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Lingli Jiang,1,&ast; Lei Peng,1,&ast; Miaoling Rong,2 Xiaozhi Liu,3 Qinxia Pang,1 Huaping Li,1 Ying Wang,1 Zhou Liu1 1Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, First Maternity and Infant Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou Liu, Department of Obstetrics and Gynecology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500, Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of China, Tel +86 18930837705, Email zp_liuz@sumhs.edu.cnBackground: The majority of women who experience spontaneous preterm delivery (SPTD) have low-risk, asymptomatic pregnancies with a cervical length (CL) ≥ 25mm and no clear risk factors. Despite the fact that cervical elastography is a potential tool for predicting SPTD, there is currently no feasible solution to make a reliable prediction for preventing SPTD.Objective: The aim of this study was to construct a nomogram including multimodal transvaginal ultrasound parameters during the second trimester to predict SPTD in low-risk women.Methods: This multi-center study enrolled 1260 women with singleton pregnancies between 20 and 24 weeks’ gestation. CL and cervical elastography data were obtained when they were undergoing the second-trimester anomaly scan. Univariate and multivariate Logistic regression were utilized to screen predictors independently related to SPTD from the maternal characteristics and multimodal ultrasound data. Then construct a nomogram to determine the likelihood of SPTD in pregnant women.Results: A total of 66 pregnancies in the training cohort (7.8%, 66/842) and 37 pregnancies (8.9%, 37/418) in the validation cohort ended in SPTD. Age, uterine curettage, CL, and strain in the anterior lip of internal os were the independent predictors of SPTD (P < 0.001, < 0.001, = 0.007, and < 0.001, respectively). These predictors constituted a nomogram to predict the probability of SPTD for a pregnant woman in her second trimester. It showed good discrimination (C-index = 0.898 and 0.839), calibration (P = 0.258 and 0.115), and yielded net benefits both in the training and validation cohorts.Conclusion: The nomogram including data of multimodal transvaginal ultrasound at 20 to 24 weeks’ gestation is expected to identify women with SPTD in the low-risk, asymptomatic population.Keywords: cervical length measurement, elasticity imaging techniques, nomograms, pregnancy trimester, second, premature birth

Heming Lu,1,&ast; Yuying Wu,2,&ast; Xu Liu,1 Huixian Huang,1 Hailan Jiang,1 Chaohua Zhu,1 Yuping Man,3 Pei Liu,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Shan Deng,1 Junzhao Gu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 3Department of Radiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 4Department of Oncology, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Nanning, 530021, People’s Republic of ChinaTel +86-771-218-6806Email luhming3632@163.comPurpose: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response.Materials and Methods: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve.Results: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656– 0.849, sensitivity of 61.3– 93.5%, specificity of 46.1– 73.1%, and maximal Youden Index of 36.5– 66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2.Conclusion: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.Keywords: cervical cancer, locally advanced disease, dynamic contrast-enhanced magnetic resonance imaging, concurrent chemoradiotherapy, prognosis prediction

Shuangchi Liu,1 Zhiduan Xu,1 Zhuling Fang,2 Dengyong Zhang,1 Zhongqiang Qin,1 Longfei Fan,1 Jiakang Duan,1 Hongxiang Yin,1 Yigang Zhang,1 Qing Pang,1,3 Yi Tan1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People’s Republic of China; 2Department of Medical Laboratory, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of ChinaCorrespondence: Yi Tan; Qing PangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of ChinaEmail doctortanyi2007@126.com; portxiu2@126.comBackground: Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis.Methods: A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model.Results: During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P< 0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669– 0.751) than BCLC stage.Conclusion: AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.Keywords: AIAG, hepatocellular carcinoma, survival, prognosis

Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of China; 2Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-qiang Yu 48 Huaishu Lane, Liangxi District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +86510-82709790Fax +86-510-82725094Email yurenqiang553@163.comQing-feng Pang 1800 Lihu Avenue, Binhu District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +8651052430172Fax +86-510-85329042Email qfpang@jiangnan.edu.cnBackground: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.Methods: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.Keywords: sodium propionate, lipopolysaccharide, Nrf2, angiogenesis, bronchopulmonary dysplasia

