Predictive value of the plasma D-dimer levels on stage and response to chemotherapy of the pancreatic cancer / 中华消化外科杂志

Objective To investigate the predictive value of the plasma D-dimer levels on stage and response to chemotherapy of the pancreatic cancer (PC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 212 PC patients who were admitted to the Fudan University Shanghai Cancer Center between December 2016 and May 2017 were collected.Plasma D-dimer levels of 212 patients were measured,and relationship between plasma D-dimer levels and clinicopathological features or response to chemotherapy were analyzed.Observation indicators:(1) relationship between clinicopathological features and positive rate of plasma D-dimer before treatment;(2) relationship between response to chemotherapy and plasma D-dimer levels;(3) follow-up and survival situations.Follow-up using telephone interview was performed to detect survival of patients up to January 2018.Comparisons of count data were analyzed using chi-square test.Measurement data with skewed distribution were described as M (range).Results (1) Relationship between clinicopathological features and positive rate of plasma D-dimer before treatment:positive rate of plasma D-dimer before treatment was respectively 18.37％ (9/49),43.64％ (24/55),53.85％ (28/52),80.36％ (45/56) in patients with stage Ⅰ-Ⅱ A,ⅡB,Ⅲ and Ⅳ of TNM staging and 43.59％(17/39),24.62％(16/65) in patients with low-differentiated tumor and high-and moderate-differentiated tumor,with statistically significantly differences (x2 =41.454,4.051,P＜0.05).(2) Relationship between response to chemotherapy and plasma D-dimer levels:of 212 PC patients,108 received pathological diagnosis by endoscopic ultrasonography or liver puncture,and then underwent 4-6 cycles chemotherapy with gemcitabine.Of 108 patients,response to chemotherapy of 59 patients was partial remission or stable disease,plasma D-dimer level before treatment was increased in 39 patients (28 with reduced plasma D-dimer level after treatment) and normal in 20 patients;response to chemotherapy of 49 patients was progressive disease,plasma D-dimer level before treatment was increased in 34 patients (8 with reduced plasma D-dimer level after treatment) and normal in 15 patients.There was no statistically significant difference in proportion of patients with increased plasma D-dimer level before treatment (x2=0.132,P＞0.05),and there was a statistically significant difference in proportion of patients with reduced plasma D-dimer level after treatment (x2 =16.929,P＜0.05).(3) Follow-up and survival situations:212 patients were followed up for 3.5-12.0 months,with a median time of 7.5 months.During the follow-up,7 patients died and 205 had survival.Conclusion The plasma D-dimer level is significantly associated with TNM staging of the PC,tumor differentiation and response to chemotherapy.

Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

The clinical interpretation of modified staging system for pancreatic neuroendocrine tumors / 中国癌症杂志

Pancreatic neuroendocrine tumor is a common pancreatic tumor with high heterogeneity and multiple management modalities. A standard and practical staging system for pancreatic neuroendocrine tumors will be beneficial to clinical management and research. At present, there are two staging systems (ENETS and AJCC). Both of them have shortcomings which limit their clinical application. In addition, the coexistence of two staging systems is confusing to clinicians. We proposed a modified ENETS staging system by keeping the ENETS TNM definition and adopting the AJCC staging definition. The modified staging system can successfully distinguish patients with different prognosis and is helpful in establishing clinical standard. This study has been published in Journal of Clinical Oncology (JCO) and was selected as 2017 Best of JCO: Gastrointestinal edition. This paper was aimed to interpret the modified staging system in clinical practice.

Clinical application value of lymph node ratio in pancreatic cancer / 中华消化外科杂志

Lymphatic metastasis is an important prognostic factor for pancreatic cancer.However,lymphatic metastatic status (N0 or N1) can not reflect the degree of lymphatic metastasis.Lymph node ratio,which is defined as the number of positive lymph nodes divided by total examined lymph nodes,can reflect the degree of lymph metastatic metastasis and give consideration to examined lymph nodes.Lymph node ratio is superior to lymph metastatic status in staging,guiding treatment,and predicting prognosis.However,currently,lymph node ratio cannot replace lymph metastatic status for the undetermined minimum number of examined lymph nodes and cut-off value.Further evidence is needed to prove its clinical value.

