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Yue-Han Huang,
Zhen-Kun Chen,
Ka-Te Huang,
Peng Li,
Bin He,
Xu Guo,
Jun-Qiao Zhong, Qi-Yu Zhang,
Hong-Qi Shi,
Qi-Tong Song,
Zheng-Ping Yu,
Yun-Feng Shan
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ABSTRACT: Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases. Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital of Wenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry. Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in the HCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascular invasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantly shorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively). Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival (P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1 expression is correlated with a lower survival rate.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(3):1985-8. · 0.66 Impact Factor
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ABSTRACT: BACKGROUND:: Extensive controversies exist over the use of preoperative biliary drainage preceding radical resection of hilar cholangiocarcinoma. This study assessed the effectiveness and safety of percutaneous transhepatic cholangiodrainage (PTCD) with bile re-infusion in the preoperative optimization of hilar cholangiocarcinoma patients. METHODS:: Eligible hilar cholangiocarcinoma patients received preoperative PTCD with bile re-infusion (treatment group, n = 56) through a nasoduodenal tube for 2 weeks, and the control group (n = 60) received conservative treatment alone. Operable patients were assigned to undergo either a radical or palliative resection. The outcome measures included the overall resection rate, R0 resection rate, surgical morbidity rate and 1-year and 5-year overall survival rates. RESULTS:: The treatment group exhibited a significant decrease in serum bilirubin levels after PTCD with bile re-infusion. The overall resection rate was significantly higher in the treatment group than in the control group (85.5% vs. 65.0%, P < 0.05), and the palliative resection rate was also significantly higher in the treatment group (53.5% vs. 35.0%, P < 0.05). However, the R0 resection rate was comparable between the 2 groups (32.1% vs. 30.0%, P > 0.05). The morbidity rate was significantly lower in the treatment group than in the control group (29.1% vs. 51.3%, P < 0.05). One-year and 5-year survival rates were similar between the 2 groups (69.6% vs. 66.7%, P > 0.05; 5.3% vs. 3.6%, P > 0.05). CONCLUSIONS:: Preoperative PTCD with bile re-infusion improves the resection rate and shows a good safety profile in patients with hilar cholangiocarcinoma.
The American Journal of the Medical Sciences 12/2012; · 1.39 Impact Factor
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ABSTRACT: To research the effects of glycogen synthase kinase (GSK3β) overexpression and GSK3β inhibitor SB-216763 on the proliferation of hepatic oval cells in rats and its regulatory mechanisms by Wnt signaling pathway.
The hepatic oval cells WBF-344 were divided into the blank control group, GSK3β over-expression group, DMSO control group and GSK3β inhibitor groups, while the inhibitor groups set up three concentration gradients, that was 1, 5, 10 µmol/L. Using the GSK3β over-expression lentivirus, which had been identified correctly, and SB-216763 dealt with the cells WBF-344. The cells morphology of each group was observed under the phase contrast inverted microscope, and the expression of fluorescence in the lentivirus-transfected group was observed under the fluorescent microscope. The proliferation of each group cells was tested by CCK8 kits. The cells' apoptosis was detected by AnnexinV-FITC/PI kits. The expression of GSK3β, β-catenin and cyclin D1 were detected by Western blot.
The cells of GSK3β over-expression group were fewer and obvious aging. However, in each inhibitor added group, the cells' division and proliferation was vigorous, and the condition was good. Moreover, the cells' proliferation was getting stronger with the concentration of SB-216763 increasing. A large number of green fluorescence was expressed in the lentivirus-transfected cells. The cells' proliferation in GSK3β over-expression group restrained (t = 7.178, P < 0.01, as compared with control), while the cells' proliferation was vigorous in inhibitor groups (F = 45.030, P < 0.01, as compared with control). Flow Cytometry showed that the cells apoptosis was significant in GSK3β over-expression group. Western blot showed that the expression of GSK3β was increased, while the expression of β-catenin and cyclin D1 was decreased in the over-expression group. The expression of GSK3β had no significant difference among the control group and inhibitor groups. However, the expression of β-catenin and cyclin D1 was significantly increased with the concentration of SB-216763 increasing.
The overexpression of GSK3β can inhibit the Wnt signaling pathway, thus restrain the cells' proliferation and promotes apoptosis. SB-216763 can activate the Wnt pathway, thus promotes cells' proliferation.
