Comparison of patency rates and complications with or without antithrombotic therapy following portal vein stent placement after pancreatic surgery, a systematic review and meta-analysis.

BACKGROUND: Portal vein stent placement is used for portal vein stenosis. However, reports on post-pancreatic surgery cases are rare. Whether antithrombotic therapy should be administered remains controversial. In this paper, we reviewed current data to evaluate the influence of antithrombosis on stent patency after pancreatic surgery. MATERIALS AND METHODS: This systematic review and meta-analysis compared studies in which patients did or did not receive antithrombotic therapy after portal vein stent placement. We compared patency after stent placement and complication rate. RESULTS: There were 22 (n=207) studies in which patients received antithrombotic therapy and 8 (n=61) in which patients did not receive therapy. Antithrombotic agents, such as aspirin, clopidogrel, heparin, and warfarin, were used. The overall patency rates were similar between the groups (79.2% in the antithrombosis group vs. 88.0% in the non-antithrombosis group). Subgroup analyses included those for the etiology of stenosis, types of antithrombotic agents, acute or chronic stenosis, and causes of stent stenosis. None revealed a significant difference between the patency rates in the antithrombosis and non-antithrombosis groups. However, bleeding complications only occurred in patients who received antithrombotic therapy. CONCLUSION: There is no significant benefit of antithrombotic therapy after portal vein stent placement following pancreatic surgery. Antithrombotic therapy should be performed with caution because it may cause complications, such as bleeding.

Percutaneous transhepatic stenting for acute superior mesenteric vein stenosis after pancreaticoduodenectomy with portal vein reconstruction: A case report.

BACKGROUND: Percutaneous transhepatic stent placement has become a common strategy for the postoperative treatment of portal vein (PV)/superior mesenteric veins (SMV) stenosis/occlusion. It has been widely used after liver transplantation surgery; however, reports on stent placement for acute PV/SMV stenosis after pancreatic surgery within postoperative 3 d are rare. CASE SUMMARY: Herein, we reported a case of intestinal edema and SMV stenosis 2 d after pancreatic surgery. The patient was successfully treated using stent grafts. Although the stenosis resolved after stent placement, complications, including bleeding, pancreatic fistula, bile leakage, and infection, made the treatment highly challenging. The use of anticoagulants was adjusted multiple times to prevent venous thromboembolism and the risk of bleeding. After careful treatment, the patient stabilized, and stent placement effectively managed postoperative PV/SMV stenosis. CONCLUSION: Stent placement is effective and feasible for treating acute PV/SMV stenosis after pancreatic surgery even within postoperative 3 d.

M6A RNA methylation in biliary tract cancer: the function roles and potential therapeutic implications.

Biliary tract cancers (BTCs) are relatively rare malignancies with a poor prognosis. For advanced BTCs, the efficacy of current chemotherapeutic approaches is limited. Consequently, there is an urgent need to deepen our understanding of the molecular mechanisms underlying BTC tumorigenesis and development for the exploration of effective targeted therapies. N6-methyladenosine (m6A), the most abundant RNA modifications in eukaryotes, is found usually dysregulated and involved in tumorigenesis, progression, and drug resistance in tumors. Numerous studies have confirmed that aberrant m6A regulators function as either oncogenes or tumor suppressors in BTCs by the reversible regulation of RNA metabolism, including splicing, export, degradation and translation. In this review, we summarized the current roles of the m6A regulators and their functional impacts on RNA fate in BTCs. The improved understanding of m6A modification in BTCs also provides a reasonable outlook for the exploration of new diagnostic strategies and efficient therapeutic targets.

YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation.

