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321. [Efficacy and Safety of Crizotinib in Advanced or Recurrent 
ALK-positive Non-small Cell Lung Cancer].

作者: Xiaoyan Li.;Huayan Xu.;Fang Gao.;Xun Kang.;Juan Zhang.;Jing Zhao.;Yi Lin.;Xiaoqing Liu.
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷8期488-493页
Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.

322. [Effect of vascular changes on prognosis after induced chemotherapy for advanced hypopharyngeal carcinoma].

作者: W Guo.;G F Yin.;J W Huang.;Z Yang.;H F Liu.;Y Zhang.;H B Xu.;Z Y Liu.;Z G Huang.
来源: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019年54卷8期591-596页
Objective: To analyze the clinical characteristics of two groups(vascular classification declines or not in narrow band imaging (NBI) of patients with advanced hypopharyngeal carcinoma after induced chemotherapy, to follow-up and compare the survival differences between the two groups, and to explore the effect of vascular changes on clinical prognosis after induced chemotherapy in patients with advanced hypopharyngeal carcinoma. Methods: Clinical data of 56 patients with advanced hypopharyngeal carcinoma from August 2014 to September 2016 in Beijing Tongren Hospital, Capital Medical University were collected. The patients were divided into two groups according to NBI vascular classification declines or not after induced chemotherapy. The survival of patients and the impact of different factors on the prognosis were retrospectively analyzed. SPSS 24.0 statistical software was used for analysis. Frequency data were compared between the two groups using χ(2) test. Kaplan-Meier method and Cox regression analysis were employed for survival analysis and Log-Rank test was used for inter-group comparison, P<0.05 was statistically significant. Results: There was significant difference in overall survival rate(OS) between two groups of patients with advanced hypopharyngeal carcinoma after induced chemotherapy (P<0.05). Multivariate analysis showed that NBI vascular classification changes after induced chemotherapy was the impact factor for prognosis of advanced hypopharyngeal carcinoma after induced chemotherapy. Conclusion: In addition to recurrence and metastasis, NBI vascular classification changes is the important impact factor for prognosis of advanced hypopharyngeal carcinoma after induced chemotherapy. Patients with NBI vascular classification declines have significant survival benefit. The patients with advanced hypopharyngeal carcinoma should be checked with NBI examination before and after induced chemotherapy. NBI should be included in the routine screening indicators for prognosis of advanced hypopharyngeal carcinoma.

323. [Laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis].

作者: J J Ma.;L Zang.;Z Y Yang.;B W Xie.;X Z Hong.;Z H Cai.;L Y Zhang.;C Yan.;Z G Zhu.;M H Zheng.
来源: Zhonghua Wei Chang Wai Ke Za Zhi. 2019年22卷8期774-780页
Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

324. [Synthesis and antitumor activity of novel indole podophyllotoxin derivatives].

作者: Dan-Li Tian.;Chun-Po Liang.;Jing Liang.;Hong Chen.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷12期2532-2537页
According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.

325. [Mechanism research of curcumin on cancer cells based on cell metabolic profiling].

作者: Jia-Hui Hu.;Pan-Pan Xu.;Li-Juan Hou.;Min Liu.;Hua Wang.;Guang-Hui Gao.;Li-Xin Sun.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷11期2359-2366页
In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

326. [Chemical constituents from green walnut husks and their antitumor activity in vitro].

作者: Dong-Xue Sun.;Xiong-Fei Guo.;La-Tengtuya A.;Xiao-Ling Ma.;Hong-Yan Wei.;Guo-Xu Ma.;Lei-Ling Shi.;Jing Zhang.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷11期2278-2282页
Fourteen chemical constituents, including 5-hydroxy-4-methoxy-1-tetralone(1), 4,8-dihydroxy-1-tetralone(2), 4,5-dihydroxy-α-tetralone(3), blumenol B(4), dehydrovomifoliol(5), megastigm-5-ene-3,9-diol(6), juglanin B(7), blumenol C(8), loliolide(9), oleracone B(10), syringarsinol(11), pinoresinol(12), methyl 4-hydroxy-3-methoxybenzoate(13), and isovanillic acid(14), were isolated from the dichloromethane fraction of 95% methanol extract of green walnut husks by silica gel and MCI column chromatography, and Pre-HPLC. Their structures were determined by spectroscopic methods, such as NMR, MS and so on. Among them, compounds 1, 4-6, 8-13 were isolated from the green walnut husks for the first time, and compounds 4-6, 8, 10, 12, 13 were isolated from the Juglans genus for the first time. All of isolates were detected their inhibitory activities against HeLa, HGC-27 and Ht-29 cell lines by the MTT assay. The result showed that compounds 2, 3, 7, 9 and 11 exhibited inhibitory activity against the tested cell line. The IC_(50) of 7 were 26.5, 9.0, 25.4 μmol·L~(-1), respectively.

