[Experimental study of radiofrequency ablation of liver in swine].

OBJECTIVE: To explore the feasibility and efficacy of multiple-radiofrequency ablation (RFA) in swine liver. METHODS: One swine undergone percutaneous and intra-operative RFA for three times in succession (an interval of 5 days) guided by real-time ultrasound. Then 6 ablated lesions formed. The outcome of RFA and the change of tissues adjacent to ablated lesions (biliary, liver vascular and abdominal wall) were observed by trans-abdominal ultrasonography (US), contrast enhanced ultrasound (CEUS), intra-operative ultrasound (IOUS) and contrast enhanced computed tomography (CT). RESULTS: Bile duct dilatation was found beside primary porta hepatis on US, CT, IOUS after RFA. There was no thrombus in liver vein through the ablated lesion with electrodes parallel to primary porta hepatis. Two ablated lesions were incompletely fused together. Small thermal injury was observed on abdominal wall after an injection of saline into subcapsular gap. Subcapsular hepatic tissue around ablation lesion changed into coagulative necrosis from hyperemia with elapsing time. Carbonizing granule formed during RFA on the top of intro-operative radio-frequency electrode easily caused bleeding along the withdrawing passage. Gelfoam was helpful to stop bleeding during intro-operative RFA. Occluding blood flow into liver definitely enlarged ablated area with the same amount of RFA energy. CONCLUSION: Multiple-RFA is feasible and efficacious for patients with RFA indication. But the complications of RFA increase if the ablation areas are adjacent to such organs as bile duct, stomach, intestine and diaphragm, etc.

Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer.

BACKGROUND: MicroRNAs have been shown to offer great potential in both the diagnosis and prognosis of cancer. Despite the well-established role of the miR-17-92 in cancer formation and progression, the contribution of each individual miRNA remains to be characterized. Thus, we investigated whether deregulation of the miR-17-92 associated with colon cancer prognosis. METHODS: Expression levels of the miR-17-92 cluster and its paralogs were determined in 48 colon tumor and 48 paired normal tissues by real-time qRT-PCR. Associations with miRNA expression, age, sex, TNM staging, and survival prognosis were evaluated. RESULTS: MiR-17-92 cluster and its paralogs were significantly overexpressed in colon tumor. No significant associations were found between the deregulation of certain miRNAs and the clinical and pathologic characteristics observed in patients. Kaplan-Meier curves demonstrated significantly reduced overall survival in patients expressing high levels of miR-17. In multivariate Cox models, miR-17 overexpression (HR 2.67; P = 0.007) and TNM staging (HR 8.87; P = 0.002) were significantly associated with a risk of death. CONCLUSIONS: The miR-17-92 cluster and its paralogs were significantly elevated in patients with colon cancer, and heightened expression of miR-17 was associated with poor survival. Moreover, miR-17 and TNM staging were both identified as significant, but independent, prognostic biomarkers in colon cancer.

Hyperthermia synergizes with tissue factor knockdown to suppress the growth and hepatic metastasis of colorectal cancer in orthotopic tumor model.

BACKGROUND: Tissue factor (TF) is a significant risk factor for tumor growth and hepatic metastasis in patients with colorectal cancer (CRC). This study aimed to investigate whether hyperthermia has synergistic anti-tumor effects with TF knockdown in suppressing CRC progression and metastasis in vitro and in vivo. METHODS: Human colorectal cancer LOVO cells were treated by hyperthermia at 44°C for 2 hr or/and TF siRNA. Then the cells were subjected to colony formation assay. Apoptosis was analyzed by flow cytometry, confocal microscopy, and transmission electron microscopy. The cell migration and invasion abilities were analyzed by wound healing and matrigel assay. In addition, orthotopic nude mice model of CRC was established. RESULTS: Hyperthermia synergized with TF knockdown to reduce colony formation ability, induce apoptosis, and suppress the migration and invasion of LOVO cells in vitro. Moreover, hyperthermia in combination with TF depletion inhibited the growth and hepatic metastasis of CRC in orthotopic nude mice model. Mechanistically, the synergistic effects were at least partly mediated by inducing JNK mediated apoptosis and suppressing matrix metalloproteinases (MMPs) mediated invasion. CONCLUSIONS: Hyperthermia in combination with TF-targeted therapy could be a potential approach for CRC treatment.

Tissue factor/activated factor VIIa induces matrix metalloproteinase-7 expression through activation of c-Fos via ERK1/2 and p38 MAPK signaling pathways in human colon cancer cell.

