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Blue laser imaging (BLI) can provide useful information on colorectal laterally spreading tumors (LSTs) by visualizing the surface and vessel patterns in detail. The present research aimed to evaluate the diagnostic performance of BLI-combined JNET (Japan NBI Expert Team) classification for identifying LSTs. This retrospective, multicenter study included 172 LSTs consisted of 6 hyperplastic polyps/sessile serrated polyps, 94 low-grade dysplasias (LGD), 60 high-grade dysplasias (HGD), 6 superficial submucosal invasive (m-SMs) carcinomas, and 4 deep submucosal invasive carcinomas. The relationship between the JNET classification and the histologic findings of these lesions were then analyzed. For all LSTs, non-experts and experts had a 79.7% and 90.7% accuracy for Type 2A (P = 0.004), a sensitivity of 94.7% and 96.8% (P = 0.718), and a specificity of 61.5% and 83.3% (P = 0.002) for prediction of LGD, respectively. The results also demonstrated 80.8% and 91.3% accuracy for Type 2B (P = 0.005), a sensitivity of 65.2% and 83.3% (P = 0.017), and a specificity of 90.6% and 96.2% (P = 0.097) for predicting HGD or m-SMs. For LST-granular (LST-G) lesions, Type 2A in experts had higher specificity (65.6% vs. 83.6%, P = 0.022) and accuracy (81.8% vs. 91.2%, P = 0.022). Type 2B in experts only had higher accuracy (82.5% vs. 92.0%, P = 0.019). However, no significant differences were noted for any comparisons between non-experts and experts for LST-non-granular (LST-NG) lesions. BLI combined with JNET classification was an effective method for the precise prediction of pathological diagnosis in patients with LSTs. Diagnostic performance of JNET classification by experts was better than that by non-experts for all examined LST or LST-G lesions when delineating between Type 2A and 2B, but there was no difference for the identification of LST-NG lesions by these two groups.

The principal objective of this paper is to show the efficient and reliable energy harvesting performance of a Lambda-shaped piezoelectric energy harvester (LPEH). The equations of motion of the harvester were derived based on Euler–Bernoulli beam theory. The accuracy of the analytical model was validated by the finite element method and experiment. Then, using the analytical model, the energy harvesting performance of the harvester was compared to that of a conventional cantilever piezoelectric energy harvester. It was found that the LPEH generated much more power than the cantilever piezoelectric harvester when the same amount of substrate and piezoelectric materials were used. Additionally, the effects of the harvester shape angle and excitation direction of the proposed harvester on the energy harvesting performance were investigated. The results showed that the LPEH could produce reliable power even though the harvester shape angle and excitation direction varied. Owing to such reliable energy harvesting characteristics, the proposed harvester has the practical advantages of fitting within limited space and functioning under uncertain excitation direction conditions.

Background. Submucosal tumors (SMTs) are primarily benign tumors, but some may have a malignant potential. Endoscopic submucosal dissection that has been used for removing esophageal SMTs could cause perforation. Submucosal tunnel endoscopic resection (STER) is an improved and an effective technique for treating esophageal SMTs.Aims. This study was conducted to evaluate the efficacy and safety of STER for treating esophageal SMTs.Methods. A retrospective study design was adopted to analyze the baseline characteristics, clinical outcomes, and follow-up data of patients with esophageal SMTs, which originated from the muscularis propria layer and were treated with STER from September 2011 to May 2018.Results. A total of 119 lesions were included from 115 patients who were successfully treated with STER. The mean age of the patients was 49.7 ± 10.7 years. The lesions were primarily located in the middle and lower esophagus. The mean size of the lesions was 19.4 ± 10.0 mm. The mean operation duration was 46.7 ± 25.6 min, and the mean duration of hospitalization was 5.9 ± 2.8 days. The total en bloc resection rate and the complete resection rate were 97.5% and 100%, respectively. Regarding complications, there were 9 (7.8%) cases of perforation, 2 (1.7%) cases of pneumothorax, and 9 (7.8%) cases of subcutaneous emphysema. Histopathological results revealed 113 (95.0%) cases of leiomyoma, 5 (4.2%) cases of gastrointestinal stromal tumors, and 1 (0.8%) case of a granular cell tumor. During the mean 15-month follow-up, there were no cases of recurrence and distant metastasis.Conclusions. STER is a safe and feasible technique for treating esophageal SMTs originating from the muscularis propria layer.

