Horizontal duodenal papilla is associated with a special spectrum of pancreaticobiliary diseases: a retrospective magnetic resonance cholangiopancreatography-based study.

Background: Horizontal duodenal papilla (HDP) is not an uncommon ectopic major papilla. The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear. Here, we explored the associations in patients who underwent magnetic resonance cholangiopancreatography (MRCP). Methods: Consecutive patients who underwent MRCP at Xijing Hospital (Xi'an, China) between January 2020 and December 2021 were eligible. Patients were divided into HDP and regular papilla (RP) according to the position of the major papilla. The primary outcome was the proportion of congenital pancreaticobiliary diseases. Results: A total of 2,194 patients were included, of whom 72 (3.3%) had HDP. Compared with the RP group (n = 2,122), the HDP group had a higher proportion of congenital pancreaticobiliary diseases, especially choledochal cyst (CC) or anomalous pancreaticobiliary junction (APBJ) (6.9% vs 1.4%, P = 0.001). More gallbladder cancer (6.9% vs 1.2%, P < 0.001) and pancreatic cysts (27.8% vs 16.3%, P = 0.01) were also identified in the HDP group. Morphologically, the HDP group had a longer extrahepatic bile duct (8.4 [7.6-9.3] cm vs 7.2 [6.5-8.1] cm, P < 0.001), and larger angles between the common bile duct-duodenum and pancreatic duct-duodenum. Multivariate analysis showed that the presence of HDP was an independent risk factor for gallbladder cancer. Conclusions: This study confirmed that HDP was not rare in patients underwent MRCP. A higher prevalence of congenital pancreaticobiliary malformations (especially CC or APBJ), gallbladder cancer and pancreatic cysts was observed in patients with HDP, as well as distinctive morphologic features.

Unprecedented Spatial Manipulation and Transformation of Dynamic Thermal Radiation Based on Vanadium Dioxide.

Reconfigurable infrared (IR) materials have widespread applications in thermal management and smart IR concealment. Although various reconfigurable IR materials can be customized by positive or negative differential VO2-based resonators, their insightful mechanism remains unknown. Here, we comprehensively investigate the fundamental design rule of reconfigurable thermal radiation between positive and negative differential thermal radiation properties for the first time. Importantly, the skin depth of VO2 film in the metal state is investigated to clarify the transformation from positive to negative differential thermal radiation properties, and the critical thickness is further derived, providing important guidance in designing the reconfigurable thermal radiation regulator. Furthermore, the reconfigurable multistate thermal images had been presented into one plate. The resulting emittance variation (△ε8-14 µm) of the VO2-based resonator can change from 0.61 to -0.53, which consummates the ability for diverse demands such as infrared concealment, thermal illusion, and thermal management. This work constitutes a promising and universal route toward designing whole smart devices and may create new scientific and technological opportunities for platforms that can benefit from reconfigurable electromagnetic manipulation.

Near-infrared-dye labeled tumor vascular-targeted dimer GEBP11 peptide for image-guided surgery in gastric cancer.

Introduction: Positive resection margins occur in about 2.8%-8.2% gastric cancer surgeries and is associated with poor prognosis. Intraoperative guidance using Nearinfrared (NIR) fluorescence imaging is a promising technique for tumor detection and margin assessment. The goal of this study was to develop a tumor-specific probe for real-time intraoperative NIR fluorescence imaging guidance. Methods: The tumor vascular homing peptide specific for gastric cancer, GEBP11, was conjugated with a near-infrared fluorophore, Cy5.5. The binding specificity of the GEBP11 probes to tumor vascular endothelial cells were confirmed by immunofluorescent staining. The ability of the probe to detect tumor lesions was evaluated in two xenograft models. An orthotopic gastric cancer xenograft model was used to evaluate the efficacy of the GEBP11 NIR probes in real-time surgical guidance. Results: In vitro assay suggested that both mono and dimeric GEBP11 NIR probes could bind specifically to tumor vascular epithelial cells, with dimeric peptides showed better affinity. In tumor xenograft mice, live imaging suggested that comparing with free Cy5.5 probe, significantly stronger NIR signals could be detected at the tumor site at 24-48h after injection of mono or dimeric GEBP11 probes. Dimeric GEBP11 probe showed prolonged and stronger NIR signals than mono GEBP11 probe. Biodistribution assay suggested that GEBP11 NIR probes were enriched in gastric cancer xenografts. Using dimeric GEBP11 NIR probes in real-time surgery, the tumor margins and peritoneal metastases could be clearly visualized. Histological examination confirmed the complete resection of the tumor. Conclusion: (GEBP11)2-ACP-Cy5.5 could be a potential useful probe for intraoperative florescence guidance in gastric cancer surgery.

