可视化思维导图在胰腺癌化疗患者健康宣教中的应用效果

目的探讨可视化思维导图在胰腺癌化疗患者健康宣教中的应用效果。方法采用方便抽样法,选取南京市某三甲医院肿瘤科2021年7月~2022年7月接收的72例胰腺癌化疗患者,按随机数字表法分为2组,各36例,对照组给予常规化疗护理,观察组则在此基础上借助可视化思维导图进行健康宣教,两组均进行4~6周期化疗,观察比较两组化疗前、化疗后的自我效能问卷及生命质量测定量表评分。结果可视化思维导图干预后,观察组的自我效能问卷评分显著高于对照组(P<0.05);观察组的生命质量测定量表评分显著高于对照组(P<0.05)。结论将可视化思维导图应用于胰腺癌化疗患者健康宣教中,能够有效提高患者的自我效能,提高患者的生命质量。

利用新型载体运转MDR1 siRNA以逆转胰腺癌化疗耐药性的研究

目的:以新型载体运转MDR1 siRNA导入胰腺癌细胞株后,观察其多药物耐药基因(MDR1)的表达及其对胰腺癌化疗耐药性的影响。方法:采用RNA干扰技术,构建可用于包装成自我复制rAAV病毒载体的质粒,以运转不同长度的MDR1 siRNA。采用实时PCR检测MDR1 mRNA的表达,Western印迹法检测总P-糖基化蛋白(P-gp)的表达水平,用流式细胞仪检测细胞表面的P-gp表达,并从不同层面检测胰腺癌细胞株P-gp表达的抑制率,从而筛选出最佳的质粒载体。采用MTT检测IC50值,进行各载体逆转胰腺癌细胞株化疗耐药性的研究。结果:拟用于构建自我复制rAAV病毒载体的25-mer MDR1 siRNA质粒能有效地将目的基因MDR1 siRNA导入胰腺癌细胞株,并予稳定的表达,发挥作用。导入胰腺癌细胞株的MDR1 siRNA能有效地在mRNA水平上沉默MDR1基因,显著抑制其表达,使其蛋白产物P-gp的表达明显减少,及其在细胞膜上的数量显著降低。结果能有效、显著地逆转胰腺癌细胞株的化疗耐药性,转染前SW1990/ADM细胞对ADM的IC50值约是转染后的50倍。结论:采用可用于构建新型sc-rAAV载体的质粒作为投递siRNA的工具,并选择MDR1为研究靶点,通过实验证实该策略在逆转胰腺癌化疗耐药性中的有效性。

健康信念教育联合多维护理干预对胰腺癌化疗患者自我效能与不良反应的影响

研究对胰腺癌化疗患者采用健康信念教育与多维护理干预相联合的方式进行护理对患者的自我效能与不良反应所产生的影响。方法:此次研究的受试者样本都来自本院所收治的胰腺癌化疗患者,数量是40,在患者本人的同意下,采用随机分组的方式。分组的数量比较平均,都是20例,对两组分别应用不同的护理方法。分别将常规护理和健康信念教育与多维护理相联合的方式应用在两组,分别观察效果。结果:GSES分数和不良反应相比,观察组分别更高和发生比更少(P<0.05)。结论:健康信念教育和多维护理相结合使用在胰腺癌化疗患者中可以促进患者自我效能的明显升高,减轻化疗治疗中的不适,从而降低患者的化疗痛苦。

快速康复护理对胰腺癌术后化疗患者癌因性疲乏、生活质量及睡眠质量的影响

目的观察快速康复护理对胰腺癌术后化疗患者癌因性疲乏、生活质量及睡眠质量的影响。方法选择2022年2月—2023年1月江苏省苏北人民医院收治的90例胰腺癌术后化疗患者,随机分为2组各45例,观察组予以快速康复护理,对照组予以常规护理,比较2组化疗不良反应发生率、癌因性疲乏Piper评分、生活质量(EORTCQLQ-C30评分)及睡眠质量PSQI评分。结果观察组和对照组化疗不良反应率分别为22.22%(10/45)、53.33%(24/45),观察组明显低于对照组(P<0.05)。护理后2组Piper评分、PSQI评分均明显低于护理前(P均<0.05),且观察组均明显低于对照组(P均<0.05)。护理后2组EORTCQLQ-C30评分均明显高于护理前(P均<0.05),且观察组明显高于对照组(P<0.05)。结论对胰腺癌术后化疗患者应用快速康复护理可明显降低化疗不良反应发生率,有助于减轻癌因性疲乏,提高睡眠质量和生活质量。

