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1.  TMPRSS4 facilitates epithelial-mesenchymal transition of hepatocellular carcinoma and is a predictive marker for poor prognosis of patients after curative resection 
Scientific Reports  2015;5:12366.
TMPRSS4 (Transmembrane protease serine 4) is up-regulated in a broad spectrum of cancers. However, little is known about the biological effects of TMPRSS4 on hepatocellular carcinoma (HCC) and the related mechanisms. In the present study, we found that overexpression of TMPRSS4 significantly promoted the invasion, migration, adhesion and metastasis of HCC. Further more, TMPRSS4 induced EMT of HCC, which was mediated via snail and slug as a result of Raf/MEK/ERK1/2 activation, and inhibition of ERK1/2 activation by its inhibitor was associated with reduced cell invasion and reversion of EMT. In addition, we demonstrated that TMPRSS4 remarkably suppressed the expression of RECK, an inhibitor of angiogenesis, and drastically induced tumor angiogenesis and growth. More important, in clinical HCC specimens, TMPRSS4 expression was significantly correlated with tumor staging and was inversely correlated with E-cadherin and RECKS expression. Expression of TMPRSS4 is significantly associated with HCC progression and is an independent prognostic factor for postoperative worse survival and recurrence. In conclusion, TMPRSS4 functions as a positive regulator of Raf/MEK/ERK1/2 pathway and promotes HCC progression by inducing EMT and angiogenesis. The increase of TMPRSS4 expression may be a key event for HCC progression and may be regarded as a potential prognostic marker for HCC.
PMCID: PMC4507176  PMID: 26190376
2.  Postoperative adjuvant transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond the Milan criteria: a retrospective analysis 
Objective: To clarify the value of postoperative adjuvant transcatheter arterial chemoembolization (TACE) for resectable multiple hepatocellular carcinoma beyond the Milan criteria. Background: Patients with multiple HCC have been shown to have a worse survival after a partial hepatectomy (PH) because of the high incidence of intrahepatic tumor recurrence. Postoperative adjuvant TACE is an optional strategy for HCC patients with a high recurrence risk. Its effects and range of applications are debatable. Methods: This retrospective study enrolled 135 HCC patients with resectable multiple hepatocellular carcinoma beyond the Milan criteria, and those patients underwent a hepatectomy with/without postoperative adjuvant TACE from Jan. 2004 to Dec. 2008. The patients were divided to the PH cohort or the PH+TACE cohort. The prognosis measures were the disease-free survival (DFS) and overall survival (OS) from the date of treatment. Univariate and multivariate analyses were used to assess the prognostic factors associated with DFS and OS, using the Cox proportional hazards model. Results: The 1-, 2-, and 5-year DFS and OS for the PH+TACE group differed significantly from the PH group (p = 0.004, p = 0.002, respectively). Multivariate analysis revealed that the significant independent risk factors associated with the DFS and OS were postoperative TACE treatment (p = 0.002, p = 0.001, respectively) and the number of tumors (p = 0.006, p = 0.037, respectively). Conclusions: Our results show that postoperative adjuvant treatment resulted in delayed intrahepatic recurrence and better survival for patients with resectable multiple hepatocellular carcinoma beyond the Milan criteria. Postoperative adjuvant TACE should be regarded as a common strategy for patients with resectable multiple HCC beyond the Milan criteria.
PMCID: PMC4300716  PMID: 25628953
TACE; multiple hepatocellular carcinoma; Milan criteria; recurrence; prognosis
3.  Crystal structure of aqua­chlorido­bis­(2-eth­oxy-6-formyl­phenolato-κ2 O 1,O 6)iron(III) aceto­nitrile hemisolvate 
In both complex mol­ecules in the asymmetric unit, the FeIII ion has a distorted O5Cl octa­hedral coordination environment defined by two bidentate 2-eth­oxy-6-formyl­phenolato ligands, one Cl atom and one water mol­ecule. In the crystal, O—H⋯O hydrogen bonds link the two independent mol­ecules to form a dimer while the solvent mol­ecule is linked to the complex mol­ecule by a weak C—H⋯O hydrogen bond. Further weak C—H⋯O inter­actions along with weak C—H⋯Cl hydrogen bonds link the components into chains parallel to [001].
In the title compound, [Fe(L)2Cl(H2O)]·0.5CH3CN, (HL is 3-eth­oxy-2-hy­droxy-benzaldehyde, C9H10O3), there are two independent complex mol­ecules and one aceto­nitrile solvent mol­ecule in the asymmetric unit. In each complex mol­ecule, the FeIII ion has a distorted O5Cl octa­hedral coordination environment defined by two bidentate 2-eth­oxy-6-formyl­phenolato ligands, one Cl atom and one water mol­ecule. In the crystal, O—H⋯O hydrogen bonds link the two independent mol­ecules to form a dimer. The solvent mol­ecule is linked to the complex mol­ecule by a weak C—H⋯O hydrogen bond. Further weak C—H⋯O inter­actions along with weak C—H⋯Cl hydrogen bonds link the components into chains parallel to [001].
PMCID: PMC4257307  PMID: 25484720
crystal structure; solvothermal synthesis; Fe(III) complex; dimer; hydrogen bonding.
4.  Incidence of pocket hematoma after electrophysiological device placement: dual antiplatelet therapy versus low-molecular-weight heparin regimen 
Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hematoma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen.