Sensitivity improved Cerenkov luminescence endoscopy using optimal system parameters.

BACKGROUND: The challenges of clinical translation of optical imaging, including the limited availability of clinically used imaging probes and the restricted penetration depth of light propagation in tissues can be avoided using Cerenkov luminescence endoscopy (CLE). However, the clinical applications of CLE are limited due to the low signal level of Cerenkov luminescence and the large transmission loss caused by the endoscope, which results in a relatively low detection sensitivity of current CLE. The aim of this study was to enhance the detection sensitivity of the CLE system and thus improve the system for clinical application in the detection of gastrointestinal diseases. METHODS: Four optical fiber endoscopes were customized with different system parameters, including monofilament (MF) diameter of imaging fiber bundles, fiber material, probe coating, etc. The endoscopes were connected to the detector via a specifically designed straight connection device to form the CLE system. The ß-2-[18F]-Fluoro-2-deoxy-D-glucose (18F-FDG) solution and the radionuclide of Gallium-68 (68Ga) were used to evaluate the performance of the CLE system. The images of the 18F-FDG solution acquired by the CLE were used to optimize imaging parameters of the system. By using the endoscope with optimized parameters, including the MF diameter of imaging fiber bundles, fiber materials, etc., the resolution and sensitivity of the assembled CLE system were measured by imaging the radionuclide of 68Ga. RESULTS: The results of 18F-FDG experiments showed that larger MF diameter led to higher collection efficiency. The fiber material and probe coating with high transmission ratios in the range of 400-900 nm also increased signal collection and transmission efficiency. The results of 68Ga evaluations showed that a minimum radioactive activity of radionuclides as low as 0.03 µCi was detected in vitro within 5 minutes, while that of 0.68 µCi can be detected within 1 minute. In vivo experiments also demonstrated that the developed CLE system achieved a high sensitivity at a submicrocurie level; that is, 0.44 µCi within 5 minutes, and 0.83 µCi within 1 minute. The weaker in vivo sensitivity was due to the attenuation of the signal by the mouse tissue skin and the autofluorescence interference produced by biological tissues. CONCLUSIONS: By optimizing the structural parameters of fiber endoscope and imaging parameters for data acquisition, we developed a CLE system with a sensitivity at submicrocurie level. These results support the possibility that this technology can clinically detect early tumors within 1 minute.

VO2-Based Infrared Radiation Regulator with Excellent Dynamic Thermal Management Performance.

Dynamic thermal management materials attract fast-increasing interest due to their adaptability to changing environments and greater energy savings as compared to static materials. However, the high transition temperature and the low emittance tunability of the vanadium dioxide (VO2)-based infrared radiation regulators limit their practical applications. This study addresses these issues by proposing a smart infrared radiation regulator based on a Fabry-Pérot cavity structure (VO2/HfO2/Al), which is prepared by high-power impulse magnetron sputtering (HiPIMS) and has the potential for large-scale production. Remarkably, the outstanding emittance tunability reaches 0.51, and the phase transition temperature is lowered to near a room temperature of 27.5 °C by tungsten (W) doping. In addition, a numerical thermal management power of 196.3 W/m2 (at 8-14 µm band) can be obtained from 0 to 60 °C. As a proof-of-concept, the demonstrated capabilities of the VO2 infrared radiation regulator show great potentials in a wide range of applications for the thermal management of buildings and vehicles.

Water exchange-assisted versus carbon dioxide-insufflated single-balloon enteroscopy: a randomized controlled trial.

BACKGROUND: Single-balloon enteroscopy (SBE) is a valuable but difficult modality for the diagnosis and treatment of small-bowel disease. The water exchange method has the advantage of facilitating intubation during colonoscopy. Here, we evaluated the effects of water exchange on procedure-related variables related to SBE. METHODS: This randomized controlled trial was conducted in a tertiary-care referral center in China. Patients due for attempted total enteroscopy were randomly allocated to undergo water exchange-assisted (water exchange group) or carbon dioxide-insufflated enteroscopy (CO2 group). All patients were planned to undergo both anterograde and retrograde procedures. The primary outcome was the total enteroscopy rate. Secondary outcomes included the maximal insertion depth, positive findings, procedural time, and adverse events. RESULTS: In total, 110 patients were enrolled, with 55 in each group. Baseline characteristics between the two groups were comparable. Total enteroscopy was achieved in 58.2 % (32/55) of the water exchange group and 36.4 % (20/55) of the control group (P = 0.02). The mean (standard deviation) estimated intubation depth was 521.2 (101.4) cm in the water exchange group and 481.6 (95.2) cm in the CO2 group (P = 0.04). The insertion time was prolonged in the water exchange group compared with the CO2 group (178.9 [45.1] minutes vs. 154.2 [27.6] minutes; P < 0.001). Endoscopic findings and adverse events were comparable between the two groups. CONCLUSIONS: The water exchange method improved the total enteroscopy rate and increased the intubation depth during SBE. The use of water exchange did not increase the complications of enteroscopy.

The tumour neovasculature-homing dimeric peptide GX1 demonstrates antiangiogenic activity in the retinal neovasculature.

Identification of molecules specific to the retinal neovasculature will promote antiangiogenic therapy with enhanced targeting ability. The specificity of phage-displayed peptide GX1 (a cyclic 7-mer peptide motif CGNSNPKSC) to gastric cancer neovasculature has been extensively confirmed both in vitro and in vivo. To investigate the potential application of GX1 in antiangiogenic therapy targeting retinal angiogenesis-related diseases, we performed immunohistochemistry and immunofluorescence analyses. GX1 demonstrated positive staining in the retinal neovasculature in an oxygen-induced mouse model of retinopathy (OIR) as well as in rat retinal microvasculature endothelial cells (RMECs), confirming the major role of the GX1 receptor during retinal angiogenesis. Dimeric GX1 was synthesized to increase the binding affinity to the GX1 receptor, and the antiangiogenic effects were examined in RMECs in vitro and the retinal neovasculature in the OIR in vivo. Cell proliferation was evaluated using a Cell Counting Kit-8 (CCK-8) assay, revealing that compared with the GX1 monomer, dimeric GX1 significantly inhibited RMEC proliferation (P < 0.05). This finding may be attributed to the enhanced (P < 0.05) apoptosis induced by dimeric GX1 in RMECs based on results obtained from TUNEL, flow cytometric and cell cycle analyses. In RMECs, in vitro cell migration and tube formation were significantly inhibited following exposure to dimeric GX1. Intravitreal administration of dimeric GX1 resulted in a greater reduction in the retinal neovascularization in vivo than administration of the GX1 monomer (P < 0.05). In conclusion, dimeric GX1 showed greater inhibition of angiogenesis than monomeric GX1 and could be a promising agent for antiangiogenic therapy in retinal angiogenesis-related diseases.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Effect of water exchange method on adenoma miss rate of patients undergoing selective polypectomy: A randomized controlled trial.

BACKGROUND: Adenomas may be missed in up to 40% of screening colonoscopies. Although the water exchange (WE) method can improve ADR, as shown in several RCTs, it remains uncertain whether it can increase the detection of missing adenomas compared with standard air-insufflated (AI) colonoscopy. METHODS: Patients aged 18-80 years who underwent selective polypectomy were randomly allocated to the WE or AI group. The primary endpoint was the adenoma miss rate (AMR), defined as the number of patients with one or more additional adenomas during the polypectomy procedure divided by the total number of patients in each group. RESULTS: A total of 450 patients were enrolled, with 225 in each group. The overall AMRs were 45.8% (103/225) in the WE group and 35.6% (80/225) in the AI group (p = 0.035). More patients in the WE group had at least one missed adenoma in the proximal colon (38.2% vs 24.4%, p = 0.002). The adenoma-level miss rate was also higher in the WE group than in the AI group (35.1% vs 29.0%, p = 0.036). Subgroup analysis showed that patients in the WE group had more missed adenomas located in the proximal colon or with flat shapes. CONCLUSIONS: This study confirmed that substantial adenomas were missed in patients undergoing selective polypectomy. The WE method significantly improved the detection of missed adenomas, especially those located in the proximal colon or with flat shapes. (ClnicalTrials.gov number: NCT02880748).