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and involved in the carcinogenesis of various malignancies. However, the functions and mechanisms of m6A in gallbladder cancer (GBC) remain unclear. In this study, we investigated the role and underlying mechanism of the RNA-binding protein YT521-B homology domain-containing family protein 2 (YTHDF2), an m6A reader, in GBC. Herein, we detected that YTHDF2 was remarkably upregulated in GBC tissues compared to normal gallbladder tissues. Functionally, YTHDF2 overexpression promoted the proliferation, tumor growth, migration, and invasion of GBC cells while inhibiting the apoptosis in vitro and in vivo. Conversely, YTHDF2 knockdown induced opposite results. Mechanistically, we further investigated the underlying mechanism by integrating RNA immunoprecipitation sequencing (RIP-seq), m6A-modified RIP-seq, and RNA sequencing, which revealed that death-associated protein kinase 3 (DAPK3) is a direct target of YTHDF2. YTHDF2 binds to the 3'-UTR of DAPK3 mRNA and facilitates its degradation in an m6A-dependent manner. DAPK3 inhibition restores the tumor-suppressive phenotype induced by YTHDF2 deficiency. Moreover, the YTHDF2/DAPK3 axis induces the resistance of GBC cells to gemcitabine. In conclusion, we reveal the oncogenic role of YTHDF2 in GBC, demonstrating that YTHDF2 increases the mRNA degradation of the tumor suppressor DAPK3 in an m6A-dependent way, which promotes GBC progression and desensitizes GBC cells to gemcitabine. Our findings provide novel insights into potential therapeutic strategies for GBC.

Construction of a prognostic model for HCC based on ferroptosis-related lncRNAs expression and its potential to predict the response and irAEs of immunotherapy.

Background: Ferroptosis is an iron-dependent programmed cell death process, and studies have confirmed that it plays an important regulatory role in the occurrence and development of various malignancies including hepatocellular carcinoma (HCC). In addition, the role of abnormally expressed long non-coding RNAs (lncRNAs) in regulating and driving the occurrence and development of HCC has attracted more and more attention. However, there is still a lack of research on the role of ferroptosis-related lncRNAs in the prognosis prediction of HCC patients. Method: In this study, we used the Pearson test method to analyze the association between differentially expressed lncRNAs and ferroptosis-related genes in HCC and normal tissues obtained from The Cancer Genome Atlas (TCGA), and found 68 aberrantly expressed and prognosis-related ferroptosis-related lncRNAs. Based on this, we established an HCC prognostic model composed of 12 ferroptosis-related lncRNAs. In addition, HCC patients were divided into a high-risk group and a low-risk group according to the risk score of this 12 ferroptosis-related lncRNAs prognostic model. Gene enrichment analysis indicated that ferroptosis-related lncRNA-based expression signatures may regulate HCC immune microenvironment signaling pathways through ferroptosis, chemical carcinogenesis-reactive oxygen species, and NK cell-mediated cytotoxicity pathways. In addition, immune cell correlation analysis showed that there were significant differences in immune infiltrating cell subtypes, such as Th cells, macrophages, monocytes, and Treg cells between the two groups. In addition, the expression of multiple immune checkpoint molecules was found to be significantly increased in the high-risk group (eg, PD1, CTLA-4, CD86, etc.). Results: Our research provides a new method for predicting prognosis using a ferroptosis-related lncRNA expression signature prognostic model in hepatocellular carcinoma. And it provides new tools for predicting patient response and adverse effects of immunotherapy. Conclusion: In conclusion, ferroptosis-related lncRNA expression signatures can be used to construct a prognostic prediction model to predict the overall survival of HCC patients, and can be used as an independent influencing factor for prognosis. Further analysis showed that ferroptosis-related lncRNAs may affect the efficacy of immunotherapy in patients with HCC by altering the tumor microenvironment, so this model may serve as a new indicator of the response and irAEs of HCC to immunotherapy.

Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats.

