Stage IIB-IVA cervix carcinoma in elderly patients treated with radiation therapy: a longitudinal cohort study by propensity score matching analysis.

OBJECTIVE: We aimed to evaluate the treatment modality and prognostic impact of the age at diagnosis on stage IIB-IVA cervix carcinoma (CC) patients who received radiotherapy (RT).The evaluation was performed using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: From the SEER database, we included the patients with a histopathological diagnosis of CC between 2004 and 2016. Subsequently, we compared the treatment outcomes between patients aged ≥ 65 years (OG) and < 65 years (YG) by propensity score matching (PSM) analysis and Cox proportional hazard regression models. RESULTS: The data of 5,705 CC patients were obtained from the SEER database. We observed that the OG patients were significantly less likely to receive chemotherapy, brachytherapy, or combination treatment compared to the YG (P < 0.001). Further, the advanced age at diagnosis was an independent prognostic factor associated with decreasing overall survival (OS) before and after PSM. Even in the subgroup analysis of patients who received trimodal therapy, an advanced age had a significant negative impact on OS compared to their younger counterparts. CONCLUSION: Advanced age is associated with less aggressive treatment regimens and is independently associated with impaired OS for stage IIB-IVA CC patients who received RT. Hence, future studies should incorporate geriatric assessment into clinical decision-making to select appropriate and effective treatment strategies for elderly CC patients.

Development and validation of a radiomics-based nomogram for the prediction of postoperative malnutrition in stage IB1-IIA2 cervical carcinoma.

Objective: In individuals with stage IB1-IIA2 cervical cancer (CC) who received postoperative radiotherapy ± chemotherapy (PORT/CRT), the interaction between sarcopenia and malnutrition remains elusive, let alone employing a nomogram model based on radiomic features of psoas extracted at the level of the third lumbar vertebra (L3). This study was set to develop a radiomics-based nomogram model to predict malnutrition as per the Patient-Generated Subjective Global Assessment (PG-SGA) for individuals with CC. Methods: In total, 120 individuals with CC underwent computed tomography (CT) scans before PORT/CRT. The radiomic features of psoas at L3 were obtained from non-enhanced CT images. Identification of the optimal features and construction of the rad-score formula were conducted utilizing the least absolute shrinkage and selection operator (LASSO) logistic regression to predict malnutrition in the training dataset (radiomic model). Identification of the major clinical factors in the clinical model was performed by means of binary logistic regression analysis. The radiomics-based nomogram was further developed by integrating radiomic signatures and clinical risk factors (combined model). The receiver operating characteristic (ROC) curves and decision curves analysis (DCA) were employed for the evaluation and comparison of the three models in terms of their predictive performance. Results: Twelve radiomic features in total were chosen, and the rad-score was determined with the help of the non-zero coefficient from LASSO regression. Multivariate analysis revealed that besides rad-score, age and Eastern Cooperative Oncology Group performance status could independently predict malnutrition. As per the data of this analysis, a nomogram prediction model was constructed. The area under the ROC curves (AUC) values of the radiomic and clinical models were 0.778 and 0.847 for the training and 0.776 and 0.776 for the validation sets, respectively. An increase in the AUC was observed up to 0.972 and 0.805 in the training and validation sets, respectively, in the combined model. DCA also confirmed the clinical benefit of the combined model. Conclusion: This radiomics-based nomogram model depicted potential for use as a marker for predicting malnutrition in stage IB1-IIA2 CC patients who underwent PORT/CRT and required further investigation with a large sample size.

A 5-year survival status prognosis of nonmetastatic cervical cancer patients through machine learning algorithms.

BACKGROUND: Prediction models with high accuracy rates for nonmetastatic cervical cancer (CC) patients are limited. This study aimed to construct and compare predictive models on the basis of machine learning (ML) algorithms for predicting the 5-year survival status of CC patients through using the Surveillance, Epidemiology, and End Results public database of the National Cancer Institute. METHODS: The data registered from 2004 to 2016 were extracted and randomly divided into training and validation cohorts (8:2). The least absolute shrinkage and selection operator (LASSO) regression was employed to identify significant factors. Then, four predictive models were constructed, including logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The predictive models were evaluated and compared using Receiver-operating characteristics with areas under the curves (AUCs) and decision curve analysis (DCA), respectively. RESULTS: A total of 13,802 patients were involved and classified into training (N = 11,041) and validation (N = 2761) cohorts. By using the LASSO regression method, seven factors were identified. In the training cohort, the XGBoost model showed the best performance (AUC = 0.8400) compared to the other three models (all p < 0.05 by Delong's test). In the validation cohort, the XGBoost model also demonstrated a superior prediction ability (AUC = 0.8365) than LR and SVM models (both p < 0.05 by Delong's test), although the difference was not statistically significant between the XGBoost and the RF models (p = 0.4251 by Delong's test). Based on the DCA results, the XGBoost model was also superior, and feature importance analysis indicated that the tumor stage was the most important variable among the seven factors. CONCLUSIONS: The XGBoost model proved to be an effective algorithm with better prediction abilities. This model is proposed to support better decision-making for nonmetastatic CC patients in the future.

