Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC.
SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice.
SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC.
SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.
Electronic supplementary material
The online version of this article (doi:10.1186/s12943-014-0276-y) contains supplementary material, which is available to authorized users.
Gallbladder cancer; SPOCK1; Tumor progression; RNA interference; Epithelial-mesenchymal transition
Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological activities. However, the precise mechanisms of the anti-proliferation and anti-metastatic effects of baicalein on gallbladder cancer (GBC) remain poorly understood. Therefore, the aim of this study was to assess the anti-proliferation and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In the present study, we found that treatment with baicalein induced a significant inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996 cells, two widely used gallbladder cancer cell lines. Additionally, treatment with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated for the first time that baicalein inhibited GBC cell growth and metastasis via down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In conclusion, our studies suggest that baicalein may be a potential phytochemical flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or predictive target for GBC.
Background and purpose: In the preoperative period, discriminating CNS lymphoma from high grade glioma is important as treatment approaches differ significantly. Hence, this meta-analysis was to evaluate the sensitivity and specificity of the relative cerebral blood volume (rCBV) values derived from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSCE-MRI) in differentiating CNS lymphoma from high grade glioma. Materials and methods: The following databases were searched from January 2000 to July 2014: Medline, PubMed and Embase. No language restrictions were applied. Data analysis was conducted using Meta-Disc 1.4. Results: A total of 79 patients (n = 30 lymphoma, n = 49 high grade glioma) and 89 lesions (n = 40 lymphoma, n = 49 high grade glioma) were included in the rCBV analysis. The pooled sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio for differentiating CNS lymphoma from high grade glioma were 0.90 (95% CI 0.76-0.97), 0.98 (95% CI 0.89-1.00), 0.13 (95% CI 0.06-0.29), 21.07 (95% CI 5.61-79.19), and 187.63 (95% CI 33.15-1061.86), respectively. And the value of I2 of DOR was 0.0%, indicating that there was no statistically significant heterogeneity of DOR between the included studies. Conclusions: Our meta-analysis suggests that the rCBV values derived from DSCE-MRI could be useful in differentiating CNS lymphoma from high grade glioma in the preoperative. Further well-designed researches involving larger patient cohorts are needed to confirm this conclusion.
CNS lymphoma; high grade glioma; rCBV values; meta-analysis
Background: Determining factors that could accurately predict pathological features of meningiomas before histological diagnosis would help surgeons to proper balance the risk of operation and the resection grade. The aim of this study was to explore the potential risk factors for atypical (WHO Grade II) and anaplastic (WHO Grade III) meningiomas. Methods: Records of 1,239 patients between January 2009 and January 2013 were included in this research. Furthermore, immunohistochemistry with Ki67 was analysed in 368 samples. Results: The Pearson’s chi-square test showed an increased risk for male gender for atypical and anaplastic meningiomas (P < 0.001) and an increased risk for cerebral convexity for atypical and anaplastic meningiomas (P < 0.001). However, significant differences in the terms of falx/sagittal sinus and intraventricular were not found. Patients with a Ki67 index ≥ 5% were significantly more likely to have atypical and anaplastic meningiomas than those patients with a Ki67 index < 5% (P < 0.001). In addition, the percentage of patients with a Ki67 index ≥ 5% in cerebral convexity meningiomas was higher than in non-cerebral convexity location (P = 0.006). Conclusions: The results indicate that male gender, cerebral convexity are significant risk factors for atypical and anaplastic meningiomas.
Cerebral convexity; risk factor; meningiomas
Taxonomic identification of pollen and spores uses inherently qualitative descriptions of morphology. Consequently, identifications are restricted to categories that can be reliably classified by multiple analysts, resulting in the coarse taxonomic resolution of the pollen and spore record. Grass pollen represents an archetypal example; it is not routinely identified below family level. To address this issue, we developed quantitative morphometric methods to characterize surface ornamentation and classify grass pollen grains. This produces a means of quantifying morphological features that are traditionally described qualitatively. We used scanning electron microscopy to image 240 specimens of pollen from 12 species within the grass family (Poaceae). We classified these species by developing algorithmic features that quantify the size and density of sculptural elements on the pollen surface, and measure the complexity of the ornamentation they form. These features yielded a classification accuracy of 77.5%. In comparison, a texture descriptor based on modelling the statistical distribution of brightness values in image patches yielded a classification accuracy of 85.8%, and seven human subjects achieved accuracies between 68.33 and 81.67%. The algorithmic features we developed directly relate to biologically meaningful features of grass pollen morphology, and could facilitate direct interpretation of unsupervised classification results from fossil material.
palynology; Poaceae; microscopy; pattern analysis; computational image analysis
Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro.
