Covering the Cover

Background/Aims: Endoscopic submucosal dissection has been widely accepted. At present, the number of antiplatelet (APT) users has been growing. Moreover, because of high risks of thromboembolism, some patients need to continuously receive APT agents. The relationship between hemorrhage and continuous therapy with low-dose aspirin (LDA) remains controversial. Materials and Methods: A systematic search was conducted; studies were screened out- if data of no-anticoagulant/APT drugs use and interrupted and continued-LDA use were reported separately. The Newcastle-scale was chosen to assess the quality of the included studies. Review Manager 5.2 was used for quality assessment statistical analysis, and the odd ratio (OR) and 95% confidence interval (CI) were calculated. Results: Pooled data suggested a significantly higher bleeding ratio in the LDA-continued group compared to both the LDA-interrupted group (OR=2.05, 95% CI=1.05-3.99) and no-anticoagulant/APT group (OR=2.89, 95% CI=1.86-4.47). However, the LDA-interrupted group did not differ significantly from the no-anticoagulant/APT group. The en bloc resection rates of the LDA-continued group versus the LDA-interrupted group, the LDAcontinued group versus no-anticoagulant/APT group, and the LDA-interrupted group versus the no-anticoagulant/APT group were similar (OR=0.82, 95% CI=0.21-3.24, p=0.78; OR=0.80, 95% CI=0.24-2.65, p=0.71; OR=1.41, 95% CI=0.38-5.24, p=0.60, respectively). Conclusion: There is an extremely high ratio of bleeding in the LDA-continued group compared to both the LDA-interrupted group and no-anticoagulant/APT group. All groups had similar ratios of en bloc resection

Apatinib has anti-tumor effects and induces autophagy in colon cancer cells

Objective(s): Apatinib recently has been used to treat patients with gastric cancer, but the function of apatinib in colon cancer remains unclear. This study was conducted to investigate the impacts of apatinib on the biological function and its potential mechanism of colon cancer cells in vitro. Materials and Methods:The effect of apatinib in colon cancer cells were detected by assessing cell viability, migration and invasion capabilities. Apoptosis cells and the cell cycle distribution of colon cancer cells were analyzed by flow cytometry. The potential mechanism was investigated via autophagy related proteins and pathways in vitro. Results: The proliferation, migration and invasion of colon cancer cells were inhibited when they were treated with different concentration of apatinib (20, 40 μM). When HCT116 and SW480 cells were treated with apatinib at the concentration of 20 μM, the apoptosis percentage were 3.7% and 5.8% respectively. As the drug concentration increased to 40μΜ, the the apoptosis percentage increased to 11.9% and 13.5%. Meanwhile, cell cycle was also altered. Furthermore, apatinib inhibited the expression of AKT-mTOR signaling pathway and increased the expression of LC3-Ⅱ. Conclusion: Apatinib can significantly inhibit the malignant phenotype of colon cancer cells, and it was involved in regulation of autophagy

Loss of CtIP disturbs homologous recombination repair and sensitizes breast cancer cells to PARP inhibitors

Breast cancer is one of the leading causes of death worldwide, and therefore, new and improved approaches for the treatment of breast cancer are desperately needed. CtIP (RBBP8) is a multifunctional protein that is involved in various cellular functions, including transcription, DNA replication, DNA repair and the G1 and G2 cell cycle checkpoints. CtIP plays an important role in homologous recombination repair by interacting with tumor suppressor protein BRCA1. Here, we analyzed the expression profile of CtIP by data mining using published microarray data sets. We found that CtIP expression is frequently decreased in breast cancer patients, and the patient group with low-expressing CtIP mRNA is associated with a significantly lower survival rate. The knockdown of CtIP in breast cancer MCF7 cells reduced Rad51 foci numbers and enhanced H2AX foci formation after f-irradiation, suggesting that deficiency of CtIP decreases homologous recombination repair and delays DNA double strand break repair. To explore the effect of CtIP on PARP inhibitor therapy for breast cancer, CtIP-depleted MCF7 cells were treated with PARP inhibitor olaparib (AZD2281) or veliparib (ABT-888). As in BRCA mutated cells, PARP inhibitors showed cytotoxicity to CtIP-depleted cells by preventing cells from repairing DNA damage, leading to decreased cell viability. Further, a xenograft tumor model in mice with MCF7 cells demonstrated significantly increased sensitivity towards PARP inhibition under CtIP deficiency. In summary, this study shows that low level of CtIP expression is associated with poor prognosis in breast cancer, and provides a rationale for establishing CtIP expression as a biomarker of PARP inhibitor response, and consequently offers novel therapeutic options for a significant subset of patients