The influence of E-cadherin/β-catenin on the glycolysis effect in PANC-1 cells / 中国癌症杂志

Background and purpose:Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods:Through treatment of transforming growth factor β (TGF-β) in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results:E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production (P<0.05). Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells (P<0.05). Moreover, key glycolysis regulator sirtuin 3 (SIRT3) could lower E-cadherin expression.Conclusion:Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.

A case-control study on the association between urinary levels of isothiocyanates and the risk of pancreatic cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between urinary levels of isothiocyanates (ITCs) and the risk of pancreatic cancer in urban Shanghai.</p><p><b>METHODS</b>A case-control study has been conducted in urban Shanghai. The cases (from December 2006 to December 2008) were identified through an newly established "instant case reporting" system. The high performance liquid chromatography (HPLC) method was applied to determine the urinary levels of isothiocyanates in 390 cases and 414 controls. A food-frequency questionnaire was administered to estimate cruciferous vegetables consumption and dietary ITC exposure.Non-conditional logistic regression model was used to analyze the relationship between dietary and urinary levels of isothiocyanates and the risk of pancreatic cancer.</p><p><b>RESULTS</b>The cruciferous vegetables intake and ITC consumption, urinary ITC levels (median (P25, P75)) were 95.0 (66.9, 135.8) g/d, 11.0 (7.1, 16.0) µmol/d, 0.95 (0.12, 2.92) µmol/g Cr respectively in cases, all lower than those in controls, separately 107.4 (80.1, 154.1) g/d, 12.3 (8.0, 18.0) µmol/d, 1.78 (0.53, 5.28) µmol/g Cr. The differences were statistically significant (t = 3.75, 3.03, 4.40, all P values <0.01). Urinary levels of ITCs in controls were correlated with cruciferous vegetables consumption and dietary ITC exposure (r = 0.189, 0.201, all P values <0.01). There was inverse association between urinary ITCs and the risk of pancreatic cancer after adjusting for possible confounding factors such as age, sex, history of diabetes and pancreatitis. Compared with the first tertile (<0.825 µmol/g Cr), the odds ratio (95%CI) for the second (0.825-3.342 µmol/g Cr) and third tertiles ( ≥ 3.343 µmol/g Cr) were 0.69 (0.49-0.97) and 0.47(0.33-0.68), respectively, Ptrend<0.01.High levels of cruciferous vegetables or ITC consumption were associated with a reduced risk of pancreatic cancer (all P trend <0.05).</p><p><b>CONCLUSION</b>indicated that high levels of dietary ITC exposure might reduce the risk of pancreatic cancer.</p>

Standard in the clinical management of the lymph metastasis in pancreatic cancer / 中国癌症杂志

Lymph metastasis has great impact on the prognosis of pancreatic cancer patients, which can relfect the biological and invasive potential of pancreatic cancer. However, currently, there is no standard in the clinical management of the lymph metastasis in pancreatic cancer. In this report, we will discuss and summarize the followings:lymph metastatic rate and its impact on prognosis, the rule of lymph metastasis, sentinel lymph node, intra-operative lymph nodes mapping, TNM staging, regional lymph nodes resection, number of lymph nodes examined, lymph node ratio, guiding adjuvant treatments, lymphatic targeted therapy.