The anti-tumor activity of UA against GBC-SD and SGC-996 cells was assessed using MTT and colony formation assays. An annexin V/PI double-staining assay was used to detect cell apoptosis. Cell cycle changes were detected using flow cytometry. Rhodamine 123 staining was used to assess the mitochondrial membrane potential (ΔΨm) and validate UA’s ability to induce apoptosis in both cell lines. The effectiveness of UA in gallbladder cancer was further verified in vivo by establishing a xenograft GBC model in nude mice. Finally, the expression levels of cell cycle- and apoptosis-related proteins were analyzed by western blotting.
Our results suggest that UA can significantly inhibit the growth of gallbladder cancer cells. MTT and colony formation assays indicated dose-dependent decreases in cell proliferation. S-phase arrest was observed in both cell lines after treatment with UA. Annexin V/PI staining suggested that UA induced both early and late phases of apoptosis. UA also decreased ΔΨm and altered the expression of molecules regulating the cell cycle and apoptosis. In vivo study showed intraperitoneally injection of UA can significantly inhibited the growth of xenograft tumor in nude mice and the inhibition efficiency is dose related. Activation of caspase-3,-9 and PARP indicated that mitochondrial pathways may be involved in UA-induced apoptosis.
Taken together, these results suggest that UA exhibits significant anti-tumor effects by suppressing cell proliferation, promoting apoptosis and inducing 7cell cycle arrest both in vitro and in vivo. It may be a potential agent for treating gallbladder cancer.
Ursolic acid; Gallbladder cancer; Proliferation; Cell cycle; Apoptosis; Mitochondrial-mediated pathway
Background and purpose: It is crucial to accurately differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) preoperatively, as treatment strategies vary. So we performed a meta-analysis to assess the sensitivity and specificity of fractional anisotropy (FA) value derived from diffusion tensor imaging (DTI) in differentiating HGGs from LGGs. Materials and methods: Between January 2005 and June 2014, relevant articles were searched from the Embase and Medline databases for analysis. Statistical analyses were performed using Meta-Disc 1.4. Results: A total of 221 patients included in the FA analysis: 127 with HGGs and 94 LGGs. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) for differentiating HGGs from LGGs were 93% (95% CI 0.87-0.97), 85% (95% CI 0.76-0.92), and 55.41 (95% CI 16.77-183.07), respectively. And computation of heterogeneity metrics revealed an acceptable level of the between-study heterogeneity of DOR (I2=30.9%). Conclusions: The results of our meta-analysis present that the FA derived from DTI act as a useful diagnostic marker could be used in distinguishing the HGGs from LGGs in the preoperative and the clinical application values are to be confirmed by further larger case-control studies.
Diffusion tensor imaging; fractional anisotropy; high grade gliomas; low grade gliomas
Background and purpose: In the preoperative period, it is very important to accurately differentiate high-grade gliomas from intracranial metastases, as treatment strategies vary. Hence we performed a meta-analysis to evaluate the sensitivity and specificity of peritumoural relative cerebral blood volume (rCBV) values derived from dynamic susceptibility contrast imaging (DSCI) in differentiating high-grade gliomas from intracranial metastases. Materials and methods: Between 2004 and June 2014, relevant studies were searched from the databases of Medline and Embase for analysis. A total of 3 eligible studies were included in this analysis. Statistical analysis was performed with Meta-Disc 1.4. Results: A total of 136 patients included in the rCBV analysis: 79 with high-grade glioma and 57 with metastasis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) for differentiating high-grade glioma from metastasis were 82% (95% CI 0.72-0.90), 96% (95% CI 0.88-1.00), 18.04 (95% CI 5.41-60.15), 0.19 (95% CI 0.12-0.31), and 90.20 (95% CI 23.10-352.27), respectively. The value of Cochran’s Q of DOR was 0.78 (P = 0.6774), and I2 was 0.0%, revealing that no statistically significant between-study heterogeneity was found. Conclusions: The results of this present study clearly present that the peritumoural rCBV values derived from DSCI could be used in distinguishing high-grade gliomas from intracranial metastases in the preoperative.