Background: Bile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats. Methods: Ten GK rats were randomly divided into the biliary diversion (BD) and sham groups. The glucose metabolism, hypothalamic POMC expression, serum bile acid profiles, and ileal bile acid-specific receptors of the two groups were analyzed. Results: Biliary diversion improved blood glucose (P = 0.001) and glucose tolerance (P = 0.001). RNA-Seq of the hypothalamus showed significantly upregulated expression of the POMC gene (log2-fold change = 4.1, P < 0.001), which also showed increased expression at the protein (P = 0.030) and mRNA (P = 0.004) levels. The POMC-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) was also increased in the hypothalamus (2.21 ± 0.11 ng/g, P = 0.006). In addition, increased taurocholic acid (TCA) (108.05 ± 20.62 ng/mL, P = 0.003) and taurodeoxycholic acid (TDCA) (45.58 ± 2.74 ng/mL, P < 0.001) were found in the BD group and induced the enhanced secretion of fibroblast growth factor-15 (FGF15, 74.28 ± 3.44 pg/ml, P = 0.001) by activating farnesoid X receptor (FXR) that was over-expressed in the ileum. Conclusions: Hypothalamic POMC neurons were upregulated after BD, and the increased TCA, TDCA, and the downstream gut-derived hormone FGF15 might activate POMC neurons.

Prediction value of plasma D-dimer level changes on venous thromboembolism during pregnancy.

OBJECTIVE: To explore the changes in plasma D-dimer (D-D) levels of pregnant women during pregnancy and their predictive value for venous thromboembolism (VTE). METHODS: A selection of 240 pregnant women who came to our hospital for routine perinatal care and delivery from January 2018 to January 2019 were selected as the observation group, and 240 cases that came to our hospital for routine physical examination were served as the control group. The D-D levels of the two groups of women were compared, and the D-D levels of pregnant women in the observation group with different delivery methods were explored; the observation group was into VTE and non-VTE groups according to the occurrence of VTE, and the D-D levels of the two groups of pregnant women in different periods were compared, and its predictive value on VTE was analyzed. RESULTS: The observation group exhibited a notably higher D-D level than the control group (p < .001), and the D-D level of the observation group during the first trimester was lower than the second and third trimesters, with statistical difference observed (p < .001), and the second trimester was much lower than the third trimester (p < .001); the D-D level in pregnant women with vaginal delivery showed lower level when comparing with women with cesarean section (p < .001); the D-D level of the VTE group was remarkably higher than that of the non-VTE group (p < .05); the D-D level during the second trimester had the highest predictive value for VTE, with the optimal cutoff value of 1.40 mg/L, the sensitivity of 69.3%, and the specificity of 76.7%, and AUC = 0.73. CONCLUSION: The D-D of pregnant women during pregnancy showed an increase trend with the gestational weeks, and they were all beyond the normal range. The D-D level in the second trimester has the highest predictive value for VTE.

Profiling of chromatin accessibility identifies transcription factor binding sites across the genome of Aspergillus species.

BACKGROUND: The identification of open chromatin regions and transcription factor binding sites (TFBs) is an important step in understanding the regulation of gene expression in diverse species. ATAC-seq is a technique used for such purpose by providing high-resolution measurements of chromatin accessibility revealed through integration of Tn5 transposase. However, the existence of cell walls in filamentous fungi and associated difficulty in purifying nuclei have precluded the routine application of this technique, leading to a lack of experimentally determined and computationally inferred data on the identity of genome-wide cis-regulatory elements (CREs) and TFBs. In this study, we constructed an ATAC-seq platform suitable for filamentous fungi and generated ATAC-seq libraries of Aspergillus niger and Aspergillus oryzae grown under a variety of conditions. RESULTS: We applied the ATAC-seq assay for filamentous fungi to delineate the syntenic orthologue and differentially changed chromatin accessibility regions among different Aspergillus species, during different culture conditions, and among specific TF-deleted strains. The syntenic orthologues of accessible regions were responsible for the conservative functions across Aspergillus species, while regions differentially changed between culture conditions and TFs mutants drove differential gene expression programs. Importantly, we suggest criteria to determine TFBs through the analysis of unbalanced cleavage of distinct TF-bound DNA strands by Tn5 transposase. Based on this criterion, we constructed data libraries of the in vivo genomic footprint of A. niger under distinct conditions, and generated a database of novel transcription factor binding motifs through comparison of footprints in TF-deleted strains. Furthermore, we validated the novel TFBs in vivo through an artificial synthetic minimal promoter system. CONCLUSIONS: We characterized the chromatin accessibility regions of filamentous fungi species, and identified a complete TFBs map by ATAC-seq, which provides valuable data for future analyses of transcriptional regulation in filamentous fungi.