基于优先心理教育的多媒体健康宣教对首程胰腺癌化疗患者照顾者的影响

目的:探讨基于优先心理教育的多媒体健康宣教对首程胰腺癌化疗患者照顾者的影响。方法:选取2018年8月至2020年8月期间菏泽医学专科学校附属医院收治的胰腺癌化疗患者照顾者116例为研究对象,采用随机数字表法将研究对象分为对照组和实验组各58例。对照组患者照顾者给予常规健康教育,实验组患者照顾者在此基础上实施基于优先心理教育的多媒体健康宣教干预,比较两组患者照顾者的照顾能力、心理状态、应对方式的变化。结果:实施基于优先心理教育的多媒体健康宣教后,实验组照顾者的照护能力评分显著高于对照组(P<0.05);实验组患者照顾者的心理状态评分显著低于对照组(P<0.05);实验组患者照顾者的应对方式显著优于对照组(P<0.05);实验组患者的化疗不良反应发生率显著低于对照组(P<0.05);实验组患者的生存质量各维度评分均显著优于对照组(P<0.05)。结论:将基于优先心理教育的多媒体健康宣教应用于胰腺癌化疗患者照顾者中,可显著提高照顾者照顾能力,改善患者照顾者的心理状态及应对方式,值得临床推广应用。

整体护理模式对胰腺癌合并肝转移化疗患者的效果

目的:探讨整体护理模式对胰腺癌合并肝转移化疗患者的效果。方法:选取2015年9月11日-2020年9月11日本院139例胰腺癌合并肝转移化疗患者,双盲随机法分为对照组(69例)和试验组(70例)。对照组给予常规护理,试验组实施整体护理模式。比较两组护理前后焦虑自测表(SAS)评分、抑郁自测表(SDS)评分、自我效能感量表(GSES)评分、机体免疫功能指标及生活质量评分、护理满意度评分;比较两组继发感染率。结果:护理后,试验组SAS评分、SDS评分低于对照组,GSES评分、机体免疫功能指标及生活质量评分高于对照组(P<0.05)。试验组护理满意度评分高于对照组(P<0.05),试验组继发感染率低于对照组(P<0.05)。结论:胰腺癌合并肝转移化疗患者实施整体护理模式效果确切,可有效提高患者的自我效能,并改善机体的免疫力和减轻患者的不良情绪,降低继发感染风险,促进患者生活质量的改善,值得推广。

灵性护理对胰腺癌术后化疗患者灵性健康水平、癌因性疲乏及睡眠质量的效果评价

目的探讨灵性护理干预对胰腺癌术后化疗患者灵性健康水平、癌因性疲乏以及睡眠质量产生的影响。方法选取2018年1月—2020年12月收治的50例胰腺癌术后化疗患者为研究对象,按照组间基本特征具有可比性的原则分为常规护理组(常规护理)和灵性护理组(常规护理+灵性护理),每组25例,比较两组患者中文版欧洲癌症治疗与研究生命质量-灵性健康量表(EORTCQLQ-SWB 32)、疲乏修订自评量表(RPFS)以及阿森斯失眠量表(AIS)评分结果。结果护理干预前,灵性护理组EORTCQLQ-SWB 32评分,RPFS评分以及AIS评分3项同常规护理组比较,差异均无统计学意义(P>0.05);护理干预后,灵性护理组EORTCQLQ-SWB 32评分高于常规护理组,灵性护理组RPFS评分/AIS评分均低于常规护理组,差异均有统计学意义(P<0.05)。结论应用灵性护理方式后,观察组灵性健康水平、癌因性疲乏以及睡眠质量均获得改善,可促进胰腺癌术后化疗患者整体预后水平提升。

