SEA Anemone-inspired Conducting Polymer Sensing Platform for Integrated Detection of Tumor Protein Marker and Circulating Tumor Cell.

Combining the detection of tumor protein markers with the capture of circulating tumor cells (CTCs) represents an ultra-promising approach for early tumor detection. However, current methodologies have not yet achieved the necessary low detection limits and efficient capture. Here, we introduced a novel polypyrrole nanotentacles sensing platform featuring anemone-like structures capable of simultaneously detecting protein biomarkers and capturing CTCs. The incorporation of nanotentacles significantly enhanced the electrode surface area, providing abundant active sites for antibody binding. This enhancement allowed detecting nucleus matrix protein22 (NMP22) and bladder tumor antigen (BTA) with 2.39 and 3.12 pg/mL detection limit, respectively. Furthermore, our developed sensing platform effectively captured MCF-7 cells in blood samples with a detection limit of fewer than 10 cells/mL, attributed to the synergistic multivalent binding facilitated by the specific recognition antibodies and the positive charge on the nanotentacles surface. This sensing platform demonstrated excellent detection capabilities and outstanding capture efficiency, offering a simple, accurate, and efficient strategy for early tumor detection. This article is protected by copyright. All rights reserved.

Inhibition of CCR1 attenuates neuroinflammation via the JAK2/STAT3 signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Neuroinflammation is an important mechanism underlying brain injury caused by subarachnoid hemorrhage (SAH). C-C chemokine receptor type 1 (CCR1)-mediated inflammation is involved in the pathology of many central nervous system diseases. Herein, we investigated whether inhibition of CCR1 alleviated neuroinflammation after experimental SAH and aimed to elucidate the mechanisms of its potential protective effects. METHODS: To analyze SAH transcriptome data R studio was used, and a mouse model of SAH was established using endovascular perforations. In this model, the selective CCR1 antagonist Met-RANTES (Met-R) and the CCR1 agonist recombinant CCL5 (rCCL5) were administered 1 h after SAH induction. To investigate the possible downstream mechanisms of CCR1, the JAK2 inhibitor AG490 and the JAK2 activator coumermycin A1 (C-A1) were administered 1 h after SAH induction. Furthermore, post-SAH evaluation, including SAH grading, neurological function tests, Western blot, the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Fluoro-Jade B and fluorescent immunohistochemical staining were performed. Cerebrospinal fluid (CSF) samples were detected by ELISA. RESULTS: CCL5 and CCR1 expression levels increased significantly following SAH. Met-R significantly improved neurological deficits in mice, decreased apoptosis and degeneration of ipsilateral cerebral cortex neurons, reduced infiltrating neutrophils, and promoted microglial activation after SAH induction. Furthermore, Met-R inhibited the expression of p-JAK2, p-STAT3, interleukin-1ß, and tumor necrosis factor-α. However, the protective effects of Met-R were abolished by C-A1 treatment. Furthermore, rCCL5 injection aggravated neurological dysfunction and increased the expression of p-JAK2, p-STAT3, interleukin-1ß, and tumor necrosis factor-α in SAH mice, all of which were reversed by the administration of AG490. Finally, the levels of CCL5 and CCR1 were elevate in the CSF of SAH patient and high level of CCL5 and CCR1 levels were associated with poor outcome. CONCLUSION: The present results suggested that inhibition of CCR1 attenuates neuroinflammation after SAH via the JAK2/STAT3 signaling pathway, which may provide a new target for the treatment of SAH.