The value of ultrasound in detecting solid pseudopapillary tumor of the pancreas / 中国癌症杂志

Background and purpose:Ultrasound is a regular screening method of solid pseudopapillary tumor of the pancreas (SPTP). This study was to summarize the diagnostic value of ultrasound to SPTP.Methods:Clinical and ultrasound data of 62 SPTP cases in Fudan University Shanghai Cancer Center were retrospectively collected and analyzed.Results:Five cases of SPTP were undetected by ultrasound in the group. The features of ultrasound including: large mass located at the body and tail of the pancreas, clear boundary and regular shape, low ultrasound with uneven signal, or low signal mixed with no signal. A few cases have calciifcation and blood signal. Most of the cases presented no dilation of main pancreatic duct and bile duct and regional lymph nodes enlargement. Conclusion:Ultrasound can be used to detect SPTP which has special ultrasound signal features.

Recent progress on pancreatic cancer stem cells / 中国癌症杂志

10.3969/j.issn.1007-3969.2013.05.011

Reduction of β-catenin expression in hepatocellular carcinoma inhibited the enhanced metastatic potential of hypoxia / 中华肝胆外科杂志

ObjectiveTo explore the role of β-catenin in the proinvasive consequences of hypoxia in hepatocellular carcinoma (HCC).MethodsWe established in vitro and in vivo hypoxic models using the highly metastatic MHCC97 and the stable red fluorescent protein-expressing MHCC97-R cells.The role of β-catenin in hypoxia-mediated aggressiveness was investigated by β-catenin knockdown.ResultsHypoxia caused a pronounced arrest of proliferation in MHCC97 cells,suppressed tumor growth in MHCC97-R xenografts,but promoted in vitro invasiveness and in vivo metastasis.β-Catenin-silencing by short hairpin significantly inhibited the enhanced invasiveness of MHCC97 cells due to hypoxia,reduced the increase in distant metastasis by hepatic arterial ligation,but failed to further restrain cell proliferation.Conclusionβ-Catenin in HCC cells plays an essential role in the hypoxia-induced metastatic potential.A reduction of βcatenin expression inhibited the proinvasive consequences of hypoxia in HCC.

The role of preoperative CA19-9 level in predicting resectability of pancreatic cancer / 中华肝胆外科杂志

Objective To study the role of preoperative CA19-9 level in predicting resectability of pancreatic cancer.Methods Preoperative CA19-9 levels were determined by radioimmunoassay.The receiver operating characteristic curve was used to determine the cut-off point.The clinical value of the level of CA19-9 as a predictive marker of resectability was evaluated by the area under curve.Results The preoperative CA19-9 levels in the resectahle group was (313.6±515.5) kU/L,which was significantly lower than (852.1± 865.1)kU/L in the unresectable group (P＜0.001).The cut-off point of CA19-9 for predicting pancreatic cancer resectability was 312.1 kU/L,which had a sensitivity of 56.6％ and a specificity of 73.3％.The area under curve was 0.67.Conclusions The preoperative CA19-9 level may be used to predict resectability of pancreatic cancer.

Prometastatic overexpression of microtubule destabilizing protein Stathmin is regulated by DNA methylation in human pancreatic cancer / 中华肝胆外科杂志

Objective To investigate the role of Stathmin in pancreatic cancer invasion and metastasis and its relationship with DNA methylation. Methods Immunohistochemical detection of MBDI and Stathmin protein expression in 40 cases of pancreatic cancer and 15 cases ot normal pancreatic tissue were performed,followed by analysis of their clinical and pathological relationship with pancreatic cancer; Human pancreatic cancer cell line BxPC-3 was treated with 5-Aza-2-dC (AZA).Both qRT-PCR and Western blot analysis of Stathmin expression were used before and after AZA treatment; Stathmin-siRNA transfected BxPC-3 cells were divided into the Stathmi-siRNA group and the empty vector control group.Transwell chamber invasion assay and animal experiment were performed to measure the changes in cell invasion and metastatic capability. Results lmmunohistochemistry showed positive MBDI and Stathmin expressions in 28 (70％) and 24 (60％) out of 40 cases of pancreatic cancer,respectively,which were significantly higher than that in the normal pancreatic tissue (P＜ 0.05); MBDI and Stathmin protein expressions were positively correlated (r =0.356,P =0.037),so were MBDI expression and lymph node metastasis (P=0.023).Stathmin expression was significantly correlated with clinical staging and lymph node metastasis (P =0.002,and P =0.001,respectively).After AZA treatment,both Stathmin mRNA and protein expression in BxPC-3 were significantly decreased.Transwell chamber invasion assay showed that compared with the control group,the cell invasion capability of the Stathmin-siRNA group was significantly decreased (P＜0.05).Animal experiment showed that the incidence of liver metastasis was significantly lower in the Stathmin-siRNA transfected group than the empty vector control group (P＜0.05).Conclusion Demethylation may contribute to the reduction of Stathmin expression in pancreatic cancer and further improve the prognosis of pancreatic cancer patients.