Impact of marital status on overall survival in patients with early-stage hepatocellular carcinoma.

The purpose of the present research was to assess the prognostic impact of marital status in hepatocellular carcinoma (HCC) patients with tumors ≤ 2 cm (stage Ia) based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received a histopathologic HCC diagnosis between 2004 and 2016 were recruited. Overall survival (OS) was the major outcome measure. The Cox regression model and the Fine-Gray regression model were used for the purpose of comparing and examining the prognostic value of marital status for OS. The data for a total of 2446 stage Ia HCC patients were extracted from the database. The median overall survival time was 96.0 months, with 5-year and 10-year overall survival rates of 58.2% and 45.8%, respectively. In both the Fine-Gray regression model and Cox regression model, marital status [married vs. unmarried and others, both P < 0.001, hazard ratio (HR) = 1.389 for Cox and HR = 1.378 for Fine-Gray], age at diagnosis, tumor grade, and surgery at the primary site independently served as prognostic indicators associated with OS. In conclusion, positive marital status was independently associated with better OS for stage Ia HCC patients, and its prognostic influence should be validated in the near future.

Survival Comparison Between Squamous Cell Carcinoma and Adenocarcinoma for Radiotherapy-Treated Patients with Stage IIB-IVA Cervical Cancer.

Objective: To compare the prognostic significance of adenocarcinoma (AC) with squamous cell carcinoma (SCC) on overall survival (OS) in patients with stage IIB-IVA cervical cancer (CC) treated by external beam radiotherapy (EBRT) and brachytherapy (BRT) with/without chemotherapy registered in the Surveillance, Epidemiology, and End Results database. Methods: Data of eligible patients were extracted between 2004 and 2016. A univariate analysis was conducted using the cumulative incidence function (CIF) by considering competing events and compared using Gray's test. The significant variables in univariate analysis were further evaluated in a multivariate analysis performed with the Fine-Gray regression model. Propensity score matching (PSM) analysis was also employed to reconfirm the results found in the present study. Results: A total of 2,243 patients with SCC and 176 patients with AC were extracted from the database. The 5-year OS rates were 57.8% in the SCC group and 52.8% in the AC group. 149 patients died of causes other than CC-considered as competing events. Compared with the SCC group, patients diagnosed with AC had statistically significant worse 5-year OS rate before and after PSM. In the multivariate Fine-Gray regression model, the histological subtype of AC was proven as an independent prognostic factor associated with poorer OS before [hazard ratio (HR) = 1.340; 95% confidence interval (CI): 1.081-1.660; P = 0.007] and after [HR = 1.376; 95% CI: 1.107-1.711; P = 0.004] PSM. Conclusions: The histological subtype of AC is significantly correlated with impaired OS as an independent prognostic variable in patients with stage IIB-IVA CC who received EBRT and BRT compared to patients with SCC. Future studies should incorporate effective and individualized treatment strategies into clinical decision-making to improve the unsatisfactory survival outcomes for patients with AC.

Prognostic Analysis and Comparison of the 2014 and 2018 International Federation of Gynecology and Obstetrics Staging System on Overall Survival in Patients with Stage IIB-IVA Cervix Carcinoma.