PURPOSE: Increased expression of tissue factor (TF) is associated with tumor invasion and metastasis in human colorectal cancer. We have previously observed that TF/FVIIa upregulates matrix metalloproteinase-7 (MMP-7) expression at the transcriptional level in colon cancer cells. MMP-7 overexpression is believed to play an important role in tumor invasion and metastasis. The aim of this study is to elucidate the molecular mechanisms by which TF/FVIIa induced MMP-7 expression and cell invasion in vitro. METHODS: Reverse transcription polymerase chain reaction, Western blot, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to determine the potential mechanism and signaling pathways by which TF/FVIIa induced MMP-7 expression and cell invasion in LoVo cells. Small interfering RNA (siRNA) and cell invasion assay was used to examine whether blocking c-Fos expression could abolish FVIIa-mediated upregulation of MMP-7 and cell invasion in vitro. RESULTS: The results showed that FVIIa induced the upregulation of MMP-7 both at the mRNA and protein levels in a time- and dose-dependent manner and increased the invasive behavior of LoVo cells. FVIIa enhanced the promoter activity of MMP-7, and the activator protein-1 (AP-1) binding site was responsible for the activation. Site mutation of the AP-1 binding site in the promoter almost completely abolished FVIIa-mediated response. Furthermore, ChIP assay confirmed that FVIIa promoted the direct binding of c-Fos with the MMP-7 promoter in vivo. FVIIa also induced the expression and nuclear accumulation of the AP-1 subunit c-Fos. siRNA-mediated knockdown of c-Fos eliminated FVIIa-stimulated MMP-7 expression and cell migration in vitro. In addition, selective mitogen-activated protein kinase (MAPK) kinase (MEK1/2) inhibitor (PD98059) and p38 MAPK inhibitor SB203580 suppressed MMP-7 upregulation induced by FVIIa. CONCLUSIONS: Our data suggest that a novel TF/FVIIa/MAPK/c-Fos/MMP-7 axis plays an important role in modulating the invasion of colon cancer cells and blockage of this pathway holds promise to treat colon cancer metastasis.

Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription.

BACKGROUND: Barrier function is essential for the maintenance of normal intestinal function. Dysregulation of the intestinal barrier underlies a wide range of disorders. AIM: Previously, we found that sodium butyrate (NaB) decreased the molecular permeability of intestinal barrier in vivo model, but the mechanism by which NaB facilitated the tightness of tight junctions (TJs) in small intestinal epithelium needed further studies. METHODS: In vitro culture of the cdx2-IEC monolayer was used to mimic barrier function. The TJs were assessed by transepithelial electrical resistance (TEER) and paracellular flux of fluorescein isothiocyanate-conjugated dextran 40,000 (FD-40), Western blot, Q-RT-PCR, and immunofluorescence. Promoter and chromatin immunoprecipitation (ChIP) assays were also done to analyze the Claudin-1 gene. RESULTS: NaB decreased FD-40 flux, increased TEER and TJ protein Claudin-1 expression, induced ZO-1 and Occludin redistribution in cellular membrane, and reversed the damage effect after calcium (Ca(2+)) switch assay. Silencing Claudin-1 prevented protective function of NaB from enhancing intestinal barrier integrity. Further studies demonstrated that NaB increased Claudin-1 transcription by facilitating the interaction between transcription factor SP1 and a specific motif within the promoter region of Claudin-1. This SP1 binding motif was located upstream of the coding region (-138 to -76 bp) and indispensable for the transcription of Claudin-1 following NaB treatment. ChIP assay confirmed the association between SP1 and Claudin-1 promoter, and the elimination of the SP1 binding site by point mutation resulted in a significant loss of Claudin-1 transcription after NaB dealing. CONCLUSIONS: NaB enhanced intestinal barrier function through increasing Claudin-1 transcription via facilitating the association between SP1 and Claudin-1 promoter.

[Analysis of prognostic factors in patients with lymph node-negative rectal cancer].

