目的:研究全蝎尾部多肽粗提物(peptide extract from scorpion tail,PEST)与蜈蚣头部多肽粗提物(peptide extract from centipede head,PECH)对肝癌细胞乙型肝炎病毒(Hepatitis B virus,HBV)合成的影响及其可能机制.方法:超滤法提取PEST与PECH.选取肝癌HepAD38和HepG2细胞,将其分组:对照组,用含10％胎牛血清的培养基培养;PEST组,不同浓度PEST(0.125、0.250、0.500和1.000 mg/mL)处理;PECH组,不同浓度PECH (0.125、0.250、0.500和1.000 mg/mL)处理;阳性对照组,拉米夫定或恩替卡韦或四环素处理.MTT法检测细胞活力,qRT-PCR检测HepAD38细胞上清液HBV DNA含量.另取HepAD38细胞,分为PEST组(1 mg/mL PEST处理)、PECH组(1 mg/mL PECH处理)、对照组、阳性对照组和阴性对照组;ELISA法检测细胞上清液中HBsAg和HBeAg含量,qRT-PCR检测HBV X、S、preC、PmRNA表达量,蛋白印迹法检测HBV核心蛋白(HBV core protein,HBc)表达.结果:PEST或PECH处理的肝癌细胞HepG2和HepAD38细胞活力均在70％以上;与对照组相比,PEST组(0.250、0.500和1.000 mg/mL)和PECH组(0.125、0.500和1.000 mg/mL)HBV DNA拷贝数明显降低(P均＜0.05);与对照组相比,PEST组和PECH组HBsAg和HBeAg含量明显降低(P均＜0.05),HBV P mRNA相对表达明显降低(P均＜0.05),PEST组HBc表达几乎无差异,而PECH组HBc表达减少.结论:PEST和PECH在HepAD38细胞株中表现出抗HBV作用,可能与其抑制HBV PmRNA合成有关.

目的:比较GEMOX方案(吉西他滨联合奥沙利铂)和吉西他滨单药方案用于美国东部肿瘤协作组(ECOG)评分0～1分、可切除胰腺癌辅助化学治疗(化疗)的疗效及安全性,并探索与无病生存(DFS)期和总生存(OS)期相关的独立预后因素.方法:回顾性分析103例ECOG评分0～1分的可切除胰腺癌患者,其中68例给予GEMOX方案辅助化疗:吉西他滨1 000 mg/m2以固定速率(FDR)静脉滴注100 min,第1天,奥沙利铂85 mg/m2静脉滴注,第2天,每2周重复,共8周期;35例接受吉西他滨单药化疗:吉西他滨1 000 mg/m2第1、8和15天静脉滴注30 min,每28 d重复,共6周期.比较2种辅助化疗方案的DFS期、OS期及毒性差异,并通过单因素及多因素生存分析探讨预后因素.结果:GEMOX组和吉西他滨单药组的中位DFS期分别为370 d和520 d(P=0.815),中位OS期分别为803 d和888 d(P=0.428),差异均无统计学意义.2种辅助化疗方案的毒性多为Ⅰ、Ⅱ度且易于控制,GEMOX组呕吐(30.8％比10.5％,P=0.019)及外周神经毒性发生率(38.5％比0％,P＜0.001)显著高于吉西他滨单药组;丙氨酸转氨酶(ALT)/天冬氨酸转氨酶(AST)升高2组发生率相似,分别为47.7％和44.7％,但吉西他滨单药组Ⅲ度以上ALT/AST升高发生率显著高于GEMOX组(7.9％比0％,P=0.048).生存分析显示,分化差(P=0.002)、R1切缘(P＜0.001)、淋巴结转移(P=0.028)、术后CA19-9≥90 U/mL(P=0.005)及未能完成全部辅助化疗疗程者(P=0.002)中位DFS期显著缩短;而分化差(P=0.001)、R1切缘(P＜0.001)、术后CA 19-9≥90 U/mL (P=0.003)及未能完成全部疗程者(P=0.001)等因素也预示中位OS期显著缩短.结论:对体力状态良好的胰腺癌患者切除术后,为期4个月的GEMOX方案,与为期6个月的吉西他滨单药化疗生存获益相似,GEMOX方案可视为辅助化疗的备选方案之一.分化差、R1切缘、术后CA19-9≥90 U/mL及未能完成全部辅助化疗疗程等因素是DFS期和OS期的独立不良预后因素.