Purpose: This study aimed to assess the prognostic factors of overall survival (OS) in patients with stage IIB-IVA cervix carcinoma (CC) who underwent external beam radiation therapy (EBRT) and brachytherapy (BRT) and to compare the prognostic accuracy of the 2014 and 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with a histopathological diagnosis of CC between 2004 and 2016 were included. The primary endpoint was OS. The prognostic significance for OS was analyzed by the Cox regression model. Prognostic accuracy in evaluating 3- and 5-year OS in different staging systems was evaluated using time-dependent receiver operating characteristic (tdROC) curves. Results: A total of 2585 patients with stage IIB-IVA CC, staged according to the 2014 FIGO staging system, were included in the study. The 3- and 5-year OS rates were 63.9% and 56.6%, respectively, with a median OS of 98 months. Independent variables, such as older age at diagnosis, histological grades apart from well or moderately differentiated, large tumor size, advanced tumor stages classified according to the 2014 and 2018 FIGO staging systems and treatment without chemotherapy or unknown were associated with a worse OS. A tdROC analysis conducted using DeLong's tests revealed no significant difference in the prediction of 3- and 5-year OS between the 2014 and 2018 FIGO staging systems (P = 0.912 and 0.863, respectively). Conclusion: Both 2014 and 2018 FIGO staging systems were strong prognostic factors for OS. No significant risk classification was observed for stage IIIC1 disease in the revised 2018 FIGO staging system for patients who underwent EBRT and BRT.

Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma.

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004-2016. Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test. Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P < 0.001, hazard ratio (HR) = 1.832], sex [P < 0.001, HR= 1.867], histology [P = 0.001, HR = 0.366], surgery at the primary site [P = 0.021, HR = 0.553], radiotherapy (RT, P = 0.017, HR = 0.637) and chemotherapy (CT, P < 0.001, HR = 0.444). Comparison among the three treatment modalities demonstrated that a triple therapy regimen consisting of surgery, RT and CT was associated with a longer survival time than the other two treatment modalities before and after propensity score matching (PSM). However, triple therapy showed no significant survival benefit over double therapy (P = 0.496 before PSM and P = 0.184 after PSM). Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.

Donor BMSC-derived small extracellular vesicles relieve acute rejection post-renal allograft through transmitting Loc108349490 to dendritic cells.

Bone marrow-derived mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are potent candidates for the suppression of acute rejection post-renal allograft and have been reported to halt dendritic cells (DCs) maturation. However, whether BMSC-derived sEVs mitigate acute rejection post-renal allograft by targeting DCs is still unclear. In this study, donor BMSC-derived sEVs (sEVs) relieved the inflammatory response and suppressed mature DCs (mDCs) location in kidney grafts, and increased regulatory T (Treg) cell population in the spleens of the rats that underwent kidney allograft. In lipopolysaccharide (LPS)-stimulated immature DCs (imDCs), sEVs suppressed the maturation and migration of DCs and inactivated toll-like receptor 4 (TLR4) signaling. Compared with LPS-treated imDCs, imDCs treated with LPS+sEVs promoted CD4+ T cells differentiated toward Treg cells. Subsequently, we found that Loc108349490, a long non-coding RNA (lncRNA) abundant in sEVs, mediated the inhibitory effect of sEVs on DC maturation and migration by promoting TLR4 ubiquitination. In rats that underwent an allograft, Loc108349490 deficiency weakened the therapeutic effect of sEVs on acute rejection. The present study firstly found that sEVs alleviated acute rejection post-renal allograft by transferring lncRNA to DCs and screened out the functional lncRNA loaded in sEVs was Loc108349490.

A Nomogram-Based Risk Classification System Predicting the Overall Survival of Patients With Newly Diagnosed Stage IVB Cervix Uteri Carcinoma.

Background: This study constructed and demonstrated a model to predict the overall survival (OS) of newly diagnosed distant metastatic cervical cancer (mCC) patients. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was used to collect the eligible data, which from 2010 to 2016. Then these data were separated into training and validation cohorts (7:3) randomly. Cox regression analyses was used to identify parameters significantly correlated with OS. Harrell's Concordance index (C-index), calibration curves, and decision curve analysis (DCA) were further applied to verify the performance of this model. Results: A total of 2,091 eligible patients were enrolled and randomly split into training (n = 1,467) and validation (n = 624) cohorts. Multivariate analyses revealed that age, histology, T stage, tumor size, metastatic sites, local surgery, chemotherapy, and radiotherapy were independent prognostic parameters and were then used to build a nomogram for predicting 1 and 2-year OS. The C-index of training group and validation group was 0.714 and 0.707, respectively. The calibration curve demonstrated that the actual observation was in good agreement with the predicted results concluded by the nomogram model. Its clinical usefulness was further revealed by the DCAs. Based on the scores from the nomogram, a corresponding risk classification system was constructed. In the overall population, the median OS time was 23.0 months (95% confidence interval [CI], 20.5-25.5), 12.0 months (95% CI, 11.1-12.9), and 5.0 months (95% CI, 4.4-5.6), in the low-risk group, intermediate-risk group, and high-risk group, respectively. Conclusion: A novel nomogram and a risk classification system were established in this study, which purposed to predict the OS time with mCC patients. These tools could be applied to prognostic analysis and should be validated in future studies.