Relative cerebral blood volume; dynamic susceptibility contrast imaging; high grade gliomas; metastases; meta-analysis
Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection.
We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration.
The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen.
Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.
Gallbladder cancer; Coagulation assays; Hyperfibrinogenemia; Prognosis
The intensive use of pesticides has attracted great attention from the Chinese government. However, current regulations have had limited influence on their safe use. Although the acute neurologic effects of pesticides have been well documented, little is known about their cumulative effects. Knowledge of the impact of pesticides on health may convince farmers to minimize their use. We conducted a cross-sectional study in three provinces of China to evaluate the relationship between pesticide exposure and neurological dysfunction. Crop farmers were divided into two groups depending on their level of pesticide exposure. A total of 236 participants were assessed by questionnaire and neurological examination for symptoms and signs of neuropathy. Characteristics of neurologic dysfunction following cumulative low-level exposure were assessed with logistic regression analysis. Farmers exposed to high-level pesticide use had greater risk of developing sensations of numbness or prickling (odds ratio (OR) 2.62, 95% confidence interval (CI): 1.08–6.36). After adjusting for recent exposure, the risk of numbness or prickling symptoms (OR 2.55, 95% CI: 1.04–6.25) remained statistically significant. Loss of muscle strength and decreased deep tendon reflexes had OR > 2, however, this did not reach statistical significance. These findings suggest that overuse of pesticides increased risk of neurologic dysfunction among farmers, with somatosensory small fibers most likely affected. Measures that are more efficient should be taken to curb excessive use of pesticides.
China; health effect; neurological deficit; pesticide overuse
Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS).
Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO2/FiO2), hepatic function, platelet count, and blood coagulation were determined.
Significant improvement was observed in HR, MAP, PaO2/FiO2, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more significantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were significantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1% (18/31), viral survival rate 36.4% (4/11), and non-viral survival rate 70% (14/20).
Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.
Severe acute liver failure; Artificial liver; Plasma exchange; Hemoperfusion; Continuous veno-venous hemodiafiltration
To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro.
Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA.
Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 μmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h).
Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis.
wear particle; bone marrow macrophage; osteoclast; TNF-α; calcineurin; nuclear factor of activated T cells (NFAT); 11R-VIVIT peptide; arthroplasty; periprosthetic osteolysis; aseptic loosening
Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis.
iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined.
102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation.
The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.
How to resect the caudate lobe safely is a major challenge to current liver surgery which requires further study.
Nine cases (6 hepatic cell carcinoma, 2 cavernous hemangioma and 1 intrahepatic cholangiocacinoma) were performed using the anterior transhepatic approach in the isolated complete caudate lobe resection. During the operation, we used the following techniques: the intraoperative routine use of Peng’s multifunction operative dissector (PMOD), inflow and outflow of hepatic blood control, low central venous pressure and selective use of liver hanging maneuver.
There were no perioperative deaths observed after the operation. The median operating time was 230 ± 43.6 minutes, the median intraoperative blood loss was 606.6 ± 266.3 ml and the median length of postoperative hospital stay was 12.6 ± 2.9 days. The incidence of complications was 22.22% (2/9).
PMOD and “curettage and aspiration” technique can be of great help of in the dissection of vessels and parenchyma, clearly making caudate lobe resection safer, easier and faster.
AIM: To assess whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the management of small bowel obstructions (SBOs) secondary to gastric cancer and its role in treatment strategies.
METHODS: The medical records of all of the patients who were admitted for an intestinal obstruction after curative resection for gastric cancer were retrospectively reviewed. PET/CT was performed before a clinical treatment strategy was established for each patient. The patients were divided into 2 groups: patients with no evidence of a tumor recurrence and patients with evidence of a tumor recurrence. Tumor recurrences included a local recurrence, peritoneal carcinomatosis or distant metastases. The primary endpoint was the 1-year survival rate, and other variables included patient demographics, the length of hospital stay, complications, and mortality.
RESULTS: The median time between a diagnosis of gastric cancer and the detection of a SBO was 1.4 years. Overall, 31 of 65 patients (47.7%) had evidence of a tumor recurrence on the PET/CT scan, which was the only factor that was associated with poor survival. Open and close surgery was the main type of surgical procedure reported for the patients with tumor recurrences. R0 resections were performed in 2 patients, including 1 who underwent combined adjacent organ resection. In the group with no evidence of a tumor recurrence on PET/CT, bowel resections were performed in 7 patients, adhesiolysis was performed in 7 patients, and a bypass was performed in 1 patient. The 1-year survival curves according to PET/CT evidence of a tumor recurrence vs no PET/CT evidence of a tumor recurrence were significantly different, and the 1-year survival rates were 8.8% vs 93.5%, respectively. There were no significant differences (P = 0.71) in the 1-year survival rates based on surgical vs nonsurgical management (0% with nonoperative treatment vs 20% after exploratory laparotomy).
CONCLUSION: 18F-FDG PET/CT can be used to identify the causes of bowel obstructions in patients with a history of gastric cancer, and this method is useful for planning the surgical management of these patients.
Positron emission tomography/computed tomography; Small bowel obstructions; Gastric cancer; Clinical treatment strategy
AIM: To investigate the effect of being overweight on the surgical results of patients with gastric cancer.
METHODS: Comprehensive electronic searches of the PubMed, Web of Science, and Cochrane Library databases were conducted. Studies were identified that included patients with surgical complications from gastric cancer who were classified as normal weight [body mass index (BMI) < 25 kg/m2] or overweight (BMI ≥ 25 kg/m2). The operative time, retrieved lymph nodes, blood loss, and long-term survival were analyzed. A subgroup analysis was conducted based on whether patients received laparoscopic or open gastrectomy procedures. All statistical tests were performed using ReviewerManager 5.1.2 software.
RESULTS: This meta-analysis included 23 studies with 20678 patients (15781 with BMI < 25 kg/m2; 4897 with BMI ≥ 25 kg/m2). Overweight patients had significantly increased operation times [MD: -29.14; 95%CI: -38.14-(-20.21); P < 0.00001], blood loss [MD: -194.58; 95%CI: -314.21-(-74.95); P = 0.001], complications (RR: 0.75; 95%CI: 0.66-0.85; P < 0.00001), anastomosis leakages (RR: 0.59; 95%CI: 0.42-0.82; P = 0.002), and pancreatic fistulas (RR: 0.486; 95%CI: 0.34-0.63; P < 0.00001), whereas lymph node retrieval was decreased significantly in the overweight group (MD: 1.69; 95%CI: 0.75-2.62; P < 0.0001). In addition, overweight patients had poorer long-term survival (RR: 1.14; 95%CI: 1.07-1.20; P < 0.0001). No significant difference was detected for the mortality and length of hospital stay.
CONCLUSION: This meta-analysis demonstrates that a high BMI not only increases the surgical difficulty and complications but also impairs the long-term survival of patients with gastric cancer.
Overweight; Body mass index; Gastric cancer; Gastrectomy
Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism.
First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student’s t-test for comparison of the results obtained from cells with or without curcumin treatment.
The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as ΔΨm decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3.
Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer.
Curcumin; Gallbladder carcinoma GBC-SD cell; Proliferation; Apoptosis
At present, radical resection remains the only effective treatment for patients with hilar cholangiocarcinoma. The surgical approach for R0 resection of hilar cholangiocarcinoma is complex and diverse, but for the biliary reconstruction after resection, almost all surgeons use Roux-en-Y hepaticojejunostomy. A viable alternative to Roux-en-Y reconstruction after radical resection of hilar cholangiocarcinoma has not yet been proposed. We report a case of performing duct-to-duct biliary reconstruction after radical resection of Bismuth IIIa hilar cholangiocarcinoma. End-to-end anastomosis between the left hepatic duct and the distal common bile duct was used for the biliary reconstruction, and a single-layer continuous suture was performed along the bile duct using 5-0 prolene. The patient was discharged favorably without biliary fistula 2 wk later. Evidence for tumor recurrence was not found after an 18 mo follow-up. Performing bile duct end-to-end anastomosis in hilar cholangiocarcinoma can simplify the complex digestive tract reconstruction process.
