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Background Nasopharyngeal carcinoma (NPC), arising from nasopharynx epithelium, is a rare type of malignant carcinoma that has a specific geographical distribution and a high risk of distant metastases. For most of the diagnosed NPC patients, the total survival rate decreased significantly due to the high local recurrence rate and metastasis rate. Concurrent chemoradiotherapy (CCRT), as routine therapy strategy of NPC, usually accompanies with high-dosage cytotoxic agents and serious toxic side reaction. Therefore, there is an urgent need for update the existing therapy strategies. In this study, we sought to investigate the effects of a combined therapy strategy, erlotinib combined with cisplatin and radiotherapy, on biological characteristics of NPC CNE2 cells and the potential reasons. Methods CNE2 cells in logarithmic phase seeding in 96-well plates received concentration gradients of erlotinib (at 0, 10, 20, 40, 80, 160, 320 mmol/L) or cisplatin (at 0, 0.25, 0.5, 1, 2, 4, 8 mg/L), in order to obtain the optimal working concentration of erlotinib and cisplatin via 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Then, cells were divided into control group and four treatment groups (Group I-IV). All treatment groups received irradiation of 4 Gy, moreover, Group II-IV respectively received erlotinib, cisplatin and erlotinib plus cisplatin at optimal working concentration. After 24 and 48 h of irradiation, growth inhibition rate was determined; invasion ability and migration ability was respectively detected by Boyden's chamber assay and cell scratch test; flow cytometry was performed for determining apoptosis rate and cell cycle distribution; the expression levels of epidermal growth factor receptor (EGFR) signal pathway proteins were semi-quantitatively analyzed by Western-blot. Results Compared with Group I, all the other treatment groups showed better inhibition effect on cell viability, invasion and migration ability and higher apoptosis rate, while Group IV showed the strongest growth inhibition effect and highest apoptosis rate. In addition, EGFR signal pathway proteins of Group IV showed the lowest expression level. Conclusions In combined therapy with radiotherapy/chemotherapy, erlotinib could enhance radiotherapy/chemotherapy sensitivity, probably because it could suppress DNA damage repair after radiotherapy/chemotherapy, thus weakening radiotherapy/chemotherapy resistance of tumor cells.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Jianfeng Huang,1,* Qinzhou Zou,1,* Danqi Qian,1 Leyuan Zhou,1 Bo Yang,1 Jianjun Chu,1 Qingfeng Pang,2 Kewei Wang,2 Fuzheng Zhang1 1Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, 2Department of Epidemiology, Wuxi Medical School of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China *These authors contributed equally to this work Objective: This study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Patients and methods: A total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2–14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin. Results: With a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%–91.72%) and 97.67% (95% CI: 84.62%–99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received≥6cycles of nimotuzumab showed a better PFS than those receiving

// Jian-feng Huang 1,2,* , Fu-zheng Zhang 2,* , Qin-zhou Zou 2 , Le-yuan Zhou 2 , Bo Yang 2 , Jian-jun Chu 2 , Jia-hua Yu 1 , Hao-wen Zhang 1 , Xiao-peng Yuan 3 , Guo-mei Tai 3 , Fen-ju Liu 1 and C-M Charlie Ma 4 1 Department of Radiobiology, School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, China 2 Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China 3 Department of Radiation Oncology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China 4 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA * These authors have contributed equally to this work Correspondence to: Fen-ju Liu, email: // Keywords : nasopharyngeal carcinoma, nimotuzumab, chemoradiotherapy, induction chemotherapy Received : October 13, 2016 Accepted : November 24, 2016 Published : December 10, 2016 Abstract Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.