Inhibition of S100A9 alleviates neurogenic pulmonary edema after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Neurogenic pulmonary edema (NPE) frequently arises as a complication subsequent to subarachnoid hemorrhage (SAH). Heterodimers of S100A8 and S100A9 are commonly formed, thereby initiating an inflammatory reaction through receptor binding on the cell surface. Paquinimod serves as a specific inhibitor of S100A9. The objective of this investigation is to assess the impact of Paquinimod administration and S100A9 knockout on NPE following SAH. METHODS: In this study, SAH models of C57BL/6J wild-type (WT) and S100A9 knockout mice were established through intravascular perforation. These models were then divided into several groups, including the WT-sham group, S100A9-KO-sham group, WT-SAH group, WT-SAH + Paquinimod group, and S100A9-KO-SAH group. After 24 h of SAH induction, pulmonary edema was assessed using the lung wet-dry weight method and Hematoxylin and eosin (HE) staining. Additionally, the expression levels of various proteins, such as interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), occludin, claudin-3, Bax, Bcl-2, TLR4, MYD88, and pNF-κB, in lung tissue were analyzed using western blot and immunofluorescence staining. Lung tissue apoptosis was detected by TUNEL staining. RESULTS: Firstly, our findings indicate that the knockout of S100A9 has a protective effect on early brain injury following subarachnoid hemorrhage (SAH). Additionally, the reduction of brain injury after SAH can also alleviate neurogenic pulmonary edema (NPE). Immunofluorescence staining and western blot analysis revealed that compared to SAH mice with wild-type S100A9 expression (WT-SAH), the lungs of S100A9 knockout SAH mice (S100A9-KO-SAH) and mice treated with Paquinimod exhibited decreased levels of inflammatory molecules (IL-1ß and TNF-α) and increased levels of tight junction proteins. Furthermore, the knockout of S100A9 resulted in upregulated expression of the apoptotic-associated protein Bax and down-regulated expression of Bcl-2. Furthermore, a decrease in TLR4, MYD88, and phosphorylated pNF-κB was noted in S100A9-KO-SAH and Paquinimod treated mice, indicating the potential involvement of the TLR4/MYD88/NF-κB signaling pathway in the inhibition of the protective effect of S100A9 on NPE following SAH. CONCLUSION: The knockout of S100A9 not only ameliorated initial cerebral injury following subarachnoid hemorrhage (SAH), but also mitigated SAH-associated neurogenic pulmonary edema (NPE). Additionally, Paquinimod was found to diminish NPE. These findings imply a correlation between the central nervous system and peripheral organs, highlighting the potential of safeguarding the brain to mitigate harm to peripheral organs.

Clinical evaluation of percutaneous endovascular radiofrequency ablation for portal vein tumor thrombus: experience in 120 patients.

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.

Blocking P2RX7 Attenuates Ferroptosis in Endothelium and Reduces HG-induced Hemorrhagic Transformation After MCAO by Inhibiting ERK1/2 and P53 Signaling Pathways.

Hyperglycemia is a risk factor for poor prognosis after acute ischemic stroke and promote the occurrence of hemorrhagic transformation (HT). The activation of P2RX7 play an important role in endotheliocyte damage and BBB disruption. Ferroptosis is a novel pattern of programmed cell death caused by the accumulation of intracellular iron and lipid peroxidation, resulting in ROS production and cell death. This study is to explore the mechanism of P2RX7 in reducing HT pathogenesis after acute ischemic stroke through regulating endotheliocyte ferroptosis. Male SD rats were performed to establish middle cerebral artery occlusion (MCAO) model injected with 50% high glucose (HG) and HUVECs were subjected to OGD/R treated with high glucose (30 mM) for establishing HT model in vivo and in vitro. P2RX7 inhibitor (BBG), and P2RX7 small interfering RNAs (siRNA) were used to investigate the role of P2RX7 in BBB after MCAO in vivo and OGD/R in vitro, respectively. The neurological deficits, infarct volume, degree of intracranial hemorrhage, integrity of the BBB, immunoblotting, and immunofluorescence were evaluated at 24 h after MCAO. Our study found that the level of P2RX7 was gradually increased after MCAO and/or treated with HG. Our results showed that treatment with HG after MCAO can aggravate neurological deficits, infarct volume, oxidative stress, iron accumulation, and BBB injury in HT model, and HG-induced HUVECs damage. The inhibition of P2RX7 reversed the damage effect of HG, significantly downregulated the expression level of P53, HO-1, and p-ERK1/2 and upregulated the level of SLC7A11 and GPX4, which implicated that P2RX7 inhibition could attenuate oxidative stress and ferroptosis of endothelium in vivo and in vitro. Our data provided evidence that the P2RX7 play an important role in HG-associated oxidative stress, endothelial damage, and BBB disruption, which regulates HG-induced HT by ERK1/2 and P53 signaling pathways after MCAO.

Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN). CASE PRESENTATION: We herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification. CONCLUSION: To our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.

Inhibition of CCR2 attenuates neuroinflammation and neuronal apoptosis after subarachnoid hemorrhage through the PI3K/Akt pathway.

BACKGROUND: Neuroinflammation and neuronal apoptosis are closely associated with a poor prognosis in patients with subarachnoid hemorrhage (SAH). We investigated the role of C-C motif chemokine receptor 2 (CCR2) in SAH. METHODS: Pre-processed RNA-seq transcriptome datasets GSE167110 and GSE79416 from the Gene Expression Omnibus (GEO) database were screened for genes differentially expressed between mice with SAH and control mice, using bioinformatics analysis. The endovascular perforation model was performed to establish SAH. RS504393 (a CCR2 antagonist) and LY294002 (PI3K inhibitor) were administered to explore the mechanism of neuroinflammation after SAH. SAH grading, neurological scoring, brain water content and blood-brain barrier (BBB) permeability determination, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence were performed. An in vitro model of SAH was induced in H22 cells by hemin treatment. The protective mechanism of CCR2 inhibition was studied by adding RS504393 and LY294002. Clinical cerebrospinal fluid (CST) samples were detected by ELISA. RESULTS: Expression of CCR2 was upregulated in both datasets and was identified as a hub gene. CCR2 expression was significantly upregulated in the cytoplasm of neurons after SAH, both in vitro and in vivo. RS significantly reduced the brain water content and blood-brain barrier permeability, alleviated neuroinflammation, and reduced neuronal apoptosis after SAH. Additionally, the protective effects of CCR2 inhibition were abolished by LY treatment. Finally, the levels of CCR2, inflammatory factors, and apoptotic factors were elevated in the CSF of patients with SAH. CCR2 levels were associated with patient outcomes at the 6-month follow-up. CONCLUSION: CCR2 expression was upregulated in both in vitro and in vivo SAH models. Additionally, inhibition of CCR2, at least partly through the PI3K/AKT pathway, alleviated neuroinflammation and neuronal apoptosis in vivo and in vitro. CCR2 levels in the CSF have a moderate diagnostic value for 6-month outcome prediction in patients with SAH.

Taurine attenuates neuronal ferroptosis by regulating GABAB/AKT/GSK3ß/ß-catenin pathway after subarachnoid hemorrhage.

Ferroptosis, characterized by lipid peroxidation and intracellular iron accumulation, has been reported to be involving in the pathophysiological of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Although taurine reportedly yields neuroprotective effects in multiple central neurological diseases and can attenuated neuron damage after stroke, its role in EBI after SAH remains unclear. The present study indicated that taurine levels in cerebrospinal fluid were significantly reduced in SAH patients, which suggested that taurine treatment after SAH could improve neurological impairment, oxidative stress, iron accumulation, BBB integrity and neuronal ferroptosis in the SAH model in vivo. Taurine could attenuate MDA levels and ROS accumulation and regulate the expression of SLC7A11 and GPX4 and the AKT/GSK3ß pathway in vitro. GABAB receptor inhibition and Ly294002 could reverse the therapeutic effects of taurine and significantly downregulate the levels of p-AKT, p-GSK3ß, ß-catenin, SLC7A11 and GPX4. The protective effects of taurine on SLC7A11 and GPX4 expression were reversed by ICG001 treatment in vitro. Taken together, our findings revealed that taurine could improve neurological function and alleviate cerebral edema, oxidative stress and BBB disruption after SAH, which reduced neuronal ferroptosis by regulating the GABAB/AKT/GSK3ß/ß-catenin signaling pathway.

Intra-tumor heterogeneity and prognostic risk signature for hepatocellular carcinoma based on single-cell analysis.