Changes in the Psychological State of Medical Personnel in the Department of Radiotherapy at a Tertiary Care Teaching Hospital in China during the Epidemic.

OBJECTIVES: The aim of the present study was to investigate changes in the psychological state of medical personnel in the Department of Radiotherapy during the COVID-19 epidemic. METHODS: Psychological state was evaluated using the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). All three questionnaires were first completed by medical personnel on 17-18 February 2020 and were repeated every 3 months thereafter until 17-18 August. The number and intentions of patients receiving radiotherapy (RT) in our department were also collected. RESULTS: Twenty medical personnel participated in the present study. The global PSQI score recorded in August was significantly lower than that recorded in February (P = 0.045). Among the seven components of the PSQI, sleep quality (P = 0.048) and daytime dysfunction (P = 0.006) in August were significantly improved compared with February, whereas SDS and SAS did not significantly differ among the three different time points. The proportion of patients who received palliative radiotherapy was significantly higher on 18 May than on 17 February (P = 0.005). CONCLUSIONS: Medical personnel in the Department of Radiotherapy experienced a significantly elevated incidence of sleeping problems during the early COVID-19 outbreak period. Multiple combinations of protective measures to avoid infection could improve sleep quality and ensure the safe delivery of RT to cancer patients.

A novel nonsense variant of the AGXT identified in a Chinese family: special variant research in the Chinese reference genome.

BACKGROUND: Primary hyperoxaluria(PH)is a rare autosomal recessive genetic disease that contains three subtypes (PH1, PH2 and PH3). Approximately 80% of PH patients has been reported as subtype PH1, this subtype of PH has been related to a higher risk of renal failure at any age. Several genetic studies indicate that the variants in gene AGXT are responsible for the occurrence of PH1. However, the population heterogeneity of the variants in AGXT makes the genetic diagnosis of PH1 more challenging as it is hard to locate each specific variant. It is valuable to have a complete spectrum of AGXT variants from different population for early diagnosis and clinical treatments of PH1. CASE PRESENTATION: In this study, We performed high-throughput sequencing and genetic analysis of a 6-year-old male PH1 patient from a Chinese family. Two variants (c.346G > A: p.Gly116Arg; c.864G > A: p.Trp288X) of the gene AGXT were identified. We found a nonsense variant (c.864G > A: p.Trp288X) that comes from the proband's mother and has never been reported previously. The other missense variant (c.346G > A: p.Gly116Arg) was inherited from his father and has been found previously in a domain of aminotransferase, which plays an important role in the function of AGT protein. Furthermore, we searched 110 pathogenic variants of AGXT that have been reported worldwide in healthy local Chinese population, none of these pathogenic variants was detected in the local genomes. CONCLUSIONS: Our research provides an important diagnosis basis for PH1 on the genetic level by updating the genotype of PH1 and also develops a better understanding of the variants in AGXT by broadening the variation database of AGXT according to the Chinese reference genome.

Trends and predictors of survival for small cell carcinoma of the cervix uteri: A SEER population study.

OBJECTIVE: Small cell carcinoma of the cervix uteri (SCCC) is an uncommon cancer associated with unsatisfactory survival outcomes. We aimed to investigate the incidence and prognostic factors of survival in SCCC patients using the Surveillance, Epidemiology, and End Results database. METHODS: Eligible patients with histopathologic diagnoses of SCCC were identified between 2004 and 2015. Overall survival (OS) and cause-specific survival (CSS) for the included patients were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of clinical factors were performed using Cox proportional hazard regression models. RESULTS: We identified 272 SCCC patients based on predefined criteria. The average incidence of SCCC was 1.01 % per year between 2004 and 2015. The median OS and CSS were 17.0 and 19.0 months, respectively, accompanying with 5-year OS rate was 26.3 % and 5-year CSS rate was 30.1 %. In the multivariate analysis, advanced age (age ≥ 65 years old), late FIGO stage, surgery at the primary site, radiotherapy (RT) and chemotherapy (CT) were strong prognostic factors for OS. The corresponding variables for CSS were: advanced age, late FIGO stage, RT and CT. In the subgroup analysis for nonsurgical management of SCCC, the combination of RT and CT provided the best survival outcomes when compared with other therapeutic modalities. Again, advanced age was interrelated to worse survival outcomes for both OS and CSS. CONCLUSIONS: SCCC is an infrequent disease with aggressive nature, which lead to poor survival outcomes. In addition to other known parameters, advanced age is a strong predictive factor for OS and CSS. The combination of RT and CT was the best therapeutic strategy for patients who received nonsurgical management.

