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Aims: In this study, a rapid, sensitive and selective Triple Quadrupole LC/MS method was developed to determine Calycosin-7-glucoside, Formononetin, Calycosin, Ononin, Cycloastragenoland Astragaloside IV from the extractive of Astragali Radixin in rat plasma, and it was validated for rat plasma as the matrix and applied for a pharmacokinetic study in rat plasma, while the internal standard was Sulfamethoxazole. Background: Besides, a simple, one-step deproteinization procedure was followed to prepare plasma samples, and separation was achieved on an InfinityLab Poroshell 120 column (3.0 mm × 50 mm, 1.8 μm)with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (methanol) at a flow rate of 0.3 mL/min. Objective: Furthermore, multiple reaction monitoring (MRM) was used with an electrospray ionization source with the Agilent Jet Steam System (AJS-ESI) in the positive mode. Method: In this study, a rapid, sensitive and selective Triple Quadrupole LC/MS method was developed to determine Calycosin-7-glucoside, Formononetin, Calycosin, Ononin, Cycloastragenoland Astragaloside IV from the extractive of Astragali Radixin rat plasma, and it was validated for plasma as the matrix and applied for a pharmacokinetic study in rats, while the internal standard was Sulfamethoxazole. Result: Furthermore, multiple reaction monitoring (MRM) was used with an electrospray ionization source with the Agilent Jet Steam System (AJS-ESI) in the positive mode. Conclusion: Apart from that, a good linear response was observed within all analytes. The pharmacokinetic study on the six analytes in rats after oral administration of Astragali Radix was successfully completed by adopting this method, thusfilling a blank in pharmacokinetic studies of Astragali Radix.

Background: The purpose of this study was to verify the radiation dose of the pelvic bone marrow of different anatomical bony sitesand the incidence of neutrophil toxicity during the concurrent chemoradiotherapy for cervical cancer.Methods: There were 117 cervical cancer patients who received concurrent chemoradiotherapy included in this research. The radiotherapy includedexternal-beam radiation therapy (EBRT) and the brachytherapy. The dosimetric parameters included V5, V10, V20, V30, V40, V50, and Dmean. The final neutrophil count was defined as the lowest neutrophil count after 2 circles of concurrent chemotherapy, during or within 1 month after the treatment. The correlation between the dosimetric parameters and the lowest neutrophil count were analyzed by linear regression, the cutoff values of the dosimetric parameters were obtained using the ROC curves,the patients were divided into subgroups based on the cutoff values. The clinicopathologic features and the dosimetric parameters were included into the multivariate regression analysis model to further prove the correlation between the dosimetric parameters and the neutrophil toxicity. Data were assessed with IBM-SPSS software version 22.0, and all values of pResults:The neutrophil toxicity (grade 1-4) rate was 58.97%. The linear regression showed the Dmean and V50 of Lumbosacral vertebrae(LS), the Dmean, V5, V10, V20, V30, V40 and V50 of the ilium correlated with the lowest neutrophil count, while none of the dosimetric parameters of the femoral correlated with the lowest neutrophil count.The multivariate analysis showed the V20, V30 and V50 of the LS, the Dmean, V5, V10, V20 and V30 of the ilium correlated well with the neutrophil toxicity; none of the dosimetric parameters of the femoral correlated with the neutrophil toxicity.Conclusion:During the process of concurrent chemoradiotherapy for cervical cancer, the volume of medium and high dose of LS and the volume of low and medium dose of ilium should be strictly limitedto reduce the risk of neutrophil toxicity, the Dmean of the ilium should also be taken into consideration. The dosimetric parameters of the femur could be ignored.Trial registration:This is a retrospective research, and it will be retrospectively registered.

