1C expression levels in primary cancer tissues had longer OS (hazard ratio [HR] 1.814, 95% CI 0.831-3.960, p=0.0341) and PFS (HR 1.798, 95% CI 0.907-3.564, p=0.0155), indicating that it could be used as a prognostic biomarker. It was also confirmed that CORO1C enhanced cells' migration and invasion abilities, by inducing morphological and marker changes typical of EMT. Finally, we found that expression was correlated with and regulated CDH11 expression in NPC cell lines. CONCLUSION: Our study provided evidence for the contribution of CORO1C to NPC metastasis, and indicated that it could be used as a new therapeutic target and prognostic biomarker.

A case report of targeted therapy with apatinib in a patient with recurrent high grade glioma.

RATIONALE: Despite the approval of antiangiogenic therapy for high grade glioma (HGG) patients, survival benefits are still limited. New treatment plans have always been developed to improve the survival. PATIENT CONCERNS: A 26-year-old woman was admitted to our hospital for distending pain of head and eye. DIAGNOSES: Resonance imaging (MRI) revealed a large spherical heterogeneously enhancing, mixed cystic and solid mass in the right frontal region, and the midline shifted. INTERVENTION: The patient received apatinib therapy for positive vascular endothelial growth factor. OUTCOMES: A partial response was observed after 4 weeks and remains sustained until now. LESSONS: It suggests that apatinib might be a feasible option for the treatment in advanced HGG patients or patients with poor physical condition.

Which is the optimal threshold for defining functional lung in single-photon emission computed tomography lung perfusion imaging of lung cancer patients?

PURPOSE: The aim of this study was to investigate the optimal threshold for the functional lung (FL) definition of single-photon emission computed tomography (SPECT) lung perfusion imaging. PATIENTS AND METHODS: Forty consecutive stage III non-small-cell lung cancer patients underwent SPECT lung perfusion scans and PET/CT scans for treatment planning, and the images were coregistered. Total lung and perfusion lung volumes corresponding to 10, 20, …, 60% of the maximum SPECT count were segmented automatically. The SPECT-weighted mean lung dose (SWMDx%) and the percentage of FL volume receiving more than 20 Gy (Fx%V20) of different thresholds were investigated using SPECT-weighted dose-volume histograms. Receiver-operator characteristic curves were used to identify SWMD and FV20 of different thresholds in predicting the incidence of radiation pneumonitis (RP). RESULTS: Eleven (27.5%) patients developed RP (grades 1, 2, 3, and 4 were 10.0, 7.5, 7.5, and 2.5%, respectively) after treatment. The largest area under the receiver-operator characteristic curve was 0.881 for the ability of SWMD to predict RP with 20% as the threshold and 0.928 for the ability of FV20 with 20% as the threshold. CONCLUSION: The SWMD20% and FV20 of FL using 20% of the maximum SPECT count as the threshold may be better predictors for the risk of RP.

Anatomic distribution of supraclavicular lymph node in patients with esophageal cancer.

PURPOSE: Definitive chemoradiation therapy remains the standard of care for patients with localized esophageal carcinoma who choose nonsurgical management. However, there is no consensus regarding delineation of the nodal clinical target volume (CTVn), especially for lower cervical lymph nodes. This study aimed to map the location of metastatic supraclavicular lymph nodes in thoracic esophageal carcinoma patients with supraclavicular node involvement and generate an atlas to delineate the CTVn for elective nodal radiation of esophageal squamous cell carcinoma. PATIENTS AND METHODS: In this study, the supraclavicular regional lymph node was further divided into four subgroups. The locations of the involved supraclavicular nodes for all patients were then transferred onto a template computed tomography (CT) image. A volume probability map was then generated with nodal volumes, and was displayed on the template CT to provide a visual impression of nodal frequencies and anatomic distribution. RESULTS: We identified 154 supraclavicular nodal metastases based on CT image in 96 patients. Of these, 29.2% were located in group I region, 59.7% in group II region, 10.4% in group III region, and 0.7% in group IV region. CONCLUSION: On the basis of our study, we suggest that the appropriate radiation field of CTVn should include the group I and II regions and the CTVn exterior margin along the lateral side of the internal jugular vein may be suitable.

Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation.

BACKGROUND AND PURPOSE: Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic radiation have been reported to predict radiation-induced lung injury (RILI). This study examined whether genetic variations in NOS2 gene is associated with the risk of RILI. MATERIAL AND METHODS: A cohort of 301 patients between 2009 and 2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2 gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was used to assess RILI risk and Cox proportional hazards analyses were performed to evaluate the effect of NOS2 genotypes on RILI. RESULTS: Multivariate analysis found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were significantly associated with risk of RILI⩾2 (P value=0.001, 0.000092, 0.001, respectively) after adjusting for other covariates. Their associations were independent of radiation dose and mean lung dose. Further haplotype analysis indicated that the ATC haplotype of three SNPs is associated with reducing the risk of developing RILI. CONCLUSION: Our results demonstrate that genetic variants of NOS2 may serve as a reliable predictor of RILI in lung cancer patients treated with thoracic radiation.

Long-term outcome of sensorineural hearing loss in nasopharyngeal carcinoma patients: comparison between treatment with radiotherapy alone and chemoradiotherapy.

The purpose of this study is to assess the long-term effect of sensorineural hearing loss (SNHL) resulted from radiotherapy (RT) alone versus chemoradiotherapy in nasopharyngeal carcinoma patients (NPC). Seventy-two patients initially diagnosed with NPC were enrolled from Shandong Tumor Hospital between March 2003 and May 2007. They were assigned into two groups: RT alone and chemoradiotherapy according to the different treatment regimens. Intensity-modulated radiation therapy was applied for both groups, concurrent and adjuvant cisplatin were administered for chemoradiotherapy group additionally. Hearing threshold test was performed at various time periods after completion of RT. Mean radiation dose to the cochlea in each ear was calculated to determine the correlation between cochlear dose and SNHL. We found that the hearing loss is more severe in the chemoradiotherapy group compared with RT group, from completion of RT up to the 5 years of follow-up period. This is especially obvious in the high frequency range. Hearing level is seriously damaged when cochlea dose exceeds 46 GY. We concluded that concurrent/adjuvant chemotherapy plus RT aggravates SNHL in NPC patients than RT alone and thus inner ear tissue tolerance should be redefined in those patients.

Efficacy and safety of accelerated partial breast irradiation after breast-conserving surgery: a meta-analysis of published comparative studies.

To compare the treatment outcomes between accelerated partial breast irradiation (APBI) and conventional whole-breast irradiation (WBI) and to explore the efficacy and safety of APBI as an adjuvant treatment for early-stage breast cancer who received breast-conserving therapy. Eligible studies were identified on Medline, Embase, and the Cochrane Library updated to July 10, 2012. Comparative studies were considered for inclusion. Analyses were carried out using Stata software. Eleven comparative studies with a total of 7,097 patients were included. The meta-analysis showed that there were no statistically significant differences between group APBI and group WBI associated with the supraclavicular failure, distant metastasis, overall survival, and disease-free survival, while local recurrence (LR) and axillary failure (AF) increased in group APBI. The sensitivity analysis indicated that both the LR and AF were not statistically significant difference between the two groups. In the subgroup analysis, LR was statistically significantly higher in group APBI for patients with the age <60, large tumor size, and unknown margin status. APBI is a safe treatment modality and could become a potential option for the delivery of adjuvant radiation therapy in patients receiving breast-conserving therapy, especially for the suitable group that was classified by the American Society of Radiation Oncology Consensus Panel.

Spect-guidance to reduce radioactive dose to functioning lung for stage III non-small cell lung cancer.