Apatinib Promotes Apoptosis of Pancreatic Cancer Cells through Downregulation of Hypoxia-Inducible Factor-1α and Increased Levels of Reactive Oxygen Species

At present, apatinib is considered a new generation agent for the treatment of patients with gastric cancer. However, the effects of apatinib on pancreatic cancer have not been clarified. This study investigated the impact of apatinib on the biological function of pancreatic cancer cells and the potential mechanism involved in this process. Using the Cell Counting Kit-8 method, we confirmed that apatinib treatment inhibited cell proliferation in vitro. Moreover, the migration rate of pancreatic cells was inhibited. The effects of apatinib on apoptosis and cell cycle distribution of pancreatic carcinoma cells were detected by flow cytometry. The number of apoptotic cells was significantly increased, and the cell cycle was altered. Furthermore, we demonstrated that apatinib inhibited the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor, and markers of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway, which increased the levels of reactive oxygen species in vitro. Apatinib significantly inhibited the biological function of pancreatic cancer cells. It promoted apoptosis, downregulated the expression of HIF-1α, and increased the levels of reactive oxygen species

Multiscale skin imaging in vivo using optical coherence tomography

Optical coherence tomography (OCT) is a noninvasive high-resolution diagnostic imaging modality that plays an increasingly important role in dermatology. Diagnosis of skin diseases using OCT requires both cellular-level high resolution and large area skin coverage. In practice, however, there exists a trade-off between the achievable spatial resolutions and the transverse scanning range. In this study, we report a Micro-OCT (μOCT) system that is capable of providing three-dimensional images of the skin at multiple spatial scales with both cellular-level resolution (1-2 μm) mode and large area (∼ mm2) scanning mode. Specifically, in the cellular-level scanning mode, we achieve a transverse resolution of ∼1.5 μm and an axial resolution of 1.7 μm (n = 1.38) which enables the visualization of cellular-level skin microstructures. While in the large-area scanning mode, the system is capable of covering an en face imaging area reaching up to with a lateral resolution of ∼5.5 μm at a scanning speed of 60 K Alines/s. We experimentally verify the imaging capabilities of such a multiscale μOCT system including in vivo visualization of epidermal cells in the cellular-level scanning mode as well as the internal fingerprints and sweat gland ducts in the large area scanning mode. Micro-anatomical imaging at multiple spatial scales could provide comprehensive information of the skin that is valuable to disease diagnosis.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio

Evaluating micro-optical coherence tomography as a feasible imaging tool for pancreatic disease diagnosis

Pancreatic cancer is one of the leading causes of cancer mortality worldwide due to the lack of reliable tools for early diagnosis of this cancer. In this study, we evaluated the feasibility of micro-optical coherence tomography (μOCT) as an imaging tool for the diagnosis of pancreatic cancers. Specifically, we constructed a μOCT device that achieves a resolution of 1.67 ± 0.01 μm and 1.79 ± 0.01 μm in axial and lateral directions, respectively, and acquired three-dimensional μOCT images of mouse, rat, and human pancreatic specimens ex vivo. We compared the results of μOCT with those of the corresponding histology. In μOCT images of normal pancreatic specimens, the detailed cellular and subcellular-level pancreatic microstructures, e.g., the islet of Langerhans (IL), IL cell nuclei, blood vessels, and serous acini, could be clearly resolved in different cases. To the best of our knowledge, this study is the first to demonstrate that the cellular and subcellular structures of pancreatic tissues were identified using OCT. More importantly, we showed that these normal cellular-level structures were lost in μOCT images of cancerous specimens, demonstrating the feasibility of differentiating malignant lesions from normal tissues using μOCT. Moving forward, the development of an intraoperative imaging device may realize optical biopsies in vivo or real-time cellular-resolution examination of specimens from needle aspiration biopsies.Ministry of Education (MOE)Nanyang Technological UniversityNational Medical Research Council (NMRC)National Research Foundation (NRF)Accepted versionThis work was supported in part by the National Natural Science Foundation of China under Grant 61705184, the Fundamental Research Funds for the Central Universities (G2018KY0308), in part by the National Research Foundation of Singapore (NRF-CRP13-2014-05), in part by the Ministry of Education of Singapore (MOE2013-T2-2-107), in part by the National Medical Research Council of Singapore (NMRC/CBRG/0036/2013), and in part by the NTU-AIT-MUV Program in Advanced Biomedical Imaging (NAM/15005)

