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To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

Using molecular beam epitaxy, we prepared seven p-type AlGaN samples of ~25% in Al content, including six samples with Mg-doped/un-doped AlGaN alternating-layer structures of different layer-thickness combinations, for comparing their p-type performances. Lower sheet resistance and higher effective hole mobility are obtained in a layer-structured sample, when compared with the reference sample of uniform Mg doping. The improved p-type performance in a layer-structured sample is attributed to the diffusion of holes generated in an Mg-doped layer into the neighboring un-doped layers, in which hole mobility is significantly higher because of weak ionized impurity scattering. Among the layer-structured samples, that of 6/4 nm in Mg-doped/un-doped thickness results in the lowest sheet resistance (the highest effective hole mobility), which is 4.83 times lower (4.57 times higher) when compared with the sample of uniform doping. The effects of the Mg-doped/un-doped layer structure on p-type performance in AlGaN and GaN are compared.

Endoscopic retrograde cholangiopancreatography (ERCP) is a high-risk procedure with a significantly high rate of complications, such as pancreatitis, bleeding, perforation, and infection. Pancreatitis is the most common post-ERCP complication with an incidence of approximately 3.5%. Although perforation is a rare complication with an incidence of 0.1–0.6%, it may be associated with a high rate of mortality of 1.0–1.5%. Here, we report a rare case of ERCP-induced double iatrogenic perforations in the duodenum and colon complicated by an intra-abdominal abscess. The post-ERCP perforation was successfully sealed using fibrin glue (Tisseel). The intra-abdominal abscess was treated with a computed tomography-guided pigtail drainage; however, the pigtail spontaneously migrated and perforated the ascending colon. The pigtail was removed, and closure of the colon perforation was successfully achieved with endoscopic clipping. Tisseel spray can be a treatment option for post-ERCP perforations. Careful consideration of procedural complications, early detection of perforations, and prompt treatment can be life-saving.

Background Radiotherapy is the standard treatment for glioblastoma (GBM). However, radioresistance of GBM cells leads to recurrence and poor patient prognosis. Recent studies suggest that secretion factors have important roles in radioresistance of tumor cells. This study aims to determine whether Rab27b, a small GTPase involved in secretory vesicle trafficking, plays a role in radioresistance of GBM. Methods Microarray analysis, cell viability analysis, apoptosis assay, immunostaining, and in vivo experiments were performed to assess the effect of Rab27b on radioresistance of GBM. We further investigated paracrine effects mediated by Rab27b after X-ray irradiation using coculture systems of glioma cell lines. Results Rab27b was specifically upregulated in irradiated U87MG cells. Furthermore, Rab27b knockdown decreased the proliferation of GBM cells after irradiation. Knockdown of Rab27b in U87MG cells combined with radiation treatment suppressed orthotopic tumor growth in the mouse brain and prolonged the survival of recipient mice. Interestingly, the co-upregulation of Rab27b and epiregulin (EREG), a member of the epidermal growth factor (EGF) family, correlated with radioresistance in glioma cell lines. Additionally, EREG, which was secreted from U87MG cells via Rab27b-mediated mechanism, activated EGF receptor and contributed to H4 cell proliferation in a paracrine manner. Conclusions Our results show that Rab27b mediates the radioresistance of highly malignant GBM cells. Rab27b promotes the proliferation of adjacent cells through EREG-mediated paracrine signaling after irradiation. Thus, the Rab27b-EREG pathway is a novel potential target to improve the efficacy of radiotherapy in GBM.

BACKGROUND AND AIM Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P

Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg–Gly–Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5- and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy., Video abstract

Radiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of &lambda, carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism. CGN treatment decreased viability in irradiated cancer cells and enhanced reactive oxygen species accumulation, apoptosis, and polyploid formation. Additionally, CGN suppressed radiation-induced chemoinvasion and invasive growth in 3D lrECM culture. We also screened target molecules using a gene expression microarray analysis and focused on Rac GTPase-activating protein 1 (RacGAP1). Protein expression of RacGAP1 was upregulated in several cancer cell lines after radiation, which was significantly suppressed by CGN treatment. Knockdown of RacGAP1 decreased cell viability and invasiveness after radiation. Overexpression of RacGAP1 partially rescued CGN cytotoxicity. In a mouse xenograft model, local irradiation followed by CGN treatment significantly decreased tumor growth and lung metastasis compared to either treatment alone. Taken together, these results suggest that CGN may enhance the effectiveness of radiation in cancer therapy by decreasing cancer cell viability and suppressing both radiation-induced invasive activity and distal metastasis through downregulating RacGAP1 expression.