胃癌治疗的关键在于早期诊断和及时手术, 但根治术后的高复发转移率, 严重影响了胃癌患者生存. 围手术期进行放化疗, 以期提高胃癌治愈率, 是国内外研究的热点. 目前常用的胃癌围手术期治疗存在明显的地区差异,大致可分3类:(1)北美模式:胃癌术后给予辅助放化疗 (基于INT0116研究) [1];(2) 欧洲模式: 化疗-手术-再化疗的围手术期化疗 (基于MAGIC和ACCORD 07等研究)[2-3];(3)亚洲模式:根治术后辅助化疗(基于ACTS-GC和CLASSIC等研究)[4-5]. 不管采用何种方式进行围手术期治疗,复发率和病死率均较单纯手术有所改善. 为进一步提高疗效,荷兰学者尝试将欧洲与北美模式结合, 开展了一项大型随机三期临床试验( CRITICS ) ,旨在术前化疗的基础上,对比术后辅助化疗和术后辅助放化疗的效果[6]. 该研究入组了788例ⅠB～ⅣA期可切除的胃或食管胃结合部腺癌 (adenocarcinoma of esophagogastric junction , AEG ) , 所有患者均接受术前新辅助化疗,方案为表柔比星加顺铂/奥沙利铂加卡培他滨(ECC/EOC),共3周期,然后接受胃癌根治术.试验起始时即在术前化疗前就进行随机分组,393例继续行ECC/EOC术后辅助化疗3周期(术后化疗组),另一组395例接受术后同步放化疗,放疗总剂量45 Gy/25 fx,联合顺铂加卡培他滨同步化疗(术后放化疗组),而两组开始术后治疗者分别为59％和62％,完成全部疗程者分别为46％和50％. 术后化疗组和术后放化疗组的中位总生存期分别为43个月和37个月(P=0.90). 由此提示,对可切除胃癌患者而言,经术前化疗和根治手术后,术后辅助放化疗并不优于术后化疗.

恶性肿瘤高居上海居民疾病死亡原因第2位,仅次于心脑血管疾病,已成为最主要的公共卫生问题之一.其传统治疗手段包括肉眼移除(手术)、结构毁损(放疗、射频等)、功能抑制(药物治疗)等.历经20世纪后半叶至今近50年的发展,各种新型肿瘤治疗手段和药物不断涌现.本文简单介绍抗肿瘤药物研发方面的进展.

Objective To investigate the efficiency and safety of neoadjuvant intraperitoneal and systemic chemothera-py (NIPS) in gastric cancer patients with peritoneal metastasis. Methods From April to October 2015, a total of 11 gastric cancer patients with peritoneal metastasis including 1 case with P1, 2 cases with P2 and 8 cases with P3 received one course of chemotherapy with 21 days. Intraperitoneal paclitaxel (PTX) was administered at 20 mg/m 2 via implanted subcu-taneous peritoneal access ports as well as intravenous PTX at 50 mg/m2 on day 1 and 8. S-1 was administered at 80 mg/(m2·d) for 14 consecutive days, followed by 7 days rest. Conversion gastrectomy was performed after NIPS in the patients who showed macroscopic disappear or apparent shrinkage of their peritoneal metastatic lesions at the second staging la-paroscopy. Results In all 11 patients, conversion gastrectomy was done in 8 patients (72.7%) with R0 gastrectomy in 5 cases (62.5%). The median number of course of NIPS chemotherapy before surgery was 6 (3-8) courses. The 1-year overall survival (OS) rate was 63.6%(7/11) in all patients. The 1-year OS rate of the patients with conversion gastrectomy and the patients with stage P3 reached to 87.5% (7/8) and 50.0% (4/8), respectively. The predominant toxicity was myelosuppres-sion with grade 3/4 both leukopenia and neutropenia in 18.2% (2/11) and 36.4% (4/11), respectively. NIPS-related and surgery-related mortality were not observed. Conclusions NIPS induction therapy was effective and safe for gastric cancer patients with peritoneal metastasis and deserved further study.

Objective · To investigate antiemetic effect of aprepitant for moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Methods · From 2014 July to 2015 August, 130 cases of gastrointestinal cancer patients were collected in Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, who received moderate emetogenic risk of chemotherapy for at least four courses. One hundred and nine patients were treated with aprepitant, palonosetron and dexamethasone on day 1, and aprepitant and dexamethasone on day 2 and 3. Twenty-one patients only received aprepitant and dexamethasone on day 1 and dexamethasone on day 2 and 3 in the first course of chemotherapy. During subsequent courses of chemotherapy they received aprepitant and treated in the same way as 109 patients. MASCC antiemetic tool (MAT) was used to evaluate the intensity of nausea. The primary endpoint was complete response (CR, no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after chemotherapy) at the second course. The secondary endpoint was complete protection (CP, CR plus no significant nausea) during the overall, acute (0-24 h), and delayed (24-120 h) phases at the second course. Results · The CR rates were 90.0%, 94.6% and 90.8% of patients in the overall, acute and delayed phases, respectively. The corresponding CP rates were 83.8%, 87.8% and 84.6 %, respectively. The CR rate increased from 42.9% to 57.1% during acute phase and increased from 9.5% to 90.5% during delayed phase for 21 patients after treatment with aprepitant. The main adverse reactions include constipation, anorexia and hiccups. Conclusion · Aprepitant combined with palonosetron and dexamethasone can effectively prevent moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Aprepitant therapy can effectively maintain antiemetic effect in patients with many chemotherapy courses.