Biliary Neuroendocrine Neoplasms: Analysis of Prognostic Factors and Development and Validation of a Nomogram.

BACKGROUND: For this study, we explored the prognostic profiles of biliary neuroendocrine neoplasms (NENs) patients and identified factors related to prognosis. Further, we developed and validated an effective nomogram to predict the overall survival (OS) of individual patients with biliary NENs. METHODS: We included a total of 446 biliary NENs patients from the SEER database. We used Kaplan-Meier curves to determine survival time. We employed univariate and multivariate Cox analyses to estimate hazard ratios to identify prognostic factors. We constructed a predictive nomogram based on the results of the multivariate analyses. In addition, we included 28 biliary NENs cases from our center as an external validation cohort. RESULTS: The median survival time of biliary NENs from the SEER database was 31 months, and the value of gallbladder NENs (23 months) was significantly shorter than that of the bile duct (45 months) and ampulla of Vater (33.5 months, p=0.023). Multivariate Cox analyses indicated that age, tumor size, pathological classification, SEER stage, and surgery were independent variables associated with survival. The constructed prognostic nomogram demonstrated good calibration and discrimination C-index values of 0.783 and 0.795 in the training and validation dataset, respectively. CONCLUSION: Age, tumor size, pathological classification, SEER stage, and surgery were predictors for the survival of biliary NENs. We developed a nomogram that could determine the 3-year and 5-year OS rates. Through validation of our central database, the novel nomogram is a useful tool for clinicians in estimating individual survival among biliary NENs patients.

Dynamic change of serum CA19-9 levels in benign and malignant patients with obstructive jaundice after biliary drainage and new correction formulas.

BACKGROUND: CA19-9 is one of the most widely used tumor markers in biliary-pancreatic diseases. The measured value may not factually reflect the genuine CA19-9 level secreted by tumor, which affected by biliary obstruction. There is an urgent need of developing a correction formula of CA19-9 in biliary obstructive patients to guide clinical practice and avoid making improper clinical decision. METHODS: Clinical characteristics were collected among patients undergoing biliary drainage in our hospital between January 2014 and January 2019. By comparing the malignant and benign patients statistically, dynamic change trend of CA19-9 levels after biliary drainage was obtained. The correction formulas of CA19-9 were generated by means of linear regression. RESULTS: 121 patients, including 102 malignant and 19 benign patients, were enrolled in this study. The baseline CA19-9 level of malignant patients is much higher than that of benign patients. Total bilirubin (TB) level was found to be not related with CA19-9 value (p = 0.109). The drop proportion of the average CA19-9 level in the malignant patients (39.2%, IQR -18.4-78.6%) was much lower than that in the benign patients (75.7%, IQR 58.1-86.6%) (p = 0.014). The correction formula, CA19-9True = 0.63 × CA19-9Measured - 20.3 (R2 = 0.693, p<0.001), was generated based on the linear relation between CA19-9 after drainage and CA19-9 before drainage in malignant patients, which had similar diagnostic value with true CA19-9 value. CONCLUSIONS: Quantitative correction formulas of CA19-9 considering the effect of biliary decompression was first proposed in this study, aiming to provide a more accurate CA19-9 level to make more accurate clinical decision and avoid making improper therapeutic schedule.

Crystal structure of fungal tannase from Aspergillus niger.

