Surgical treatment of carotid artery stenosis / 中国医师杂志

Carotid artery stenosis is identified more and more common in clinical,and gradually become one of the causes of death and disablement.With the continuous development of medical technology,and medical device and apparatus equipment,surgical therapy and endovascular therapy have become one of the major principal methods in treatment of carotid artery stenosis.This article briefly discusses the current several processes and techniques of the surgical and endovascular treatment of carotid stenosis disease,and carries on the evaluation.

An analysis of clinical characteristics of 459 pulmonary embolism cases / 中华普通外科杂志

Objective To investigate pulmonary embolism (PE) clinical characteristics, the first clinical symptoms, and risk factors.Methods Incidence trends, clinical manifestations, etiology and inducing factors of 459 PE cases were analyzed retrospectively.Results For women the two peak period of PE incidence are 20-25 years of age and 60-70 years of age, for men are 20-30 years and 60-70 years;For both men and women PE incidence is peaked at 40-65 years of age.Circular distribution statistics showed the peak incidence of PE falls from November 30 through April 4, roughly in seasons of winter and spring.Dyspnea, chest distress, were among the most common symptoms (64.04％).Pulmonary infarction trilogy accounted for only 8.50％.Surgery, trauma, fracture were the primary causes for PE (44.88％), with tumor accounting for 13.0％.The veins affected by DVT are plexus venosus leg muscle, femora popliteal vein, iliac veins, tibial and peroneal veins.Conclusions The incidence of PE has obvious central tendency of age, season.Clinical symptoms are varied and non-specific.Surgery, trauma and fractures are the primary cause of PE, tumor is an independent risk factor for PE.

Analysis of 36 patients with type B aortic intramural hematoma: clinical presentations, treatments and outcomes in a single center / 中国医师杂志

Objective To review the clinical manifestation,diagnosis method,misdiagnosis,risk factors,treatments and prognosis of Stanford B aortic intramural hematoma (IMHB).Methods All of the Stanford B aortic IMHB patients admitted in Wuhan Union hospital from January 2008 to December 2013 were analyzed.The clinical manifestation,diagnosis method,misdiagnosis,managements and prognosis were studied.Furthermore,the effect and long-term survival of different therapies were compared,including medical treatment and endovascular repair.The statistics was performed with SPSS 16.0.Results There were 36 B aortic IMHB patients,and the percent of male patients was 72.22％.The mean age of IMHB was 60.19 ± 11.12.Most patients complained of acute chest and back pain,accompanied with hypertension.Twenty-eight patients (77.78％) received medication therapy,among them,there were 5 patients died of aortic rupture; eight patients (22.22％) received endovascular surgery,one died of cerebral hemorrhage (12.5％).No difference was found between medication therapy and endovascular surgery (17.86％ vs 12.5％,P ＞0.05).Conclusions For simple type B aortic IMHB patients,medication therapy and a dynamic monitoring of full aortic CT angiography was recommended,and for pejorative patients the endovascular treatment should be taken actively.

Evaluation of the association between carotid arterial stiffness and left ventricular diastolic function in patients with lower limb extremity atherosclerosis obliterans using ultrasonography / 中华超声影像学杂志