OBJECTIVE: To investigate the treatment effect of additional information obtained by single photon emission computed tomography (SPECT) lung perfusion imaging (LPI) in the radiotherapy planning process for patients with stage III non-small cell lung cancer (NSCLC). METHODS: 39 patients with stage III NSCLC were enrolled. Gross tumor volume (GTV) was outlined by SPECT/CT images, SPECT-LPIs being used to define functional lung (FL) and non-functional lung (NFL) regions. Two sets of IMRT plans were designed to deliver 64Gy to PTV. One was a regular IMRT plan using CT images only (Plan 1), and the other was a corresponding IMRT plan using co-registered images (Plan 2). FLVx (the % volume of functional lung receiving ≥x Gy) and WLVx (% volume of whole lung to receive ≥x Gy) were compared by paired Student's t test. Kendalls correlation was used to analyze the factor (s) related with the FLV20 decrease. RESULTS: Compared with plan 1, both WLVx and FLVx were decreased in plan 2. WLV10, WLV15, WLV20, WLV25, WLV30 and WLV35 decreased 9.7%, 13.8%, 17.2%, 12.9%, 9.8% and 9.8%, and FLV10, FLV15, FLV20, FLV25, FLV30 and FLV35 decreased 10.8%, 14.6%, 17.3%, 14.5%, 14.5% and 10.5%. FLVx decreased significantly compared with WLVx. There were significant differences in WLV10, WLV15, WLV20, WLV25, WLV3 and FLV10, FLV15, FLV20, FLV25, FLV30 between plan 1 and plan 2 (P=0.002, 0.000, 0.000, 0.005, 0.027 and 0.002, 0.000, 0.000, 0.006, 0.010). According to Kendall correlation analysis, NFL had a negative relation with the percentage FLV20 decrease (r=-0.559, P<0.01), while the distance of PTV and NFL center had a significantly positive relation with the percentage of FLV20 decrease (r=0.768, P<0.01). CONCLUSION: Routine use of SPECT-LPI for patients undergoing radiotherapy planning for stage III NSCLC appears warranted.

A clinical study of shrinking field radiation therapy based on (18)F-FDG PET/CT for stage III non-small cell lung cancer.

The aim is to investigate the feasibility of shrinking field technique after 40 Gy for stage III non-small cell lung cancer (NSCLC) during radiation therapy. Eighty-seven consecutive patients treated with intensity-modulated radiation therapy or three-dimensional conformal radiation therapy were enrolled in this study. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scanning was performed prior to treatment and repeated after 40 Gy, and the delineation of target volume was based on fused images of PET and CT. After 40 Gy of conventional fractionated radiotherapy to the initial planning target volume (PTV), a boost of 19.6-39.2 Gy was delivered to the shrunken PTV through late course accelerated hyperfractionated radiotherapy, and the median total dose was 66.0 Gy (range, 59.6-79.2 Gy). Gross tumor volume (GTV) and PTV regressions were recorded, and prescription doses with or without shrinking field were calculated. Local recurrence patterns were investigated through follow-up. The tumor volumes regressed in 84 (96.6%) patients and increased in 3 (3.4%) patients after 40 Gy. The mean GTV and PTV reduction was 38% (range, -13-95%) and 30% (range, -5-95%). Mean total prescription dose escalated from 62.0 Gy to 68.5 Gy through shrinking field technique. The median follow-up was 17 months, ranging from 5 to 46 months, and the 1- and 2-year overall survival rates in our study were 74.7% and 34.6%. The response rate was 79.5%, and radiation toxicity was acceptable. Tumor progression occurred in 67.8% (59/87) patients. Numbers of patients who had outfield, infield and both infield and outfield recurrences were 3 (3.4%), 26 (29.5%), and 3 (3.4%), respectively. In conclusion, significant tumor regression was observed after 40 Gy, and radiation dose escalated after shrinking field with acceptable toxicity and outfield relapse. Shrinking field radiotherapy based on (18)F-FDG PET/CT after 40 Gy was safe and feasible for stage III NSCLC.

Feasibility of shrinking field radiation therapy through 18F-FDG PET/CT after 40 Gy for stage III non-small cell lung cancers.