This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma development with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.
The incidence of pocket hematoma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49% vs. 16.47%, respectively; X2 = 6.66, P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggregation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients undergoing DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic regression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012–0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket hematomas than were DAP-treated individuals.
Continuance of DAP therapy does not increase the risk of pocket hematoma formation after EPD placement.
PMCID: PMC4178510  PMID: 25278967
Antiplatelet drug; Hematoma; Low-molecular-weight heparin; Electrophysiological device
5.  Comprehensive Multiple Molecular Profile of Epithelial Mesenchymal Transition in Intrahepatic Cholangiocarcinoma Patients 
PLoS ONE  2014;9(5):e96860.
The aim of this study is to investigate the expression profile of multiple epithelial mesenchymal transition (EMT)-related molecules in intrahepatic cholangiocarcinoma (ICC) and the related prognostic significance.
Immunohistochemistry was performed to determine the expression of E-cadherin, Vimentin, Snail, slug and β-catenin in a tissue microarray consisting of tumor tissues of 140 ICC patients undergoing curative resection. The correlation between the expression of these molecules and the clinicopathological characteristics of ICC patients was analyzed, and their prognostic implication was evaluated.
Reduced E-cadherin and increased Vimentin expression, the characteristic changes of EMT, identified in 55.0% and 55.7% of primary ICCs, respectively, were correlated with lymphatic metastasis and poorer overall survival (OS) and disease-free survival (DFS) of ICCs. The overexpression of snail and nonmembranous β-catenin, which are the major regulators of the EMT, were identified in 49.2% and 45.7% of primary ICCs, while little slug expression was detected in ICCs. Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss. The overexpression of snail predicted worse OS and DFS. Snail overexpression correlated with the down-regulation of E-cadherin and the up-regulation of Vimentin. Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.
These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.
PMCID: PMC4016113  PMID: 24816558
6.  Increased Peripheral Proinflammatory T Helper Subsets Contribute to Cardiovascular Complications in Diabetic Patients 
Mediators of Inflammation  2014;2014:596967.
Background. Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.
PMCID: PMC3997161  PMID: 24803740
7.  Marjolin’s ulcer: a preventable malignancy arising from scars 
Marjolin’s ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy.
A retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU.
An incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = −0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = −0.7, P <0.01).
Patients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.
PMCID: PMC3896958  PMID: 24341890
Marjolin’s ulcer; Squamous cell carcinoma
8.  Tris[4-bromo-2-(methyl­imino­meth­yl)phenolato-κ2 N,O]cobalt(III) 
In the title compound, [Co(C8H7BrNO)3], the CoIII ion is coordinated in a slightly distorted octa­hedral environment by three N atoms and three O atoms from three bidentate 4-bromo-2-(methyl­imino­meth­yl)phenolate ligands. The dihedral angles between the benzene rings are 82.6 (2), 57.1 (2) and 62.9 (2)°. In the crystal, mol­ecules are linked by pairs of weak C—H⋯Br hydrogen bonds, forming inversion dimers.
PMCID: PMC3884257  PMID: 24454033
9.  Nipple Retractor to Correct Inverted Nipples 
Breast Care  2011;6(6):463-465.
Inverted nipples are a common problem and a challenging clinical condition to repair. Multiple methods have been reported to correct inverted nipples, most of which will destroy breastfeeding function.
Patients and Methods
We have designed a simple nipple retractor to correct inverted nipples. A total of 53 patients with 95 inverted nipples underwent an operation in which the nipples were retracted into a normal position and fixated with the nipple retractor and wires under local anesthesia. Nipple retractors were to be worn for 6 months. Postoperatively, the patients were invited to follow-up on the 1st day, the 7th day, after 1 month, 3 months and 6 months, and yearly thereafter. Wire adjustments were performed as needed. Mean follow-up was 11.9 months (range 8–18 months).
Improvement occurred in all patients and was sustained in all cases throughout the follow-up period. The total complication rate was 5.26% (5/95). The main complications included depigmentation (2.11%, 2/95), areolar ulcer (2.11%, 2/95), and wire dislocation (1.05%, 1/95).
The nipple retractor is a simple tool with which severely inverted nipples can be successfully corrected with a low complication rate. Close follow-up and careful postoperative care are important to avoid complications.
PMCID: PMC3290018  PMID: 22419901
Inverted nipple; Surgery; Nipple retractor
10.  Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets 
AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets.
METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H+-K+-ATPase mRNA in gastric mucosa. H+-K+-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H+-K+-ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H+-K+-ATPase and somatostatin (SS) as well as the H+-K+-ATPase activity were determined.
RESULTS: in vivo, both mRNA expression and activity of H+-K+-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H+-K+-ATPase was affected significantly by weaning. CS increased the mRNA expression of H+-K+-ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H+-K+-ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H+-K+-ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H+-K+-ATPase expression: P=0.03; H+-K+-ATPase activity: P = 0.014) and high concentrations (H+-K+-ATPase expression: P=0.017; H+-K+-ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H+-K+-ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H+-K+-ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells.
CONCLUSION: No significant changes are observed in mRNA expression and activity of H+-K+-ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H+-K+-ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H+-K+-ATPase expression and activity in weaning piglets.
PMCID: PMC4355770  PMID: 16425370
Cysteamine; Weaning piglets; H+-K+-ATPase; Gastric mucosal cells; Somatostatin

Results 1-10 (10)