By forming nanodisk (ND) structures on a blue-emitting InGaN/GaN quantum-well (QW) template, the QWs become close to the red-emitting quantum dots (QDs) and Ag nanoparticles (NPs) attached onto the sidewalls of the NDs such that Förster resonance energy transfer (FRET) and surface plasmon (SP) coupling can occur to enhance the efficiency of blue-to-red color conversion. With a larger ND height, more QWs are exposed to open air on the sidewall for more QD/Ag NP attachment through QD self-assembly and Ag NP drop casting such that the FRET and SP coupling effects, and hence the color conversion efficiency can be enhanced. A stronger FRET process leads to a longer QD photoluminescence (PL) decay time and a shorter QW PL decay time. It is shown that SP coupling can enhance the FRET efficiency.

Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression of ARL8B and BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis., Wu et al. discover a role for Arl8b-dependent lysosomal trafficking and exocytosis in promoting invasion and metastasis of breast cancer cells and tumours that survive irradiation treatment. These findings provide insights that may aid future strategies to improve radiotherapy outcome.

The plasmonic Dicke effect means a cooperative emission mechanism of multiple light emitters when they are simultaneously coupled with the same surface plasmon (SP) mode of a metal nanostructure to achieve a higher collective emission efficiency. Here, we compare the enhancements of emission efficiency among a series of SP-coupled InGaN/GaN quantum-well (QW) structures of different QW period numbers to show an emission behavior consistent with the plasmonic Dicke effect. The relative enhancement of overall emission efficiency increases with QW period number until it reaches a critical value, beyond which the enhancement starts to decrease. This critical QW period number corresponds to the effective depth range of the plasmonic Dicke effect in a multiple-QW system. It also represents an optimized QW structure for maximizing the SP coupling effect. Internal quantum efficiency and time-resolved photoluminescence are measured for comparing the enhanced emission efficiencies of blue and green QW structures with different QW period numbers through SP coupling induced by surface Ag nanoparticles.

Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells. Integrins are one of the cell surface receptors that regulate the communication between cells and their microenvironment. Several integrins are overexpressed in many types of cancer cells and the tumor microvasculature and function in the mediation of various cellular events. Therefore, the surface modification of nanomaterials with integrin-specific ligands not only increases their binding affinity to cancer cells but also enhances the cellular uptake of nanomaterials through the intracellular trafficking of integrins. Moreover, the integrin-specific ligands themselves interfere with cancer migration and invasion by interacting with integrins, and this finding provides a novel direction for new treatment approaches in cancer nanomedicine. This article reviews the integrin-specific ligands that have been used in cancer nanomedicine and provides an overview of the recent progress in cancer diagnostics and therapeutic strategies involving the use of integrin-targeted nanomaterials.

Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD), which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which showed positive results for CD3, CD45RO and LCA antibodies confirming the diagnosis of lymphoma. The endoscopic diagnosis of ulcerative colon T-cell lymphoma is frequently confused with inflammatory conditions of the large bowel such as CD, and tuberculosis colitis. Our study aims to emphasize the difficulty in differentiating this ulcerative form of colon T-cell lymphoma from the inflammatory bowel diseases and the importance of its differential diagnosis due to the much more aggressive clinical behavior of the T-cell lymphoma.

Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain.A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations.The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P 0.05).A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.

Background: The Taiwanese government has proposed a population-based colorectal tumor detection program for the average-risk population. This study's objectives were to understand the outcomes of these screening policies and to evaluate the effectiveness of the program. Methods: We compared two databases compiled in one medical center. The “policy-promoted cancer screening” (PPS) database was built on the basis of the policy of the Taiwan Bureau of National Health Insurance for cancer screening. The “health promotion service” (HPS) database was built to provide health check-ups for self-paid volunteers. Both the PPS and HPS databases employ the immunochemical fecal occult blood test (iFOBT) and colonoscopy for colorectal tumor screening using different strategies. A comparison of outcomes between the PPS and HPS included: (1) quality indicators—compliance rate, cecum reaching rate, and tumor detection rate; and (2) validity indicators—sensitivity, specificity, positive, and negative predictive values for detecting colorectal neoplasms. Results: A total of 10,563 and 1481 individuals were enrolled in PPS and HPS, respectively. Among quality indicators, there was no statistically significant difference in the cecum reaching rate between PPS and HPS. The compliance rates were 56.1% for PPS and 91.8% for HPS (p