Intra-tumor heterogeneity poses a serious challenge in the treatment of cancer, including hepatocellular carcinoma (HCC). Recent developments in single-cell RNA sequencing (scRNA-seq) make it possible to examine the heterogeneity of tumor cells. The Gene Expression Omnibus (GEO) database was retrieved to obtain scRNA-seq data of 13 HCC and 8 para cancer samples, and the cells were clustered using FindNeighbors and FindClusters functions. Cell subsets were defined using the "Enricher" function of the clusterProfiler package. Monocle was used to predict cell developmental trajectory. The LIMMA package included in the R program was utilized to detect differentially expressed genes (DEGs) between HCC and paracancerous tissues. Univariate Cox analysis and Least Absolute and Selection Operator (Lasso) Cox regression analysis were conducted to establish a risk assessment model. Thirteen cell subpopulations were identified from the sequencing data of 64,634 single cells. Four cell subgroups (dendritic cells, hepatocytes, liver bud hepatic cells, and liver progenitor cells) in tumor tissues were highly enriched. Between HCC and para cancer tissues, 3024 DEGs were identified, and 641 were specific markers of four cell subgroups. To develop a prognostic risk model, 9 genes among the 641 genes were selected. In the training and validation sets, the model demonstrated a higher 5-year AUC and independently served as a prognostic marker as confirmed by multivariate and univariate Cox analyses. This study revealed the characteristics of different cell subpopulations of immune cells and tumor cells from the HCC microenvironment. We established a novel nine-gene prognostic model to determine the death risk of HCC patients. The discoveries in this research improved the current knowledge of HCC heterogeneity and may inspire future research.

Endobiliary Ablation Combined with Immune Nutrition Improves Quality of Life: A Preliminary Clinical Study in Patients with Advanced Malignant Obstructive Jaundice.

BACKGROUND In patients with advanced malignant obstructive jaundice (MOJ), it remains an intractable problem to maintain biliary patency, because repeated stent occlusion and poor immune condition can lead to serious infection. The aim of this study was to investigate the effect of endobiliary ablation combined with immune nutrition (IN) on advanced MOJ. MATERIAL AND METHODS A prospective randomized pilot study of patients undergoing percutaneous transhepatic biliary drainage (PTBD) for advanced MOJ was conducted. From January 2018 to December 2020, patients fulfilling eligibility criteria were enrolled and randomized into 2 groups: patients who received only PTBD and standard early enteral nutrition were defined as the control group, and those who underwent additional endobiliary ablation and early IN on basis of the standard therapy were defined as the study group. Primary outcome was assessment of the quality of life based on time to resuming normal daily activities, duration of stent patency, and the overall survival (OS). Secondary outcomes included time before relief of jaundice, hospital stay, inflammation responses, and related complications. RESULTS We included 59 patients: 28 in the study group and 31 in the study group. Baseline characteristics were well balanced between the 2 groups. No statistically significant difference was found in time to resuming normal daily activities between the 2 groups. However, the study group presented statistically longer median duration of stent patency and survival time compared to the control group (stent patency 10.2 months vs 6.8 months, survival 9.6 months vs 7.1 months). The median time for relief of jaundice and the incidence of infection were similar between the 2 groups, but values of inflammatory response markers 3 days after the operation were significantly lower in the study group. No significant difference was found between the 2 groups in overall incidence of complications. CONCLUSIONS For patients at the advanced stage of MOJ, endobiliary ablation combined with postoperative IN therapy can significantly improve the quality of life.

Plasmon-Enhanced Electrocatalysis of Conductive Polymer-Based Nano-Heterojunction for Small Molecule Metabolites Diagnostics.