Learning curve of double-guidewire technique by trainees during hands-on endoscopic retrograde cholangiopancreatography training.

BACKGROUND AND AIMS: Double-guidewire technique (DWT) has been successfully performed by experts in difficult biliary cannulation as an advanced technique. This study aimed to define the learning curve and safety of DWT by trainees during hands-on endoscopic retrograde cholangiopancreatography (ERCP) training. METHODS: Patients were eligible for inclusion in the study if the biliary cannulation was difficult and the pancreatic duct was inadvertently cannulated. DWT was performed by two trainees randomly under trainers' guidance. The primary outcome was the success rate of DWT biliary cannulation of trainees. Cumulative sum analysis was used to generate visual learning curves. RESULTS: A total of 60 patients with difficult cannulation were enrolled. The main indications for ERCP were common bile duct stones (65%) and biliary stricture (31.7%). The learning curve analysis showed that to achieve a 70% rate of successful DWT, 12 procedures were needed for trainee A and 15 for trainee B. Higher targeted success rate of DWT could be achieved if the number of DWT procedures increased. Compared with the early stage of learning DWT (case 1 to 15 for each trainee), trainees had significantly higher DWT success rate in the late stage (36.7% [11/30] vs 80% [24/30], P = 0.001). The final success rate of cannulation was 98.3% (59/60). The overall rate of post-ERCP pancreatitis and adverse events was 6.7% (4/60) and 8.3% (5/60), respectively. CONCLUSIONS: Double-guidewire technique was safely performed by two novel trainees during hands-on ERCP training. Fifteen procedures may be enough for trainees to achieve the competency of performing DWT. (Clinicaltrials.gov number: NCT03707613).

Effect of cap-assisted esophagogastroduodenoscopy on examination of the major duodenal papilla: a noninferior, randomized controlled trial.

BACKGROUND: Cap-assisted esophagogastroduodenoscopy (CA-EGD) using a transparent cap fitted to the tip of the scope has emerged as an alternative method for examination of the major duodenal papilla (MDP). However, it remains unclear whether CA-EGD is noninferior to standard duodenoscopy for MDP examination. The aim of this study was to compare the efficacies of the two methods for complete examination of the MDP. METHODS: This prospective, noninferior, randomized controlled study was conducted at two endoscopy centers. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomized (1:1) to undergo CA-EGD or standard duodenoscopy for MDP examination. The primary outcome was complete examination of the MDP, defined as visualization of the upper end, opening, and lower end of the papilla. Secondary outcomes included endoscopic findings and the time taken for the MDP examination. RESULTS: The study was terminated for futility after the interim analysis. A total of 171 patients were randomly allocated to CA-EGD (n = 85) or standard duodenoscopy (n = 86). The baseline characteristics were comparable between the two groups. Complete examination of the MDP was achieved in 58/85 patients (68.2 %) in the CA-EGD group and in 74/86 (86.0 %) in standard duodenoscopy group. The difference in proportions was - 17.81 percentage points (95 % confidence interval [CI] -28.14 to -7.48) by intention-to-treat analysis and - 18.22 percentage points (95 %CI -28.34 to -8.10) by per-protocol analysis, both of which were significantly lower than the noninferiority margin of -5 %, and therefore the noninferiority of CA-EGD could not be confirmed. Examination time was significantly longer with CA-EGD (69.5 [SD 46.4] vs. 33.0 [SD 28.9] seconds; P < 0.001). CONCLUSIONS: Although complete examination of the MDP can be achieved by CA-EGD in most patients, it could not replace duodenoscopy as the standard method for examination of the MDP.

Multimodality Imaging of Angiogenesis in a Rabbit Atherosclerotic Model by GEBP11 Peptide Targeted Nanoparticles.