Jing Zeng,1,2 Ziqi Liu,3 Shan Jiang,3 Qingsong Pang,1 Ping Wang1 1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University, Tianjin, People’s Republic of China; 3School of Mechanical Engineering, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Ping WangTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaEmail wangping2019@foxmail.comPurpose: Our previous research demonstrated that under ideal conditions, rigid registration between MRI images and US images had high accuracy for real-time image guidance. The work presented in this paper focused on the application of the previously established procedures to a new context, including preoperative CT images.Materials and Methods: We used a template to calibrate the US probe and completed the registration between preoperative CT images and US images. Marker experiments on the accuracy of real-time needle trajectories in CT images were performed using micro electromagnetic sensors. Pelvic phantom experiments were carried out to test the registration accuracy between CT and US images, in addition to registration accuracy between US images and real-time needle trajectories (real-time space model).Results: The US probe calibration error in CT images was 0.879 ± 0.149 mm. The difference of registration between US images and CT images was 0.935 ± 0.166 mm in the axial plane (n = 30) and 0.916 ± 0.143 mm in the sagittal plane (n =12). The difference of registration between US images and the needle’s real-time trajectories was 0.951 ± 0.202 mm.Conclusion: Under ideal conditions, rigid registration between CT images and US images had high accuracy for real-time image guidance.Keywords: registered ultrasound image, gynecologic brachytherapy, rigid registration, image-guidance

Defeng Qing,1,* Yuying Wu,2,* Xu Liu,1,* Hailan Jiang,1,* Chaohua Zhu,1,* Pei Liu,3 Junming Dang,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Luxing Peng,1 Shan Deng,1 Junzhao Gu,1 Renfeng Zhao,2 Changyi Chen,2 Heming Lu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 3Department of Radiation Oncology, Youjiang Medical University for Nationalities, Baise 533000, People’s Republic of China; 4Department of Oncology, Guangxi University of Chinese Medicine, Nanning 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City 530021, People’s Republic of ChinaTel +86-771-218-6504Email luhming3632@163.comPurpose: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and Methods: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.Results: Between June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.Conclusion: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery

Qing Pang,1,2,* Shuangchi Liu,1,* Luyao Wang,3,* Huadong Pan,3 Chunfang Wang,3 Lei Zhou,1 Yimin Lu,1 Huichun Liu1 1Department of Hepatobiliary Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710061, People’s Republic of China; 3Clinical Medical College of Bengbu Medical College, Bengbu, Anhui Province 233000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huichun Liu; Yimin LuDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of ChinaEmail liuhcdoctor@126.com; yimludoctor@126.comBackground: Platelet–albumin–bilirubin (PALBI) has been demonstrated to be superior to conventional Child–Pugh (C-P) grade in evaluating liver function and prognosis of HCC patients. However, both thrombocytosis and thrombocytopenia are unfavorable for HCC survival. The aim of this study was to preliminarily investigate the prognostic value of PALBI in HCC patients with thrombocytopenia and excluding thrombocytopenia.Methods: In this retrospective cohort study, we reviewed 465 cases of HCC patients who underwent radical surgery. PALBI grade was calculated based on preoperative serological examinations. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), which were assessed by Kaplan–Meier method and Cox regression. The prognostic performances of PALBI and other models were estimated by using the concordance index (C-index).Results: During a median follow-up time of 28 months, 31.6% (147/465) of patients died and 33.5% (156/465) experienced recurrence. Multivariate analyses revealed that both thrombocytosis and thrombocytopenia were independently associated with poor OS and RFS compared with normal platelet count (PLT) in HCC patients. Stratified analysis further revealed that PALBI was a significant predictor for HCC survival in patients excluding thrombocytopenia but not in patients with thrombocytopenia. In particular, in HCC patients excluding thrombocytopenia, the combination of tumor size with PALBI (C-index = 0.730, 95% CI: 0.674– 0.786) may be superior to the classical Barcelona Clinic Liver Cancer (BCLC) and Cancer of Liver Italian Program (CLIP) staging systems in predicting survival.Conclusion: In conclusion, PALBI grade, in particular the combination with tumor size, is an effective model for discriminating survival in HCC patients excluding thrombocytopenia but not in thrombocytopenic HCC patients.Keywords: hepatocellular carcinoma, survival, platelet–albumin–bilirubin, platelet count

