IMPORTANCEThe role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. OBJECTIVE To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. EXPOSURES History of taking ACEIs or ARBs at the time of COVID-19 testing. MAIN OUTCOMES AND MEASURES Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive.RESULTS A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). CONCLUSIONS AND RELEVANCEThis study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.

Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. miRNAs are singlestranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3 0 -untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis. Mol Cancer Res; 9(7); 824-33. Ó2011 AACR.

Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors.