A novel tissue-engineered corneal epithelium based on ultra-thin amniotic membrane and mesenchymal stem cells.

Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin-eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype.

What Causes Death in Esophageal Cancer Patients Other Than the Cancer Itself: A Large Population-Based Analysis.

Background: Researches on noncancer causes of death in patients with esophageal cancer (EC) are not in-depth. The objective of this paper is to broadly and deeply explore the causes of death in patients with EC, especially noncancer causes. Methods: Information about the demographics, tumor-related characteristics, and causes of death of patients with EC who met the inclusion criteria were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Calculated standardized mortality ratio (SMR) for all causes of death at different follow-up times and performed subgroup analyses. Results: In total, 63,560 patients with EC were retrieved from the public database. And 52,503 died during the follow-up period. Most deaths were due to EC itself within 5 years after diagnosis, but over 10 years, 59% EC patients died from noncancer causes. Cardiovascular disease was the major noncancer cause of death in patients with EC, accounting for 43%. Suicide and self-injury (2%) of EC patients should not be ignored. During the 1-year follow-up period, patients with EC had statistically highest risk of death from septicemia (SMR: 7.61; 95% CI: 6.38-9.00). Within more than 10 years after EC diagnosis, more and more patients died from chronic obstructive pulmonary disease (SMR: 2.38; 95% CI: 1.79-3.10). Conclusions: Although most patients with EC still died from the cancer itself, the role of noncancer causes of death should not be underestimated. These prompt clinicians to pay more attention to the risk of death caused by these noncancer causes, which can provide relevant measures in advance to intervene.

Taxus wallichiana var. chinensis (Pilg.) Florin Aqueous Extract Suppresses the Proliferation and Metastasis in Lung Carcinoma via JAK/STAT3 Signaling Pathway.

As one of the most common neoplasms globally, lung cancer (LC) is the leading cause of cancer-related mortality. Recurrence and metastasis negatively influencing therapeutic efficacy and overall survival demand new strategies in LC treatment. The advantages of TCM are increasingly highlighted. In this study, we obtained the major chemical components and their ratios in the aqueous extract of Taxus wallichiana var. chinensis (Pilg.) Florin (AETW) by UPLC-Q/TOF-MS/MS detection. The CCK-8 assay revealed that AETW could selectively inhibit the growth of A549 and HCC827 cells in a dose-dependent manner with little effect on normal human lung cells. Moreover, both in vitro and in vivo experiments showed that AETW was able to suppress the capacities of cell migration and invasion and downregulate the EMT and the JAK/STAT3 signaling pathway. To further probe into the molecular mechanism, the overexpression of STAT3 was performed into LC cells with AETW treatment, which counteracted the inhibitory effect on malignant behaviors of A549 and HCC827 cells with the decline in the expressions of p-JAK and p-STAT3. Taken together, we propose that AETW may inhibit the proliferation and metastasis by inactivating the JAK/STAT3 axis.

Incidence, prognosis and nomograms of breast cancer with bone metastases at initial diagnosis: a large population-based study.

BACKGROUND: Bone is the most common metastatic site for breast cancer, and patients' condition will deteriorate when it occurs. METHODS: We performed a retrospective analysis on 6482 breast cancer patients with bone metastases (BCBM), who were selected from the Surveillance, Epidemiology, and End Result (SEER) 18 registry database. The optimal age cut-points were generated by using the X-tile software. By using Cox regression, we selected independent prognostic factors from 21 variables, and plotted a visual nomogram to predict the probability of surviving to the median survival time. We also diagrammed a competing risk nomogram on the basis of competitive risk model. RESULTS: Compared with other three common metastatic sites, the incidence of bone metastasis was the highest for patients with breast cancer. The incidence of BCBM peaked around the age of 60, and a large majority of patients were between the ages of 50 and 70. The survival rate decreased with age, and the median survival time was about 19 months. Factors of age, race, marital status, grade, human epidermal growth factor receptor-2 (HER2) receptor, hormone receptor, concurrent brain metastasis, concurrent liver metastasis, concurrent lung metastasis, surgery and chemotherapy are strongly related to the prognosis of patients with BCBM. It was revealed that the C-index of the nomogram was 0.72 and the calibration curves showed good agreement between the nomogram prediction and actual observation. CONCLUSION: Our practical nomograms provide a visual and user-friendly tool in the risk evaluation and prognostic prediction for breast cancer patients with bone metastases.