Jing Zeng,1,2 Pengpeng Qu,1 Qingsong Pang,2 Ping Wang2 1Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University, Tianjin 300100, People’s Republic of China; 2Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of ChinaCorrespondence: Pengpeng Qu Email qu.pengpeng@hotmail.comIntroduction: This study aims to measure the air-kerma rate of 192-Ir-HDR-afterloading source with an ionization chamber in air and a solid cylindrical phantom separately and to compare the dose calibration by the American Association of Physicists in Medicine (AAPM) Task Group TG-43U1 formalism with the Abacus treatment planning system (TPS).Materials and Methods: The air-kerma rate of 192Ir source was measured by an ionization chamber in air and a solid cylindrical phantom separately. For the interesting point position P (8cm, 90°), the values of the dose were calculated with the TG-43U1 formula and compared with data from the Abacus TPS with single and multiple dwell positions, respectively.Results: The air-kerma rate percentage deviations between the detector measurements in air and the source certificate were − 1.28%, − 0.91%, − 0.71%, and 0.33% at the distances of 25cm, 50cm, 75cm, and 100cm, respectively. For the measurement in solid cylindrical phantom, the percent deviation from the air-kerma rate certificate was 1.85%. The percentage deviations of the dose calibration between Abacus TPS and TG-43U1 formalism at P (8cm, 90°) were − 2.30%, 1.76%, and 2.10% with different distances (between the dwell positions) of 0cm, 0.5cm, and 1cm, respectively.Conclusion: The in-air technique was a new attempt for clinic routine measurement. Further studies are still necessary. As a treatment planning system, the Abacus TPS should apply the AAPM TG-43U1 formulism for the development required in the future.Keywords: brachytherapy, 192Ir source, calibration, ionization chamber

Jiaqi Zhang, Wencheng Zhang, Baozhong Zhang, Dong Qian, Xiaoxia Li, Hualei Zhang, Qi Wang, Lujun Zhao, Qingsong Pang, Ping Wang Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of ChinaCorrespondence: Ping WangTianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin 300060, People’s Republic of ChinaTel +86 222 334 1405Fax +86 222 334 1405Email wangping@tjmuch.comPurpose: To evaluate and analyze the efficacy and prognostic factors of intensity-modulated radiotherapy in 250 patients with cervical and upper esophageal carcinoma.Patients and methods: From September 2009 to September 2016, we retrospectively analyzed 250 patients with cervical and upper esophageal carcinoma treated with intensity-modulated radiotherapy (IMRT). In our study, all patients received IMRT, 54 patients with cervical esophageal carcinoma and 196 patients with upper esophageal carcinoma. Treatment response, survival status and failure modes of treatment were observed, and prognostic factors were analyzed.Results: The median survival time was 22.60 months and 3-year survival rate was 42%. The median progress-free survival time was 14.52 months and 3-year progress-free survival rate was 29.3%. The median survival time and the median progress-free survival time for cervical esophageal carcinoma were 20.40 and 15.15 months, respectively. The median survival time and the median progress-free survival time for upper esophageal carcinoma were 25.80 and 14.52 months, respectively (P>0.05). The significant clinical factors associated with survival were patient age, radiotherapy dose and T stages (P

Yanjun Wang,1,* Bo Pang,2,* Rui Zhang,1 Yibing Fu,3 Qi Pang1 1Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China; 2Department of Neurosurgery, Shandong University, Jinan 250021, People’s Republic of China; 3Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi PangDepartment of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, People’s Republic of ChinaTel +86 136 1531 6688Email pangqi@sdu.edu.cnYibing FuDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, People’s Republic of ChinaTel +86 151 6888 9696Email fuyi_bing@163.comPurpose: Ubenimex, an aminopeptidase N (APN) inhibitor, is widely known for its use as an adjunct therapy for cancer therapy. However, in recent studies, it has also conferred antitumour effects in many cancers, but its anticancer mechanism is largely unknown. This study aims to investigate the specific anticancer activities and mechanisms of ubenimex in GH3 and MMQ cells.Materials and methods: In this study, we investigated the anticancer effects of ubenimex in GH3 and MMQ cells. Cell viability and cell death were assessed by the Cell Counting Kit-8 kit (CCK-8) and a LIVE/DEAD cell imaging kit. Apoptosis and intracellular reactive oxygen species (ROS) generation were assessed by flow cytometry and fluorescence microscopy. Autophagosome formation was detected by transmission electron microscopy, and autophagic flux was measured with mRFP-GFP-LC3 adenoviral transfection. The protein expression level was detected by Western blotting.Results: The results revealed that treatment with ubenimex induced apoptotic and autophagic cell death in GH3 and MMQ cells, which resulted in decreased viability, an increased proportion of apoptotic cells, and autophagosome formation. Further experiments showed that ubenimex induced ROS generation and activated the ROS/ERK pathway. The ROS scavenger NAC could attenuate ubenimex-induced apoptosis and autophagy.Conclusion: Our studies revealed that ubenimex exerted anticancer effects by inducing apoptotic and autophagic cell death in GH3 and MMQ cells, rendering it a possible effective adjunctive therapy for pituitary treatment.Keywords: pituitary, ubenimex, autophagy, apoptosis, ROS