Increasing number of studies report that microRNAs play important roles in radiosensitization. miR-30a has been proved to perform many functions in the development and treatment of cancer, and it is downregulated in non-small cell lung cancer (NSCLC) tissues and cells. This study was conducted to understand if miR-30a plays a role in the radiosensitivity of NSCLC cells. Radiosensitivity was examed by colony survival assay and tumor volume changing in vitro and in vivo, respectively. Bioinformatic analysis and luciferase reporter assays were used to distinguish the candidate target of miR-30a. qRT-PCR and western blotting were carried out to detect the relative expression of mRNAs and proteins. Cell cycle and cell apoptosis were determined by flow cytometry. Our results illustrated miR-30a could increase the radiosensitivity of NSCLC, especially in A549 cell line. In vivo experiment also showed the potential radiosensitizing possibility of miR-30a. Further exploration validated that miR-30a was directly targ-eting activating transcription factor 1 (ATF1). In studying the ataxia-telangiectasia mutated (ATM) associated effects on cell radiosensitivity, we found that miR-30a could reduce radiation induced G2/M cell cycle arrest and may also affect radiation induced apoptosis. Together, our results demonstrated that miR-30a may modulate the radiosensitivity of NSCLC through reducing the function of ATF1 in phosphorylation of ATM and have potential therapeutic value.

Purpose The aim of this study was to investigate polymorphisms in DNA repair genes as potential predictive factors among Chinese cervical cancer patients. Methods A total of 72 patients with cervical carcinoma, who received cisplatin-based chemoradiotherapy and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors, were included. The association between response to chemoradiotherapy and the genotypes for 29 single-nucleotide polymorphisms (SNPs) in 25 DNA repair genes were analyzed. Results A minor allele of SNP rs9350 in the exonuclease 1 gene was associated with a better response rate, regardless of age and tumor stage (odds ratio, 8.316; p = 0.002). Conclusion SNP rs9350 in the exonuclease 1 gene is involved in inter-individual differences in the response to cisplatin-based chemoradiotherapy, in patients with cervical carcinoma.

Radiation-induced acute intestinal symptoms (RIAISs) are the most frequent complication of radiotherapy that causes great pain and limits the treatment efficacy. The aim of this study was to identify serum biomarkers of RIAISs in cervical cancer patients by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples were collected from 66 cervical cancer patients prior to pelvic radiotherapy. In our study, RIAISs occurred in 11 patients. An additional 11 patients without RIAISs were selected as controls, whose age, stage, histological type and treatment methods were matched to RIAISs patients. The 22 sera were subsequently analyzed by SELDI-TOF MS, and the resulting protein profiles were evaluated to identify biomarkers using appropriate bioinformatics tools. Comparing the protein profiles of serum samples from the RIAIS group and the control group, it was found that 22 protein peaks were significantly different (P < 0.05), and six of these peaks with mass-to-charge (m/z) ratios of 7514.9, 4603.94, 6887.41, 2769.21, 3839.72 and 4215.7 were successfully identified. A decision tree model of biomarkers was constructed based on three biomarkers (m/z 1270.88, 1503.23 and 7514.90), which separated RIAIS-affected patients from the control group with an accuracy of 81%. This study suggests that serum proteomic analysis by SELDI-TOF MS can identify cervical cancer patients that are susceptible to RIAISs prior to pelvic radiotherapy.

The occurrence of a peritoneal bladder fistula as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare and, to the best of our knowledge, has not been reported previously. The present study reports the case of a 50-year-old woman who was diagnosed with cervical cancer 20 years previously and was treated with radiotherapy. The patient was diagnosed with radiation cystitis 10 years ago, which was treated with Chinese medicine, and began experiencing sudden abdominal pain and bowel difficulties following urination 3 years ago. B-ultrasound examination at The People's Hospital of Tongchuan (Tongchuan, China) detected the presence of abdominal pelvic fluid. Following antibiotic (levofloxacin for 5 days) and ascites extraction treatment, symptoms were relieved without recurrence. However, 5 days prior to admission to the First Affiliated Hospital of Xi'an Jiatong University (Xi'an, China) on June 25, 2014, the patient experienced difficulty when urinating, abdominal pain and bloating, but did not experience frequent urination, hematuria or fever. Cystoscopic examination revealed a visible fistula on the bladder wall measuring 1×1 cm in diameter. Cytoscopic examination 1 month after catheterization and ascites extraction revealed no evidence of the fistula. The patient was followed up every 3 months for a year and a half, and is currently alive and well. In conclusion, the occurrence of peritoneal bladder fistula following radiation therapy is rare and cystoscopy is the preferred method of examination and diagnosis. Early detection and treatment may significantly improve the prognosis of patients.