Hilar cholangiocarcinoma; Biliary reconstruction; Duct-to-duct; Radical resection; Digestive tract reconstruction; Hepaticojejunostomy; Bile duct anastomosis
The patatin-related phospholipase A (pPLA) hydrolyzes membrane glycerolipids to produce monoacyl compounds and free fatty acids. Phospholipids are cleaved by pPLAIIα at the sn-1 and sn-2 positions, and galactolipids, including those containing oxophytodienoic acids, can also serve as substrates. Ablation of pPLAIIα decreased lysophosphatidylcholine and lysophosphatidylethanolamine levels, but increased free linolenic acid. pPLAIIα-deficient plants displayed a higher level of jasmonic acid and methyl jasmonate, as well as the oxylipin-biosynthetic intermediates 13-hydroperoxylinolenic acid and 12-oxophytodienoic acid than wild-type (WT) plants. The expression of genes involved in oxylipin production was also higher in the pPLAIIα-deficient mutant than in WT plants. The mutant plants lost water more quickly than WT plants. The stomata of WT and mutant plants responded similarly to abscisic acid. In response to desiccation, the mutant and WT leaves produced abscisic acid at the same rate, but, after 4 h of desiccation, the jasmonic acid level was much higher in mutant than WT leaves. These results indicate that pPLAIIα negatively regulates oxylipin production and suggest a role in the removal of oxidatively modified fatty acids from membranes.
patatin-related phospholipase A; oxidative modified lipids; jasmonate synthesis; water loss; Arabidopsis thaliana
Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants of M. hyopneumoniae, we determined the whole genome sequence of M. hyopneumoniae strain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses.
We performed the first comprehensive analysis of M. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence.
We studied the virulence attenuation mechanism of M. hyopneumoniae by comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form the foundation of future investigations into the pathogenesis of M. hyopneumoniae and facilitate the design of new vaccines.
Mycoplasma hyopneumoniae; Genetic variation; Virulence attenuation; Sequence analysis; Repetitive sequences; Virulence factors
Bioimpedance analysis (BIA) has been reported as helpful in identifying hypervolemia. Observation data showed that hypervolemic maintenance hemodialysis (MHD) patients identified using BIA methods have higher mortality risk. However, it is not known if BIA-guided fluid management can improve MHD patients’ survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management compared with standard care.
This is a multicenter, prospective, randomized, controlled trial. More than 1300 participants from 16 clinical sites will be included in the study. The enrolment period will last 6 months, and minimum length of follow-up will be 36 months. MHD patients aged between 18 years and 80 years who have been on MHD for at least 3 months and meet eligibility criteria will be invited to participate in the study. Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arms of the study. In the BIA arm, additional BCM measurements will be performed every 2 months. The primary intent-to-treat analysis will compare outcomes for a composite endpoint of death, acute myocardial infarction, stroke or incident peripheral arterial occlusive disease between groups. Secondary endpoints will include left ventricular wall thickness, blood pressure, medications, and incidence and length of hospitalization.
Previous results regarding the benefit of strict fluid control are conflicting due to small sample sizes and unstable dry weight estimating methods. To our knowledge this is the first large-scale, multicentre, prospective, randomized controlled trial to assess whether BIS-guided volume management improves outcomes of MHD patients. The endpoints of the BOCOMO study are of utmost importance to health care providers. In order to obtain that aim, the study was designed with very careful important considerations related to the endpoints, sample size, inclusion criteria, exclusion criteria and so on. For example, annual mortality of Beijing MHD patients was around 10%. To reach statistical significance, the sample size will be very large. By using composite endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to patients with urine volume less than 800 ml/day the day before dialysis session will limit confounding due to residual renal function effects on the measured parameters. Patients who had received BIS measurement within 3 months prior to enrolment are excluded as data from such measurements might lead to protocol violation. Although not all patients enrolled will be incident patients, we will record the vintage of dialysis in the multivariable analysis.