Objective To evaluate the association between the left carotid arterial stiffness and left ventricular diastolic function in patients with lower extremity atherosclerosis (AS).Methods ①A total of 32 patients with AS and 34 control objects were enrolled.The carotid arterial stiffness parameters:compliance coefficient (CC),distensibility coefficient (DC),stiffness parameter (α,β),pulse wave velocity β (PWVβ) were measured by using quality arterial stiffness(QAS) technology.And the values were compared between the two groups.②The parameters of left ventricular (LV) structure and function:LV end-diastolic interventricular septal thickness (IVSd),LV end-diastolic diameter (LVDd),LV end-diastolic wall thickness (PWd),LV ejection fraction (EF),systolic velocity (s'),early-diastolic velocity (e'),Tei index and E/e' ratio were measured by using two-dimensional echocardiography and tissue Doppler.These parameters were compared between the two groups.The association between the carotid arterial stiffness parameters and LV function parameters were analyzed by correlative analysis.Results ①Compared with the control group,the DC and CC were lower,and α,β,PWVβ,IMT were higer than the control group,with statistically significant differences(P ＜0.05).②The IVSd,Tei index and E/e'was significantly higher in the AS group than those in the control group.And the PWd,s',e' were lower than those in the control group (P ＜ 0.05).There was no significant difference in EF between the two groups (P ＞0.05).③The e' was correlated positively with DC and CC (r =0.39,0.36,P ＜0.01),and negatively with α,β,and PWVβ (r =-0.42,-0.42,-0.49,P ＜0.01).Tei index was correlated negatively with DC and CC (r =-0.50,-0.52,P ＜0.01),and positively with α,β,and PWVβ (r =0.58,0.58,0.62,P ＜0.01).The E/e' was correlated regatively with CC (r =-0.27,P ＜0.05),and positively with PWVβ (r =0.28,P ＜0.05).There were no significant correlation between s',EF and the stiffness parameters of carotid artery (P＞0.05).Conclusions In patients with AS,the left carotid artery stiffness increases and left ventricular systolic and diastolic function are impaired.The carotid artery stiffness and left ventricular diastolic function is correlated.Changes in carotid artery stiffness reflect the change in left ventricular diastolic function.

Preliminary study on the correlation between femoral stiffness and cardiac function in patients with lower extremity atherosclerotic disease / 中华超声影像学杂志

Objective To evaluate the correlation between left ventricular function and arterial stiffness of left femoral artery in patients with lower extremity atherosclerotic disease (LEAD).Methods Thirty-three patients with LEAD and 37 healthy subjects (control group) were enrolled in this study.The intima-media thickness (IMT),diameter and parameters of arterial stiffness [dispensability coefficient (DC),compliance coefficient (CC),stiffness α,stiffness β,pulse wave velocity (PWVβ) ]were measured by ultrasonography with the technology of QIMT and QAS.The thickness of the interventricular septum (IVSd),end-diastolic left ventricular diameter (LVDd) and left ventricular mass (LVM),and parameters of the left ventriculsr function (EF,E/A,E'/A',E/E' and Tei index) were measured by echocardiography.These parameters were compared between two groups.Correlations between the parameters of the arterial stiffness and those of the cardiac function were evaluated by Pearson correlative analysis.Results ①The IVSd,LVM and E/E' ratio were significantly higher in LEAD group than those in control group ( P ＜0.05).There were no significant differences in EF,E/A,E'/A',and Tei index between two groups ( P ＞0.05).②The IMT,α,β,PWVβ of left femoral artery were significantly higher in LEAD group than those in control group,while DC and CC were significantly lower in LEAD group than those in control group ( P ＜0.05).③The E/E' ratio,one of the parameters representing the left ventricular diastolic function,was correlated negatively with CC and positively with α,β,and PWVβ ( P ＜0.05 or P ＜0.01 ).The E'/A' ratio was correlated positively with DC and CC,and negatively with α,β,and PWVβ ( P ＜0.05 or P ＜0.01 ).Both EF and Tei index were not significantly correlated with the above parameters of arterial stiffness ( P ＞0.05).Conclusions Patients with LEAD have thickened femoral IMT,higher arterial stiffness of left femoral artery,as well as impaired left ventricular function.There is a close correlation between the atherosclerosis of the femoral artery and the early left vcntricular dysfunction.

Inhibitory effects of Rap1GAP overexpression on proliferation and migration of endothelial cells via ERK and Akt pathways / 华中科技大学学报（医学）（英德文版）