OBJECTIVE: To investigate the risk factors for the prognosis in patients with node-negative rectal cancer. METHODS: Clinicopathological characteristics of 117 patients with lymph node-negative rectal carcinoma undergoing curative rectectomy from January 2005 to December 2008 were retrospectively analyzed. RESULTS: The overall 5-year survival rate was 91.5%. The univariate analysis revealed that tumor size(χ(2)=8.422,P=0.004), invasive depth(T staging, χ(2)=9.448,P=0.024), cell differentiation(χ(2)=26.571,P=0.000), pathologic type(χ(2)=4.712,P=0.030) and preoperative level of carcinoembryonic antigen(χ(2)=4.131,P=0.042) had significant effects on the survival. In multivariate analysis, the independent prognostic factors for these patients were tumor size (Wald=5.286,P=0.022), cell differentiation (Wald=7.172, P=0.007) and invasive depth (T staging, Wald=5.741, P=0.017). CONCLUSION: For node-negative rectal cancer patients, tumor size, poor differentiation and invasive depth are important markers to evaluate their prognosis.

[Logistic regression analysis of clinical and ultrasonic features of breast nodules].

OBJECTIVE: To create a breast nodule estimation model based on grayscale and color Doppler ultrasonography using Logistic regression that can screen out the specific features for distinguishing breast malignancy from benignancy. METHODS: From July, 2009 to May, 2010, 217 patients were enrolled in the study in peking university first hospital. Clinical data and ultrasonic features were evaluated in 219 breast nodules of 217 patients confirmed by surgical pathology. Logistic regression model was established to screen out significant ultrasonic indexes for differentiating breast malignancy from benignancy. A receiver operating characteristics curve was made to assess diagnostic value of the Logistic regression model. Correlation was analyzed between the Logistic regression model and surgical pathology. RESULTS: Logistic regression model: Logit(p) = -16.884 + 0.037 × age + 3.228 × longitudinal-transverse axis ratio + 1.412 × border + 2.663 × halo + 1.813 × microcalcium + 1.157 × resistance index + 2.204 × enlarged axillary lymph node (χ(2) = 167.107, P = 000). The areas of ROC curve for probability and identification of breast malignant and benign nodule were 0.948 and 0.882 respectively. Diagnostic sensitivity, specificity and accuracy were 91.6%, 84.9% and 88.9%. Logistic regression model positively correlated with surgical pathology (r = 0.768, P = 0.000). CONCLUSION: Our Logistic regression model can effectively differentiate malignant breast nodules from benign and can identify the ultrasonic features associated with breast cancer.

[Surgical complications after pancreatoduodenectomy: risk factors and treatments].

OBJECTIVE: To explore the impact factors and treatment of post pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications. RESULTS: The overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.

[Ectopic expression and clinical significance of tissue factor/coagulation factor VII complex in colorectal cancer].

OBJECTIVE: To study the expression of coagulation factor VII(FVII)/tissue factor(TF)complex in colorectal carcinoma (CRC)and its correlation with clinicopathologic factor. METHODS: The expression of coagulation factor VII protein was studied by immunohistochemistry and Western blot.The expression of tissue factor and coagulation factor VII at the mRNA levels were evaluated by quantitative realtime RT-PCR in 45 cases of CRC. RESULTS: (1) FVII overexpression was ectopicly detected in CRC specimens at protein level by immunohistochemistry and Western blot, but not in adjacent non-cancerous mucosa of colorectum;(2)FVII protein mainly localized in the cytoplasm of colon cancer cells.The positive ratios of FVII protein expression in stages I, II, III and IV by immunohistochemistry assay were 33.3%, 40.0%, 64.7% and 80.0% respectively(P=0.001); (3)The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than that in CRC without hepatic metastasis.The relative expression was 5.33+/-2.88 and 1.47+/-0.51 respectively(P=0.03). Overexpression FVII gene was unrelated with tumor size, differentiation, depth of invasion, lymph node metastasis and TNM staging.There existed some relation between the gene and protein level by Spearman correlation, r=0.58, P=0.003;(4)The expression of TF mRNA in CRC significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging.The expression of tissue factor was a critical factor to predict liver metastasis by logistic regression analysis(P=0.001). CONCLUSION: Colorectal cancer can ectopicly synthesize coagulation factor VII.Tissue factor expression may play a role in the process of developing hepatic metastasis.The microenvironment of high dose FVII protein may promote tumor metastasis.

[Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer].