Impact of preoperative chemoradiotherapy on survival in patients with resectable pancreatic cancer

AIM:To explore whether preoperative chemoradiation therapy improves survival of patients with pancreatic cancer undergoing resectional surgery. METHODS:Forty-seven patients with a malignant pancreatic tumor localized in the head or uncinate process of the pancreas underwent radical pancreaticoduodenectomy. Twenty-two received chemoradiation therapy (gemcitabine and radiation dose 50.4 Gy) before surgery (CRR) and 25 patients underwent surgery only (RO). The study was non-randomised. Patients were identified from a prospective database. RESULTS:The median survival time was 30.2 mo in the CRR group and 35.9 mo in the RO group. No statistically significant differences were found in subclasses according to lymph node involvement,TNM stages,tumor size,or perineural invasion. The one,three and five year survival rates were 81%,33% and 33%,respectively,in the CRR group and 72%,47% and 23%,respectively,in the RO group. In ductal adenocarcinoma,the median survival time was 27 mo in the CRR group and 20 mo in the RO group. No statistically significant differences were found in the above subclasses. The one,three and five year survival rates were 79%,21% and 21%,respectively,in the CRR group and 64%,50% and 14%,respectively,in the RO group. The overall hospital mortality rate was 2%. The morbidity rate was 45% in the CRR group and 32% (NS) in the RO group. CONCLUSION:Major multicenter randomized studies are needed to conclusively assess the impact of neoadjuvant treatment in the management of pancreatic cancer.

Importance of performance status for treatment outcome in advanced pancreatic cancer

Despite progress in the treatment of advanced and metastatic pancreatic cancer （PC）, the outcome of this disease remains dismal for the majority of patients. Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Kamofsky performance status （KPS） below 70% only have a marginal benefit from chemotherapy with gemcitabine （Gem） and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status （KPS = 90%-100%） may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status （KPS ≤ 80%） have no advantage from intensified therapy and should rather receive single-agent treatment.

Ultrasonic interventional analgesia in pancreatic carcinoma with chemical destruction of celiac ganglion

AIM： To detect the therapeutic effects of chemical destruction of celiac ganglion in patients with pancreatic carcinoma with intractable pain. METHODS： Ninety-seven cases with advanced pancreatic carcinoma received chemical destruction of celiac ganglion-5 mL pure alcohol injection around celiac artery under ultrasonic guidance. The changes of visual analogue scale （VAS）, serum substance P （Sub P）, β-endopeptide （β-EP） and T-lymphocyte subtypes level were compared between pre- and post-therapy. RESULTS： Successful rate of puncture was 98.7%, with one failure. No serious complications such as traumatic pancreatitis, pancreatic fistula, abdominal cavity hemorrhage or peritoneal infection occurred. VAS, serum Sub P and β-EP level significantly changed after treatment （8.0 ± 2.3 vs 4.6 ± 2.1, 254.1 ± 96.7 vs 182.4 ± 77.6, 3.2 ± 0.8 vs 8.8 ± 2.1, P 〈 0.01, P 〈 0.05, P 〈 0.01） with complete relief rate 54.2%, partial relief rate 21.9%, ineffective rate 12.5% and recurrent rate 10.7%. The T-lymphocyte subtypes level remarkably increased when compared with that of pre-therapy （46.7 ± 3.7 vs 62.5 ± 5.5, P 〈 0.01）. CONCLUSION： Our study suggests that chemical destruction of celiac ganglion under ultrasonic guidance is highly safe, and can evidently relieve cancer pain and improve the cellular immunity in patients with advanced pancreatic carcinoma.

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.

Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition

AIM： TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ （PPARγ）, a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METHODS： Expressions of PPARy and retinoid acid receptor （RXRα） were examined by reverse-transcription polymerase chain reaction （RT-PCR） with immunocyto- chemical staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy-△12,14 prostaglandin J2 （15d-PGJ2）, a ligand of PPART, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium （MTT） assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARy, was administered via water drinking in experimental group of nude mice. After 75 d, all mice were sacrificed. Expression of proliferating cell nuclear antigen （PCNA） in tumor tissue was examined with immunohistochemical staining. Expression of vascular endothelial growth factor （VEGF） mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosi- glitazone on changes of microvascular density （MVD） and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immu- nohistochemistry staining labeled with anti-Ⅳ collagen antibody, and indicated by MVD. RESULTS： RT-PCR and immunocytochemical stain- ing showed that PPARγ and RXRα were expressed in PANC-1 cells at both transcription level and translation level. MTT assay demonstrated that 15d-PGJ2, 9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a com- bined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carcinoma as compared to control group （0.48 ± 0.23 cm^3 vs 2.488 ± 0.59 cm^3, P 〈 0.05）, and the growth inhibition rate was 80.7%. Immuno- histochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group. 15d-PGJ2, 9-cis-RA and their com- bination inhibited the expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD was decreased more significantly in Rosiglitazone- treated mice （10.67±3.07） than in the control group （31.44±6.06） （P 〈 0.01）. VEGF expression in xeno- graft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION： Activation of PPARγ, inhibits the growth of pancreatic carcinoma both in vitro and in vivo. Sup- pression of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγ, activation inhibits the growth of pancre- atic carcinoma.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

Pseudocirrhosis in a pancreatic cancer patient with liver metastases: A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.

Expression profiles of miRNAs in human pancreatic cancer cell lines

Objective： To analyze initially the differences of miRNAs expression profiles in human pancreatic cancer cell lines by microarray technique. Methods： A total of 743 probes were designed according to the known miRNAs sequences of human, mice, and rats. miRNAs microarray was manufactured and its credibility was verified. Total RNAs were extracted and miRNAs were separated from human pancreatic cancer cell lines （SW1990, Capan-2, BxPC-3, Aspc-1, and Pancl） and immortal human pancreatic duct epithelial cell line H6C7. They were labeled with T4 RNA ligase, then were hybridized with microarray. Through array scan and analysis, miRNAs expression profiles in pancreatic cancer were obtained. The results were verified by Northern blotting and RT-PCR. Results： A total of 63 rniRNAs related to pancreatic cancer were found to be differentially expressed in 5 pancreatic cancer cell lines, including 25 down-regulated and 38 up-regulated miRNAs. Expressions of mir-21 and let-7 were also confirmed： Conclusion： The results suggested that miRNAs expression profiles could be found in pancreatic cancer cells.

Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However,the response rates have been highly variable,and are often irreproducible. To improve this low response rate,various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug,generating higher local drug concentrations in tumor cells with lower toxicity. Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and,simultaneously,a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

A study of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy for local advanced pancreatic cancer

Objective: To evaluate the clinical effect of transarterial infusion chemotherapy of gemcitabine plus three dimen- sional conformal radiotherapy on patients with local advanced pancreatic cancer. Methods: Fifty-one patients with local ad- vanced pancreatic cancer from June 2002 to February 2004 were enrolled, twenty-four patients of combined group were treat- ed with transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy, while twenty-seven patients of control group were treated only with transarterial infusion chemotherapy of gemcitabine. Results: There were significant statistical differences between two groups in clinical benefit response (91.7% versus 74.1%, P < 0.01) and overall remission rate (70.8% versus 33.3%, P < 0.01). The 6-month survival rate, 12-month survival rate and 24-month survival rate of combined group were 83.3%, 62.5% and 37.5% respectively, while that of control group were 55.6%, 33.3% and 11.1% respectively. This showed significant difference between the two groups. Conclusion: Transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy may be better than single transarterial infusion chemotherapy of gemcitabine in improving survival rates and elongating survival time of patients with local advanced pancreatic cancer.

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.