Diagnosis, therapy and prognosis of pancreatic gastrointestinal stromal tumor / 中华肝胆外科杂志

Objective To investigate the clinical characteristics, diagnosis, treatment and prognosis of pancreatic gastrointestinal stromal tumor (GIST). Methods We reported a case and reviewed the medical literature on pancreatic malignant GIST. We searched the Pubmed and main domestic database. The clinical data of the reported cases were studied, and their predictive factors for postoperative recurrence and metastasis were analyzed. Results Between January 1980 and July 2010, 16 cases of pancreatic GIST were reported. There were 7 males and 9 females, with a median age pf 56.5 (31-72)years. The clinical symptoms were nonspecific. The main presentation was upper abdominal pain or discomfort. A preoperative diagnosis was suspected on radiological examination. The tumor mainly appeared as a well-defined solid-cystic mass. Irregular enhancement appeared in the circumferential and solid portion of the tumor on enhanced CT scan sequences. The pancreatic and biliary ducts were rarely dilated. Endoscopic ultrasound guided fine needle aspiration cytology (EUS-FNA) was helpful in preoperative diagnosis. Of the 15 surgical patients, 14 underwent complete resection, while the remaining received cyst-jejunostomy. A correct diagnosis was made on histopathology and immunohisto-chemistry. On a mean follow up of 21 months (range, 1-60) in 14 patients, all patients were alive.Recurrence or metastasis occurred in 4 patients with tumors of high malignant potential. On univariate analysis, the only significant predictor for adverse outcome was mitoses≥10/50 HPF. Conclusions Pancreatic GIST is a rare tumor of relatively low malignant potential. It has a better prognosis than ductal adenocarcinoma. It is important to arrive at a correct diagnosis and treat the tumor with radical resection. Aggressive surgical resection is potentially curative. Imatinib is recommended in the treatment of patients with tumors with high malignant potential.

Safe pancreaticojejunostomy after pancreaticoduodenectomy:basic requirements and criteria for selecting methods of anastomisis / 中华肝胆外科杂志

Postoperative pancreatic fistula (POPF) is the most common complication after pancreaticoduodenectomy (PD) and remains a challenge to pancreatic surgeons.In pancreaticojejunostomy,the methods of reconstruction,experience and operational techniques of surgeons are closely related to POPF.Based on a literature review and on personal experience,the author presented the basic requirements and principle in reconstructing a safe pancreaticojejunostomy (PJ).The traditional methods of pancreaticojejunostomy and their recent developments were evaluated,with their advantages and disadvantages compared.The indications of various types of PJ and the special skills required were summarized.According to his own experience,the author described in detail his recommended method of anastomosis.