Tannases are serine esterases that were first discovered in fungi more than one and half centuries ago. They catalyze the hydrolysis of the gallolyl ester bonds in gallotannins to release gallic acid, which is an important intermediate in the chemical and pharmaceutical industries. Since their discovery, fungal tannases have found wide industrial applications, although there is scarce knowledge about these enzymes at the molecular level, including their catalytic and substrate-binding sites. While this lack of knowledge hinders engineering efforts to modify the enzymes, many tannases have been isolated from various fungal strains in a search for the desired enzymatic properties. Here, the first crystal structure of a fungal tannase, that from Aspergillus niger, is reported. The enzyme possesses a typical α/ß-hydrolase-fold domain with a large inserted cap domain, which together form a bowl-shaped hemispherical shape with a surface concavity surrounded by N-linked glycans. Gallic acid is bound at the junction of the two domains within the concavity by forming two hydrogen-bonding networks with neighbouring residues. One is formed around the carboxyl group of the gallic acid and involves residues from the hydrolase-fold domain, including those from the catalytic triad, which consists of Ser206, His485 and Asp439. The other is formed around the three hydroxyl groups of the compound, with the involvement of residues mainly from the cap domain, including Gln238, Gln239, His242 and Ser441. Gallic acid is bound in a sandwich-like mode by forming a hydrophobic contact with Ile442. All of these residues are found to be highly conserved among fungal and yeast tannases.

Biliary diversion increases resting energy expenditure leading to decreased blood glucose level in mice with type 2 diabetes.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is a group of metabolism abnormalities in carbohydrates and energy. Our aim was to investigate resting energy expenditure (REE) and blood glucose changes after biliary diversion in mice with diabetes. MATERIALS AND METHODS: Male mice with diabetes were randomly divided into biliary diversion and sham groups. REE was detected by indirect calorimetry, the levels of fasting blood glucose, total bile acids and triiodothyronine were analyzed. After mice were killed, the weight amount of brown adipose tissue (BAT) and gastrocnemius was measured, and the expression level of G protein-coupled bile acid receptor and type 2 iodothyronine deiodinase in BAT and gastrocnemius were examined. RESULTS: The two groups of mice were pair-fed, the bodyweights (P < 0.001) and the fasting blood glucose level (P < 0.001) in the biliary diversion group significantly decreased 24 weeks after surgery. The intraperitoneal glucose tolerance test (P = 0.035) and oral glucose tolerance test (P = 0.027) showed improvement in glucose tolerance after surgery. The REE level significantly increased 24 weeks after surgery (P = 0.005), the levels of total bile acids (P = 0.014) and triiodothyronine (P < 0.001) increased at the 24th postoperative week. The weight ratio of BAT (P = 0.038) and gastrocnemius (P = 0.026) in the biliary diversion group were higher than that in the sham group. The expression of G protein-coupled bile acid receptor in BAT (P < 0.001) and gastrocnemius (P = 0.003) were upregulated after surgery, and the type 2 iodothyronine deiodinase expression also increased in BAT (P = 0.015) and gastrocnemius (P = 0.015). CONCLUSIONS: The REE level increased and the glucose metabolism improved in mice with diabetes after biliary diversion.

Author Correction: Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The transcription factor PrtT and its target protease profiles in Aspergillus niger are negatively regulated by carbon sources.

OBJECTIVE: To survey genome-scale protease profiles regulated by the Aspergillus niger transcription factor PrtT and further controlled by carbon sources. RESULTS: The PrtT disruption mutant (delprtT) and overexpression (OEprtT) strains were successfully generated and further confirmed by phenotypic and protease activity analysis. RNA-seq analysis of WT and mutants identified 32 differentially expressed protease genes, which mostly belonged to serine-type peptidases, aspartic-type endopeptidases, aminopeptidases and carboxypeptidases. Furthermore, based on the MEME predicted motif analysis of the PrtT promoter, EMSA and phenotypic and qRT-PCR analyses confirmed that the carbon metabolism regulator AmyR directly regulated the protease genes and their regulatory factor PrtT. CONCLUSION: Thirty-two PrtT-regulated protease genes were identified by RNA-seq, and the secondary carbon source regulator AmyR was found to have a negative regulatory effect on the expression of PrtT and its target protease genes.