Zhonghua wai ke za zhi [Chinese journal of surgery] 11/2012; 50(11):1003-6.
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ABSTRACT: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro.
HSCs were derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was evaluated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting.
IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure.
Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.
World Journal of Gastroenterology 07/2012; 18(28):3696-704. · 2.47 Impact Factor
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ABSTRACT: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP).
The animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, α-tumor necrosis factor (TNF-α), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto- prostaglandin F1α were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study.
Pathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-α and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B(2) level increased in SAP, but the ratio of thromboxane B(2)/6-keto- prostaglandin F(1α) decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05).
The findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.
PLoS ONE 01/2012; 7(5):e37347. · 4.09 Impact Factor
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ABSTRACT: Recently, two hepatic lineage markers epithelial cell adhesion molecule (EpCAM) and α-fetoprotein (AFP) were used to classify hepatocellular carcinoma (HCC) into four subtypes with prognostic implication. In the present study, we further evaluated the clinicopathologic and angiogenic characteristics among these HCC subtypes. EpCAM expression was investigated by immunohistochemistry in 115 HCC primary tumors. Based on EpCAM immunostaining and serum AFP levels, 115 HCC cases were classified into four subtypes: EpCAM+AFP+ (26.1%), EpCAM-AFP+ (20.0%), EpCAM+AFP- (20.8%), and EpCAM-AFP- (33.1%). EpCAM+AFP+ and EpCAM-AFP+ HCC were associated with late TNM stages and high frequencies of venous invasion, whereas EpCAM+AFP- and EpCAM-AFP- subtypes were associated with early TNM stages and low frequencies of venous invasion. Furthermore, EpCAM+AFP+ HCC had a significantly higher microvessel density (MVD) and higher level of VEGF (Vascular epithelial growth factor) expression than the other three subtypes. In conclusion, our study indicated that subtype classification of HCC based on EpCAM and AFP status had clinicopathologic and biologic implications in aggressive phenotype and angiogenesis. We also suggest that the EpCAM+AFP+ HCC patients might be potential therapeutic candidates for anti-angiogenesis therapy.
Medical Oncology 12/2011; 28(4):1012-6. · 2.14 Impact Factor
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ABSTRACT: A fast-track clinical pathway is designed to streamline patient care delivery and maximize cost effectiveness. It has decreased postoperative length of stay (LOS) and hospital charges for many surgical procedures. However, data on clinical pathways after liver surgery are sparse. This study examined whether use of a fast-track clinical pathway for patients undergoing elective liver resection affected postoperative LOS and hospital charges. A fast-track clinical pathway was developed and implemented by a multidisciplinary team for patients undergoing liver resection. Between July, 2007 and May, 2008, a total of 117 patients underwent elective liver resection: the fast-track clinical pathway (education of patients and families, earlier oral feeding, earlier discontinuation of intravenous fluid, no drains or nasogastric tubes, early ambulation, use of a urinary catheter for less than 24 h and planned discharge 6 days after surgery) was studied prospectively in 56 patients (postpathway group). These patients were compared with the remainder who had usual care (prepathway group). Outcome measures were postoperative LOS, perioperative hospital charges, intraoperative and postoperative complications, mortality, and readmission rate. Among all patients, 69 (59%) had complicating diseases and/or a history of surgery and 24 patients belonged to American Society of Anesthesiologists grade III-IV. Compared with the prepathway group, the postpathway group had a significantly shorter postoperative LOS (7 vs. 11 days, P < 0.01). The average perioperative hospital charges were RMB 26,626 for patients in the prepathway group and only RMB 21,004 for those in the postpathway group (P < 0.05), with no differences in intraoperative and postoperative complications (P = 0.814), mortality (P = 0.606), and readmission rate (P = 0.424). Implementation of the fast-track clinical pathway is an effective and safe method for reducing postoperative LOS and hospital charges for high-risk patients undergoing elective liver resection. The result supports the further development of fast-track clinical pathways for liver surgical procedures.
Cell biochemistry and biophysics 05/2011; 61(2):413-9. · 3.34 Impact Factor
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ABSTRACT: To investigate the clinical characteristics, surgical treatment and prognostic analysis of retroperitoneal paragangliomas and to enhance the diagnostic and therapeutic levels of retroperitoneal paragangliomas.