Current status of the combined therapy for pancreatic cancer / 中华消化外科杂志

Pancreatic cancer is one of the worst digestive malignancies characterized by non-specific symptoms, rapid progression and high mortality. Despite great efforts that have been made in basic and clinical research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection is the only curative treatment option, but the curative resectabillty is still about 15% in China. Pancreatic surgery is considered one of the most techni-cally demanding and challenging procedures. The development of pancreatic surgery in China depends not only on the progress in surgical techniques, but also the specialization on pancreatic surgery. There has been advancement in combined therapy with a modern interdisciplinary approach including chemotherapy,radiotherapy, biotherapy and thermotherapy. The research pro-gress of gene therapy on pancreatic cancer showed us some hopes for the future. The outcome of pancreatic cancer treated by Chinese medicine with herbal drugs is encouraging, but still needs the support of more solid evidences from randomized con-trolled trials. It is suggested that the combined therapy should play an important role in the treatment of pancreatic cancer, and the fallow-up should be paid more attention.

Effects of preoperative regional intra-arterial chemotherapy on lymphatic metastasis of pancreatic head carcinoma / 中华消化外科杂志

Objective To evaluate the efficacy of preoperative regional intra-arterial chemotherapy (RIAC) in the treatment of resectable pancreatic head carcinoma. Methods The clinical data of 50 patients with resectable pancreatic head carcinoma who had been admitted to the Research Institute of Pancreatic Diseases of Fudan University from December 2006 to July 2007 were retrospectively analyzed. Patients were randomly divided into2 groups (n =25 in each group): patients in group A were treated with preoperative RIAC followed by regional pancreaticoduodenectomy, and patients in group B were treated with surgical procedure routinely. The lymphatic metastases in the 50 specimens of pancreatic head carcinoma were detected by histological examination with hematoxylin and eosin (HE) staining, and lymphatic micrometastases were detected by immunohistochemical method with staining of cytokeratin AE1/AE3 in 10 specimens with negative HE staining of the lymph nodes in each group. Results There was no significant difference in the incidence of complications, the length of hospital stay and the 1-, 2-year survival rates between the 2 groups (χ2 = 0.12, 2.88, P > 0.05). The incidence of positive lymph node metastasis in group A was 7.1% (52/734), which was significantly higher than 22.1% (118/532) in group B (χ2 = 60.01, P < 0.05). The incidence of lymphatic micrometastasis was 9.4% (30/319) in group A, and 9.1% (23/252) in group B, with no statistical difference between the 2 groups (χ2= 0.01, P > 0.05). Conclusions Preoperative RIAC is helpful in improving the prognosis of patients with resectable pancreatic head carcinoma by reducing the incidence of lymphatic metastasis and decreasing tumor stage.

Detection of lymph node micrometastasis in pancreatic head carcinoma / 中华胰腺病杂志

Objective To detect the lymph node micrometastasis in resected pancreatic head carcinoma, to investigate the role of lymphatic micrometastasis in clinical staging and predicting prognosis of the pancreatic head carcinoma. Methods Pancreaticoduodenectomy with extended lymph nodes dissection were performed in 20 patients with pancreatic head carcinoma. All the lymph nodes were taken out by operating microscope method and metastasis was diagnosed by routine histological examination with hematoxylin and eosin staining, and the presence of lymph node micrometastasis was examined by immunohistochemisty. Results A total of 677 lymph nodes were found in the 20 eases, routine histological examination revealed metastasis occurred in 87 lymph nodes in 13 cases. Of the 590 negative lymph nodes by routine histological examination, 57 lymph nodes in 3 cases were diagnosed as having micrometastasis by immunohistochemisty. With the combination of routine histological examination and immunohistochemisty, the percent of patients with positive lymph nodes increased from 65% (13/20) to 80% (16/20), the detection rate of metastasis lymph node increased from 12.9% (87/677) to 21.3% (144/677) with significant difference (P <0.05). The detection of lymph node micrometastasis changed the staging of Ⅱ A to Ⅱ B in 3 patients. Tumor metastasis and recurrence rate of patients with lymph nodes micrometastasis within one year after operation was 75%, while it was 25% of patients without lymph nodes micrometastasis. Conclusions The detection of lymph node mierometastasis metastasis was helpful in the determination of clinical staging and predication of prognosis.