Improving expression of thermostable trehalase from Myceliophthora sepedonium in Aspergillus niger mediated by the CRISPR/Cas9 tool and its purification, characterization.

Trehalase catalyzes the conversion of one molecule of trehalose into two glucose molecules. The trehalase TreM from thermophilic fungus Myceliophthora sepedonium was expressed in Aspergillus niger via traditional homologous recombination with trehalase activity of 406.44 U/mL. The multi-copy knock-in expression strategy mediated by the CRISPR/Cas9 tool was used to improve the production of the TreM trehalase in Aspergillus niger, which was up to 1943.06 U/mL with a low-background of secreted proteins, 4.8-fold than the transformant obtained via the traditional method. The highest recombinant trehalase activity of the shake fermentation supernatant achieved 4268.29 U/mL when 1.5% glucose was added. Activity assaying showed that the recombinant TreM possessed a specific activity of 679.09 U/mg after gel filtration chromatography purification. The recombinant TreM displayed optimal activity at pH 5.6 and 60 °C and exhibited prominent stability under the conditions of 45-50 °C and pH 4.0-7.5. The activity of recombinant TreM was strongly enhanced by Co2+ (1, 5 mM), Cu2+ (1 mM), Mn2+ (1, 5 mM) and ATP (5 mM), and was greatly inhibited by Cu2+ (10 mM), EDTA (10 mM) and SDS (10 mM).

High-level expression and characterization of the thermostable leucine aminopeptidase Thelap from the thermophilic fungus Thermomyces lanuginosus in Aspergillus niger and its application in soy protein hydrolysis.

Leucine aminopeptidase (LAP), an exopeptidase that releases amino acid residues, especially leucine, from the N-terminus of polypeptides, is often applied to debitter protein hydrolysate in the food industry. However, there are no thermostable and high activity enzymes that can be used in the food industry. In this study, we obtained the highly active and thermostable leucine aminopeptidases screened from the thermophilic fungi Thermomyces lanuginosus, Talaromyces thermophilus, and Malbranchea cinnamomea. The activity of the recombinant leucine aminopeptidase Thelap was significantly increased to 2771.5 U/mL, as mediated by the CRISPR/Cas9 tool. The recombinant Thelap was easily purified from fermentation broth by Ni-affinity chromatography, and the specific activity of the purified Thelap was increased to 7449.6 U/mg. The recombinant Thelap showed optimal activity at pH 8.5 and 75 °C and remained above 70% of the maximum activity over a wide temperature range (30-80 °C). With regard to temperature stability, Thelap retained more than 90% activity when it was incubated at 65-75 °C for 2 h. K+ and Co2+ increased the enzyme activity of the recombinant Thelap, while Ba2+, Mn2+, Ni2+, Ca2+, Mg2+ and SDS inhibited its enzyme activity, and the inhibition capacity of Mg2+ was the weakest. Upon application in soy protein hydrolysis, Thelap could significantly increase the degree of hydrolysis and remove more hydrophobic amino acids from the N-terminal region of the polypeptide to decrease the bitterness.

High-level expression of highly active and thermostable trehalase from Myceliophthora thermophila in Aspergillus niger by using the CRISPR/Cas9 tool and its application in ethanol fermentation.