Prognostic Value of the Geriatric Nutritional Risk Index in Patients Exceeding 70 Years Old with Esophageal Squamous Cell Carcinoma.

To investigate the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) or definitive concurrent chemoradiotherapy (dCRT). Fifty-two ESCC patients were included from July 2014 to December 2018. RT was delivered at a dose of 1.8-2.0 Gy per day to a total dose of 50-60 Gy. Tumor response was assessed using the RECIST 1.1 system. Overall survival (OS) and progression-free survival (PFS) were calculated and compared with the Kaplan-Meier method. Multivariate analysis of predictive factors of response and survival was performed using a logistic regression and a Cox model, respectively. In multivariate analysis, GNRI score (HR 0.278, P = 0.036) was the only independent prognostic factor for tumor response. As for survival outcomes, GNRI score (OS: HR 0.505, P = 0.028; PFS: HR 0.583, P = 0.045) and treatment modality (OS: HR 0.356, P = 0.015; PFS: HR 0.392, P = 0.0014) were both independent prognostic factors for better OS and PFS. Additionally, there was no correlation between GNRI score and treatment modality (Spearman's ρ = 0.200; P = 0.154). In conclusion, routine use of the GNRI criteria may help in the risk stratification of elderly patients undergoing RT/dCRT. The dCRT treatment could provide survival benefits for elderly ESCC patients.

Evolutionary dynamics of transposable elements during silkworm domestication.

Although there are some documented examples on population dynamics of transposable elements (TEs) in model organisms, the evolutionary dynamics of TEs in domesticated species has not been systematically investigated. The objective of this study is to understand population dynamics of TEs during silkworm domestication. In this work, using transposon-display we examined the polymorphism of seven TE families [they represent about 59% of silkworm (Bombyx mori) total TE content] in four domesticated silkworm populations and one wild silkworm population. Maximum likelihood (ML) was used to estimate selection pressure. Population differentiation and structure were performed by using AMOVA analysis and program DISTRUCT, respectively. The results of transposon-display showed that significant differentiation occurred between the domesticated silkworm and wild silkworm. These TEs have experienced expansions and fixation in the domesticated silkworm but not in wild silkworm. Furthermore, the ML results indicated that purifying selection of TEs in the domesticated silkworm were significantly weaker than that in the wild silkworm. Interestingly, an adaptation insertion induced by BmMITE-2 was found, and this insertion can reduce the polymorphism of the flanking regions of its neighboring COQ7 gene. Our results suggested that TEs expanded and were fixed in the domesticated silkworm might result from demographic effects and artificial selection during domestication. We concluded that the data presented in this study have general implication in animal and crop improvements as well as in domestication of new species.

Allergic conditions are not associated with the risk of non-Hodgkin's lymphoma or Hodgkin's lymphoma: a systematic review and meta-analysis.

We aimed to systematically evaluate the association between allergic conditions and the risk of Hodgkin's lymphoma (HL) and non-HL (NHL). Systematic literature searches in PubMed and Embase were conducted up to October 2015 to identify eligible studies. Either a fixed-effects model or a random-effects model was adopted to estimate overall odds ratios (ORs) according to heterogeneity across studies. Subgroup and publication bias analyses were applied. A total of 24 case-control studies and 13 cohort studies (conducted from 1987 to 2015) were included in the analysis of the risk of NHL. History of any allergic condition was inversely associated with the risk of NHL in case-control studies (OR =0.83, 95% CI 0.76-0.91), while the reduction in the risk of NHL was not observed in cohort studies (OR =1.18, 95% CI 0.98-1.42). Significant association with the risk of NHL was found for asthma, hay fever, food allergy, allergic rhinitis, and hives. In the pooled analysis of the risk of HL, 12 studies (two were cohort studies) were included. The pooled OR was 0.96 (95% CI 0.84-1.09) for case-control studies and 1.46 (95% CI 0.63-3.38) for cohort studies. For specific allergic condition, we observed a reduced risk of HL in individuals with hay fever and food allergy. In conclusion, history of any allergic condition was not significantly associated with the risk of NHL or HL. Several specific allergic conditions, including asthma, hay fever, food allergy, and allergic rhinitis, might be associated with a reduced risk of NHL, while individuals with hay fever or food allergy may have a reduced risk of HL.