Yanlan Chai,* Juan Wang,* Tao Wang, Fan Shi, Jiquan Wang, Jin Su, Yunyi Yang, Xi Zhou, Hailin Ma, Bin He, Zi LiuDepartment of Radiation Oncology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally tothis work Objective: Recent literature reports that radical hysterectomy followed by adjuvant radiotherapy has comparable progression-free survival and overall survival compared to radical radiotherapy for International Federation of Gynecology and Obstetrics stage IIB cervical cancer. Now, we evaluate the cost-effectiveness (CE) of these two treatment regimens.Primary and secondary outcome measures: A decision-tree model was constructed comparing CE between treatment arms using the published studies for overall survival rates and treatment-related toxicity rates for 5 years. The cost data were obtained from the hospital system of the First Affiliated Hospital of Xi’an Jiaotong University. Effectiveness was measured as quality-adjusted life year (QALY). Treatment arms were compared with regard to costs and life expectancy using incremental CE ratio, and the results were presented using costs per QALY.Results: The mean cost was $10,872 for radical hysterectomy followed by adjuvant radiotherapy versus $5,702 for radical radiotherapy. The incremental CE ratio for surgery-based treatment compared to radiotherapy-based treatment was –$76,453 per QALY.Conclusion: Radical radiotherapy would be a cost-effective method for FIGO stage IIB cervical cancer and would be favored in settings where resources are limited. Keywords: cost-effectiveness, cervical cancer, FIGO stage IIB, surgery, radiotherapy

Objective The objective of this study was to investigate the predictive value of common genetic alterations of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways in patients with locally advanced cervical squamous cell carcinoma (LACSCC) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). Methods Patients with LACSCC, treated at a single institution with CCRT were eligible for this retrospective study. A total of sixty pre-treatment tumor biopsies were retrieved. Somatic mutations were detected by pyrosequencing and CNV was determined by quantitative realtime PCR. The association of genetic alterations with clinicopathological characteristics and treatment response were analyzed. Results Patients without genetic alterations (mutations or amplification) of PIK3CA had a significantly higher response rate than patients with these alterations ( p = 0.006). In the logistic regression analysis, PIK3CA genetic alterations retained an independent factor in predicting response to CCRT. Conclusions Somatic mutations and copy number amplification of PIK3CA were associated with response to CCRT in patients with cervical squamous cell carcinoma.

Metabonomics has developed rapidly in post-genome era, and becomes a hot topic of omics. The core idea of metabonomics is to determine the metabolites of relatively low-weight molecular in organisms or cells, by a series of analytical methods such as nuclear magnetic resonance, color spectrum and mass spectrogram, then to transform the data of metabolic pattern into useful information, by chemometric tools and pattern recognition software, and to reveal the essence of life activities of the body. With advantages of high-throughput, high-sensitivity and high-accuracy, metabolomics shows great potential and value in cancer individualized treatment. This paper introduces the concept,contents and methods of metabonomics and reviews its application in cancer individualized therapy.