Feasibility evaluation of micro-optical coherence tomography (μOCT) for rapid brain tumor type and grade discriminations:μOCT images versus pathology

Background: Precise identification, discrimination and assessment of central nervous system (CNS) tumors is of critical importance to brain neoplasm treatment. Due to the complexity and limited resolutions of the existing diagnostic tools, however, it is difficult to identify the tumors and their boundaries precisely in clinical practice, and thus, the conventional way of brain neoplasm treatment relies mainly on the experiences of neurosurgeons to make resection decisions in the surgery process. The purpose of this study is to explore the potential of Micro-optical coherence tomography (μOCT) as an intraoperative diagnostic imaging tool for identifying and discriminating glioma and meningioma with their microstructure imaging ex vivo, which thus may help neurosurgeons to perform precise surgery with low costs and reduced burdens. Methods: Fresh glioma and meningioma samples were resected from patients, and then slices of such samples were excised and imaged instantly ex vivo with a lab-built μOCT, which achieves a spatial resolution of ~ 2.0 μm (μm). The acquired optical coherence tomography (OCT) images were pathologically evaluated and compared to their corresponding histology for both tumor type and tumor grade discriminations in different cases. Results: By using the lab-built μOCT, both the cross-sectional and en face images of glioma and meningioma were acquired ex vivo. Based upon the morphology results, both the glioma and meningioma types as well as the glioma grades were assessed and discriminated. Comparisons between OCT imaging results and histology showed that typical tissue microstructures of glioma and meningioma could be clearly identified and confirmed the type and grade discriminations with satisfactory accuracy. Conclusions: μOCT could provide high-resolution three-dimensional (3D) imaging of the glioma and meningioma tissue microstructures rapidly ex vivo. μOCT imaging results could help discriminate both tumor types and grades, which illustrates the potential of μOCT as an intraoperative diagnostic imaging tool to help neurosurgeons perform their surgery precisely in tumor treatment process.Published versio

Feasibility evaluation of micro-optical coherence tomography (μOCT) for rapid brain tumor type and grade discriminations : μOCT images versus pathology

Background: Precise identification, discrimination and assessment of central nervous system (CNS) tumors is of critical importance to brain neoplasm treatment. Due to the complexity and limited resolutions of the existing diagnostic tools, however, it is difficult to identify the tumors and their boundaries precisely in clinical practice, and thus, the conventional way of brain neoplasm treatment relies mainly on the experiences of neurosurgeons to make resection decisions in the surgery process. The purpose of this study is to explore the potential of Micro-optical coherence tomography (μOCT) as an intraoperative diagnostic imaging tool for identifying and discriminating glioma and meningioma with their microstructure imaging ex vivo, which thus may help neurosurgeons to perform precise surgery with low costs and reduced burdens. Methods: Fresh glioma and meningioma samples were resected from patients, and then slices of such samples were excised and imaged instantly ex vivo with a lab-built μOCT, which achieves a spatial resolution of ~ 2.0 μm (μm). The acquired optical coherence tomography (OCT) images were pathologically evaluated and compared to their corresponding histology for both tumor type and tumor grade discriminations in different cases. Results: By using the lab-built μOCT, both the cross-sectional and en face images of glioma and meningioma were acquired ex vivo. Based upon the morphology results, both the glioma and meningioma types as well as the glioma grades were assessed and discriminated. Comparisons between OCT imaging results and histology showed that typical tissue microstructures of glioma and meningioma could be clearly identified and confirmed the type and grade discriminations with satisfactory accuracy. Conclusions: μOCT could provide high-resolution three-dimensional (3D) imaging of the glioma and meningioma tissue microstructures rapidly ex vivo. μOCT imaging results could help discriminate both tumor types and grades, which illustrates the potential of μOCT as an intraoperative diagnostic imaging tool to help neurosurgeons perform their surgery precisely in tumor treatment process.Published versio