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      Apolipoprotein A1 and B as risk factors for development of intraocular metastasis in patients with breast cancer

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          Abstract

          Objective: Breast cancer is the most common primary lesion resulting in intraocular metastasis (IOM). In this study, we investigated the differences between breast cancer patients with and without IOM, and clarified the risk factors for IOM in patients with breast cancer.

          Methods: A total of 2,381 patients with breast cancer were included in this study from January 2005 to December 2017. The chi-square test and Student’s t-test were applied to evaluate differences between the IOM and non-IOM (NIOM) groups. Risk factors were calculated using binary logistic regression analysis. Receiver operating curve (ROC) analysis was used to assess the diagnostic value of IOM in patients with breast cancer.

          Results: The IOM incidence in patients with breast cancer was 1.35%. No significant differences were detected in age, gender, menopausal status, or histopathology between the IOM and NIOM groups. The IOM group had more axillary lymph node metastases, lower ApoA1 and higher ApoB, compared with the NIOM group. Binary logistic regression indicated that ApoA1 and ApoB were risk factors for IOM in breast cancer patients ( P-values<0.001 and P-values=0.005, respectively). ROC curve analysis revealed area under the curve values for ApoA1 and ApoB of 0.871 and 0.633, using cutoff values of 1.165 and 0.835 g/L, respectively. The sensitivity and specificity values for ApoA1 were 0.813 and 0.849, respectively, while those for ApoB were 0.813 and 0.481.

          Conclusion: Our data indicate that ApoA1 and ApoB are risk factors for IOM in patients with breast cancer and that ApoA1 is more reliable than ApoB at distinguishing IOM from NIOM in patients with breast cancer.

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          Genes that mediate breast cancer metastasis to the brain.

          The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.
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            Survey of 520 eyes with uveal metastases.

            The purpose of this investigation is to report the clinical features of patients with uveal metastases seen at a major ocular oncology center. A retrospective chart review was performed on all patients with uveal metastases evaluated at an ocular oncology outpatient facility over a 20-year period. To assess the systemic and ophthalmic features of uveal metastases. A total of 950 uveal metastases were diagnosed in 520 eyes of 420 consecutive patients. Of the 950 metastatic foci, the uveal involvement included iris in 90 (9%), ciliary body in 22 (2%), and choroid in 838 (88%). The total number of uveal metastases per eye was 1 (71%) in 370 eyes, 2 (12%) in 63 eyes, and 3 or more (17%) in 87 eyes. The mean number of uveal metastases per eye was two (median, one). Iris metastases presented most often as a yellow-to-white solitary nodule in the inferior quadrant. Ciliary body metastases typically presented as a solitary, sessile, or dome-shaped yellow mass in the inferior quadrant, but were difficult to visualize directly. The choroidal metastases typically were yellow in color, plateau shaped, and associated with subretinal fluid. In the 479 eyes with choroidal metastases, the epicenter of the main tumor was found in the macular area in 59 eyes (12%), between the macula and equator in 383 eyes (80%), and anterior to the equator in 37 eyes (8%). The mean size of the main (largest) choroidal tumor in each eye was 9 mm in base and 3 mm in thickness. At the time of ocular diagnosis, 278 patients (66%) reported a history of a primary cancer and 142 patients (34%) had no history of a cancer. Subsequent evaluation of these 142 patients after the ocular diagnosis of uveal metastasis showed a primary tumor in the lung in 50 patients (35%), breast in 10 (7%), others in 9 (6%), and no primary site was found in 73 patients (51%). Nearly half of the patients with no known primary site eventually died of diffuse metastatic disease. In the entire group of 420 patients, the uveal metastasis came from a primary cancer of the breast in 196 (47%), lung in 90 (21%), gastrointestinal tract in 18 (4%), kidney in 9 (2%), skin in 9 (2%), prostate in 9 (2%), and other cancers in 16 (4%). In 73 cases (17%), the primary site was never established despite systemic evaluation by medical oncologists. Iris, ciliary body, and choroidal metastases have typical clinical features that should suggest the diagnosis. The choroid is the most common site for uveal metastases, and the tumors occur most often in the posterior pole of the eye with an average of two tumors per eye. Approximately one third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung cancers represent more than two thirds of the primary tumor sites.
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              Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium.

              Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IkappaB kinase-dependent nuclear factor-kappaB activation pathway. H. pylori-mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                CMAR
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                09 April 2019
                2019
                : 11
                : 2881-2888
                Affiliations
                [1 ]Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute , Nanchang, Jiangxi 330006, People’s Republic of China
                Author notes
                Correspondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute , 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi330006, People’s Republic of ChinaEmail freebee99@ 123456163.com
                [*]

                These authors contributed equally to this work 

                Article
                191352
                10.2147/CMAR.S191352
                6497843
                31114339
                2a94ec3b-9e25-4cba-a98f-594915dd03af
                © 2019 Liu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 October 2018
                : 17 January 2019
                Page count
                Figures: 2, Tables: 5, References: 52, Pages: 8
                Categories
                Original Research

                Oncology & Radiotherapy
                breast cancer,intraocular metastases,apolipoprotein a1,apolipoprotein b

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