健择对胰腺癌细胞株蛋白质表达的影响

目的观察健择致胰腺癌细胞株蛋白质变化的影响,寻找一些在化疗过程中出现的蛋白质,为临床治疗提供理论依据.方法利用蛋白质组学技术,分析胰腺癌细胞株SW-1990在加入健择和5-FU后其蛋白质谱的变化,最后鉴定其差异表达的蛋白质.结果培养细胞受抑制约50%时,健择为1～100 ng/ml,5-FU为250～2 500 ng/ml.质谱鉴定了9个差异表达的蛋白质,其中对照组3个,加药组6个.结论健择对细胞株的作用明显优于5-FU.β-肌动蛋白、MGC:19713等某些高表达的蛋白质可能成为观察化疗效果的重要指标.     

动脉灌注吉西他滨治疗晚期胰腺癌临床研究

目的：评价吉西他滨（健择）动脉灌注治疗晚期胰腺癌的疗效和安全性。方法：对20例胰腺癌病人采用吉西他滨动脉灌注支结合静脉化疗，并与9例采用5－氟尿嘧啶（1000mg)、阿霉素（40－50mg)、卡铂（200mg)经胰十二指肠动脉灌注治疗的胰腺癌病人为对照，对病人的疾病相关症状改善、疗效和毒副反应进行评价。结果：吉西他滨组治疗后疼痛改善率为75％，对照组疼痛改善率为44．4％，两比较无显性差异。治疗后Karnofsky评分吉西他滨组好转率为60％，对照组为44．4％。吉西他滨组部分缓解率（PR）为30％，半年及1年生存率分别为85％及25％，中位生存时间为9．2个月；对照组PR为22．2％，半年生存率为66．7％，无1年生存，中位生存时间为7．9个月（P＞0．05）。两组均有不同程度的胃肠道和骨髓抑制等不良反应（P＞0．05），3、4级不良反应较少见。结论：吉西他滨动脉灌注治疗晚期胰腺癌能够改善病人的生存质量，延长病人的生存期，无严重毒副反应。     

胰腺癌化疗药物治疗现状

胰腺癌的化疗在胰腺癌综合治疗中占有非常重要的地位。鉴于吉西他滨治疗胰腺癌效果明显优于5-FU，1997年美国FDA批准吉西他滨作为胰腺癌的一线化疗用药。从此，在临床研究中，以吉西他滨为基础的联合化疗大量展开。     

GABA对胰腺癌细胞株SW1990生长的影响

目的:观察γ-氨基丁酸(GABA)对胰腺癌SW1990细胞生长的影响．方法:采用MTT法和流式细胞术检测GABA对胰腺癌SW1990细胞增殖、细胞凋亡、细胞周期的影响,放射免疫分析法检测cAMP含量．结果:不同浓度的GABA(20-320μmol／L)促进胰腺癌SW1990细胞的生长,促进细胞周期比例的分布,使G0／G1细胞减少,S期和G2／M细胞增多,同时促进胰腺癌SW1990细胞内cAMP含量的增加,且呈剂量依赖性(P<0．01)．显著抑制细胞凋亡,凋亡率由27．4％降低到5．4％(X2=10．19,P<0．01)．结论:GABA促进胰腺癌SW1990细胞生长,可能通过受体后信息介导．     

晚期胰腺癌区域性动脉灌注化疗

胰腺癌的发病率逐年呈上升趋势，确诊时往往已有远处转移，而失去手术机会。我们从1998年1月～2002年10月对8例晚期胰腺癌患者进行了区域性动脉灌注化疗(介入治疗)，达到了减轻症状和延长生存的目的，现就其应用价值报道如下。     

促红细胞生成素对胰腺癌细胞株 SW1990吉西他滨化疗敏感性的影响

o处理组对SW1990生长抑制率较0浓度组显著降低,而MDR-1 mRNA、RRM1 mRNA表达量增加(P＜0.01或＜0.05).吉西他滨对SW1990的抑制率与MDR-1 mRNA和RRM1 mRNA表达均呈负相关(r=-0.964,P=0.036;r=-0.968,P=0.032).结论 Epo可降低胰腺癌SW1990细胞对吉西他滨的化疗敏感性,其机制可能是上调MDR-1、RRM1的基因表达水平.     