Current Controlled Trials NCT01509937
Hemodialysis; Bioimpedance; Dry weight; Body composition monitor; Randomized controlled trial
With the increase in joint revision surgery after arthroplasty, defects of hydroxyapatite (HA)-coated prostheses have been observed increasingly often. These defects adversely affect the prosthetic stability in vivo. This study has analyzed the potential effect of the adhesive strength of HA coating on the stability of HA-coated prostheses in vivo after its implantation.
Material and methods
Sixty experimental rabbits were divided into HA- and Ti-coated groups. HA-coated prostheses were implanted into the bilateral epicondyle of rabbits femurs. Ti-coated prostheses were implanted as control. At different time points(4, 9, and 15 weeks) after implantation, bone tissue samples were fetched out respectively for histomorphometric analysis. Push-out testing was used to detect the ultimate shear strength at the bone-prosthesis interface. Scanning electron microscope (SEM) observation and energy-dispersive X-ray spectroscopy (EDX) analysis were used to observe the changes in surface composition of the prostheses after the ultimate shear strength testing. The coating adhesive strength of two kinds of coatings were also examined by scratch testing.
Hydroxyapatite coating has an obvious advantage in facilitating osteogenesis and its plays a critical role in the stability of prostheses. However, the ultimate shear strength of HA-coated prostheses is much lower than that of Ti-coated implants (p < 0.01). Further study has demonstrated that the stability of HA-coated prostheses in vivo is affected by the relatively low adhesive strength between coating and substrate.
Obvious advantage in facilitating osteogenesis around HA-coated prostheses is not the only factor that determines the stability of prostheses in vivo.
hydroxyapatite coating; artificial joints; stability; biomechanical; adhesive strength
With the superiority of digital imaging, conventional preoperative acetate templating is gradually being replaced by digital templating in total hip arthroplasty (THA). The purpose of this study was to assess the utility of digital templating for patients with Crowe type II and III dysplastic hips. In this study, 41 THA patients with Crowe type II or III dysplastic hips and 48 THA patients with other primary diseases were retrospectively reviewed. All patients were fitted with cementless prostheses in 2008. For the THA patients with dysplastic hips, we attempted to restore their hip centres to the position of the true acetabulum. Digital templating was the method chosen to achieve hip centre restoration. The prosthesis prediction accuracy (within ± one size using digital templating) was 20 (48.8%) for the cup size and 30 (73.2%) for the stem size. Meanwhile, for patients with other primary diseases, the accuracy for the cup size within ± one size was 34 (70.8%) and for the stem size accuracy was within ± one size in 38 (79.2%). Between the two patient groups, there was a significant difference in the predicted cup size. In patients with dysplastic hips, the low accuracy of the predicted cup size may have resulted from difficulty in predicting the vertical location of the hip centre. Despite this limitation, preoperative planning using digital templating is a convenient technique for THA patients with Crowe type II and III dysplastic hips.
In the title coordination polymer, [Cd(C8H5N2O2S)2(C10H8N2)]n, the CdII ion is coordinated by a bidentate 2,2-bipyridyl ligand, two O,O′-chelating 2-amino-1,3-benzothiazole-6-carboxylate (ABTC) ligands and one N-bonded ABTC ligand. The resulting CdN3O4 coordination polyhedron approximates to a very distorted pentagonal bipramid with one O and one N atom in axial positions. One of the ABTC ligands is bridging to an adjacent metal atom, generating an infinite chain propagating in . A three-dimensional network is constructed from N—H⋯O and N—H⋯N hydrogen bonds and aromatic π–π stacking interactions [centroid–centroid separations = 3.641 (2) and 3.682 (3) Å].
Two virtually superimposable molecules comprise the asymmetric unit of the title compound, C27H27N3. The range of dihedral angles between the central 1,3,5-triazine ring and the attached benzene rings is 20.88 (14)–31.36 (14)°, and the shape of each molecule is of a flattened bowl. The crystal packing features weak C—H⋯π bonds and π–π interactions between triazine and benzene rings [centroid–centroid separations = 3.7696 (17) and 3.7800 (18) Å] that result in the formation of supramolecular layers in the ac plane. The crystal studied was a non-merohedral twin with a minor twin component of 20.7 (3)%.