Comparative study of cisplatin-based definitive concurrent chemoradiotherapy with S-1 versus paclitaxel for unresectable locally advanced esophageal squamous cell carcinoma.

This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer.

OBJECTIVE: The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer. PATIENTS AND METHODS: From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8-2.0 Gy to a total radiation dose of 54.0-60.0 Gy. Preplanned concurrent S-1 (80 mg/m(2)/d) was given on days 1-14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles. RESULTS: The median age of the enrolled patients was 76 years (range: 70-88 years), and the clinical stages were stage I (two patients), stage II (24 patients), stage III (28 patients), and stage IV (14 patients). A total of 51 (75.0%) patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5%) patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS) and progression-free survival (PFS) times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade ≥3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS. CONCLUSION: For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory survival outcomes with tolerable toxicities. More studies are highly warranted to further clarify this issue.

Spy: a new group of eukaryotic DNA transposons without target site duplications.

Class 2 or DNA transposons populate the genomes of most eukaryotes and like other mobile genetic elements have a profound impact on genome evolution. Most DNA transposons belong to the cut-and-paste types, which are relatively simple elements characterized by terminal-inverted repeats (TIRs) flanking a single gene encoding a transposase. All eukaryotic cut-and-paste transposons so far described are also characterized by target site duplications (TSDs) of host DNA generated upon chromosomal insertion. Here, we report a new group of evolutionarily related DNA transposons called Spy, which also include TIRs and DDE motif-containing transposase but surprisingly do not create TSDs upon insertion. Instead, Spy transposons appear to transpose precisely between 5'-AAA and TTT-3' host nucleotides, without duplication or modification of the AAATTT target sites. Spy transposons were identified in the genomes of diverse invertebrate species based on transposase homology searches and structure-based approaches. Phylogenetic analyses indicate that Spy transposases are distantly related to IS5, ISL2EU, and PIF/Harbinger transposases. However, Spy transposons are distinct from these and other DNA transposon superfamilies by their lack of TSD and their target site preference. Our findings expand the known diversity of DNA transposons and reveal a new group of eukaryotic DDE transposases with unusual catalytic properties.

The origin and evolution of six miniature inverted-repeat transposable elements in Bombyx mori and Rhodnius prolixus.

Miniature inverted-repeat transposable elements (MITEs) are a specific group of nonautonomous DNA transposons, and they are distributed in a wide range of hosts. However, the origin and evolutionary history of MITEs in eukaryotic genomes remain unclear. In this study, six MITEs were identified in the silkworm (Bombyx mori). Five elements are grouped into four known superfamilies of DNA transposons, and one represents a novel class of MITEs. Unexpectedly, six similar MITEs are also present in the triatomine bug (Rhodnius prolixus) that diverged from the common ancestor with the silkworm about 370 Ma. However, they show different lengths in two species, suggesting that they are different derivatives of progenitor transposons. Three direct progenitor transposons (Sola1, hobo/Ac/Tam [hAT], and Ginger2) are also identified in some other organisms, and several lines of evidence suggested that these autonomous elements might have been independently and horizontally transferred into their hosts. Furthermore, it is speculated that the twisted-wing parasites may be the candidate vectors for these horizontal transfers. The data presented in this study provide some new insights into the origin and evolutionary history of MITEs in the silkworm and triatomine bug.

BmTEdb: a collective database of transposable elements in the silkworm genome.

The silkworm, Bombyx mori, is one of the major insect model organisms, and its draft and fine genome sequences became available in 2004 and 2008, respectively. Transposable elements (TEs) constitute ~40% of the silkworm genome. To better understand the roles of TEs in organization, structure and evolution of the silkworm genome, we used a combination of de novo, structure-based and homology-based approaches for identification of the silkworm TEs and identified 1308 silkworm TE families. These TE families and their classification information were organized into a comprehensive and easy-to-use web-based database, BmTEdb. Users are entitled to browse, search and download the sequences in the database. Sequence analyses such as BLAST, HMMER and EMBOSS GetORF were also provided in BmTEdb. This database will facilitate studies for the silkworm genomics, the TE functions in the silkworm and the comparative analysis of the insect TEs. Database URL: http://gene.cqu.edu.cn/BmTEdb/.