Background In our previous work, we developed a modified method for the removal of gastric submucosal tumors (SMTs), called endoscopic mucosa-sparing lateral dissection (EMSLD). This prospective study aimed to evaluate the efficacy and postoperative outcomes of EMSLD. Methods We prospectively enrolled 25 consecutive patients with gastric SMTs, who received EMSLD treatment. Clinicopathological characteristics and operation-related outcomes were analyzed. Results The mean age of patients was 49.3 ± 9.7 years, and the mean tumor size was 14.6 ± 6.1 mm. En bloc resection was achieved in all cases. The mean procedure time was 47.3 ± 25.9 minutes, and the estimated blood loss was 4.8 ± 3.5 mL. Endoscopic full-thickness resection was performed in six patients (24 %) because the tumors originated from the deep muscularis propria layer. All perforations and resection defects were successfully closed by the retained mucosa and endoclips. No serious complications related to EMSLD were encountered during or after the procedure. Conclusions EMSLD was reliable and effective for the removal of gastric SMTs. However, large-scale randomized controlled trials are needed.

Endoscopic submucosal tunneling dissection (ESTD) has been proved to be safe and effective for removal of esophageal submucosal tumors (SMTs) and can maintain the mucosal integrity compared with other endoscopic methods. The aim of the study was to estimate the safety and efficacy of ESTD as well as compare its efficacy with thoracoscopic enucleation for esophageal SMTs, which is used increasingly as a minimally invasive approach.We retrospectively collected the clinical data of patients with esophageal SMTs 40 mm who underwent ESTD or thoracoscopic enucleation at Nanfang Hospital between January 2008 and August 2016. Epidemiologic data (sex, age), tumor location, tumor size, en bloc resection rate, adverse events, pathologic results, length of postoperative hospital stay, and cost were compared between ESTD and thoracoscopic enucleation.A total of 126 patients were included. A total of 74 patients underwent ESTD, and the other 52 underwent thoracoscopic enucleation. There was no significant difference between the 2 groups in sex, age, tumor size, hospitalization expense, infection, adverse events, and en bloc resection rate (P .05). However, patients in the ESTD group had a shorter operating time, less estimated blood loss, shorter length of postoperative hospital stay, and lower chest pain level (P .05). Kaplan-Meier curves for disease-free survival also showed no statistically significant difference between ESTD and thoracoscopic enucleation groups during the median follow-up of 19.5 and 42 months, respectively.The treatment efficacy was comparable between the ESTD and thoracoscopic enucleation for esophageal SMTs 40 mm. However, there was a significant advantage in the ESTD group for a shorter operating time, reduced postoperative chest pain, and shorter hospitalization.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Despite improved diagnosis and treatment, the prognosis for HCC patients remains poor. The goal of this study was to identify key regulatory proteins and signaling pathways important for cell apoptosis and proliferation as biomarkers for prognostication and targeted therapy. Protein Pathway Array was applied to screen 38 signaling proteins and phosphoproteins in 12 paired HCC tumors and surrounding benign tissues and found that 20 of them, including XIAP, CDK4, CDK6, and Cyclin D1, were overexpressed in HCC tissues. Immunostaining results of XIAP, CDK4, and Cyclin D1 in an additional 59 HCC tissues showed that the expression of XIAP correlated with the expression of CDK4/Cyclin D1, and that the increased expression of these proteins correlated with poor overall survival in these patients. Further studies using the HCC Huh7 cell line transfected with XIAP siRNA or expression vector demonstrated that XIAP regulated the expression of CDK4, CDK6, and Cyclin D1 via NF-êB and PTEN pathways. Finally, inhibition of XIAP using embelin, a XIAP-specific small molecule, leads to an increased apoptosis and decreased cell proliferation via arrest at G1 phase. Taken together, XIAP is a central modulator regulating cell apoptosis and cell cycle progression. Therefore, XIAP together with cell cycle regulatory proteins can be used as prognostic markers and therapeutic targets.

p21-activated kinase 5 (PAK5) is a recently identified member of the group B PAK family. The PAK proteins are effectors of the small GTPase Cdc42 and Rac1 and are known to regulate cell motility and activate cell-survival signaling pathways. Especially, the mitochondrial localization of PAK5 is vital to its effects on apoptosis and cell survival. Previously, we demonstrated that PAK5 expression increased significantly during the malignant progression of colorectal carcinoma (CRC) and that PAK5 promoted CRC metastasis by regulating CRC cell adhesion and migration. In the present study, we aim to investigate the role of PAK5 in camptothecin-induced apoptosis and its potential mechanism of action. Our results showed that overexpression of PAK5 inhibited camptothecin-induced apoptosis by inhibiting the activity of caspase-8 in CRC cells. Accordingly, knockdown of PAK5 in LoVo cells resulted in increased apoptosis. Mechanistically, we found that PAK5 directly phosphorylated Bad on serine 112 and indirectly led to phosphorylation of serine 136 via the Akt pathway. In conclusion, our study revealed previously unappreciated inhibitory role of PAK5 in camptothecin-induced apoptosis, thus suggesting PAK5 as a novel therapeutic target in CRC.