Rap1 is expressed in human umbilical vein endothelial cells (HUVECs). Rap1-GTPase activating protein (Rap1GAP), with its specific target, Rap1, has been shown to be important in the regulation of many physiological and certain pathological processes. In this study, we investigated the effect of Rap1GAP expression on endothelial cell function, or, more specifically, proliferation and migration of endothelial cells. HUVECs were transfected with pcDNA3.1 (empty vector), pcDNA3.1 containing Flag-tagged-Rap1GAP or Myc-tagged-Rap1N17. The proliferation, migration and tube formation were examined and compared among the 3 groups. Expression of Rap1, Rap1GAP, extracellular signal-regulated kinase (ERK), phospho-ERK, Akt, phosphor-Akt was detected by Western blotting. The results showed that the proliferation, migration and tube formation were significantly reduced in Rap1GAP- and Rap1N17-transfected HUVECs as compared with empty vector-transfected control. These changes were coincident with increased expression of Rap1GAP and decreased expression of activated Rap1, phospho-ERK and -Akt. After treatment of Rap1GAP-transfected HUVECs with a stimulator of Rap1 guanine-nucleotide-exchange factor (Rap1GEF) 8CPT-2'OMe-cAMP, it was found that Rap1 activity was decreased as compared with empty vector-transfected control. Pretreatment of HUVECs with an ERK inhibitor PD98059 or a PI3K inhibitor LY294002 prior to stimulation not only blocked 8CPT-2'OMe-cAMP-induced phosphorylation of ERK and Akt, but also significantly reduced cell proliferation and migration. Finally, we examined the effect of vascular endothelial growth factor (VEGF) on HUVECs overexpressing Rap1GAP. VEGF-stimulated Rap1 activity, phosphorylation of ERK and Akt, cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing Rap1GAP as compared to empty vector-transfected control. Taken together, our findings demonstrate that Rap1GAP/Rap1 and their downstream effectors regulate proliferation and migration of HUVECs via ERK and Akt pathways.

Deep vein thrombosis: Related to anemophilous pollen? / 华中科技大学学报（医学）（英德文版）

The etiology of deep vein thrombosis (DVT) is still not elucidated nowadays. Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air, we proposed the hypothesis that allergic reaction induced by anemophilous pollen may cause "idiopathic" DVT, and proinflammatory factors may play an important role in the thrombosis process.

Intravenous leiomyomatosis with right heart involvement-A report of 4 cases and literature review / 华中科技大学学报（医学）（英德文版）

Intravenous leiomyomatosis (IVL) is a rare benign neoplasm which originates from the smooth muscle cells and is usually confined to the pelvic venous system. Rarely, intracaval and intracardiac extension has been described. Death can occur as a result of intracardiac involvement. We reported 4 cases of IVL with right heart involvement (intracardiac leiomyomatosis, ICL). Three of them suffered recurrent sudden syncope, and the other one was totally asymptomatic. All of them were successfully treated through one-stage operation under extracorporeal circulation.

Analysis of 287 patients with aortic dissection: General characteristics, outcomes and risk factors in a single center / 华中科技大学学报（医学）（英德文版）

The general characteristics, outcomes and risk factors of the patients with aortic dissection (AD) were evaluated in a single medical center. From January 2002 to December 2008, 284 patients with AD were treated and followed-up at our institution, including 105 cases of type A AD and 179 cases of type B AD. The patients in each type were divided into three groups according to management: medical treatment group (A or B), open surgery group (A or B), and stent-graft group (A or B). The characteristics and follow-up outcomes were compared between the groups or subgroups. The results showed that there was significant difference in the prognosis for type A AD between medical treatment group and open surgery group, but there was no significant difference in the prognosis for type B AD between medical treatment group and stent-graft group. Independent risk factors of follow-up mortality for patients with type A AD included a history of atherosclerosis (HR, 3.807; 95% confidence interval [CI], 1.489 to 7.611; P=0.003), in-hospital hypotension/shock (HR, 4.687; 95% CI, 1.846 to 11.900; P=0.001), in-hospital myocardial ischemia or infarction (HR, 3.734; 95% CI, 1.613 to 8.643; P=0.002), pleural effusion (HR, 2.210; 95% CI, 1.080 to 4.521; P=0.030), branch vessel involvement (HR, 2.747; 95% CI, 1.202 to 6.278; P=0.016) and surgical treatment (HR, 0.177; 95% CI, 0.063 to 0.502; P=0.001). And there were insignificant independent predictors for mortality of the patients with type B AD. It was concluded that there were significant differences in characteristics and one year mortality between type A AD and type B AD, but after one year, there was no significant difference in the mortality and complications of them. There were several discordant risk factors of AD, such as female gender, age, thrombus, abrupt onset of pain that were considered as the risk factors in some papers. And there was no definite risk factor of mortality in this study in the patients with type B AD.