Objective.To evaluate the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the first line treatment of advanced gastric adenocarcinoma.Methods.A total of 37 patients were enrolled into this study, and they received DOX regimen (docetaxel 75 mg/m2and oxaliplatin 130 mg/m2intravenous infusion on day 1, and capecitabine 1000 mg/m2orally twice daily on d1–14); treatment was repeated every 3 weeks.Results.All 37 patients were assessable for evaluation. The numbers of patients with complete response (CR), partial responses (PR), stable disease (SD), and progressive disease (PD) were 1, 10, 23, and 3, respectively. The objective response rate (ORR) was 29.7%, with the disease control rate (DCR) of 91.9%. Median progression-free survival (mPFS) and overall survival (mOS) were 197 days and 364 days, respectively. The most common grade 3/4 toxicities were hematological toxicities. The most common grade 3/4 nonhematological toxicities were fatigue, nausea, vomiting, anorexia, diarrhea, and hand-foot syndrome.Conclusion.The DOX regimen demonstrated a promising efficacy as the first line regimen in treating advanced gastric cancer patients with good performance status, the toxicities were tolerated and controllable. Large-scale clinical observation is necessary to get further evidence.

1 病例报告 女性,57岁,于2009年12月无明显诱因下出现左下肢疼痛伴腰背疼痛,2010年于外院行腰椎CT检查示:L3-4,L4-5,L5-S1椎间盘突出.予针灸等对症治疗后症状无改善,疼痛逐渐加重,只能平卧无法下床活动,体重下降10余公斤.

Objective:CA15-3 and CEA,the most common serum markers of follow-up study,seem not so sensitive to monitor the tumor progression of breast cancer in our clinical practice nowadays.Whereas it is reported that the overexpression of Her-2/neu in breast tissue was well related to the poor prognosis of patients.This study was to find out the more accurate serum markers,single or combined,to follow-up in breast cancer patients.Methods:ELISA essay was applied to test the serum expressions of HER-2 in 44 female breast cancer patients before and after chemotherapy and/or radiation therapy.Meanwhile the diagnostic value of the HER-2 expression was in comparison with that of the vascular endothelial growth factor(VEGF),basic fibroblast growth factor/(b-FGF),epidermal growth factor(EGF),CEA and CA15-3 detected concurrently.Follow-up studies were performed every six months until disease progression.Results:The serum HER-2 in breast cancer had a significant decrease after the treatment(14.23ng/ml vs.6.39ng/ml).They were related to the tumor progression,and their levels significantly elevated in the progression group(21.73ng/ml vs.5.36ng/ml).We also found that the specificity of serum HER-2 alone in determination of disease progression was 80.95%,combined determination of serum HER-2 and b-FGF showed the highest sensitivity of 90.91%,while serum HER-2 and CA15-3 showed the highest accuracy rate of 78.05%.The logistic model demonstrated that serum HER-2 level and CA15-3 level after treatment were the main prognostic factors of progression-free survival.Conclusion:Serum HER-2 level increased with tumor progression.As it is easy to detect,it can be used alone or combined with CA15-3 in follow-up studies for breast cancer patients.

Objective To investigate the effective relationship between gastric cancer cell lines with different Tau gene expression and their treatment sensitivity to paclitaxel,and possible drug-resistance mechanisms.Methods One cell line with high Tau gene expression and another cell line with lower Tau gene expression were used,and their response to paclitaxel treatment were screened by real time fluorescence quantitative PCR among a total of 10 gastric cancer cell lines.The influence to the proliferation,apoptosis and cell cycle of these two cell lines were evaluated by CCK-8 kit and Annexin-Ⅴ+PI.To the cell line having the higher Tau gene expression,we tried to knock it down by siRNA,and watched the change in sensitivity to paclitaxel treatment.Results The status of cell proliferation in vitro showed that paclitaxel produced an obvious inhibition effect on the gastric cancer cell proliferation which possessed the lower Tau gene expression(P<0.05).In vitro experiments also showed that paclitaxel could also promote apoptosis on low Tau gene expression gastric cancer cell line(P<0.05).Cell cycles were mainly effected on the G2 stage.Application of siRNA technology showed that after reduction in expression of Tau gene expression,paclitaxel significantly increased the state of proliferation in the cell line(P<0.05),and promoted their apoptosis(P<0.05).Conclusions Paclitaxel has a stronger inhibitory effect on proliferation in the low Tau gene expression gastric cancer cell line,and can promote apoptosis on these cells.As to the gastric cancer cells having experienced knock-down in Tau gene expression,paclitaxel can both increase their proliferation and promote their apoptosis.