CD24 is a glycosylphosphatidylinositol-anchored membrane protein reported to be overexpressed in human tumorigenesis and progression. Our purpose was to determine the role of CD24 in the proliferation of colorectal cancer cells and the potential mechanisms in this process. Our data showed that CD24 promoted cell growth and induced activation of extracellular signal-regulated kinases, Raf-1, and p38 mitogen-activated protein kinase. Furthermore, suppression of extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activity by their specific inhibitors, U0126 and SB203580, abrogated CD24-induced proliferation in vitro. By tumorigenicity assay in female BALB/c nude mice, we further demonstrated that CD24 promoted tumor growth in vivo. Immunohistochemical analysis revealed that CD24 expression occurred in 92.5% of human colorectal cancer tissue, and increased with tumor progression. More importantly, the stainings of phospho-extracellular signal-regulated kinases and phospho-p38 mitogen-activated protein kinase were strongly correlated with CD24 expression. Taken together, our data suggest that CD24-dependent extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activations are required for colorectal cancer cell proliferation in vitro and in vivo. The linkage of CD24 and the mitogen-activated protein kinase pathway may unravel a novel mechanism in the regulation of colorectal cancer proliferation.

CD24 is involved in tumor progression of various cancers, but the effects of CD24 on tumor angiogenesis in colorectal cancer are still unknown. We aimed to investigate the underlying mechanism and role of CD24 on colorectal cancer (CRC) angiogenesis. Our data showed that the microvessal density (MVD) was related to the expression of CD24 in primary and metastasis CRC. Silencing of CD24 could dramatically decrease human umbilical vein endothelial cell (HUVEC) migration, invasion and tubule formation, but trivially affected cell proliferation. We also mechanically showed that silencing CD24 could downregulate the expression of VEGF via inhibiting the phosphorylation and translocation of STAT3. Moreover, Hsp90 was identified as the down-interaction protein of CD24 with co-immunoprecipitation assay and systematic mass spectrometry. Immunofluorescence results showed Hsp90 partly co-localized with CD24 in CRC cell membrane and there was a positive correlation between CD24 and Hsp90 expression in CRC tissues. We gradually evidenced that Hsp90 modulated the stability and degradation of CD24 in a proteasome-depended manner, and transferred the signal transmission from CD24 to STAT3. 17-AAG, a specific Hsp90, could abrogate the CD24 induce- HUVEC migration, invasion and tubule formation in vitro and in vivo. Collectively, our results suggested that CD24 induced CRC angiogenesis in Hsp90-dependent manner and activated STAT3-mediated transcription of VEGF. We provided a new insight into the regulation mechanism of tumor angiogenesis by exploring the role of CD24 in angiogenesis.

P21-activated protein kinase1 (PAK1), a main downstream effector of small Rho GTPases, Rac1, and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis. Despite its importance, the molecular mechanisms of PAK1 that contributed to colorectal carcinogenesis remain unclear. Our immunohistochemistry showed that PAK1 expression was increased with colorectal cancer (CRC) progression through the adenoma to carcinoma sequence. Furthermore, our results suggested a relationship between PAK1 nuclear localization and the Dukes staging. In the present study, we showed that PAK1 knockdown decreased proliferation and delayed the G1/S cell-cycle transition, and increased apoptosis in vivo and in vitro. In addition, PAK1 knock-down downregulated c-Jun amino terminal kinases (JNK) activity and the levels of cyclinD1, CDK4/6. Inhibition of the JNK activity by chemical inhibitor (SP600125) significantly reduced the effects of PAK1 on CRC proliferation via accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In conclusion, our results demonstrate that knockdown of PAK1 could enhance the chemosensitivity of CRCs to 5-fluorouracil through G1 arrest. The mechanism by which PAK1 induced cancer growth might involve activation of JNK as well as downregulation of PTEN. Targeting PAK1 may represent a novel treatment strategy for developing novel chemotherapeutic agents.