Background and Aims: Angiogenesis is an important pathological process during progression of plaque formation, which can result in plaque hemorrhage and vulnerability. This study aims to explore non-invasive imaging of angiogenesis in atherosclerotic plaque through magnetic resonance imaging (MRI) and positron emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis were performed to detect the effects of NGD-MNPs on cell proliferation, cell cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo MRI and PET imaging of atherosclerotic plaque were carried out at different time points after intravenous injection of nanoparticles. Results: The NGD-MNPs with hydrodynamic diameter of 130.8 nm ± 7.1 nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co-localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a promising MR and PET dual imaging probe for visualizing the vulnerable plaques.

In Vivo Magnetic Resonance and Fluorescence Dual-Modality Imaging of Tumor Angiogenesis in Rats Using GEBP11 Peptide Targeted Magnetic Nanoparticles.

Angiogenesis is an essential process for tumor progression. Tumor vasculature-targeting peptides have shown great potential for use in cancer imaging and therapy. Our previous studies have shown that GEBP11, a novel vasculature-specific binding peptide that exhibits high affinity and specificity to tumor angiogenesis, is a promising candidate for the diagnosis and targeted radiotherapy of gastric cancer. In the present study, we developed a novel magnetic resonance and fluorescence (MR/Fluo) dual-modality imaging probe by covalently coupling 2,3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and Cy5.5 to the GEBP11 peptide. The probe Cy5.5-GEBP11-DMSA-MNPs (CGD-MNPs), with a hydrodynamic diameter of 82.8 ± 6.5 nm, exhibited good imaging properties, high stability and little cytotoxicity. In vivo MR/Fluo imaging revealed that CGD-MNPs were successfully applied to visualize tumor angiogenesis in SGC-7901 xenograft mouse models. Prussian blue and CD31 immunohistochemical staining confirmed that CGD-MNPs co-localized with tumor blood vessels. In conclusion, CGD-MNPs are promising candidates for use as MR and fluorescence imaging probes for visualizing gastric cancer angiogenesis in vivo.

Mechanism study of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR by iTRAQ-based proteomic analysis.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which specifically binds to the surface of MDR gastric cancer cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. The present study aimed to investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR. METHODS: Fluorescence-activated cell sorting (FACS) and immunofluorescence staining were used to investigate the subcellular location and mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated downstream targets of GMBP1. Differentially expressed proteins were identified in GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and KEGG pathway analyses of the differentially expressed proteins revealed the interconnection of these proteins, the majority of which are involved in MDR. Two differentially expressed proteins were selected and validated by western blotting. RESULTS: GMBP1 and its receptor GRP78 were found to be localized in the cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749 proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells, respectively, involving 38 and 79 KEGG pathways. Two differentially expressed proteins, CTBP2 and EIF4E, were selected and validated by western blotting. CONCLUSION: This study explored the role and downstream mechanism of GMBP1 in GC MDR, providing insight into the role of endoplasmic reticulum stress protein GRP78 in the MDR of cancer cells.

In vivo molecular imaging of gastric cancer in human-murine xenograft models with confocal laser endomicroscopy using a tumor vascular homing peptide.

The early detection of premalignant lesions and cancers are very important for improving the survival of patients with gastric malignancies. Confocal laser endomicroscopy (CLE) is a novel imaging tool for achieving real-time microscopy during the ongoing endoscopy at subcellular resolution. In the present study, to evaluate the feasibility of real-time molecular imaging of GEBP11 by CLE in gastric cancer, CLE was performed on two types of tumor-bearing mice models, as well as surgical specimens of patients with gastric cancer, after the application of GEBP11. A whole-body fluorescent imaging device was first used to screen for the strongest specific fluorescent signal in xenograft models. Next, the tumor sites, as well as human tissues, were scanned with CLE. After this, targeted specimens were obtained for fluorescence microscopy and histology. We confirmed that GEBP11 could specifically bind to co-HUVECs by means of CLE in cell experiments. Thereafter, a specific signal was observed in both subcutaneous and orthotopic xenograft models in vivo after the injection of FITC-GEBP11 via tail vein, whereas the group injected with FITC-URP showed no fluorescent signals. In human tissues, a specific signal of GEBP11 was observed in 26/28 neoplastic specimens and in 8/28 samples of non-neoplastic specimens from the patients (p < 0.01). The findings from ex vivo immunofluorescence microscopy of cryostat sections correlated well with that obtained by CLE. These findings indicate that the peptide, GEBP11, might be a potential candidate for the molecular imaging of gastric cancer.