Yanjun Wang,1 Jiachen Zhang,1 Yihang Yang,1 Qian Liu,2 Guangming Xu,1 Rui Zhang,1 Qi Pang1 1Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China; 2Department of Histology and Embryology, Shandong University Cheeloo College Medicine, Jinan, 250012, Shandong, China Purpose: Chemotherapy after surgery can prolong the survival of patients with gliomas. Dimethylaminomicheliolide (DMAMCL), a novel chemotherapeutic agent, exhibited antitumor properties in acute myeloid leukemia stem cells and showed an increased drug concentration in the brain. This study aims to investigate the specific anticancer activities and mechanisms of DMAMCL in glioma cells.Materials and methods: In this study, the effects of DMAMCL were evaluated and characterized in U87-MG and U251 glioma cells. Cell viability was assessed by Cell Counting Kit-8. Apoptosis, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) generation were assessed by fluorescence microscopy. Autophagosome formation was observed with transmission electron microscopy, and the autophagy flux was measured by transfecting cells with mRFP-GFP-LC3 adenoviral vectors. Immunofluorescence and Western blot analyses were used to determine the expression of proteins.Results: In the present study, treatment with DMAMCL decreased cell viability and induced apoptosis in U87-MG and U251 glioma cells. Additionally, DMAMCL activated autophagy-mediated cell death as evidenced by the formation of autophagosomes, accumulation of LC3B-II, inhibition of autophagy flux, and increase in cell viability after cotreatment with an autophagy inhibitor. Subsequent experiments showed that the DMAMCL-induced apoptosis and autophagy were possibly mediated by ROS generation and Akt/mTOR signaling pathway inhibition. On the other hand, the ROS scavenger N-acetyl-l-cysteine and the Akt activator insulin-like growth factor-1 attenuated the DMAMCL-induced autophagy and cell death.Conclusion: Our findings revealed that DMAMCL induced apoptosis and autophagic cell death by regulating the ROS/mitogen-activated protein kinase signaling pathway and suppressing the Akt/mTOR signaling pathway in human glioma cells. DMAMCL may be a novel effective anticancer agent, which can target gliomas. Keywords: DMAMCL, apoptosis, autophagy, ROS, glioma

Zhiguo Liu,1 Haixia An,2 Peng Song,3 Dejing Wang,4 Shichun Li,5 Kai Chen,6 Qi Pang7 1Department of Neurosurgery, People’s Hospital of Zhangqiu, Shandong Provincial Hospital Affiliated to Shandong University, Zhangqiu, Jinan, Shandong 250200, People’s Republic of China; 2Department of Oncology, Jinan Zhangqiu Hospital of Traditional Chinese Medicine, Zhangqiu, Jinan, Shandong 250200, People’s Republic of China; 3Department of Orthopedics, People’s Hospital of Zhangqiu, Zhangqiu, Jinan, Shandong 250200, People’s Republic of China; 4Department of Stomatology, People’s Hospital of Zhangqiu, Zhangqiu, Jinan, Shandong 250200, People’s Republic of China; 5Department of Doppler Ultrasonic, People’s Hospital of Zhangqiu, Zhangqiu, Jinan, Shandong 250200, People’s Republic of China; 6Department of Neurology, The Fourth People’s Hospital of Jinan, Tianqiao, Jinan, Shandong 250200, People’s Republic of China; 7Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Huaiyin, Jinan, Shandong 250200, People’s Republic of China Background: Human transmembrane protein 176A (TMEM176A) is upregulated in several tumors. Growing evidence has suggested the high clinical value of TMEM176A as a biomarker for early tumor diagnosis. However, less is known about the function of TMEM176A in glioblastomas (GBMs).Methods: In this study, we systematically analyzed the effect of TMEM176A knockdown and overexpression in GBM cells (U87, T98G and A172) on cell proliferation, cell cycle and cell apoptosis.Results: Our results indicated that TMEM176A acted as a tumor-promoting factor in GBM cells. Moreover, a specific ERK1/2 inhibitor, U0126, suppressed the function of TMEM176A in GBM cells. Therefore, we proposed that TMEM176A may be involved in a pathway including ERK1/2 in the regulation of the cell cycle. Moreover, we also found that TMEM176A affected the expression of Bcl2 and played a central role in apoptosis of GBM cells.Conclusion: Taken together, our results not only elucidated the multiple functions of TMEM176A in GBM cells but also provided a deep insight into the potential targets of TMEM176A in the growth of GBM cells. Keywords: TMEM176A, cell cycle, cell apoptosis, ERK1/2, glioblastomas

Daquan Wang,* Wencheng Zhang,* Dong Qian, Yong Guan, Xi Chen, Hualei Zhang, Jun Wang, Qingsong Pang Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China *These authors contributed equally to this work Background: Nab-paclitaxel is produced by the combination of paclitaxel particles with human serum albumin. Encouraging efficacy has been observed with nab-paclitaxel-based chemotherapy in a variety of solid tumors. The aim of the study reported here was to evaluate the efficacy and safety of weekly nab-paclitaxel plus cisplatin with concurrent intensity-modulated radiotherapy in patients with locally advanced esophageal cancer. Methods: Seventeen patients with esophageal cancer were enrolled between July 2014 and December 2015.The treatment included radical radiotherapy (95% planning target volume 60Gy/30f) and concurrent chemotherapy comprising nab-paclitaxel 60mg/m2/week plus cisplatin 25mg/m2/week, administered on days 1, 8, 15, and 22 of each 28-day cycle. The end point of this study included objective response rate (ORR), local-recurrence free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). Results: All the patients enrolled in the trial had squamous cell carcinoma. The median follow-up duration was 20.47 months. The ORR was 88.2%. LRFS, DMFS, PFS and OS at 3 years were 61%, 40%, 17% and 35%, respectively. The trial regimen was well tolerated, with grade 3–4 myelosupression, grade 3 radioactive esophagitis, and grade 3 radiation pneumonitis rates of 17.6%, 17.6%, and 11.8%, respectively. Conclusion: Weekly nab-paclitaxel plus cisplatin with concurrent intensity-modulated radiotherapy is an effective and well-tolerated treatment option for inoperable, locally advanced squamous cancer of esophageal. Keywords: nab-paclitaxel, esophageal cancer, squamous cell carcinoma

Hao Xu, Shangchen Xu, Rui Zhang, Tao Xin, Qi Pang Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China Purpose: SIL1 is a ubiquitous protein localized to the endoplasmic reticulum and functions as a cochaperone of BiP. Previous studies have shown that function loss of SIL1 is often associated with neurological diseases, such as Marinesco-Sjögren Syndrome. However, no studies have investigated the function of SIL1 in tumors. In this study we aim to reveal functions of SIL1 and the underlying mechanisms in glioma. Materials and methods: First, by searching on Gene Expression Profiling Interactive Analysis, we examined SIL1 expression and prognostic value in glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Immunohistochemical analysis (IHC) was also performed to determine the endogenic SIL1 level. Cell counting kit-8 (CCK8) and clone formation assays were used to detect cell proliferation of U251 cells. Cell migration was detected by transwell assay and cell cycle and apoptosis were detected by flow cytometry. Western blot was performed to determine protein expression. Results: We found that the expression of SIL1 was increased by approximately 1.5-fold in GBM and 1.3-fold in LGG compared with normal controls (P

Heming Lu,1,2 Yuying Wu,3 Xu Liu,2 Hailan Jiang,2 Qiang Pang,2 Luxing Peng,2 Jinjian Cheng,2 Shan Deng,2 Junzhao Gu,2 Renfeng Zhao,3 Xiaoxia Hu,3 Changyi Chen,3 Jinming Yu1 1Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China; 2Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; 3Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China Background: To investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus anti-epidermal growth factor receptor monoclonal antibody followed by surgery for locally advanced cervical cancer (LACC). Patients and methods: Patients with histologically proven LACC were enrolled into this prospective study. All patients received intensity-modulated radiation therapy with conventional fractionation. Weekly cisplatin or nedaplatin was administered concurrently with intensity-modulated radiation therapy. Nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, was given at a dose of 200 mg per week for 6 cycles. Approximately 1 month after the completion of neoadjuvant treatment, the patients were assessed for clinical tumor response and operability based on MRI and gynecological examination. For those who were considered to be candidates for surgery, radical hysterectomy, and pelvic lymph node dissection were performed 5–6 weeks after the completion of neoadjuvant therapy. Results: Twenty-eight patients were enrolled. Clinical complete response and partial response were found in 8 (28.5%) and 20 (71.5%) patients, respectively. Four patients were not eligible for surgery and 2 patients refused surgery although they were assessed as surgical candidates. They were not included in this analysis. Radical hysterectomy and pelvic lymph node dissection were performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease, according to the pathological evaluation. Median follow-up time was 22 months (range, 5–39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicities were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed. Conclusion: Concurrent chemoradiotherapy plus nimotuzumab followed by surgery is highly effective and safe in LACC. Further studies are warranted to confirm the findings. Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery, hysterectomy