Background: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs), but the risk factors for postoperative stricture have not been elucidated. The objective of this study was to identify and validate a predictor for post-RFA stenosis. Methods: We consecutively enrolled patients with flat-type ‘large’ (length no less than 3 cm extending no less than half the circumference of the esophagus), early ESCNs, treated with balloon-based RFA (12 J/cm2–clean–12 J/cm2 regimen). The tumor and technical factors for postoperative stricture were investigated and we validated the results externally with a society-based multicenter cohort using the same ablation regimen. Results: A total of 51 patients were enrolled (30 in the development set and 21 in the validation set). The complete remission rate at 12 months was 93%, and the rates of perforation and postoperative stenosis were 0% and 17%, respectively. Patients with post-RFA stenosis had a significantly larger longitudinal tumor size (mean 115 versus 61 mm, p = 0.003). There were no significant differences in age, body mass index, tumor circumferential extension, pretreatment histological grade, treatment efficacy or size of balloon catheter between the groups with or without stenosis. The optimal cut-off value was set as 9 cm to predict post-RFA stenosis by receiver operating characteristic curve [area under curve (AUC) = 0.881], which was then confirmed to be a reliable predictor by multivariate analysis (odds ratio, 12.7, 95% confidence interval, 1.18–136.28, p = 0.03) and have a good predictive performance in the validation set (AUC = 0.876). Conclusions: The most frequent adverse event of RFA was esophageal stenosis, for which the longitudinal tumor size was a significant predictive factor. Early intervention or prevention for stricture should be applied for those with long segment (⩾9 cm) ESCNs.

OBJECTIVE: Epiploic appendagitis (EA) is a rare cause of focal abdominal pain in otherwise healthy patients. It may mimic diverticulitis, appendicitis or mesenteric infarction on clinical manifestation. The diagnosis of EA is very infrequent due in part to low awareness by clinical physicians. The aim of this study was to review and describe the clinical presentation and computed tomography (CT) findings of EA. METHODS: Twenty-one patients (6 women and 15 men, average age 40 years [range 27–65 years]) were diagnosed with EA by CT between January 2006 and October 2009. The patients' medical records were retrospectively reviewed with regard to their socioeconomic data, characteristics of abdominal pain, associated symptoms, laboratory results, radiological findings and treatment. RESULTS: Abdominal pain was the leading symptom. The pain was localized in the left lower quadrant (17 patients, 81.0%), left middle abdomen (2 patients, 9.5%) and right lower quadrant (2 patients, 9.5%), respectively. Leukocytosis (white blood cell > 10 × 109/L) without left shift was found in 6 patients but all patients were afebrile. Characteristic CT findings of paracolonic oval hypodense fat tissue with thickened peritoneal ring and periappendageal fat stranding were all presented in 21 patients, but the central dot sign was presented in only 7 patients. They were all treated was conservative therapy. CONCLUSIONS: Epiploic appendagitis is the inflammatory response of an appendage to infarction or spontaneous venous thrombosis. A CT scan provides a definite diagnosis of epiploic appendagitis, thus avoiding unnecessary surgical intervention and antibiotics.

Radiotherapy is a standard treatment for many localized solid cancers. However, previous studies have shown that radiation may increase the invasive activity of cancer cells and potentially distant metastasis. Recently, lysosome exocytosis has been linked to cancer cell invasiveness and progression. In this study, we evaluate the role of lysosome exocytosis on invasive activity of breast cancer cells upon radiation.We used both human and murine breast cancer cell lines (MDA-MB-231 and 4T1). The cells were treated with a single radiation dose of 4 Gy. Cell invasive activity was measured by matrigel chemoinvasion assay. Lysosome exocytosis was quantified by fluorescein isothiocyanate conjugated dextran (FITC-dextran) intake assay, cell-surface lysosomal associated membrane protein 1 (LAMP1) expression and cellular lysosome distribution assay. To validate the lysosome function, lysosome inhibitors, bafilomycin A1 and chloroquine were used. Short hairpin RNA (shRNA) was used to knockdown ARL8B, which is a small GTPase protein that regulates lysosome distribution and exocytosis. The invasive activity and lysosome exocytosis of tested breast cancer cell lines were increased after radiation treatment. Treatment with lysosome inhibitor bafilomycin A1 or chloroquine decreased the invasive activity of cancer cells, with or without radiation treatment. The protein level of ARL8B increased in the lysosome fraction upon radiation. Down-regulation of ARL8B with shRNA led to a decrease in lysosome exocytosis with a concomitant inhibition radiation induced invasive activity of the breast cancer cells without affecting the basal invasiveness. In addition, overexpression of ARL8B increased the invasive activity of breast cancer cells, which was similar to the result obtained after radiation.In summary, radiation enhances lysosome exocytosis in breast cancer cells that can lead to their increased invasive activity. Our findings provide a novel mechanism to understand cancer invasion after radiotherapy and suggest novel approaches to counteract this undesirable effect of radiotherapy in the future. Citation Format: Ping-Hsiu Wu, Yasuhito Onodera, Amato J. Giaccia, Quynh-Thu Le, Hiroki Shirato, Jin-Min Nam. Radiation increases invasive activity of breast cancer cells via altering lysosome exocytosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3202.