Trehalase catalyzes the hydrolysis of the non-reducing disaccharide trehalose. The highly active trehalase MthT from Myceliophthora thermophila was screened from the trehalase genes of six species of filamentous fungi. An ingenious multi-copy knock-in expression strategy mediated by the CRISPR/Cas9 tool and medium optimization were used to improve MthT production in Aspergillus niger, up to 1698.83 U/mL. The protein background was dramatically abated due to insertion. The recombinant MthT showed optimal activity at pH 5.5 and 60 °C, and exhibited prominent thermal stability between 50 and 60 °C under acid conditions (pH 4.5-6.5). The ethanol conversion rate (ethanol yield/total glucose) was significantly improved by addition of MthT (51.88%) compared with MthT absence (34.38%), using 30% starch saccharification liquid. The results of this study provided an effective strategy, established a convenient platform for heterologous expression in A. niger and showed a potential strategy to decrease production costs in industrial ethanol production.

Surgical management of Zollinger-Ellison syndrome: Classical considerations and current controversies.

Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors, but surgical management to control gastrinoma itself remains controversial. Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations: (1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location (including the duodenum, pancreas, lymph nodes, hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries, heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed; (2) For multiple endocrine neoplasia type 1-related ZES (MEN1/ZES), surgery should not be performed routinely except for lesions > 2 cm. An attempt to perform radical resection (pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and (3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.

A novel prognostic marker and immunogenic membrane antigen: prohibitin (PHB) in pancreatic cancer.

BACKGROUND: Previous study, using immunoblotting with IgG and membrane proteins, identified prohibitin (PHB) as a potential immunogenic membrane antigen. Now, investigate PHB expression and biological functions in pancreatic cancer. METHODS: PHB expression was analysed in PDAC cell lines, normal pancreas tissues, cancer tissues, PDAC patient sera and healthy volunteer sera using QRT-PCR, Western blotting, IHC, and ELISA, and a survival analysis and a COX regression analysis were performed. Low and high PHB expression levels were accomplished using RNA interference technology and gene transfer techniques. Cell proliferation, migration, and invasion, apoptosis-related proteins were assessed 48 h after transfection. RESULTS: PHB was generally expressed in the 8 tested PDAC cell lines. PHB was significantly increased in PDAC tissues and negatively correlated with overall survival (p < 0.01). PHB was an independent prognostic factor in PDAC (p < 0.01). PHB was increased in PDAC patient sera (p < 0.01). siRNA-PHB decreased cell growth, migration and invasion. However, PHB overexpression resulted in the opposite effects. Western blotting and Flow cytometric analysis revealed apoptosis inhibition in siRNA-PHB PDAC cells. CONCLUSIONS: PHB plays a key role in modulating the malignant phenotype and apoptosis induction, which may be a novel prognostic predictor and a candidate for targeted therapy against PDAC.

Review of the possible association between thyroid and breast carcinoma.

BACKGROUND: Thyroid and breast cancer are two of the malignant diseases with highest incidence in females. Based on clinical experience, breast and thyroid cancer often occur metachronously or synchronously. Therefore, thyroid and breast cancer might share some common etiological factors. The relationship between these diseases has attracted substantial attention, and because these two glands are both regulated by the hypothalamic-pituitary axis, such a relationship is not surprising. A study of this relationship will be useful for obtaining a better understanding of the mechanism by which these two malignancies co-occur. MAIN BODY: This study reviewed the progress in research on the roles of iodine intake, folate metabolism, obesity, gonadal hormones, and thyroid hormone in thyroid and breast cancer. These studies evaluating the etiological roles of these factors in linking breast and thyroid cancer might also improve our understanding and identify new therapeutic approaches, such as sodium/iodide symporter-mediated radioiodine therapy and thyroid-stimulating hormone receptor antagonists, for breast cancer. In addition, some specific treatments for each cancer, such as radiotherapy for breast cancer or radioactive iodine therapy for thyroid cancer, might be risk factors for secondary malignances, including breast and thyroid cancer. CONCLUSIONS: Studies of the precise relationship between the co-occurrence of breast and thyroid cancer will certainly improve our understanding of the biological behaviors of these two malignancies and direct evidence-based clinical practice.