Qing Pang,1,* Hao Jin,1,* Kai Qu,2,* Zhongran Man,1 Yong Wang,1 Song Yang,1 Lei Zhou,1 Huichun Liu1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China *These authors contributed equally to this work Background: Recent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial. Methods: To assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications. Results: A total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR =0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06). Conclusion: Taken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC. Keywords: NSAIDs, aspirin, hepatocellular carcinoma, incidence, recurrence

Hao Jin,1–3 Geliang Xu,2 Qiang Zhang,3 Qing Pang,3 Meifang Fang3 1School of Medicine, Shandong University, Jinan, 2Department of Hepatic Surgery, Anhui Provincial Hospital, Hefei, 3Department of Hepatobiliary Surgery, The First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China Background: Synaptotagmin-7 (Syt-7) is a member of the synaptotagmin (Syt) family, which plays an important role in many physiological and pathological processes. However, to the best of our knowledge, there is no study describing its function in tumors, particularly in hepatocellular carcinoma (HCC). Therefore, in this study, we examined the role of Syt-7 in HCC and attempted to elucidate its underlying mechanism. Materials and methods: We examined the expression levels of Syt-7 in HCC cell lines and normal hepatocytes by real-time quantitative polymerase chain reaction analysis. The effects of Syt-7 knockdown on in vitro cell growth were assessed by Celigo image cytometry, MTT assay, colony formation assay, and cell cy cle analysis. In vivo tumorigenesis was evaluated using a nude mouse model. The underlying molecular mechanism was evaluated using a PathScan Stress Signaling Antibody Array. Results: Syt-7 mRNA levels were highly expressed in Huh-7 and Hep3B cells; moderately expressed in SMMC-7721, HepG2, and BEL-7402 cells; and lowly expressed in normal hepatocytes L-O2. Functional experiments demonstrated that Syt-7 knockdown significantly suppressed cell proliferation and induced cell cycle arrest by increasing phosphorylation of Chk1 and p53. Furthermore, Syt-7 knockdown remarkably reduced the growth of xenograft tumors in mice. Conclusion: The results of this study suggest that Syt-7 plays a vital role in tumorigenesis and in the development of HCC. Syt-7 can be used as a new diagnostic and therapeutic target in HCC. Keywords: hepatocellular carcinoma, Syt-7, Chk1, p53, cell cycle

Fei Lu,1,2 Zhiyong Pang,2,3 Jingjing Zhao,2 Kai Jin,4 Haichun Li,2 Qiang Pang,2 Long Zhang,2 Zhiqing Pang2 1Department of Pharmacy, Xianju People’s Hospital, Xianju, Zhejiang, 2Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 3Chongyang Center for Disease Control and Prevention, Xianning, Hubei, 4School of Life Science, Fudan University, Shanghai, People’s Republic of China Abstract: The blood–brain barrier is a formidable obstacle for glioma chemotherapy due to its compact structure and drug efflux ability. In this study, a dual-targeting drug delivery system involving Angiopep-2-conjugated biodegradable polymersomes loaded with doxorubicin (Ang-PS-DOX) was developed to exploit transport by the low-density lipoprotein receptor-related protein 1 (LRP1), which is overexpressed in both blood–brain barrier and glioma cells. The polymersomes (PS) were prepared using a thin-film hydration method. The PS were loaded with doxorubicin using the pH gradient method (Ang-PS-DOX). The resulting PS were uniformly spherical, with diameters of ~135 nm and with ~159.9 Angiopep-2 molecules on the surface of each PS. The drug-loading capacity and the encapsulation efficiency for doxorubicin were 7.94%±0.17% and 95.0%±1.6%, respectively. Permeability tests demonstrated that the proton diffusion coefficient across the PS membrane was far slower than that across the liposome membrane, and the common logarithm value was linearly dependent on the dioxane content in the external phase. Compared with PS-DOX, Ang-PS-DOX demonstrated significantly higher cellular uptake and stronger cytotoxicity in C6 cells. In vivo pharmacokinetics and brain distribution experiments revealed that Ang-PS-DOX achieved a more extensive distribution and more abundant accumulation in glioma cells than PS-DOX. Moreover, the survival time of glioma-bearing rats treated with Ang-PS-DOX was significantly prolonged compared with those treated with PS-DOX or a solution of free doxorubicin. These results suggested that Ang-PS-DOX can target glioma cells and enhance chemotherapeutic efficacy. Keywords: Angiopep-2, dual targeting, biodegradable polymersomes, doxorubicin, glioma treatment