Regulatory Effects of X-linked Inhibitor of Apoptosis Protein and Pro-apoptotic Protein Smac on Apoptosis Resistance to Chemotherapy in Pancreatic Cancer Cells~*

Objective： To investigate the relation of X-linked inhibitor of apoptosis （XIAP） and second mitochondria-derived activator of caspase （Smac） signaling pathway to chemoresistance in human pancreatic cancer Panc-1 and BXPC-3 cells. Methods： Apoptosis and the changes of XIAP expression in permeabilized cells induced by cisplatin and 5-fluorouracil （FU） were measured by flow cytometry. The cytosolic expression of XIAP, Smac and caspase-3 was detected by Western blot. A recombinant plasmid vector pEGFP-N1/Smac was constructed and transfected into of Pancol cells. The effect of cytosolic overexpression of Smac on apoptosis of Panc-1 cells was evaluated by flow cytometry. Results： Panc-1 was more resistant to cisplatin or 5-FU induced apoptosis than BXPC-3. Western blot revealed that chemoresistant Panc-1 highly expressed XIAP, and increased cytosolic expression of Smac might be responsible for the marked down-regulation of XIAP in chemo-sensitive BXPC-3 cells after exposure to cisplatin or 5-FU. Furthermore, cytosolic overexpression of Smac could significantly down-regulate the levels of XIAP and promote the activity of caspase-3, as well as sensitize Panc-1 cells to anticancer drug-induced apoptosis. Conclusion： Anticancer drug-induced apoptosis requires mitochondrial release of Smac and downregulation of XIAP, which may be an important determinant of chemo-sensitivity in pancreatic cancer cells. Up-regulation of cytosolic expression of Smac may act as an effective modifying signal to overcome apoptosis resistance to chemotherapy in pancreatic cancer cells.

ERK signaling pathway may induce gemcitabine chemoresistance in pancreatic cancer cell line SW1990 by regulating the expression of mdr-1 and RRM1 gene

Objective： To investigate the relationship between extracellular signal-regulated kinase （ERK） pathway, multidrug resistance gene （mdr-1）, ribonucleotide recluctase M1 （RRM1） gene and their roles in gemcitabine （GEM） chemoresistance in pancreatic cancer cell line SW1990. Methods： The GEM-resistance cell model was constructed by a stepwise method. Immunohistochemistry was used to measure the expression of ERK protein （ERK1/2） in the established cell strains in a semiquantitative way. The mRNA expression of mdr-1 and RRM1 were detected by RT-PCR. MTT assay was performed to determine the IC50 value. Results： The established GEM-resistant cell strains were able to gain stable growth and passage ability in the medium contained different concentration levels of GEM （0, 30, 60, 100, 150 and 200 nmol/L）. The expression of ERK protein, mdr-1 and RRM1 gene were elevated accompanied by the increase of GEM concentration. There was a highly positive correlation between mdr-1, RRM1 expression and GEM-resistanca level （r = 0.960, P = 0.002 and r = 0.966, P = 0.002）. The expression of ERK protein also correlated with the mdr-1 and RRM1 level （r = -0.943, P = 0.005 and r = -0.883, P = 0.02）. At the GEM-resistance level of 200 nmol/L, the grey scale value of ERK1/2 was 164.22 ±13.17, mdr-1/β-actin and RRM1/β-actin were 1.41 ±0.04 and 1.45 ± 0.18, respectively; after treated with ERK pathway inhibitor U0126, these values synchronously decreased to 186.85 ± 13.14, 0.2 3± 0.02 and 0.21 ± 0.03, respectively; inversely, the ERK1/2 grey scale value was 106.55 ± 16.45, mdr-l/β-actin and RRMl/β-actin were 1.50± 0.07 and 1.52 ± 0.12, respectively, which presented a tendency of synchronously increase after treated with ERK pathway activator EGF. The IC50 values in GEM-resistant cells of 0 nmol/L and 200 nmol/L levels were 4.104 and 10.20, respectively. After treated with U0126, these values decreased to 3.26 and 4.50, respectively; while treated with EGF, the IC50 values increased to 8.89 and 17.17, respectively. Conclusion： The ERK pathway may induce the GEM-chemoresistance in pancreatic cell line SW1990 through the participation in the regulation of the mdr-1 and RRM1 gene expression.