小柴胡汤联合吉西他滨化疗对晚期胰腺癌的疗效观察

[目的]观察小柴胡汤联合吉西他滨化疗对晚期胰腺癌的临床疗效.[方法]晚期胰腺癌患者72例,随机分为对照组(36例)和治疗组(36例),对照组仅予吉西他滨单药静脉化疗,治疗组在吉西他滨化疗间歇期口服小柴胡汤,2个周期后评价2组近期疗效、临床受益反应率及不良反应.[结果]治疗组客观有效率、临床受益反应率均高于对照组(38.89％:27.78％、83.33％:58.33％),差异均有统计学意义(P＜0.05).治疗组与化疗药物有关的消化道不良反应和骨髓抑制发生率,均略低于对照组.[结论]对晚期胰腺癌患者采用小柴胡汤联合吉西他滨化疗在改善症状,提高生活质量及近期疗效方面较单一药物化疗优势明显,值得临床推广应用.     

血管紧张素转化酶Ⅱ对吉西他滨治疗胰腺癌细胞株敏感性的影响

目的探讨血管紧张素转化酶Ⅱ（ACE2）在胰腺癌细胞化学治疗中的作用。方法构建质粒,通过脂质体转染技术将质粒DNA转入胰腺癌细胞株SW1990并建立稳定高表达ACE2的胰腺癌细胞克隆。设实验组（转染ACE2表达质粒）、阴性对照组（转染GFP对照质粒）及未转染组,Western印迹法检测转染后各组细胞ACE2蛋白的表达。采用化学治疗药物吉西他滨作用不同处理组细胞,应用MTT法检测细胞增殖变化,流式细胞仪和TUNEL法检测细胞的凋亡变化。结果50μmol／L吉西他滨干预细胞24h后,实验组、阴性对照组和未转染组的细胞增殖抑制率分别为（51．2±4．8）％、（24．2±3．3）％和（21．3±2．6）％,3组间差异有统计学意义（P〈0．05）;流式细胞计数检测实验组细胞凋亡较阴性对照组及未转染组明显增加[（31．2±3．8）％、（17．64±2．3）％、（15．9±1．7）％,P〈0．05],TUNEL标记分析发现典型凋亡特征。结论稳定高表达ACE2基因可明显增强SW1990对吉西他滨的治疗敏感性,两者联合应用在胰腺癌治疗中具有潜在的价值。     

抑制脯氨酸羟化酶-2对胰腺癌吉西他滨化疗敏感性及肿瘤转移的影响

目的 探究抑制脯氨酸羟化酶结构域(PHD)2对胰腺癌化疗敏感性与肿瘤转移的影响。方法 将SW1990细胞随机分为对照组、sh-NC组和sh-PHD2组,分别使用shRNA-NC与shRNA-PHD2慢病毒感染sh-NC组和sh-PHD2组细胞,对照组细胞不进行处理,实时荧光定量聚合酶链反应(PCR)和Western印迹检测转染效果;细胞划痕实验和Transwell小室实验检测细胞迁移与侵袭能力,免疫荧光染色检测细胞上皮-间质转化能力,细胞计数试剂盒(CCK)-8检测吉西他滨处理下的细胞存活率。将45只裸鼠随机分为3组,每组15只,通过接种转染后的SW1990细胞构建移植瘤模型,分组包括sh-NC组、sh-NC+吉西他滨组和sh-PHD2+吉西他滨组,治疗8 w后,计算肿瘤组织体积、重量及肝转移情况,苏木素-伊红(HE)染色观察肿瘤组织病理学改变,免疫组织化学染色检测肿瘤组织Ki-67表达,TUNEL染色检测肿瘤组织细胞凋亡。结果 shRNA-PHD2慢病毒感染SW1990细胞后,与对照组比较,sh-PHD2组PHD2 mRNA与蛋白表达水平显著下降(P<0.05),细胞划痕愈合率...     

以吉西他滨为主的化疗方案治疗老年晚期胰腺癌

胰腺癌是恶性程度很高的消化系统恶性肿瘤，其病程短、进展快，治疗效果差，5年生存率不足5％。近年来发病率逐年上升，约80％患发病年龄在60～80岁之间。手术是目前最为有效的治疗手段，但胰腺癌发病隐匿，缺乏有效的早期诊断手段，就诊时多不能行根治性手术。因此，不能手术的老年晚期胰腺癌患的治疗仍是临床上面临的最为棘手问题。本回顾性分析42例老年晚期胰腺癌患以吉西他滨（GEM）为基础的联合化疗的临床疗效。     

Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade?