327. [Study on sesquiterpenes from agarwood originating from Gyrinops salicifolia].

作者: Hui-Qin Chen.;Feng-Juan Guo.;Cai-Hong Cai.;Wen-Hua Dong.;Hao Wang.;Wei Li.;Wen-Li Mei.;Hao-Fu Dai.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷11期2274-2277页
Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4β,5β,7β-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].

328. [Preparation of docetaxel-loaded nanomicelles and their anti-Lewis lung cancer effect in vitro].

作者: Ya-Jie Wang.;Jie Wang.;Dan-Li Hao.;Qiao-Xin Yue.;Ran Xie.;Ge-Jing DE.;Hong Yi.;Chen Zang.;Qing-He Zhao.;Yan-Jun Chen.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷11期2251-2259页
Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.

329. [Effects of miR-144 on proliferation, apoptosis and cisplatin resistance by targeting MYCN in pediatric neuroblastoma].

作者: H J Liu.;G L Li.;P C Lei.
来源: Zhonghua Zhong Liu Za Zhi. 2019年41卷7期516-521页
Objective: To investigate the effects and mechanisms of miR-144 on proliferation, apoptosis and cisplatin (DDP) resistance of neuroblastoma cells. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expressions of miR-144 and MYCN in neuroblastoma cell lines, including SH-SY5Y and SK-N-SH, and human umbilical vein endothelial cells HUVEC. The miR-negative control, miR-144 mimics, si-negative control, si-MYCN, miR-144 mimics and pcDNA, miR-144 mimics and pcDNA-MYCN co-transfected SH-SY5Y cells were described as miR-NC, miR-144, si-NC, si-MYCN, miR-144+ pcDNA and miR-144+ pcDNA-MYCN group, respectively. The half maximal inhibitory concentration (IC(50)) and cell proliferation were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The protein expressions of MYCN, p21, cyclin D1, Bax, Bcl-2 were analyzed by western blot. Cell apoptosis was detected by flow cytometry. The cell fluorescence activity was detected by double luciferase reporter gene assay. Results: Compared with HUVEC cells, the expressions of miR-144 in neuroblastoma cells SH-SY5Y and SK-N-SH significantly decreased, while the mRNA and protein expression of MYCN significantly increased. The IC(50) of DDP was 9.16 μg/ml in SH-SY5Y cells. The absorbance value in 490nm (A(490) value) of miR-144 group was 0.30±0.03, significantly lower than 0.46±0.03 of miR-NC group. The cell apoptotic rate of miR-144 group was 26.94%±2.01%, significantly higher than 9.68%±0.52% of miR-NC group. The IC(50) value of DDP in miR-144 group was 2.95±0.26, significantly lower than 9.23±0.61 of miR-NC group. The expressions of p21, cyclin D1, Bax, Bcl-2 in miR-NC and miR-144 group were 2.67±0.19, 0.41±0.04, 2.12±0.21, 0.18±0.01 and 1.01±0.07, 1.00±0.06, 1.00±0.05, 1.00±0.06, respectively, with statistical significance (all P<0.05). Knockdown of MYCN showed the similar effects with those of miR-144 overexpression in SH-SYSY cells. MiR-144 significantly inhibited the fluorescence activity of ectopic MYCN expressing cells and negatively regulated the expression of MYCN. Overexpression of MYCN can reverse the effects of miR-144 on proliferation inhibition, apoptosis promotion and sensitization of SH-SY5Y cells to DDP. Conclusion: MiR-144 inhibits proliferation, promotes apoptosis and enhances the sensitivity of neuroblastoma cells to DDP through targeting MYCN, which provides a potential treatment for neuroblastoma.

330. [Chemical constituents from stems and leaves of Clausena emarginata].

作者: Shi Hu.;Jia-Ming Guo.;Wen-Hao Zhang.;Ming-Ming Zhang.;Yan-Ping Liu.;Yan-Hui Fu.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷10期2096-2101页
The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.

331. [In vivo anti-tumor activity of tumor-targeting pH-sensitive lipoprotein-mimic nanocarrier with paclitaxel loaded].

作者: Cong-Hui Chen.;Meng-Yu Liu.
来源: Zhongguo Zhong Yao Za Zhi. 2019年44卷10期2072-2077页
Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.

332. [Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer].

