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// Yufeng Wu 1 , Ruirui Si 2 , Sen Yang 1 , Suhua Xia 3 , Zelai He 4 , Lili Wang 1 , Zhen He 1 , Qiming Wang 1 , Hong Tang 1 1 Department of Internal Medicine, Affiliated cancer hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, P. R. China 2 Department of Health Center, Henan Airport Group Co., Ltd., Henan, 450000, P. R. China 3 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, P. R. China 4 Department of Oncology, The 2nd Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, PR China Correspondence to: Qiming Wang, email: qimingwang1006@163.com Hong Tang, email: 852261201@qq.com Keywords: depression, chemotherapy, small cell lung cancer, brain derived neurotrophic factor, ABCG2 Received: August 04, 2016 Accepted: November 07, 2016 Published: November 11, 2016 ABSTRACT Patients with lung cancer often experience a state of depression, and these conditions may severely affect their quality of life (QoL) and prescription compliance. The current study was conducted to delineate the complex links between depression and the prognosis of patients with small cell lung cancer (SCLC) and the underlying mechanism was also explored. 186 patients who received platinum-based chemotherapy for newly diagnosed stage III or stage IV SCLC were enrolled. The Self-Rating Depression Scale (SDS) questionnaire was completed the day before the start of chemotherapy to assess the depression status of the patients. Patients with stage IV SCLC or lower BMI have higher depression scores. In terms of the adverse effects of chemotherapy, depression severely decreases patient tolerance to chemotherapy and their QoL score (R 2 = 0.2385) and is also associated with severe vomiting ( P < 0.001), leukopenia (R 2 = 0.2332), and prolonged hospital stay (R 2 = 0.1961). More importantly, severe depression reduces the PFS (R 2 = 0.1943) and OS ( P < 0.01) of the patients. We found that patients with severe depression displayed a downregulated level of serum BDNF and that the level of serum BDNF was highly correlated with the OS of the patients (R 2 = 0.2292). Using the MTT cell viability assay in vitro , we observed that cotreatment with BDNF clearly enhanced the chemosensitivity of NCI-H69 tumor cells to Cisplatin and induced the downregulation of ABCG2. Based on this evidence, it appears that a relationship does exist between depression and prognosis in SCLC and that the mechanism by which depression affects prognosis is achieved via the downregulation of BDNF expression.

// Zelai He 1, 3, * , Xiangyu Zhang 4, * , Jingwen Huang 1, 3, * , Yufeng Wu 5 , Xuanzhang Huang 1 , Jie Chen 1 , Junyong Xia 6 , Hao Jiang 3 , Jing Ma 2 , Jian Wu 1 1 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 2 Ultrasonic Department, Shanghai Songjiang Center Hospital, Shanghai, China 3 The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 4 Department of Pathology, Jining No.1 Peoples’ Hospital, Jining, China 5 Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China 6 Department of Nuclear Medicine, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China * These authors contributed equally to this work Correspondence to: Junyong Xia, email: xiabingbing@126.com Hao Jiang, email: jianghao1223@163.com Jing Ma, email: majing0709@163.com Jian Wu, email: wzzjian@hotmail.com Keywords: K237, folate, PEG-PLGA, nanoparticles, biodistribution Received: July 29, 2016 Accepted: October 12, 2016 Published: October 24, 2016 ABSTRACT In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo . In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m ( 99m Tc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor.

// Zelai He 1,2 , Jingwen Huang 2 , Yuanyuan Xu 3 , Xiangyu Zhang 3 , Yanwei Teng 3 , Can Huang 3 , Yufeng Wu 4 , Xi Zhang 2 , Huijun Zhang 5 and Wenjie Sun 1 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 3 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 4 Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China 5 Department of Cardio-thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China Correspondence to: Xi Zhang, email: // Huijun Zhang, email: // Wenjie Sun, email: // Keywords : nanoparticles, PLGA, biocompatibility, chemotherapy, cytotoxicity Received : January 31, 2015 Accepted : October 11, 2015 Published : October 26, 2015 Abstract An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles ( p < 0.05). In addition, more importantly, the enhanced anti-tumor efficacy of the CDDP+PTX-encapsulated nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with high FA receptor expression.