Conductive polymers are promising electrode candidates in the nonenzymatic catalytic detection of small molecule metabolites, due to the tunable electronic conductivity and versatile modifiability. However, the complex catalytic reaction pathway of conductive polymers results in lower detection sensitivity and a narrower linear range compared with clinical metal-based and carbon-based electrodes. Localized surface plasmon resonance (LSPR), characterized by deep strong light-matter coupling, has great potential in driving surface catalytic reactions at an ultrafast rate. Here, we constructed a salix argyracea-like polypyrrole nanowires/silver nanoparticles (PPy/AgNPs) heterojunction electrode using polydopamine as a dopant and chelator. Through cyclic voltammetry, the Mott-Schottky curve, and COMSOL simulation, we demonstrated that the LSPR-excited photocarriers enhanced PPy/AgNPs electrode electrocatalysis. Thus, the detection current response and linear range were significantly improved under the LSPR excitation when taking glucose and hydrogen peroxide as models of small molecule metabolites. Furthermore, we discussed the LSPR-enhanced detection mechanism of PPy/AgNPs electrode from the aspects of the Tafel slope, the apparent electron diffusion coefficient, and the charge transfer resistance. This strategy opens a new avenue toward the design of LSPR-enhanced conductive polymer electrodes.

Improving biliary stent patency for malignant obstructive jaundice using endobiliary radiofrequency ablation: experience in 150 patients.

BACKGROUND: Although self-expandable mental stents (SEMS) placement is the standard care for relieving obstructive jaundice caused by unresectable malignant biliary stricture, how to maintain stent potency remains an intractable problem. This study was to evaluate the efficacy and safety of endobiliary radiofrequency ablation (RFA) through percutaneous transhepatic cholangiography (PTC) pathway in treating such patients. METHODS: Consecutive patients who were performed endobiliary RFA as well as SEMS placement because of unresectable malignant obstructive jaundice in single institution in recent 8 years were retrospectively reviewed. As comparison, patients who underwent only percutaneous SEMS placement for unresectable malignant biliary stricture during the contemporary period were reviewed. Stent patency, complications, complications, and overall survival (OS) were investigated and analyzed. RESULTS: One hundred and fifty patients who underwent endobiliary RFA and 127 patients who underwent only stent placement were included in this study. In the study group of endobiliary RFA, 87 patients (58.0%) underwent ablation for 1 time, 49 (32.7%) for 2 times, and 14 (9.3%) for 3 times. Complications related to RFA as well as SEMS placement happened in 113 patients (75.3%), without severe complications that needed emergent surgery or interventional therapy. The median duration of stent patency after ablation was 11.2 month, and the median survival time was 12.3 month. As comparison, difference was found in the number of interventional procedures and stents placed, duration of initial stent patency, and the incidence of moderate bleeding and pain. In the study group, only the type of tumor that caused biliary obstruction (intrahepatic carcinoma vs. extrahepatic carcinoma) was a poor independent factor (P = 0.035) for recurrent biliary obstruction. Repeated interventional therapy and adoption of subsequent therapy were only independent factors for OS. CONCLUSIONS: Endobiliary RFA and SEMS placement is technically safe and feasible for unresectable malignant obstructive jaundice to improve the quality of life and prolong survival.

HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6.

The functional inactivation of tumor suppressor microRNA (miRNA) is closely related to the tumorigenesis of cancer. There are instances where the miRNA and the corresponding target both exist in a cell, but the target gene silencing do not occur as expected. Herein, we found that both miR-506 and its target CDK6 are highly co-expressed in lung cancer cells. Sequence analyses suggested that a miR-506 binding site (1648-1654) and a cis-element (1785-1795) for binding by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) are evolutionarily conserved and forms a stem structure in the 3' untranslated region (3'UTR) of CDK6. Furthermore, HNRNPA2B1 can bind to the stem structure to denature it and recruit the RNA helicase DExH-box helicase 9 (DHX9) to the 3'UTR, which ultimately facilitates miRNAs-mediated CDK6 silencing. These results indicate that the cis-element of the 3'UTR of CDK6, where HNRNPA2B1 binds, serves as an RNA switch to regulate miRNAs' function in cancer cells.

Modified Procedures for ALPPS Based on a Risk-Reduced Strategy: Paralleled Clinical Evaluation at Multiple Institutions.

PURPOSE: We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. MATERIALS AND METHODS: Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. RESULTS: Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. CONCLUSION: Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.

Yes-Associated Protein in Hepatocellular Carcinoma is Associated with Tumor Differentiation and Patient Age at Diagnosis, but not Markers of HBV Infection.