作者: Sixuan Wu.;Chunhong Hu.;Fang Wu.;Yuanqiang Wu.;Ping Liu.
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷7期440-448页
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have made a breakthrough in the treatment of NSCLC and changed the treatment pattern for NSCLC. Immunological checkpoint inhibitors targeting PD-1/PD-L1 are beneficial to patients, both in the first-line and second-line treatment of advanced NSCLC, in the adjuvant treatment of locally-advanced NSCLC, and in the neoadjuvant therapy of early NSCLC, which show an important role in the comprehensive treatment of NSCLC. This article reviews the clinical research progress of immunological checkpoint inhibitors targeting PD-1/PD-L1 in NSCLC.
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333. [Chinese Expert Consensus on Antiangiogenic Drugs for Advanced Non-small Cell Lung Cancer (2019 Edition)].

作者: .
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷7期401-412页

334. [Hypoxia increases chemotherapy resistance in nasopharyngeal carcinoma via inducing CDK6 deSUMOylation].

作者: Q Ren.;F T Liu.;C Y Zhang.;L L Li.;R Z Cheng.;X Z Liu.;Q Liu.;H F Zhou.
来源: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019年54卷7期524-528页
Objective: To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification. Methods: Cobalt chloride (CoCl(2)) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC(50)) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level. Results: The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)). Conclusion: Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.

335. [Efficacy and safety of vandetanib on advanced medullary thyroid carcinoma: single center result from a phase Ⅲ study].

作者: S X Wang.;X W Zhang.;X X Wang.;C M An.;Y B Zhang.;W Liu.;Y F Zhao.;X H He.;Z J Li.;L J Niu.;P Z Tang.
来源: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019年54卷6期439-444页
Objective: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC. Methods: This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria. Results: The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred. Conclusions: Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.

336. [A Case of Pseudoprogression During Atezolizumab Therapy 
in Lung Adenocarcinoma].

作者: Xue Wang.;Yi Zhao.;Zhiwei Chen.
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷6期389-394页
Lung cancer is the most common cause of cancer-related death worldwide. There are two classes of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC represents approximately 85% of all lung cancer cases. Immune checkpoint inhibitors (ICIPs) are a class of inhibitors of programmed death-1 and programmed death-ligand 1. Preclinical studies have shown that ICIPs have shown good clinical efficacy and durable response in diverse cancers. Among them, atezolizumab (MPDL3280), an anti-PD-L1 monoclonal antibody, is being investigated as a potential therapy against solid tumors and hematologic malignancies in humans. Pseudoprogression is reported as one of the unique phenomena with immune therapeutic agents. Here we report case of a person with advanced NSCLC who developed pseudoprogression after receiving immunotherapy. We hope this case could help clinicians to make appropriate decision when assessing therapeutic effects of immunotherapy.
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337. [New Advances in the Treatment for Small Cell Lung Cancer].

作者: Xiaoxia Cui.;Peng Song.;Li Zhang.
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷6期355-362页
Small cell lung cancer (SCLC) is a refractory cancer with high degree of malignancy, rapid disease progression, poor prognosis and easy recurrence. In the past 30 years, the traditional treatment of SCLC, mainly chemotherapy and radiotherapy, has not changed significantly, and the effective treatment method for clinical needs is extremely urgent. The rapid development of precision medicine has revealed the molecular biological characteristics of SCLC, so its diagnosis and treatment will into a new era. At present, some studies have shown that anti-angiogenic drugs, immunotherapy and so on have improved the efficacy of SCLC treatment to some extent, and there are more studies on the diagnosis and treatment of SCLC, so a new field of SCLC treatment are coming and bringing more survival benefits to patients. New studies on targeted therapy, anti-angiogenesis drugs and immunotherapy of molecular pathology of SCLC are emerging. This paper reviews the new diagnosis and treatment methods of SCLC to provide new guidance for its clinical treatment.
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338. [Chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer: a short-term efficacy and safety analysis].

作者: P H Xu.;Y J Shen.;W J Xiao.;G W Lin.;X J Qin.;Y Zhu.;B Dai.;D W Ye.
来源: Zhonghua Wai Ke Za Zhi. 2019年57卷6期418-421页
Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q(R))) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m(2) intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) μg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 μg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 μg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions: The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

339. [Role of PPAR-γ-regulated autophagy in genistein-induced inhibition of hepatic stellate cell activation].

作者: Xipeng Liu.;Meifang Zhang.;Haifeng Zhang.;Anda Zhao.;Juan Sun.;Wen Tang.
来源: Nan Fang Yi Ke Da Xue Xue Bao. 2019年39卷5期561-565页
To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) in vitro and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect.

340. [Effect of Apatinib on Invasion and Migration of Lung Cancer Cells
and Its Mechanism].

作者: Yin Yuan.;Hao Gong.;Yongwen Li.;Hongbing Zhang.;Ying Li.;Weiting Li.;Pan Wang.;Ruifeng Shi.;Hongyu Liu.;Jun Chen.
来源: Zhongguo Fei Ai Za Zhi. 2019年22卷5期264-270页
Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism.
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