Fascin Regulates the Hippo Pathway and Is Important for Melanoma Development.

BACKGROUND/AIM: Fascin, an actin-bundling protein, plays an essential role in cancer metastasis. The Hippo pathway is critical for carcinogenesis and cancer stem cell self-renewal. Mammalian STE20-like kinase (MST) is a core component of the Hippo pathway. However, whether fascin and MST2 affect melanoma remain largely unknown. This study aimed to investigate the role of fascin and MST2 in melanoma development. MATERIALS AND METHODS: Surgically excised skin melanomas and the adjacent non-tumorous skin tissue from 30 cases were analyzed using immunohistochemistry for fascin and MST2. The melanoma cell line WM793 was employed for fascin and MST2 knock-down followed by western blotting, and melanoma xenografting in BALB/c mice. RESULTS: Immunohistochemistry revealed increased expression of fascin and decreased expression of MST2 in melanoma. The reverse correlation of fascin and MST2 was statistically significant. Fascin siRNA upregulated MST2 expression; however, MST2 siRNA did not significantly affect fascin expression in the WM793. WM793 xenografting followed by fascin knock-down inhibited tumor growth significantly in the animal study. CONCLUSION: Fascin is a regulator of the Hippo pathway and plays an important role in melanoma development. Therefore, fascin could be a potential therapeutic target for melanoma.

Peripheral blood BRCA1 methylation profiling to predict familial ovarian cancer.

OBJECTIVE: Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with BRCA1/2 mutations (BRCAm). In this study, we investigated BRCA1 methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without BRCA1/2 mutations (BRCAwt). METHODS: Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(-)] and 52 ovarian cancer patients, we examined BRCA1 promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the BRCA1 promoter methylation according to BRCA1/2 germline mutations. RESULTS: BRCA1 methylation was more prevalent in the BRCAm cancer(-) group than in the BRCAwt cancer(-) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(-) group, BRCA1 methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(-) group with an FHC (p=0.001 and p<0.001, respectively). CONCLUSION: Our data suggest a predictive role of BRCA1 methylation profile for ovarian cancer in those without a history of cancer but with an FHC. BRCA1 methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(-) status with FHC.

Extracellular Acidity-mediated Expression of cPLA2γ Confers Resistance in Gastric Cancer Cells.

BACKGROUND/AIM: Extracellular acidity, a characteristic of solid tumors, has been proposed to be a critical factor for aggravating tumor malignancy and conferring resistance to therapeutics. Recently, acidity has been implicated in inflammatory responses, which are mediated through active lipid metabolites in various human tissues. In the present study, we investigated whether acidity can affect lipid-mediated signaling, and found that phospholipase A2 (PLA2) activity increased at acidic pH in SNU601 and AGS gastric carcinoma cell lines. MATERIALS AND METHODS: To identify the PLA2 isoform that is responsible for the acidity-induced activity, we assessed mRNA levels of cPLA2 isotypes through real-time qPCR, and protein levels through immunoblot assay in cells cultured in acidic medium. RESULTS: It was found that acidic pH conditions markedly elevated the PLA2γ expression. A gene interference study using specific siRNA of cPLA2γ suggested that expression of cPLA2γ in acidic culture conditions may be associated with protection of cancer cells in acidic environment, as shown by cell viability and clonogenic assays. In addition, expression of cPLA2γ appeared to confer cell resistance to anticancer drugs under acidic pH conditions. CONCLUSION: Acidity-induced cPLA2γ expression may exert protective effects by imparting resistance to the gastric cancer cells under acidic environment.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.

Double-balloon enteroscopy in elderly patients: is it safe and useful?

BACKGROUND/AIMS: Providers may be hesitant to perform double-balloon enteroscopy (DBE) in the elderly because the increased number of co-morbidities in this population poses a greater risk of complications resulting from sedation. There are limited data on the use of DBE in the elderly. Here, we assessed the safety and efficacy of DBE in the elderly compared to those in younger patients. METHODS: We retrospectively analyzed the medical records of 158 patients who underwent 218 DBEs. Patients were divided into an elderly group (age ≥65 years; mean 71.4±5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5±13.5; n=124; 177 DBEs). RESULTS: In both groups, the most common indication for DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%; P=0.002) were the most common finding in both groups, followed by tumors (30.8% vs. 14.1%; P=0.036). The elderly were more likely to receive interventional therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically significant. The therapeutic success rate of DBE was 100% in the elderly group compared to 87.5% in the younger group (P=0.536). The overall DBE complication rate was 1.8% overall, and this rate did not differ significantly between the groups (2.6% vs. 1.7%; P=0.548). CONCLUSIONS: DBE is safe and effective in the elderly, and has a high diagnostic yield and high therapeutic success rate.

Improved neural differentiation of human mesenchymal stem cells interfaced with carbon nanotube scaffolds.

AIM: The authors aimed to investigate the effect of carbon nanotube (CNT)-based extracellular environments on the neural differentiation of human mesenchymal stem cells (hMSCs) when combined with chemical inducers. MATERIALS & METHODS: CNT-based nanoscaffolds (linear CNT network patterns and CNT bulk network films) were prepared on solid substrates for hMSC culturing. After the hMSCs were differentiated in neural differentiation media for 2 weeks, the authors examined the neural differentiation of the hMSCs using immunocytochemistry and real-time PCR. RESULTS: The authors found that the linear CNT network patterns could effectively control the cell elongation and nuclear shape of hMSCs during the neural differentiation process, further enhancing neural gene expression compared with the bulk CNT-based films. Moreover, the CNT network films could significantly upregulate the gene expression of voltage-gated ion channels, which should be a key component for the neural activity of differentiated hMSCs. CONCLUSION: These findings suggest that CNT-based nanoscaffolds can be used as an excellent extracellular nano-/micro-environment for applications requiring effective neural differentiation of stem cells, such as regenerative medicine and tissue engineering.

Recurrence of coronary-subclavian steal syndrome after successful angioplasty of malfunctioning arteriovenous fistula.

We report a case of coronary-subclavian steal syndrome, which had been masked by a malfunctioning hemodialysis access vessel and then reappeared after a successful angioplasty of multiple stenoses in the arteriovenous fistula of the left arm in a 61-year-old man. This case suggests that coronary-subclavian steal syndrome should be considered before a coronary artery bypass grafting surgery using internal mammary artery conduit is done, especially when hemodialysis using the left arm vessels is expected.