Dunlapadams2669

Bone metastasis is the major cause of morbidity and mortality in patients with prostate cancer (PCa). However, the underlying mechanism of bone-specific metastasis remain vague. Recently, with the deep research of N6-methyladenine (m6A) mRNA methylation, many studies directly focus on the role of m6A modification in human diseases, especially in cancers. Here we found that methyltransferase-like 3 (METTL3) expression is higher in PCa than in normal prostate tissues, especially in PCa with bone metastasis. High METTL3 expression was positively correlated with advanced progression and a poor prognosis of PCa. Functional assays demonstrated that METTL3 regulates the expression of Integrin β1 (ITGB1) through m6A-HuR-dependent mechanism, which affects the binding of ITGB1 to Collagen I and tumor cell motility, so as to promote the bone metastasis of PCa. The findings of this study reveal a novel mechanism of PCa osteotropism and suggest METTL3 as a therapeutic target for PCa bone metastasis. AJCR Copyright © 2020.Cancer metastasis is a significant challenge in colorectal cancer (CRC) therapy. SET and MYND domain-containing protein 2 (SMYD2) is highly expressed in multiple cancers but is rarely studied in CRC. This study aims to identify whether abnormal expression of SMYD2 is associated with cancer metastasis in CRC. In this study, we demonstrated that SMYD2 not only promoted cell proliferation but also increased the metastatic ability of CRC. The expression of adenomatous polyposis coli 2 (APC2), an inhibitor of the Wnt/β-catenin pathway, was suppressed by SMYD2 overexpression. Overexpression of SMYD2 activated the Wnt/β-catenin pathway and then induced the epithelial-mesenchymal transition (EMT) program in CRC. Mechanistically, low APC2 expression in CRC cells was due to SMYD2-mediated DNA methylation modification. This modification might require synergism with DNMT1. In summary, our study provides new insights into SMYD2-related transcriptional regulation patterns and indicates that SMYD2 could be a potential therapeutic target for CRC patients. AJCR Copyright © 2020.Apatinib, a VEGFR2 receptor tyrosine kinase inhibitor, showed survival benefits in Asian patients with heavily pretreated advanced gastric cancer. However, the adverse event (AEs) profile of apatinib has limited its use. Dosing schedules are used to alleviate toxicities despite no supportive evidence. This study aimed to analyze the toxicity and effectiveness of apatinib alone, especially with different dosing strategies in advanced gastric cancer patients under a real-world setting. Data from the subpopulation of patients who failed ≥2 chemotherapy regimens enrolled in the AHEAD-G202 trial were analyzed. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Totally 120 patients were included into three groups by the initial daily doses 43 (35.8%) patients in the low-dose (250 mg) group, 67 (55.8%) patients in the mid-dose (425 mg to 500 mg) group, and 10 (8.3%) patients in the high-dose (675 to 850 mg) group. Grade 3/4 treatment-emergent AEs were infrequent ( less then 5%), with the most commonly reported grade 3/4 AEs being hand-foot syndrome (4.2%), hypertension (4.2%,), fatigue (4.2%), and difficulty in swallowing (4.2%) which gradually decreased among the high-, mid-, and low-dose groups. The median OS and PFS were 6.33 months (95% CI, 4.57-7.73) and 3.83 months (95% CI 1.40-4.20), respectively and were comparable among the three doses groups. We found heavily pretreated advanced gastric cancer patients can tolerate and benefit from lower-doses of apatinib therapy. The lower initial daily dosing strategy represents an alternative approach for optimizing apatinib dosing in clinical practice. AJCR Copyright © 2020.The associations between different combinations of metabolic abnormalities and the risk of all and site-specific cancers remain unclear. We aimed to estimate the association and interplay between serum cholesterol, glycemic status and risk of cancer in the China Cardiometabolic Disease and Cancer Cohort (4C)-Study, a nationwide, multicenter, prospective, population-based study. The investigation was performed in 137,884 participants during 2014-2016. Incident cancer was defined as the first occurrence of any type cancer of all sites during follow-up. After 510,164 person-years of follow-up, 1,710 were detected as incident cancer after exclusion of participants diagnosed as cancer within 6 months from baseline. A relatively low level of LDL cholesterol ( less then 100 mg/dl) was related to a significant higher risk of incident cancer [1.20 (1.08-1.34); P=0.0007]. Diabetic individuals have a significantly higher risk of incident cancer, especially those with poorly glycemic control. Diabetic participants with both lower levels of LDL cholesterol and poorly glycemic control were at a higher risk of incident cancer [1.42 (1.10-1.81); P=0.006]. Our study showed a positive association of cancer risk with low-level LDL cholesterol and diabetes and found that participants with both lower levels of LDL cholesterol and poorly controlled diabetes had the higher risk of incident cancer, which indicates the compelling need of achieving glycemic control goal and maintaining appropriate LDL cholesterol levels. AJCR Copyright © 2020.miR-590-3p acts as a tumor suppressor in glioblastoma multiform, medulloblastoma, hepatocellular carcinoma, and nephroblastoma. Here, we studied the role of miR-590-3p in triple-negative breast cancer (TNBC). The miR-590-3p levels in TNBC specimens were significantly lower than those in non-TNBC specimens. Overexpression of miR-590-3p significantly inhibited migration and invasion of TNBC cells and lung metastasis in vivo. Interestingly, miR-590-3p decreased the Slug mRNA and protein levels in TNBC cells, and luciferase reporter assay showed that miR-590-3p directly targeted 3'-UTR of Slug in TNBC cells. Importantly, overexpression of Slug reversed the inhibitory effect of miR-590-3p on migration and invasion of TNBC cells. Idasanutlin Taken together, miR-590-3p inhibits TNBC migration and invasion by directly targeting Slug, suggesting a potential therapeutic effect of miR-590-3p for TNBC. AJCR Copyright © 2020.