Objective There are numerous reports about the leptin concentration (LC) in postmenopausal women (PW). Changes in LC can elicit different clinical outcomes. We systematically analyzed the LC in PW. Methods A search was conducted in original English-language studies published from 1994 to October 2012 in the following databases: Medline (78), Cochrane Center (123) Embase (505), Biological abstracts (108), Cochrane (53) and Science Finder Scholar (0). A meta-analysis was undertaken on the correction coefficient (r) between the serum LC and body mass index (BMI) for healthy PW across studies containing a dataset and sample size. Pre-analytical and analytical variations were examined. Pre-analytical variables included fasting status (FS) and sampling timing. Analytical variation comprised assay methodology, LC in those undertaking hormone replacement therapy (HRT) and those not having HRT as well as LC change according to age. Results Twenty-seven studies met the inclusion criteria. Eighteen studies detected LC in the morning in a FS, 15 studies denoted the r between leptin and the BMI. A combined r was counted for the 15 studies (r = 0.51 [95% confidence interval (CI), 0.46-0.54], P = 0.025), and if sampling collection was in the FSat morning, a combined r was form 10 studies (r = 0.54 [95% CI, 0.45-0.54], P = 0.299) and heterogeneity was diminished. LC did not change between HRT users and non-users in 7 studies. Five studies analyzed changes in LC according to age. Conclusion Based on all studies that investigated both LC and BMI, LC was positively correlated with the BMI. No studies established reference ranges according to the Clinical and Laboratory Standards Institute (CLSI) in healthy PW, and there was a wide variation in LC values. These differences suggest that caution should be used in the interpretation and comparison between studies.

Objective Radiation-induced acute intestinal symptoms (RIAISs) are a common complication of radiotherapy for cervical cancer. The aim of this study was to use 1 H nuclear magnetic resonance ( 1 H NMR) combined with chemometric analysis to develop a metabolic profile of patients with RIAISs. Methods Fecal samples were collected from 66 patients with cervical cancer before and after pelvic radiotherapy. After radiotherapy, RIAISs occurred in eleven patients. We selected another 11 patients from participants without RIAISs whose age, stage, histological type and treatment methods are matched with RIAIS patients as the control group. 1 H NMR spectroscopy combined with multivariate pattern recognition analysis was used to generate metabolic profile data, as well as to establish a RIAIS-specific metabolic phenotype. Results Orthogonal partial least-squares discriminant analysis was used to distinguish samples between the pre- and post-radiotherapy RIAIS patients and between RIAIS patients and controls. Fecal samples from RIAIS patients after pelvic radiotherapy were characterized by increased concentrations of α-ketobutyrate, valine, uracil, tyrosine, trimethylamine N -oxide, phenylalanine, lysine, isoleucine, glutamine, creatinine, creatine, bile acids, aminohippurate, and alanine, accompanied by reduced concentrations of α-glucose, n -butyrate, methylamine, and ethanol relative to samples from RIAIS patients before pelvic radiotherapy, while in RIAIS patients relative to controls, trimethylamine, n -butyrate, fumarate and acetate were down-regulated and valine, TMAO, taurine, phenylalanine, lactate, isoleucine and creatinine were up-regulated. Conclusions We obtained the metabolic profile of RIAIS patients from fecal samples using NMR-based metabonomics. This profile has the potential to be developed into a novel clinical tool for RIAIS diagnosis or therapeutic monitoring, and could contribute to an improved understanding of the disease mechanism. However, because of the limitations of methods, technique, bacterial contamination of feces and small sample size, further research and verification are needed.

Background The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy. Methods Medical records of FIGO stage IIB cervical cancer patients treated between July 2008 and December 2011 were retrospectively reviewed. A total of 148 patients underwent radical hysterectomy with pelvic lymph node dissection followed by adjuvant radiotherapy (surgery-based group). These patients were compared with 290 patients that received radical radiotherapy alone (RT-based group). Recurrence rates, progression-free survival (PFS), overall survival (OS), local control rates, and treatment-related complications were compared for these two groups. Results Similar rates of recurrence (16.89% vs. 12.41%, p = 0.200), PFS (log-rank, p = 0.211), OS (log-rank, p = 0.347), and local control rates (log-rank, p = 0.668) were observed for the surgery-based group and the RT-based group, respectively. Moreover, the incidence of acute grade 3–4 gastrointestinal reactions and late grade 3–4 lower limb lymphedema were significantly higher for the surgery-based group versus the RT-based group. Cox multivariate analyses found no significant difference in survival outcome between the two groups, and tumor diameter and histopathology were identified as significant prognostic factors for OS. Conclusions Radical radiotherapy was associated with fewer treatment-related complications and achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer compared to radical hysterectomy followed by postoperative radiotherapy.