Prevention and treatment of cerebral complications in patients with carotid stenosis in perioperative period / 中华普通外科杂志

Objective To investigate the causes of and prevention for cerebral complications in perioperative period in patients with carotid stenosis. Methods The causes and treatment of cerebral complications among 133 cases of carotid stenosis during perioperative period from May 2004 to Jun 2009 were analysed retrospectively. Results Among 133 cases, 94 cases underwent carotid endarterectomy (CEA) and 39 cases had carotid artery stenting(CAS). Cerebral complications developed in 16 cases including 3 cases of more than two attacks. 5 cases suffered from tansient ischemia attacks (TIA)or cerebral ischemia before operation. 5 developed TIA or cerebral hyperperfusion syndrome (CHPS) among those undergoing CEA and 4 developed TIA or CHPS among CAS cases. During postoperative period, 8 cases developed TIA, CHPS,cerebral infarction or cerebral hemorrhage. Conclusions Prevention and treatment of cerebral complications is extremely important durning surgical therapy of carotid stenosis.

Acute phase reaction of different macromolecule vascular grafts healing in rat muscle / 生物工程学报

To find out which biomaterial had the best biocompatibility, we compared the acute phase reaction of common biomaterials preparing for vascular grafts with the material of polyurethane modified by silk fibroin (SF-PU(1:1)). After transplanted the materials of dacron, polyterafluoroethylene (e-PTFE), polyurethane (PU), SF-PU(1:1) in rat muscle for one week, we studied the influence of different biomaterials on the histocompatibility by using rat acute toxicity test, test of local reaction in muscle, tissue section staining, WBC and PLT count. As a result, dacron had the worst histocompatibility. The other biomaterials had slight local inflammatory reaction. The WBC and PLT was nearly the same with the blank except dacron. e-PTFE, pure PU and SF-PU(1:1) had the better histocompatibility than traditional dacron. Especially SF-PU(1:1) had the best histocompatibility. Because of the better physical properties and histocompatibility of SF-PU( 1:1), the prospect of preparing small-diameter vascular grafts with SF-PU was cheerful.

Assessment of risk factors for acute lower-limb deep venous thrombosis / 中华普通外科杂志

Objective To observe the changes of coagulation function in patients with acute lowerlimb deep venous thrombosis(DVT)and evaluate the risk factors for DVT. Methods Plasma APTT.PT,TT,D-dimer and fibrinogen(Fbg)were detected by an automated coagulation analyzer in 62 acute lower-limb DVT patients and 70 controls:Retrospective studies on the clinical data of all patients were done by binary logistic regression analysis.Results (1)In DVT group,plasma APTT,PT and TT,the levels of D-dimer and fibrinogen.and D-dimer/fibrinogen ratio(D/F ratio)were higher when compared with control group(au P＜0.01);(2)There were positive correlations between D-dimer and fibrinogen both in DVT and control groups(r=0.475,P＜0.01;r=0.564,P＜0.01,respectively);(3)Logistic analysis indicated that acute lower-limb DVT was associated with the presence of hypertension and increased plasma level of fibrinogen(OR=24.99,P＜0.01: OR=4.346.P＜0.01,respectively).Conclusions Hypertension and elevated plasma level of fibrinogen are independent risk factors for acute lower-limb DVT.

Diagnosis and surgical management of intracaval venous tumor in 6 cases / 中华普通外科杂志

Objective To investigate the diagnosis and surgical treatment of intracaval venous tumors. Methods Clinical data of 6 cases were retrospectively analyzed, including signs and symptoms diagnostic means such as type-B ultrasound, CTA, MRA, surgical procedures and prognosis. Results All six cases received type-B ultrasonic examination, final definite diagnosis was achieved by CTA exam in 2 cases and through MRA in 4 cases. Heart involvement was found in 3 cases. All patients underwent a surgery. According to the extent of the tumor,3 cases had thoraco-abdominal incision,3 cases with extracorporeal circulation and right atrium opening. All of the tumors were completely resected. Pathological exam revealed that 4 cases were of leiomyomatosis and 2 cases were of leiomyosarcoma. One case with leiomyosarcoma died of liver disfunction postoperatively.The other 5 cases recovered without major complications. An average 51 months of follow-up found no recurrence. Conclusions CT and MRI are the mainstay for the diagnosis,and MRI can provide clear anatomy image to the surgeons, help choose the surgical procedures. The one-stage operation is effective. During the operation, the main branches of the vena cava system should be detected, and the attachment of the tumor should be found and removed thoroughly to prevent the recurrence of the tumor. When the attachment point is lower than the iliac vein level, ligation of the involved iliac vein should be mandatory.