BACKGROUND: It was necessary to assess the relationship between Yes-associated protein (YAP) and some clinical features of hepatocellular carcinoma (HCC), especially hepatitis B virus (HBV) correlation factors as they relate to tumorigenesis. METHODS: A tissue microarray including 84 HCC samples was retrospectively analyzed by immunohistochemistry. RESULTS: This study showed that YAP expression was associated with HCC differentiation and the patient age at diagnosis of HCC. The mean age at diagnosis of YAP(+) HCC patients was 46.19 ± 9.45 years old, which is youn- ger than 51.40 ± 12.51 years old found for YAP(-) HCC patients (< 0.048). There was no significant correlation between YAP expression and HBV correlation factors (HBsAg, HBV DNA, and the duration of hepatitis B infec- tion). CONCLUSIONS: YAP(+) HCC patients had a younger mean age at diagnosis and more poor-differentiation charac- teristics of HCC. However, there were no independent HBV correlation factors.

A prospective, randomized trial of pancreatectomy combined with isolated hepatic perfusion via a dual route or conventional postoperative adjuvant therapy in patients with advanced pancreatic head carcinoma.

Prognosis of locally advanced pancreatic head carcinoma after Whipple remains poor. This study is to investigate the efficacy and safety of regional lymphadenectomy and chemotherapy of isolated hypoxic perfusion (IHP) via dual-route, and to analyze the effect for survival period. Consecutive patients subjected to our department from January 1, 2006 to December 31 2011 for locally advanced pancreatic head carcinoma were prospectively divided into two groups according to therapeutic modality, and clinical and follow-up data was recorded. In study group, operation duration and postoperative stay time were shorter, blood loss and blood transfusion were less, and incidence of complications was lower. The mean and median survival time was 17.4 ± 0.76 months and 18.0 months in study group, longer than control group of 14.1 ± 0.85 months and 17.6 months. Regional lymphadenectomy can be performed with low mortality and morbidity, and combined postoperative IHP via dual-route can improve survival time.

The influence of SnoN gene silencing by siRNA on the cell proliferation and apoptosis of human pancreatic cancer cells.

BACKGROUND: The prognosis for pancreatic cancer (PC) is very poor. The SnoN gene may have a role in cell proliferation and apoptosis in human cancer. However, the influence of SnoN on cell proliferation and apoptosis in human PC cells remains unknown. METHODS: SnoN expression was assessed in SW1990 PC cell lines using real-time polymerase chain reaction (PCR). A luciferase reporter assay was used to confirm the target associations. The effect of SnoN on cell proliferation in vitro was confirmed using Cell Counting Kit-8. Apoptosis was confirmed using flow cytometry. Gene and protein expression were examined using real time PCR and Western blotting, respectively. RESULTS: SnoN siRNA significantly inhibited the growth of SW1990 cells by decreasing cell proliferation (P < 0.05) and increasing cell apoptosis (P < 0.05), compared with the blank group and the negative control group. The highest inhibition of cell proliferation appeared at 3 days post-transfection. Cell apoptosis more obvious at 48 h after transfection. CONCLUSIONS: In summary, our results reveal that the RNAi-mediated downregulation of SnoN effectively inhibited the proliferation of PC cells. SnoN-siRNA also enhanced SW1990 PC cell apoptosis. These findings indicate that SnoN gene plays an important role in pancreatic cancer development, and might serve as a potential therapeutic target for pancreatic cancer. However, further in vivo studies are needed to clarify the influence of SnoN gene silencing by siRNA on pancreatic cancer therapy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7609324661510147.

Expression and clinical significance of HSPA2 in pancreatic ductal adenocarcinoma.