Objective To investigate the incidence and severity of adverse events in Han pateints with advanced digestive tumor treated with irinotecan-based chemotherapy, and their relationship with UGT1A1 gene promoter polymorphism. Methods Sixty-six advanced digestive tumor patients treated with irinotecan-based chemotherapy were enrolled, and the adverse events during chemotherapy, the pretreatment bilirubin level, and the time to the occurrence of degree Ⅲ toxicity were observed. Genomic DNA was extracted from peripheral blood to examine the frequency of UGT1A1 TATA box thymine-adenine (TA) repeats, and its relationship with adverse events was analyzed. The differences of the pretreatment bilirubin level and the time to the occurrence of severe toxicity were also compared. Results Fifty-five patients (83.3%) were identified with (TA)6/(TA)6 genotype, and eleven patients (16.7%) with UGT1A1*28/*1 polymorphism [thymine-adenine (TA)6/(TA)7 genotype, no (TA)7/(TA)7 genotype was found]. In the two groups, 26 and 5 patients (47.3% vs 45.5%,P=1.000) had grade 3 and 4 neutropenia and 5 and 4 patients (9.1% vs 36.4%,P=0.036) had grade 3 and 4 diarrhea, respectively. The pretreatment bilirubin levels of the two groups were (15.1±1.1) μmol/L and (20.8±5.1) μmol/L, respectively (P =0.09). The time to occurrence of severe toxicity of the two groups were 9 weeks and 3 weeks of postchemotherapy, respectively (P=0.186). Conclusions The marked increase in grade 3 or 4 diarrhea, but not in grade 3 or 4 neutropenia may occur in patients treated with irinotecan-based chemotherapy who had (TA)6/(TA)7 genotype.

Objective To investigate the expressions and prognostic values of dihydropyrimidine dehydrogenase(DPD),thymidylate synthase(TS) and thymidine phosphorylase(TP) in gastric carcinoma,and to analyze the correlations between the expressions of these enzymes and the clinicopathological features and prognosis.Methods Expressions of DPD,TS and TP were determined by immunohistochemistry in 42 gastric carcinoma patients who had received 5-fluorouracil(5-FU)-based adjuvant chemotherapy after curative resection,and the relationships between the expressions of these metabolic enzyme and the clinicopathological features and prognosis were analyzed.Results In gastric carcinoma,the expression rate of DPD in intestinal type was significantly higher than that in diffused type(65% vs 25%,P=0.025),TS and TP tended to be higher in patients with gastric carcinoma in advanced stage(P0.05).Patients with DPD negative gastric carcinoma had a significantly better disease free survival compared to those with DPD positive tumor(25 months vs 16 months,P=0.012),and the median survival of patients with DPD negative carcinoma was significantly longer(48 months vs 26 months,P=0.005).DPD was an independent prognostic factor of disease free survival and overall survival of gastric carcinoma patients.There was no correlation between expressions of TS or TP and prognosis(P0.05).Conclusions Expression of DPD might be an important prognostic indicator of patients with gastric carcinoma receiving 5-FU-based adjuvant chemotherapy.Expression of TS or TP correlated closely with tumor progression and clinical stage.

Objective:To investigate the expressions and prognostic values of 5-FU metabolic enzymes in colorectal carcinoma.Methods:The expressions of dihydropyrimidine dehydrogenase(DPD),thymidylate synthase(TS)were detected by immunohistochemistry in 44 colorectal carcinoma patients,who have received 5-FU based adjuvant chemotherapy after curative surgical resection.Results:The patients with DPD positive colorectal carcinoma had a significantly poorer disease free survival compared to those with DPD negative tumors(P=0.047),and the disadvantage of overall survival was seen in DPD positive carcinoma,but did not reach significance(P=0.136).There was no correlation between TS expression and prognosis when adjusted for chemotherapy regimens(P0.05),but TS tended to be highly expressed in tumors with late stage(P0.05).Conclusion:DPD expression should be applied as a potential indicator for predicting the prognosis of colorectal carcinoma receiving 5-FU based adjuvant chemotherapy.TS expression correlated very well with clinical stage and would be considered as a biomarker of tumor progression in colorectal carcinoma.