Analysis of management on 23 cases of carotid body tumors / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#By reviewing the clinical material in 23 cases (25 tumors) of carotid body tumors, we concluded our experience in selecting the appropriate diagnostic modality and surgical therapy to facilitate surgical maneuvers and decrease the incidence of postoperative complications.@*METHOD@#From 2003 to 2008, 23 cases of carotid body tumors were admitted and treated in Wuhan Union Hospital. All the 23 cases were operated after determining diagnosis that was deterred by angiography and noninvasive examinations including color Doppler scan, computed tomography angiography and magnetic resonance angiography.@*RESULT@#There was no patient died, no cerebral infarctions, no recurrence after operation. Nervous complications occurred in 5 cases post operatively.@*CONCLUSION@#Preoperative angiography is a appropriate diagnostic modality for carotid body tumor, which can shows the supply arteries of the tumor and estimate the structure of the Willis Circle, so that we can judge the possibility to temporarily clamp the carotid artery during the operation to control the hemorrhage and eliminate the postoperative nervous complications.

Endovascular covered stent graft exclusion and prosthetic vessel replacement for treatment of abdominal aortic aneurysm: Comparison of 1-year follow-up outcomes / 中国组织工程研究

BACKGROUND:Conventional prosthetic vessel replacement has been gradually replaced by endovascular covered stent graft exclusion in the treatment of abdominal aortic aneurysm (AAA).However,whether it has advantages over conventional prosthetic vessel replacement in clinical curative effects and biocempatibility produced in the implantation of new type of biomaterials remains unclear.OBJECTIVE:To compare the curative effects and complications of endovascular covered stent graft exclusion and prosthetic vessel replacement in the treatment of AAA.DESIGN: A controlled observation analysis.SETTING: Department of Vascular Surgery,Wuhan nion Hospital.PARTICIPANTS: Forty-two patients with AAA (renal artery not involved) who received the treatment in the Department of Vascular Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology between September 2001 and July 2006,were recruited in this study.They were all confirmed by CT angiography (CTA) and other examinations.According to the selected operative way,patients were allocated into interventional therapy group (n =17) and conventional therapy group (n =25).In the interventional therapy group,the patients,including 16 males and 1 female,were averaged (68±10)years old,and their mean tumor diameter was (6.4±1.3) cm.In the conventional therapy group,the patients,including 23 males and 2 females,were averaged (64±9) years,and their mean tumor diameter was (6.2±1.1) cm.Significant difference did not exist in the baseline material between two groups (P ＞ 0.05).This study was approved by the Hospital Ethics Committee.Written informed consents were obtained from all the patients.METHODS:In the interventional therapy group,patients underwent ndovascular covered stent graft exclusion by an interventional means.After being generally anesthetized,patients were dissected at unilateral femoral artery.Under the perspective condition,a covered stent graft was placed at a proper position with a forwarder,and then it was released and expanded.Following the position and xpansion of a covered stent being examined by CTA,femoral artery was anastomosed and incision was closed.If arteria iliaca was involved,then another covered stent was implanted from contralateral femoral artery and connected to stem.In the conventional therapy group,patients underwent prosthetic vessel replacement by a conventional means.Postoperatively,patients in the two groups all received anti-inflammation,anti-coagulation and other symptomatic and supportive treatments necessarily.MAIN OUTCOME MEASURES:① Postoperative complications of patients in two groups.② Recovery was observed by B-ultrasonography and CTA examination 1,3,6 and 12 months after operation.③ Follow-up of biocompatibility of biomaterials and host during 1 year postoperatively.RESULTS:Forty-two patients participated in the finial analysis.①Patients who exhibited pulmonary infection and renal function deterioration in the interventional therapy group were fewer than those in the conventional therapy group (P ＜0.05).② In the interventional therapy group,patients with covered-stent graft displacement,aortic injury and hematoma formed at the puncture point of femoral artery were not found.In the conventional therapy group,one patient died of acute large-area myocardial infarction at the 6th week postoperatively,and patients,who suffered from stomal leakage,prosthetic vessel thrombogenesis and infection,etc.,were not found.③ Neither obvious inflammatory reactions in the peripheral tissue of prosthetic vessel nor thrombogenesis in the prosthetic vessel was found in patients of two groups.It was demonstrated that both covered stent graft and prosthetic vessel had good biocompatibility.CONCLUSION:Endovascular covered stent graft exclusion can treat AAA due to its less surgical trauma,rapid postoperative recovery,good biocompatibility and other advantages.

Effect of anti-KDR antibody on the proliferation of hemangioma vascular endothelial cells in vitro / 华中科技大学学报（医学）（英德文版）

The suppressive effect of anti-KDR antibody against VEGF on proliferation of hemangioma-derived vascular endothelial cells (HVECs) was investigated. HVECs from one case of hemangioma in proliferative phase were cultured. Both primary culture and sub-culture were conducted in M199 medium. The HVECs of passage 3 were divided into 4 groups based on the concentrations of anti-KDR antibody. Cell count was performed and inhibitory rate of HVECs was measured before and 9 days after interference. The results showed that the number of HVECs in the anti-KDR antibody-treated groups was significantly decreased and the inhibitory rate of HVECs by anti-KDR antibody (50, 10 and 2 microg/mL) was 84%, 63% and 39% respectively at 9th day after interference, with the difference being significant. In the control group, the number of HVECs was increased significantly. In was concluded that the anti-KDR antibody could suppress the activity of VEGF through blocking the KDR, indicating the potential clinical applications of anti-KDR antibody in the treatment of hemangioma.

Endovascular covered stent graft exclusion and prosthetic vessel replacement for treatment of abdominal aortic aneurysm:Comparison of 1-year follow-up outcomes / 中国组织工程研究

0.05).This study was approved by the Hospital Ethics Committee.Written informed consents were obtained from all the patients.METHODS:In the interventional therapy group,patients underwent endovascular covered stent graft exclusion by an interventional means.After being generally anesthetized,patients were dissected at unilateral femoral artery.Under the perspective condition,a covered stent graft was placed at a proper position with a forwarder,and then it was released and expanded.Following the position and expansion of a covered stent being examined by CTA,femoral artery was anastomosed and incision was closed.If arteria iliaca was involved,then another covered stent was implanted from contralateral femoral artery and connected to stem.In the conventional therapy group,patients underwent prosthetic vessel replacement by a conventional means.Postoperatively,patients in the two groups all received anti-inflammation,anti-coagulation and other symptomatic and supportive treatments necessarily.MAIN OUTCOME MEASURES:① Postoperative complications of patients in two groups.② Recovery was observed by B-ultrasonography and CTA examination 1,3,6 and 12 months after operation.③ Follow-up of biocompatibility of biomaterials and host during 1 year postoperatively.RESULTS:Forty-two patients participated in the finial analysis.①Patients who exhibited pulmonary infection and renal function deterioration in the interventional therapy group were fewer than those in the conventional therapy group(P

Effect of Anti-KDR Antibody on the Proliferation of Hemangioma Vascular Endothelial Cells in vitro / 华中科技大学学报（医学）（英德文版）

The suppressive effect of anti-KDR antibody against VEGF on proliferation of beman-gioma-derived vascular endothelial cells (HVECs) was investigated. HVECs from one case of he-mangioma in proliferative phase were cultured. Both primary culture and sub-culture were conducted in M199 medium The HVECs of passage 3 were divided into 4 groups based on the concentrations of anti-KDR antibody. Cell count was performed and inhibitory rate of I-IVECs was measured before and 9 days after interference. The results showed that the number of HVECs in the anti-KDR anti-body-treated groups was significantly decreased and the inhibitory rate of HVECs by anti-KDR anti-body (50, 10 and 2 μg/mL) was 84%, 63% and 39% respectively at 9th day after interference, with the difference being significant. In the control group, the number of HVECs was increased signifi- cantly. In was concluded that the anti-KDR antibody could suppress the activity of VEGF through blocking the KDR, indicating the potential clinical applications of anti-KDR antibody in the treat-ment of hemangioma.