BACKGROUND: It has been shown that heat shock-related 70-kDa protein 2 (HSPA2), a member of the HSP70 family of heat shock proteins, is important for cancer cell growth and metastasis. However, the status of HSPA2 expression and its prognostic significance in pancreatic cancer remain unknown. METHODS: Quantitative reverse transcriptase ploymerase chain reaction (qRT-PCR) was applied to examine HSPA2 messenger RNA (mRNA) expression in 104 pairs of pancreatic cancer tissues and adjacent noncancerous tissues. Statistical analyses were applied to evaluate the diagnostic value and associations of HSPA2 expression with clinicopathological characteristics. RESULTS: HSPA2 mRNA was significantly overexpressed in pancreatic cancer tissues (3.9 ± 0.8) than in adjacent normal tissues (1.1 ± 0.4) (P < 0.001). Clinicopathological analysis showed that HSPA2 expression was significantly correlated with tumor size (P = 0.024), histological differentiation (P = 0.012), TNM stage (P = 0.006), lymph node metastasis (P = 0.043) and serum CA19-9 level (P = 0.046). Moreover, patients with higher HSPA2 expression levels had shorter overall survival time than those with lower HSPA2 expression levels (P = 0.019). Furthermore, Cox regression analyses showed that HSPA2 expression was an independent predictor of overall survival (P = 0.011). CONCLUSIONS: Our results suggest that overexpression of HSPA2 in pancreatic cancer is associated with aggressive progression and poor prognosis and that HSPA2 may be served as a prognostic marker. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5988744821527257 .

Knockdown of yes-associated protein inhibits proliferation and downregulates large tumor suppressor 1 expression in MHCC97H human hepatocellular carcinoma cells.

The pathogenesis of hepatocellular carcinoma (HCC) is thought to involve the interaction of numerous genes. Identification of these genes and proteins which regulate liver carcinogenesis is critical for the exploration of novel targeted therapies. Yes­associated protein (YAP) and large tumor suppressor 1 (LATS1) are associated with HCC cells. LATS1 is an upstream inhibitory factor of YAP in the Hippo pathway. The aim of the present study was to measure the expression of LATS1 in Yap­downregulated cancer cells. Immunohistochemistry was used to determine YAP and LATS1 levels in HCC tissue samples. High YAP­expressing cell lines were selected from two human hepatocellular carcinoma cells with different metastatic potential. In addition, changes in cell growth rates and LATS1 expression in human HCC 97H cells, in which YAP had been knocked down using RNA interference (RNAi). The proliferation of cells was evaluated using an MTS assay and changes in the progression of cell division were assessed through cell cycle analysis. Western blot analysis was then used to determine YAP and LATS1 expression levels in 97H cells. The results of the present study demonstrated that overexpression of YAP was negatively correlated with LATS1 expression in HCC cells (P=0.016). Knockdown of YAP using lentivirus­small hairpin (sh)RNA significantly inhibited 97H cell growth; in addition, the downregulation of YAP protein levels (33.4%) was accompanied by downregulation of LATS1 protein levels (68.5%). In conclusion, these results demonstrated that as an inhibitor of YAP, LATS1 was decreased via downregulation of YAP using RNAi. This therefore indicated that the change in YAP levels in HCC cells may regulate LATS1 in a feedback manner.

Association between CLPTM1L-TERT rs401681 polymorphism and risk of pancreatic cancer: a meta-analysis.

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Several recent studies have provided evidence that rs401681 polymorphisms in intronic region of cleft lip and palate trans-membrane 1-like (CLPTM1L) gene sequence are associated with pancreatic cancer (PC) development, but a comprehensive synopsis is not available. We performed a meta-analysis of 6 case-control studies that included 8,253 pancreatic cancer cases and 37,646 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, this meta-analysis showed that rs401681 allele T was associated with a significantly increased PC risk (OR = 1.17, 95 % CI = 1.12-1.22, P heterpgeneity = 0.596 and I (2) = 0). Similarly, in the subgroup analysis by ethnicity, a significantly increased risk was found among Asians (OR = 1.15, 95 % CI = 1.07-1.24, P heterpgeneity = 0.297 and I (2) = 8.0 %) and among Caucasian (OR = 1.13, 95 % CI = 1.02-1.26, P heterpgeneity = 0.385 and I (2) = 0). No publication bias was found in the present study. This meta-analysis suggests that T allele of CLPTM1L-telomerase reverse transcriptase rs401681 polymorphism is associated with an increased PC risk, especially among Chinese. Further large and well-designed studies are needed to confirm this association.