Objective:To observe and evaluate the efficacy and adverse events of the combination of irinotecan plus capecitabine in the treatment of advanced colorectal cancer as second-line regimen.Methods:Thirty-eight advanced colorectal cancer received a dose of 200mg/m2 irinotecan on d1,and an oral dose of 1000mg/m2 capecitabine twice daily on d1-14,every 3 weeks,at least two cycles were given for each patient.Results:The overall response rate was 7.9%(3/38),the disase control rate was 55.3%(21/38),including 3 partial response(PR),18 stable disease(SD)and 17 progression(PD).The median time to progression(TTP)and the median overall survival(OS)was 4 months and 11 months respectively,and clinical response was the important prognostic factor of time to progression and overall survival.Neutropenia(18.4%)and diarrhea(10.5%)were the most commonly observed grade 3 or 4 adverse events.Conclusion:Irinotecan combined with capecitabine as second-line regimen is efficacious and well-tolerated for the treatment of advanced colorectal cancer.

OBJECTIVE:EGFR-mediated tumor proliferation plays an important role in the development of cancer, and is a key candidate for targeted therapy. The aim of this study is to evaluate the impact of EGFR monoclonal antibody Cetuximab (C225) on the growth, proliferation and apoptsis of gastric cancer xenograft in nude mice, and its possible mechanisms.METHODS:A gastric cancer cell line SGC-7901 with high EGFR expression level was screened from 7 gastric cancer cell lines. Gastric cancer xenografts in nude mice were established, and randomly divided into C225 treatment group and PBS control group. Tumor growth curves were calculated, the impact of C225 on the tumor growth, proliferation and angiogenesis was evaluated by immunohistochemical (IHC) staining Ki67 and CD34, respectively. The effect of C225 on apoptosis in the gastric cancer cells was evaluated by TUNEL assay. The expression levels of EGFR and its transcription factor Sp1 were detected by IHC staining and Western blot.RESULTS:After C225 treatment, the proliferation and growth of gastric cancer xenograft in nude mice were significantly decreased. In the contrast, the apopotic indexes in C225 treatment group and PBS control group were (16.4% +/- 0.3%) and (3.1% +/- 0.9%), respectively, with a significant difference (P < 0.001). There was no significant difference of the densities of CD34-positive microvessels between C225 treatment group and control group. Elevated expression of EGFR and Sp1 after C225 treatment was observed by IHC staining and Western blot assay.CONCLUSION:EGFR monoclonal antibody cetuximab (C225) can effectively inhibit the growth of gastric cancer xenografts in nude mice, and trigger its apoptosis. Yet, C225 treatment may upregulate the expression of EGFR and its transcription factor Sp1. A "block-transcription activation-compensation" mechanism may exist to explain the molecular mechanism of acquired resistance of a single target blockade treatment.

<正>病例1:男,48岁,于2006年7月出现血尿、腰痛,B超发现左肾占位,双肾CT检查拟诊左肾癌。即行左肾癌根治术,术后病理:肾透明细胞癌。9月予干扰素α-1b 100万U,隔日1次,肌肉注射(肌注),1个月后改为300万U。至2007年6月停药。患者每3～4个月定期复查,未见复发、转移,无不

<正>病例:女,35岁。纳差、乏力、进食后腹胀,时有胸背部疼痛,并出现左锁骨上淋巴结无痛性肿大(大小约3cm×4cm)1月余后行胃镜检查,发现胃体下部有溃疡增殖性病灶,活检病理为低分化腺癌;胸部CT检查发现纵隔内主动脉旁及左上纵隔血管周围有异常肿大淋巴结,

<正>病例:男,58岁,无明显诱因下反复中上腹疼痛1年余,背部伴有胀痛,夜间更甚,食欲差,有明显饱胀感。予抗酸剂、胃黏膜保护剂等对症处理,无明显缓解。外院CT示:胰体尾部占位性病变,考虑胰腺体尾部癌,累及后腹膜,左肾上腺部分累及,脾脏内低密度。

<正>病例:女,75岁,因中上腹闷胀不适伴烧心感近1个月、发热2周就诊。体检:中上腹及右上腹轻压痛,无反跳痛及肌卫,肝右肋下3cm、剑突下8cm,肝区叩痛阳性。B超示肝多发实性占位,伴部分液化;CT示肝内多发实性占位,转移

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma.METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system.RESULTS: The positive! expression rates of IL-12 and IL-18 were 440% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors.CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.