OBJECTIVE: To explore the feasibility of shrinking field technique after 40 Gy radiation through 18F-FDG PET/ CT during treatment for patients with stage III non-small cell lung cancer (NSCLC). METHODS: In 66 consecutive patients with local-advanced NSCLC, 18F-FDG PET/CT scanning was performed prior to treatment and repeated after 40 Gy. Conventionally fractionated IMRT or CRT plans to a median total dose of 66 Gy (range, 60-78 Gy) were generated. The target volumes were delineated in composite images of CT and PET. Plan 1 was designed for 40 Gy to the initial planning target volume (PTV) with a subsequent 20-28 Gy-boost to the shrunken PTV. Plan 2 was delivering the same dose to the initial PTV without shrinking field. Accumulated doses of normal tissues were calculated using deformable image registration during the treatment course. RESULTS: The median GTV and PTV reduction were 35% and 30% after 40 Gy treatment. Target volume reduction was correlated with chemotherapy and sex. In plan 2, delivering the same dose to the initial PTV could have only been achieved in 10 (15.2%) patients. Significant differences (p<0.05) were observed regarding doses to the lung, spinal cord, esophagus and heart. CONCLUSIONS: Radiotherapy adaptive to tumor shrinkage determined by repeated 18F-FDG PET/CT after 40 Gy during treatment course might be feasible to spare more normal tissues, and has the potential to allow dose escalation and increased local control.

An automated method of on-line extraction coupled with flow injection and capillary electrophoresis for phytochemical analysis.

In this study, an automated system for phytochemical analysis was successfully fabricated for the first time in our laboratory. The system included on-line decocting, filtering, cooling, sample introducing, separation, and detection, which greatly simplified the sample preparation and shortened the analysis time. Samples from the decoction extract were drawn every 5 min through an on-line filter and a condenser pipe to the sample loop from which 20-µL samples were injected into the running buffer and transported into a split-flow interface coupling the flow injection and capillary electrophoresis systems. The separation of glycyrrhetinic acid (GTA) and glycyrrhizic acid (GA) took less than 5 min by using a 10 mM borate buffer (adjusted pH to 8.8) and +10 kV voltage. Calibration curves showed good linearity with correlation coefficients (R) more than 0.9991. The intra-day repeatabilities (n = 5, expressed as relative standard deviation) of the proposed system, obtained using GTA and GA standards, were 1.1% and 0.8% for migration time and 0.7% and 0.9% for peak area, respectively. The mean recoveries of GTA and GA in the off-line extract of Glycyrrhiza uralensis Fisch root were better than 99.0%. The limits of detection (signal-to-noise ratio = 3) of the proposed method were 6.2 µg/mL and 6.9 µg/mL for GTA and GA, respectively. The dynamic changes of GTA and GA on the decoction time were obtained during the on-line decoction process of Glycyrrhiza uralensis Fisch root.

Enantioseparation of palonosetron hydrochloride by capillary zone electrophoresis with high-concentration beta-CD as chiral selector.

The enantioseparation of four stereoisomers of palonosetron hydrochloride (PALO) by capillary zone electrophoresis using high concentration beta-CD as chiral selector was described in this study. For optimization of the method of enantioseparation, several parameters such as beta-CD concentration, separation buffer pH and concentration, the types and concentration of organic modifiers, and the applied voltage were evaluated. The optimum conditions were obtained as follows: 30 mmol L(-1) NaH2PO4 (pH 3.0) containing 150 mmol L(-1) beta-CD and 10% (v/v) methanol with an applied voltage of 15 kV. Under these conditions, baseline separation of the four PALO stereoisomers was achieved within 35 min, and the reproducibility (expressed as relative standard deviation, RSD) of the migration times and the peak areas were below 0.5, 2.5% (intra-day), and 1.9, 4.4% (inter-day), respectively.

Microemulsion electrokinetic chromatography for the separation of arctiin and arctigenin in Fructus Arctii and its herbal preparations.

A microemulsion electrokinetic chromatography method was used to separate arctiin and arctigenin in Fructus Arctii and its herbal preparations. The separation of arctiin and arctigenin was performed using a 1-butanol-SDS-ethyl acetate-water microemulsion in 10mM sodium tetraborate buffer. The analytes were baseline-resolved within 4 min. In the concentration range 5-500 microg/mL, the calibration curves reveal linear relationships between the peak area for each analyte and its concentration (correlation coefficients: 0.9993 for arctiin and 0.9998 for arctigenin). The method was applied to the analysis of arctiin and arctigenin in herbal preparations, and the recoveries were 98.7-103.1% for arctiin and 97.6-103.2% for arctigenin, respectively.