Wencheng Zhang,1 Qingsong Pang,1 Cihui Yan,2 Qifeng Wang,3 Jingsong Yang,3 Shufei Yu,3 Xiao Liu,3 Zhiyong Yuan,1 Ping Wang,1 Zefen Xiao3 1Department of Radiation Oncology, 2Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR) signaling pathway on the expression of programmed death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) cells with EGFR overexpression. Methods: Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF) with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved. Results: This study found that PD-L1 expression increased significantly in an EGFR-dependent manner by the activation of EGFR signaling and decreased sharply when EGFR signaling was blocked. The upregulated expression of PD-L1 was not associated with EGFR-STAT3 signaling pathway, but may be affected by EGFR–PI3K–AKT, EGFR–Ras–Raf–Erk, and EGR–PLC-γ signaling pathways. Conclusion: The expression of PD-L1 can be regulated by EGFR signaling activation in ESCC, which indicates an important role for EGFR-mediated immune escape and potential molecular pathways for EGFR-targeted therapy and immunotherapy. Keywords: epidermal growth factor receptor, programmed death-ligand 1, esophageal squamous cell carcinoma, immune checkpoint

Baozhong Zhang, Lujun Zhao, Zhiyong Yuan, Qingsong Pang, Ping Wang Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People’s Republic of China Objective: The use of postoperative radiotherapy (PORT) remains controversial for Stage IIIA-N2 non-small-cell lung cancer (NSCLC) patients, a possible reason is that IIIA-pN2 NSCLC diseases are a heterogeneous group with different clinicopathologic features. The aim of this research was to prove whether the mediastinal lymph nodes’ (LNs) skipping status could indicate the necessity of the PORT for the pN2 NSCLC patients.Methods: The skip metastasis was defined as pN0N2 (no N1 LN involved), and nonskip metastasis was pN1N2 (one or more N1 LNs involved). Patients were divided into two groups: LNs nonskip and LNs skip, and postoperative chemoradiotherapy (POCRT) and postoperative chemotherapy. Then, the LN nonskip and LN skip groups were further divided into subgroups: POCRT and point of care testing (POCT) for subgroup analysis.Results: There were 220 cases included in the analysis, and 43 of them received PORT. On univariate analysis, the median 3-year progression-free survival (PFS) was, respectively, 16 months (27.7%) for the LN skip group and 11 months (15.3%) for the LN nonskip group (P=0.001). The median 3-year overall survival (OS) was, respectively, 35 months (47.0%) for the LN skip group and 27 months (38.7%) for the LN nonskip group (P=0.025). The median 3-year local recurrence-free survival (LRFS) was, respectively, 25 months (41.0%) for the LN skip group and19 months (29.9%) for the LN nonskip group (P=0.014). The median 3-year distant metastasis-free survival (DMFS) was, respectively, 22 months (32.5%) for the LN skip group and 15 months (20.4%) for the LN nonskip group (P=0.013). The median 3-year PFS was, respectively, 17 months (25.6%) for the POCRT group and 12 months (18.6%) for the POCT group (P=0.037). Although the POCRT group showed better OS, LRFS, and DMFS than the POCT group, the results showed no statistical significance. In subgroup analysis, there was no statistical significance in the Kaplan–Meier analysis between subgroups, but it showed that POCRT resulted in better PFS, OS, and DMFS in both LN skip and LN nonskip subgroups; this advantage was more obvious in the LN skip subgroup.Conclusion: The LN skip status is closely related to the survival of the IIIA-N2 NSCLC disease, and the LN skip patients may get more benefit in PFS and LRFS than the LN nonskip patients from PORT. Keywords: non-small-cell lung cancer (NSCLC), N2, postoperative chemoradiotherapy (POCRT), LN skip/nonskip, PFS, OS, DMFS

Dong Qian,1 Jingjing Cheng,1 Xiaofeng Ding,1 Xiuli Chen,1 Xi Chen,1 Yong Guan,1 Bin Zhang,2 Jiefu Wang,3 Puchun Er,1 Minghan Qiu,1 Xianliang Zeng,1 Yihang Guo,1 Huanhuan Wang,1 Lujun Zhao,1 Dan Xie,4 Zhiyong Yuan,1 Ping Wang,1 Qingsong Pang1 1Department of Radiotherapy, 2Department of Lung Cancer, 3Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 4State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China Abstract: PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls. PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, and the rate of PinX1 protein low/negative expression in CRC and normal tissues was 60% (52/86) and 24% (6/25), respectively (P=0.037). In addition, PinX1 downregulation was significantly associated with short overall survival (P=0.016) and disease-free survival (P=0.042) in CRC patients. Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting overall survival and disease-free survival for CRC patients. Furthermore, we demonstrated that ectopic overexpression of PinX1 in CRC cells inhibited their proliferation, promoted apoptosis, repressed telomerase activity, and induced telomere shortening. These findings suggest that PinX1 may be a prognostic biomarker for CRC patients’ survival and that it inhibits cell proliferation and promotes apoptosis by repressing telomerase activity and inducing telomere shortening. Targeting PinX1 may therefore provide a novel therapeutic strategy for CRC patients. Keywords: colorectal carcinoma, PinX1, cell proliferation, apoptosis, telomerase, telomere, prognostic biomarker