The clinical data of all patients undergoing paraganglioma resection at our department from November 1999 to March 2009 were retrospectively analyzed. The parameters included clinical manifestations, tumor function, surgical findings, operative approach, tumor pathology, imaging study and post-operative survival time.
(1) The ratio of male to female was 1.375:1 and the median age 50 years old. The most common presenting symptom was abdominal mass (9/19, 47%). And the preoperative CT misdiagnosis rate was high (89%). (2) The most common tumor location was periaortic and percival (9/19, 47%). The average maximal diameter of tumors was 8.6 cm. 58% (11/19) tumors had integral peplow, 42% (8/19) adhered to adjacent organs and 26% (5/19) required adjacent organ resection. (3) The rate of functional tumor was 63% (12/19). Preoperative and intra-operative hypertension occurred in 67% (8/12) and 33% (4/12) respectively. (4) Immunohistochemical staining was performed in 18 tumors of 16 patients. Among all tumors, 89% (16/18) showed positive immunoreactivity for chromogranin and 67% (12/18) for S-100. PCNA staining showed different proliferative activities (0%-48% positive). Only malignant tumors showed positive immunoreactivity for Ki-67 staining and P53 staining (20% & 34% respectively). (5) The overall 5-year survival was 77%. Survival was significantly worse after metastasis (χ2=6.604, P=0.01). But it was not dependent on tumor diameter (χ2=3.208, P=0.201), the secreting function of tumor (χ2=0.121, P=0.728) and the status of tumor margins (χ2=0.036, P=0.849).
It is difficult to make an early diagnosis of retroperitoneal paragangliomas. Survival is significantly worse after metastasis. Lifelong follow-up for recurrence is important. And it is absolutely essential to perform immunohistochemical staining for tumors.
Zhonghua yi xue za zhi 09/2010; 90(34):2385-8.
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ABSTRACT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem, with a mortality rate in the range of 30%-40%. The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications. Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS. The initial exudative phase is characterized by diffuse alveolar damage, microvascular injury and influx of inflammatory cells. This phase is followed by a fibro-proliferative phase with lung repair, type II pneumocyte hypoplasia and proliferation of fibroblasts. Proteases derived from polymorphonuclear neutrophils, various pro-inflammatory mediators, and phospholipases are all involved, among others. Contributing factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric lymphatics. There is a lack of complete understanding of the underlying mechanisms, and by improving our knowledge, novel tools for prevention and intervention may be developed, thus contributing to improved outcome.
World Journal of Gastroenterology 05/2010; 16(17):2094-9. · 2.47 Impact Factor
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ABSTRACT: Many physicians express a relatively nihilistic approach to the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Consensus among surgeons regarding the indications for an aggressive approach has not been reached. Current study was aimed to determine whether an aggressive approach, with an extended resection with thrombectomy and adjuvant therapy, would lead to an improved survival for HCC patients with PVTT.
A retrospective review of 116 HCC patients with PVTT admitted from 1996 to 2006 was conducted. Patients were divided into 2 time-period (TP) cohorts, of them, 51 cases in the first 5 years (TP1) and 65 in the last 5 years (TP2).
Surgical operations were performed on 68 patients. Twenty-one surgical resections were performed in TP1 and forty-seven in TP2. The extent of liver resections, as well as the frequency of thrombectomy, was greater in TP2 (P = 0.039). During both time-periods, an aggressive therapy was associated with improved survival (P < 0.02 TP1, P < 0.001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.001), with a median survival of 15 months in TP2, whereas in TP1, the survival was only 9 months. The median 1-, 3-year survivals in TP2 (54 and 34%, respectively) were also greater than that in TP1 (31 and 7%, respectively). A multiple logistic regression analysis revealed that radical resection and adjuvant therapy were the independent predictors of overall survival.
An aggressive approach, combining extended liver resection with thrombectomy and adjuvant therapy, leads to an improved survival in the HCC patients with PVTT.
Journal of Cancer Research and Clinical Oncology 03/2010; 137(1):139-49. · 2.56 Impact Factor
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ABSTRACT: Aim: To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.
Acta Pharmacologica Sinica 10/2009; 30(11):1537-1542. · 1.95 Impact Factor
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ABSTRACT: To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.
The effects of tanshinone II-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone II-A anti-cancer actions.
Tanshinone II-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone II-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-kappaB) signal.
Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1 and TIMP-2, and apparent inhibition of the NF-kappaB signal transduction pathway.
Acta Pharmacologica Sinica 10/2009; 30(11):1537-42. · 1.95 Impact Factor
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2008; 16(3):234-5.
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ABSTRACT: To detect the DNA binding activity of nuclear factor-kappaB (NF-kappaB) in rat hepatocyte and to investigate the effects of NF-kappaB on rat hepatocyte regeneration and apoptosis after 70% portal branch ligation.
Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-kappaB was measured by EMSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope.
Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-kappaB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope.
After 70% portal branch ligation, DNA binding activity of NF-kappaB in hepatocyte is significantly increased and NF-kappaB plays an important role in hepatocyte regeneration and apoptosis.
World Journal of Gastroenterology 12/2005; 11(43):6775-9. · 2.47 Impact Factor
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ABSTRACT: To better understand mucobilia as well as its diagnosis and treatment.
The etiological factors, diagnosis, and treatment of 8 patients with mucobilia were discussed.
Mucobilia characterized by copious mucin secretion in the extrahepatic bile duct resulted in obstructive jaundice and cholangitis. Four patients receiving curative resection of primary lesions were free from jaundice and cholangitis while the other 4 who had had palliative biliary drainage showed persistent symptoms.
Mucobilia is attributable to biliary mucous metaplasia, and benign or malignant biliary tumors. Cholangioscopy and biopsy can offer precise information about the location and extension of the primary lesion. The best choice of treatment is curative resection of the primary lesion.
Hepatobiliary & pancreatic diseases international: HBPD INT 03/2003; 2(1):106-9. · 1.08 Impact Factor
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ABSTRACT: To discuss the clinical features of patients with heterotopic pancreas, their diagnosis and surgical treatment.
Seven patients with heterotopic pancreas were treated surgically in our hospital from August 1992 to March 1999.
Of the 7 patients, 4 had heterotopic pancreas located in the duodenum, 2 in the jejunum, and 1 in the stomach. Four patients experienced abdominal pain, 3 icterus, 1 duodenal obstruction, and 1 digestive tract bleeding. Three patients were complicated by cholelithiasis, and 1 patient was complicated by diverticulum of the jejunum. All seven patients were misdiagnosed or undefined preoperatively. They underwent surgery and were confirmed pathologically.
Heterotopic pancreas is extremely difficult to diagnose before operation since no specific clinical signs are seen in such patients. Once diagnosed with symptoms or not, the patients should undergo surgery for correct diagnosis and avoidance of relative complications.
Hepatobiliary & pancreatic diseases international: HBPD INT 06/2002; 1(2):299-301. · 1.08 Impact Factor
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ABSTRACT: This study aims to explore the relationship between spleen arterial blood flow (SBF) with platelet count, spleen index (SPI) and the serum nitric oxide (NO) level of patients with liver cirrhosis and to investigate the role of SBF in the development of hypersplenism.
Platelet count, SPI, SBF and serum NO levels were evaluated in 100 patients with liver cirrhosis caused by hepatitis B with hypersplenism (cirrhosis group) and 30 healthy persons without hypersplenism (control group).
Platelet count in cirrhosis group and control group was 57.0 +/- 25.6 x 109/L and 205.8 +/- 47.4 x 109/L (p = 0.000), SBF was 535.7 +/- 263.7 milmin and 172.2 +/- 66.9 ml/min (p = 0.000), and serum NO level was 98.51 +/- 23.06 micromol/L and 48.43 +/- 19.47 micromol/L (p = 0.000). Linear correlations were made between SBF and platelet count in cirrhosis group (r = -0.573, p = 0.000), SBF and SPI (r = 0.607, p = 0.01), SBF and serum NO level (r = 0.754, p = 0.000). Moreover, serum NO level increased as liver disease aggravated (82.50 +/- 15.04 pmol/L in Child grade A, 94.61 +/- 21.00 micromol/L in grade B and 116.83 +/- 18.03 micromol/L in grade C; grade A versus grade C, p = 0.003).
The elevation of SBF may play an important role in the development of hypersplenism and disorders in vasoactive factors such as the serum NO caused by liver cirrhosis may play an important role in the elevation of SBF.
Hepato-gastroenterology 57(104):1360-2. · 0.66 Impact Factor
