miR-29a-SIRT1-Wnt/ß-Catenin Axis Regulates Tumor Progression and Survival in Hepatocellular Carcinoma.

Sirtuin 1 (SIRT1) participates in the initiation and evolution of hepatocellular carcinoma (HCC). However, the specific mechanism of SIRT1 in HCC remains unclear. The mRNA expression of miR-29a in HCC were identified by qRT-PCR. miR-29a mimic and inhibitor were employed. The alteration of biological behavior was evaluated by Cell Counting Kit-8 (CCK8), clone formation, transwell and wound-healing assay. SIRT1 was verified to be a target gene which directly regulated by miR-29a. Luciferase reporter assay and co-IP were employed to evaluate the direct binding of miR-29a and SIRT1. Animal model was used to evaluate its function on tumor growth and metastasis in vivo. The relationship between miR-29a/SIRT1 and prognosis of HCC patients was analyzed. SIRT1 overexpression accompanied by low expression of miR-29a were detected in HCC which was negatively correlated, and associated with overall survival, vascular invasion and TNM stage. Up-regulation of miR-29a suppressed cell growth and motility. Deprivation of miR-29a expression led to opposite effect. The direct binding of miR-29a to SIRT1 was confirmed by luciferase reporter assay and co-IP. miR-29a repressed SIRT1, DKK2 and ß-catenin, but their expression was obviously elevated by miR-29a inhibitor. Animal model suggested miR-29a could reduce the expression of SIRT1, thereby inhibiting HCC growth and metastasis by inactivating Wnt/ß-catenin pathway. Low expression of miR-29a and high expression of SIRT1 predicted shorter survival time in HCC patients. miR-29a had the function of tumor suppressor which directly inhibited oncogenic SIRT1. The loss of miR-29a led to up-regulation of SIRT1, aggravate malignant transformation and poor prognosis of HCC.

Pathological underestimation and biomarkers concordance rates in breast cancer patients diagnosed with ductal carcinoma in situ at preoperative biopsy.

Ductal carcinoma in situ (DCIS) often upgrade to invasive breast cancer at surgery. The current study aimed to identify factors associated with pathological underestimation and evaluate concordance rates of biomarkers between biopsy and surgery. Patients diagnosed with DCIS at needle biopsy from 2009 to 2020 were retrospectively reviewed. Univariate and multivariate analyses were performed to identify factors associated with pathological underestimation. Concordance rates between paired biopsy samples and surgical specimens were evaluated. A total of 735 patients with pure DCIS at biopsy were included, and 392 patients (53.3%) underwent pathological underestimation at surgery. Multivariate analysis demonstrated that tumor size > 5.0 cm [odds ratio (OR) 1.79], MRI BI-RADS ≥ 5 categories (OR 2.03), and high nuclear grade (OR 2.01) were significantly associated with pathological underestimation. Concordance rates of ER, PR, HER2 status and Ki-67 between biopsy and surgery were 89.6%, 91.9%, 94.8%, and 76.4% in lesions without pathological underestimation, and were 86.4%, 93.2%, 98.2% and 76.3% for in situ components in lesions with pathological underestimation. Meanwhile, in situ components and invasive components at surgery had concordance rates of 92.9%, 93.8%, 97.4%, and 86.5% for those biomarkers, respectively. In conclusion, lesions diagnosed as DCIS at biopsy have a high rate of pathological underestimation, which was associated with larger tumor size, higher MRI BI-RADS category, and higher nuclear grade. High concordances were found in terms of ER, PR, and HER2 status evaluation between biopsy and surgery, regardless of the pathological underestimation.

Oct4 promotes cancer cell proliferation and migration and leads to poor prognosis associated with the survivin/STAT3 pathway in hepatocellular carcinoma.

Octamer­binding transcription factor 4 (Oct4) has been identified as a novel transcription factor associated with tumorigenesis, acquisition and maintenance of cancer stem cell characteristics and poor prognosis in tumors. However, the role of Oct4 in tumorigenesis and progression of hepatocellular carcinoma (HCC) has not yet been fully elucidated. In our present study, we observed that the Oct4 expression level was upregulated in HCC specimens as well as in different HCC cell lines. In in vitro experiments, decreased expression of Oct4 by shRNA inhibited the viability and mobility of HCC cells. Furthermore, the loss of Oct4 inhibited HCC cell malignant progression accompanied by downregulated expression of the survivin/signal transducer and activator of transcription 3 (STAT3) pathway. Liver cancer patients with high expression of Oct4 exhibited significantly shorter overall and disease­free survival. These findings demonstrated that Oct4 plays a vital role in the malignant progression of HCC cells through the survivin/STAT3 signaling pathway, and it may prove to be a novel biomarker associated with patient prognosis and survival.

Preparation of poly(L-lactic acid)-modified polypropylene mesh and its antiadhesion in experimental abdominal wall defect repair.

A new type of polypropylene (PP) hernia mesh, modified with poly(L-lactic acid) (PLLA), was developed and used to repair rat abdominal wall defect. The PP mesh was first treated with oxygen plasma and then grafted with PLLA in phosphorus pentachloride (PCl5 ) solution in dichloride methane. The water contact angle changed during the procedure, and the coverage percentage of PLLA on the PP was about 80%. ATR-FTIR spectroscopy measurements showed the existence of carbonyl group absorption peak (1756.9 cm(-1) ), and atomic force microscope and scanning electron microscope morphological observation indicated that the surface of the PP mesh was covered with PLLA graft. X-ray photoelectron spectroscopy spectra was used to probe chemical group changes and confirmed that the PLLA was grafted onto the PP. A total of 36 Sprague-Dawley rats were randomly divided into six groups, and they received either modified meshes (experimental groups) or PP meshes (control groups) to repair abdominal wall defects. All animals survived until the end of the experiment. Rats in each group were dissected after the operation (after 1 week, 2 weeks, and 1 month, respectively), and the adhesion effects were evaluated. Sections of the mesh parietal peritoneum overlap were examined histologically and graded for inflammation reaction. Compared with the control groups, the experimental groups showed a better ability to resist peritoneal cavity adhesions (P < 0.05), and there was no increase in inflammation formation (P > 0.05). This new type of PLLA-modified PP mesh displayed an additional property of antiadhesion in animal abdominal wall defect repair.