OBJECTIVE: To evaluate the prognostic value of lateral pelvic lymph node metastasis on low rectal cancer. METHODS: One hundred and seventy-six patients with low rectal cancer who underwent radical resection combined with lateral pelvic lymph node dissection between 1994 and 2005 were reviewed. The data of the cases was investigated to define the prognostic value of lateral pelvic lymph node metastasis on the patients. RESULTS: Lateral node metastasis occurred in 33 patients (18.8%), and 51.5% of the metastasis occurred in internal iliac nodes or nodes at middle rectal roots and 39.4% in obturator nodes. Age < or =40 years, infiltrative cancer, T34 tumor, upward lymph node metastasis were risk factors for lateral node metastasis in low rectal cancer (P < 0.05). The overall 5-year survival rate was 64.1%, and it was 94.1%, 79.1%, 42.1% for patients with TNM stage I, II, III cancer, respectively. Tumor size, depth of infiltration, upward lymph node metastasis, lateral node metastasis was correlated significantly with prognosis (P < 0.05). The 5-year survival rate of the patients without lateral metastasis was 73.6%, which was significant higher than that of patients with lateral metastasis (21.4%, P < 0.05). CONCLUSION: Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer.

[Surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease: a study of 20 cases].

OBJECTIVE: To investigate the clinical characteristics, surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease (CD), and to improve the level of diagnosis and treatment of retroperitoneal Castleman disease with paraneoplastic pemphigus (PNP). METHODS: The clinical data of retroperitoneal CD with PNP from January 1993 to May 2009 were compared with CD without PNP retrospectively, including clinical features, tumor site, lab examination, surgical treatment, pathologic subtype and results of surgery. RESULTS: (1) Retroperitoneal Castleman disease more likely originated in para-kidney and iliac fossa with middle age of 36 years old, especially in left retroperitoneum. Of the 20 cases, 18 tumors (90%) were hyaline vascular variants and 2 were mixed variants. There was no statistical difference in gender, age, tumor site and pathological subtype between two groups. (2) Retroperitoneal CD with PNP more likely complicated with bronchiolitis obliterans (BO) and high level of serum CEA/CA242. (3) Retroperitoneal Castleman tumors had clear margin, intact envelop and were easily resectable, however the biological behavior of CD with PNP might tend malignant changing, invade adjacent blood vessel or seed locally, and eventually relapse after operation. (4) The 5-year survival rate of retroperitoneal CD with PNP was 42.8%, significantly lower than those without PNP. The average survival time was 30 months. Bronchiolitis obliterans and radical resection were the key effect in prognosis of retroperitoneal CD. CONCLUSIONS: Retroperitoneal CD with PNP has distinctive clinical features. Early diagnosis, prompt removal of tumor and termination secretion of causative antibody are critical to the management of this disease.

Crosstalk between TF/FVIIa and EGFR signaling in colorectal cancer cells.

TF/FVIIa (Tissue Factor/Active Coagulation factor VII) and EGFR (Epidermal Growth Factor Receptor) signaling both promote malignant progression of colorectal cancer. However, the crosstalk of these two signaling pathways in human colorectal cancer cells remains unclear. Here we detected the changes of mRNA profile in human colorectal cancer cell SW620 exposed to FVIIa. Microarray showed that mRNA levels of EGFR ligands were significantly upregulated. Western blot analysis confirmed the upregulation of EGFR ligands and the phosphorylation of EGFR at tyrosine-845 in colorectal cancer cells exposed to FVIIa. However, knockdown of TF by RNAi could block the upregulation of EGFR ligands induced by FVIIa stimulation. On the other hand, the expression of components of TF/FVIIa signaling was significantly upregulated in LoVo cells stimulated by EGF. However, the crosstalk between the two signaling pathways could not be detected in HT-29 colon cancer cells bearing wild-type KRAS. Taken together, our study suggest that the crosstalk between TF/FVIIa and EGFR signaling pathways in colon cancer cells depends on KRAS mutation.

[Genomic comparisons of multiresistant Pseudomonas aeruginosa isolates obtained from surgical intensive care unit].

OBJECTIVE: To investigate the genetic differences and their relativity with multi-drug resistance of Pseudomonas aeruginosa isolated. METHODS: Forty-nine Pseudomonas aeruginosa isolates were characterized by antimicrobial susceptibility and four-enzyme (I-CeuI, SpeI, SwaI, PacI) pulsed-field gel electrophoresis (PFGE). RESULTS: 85.7% of the P.aeruginosa isolates were MDR strains. Strains with PFGE pattern A were all susceptible to amikacin and cefepime, but were resistant to levofloxacin and meropenem. Strains with PFGE Patterns H and P had resistance to 6 - 8 different kinds of antibiotics. Strains with PFGE Patterns I and J were susceptible to all antibiotics tested in this study. Strains with other PFGE Patterns had intermediate resistance. PFGE pattern A was the dominant pattern, which accounted for 61.2% of all P.aeruginosa strains, 100% (2/2) in 2001, 65% (13/20) in 2002, 44.4% (8/18) in 2003 and 77.8% (7/9) in 2004. CONCLUSION: Four-enzyme combined PFGE analysis is highly discriminatory for the subtyping of MDR P.aeruginosa isolates.

[Hic-5/ARA55 inhibits the growth of Lovo cells by up-regulating the expression of P27].

OBJECTIVE: To investigate the effects of Hic-5/ARA55 on the growth of the human colorectal cancer cells (Lovo cells) and its mechanism. METHOD: Flow cytometry (FCM) was used to study the cell cycle of Lovo cells (Lovo group), Lovo cells stably transfected with empty vector (Lovo-Vector group) and the Lovo cells stably transfected with vector containing Hic-5/ARA55 (Lovo-Hic-5/ARA55 group). Western blot assay was used to detect the principal cyclins in the three groups, and Luciferase assay was used to study the mechanism between Hic-5/ARA55 and the only target cyclin. The cells from the three groups were inoculated subcutaneously into 7 nude mice (Balb/c nu/nu) respectively to observe the effects of Hic-5/ARA55 on the growth of the cells in vivo. Seven weeks later, the subcutaneous tumors were harvested and weighed. Then immunohistochemistry assay was used to detect Hic-5/ARA55 and the target cyclin in the tumors. RESULTS: The cell cycle was obviously delayed from G0/G1 to S stage in Lovo-Hic-5/ARA55 cells. A significantly higher expression of P27 was found in Lovo-Hic-5/ARA55 cells than in the other two groups. The weight of the subcutaneous tumors of Lovo-Hic-5/ARA55 cells, Lovo cells and Lovo-Vector cells were (0.33 +/- 0.23) g, (1.20 +/- 0.39) g and (1.30 +/- 0.49) g, respectively; the tumors of Lovo-Hic-5/ARA55 cells was significantly lighter than those of the other two groups (P<0.05). Hic-5/ARA55 and P27 were both over-expressed in implanted tumors of Lovo-Hic-5/ARA55 cells, while were both expressed lower or not expressed in the other two groups. And the expressions of Hic-5/ARA55 and P27 were highly positive correlated (r=0.816, P<0.05). CONCLUSION: Hic-5/ARA55 could inhibit the growth of Lovo cells both in vitro and in vivo by up-regulating the transcription of P27.

[The diagnosis and surgical management for patients with variants of hepatic arteries in the procedure of pancreaticoduodenectomy].

OBJECTIVE: To study the principle and surgical managements for the patients with anatomic variants of hepatic artery in the procedure of pancreaticoduodenectomy (PD). METHODS: One hundred and seventy-six patients who underwent PD between January 2000 and July 2007 were investigated retrospectively. Hepatic arterial variants were analyzed according to the intraoperative finding and CT imaging were reviewed postoperatively. RESULTS: Hepatic arterial variants were found intraoperatively in 20 cases of all 176 patients. Accessory right heptic artery, replaced right heptic artery and common heptic artery arising from the superior mesenteric artery (SMA) were present in 9 (5.1%), 5 (2.8%), 4 (2.3%) cases respectively,and replaced right heptic artery coming from the gastroduodenal artery was present in 2 cases (2.9%). All the variants of hepatic arteries arising from the superior mesenteric artery could be observed in spiral CT imaging. Most of the variant arteries were dissected intact intraoperatively except 2 cases with accessory right heptic artery arising from SMA. CONCLUSIONS: Performing CT scan preoperatively, especially CTA,is effective to diagnose these disorders. Skillful surgical techniques can manage the anatomic variants safely.

[Expression of proline-rich tyrosine kinase-2 in human primary colorectal carcinoma and its prognostic implication].

OBJECTIVE: To investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance. METHODS: The expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed. RESULTS: The rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis. CONCLUSIONS: Pyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

[Clinical analysis of post pancreatoduodenectomy hemorrhage].

OBJECTIVE: To explore the factors of post pancreatoduodenectomy hemorrhage. METHODS: The clinical data of 263 cases between January 1998 and April 2008 underwent pancreatoduodenectomy were analyzed prospectively. RESULTS: The overall mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child classification, caput total resection and pancreatic leakage were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. The multivariate Logistic regression analysis revealed that all of the five factors turned out to be the independent risk factors. CONCLUSIONS: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. The pancreatic leakage is also one of the most important factors due to postoperative bleeding. The prophylactic use of somatostatin is not necessary.