Prevalence of colorectal cancer in patients with ulcerative colitis: A retrospective, monocenter study in China.

BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is a serious complication of UC. Data on the clinical characteristics of patients in China are scarce. AIMS: We aimed to study the incidence, characteristics, treatment, and prognosis of CRC patients with a history of UC. MATERIALS AND METHODS: We identified patients with UC and followed them until the first occurrence of cancer, death, or emigration in a single study center in China. RESULTS: A total of 4 UC-associated CRC patients were identified among the 642 cases recorded from January 2000 to December 2012. The overall risk of cancer was 0.64%. The overall median duration of UC was 15.5 years (range 6-21 years) in patients with UC-associated CRC. Of these patients, 75% (3/4) were at an advanced stage when they were diagnosed. Longer disease duration and extensive colitis were identified as risk factors for developing CRC, and 5-aminosalicylic acid and steroid therapies were not identified as protective factors against UC-associated CRC. CONCLUSIONS: Patients with UC are at an increased risk for CRC. However, the prevalence of CRC in China remains lower than that in the West.

Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.

Adhesion of cancer cells to the extracellular matrix (ECM) causes a novel acquired chemotherapeutic drug­resistant phenotype, referred to as cell adhesion-mediated drug resistance (CAM-DR). Our previous studies suggested that the adhesion molecule MGr1-Ag/37LRP may promote multidrug resistance in gastric cancer cells. Therefore, we investigated MGr1-Ag/37LRP binding-induced adhesion, and its role in CAM-DR. Initial studies revealed that, after adhesion to the ECM, the multidrug-resistant gastric cancer cell lines SGC7901/VCR and SGC7901/ADR showed significantly higher mean adhesive cell numbers than non­resistant SGC7901 cells. We then investigated expression of MGr1-Ag/37LRP in gastric cancer cells adhering to laminin. Western blotting, RT-PCR and dual-luciferase reporter assays showed that laminin induced MGr1-Ag/37LRP expression and activity. In vitro and in vivo assays revealed that small interfering RNA against MGr1-Ag/37LRP significantly reduced CAM-DR in SGC7901/VCR cells. In vivo and in vitro analyses revealed that binding of MGr1-Ag/37LRP decreased intracellular drug accumulation by increasing P-glycoprotein and multidrug-associated protein expression, and inhibited drug-induced apoptosis by regulating Bcl-2 and Bax expression. These results indicate that MGr1-Ag/37LRP contributes to laminin-mediated CAM-DR in gastric cancer cells, and is a potentially effective target for reversing this phenomenon in gastric cancer.

Increased expression of HSP27 inhibits invasion and metastasis in human esophageal squamous cell carcinoma.

Previous studies have indicated that heat shock protein 27 (HSP27) had high correlation with the development and progression in several tumors. However, the roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The aim in this study is to investigate the potential roles of HSP27 in the metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human esophageal cancer cell lines were examined by immunohistochemistry and Western blotting, respectively. Wound healing assays, transwell assays, and in vivo assays were used to identify the differences of metastasis potential between normal and HSP27 overexpressed cells. HSP27 expression was downregulated in cancer tissue compared to the matched normal tissue. And the positive staining was mainly located in the cytoplasm. Statistical analyses showed that the expression of HSP27 in ESCC was significantly correlated with the tumor differentiation (P = 0.023), the patient's TNM stage (P = 0.013), lymph metastasis (P = 0.020), and distant metastasis (P = 0.017). HSP27 expression was significantly lower in highly metastatic cells than the less ones. The metastatic potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly metastatic cells dramatically decreased their metastatic capacity. This study indicated that the expression level of HSP27 may be inversely correlated with the metastasis behavior of ESCC, and HSP27 may play an important role in this progression. HSP27 may be a potential molecular target for the therapy and prognosis of patients with ESCC.

MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion-mediated drug resistance (CAM-DR), a form of de novo drug resistance. In our previous study, we reported that MGr1-Ag/37LRP ligation-induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1-Ag could prompt CAM-DR through interaction with laminin. However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM-DR through upregulation of Bcl-2 by MGr1-Ag interaction with laminin. Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK. Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1-Ag-mediated CAM-DR in gastric cancer. MGr1-Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer.