PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear. METHODS: PFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial-mesenchymal transition (EMT) were detected by Western blot analysis. RESULTS: Compared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Our findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.

[Progress in studies on effects of extracellular matrix in occurrence of proliferative vitreoretinopathy].

It has been found that various extracellular matrix (ECM) probably play an important role in the occurrence of proliferative vitreoretinopathy (PVR), including structural proteins, adhesive proteins, anti-adhesive proteins, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP) Structural proteins, including collagen and elastic fiber family, are the major non-cellular components of PVR membrane, and could promote contraction of membrane. Adhesive proteins, including fibronectin, vitronectin, laminin, could promote adhesion between cells and ECM in PVR, they promote the attachment, migration and differentiation of retinal pigment epithelium (RPE). Anti-adhesive proteins, including thrombospondin-1, osteonectin, tenascin, could promote RPE migration and tissue remodeling of PVR, etc. MMPs and TIMPs could degrade some components of ECM, enhance permeability of blood vessel and promote neovascularization in PVR.

[Study on the setup of a new technique of tissue and cell culture for vitreous fluid of vitrectomy].

OBJECTIVE: To setup a new technique of tissue and cell culture for vitreous aspirates. METHODS: Experiment study. Specimens used for supporting new culture technique were selected based on random digit table. Thirty cases with rhegmatogenous retinal detachment (RRD) and forty-eight with proliferative diabetic retinopathy (PDR), which undergoing primary pars plana vitrectomy, were selected randomly and included in the study. After being antiphase stained with fluorescein-natrium (0.5%) and digested with hyaluronidase (10(5) U/L) combined with collagenase I (10(6) U/L) for removing vitreous gel, sediment of vitreous fluid after centrifugation were inoculated into standard culturing bottle with which polylysine (0.01%) was pre-set. The bottle which contained F12 medium with 30% fetal bovine serum was placed upside down for 24 hours and consecutively upside for 6 days. During which, F12 medium was replaced once in half volume, and cell growth along the edge of sedimentary membrane was observed at time of the 3rd and the 6th day after upside culture. RESULTS: Under condition of pre-setting by polylysine (0.01%) and being placed upside down for 24 hours, pieces from vitreous fluids could adhere to the bottom of bottle in a way of semi-xerosis with adherence rate of 100% (78/78). No bacteria, fungus and mycoplasma contamination was found within 7 days. Antiphase stained with fluorescein-natrium (0.5%) and digested with hyaluronidase (10(5) U/L) combined with collagenase I (10(6) U/L) for 30 minutes, vitreous gel in 78 specimens could be digested (78/78). Cell emigration could be found in edge area of some pieces of vitreous fluid and cell growth as well as proliferation was shown. In 30 specimens of RRD, cell growth rate were 43.33% (13/30). In 48 specimens of PDR, cell growth rate were 37.50% (18/48). Concerning PDR phase V (PDR-V), cell growth rate reach 41.67% (10/24). CONCLUSIONS: Enzymolysis with upside down and semi-xerosis could ensure good adherence of membrane, moreover, no contamination and obvious cell growth could be found within short-term culture. These suggested that a new technique for judging viability of cell from proliferative membrane and predicting recurrent risk after surgery of proliferative ocular fundus disease could be expected.

Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma.

Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3'UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.

Type-specific detection of human papillomaviruses in Kazakh esophageal squamous cell carcinoma by genotyping both E6 and L1 genes with MALDI-TOF mass spectrometry.

BACKGROUND: Many studies have suggested a relationship between human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma (ESCC). However, findings are inconclusive, potentially because of geographic heterogeneity and variations in detection methods. OBJECTIVES: We sought to further investigate the prevalence of HPV with a new detection method, the MassARRAY Sequenom technique, in esophageal squamous cell carcinomas occurring in patients belonging to Kazakh populations in Xinjiang, China. STUDY DESIGN: In the present study, a novel genotyping method for detecting 30 HPV genotypes, specifically by genotyping both the HPV E6 and L1 genes with multiplex PCR using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS) was first adopted to evaluate HPV genotypes in 89 esophageal cancer samples and 49 matched adjacent normal esophageal tissues. RESULTS: Six HPV genotypes (HPV6, HPV16, HPV33, HPV39, HPV51, and HPV82) were present in at least 51.7% of the esophageal carcinoma tissues, which was significantly greater than 28.6% prevalence among controls (P < 0.05). HPV16 was the most common of all the genotypes investigated (HPV16 prevalence in carcinoma tissue: 49.4%; odds ratio 3.02, 95% confidence interval 1.39-6.53). HPV-positive ESCC patients were generally younger than HPV-negative patients (P = 0.04). In addition, HPV infection was more common in cases of well-differentiated and shallower invasive depth. CONCLUSIONS: Based on this new detection method, our findings reiterate the possibility that HPV infection (especially HPV16) may be involved in the etiology of esophageal carcinoma in the Kazakh populations and that HPV E6 gene positivity may be associated with prognosis of patients.

Epidemiology of hospitalized pediatric glaucoma patients in Beijing Tongren Hospital.

BACKGROUND: No population-based assessment of the prevalence and incidence of pediatric glaucoma in China are available. Here we describe the spectrum of hospitalized pediatric glaucoma patients in Beijing Tongren Hospital in China. METHODS: We reviewed the charts of pediatric patients, from birth to 18 years old, with a discharge diagnosis of glaucoma in Beijing Tongren Hospital, from 2002 to 2008. All children were admitted for anti-glaucoma surgery, treating the sequelae of the glaucoma, or managing postoperative complications. We evaluated the demographic characteristics and the proportion of different glaucoma subtypes. RESULTS: Pediatric patients (n = 1452) accounted for 12.91% of the total glaucoma in-patients from 2002 to 2008, and at last data of pediatric glaucoma were presented for 1055 children who came from 28 provinces, municipalities and autonomous regions in China. Boys were more common in all subtypes and at all ages, with a total ratio of boys to girls of 2.32:1. Congenital glaucoma was the most common subtype, accounting for 46.07% in all patients and accounting for 69.95% in children under 3 years of age. The median presenting age of congenital glaucoma patients was 2 years. Patients with traumatic glaucoma were the second most common group (n = 128, 12.13%), and presented at older age (the median presenting age was 11 years). The majority of traumatic glaucoma occurred in children between 10 and 15 years of age (n = 72, 56.25%). Aphakic glaucoma was the third most common (9.19%) subtype. CONCLUSIONS: Congenital glaucoma is the most prevalent glaucoma subtype in hospitalized pediatric patients in Beijing Tongren Hospital. The prevention and treatment of traumatic glaucoma can reduce the incidence of visual damage in developing countries. Close follow-up for glaucoma is important after pediatric cataract surgery.