BACKGROUND AND AIM OF STUDY: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade. PATIENTS AND METHODS: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted. RESULTS: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001). CONCLUSIONS: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.     

Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs

PURPOSE: Cancer-specific immunotherapy holds great promise as an emerging treatment for advanced colorectal cancer and may be combined with standard chemotherapy to provide a synergistic inhibitory action against tumor cells. To examine the interrelationship between the immune system and chemotherapy, we studied the induction of both CEA, a tumor-associated antigen, and MHC class I, a major component of the antigen presenting system, in response to a number of chemotherapeutic agents. METHODS: The effect of a selection of standard chemotherapeutics on MHC class I and CEA expression in human colorectal cancer cell lines was determined by flow cytometry and semi-quantitative RT-PCR. In addition, studies using mice bearing tumors derived from an injected murine colon cancer cell line were performed to determine if alteration in MHC class I expression occurs in vivo following continuous infusion of chemotherapeutic agents into the peritoneal cavity, as well as to facilitate correlations between expression of this factor and therapeutic effectiveness. RESULTS: All anti-cancer drugs examined, when given at IC50 values, induced expression of MHC class I protein in the human colon cancer cell line, COLO201. However, expression of CEA mRNA was only induced upon exposure to 5-FU, in contrast to obscure induction following CDDP and SN-38 treatment. Combined treatment with 5-FU and CDDP gave additional effect on CEA expression in COLO201 cells. Regarding the in vivo studies in mice, the size of the murine colon cancer cell-derived tumors was reduced only in response to treatment with CDDP, which also mediated the highest induction of MHC class I expression. CONCLUSION: These results suggest that chemotherapeutic agents trigger the immune system and cancer-specific immunotherapy may be effective when used in combination with systemic chemotherapy.     

吉西他滨对人胰腺癌SW1990和BxPC3细胞株Notch信号通路的诱导作用

目的 观察吉西他滨对人胰腺癌细胞(SW1990和BxPC3)Notch信号通路活性的影响,探讨其与胰腺癌对吉西他滨化疗耐药的关系.方法 不同浓度吉西他滨处理人胰腺癌SW1990和BxPC3细胞株48 h,实时定量PCR检测Notch信号通路受体Notch1、2、3、4,配体Jagged1、2和下游靶基因Hes1 mRNA的表达,Western blotting测定细胞Hes1蛋白表达.结果 2μmol/L吉西他滨作用胰腺癌细胞株48 h,SW1990细胞的Notch1、2、3、Jagged1、2和Hes1 mRNA表达量分别为8.26±0.48、39.12±4.87、0.84±0.06、105.8±17.92、6.59±0.32和17.30±2.96,均较未处理细胞的1.02±0.15、15.25±1.28、0.12±0.02、32.66±1.98、1.88±0.29和5.02±0.64明显升高(P<0.05或P<0.01);BxPC3细胞上述各项表达量分别为7.87±0.59、109.4±10.98、0.74±0.19、62.73±13.50、2.09±0.16和15.38±1.06,也均较未处理细胞的1.14±0.43、58.96±2.63、0.10±0.02、16.95±3.79、0.98±0.02和2.04±0.16,明显升高(P<0.05或P<0.01).1、2 μmol/L吉西他滨作用胰腺癌细胞株48 h,SW1990细胞Hes1蛋白表达量分别为0.30±0.03、0.42±0.03;BxPC3细胞分别为0.33±0.02、0.45±0.03,均较未处理细胞显著增高(0.13±0.01、F=33.71;0.09±0.02、F=38.54,P值均<0.01).结论 吉西他滨可明显激活SW1990和BxPC3细胞的Notch信号通路,这可能是胰腺癌细胞获得化疗耐受性的机制之一.     

Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy

Purpose Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues Methods Twenty-five colorectal cancer patients were included in our study; these had undergone surgical resection of the primary tumor, received post-operatively 5-FU-based adjuvant chemotherapy and then suffered from recurrences. In a standard three-step immunohistochemical procedure, a monoclonal antibody to topo I was applied in both specimens from each patient (one from the primary location and a second one from the recurrence). Statistical analysis was subsequently performed. Results Malignant cells from the recurrences displayed a statistical significant increase, concerning the levels of topoisomerase I, by comparison with the primary tumors (P = 0.01). The increase in topo I levels did not demonstrate significant correlations with Duke’s stage (Fisher’s Exact Test P value = 0.496), differentiation grade (P value = 0.661), localization (P value = 0.072), patient sex (P value = 0.434), nor with relapse free interval (P value = 0.493). There was a statistically significant relationship between the age of patients and increase in topo I levels (P = 0.011). Conclusions Topo I expression may be part of the malignant cells’ phenotype in recurrent colorectal carcinomas, suggesting a potential role for Topo I in the acquisition of a metastatic phenotype. The increase of topo I immunohistochemical status is likely to be attributed to 5-FU and given the fact that high levels of topo I correlate with sensitivity to camptothecin, advanced colorectal cancer patients seem to benefit from topo I targeted anticancer drug therapy.     

5-脂氧合酶抑制剂齐留通对胰腺癌细胞SW1990的生长抑制作用

目的观察5-脂氧合酶(5-LOX)在胰腺癌细胞SW1990中蛋白、mRNA水平的表达,探讨5-LOX特异性抑制剂齐留通对胰腺癌细胞SW1990增殖和凋亡的影响及可能机制。方法2003-05-10—2004-05-25,南通大学附属医院消化实验室采用半定量反转录-聚和酶链反应(RT-PCR)法和免疫细胞化学方法检测5-LOX在胰腺癌细胞SW1990中的表达,采用四甲基偶氮唑盐(MTT)法和流式细胞仪检测齐留通对细胞的生长抑制作用。结果胰腺癌细胞SW1990中5-LOXmRNA及蛋白表达阳性,齐留通明显抑制胰腺癌细胞生长,并呈时间、浓度依赖性。结论5-LOX特异性抑制剂齐留通对胰腺癌细胞有显著的生长抑制作用,为胰腺癌的防治提供了一个新的实验依据。     

Usefulness of contrast-enhanced ultrasonography in determining treatment efficacy and outcome after pancreatic cancer chemotherapy

AIM：To investigate if contrast-enhanced ultrasonography（CE-US） is useful for determining treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy by assessing changes in intratumor hemodynamics using CE-US with a contrast agent.METHODS：The subjects were 34 patients with unresectable advanced pancreatic cancer treated by chemotherapy.CE-US was assessed after every treatment（course） completion under the same conditions,and patients were divided into two groups according to the intratumor enhancement pattern：Vascular rich（R） group and vascular poor（P） group.RESULTS：After the second course of treatment,R group in intratumor hemodynamics had 18 patients,and P group had 16 patients.The reduction rates of serum CA19-9 level after chemotherapy which decreased to half or less of the baseline level were 2/15（0.1%） in P group,but 11/16（69%） in R group（P = 0.006）.When the mean number of courses of chemotherapy and outcome were compared,P group had a mean number of courses of 4.9（R group,10.2） and mean survival time（MST） of 246 d（R group,402 d）,showing that outcome was significantly better in R group（P=0.006）.CONCLUSION：CE-US revealed that the change in intratumor blood flow correlated with both serum CA19-9 level and outcome.Patients with serum CA19-9 that decreased to less than half the baseline level,and patients with an abundant intratumor blood flow,had a significantly better outcome.Thus,CE-US is potentially useful for evaluating treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy.     

Systemic chemotherapy using cisplatin plus 5-fluorouracil for inoperable gallbladder cancer

We report a case of advanced gallbladder cancer in a 37-year-old man who presented in June 1993 with malignant obstructive jaundice. After percutaneous transhepatic biliary drainage and several diagnostic imaging examinations, the patient underwent laparotomy under a diagnosis of extremely advanced gallbladder cancer involving the confluence of the hepatic ducts. The tumor, however, was judged to be unresectable because of its massive spread into the liver along Glisson's sheath, and because of histologically proven peritoneal dissemination. After exploratory laparotomy, one course of anticancer chemotherapy (cisplatin, 100 mg/body IV, on day 1, and 5-fluorouracil, 1000 mg/body, on days 1–5, by continuous infusion) was administered and the completely obstructed hepatic duct was dramatically re-canalized. Four courses of chemotherapy were administered over a 16-month period until jaundice recurred. For these 16 months, the patient's quality of life was well maintained without biliary drainage. He died of increased peritoneal dissemination approximately 2 years after the first course of anticancer chemotherapy.