Preliminary analysis of 64 slices helical CT perfusion imaging of pancreatic tumors / 中华胰腺病杂志

Objective To describe the hemodynamic characteristics of normal pancreas and pancreatic tumors by 64 slices helical CT perfusion imaging, to evaluate the role of CT perfusion in the diagnosis of pancreatic tumors. Methods Perfusion CT scan was performed in 149 patients, including 36 patients with normal pancreas, 105 patients with pancreatic tumors and 8 patients with duodenal papillary carcinoma. The parameters including blood flow (BF) ,blood volume (BV) and permeability surface area product (PS) were measured. Results The mean value of BF, BV and PS of normal pancreas were (135.24±48.36) ml· min-1·kg-1, (200.55±54.96)ml/kg and (49.75±24.27) ml·min-1·kg-1, respectively. Pancreatic carcinoma has a lower BF, BV and PS,whieh were 31.77±19.36 ml·min-1· kg-1, (66.84±39.49)ml/kg and (37.64±27.14) ml·min-1·kg-1, respectively. The aforementioned parameters in pancreatic cysts were close to zero. The parameters in pancreatic carcinoma were significantly lower than those in normal pancreas(P<0.05); the BF and BV in duodenal papillary carcinoma were significantly lower than those in normal pancreas(P<0.05), while the value of PS was not significantly different from that in normal pancreas; the aforementioned parameters in pancreatic cysts were significantly different from those in normal pancreas(P <0.01). Conclusions In perfu sion CT, normal pancreas was an organ with symmetrical BF,BV and PS. Pancreatic carcinoma was a tumor with low perfusion and decreased PS. Duodenal papillary carcinoma had decreased BF and BV with no significant change in PS. Pancreatic cyst had no blood perfusion. The 64 slice helical CT peffusion imaging was invaluable in differential diagnosis of pancreatic tumors.

Preparation of bovine serum albumin nanoparticles loaded with gemcitabine and the cytotoxic effect on pancreatic cancer cells in vitro / 中华胰腺病杂志

Objectives To investigate preparation of gemcitabine albumin nanoparticles, and its property of slow-release, the cytotoxic effect on pancreatic cancer cells (PANC1) in vitro, for improving the effect of regional intra-arterial infusion chemotherapy in pancreatic cancer with new medicament in the future. Methods The gemcitabine albumin nanoparticles were prepared with bovine serum albumin and gemcitabine with the desolvation-crosslink method, the concentration of gemcitabine was detected by high performance liquid chromatography (HPLC). The cytotoxic effect on pancreatic cancer cells in vitro were detected with MTT colorimetric assay. Results The mean diameter of gemcitabine albumin nanoparticles was (156.2±2.2) nm, and Zeta potential was (-20.4±1.41)mV, drug loading was 10.8%, drug release time in virto was 3 hours respectively. Gemcitabine albumin nanoparticles (0.01～50 μg/ml) had a 31%～44% inhibitory rate on PANC1 cell, which was similar to the inhibitory rate of same concentration of gemcitabine (26%～47%). Conclusions The new preparation of gemcitabine albumin nanoparticles had obvious drug slow-release effect, which may help improve the effect of regional intra-arterial infusion chemotherapy for pancreatic cancer.

p14ARF upregulation of p53 and enhanced effects of 5-fluorouracil in pancreatic cancer / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer.</p><p><b>METHODS</b>A human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays.</p><p><b>RESULTS</b>After transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G(1) phase. The proportion of cells in the G(1) phase was significantly increased from 58.51% to 75.92%, and in the S and G(2)/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48%, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G(2)/M phase accumulation, from 11.48% to 53.47%. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01 - 10 mg/L) than those devoid of p14ARF expression (P < 0.01). Western blotting showed p14ARF upregulates p53 expression.</p><p><b>CONCLUSION</b>Combined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.</p>