Yan Deng, Qing Pang, Run-Chen Miao, Wei Chen, Yan-Yan Zhou, Jian-Bin Bi, Su-Shun Liu, Jing-Yao Zhang, Kai Qu, Chang Liu Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Background: Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. Patients and methods: This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. Results: Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P

Qing Pang, Jian-Bin Bi, Zhi-Xin Wang, Xin-Sen Xu, Kai Qu, Run-Chen Miao, Wei Chen, Yan-Yan Zhou, Chang Liu Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Shaanxi Province, People’s Republic of China Background: Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. Methods: We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. Results: During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P

Kai Qu,1,* Qing Pang,1,* Ting Lin,1 Li Zhang,2 Mingliang Gu,3 Wenquan Niu,4 Chang Liu,1,* Ming Zhang5 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 3Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein–Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both PG was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P

Hongqing Zhuang,* Hailing Hou,* Zhiyong Yuan, Jun Wang, Qingsong Pang, Lujun Zhao, Ping WangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People's Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to investigate radiation pneumonitis and its associated risk factors in patients with non-small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy.Materials and methods: We conducted an analysis of patients with nonoperable stage IIIA–IV non-small-cell lung cancer who were treated with concurrent thoracic radiotherapy and erlotinib (ClinicalTrials.gov identifier: NCT00973310). The Common Terminology Criteria for Adverse Events version 3.0 grading system was applied to evaluate the incidence of radiation pneumonitis. The lung dosimetric parameters were recorded in accordance with the treatment plan, and the study endpoint was radiation pneumonitis at grade 2 or more.Results: Among the 24 selected clinical cases, nine were identified with radiation pneumonitis of grade 2 or above (37.5%). This included four cases with grade 2 (16.7%), two cases with grade 3 (8.3%), and three cases with grade 5 (12.5%). The results showed that the planning target volume was a significant factor affecting the incidence of radiation pneumonitis. All lung dosimetric parameters exhibited statistically significant differences between patients with pneumonitis and patients without pneumonitis. The receiver operating characteristic (ROC) curve analysis showed that all lung dosimetric parameters were useful in predicting the incidence of radiation pneumonitis. In addition, the threshold values of V5, V10, V15, V20, V30, and mean lung dose were >4%, >29%, >27%, >22%, >17% and >1,027 cGy, respectively.Conclusion: Special attention should be paid to the adverse effects of radiation pneumonitis in concurrent thoracic radiotherapy and erlotinib treatment. Lung dosimetric parameters are important predictive factors in radiation pneumonitis.Keywords: erlotinib, thoracic radiotherapy, radiation pneumonitis, dosimetric parameter, threshold value for lung radiation

Hongqing Zhuang,1–4 Zhiyong Yuan,1–4 Jun Wang,1–4 Lujun Zhao,1–4 Qingsong Pang,1–4 Ping Wang1–41Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, 2National Clinical Research Center of Cancer, 3Tianjin Key Laboratory of Cancer Prevention and Therapy, 4Tianjin Lung Cancer Center, Tianjin, People’s Republic of ChinaAbstract: The aim of this paper is to explore the efficacy of whole brain radiotherapy (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both arms. In the combination arm, 150 mg erlotinib was given each day, starting the first day of radiotherapy and continuing for 1 month following the end of radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best supportive therapy was given to both arms. The intracranial objective response rate and the local progression-free survival (LPFS) were primary endpoints. Toxicity, progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the combination group were enrolled from November 2009 to December 2011. In the WBRT and the combination arms, respectively, the objective response rate was 54.84% and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P = 0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the combination group, there were no differences of LPFS, PFS, and OS between the epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type patients. No Grade 4 or higher side effects were observed in either group. A multivariate analysis indicated that erlotinib was the most important prognostic factor for a prolonged survival. Data showed that erlotinib in combination with WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung adenocarcinoma patients with multiple brain metastases compared with WBRT monotherapy.Keywords: WBRT, tyrosine kinase inhibitor, radiosensitizer, erlotinib