The effect of celecoxib on tissue factor expression in pancreatic cancer cells.

BACKGROUND: Tissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor alpha (TNFalpha) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect. METHODS: Various doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFalpha for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor kappaB was tested by electromobility shift assay. RESULTS: As the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor kappaB. CONCLUSIONS: Celecoxib can downregulate the expression of tissue factor induced by TNFalpha in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor kappaB.

[Regulation of promatrilysin expression by tissue factor/actived coagulation factor VII complex in LoVo colon cancer cell line].

OBJECTIVE: To assess the expression of Promatrilysin in LoVo colon cancer cell by FVIIa stimulation,and to investigate the effect of MAPKs signal transduction pathway on up-regulation of Promatrilysin. METHODS: (1) The expression of ProMMP-7 was detected by Western blot at different time points (0,2,4,6,9,12 and 24 h) and with different doses of (0,0.1,1,5,10,25 and 100 nmol/L) FVIIa stimulation. The change of ProMMP-7 expression was observed with 5 mg/L tissue factor (TF) antibody prior to 100 nmol/L FVIIa. (2) The activation of MAPKs (ERK, p38, JNK) signaling pathways were assessed at different time points after being stimulated with 100 nmol/L FVIIa and the changes of ProMMP-7 expression were detected after the special signal pathway inhibitors (PD98059,SB203580,SP600125) were applied,respectively. RESULTS: (1) The expression of ProMMP-7 in LoVo cells was up-regulated by FVII a in a time-effect dependent and dose-effect dependent manner,and markedly reached the peak level at h12, 5.5 folds that of the control group (P=0.006).The up-regulation of ProMMP-7 was completely inhibited by blockade with TF antibody. (2) A time-dependent phosphorylation of ERK1/2 and P38 in LoVo cells was induced with FVIIa incubation,reached the peak at min10,2.2 folds and 3.9 folds those of the control groups respectively, but not JNK. (3) The upregulation effect of ProMMP-7 was partially blocked after incubation of ERK1/2 inhibitors PD98059 and P38 inhibitors SB203580 prior to FVIIa, The expression of ProMMP-7 decreased by 32%+/-5% and 61%+/-10% respectively (P<0.05).whereas JNK inhibitors SP600125 did not have the effect. CONCLUSION: FVIIa induces tissue factor-dependent up-regulation of ProMMP-7 in LoVo cells. ERK1/2 and p38 signal pathways are not only involved in TF/FVIIa mediated signaling,but also related to the upregulation of MMP-7 in LoVo cells.

[Therapeutic effects of transabdominal radical total gastrectomy on cardiac cancer: analysis of 56 cases].

OBJECTIVE: To evaluate the therapeutic effects of transabdominal radical total gastrectomy on cardiac cancer and analyze the factors influencing the prognosis. METHODS: The clinicopathologic data of 56 cardiac cancer patients, 42 males and 14 females, aged 59 (27 - 81), who underwent transabdominal radical total gastrectomy from April 1993 to March 2003 were analyzed retrospectively. RESULTS: The total lymph node metastatic incidence of the 56 patients was 71.4% (40/56). In 19 patients who underwent para-aortic lymphadenectomy, the metastatic rate of lymph node group 16 was 31.6% (6/19). The important factors influencing lymph node metastasis included the depth of tumor invasion, Borrmann type of the tumor, tumor size, and esophageal infiltration. The postoperative morbidity rate was 21.4% (12/56) and the postoperative complication rate was 3.6% (2/56). The overall 1-, 3-, and 5-year postoperative survival rates for the entire patient cohort were 77.6%, 47.7%, and 37.1% respectively. Univariate analysis showed that lymph node metastases, tumor size, histopathological type of the tumor, Borrmann type of the tumor, depth of tumor invasion, and esophageal infiltration significantly influenced the postoperative survival. The 5-year survival rate of the patients without lymph node metastasis was 63.3%, significantly higher than that of the patients with lymph node metastasis (25.4%, P = 0.011). Multivariate analysis by Cox regression showed that lymph node metastasis was an independent prognostic factor (P = 0.042). CONCLUSION: Transabdominal radical total gastrectomy is an effective and safe procedure for treatment of Siewert type II and type III cardiac cancer. Lymph node metastasis is an important prognostic factor of these tumors.