Antiproliferative Effect of Phenylbutyrate in AsPC-1 Pancreatic Cancer Cell Line

PURPOSE: Phenylbutyrate is an effective redifferentiating agent in several human cancers. Recently phenylbutyrate has been reported to inhibit histone deacetylase activity. We investigated the effects of sodium 4-henylbutyrate (Na-4-PB) on cell proliferation in a human pancreatic cancer cell line. METHODS: A human pancreatic cancer cell line, Aspc-1 was purchased from Korean Cell Line Bank. Antiproliferative effects of sodium 4-phenylbutyrate were measured by MTT assay and their mechanisms were evaluated by apoptosis assay and cell cycle analysis. RESULTS: After 3 days of treatment with Na-4-PB at the concentration of 2.5, 5, 7.5, and 10 mM, relative growth inhibition compared to control was 21.3+/-8.3% (mean+/-SD), 37.8+/-2.3%, 46.7+/-0.5%, and 56.7+/-1.7% respectively (p < 0.05). Antiproliferative effect of Na-4-PB was also time-dependent. Combination treatment with Na-4-PB and troglitazone, a PPARg agonist, increased antiproliferative effects but was not synergistic. After 48 hour treatment with Na-4-PB, early apoptotic cell population in control, 2.5, and 5 mM of Na-4-PB was 29.6%, 44.2%, and 65.9%, respectively. After 24 hour treatment with Na-4- PB, G0/G1 phase population in control, 2.5, and 5 mM of Na-4-PB was 55.0%, 67.4%, and 65.8%, respectively. CONCLUSION: Na-4-PB inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest at G0/G1 phase in time- and dose-dependent manner. Combination treatment with Na-4-PB and other chemotherapeutic agents such as troglitazone, a PPARg agonist, can enhance antiproliferative effects. Na-4-PB might be a promising potential therapeutic agent for patients with pancreatic cancer.

Antiproliferative Effect of NS-398, a Cyclooxygenase-2 Inhibitor, in Pancreatic Cancer Cell Lines

PURPOSE: Selective cyclooxygenase (COX)-2 inhibitors have been reported to inhibit cancer cell proliferation. We investigated the effects of NS-398, a selective COX-2 inhibitor, on cell proliferation in human pancreatic cancer cell lines. METHODS: Human pancreatic cancer cell lines, Aspc-1, Capan-1, and Capan-2 were used. We used western blot and/or RT-PCR to evaluate COX-2 and vascular endothelial growth factor expression. Antiproliferative effects were measured by MTT assay, apoptosis assay and cell cycle analysis. Epidermal growth factor (EGF) and troglitazone were used for combined treatment. RESULTS: COX-2 was relatively overexpressed in Capan-1 and Capan- 2, but minimal in Aspc-1 cell line. COX-2 mRNA expression was upregulated by 50 microM of NS-398 in Aspc-1 cell line but was downregulated at 100 microM in all cell lines. Treatment with NS-398 increased cell population of G0/G1 phase and also induced early apoptotic changes in a dose-dependent manner in all three cell lines. Combined treatment with EGF or troglitazone did not seem to affect antiproliferative effects of NS-398. All three cell lines expressed vascular endothelial growth factor constitutively and its expression was downregulated by treatment with NS-398. Pretreatment with NS-398 prior to radiation exposure increased radiosensitivity in Capan-2 cells. CONCLUSION: COX-2 expression was variable in pancreatic cancer cell lines. NS-398 inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest in a dose-dependent manner. Treatment with NS-398 also inhibited expression of VEGF and enhanced radiosensitivity in pancreatic cancer cell lines. COX-2 inhibitors might be promising potential therapeutic agents for patients with pancreatic cancer.