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors.

Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4'-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

A population-based study: how to identify high-risk T1 gastric cancer patients?

In T1 gastric cancer (GC), lymph nodes metastasis (LNM) is considered as a significant prognostic predictor and closely associated with following therapeutic approaches as well as distant metastasis (DM). This study aimed to not only seek risk factors of LNM and DM but also unpack the prognosis in T1 GC patients. We performed a retrospective study enrolling 5547 patients in T1 GC from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression models were produced to recognize independent risk factors of LNM and DM. Cox regression analyses were performed to identify important prognostic factors of overall survival (OS). Cancer-specific cumulative incidence was plotted by cumulative incidence function. Three nomograms of LNM, DM and OS were established and validated by receiver operating characteristic (ROC) and calibration curves to evaluate discrimination and accuracy. Decision curve analysis (DCA), clinical impact curves (CIC) and subgroups based on risk scores were constructed to measure nomograms clinical utility. The area under the curve (AUC) of LNM nomogram and DM nomogram were 0.735 and 0.896, respectively. OS nomogram was constructed and the corresponding C-index was 0.797. In conclusion, our user-friendly nomograms, which aimed to predict LNM, DM and OS in T1 gastric cancer patients, have shown high efficiency of discrimination and accuracy. These useful and visual tools may have advantageous clinical utility to identify high-risk T1 gastric patients and help clinicians to draw up an individual therapeutic strategy.

Risk of Second Primary Malignancies in Colon Cancer Patients Treated With Colectomy.

Background: Second primary malignancy (SPM) attracts a growing attention. However, the clinical features of colon cancer (CC) survivors with SPMs are not clear and could help guide clinicians to develop a better surveillance strategy. Methods: We reviewed 56,930 CC survivors treated with colectomy from the Surveillance, Epidemiology, and End Results (SEER) database during 1998-2011. Competing risk models and nomograms were conducted for predicting the risk of occurring SPMs. The clinical utility of the models was measured by decision curve analysis (DCA) using net benefit approaches. Results: Five thousand thirteen (17.1%) of male patients developed SPMs and sites of SPMs included prostate (32.2%), lung and bronchus (11.6%), urinary bladder and kidney (10.8%), colon (10.0%), and melanoma of the skin (3.9%), while 3,592 (13.0%) of female patients occurred SPMs and sites of SPMs involved breast (25.8%), lung and bronchus (13.6%), colon (11.6%), uterus (8.2%), urinary bladder, and kidney (5.6%). Survivors with a second carcinoma of lung and bronchus showed the worst prognosis. Older age increased the risk of SPMs in both male (Subdistribution hazard ratio =2.85 [95% confidence interval = 2.53-3.21]) and female (1.80 [1.59-2.04]) survivors, especially for the risk of a second prostate carcinoma in male (5.33 [4.03-7.03]). Compared with white race, black male survivors remained at higher risk to develop the second prostate carcinoma (1.98 [1.74-2.26]). Competing-risk nomograms for CC survivors were established to help clinicians predict the probabilities of overall SPMs and prostate carcinoma. Validation of nomograms showed good discrimination and accuracy, and DCAs revealed the clinical effectiveness. Conclusions: We profiled the clinical characteristics of a large population-based cohort of CC survivors with SPMs. These features may improve future follow-up management, especially for the surveillance of second prostate cancer in men and second breast cancer in women.