Water-Absorbing Bioadhesive Poly(Acrylic Acid)/Polyvinylpyrrolidone Complex Sponge for Hemostatic Agents.

BACKGROUND: Poly(acrylic acid) (PAA) is a water-soluble synthetic polymer with tissue-adhesive properties. When PAA is mixed with polyvinylpyrrolidone (PVP) in water, it forms a water-insoluble precipitate that neither swells nor adheres to tissues. METHODS AND RESULTS: We developed a novel solid/solution interface complexation method to obtain a water-swellable PAA/PVP complex. First, PAA solution was dried up in a vessel to form a film. The PAA film was then immersed in an aqueous PVP solution to obtain a highly swollen PAA/PVP hydrogel. Heat drying of the hydrogel yielded a transparent film, while freeze-drying the hydrogel provided a soft sponge. Both the PAA/PVP film and sponge could be re-swelled by water to obtain a bioadhesive gel. A relatively larger specific surface area of the sponge than that of the film led to a more rapid swelling and water absorption behavior and quick adhesion to tissues. The addition of hyaluronic acid (HA) improved the mechanical characteristics of the sponges. PAA/PVP/HA sponges had low cytotoxicity, and they exhibited high hemostatic efficiency in clinical studies after dialysis treatment or tooth extraction, even in patients on antithrombotic drugs. CONCLUSIONS: Such bioadhesive materials consisting of low-toxicity polymers have a high potential for use in medical hemostatic devices.

Preparation of a Bioadhesive Poly(Acrylic Acid)/Polyvinylpyrrolidone Complex Gel and Its Clinical Effect on Dental Hemostasis.

Poly(acrylic acid) (PAA) is a water-soluble synthetic polymer that exhibits bioadhesive properties and has been applied in various novel medical devices, such as drug-delivery carriers and hemostatic agents. PAA forms a water-insoluble complex when mixed with polyvinylpyrrolidone (PVP). If PAA and PVP are mixed in water, they form an aggregated precipitate, which neither swells nor adheres to tissues. The formation of the hydrophobic complex was caused by hydrophobic interactions between the main chains of both polymers aligned the same as a zipper. To hinder the zipper-like alignment of the polymer main chains, hyaluronic acid (HA), a macromolecular viscous polysaccharide, was added to the PVP solution prior to complex formation. When the initial concentration of PAA was lower than 0.05%, HA effectively prevented the aggregation of PAA/PVP complexes and resulted in a slightly clouded suspension. Freeze-drying of the mixture yielded a soft white sponge, which could immediately swell in water to form a highly bioadhesive hydrogel. The PAA/PVP complex prepared with HA exhibited high hemostatic efficiency in clinical studies, even in patients on antithrombotic drugs.

Differential expression of vascular endothelial growth factor in high- and low-metastasis cell lines of salivary gland adenoid cystic carcinoma.

We used high- (ACCM) and low- (ACC2) metastasis cell lines of human adenoid cystic carcinoma (ACC) as an experimental model to study metastatic mechanisms and compare their expression levels for angiogenic-related factor vascular endothelial growth factor (VEGF). By using a series of extensive analyses, hypoxia-inducible factor-1 (HIF-1) α-dependent VEGF expression levels were observed to be higher in ACCM cell lines, increasing the possible development of tumor metastasis, compared to ACC2 cell lines. Our findings provide the novel insight that HIF-1α-dependent VEGF overexpression under hypoxic conditions shows to some extent associations with the metastatic tendency of ACC cells and may function as a potential target for ACC therapy.

Aberrant expression of EZH2 is associated with pathological findings and P53 alteration.

AIM: Enhancer of zeste homolog-2 (EZH2) and B lymphoma Mo-MLV insertion region-1 homolog (BMI1) are members of the polycomb group of proteins, which function as transcriptional repressors through chromatin modification. EZH2 forms part of the polycomb repressive complex (PRC)-2, while BMI1 is a component of PRC1. Previous studies have shown that EZH2 is highly expressed in various type of cancers. Expression of EZH2 is reported to be regulated by the P53-E2F/retinoblastoma (RB)-related pathway, and a correlation between P53 mutation and EZH2 expression was recently found in breast cancer. Here, we examined the relationship between P53 and EZH2 in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Using immunohistochemistry, we investigated the expression of EZH2 and BMI1 in 99 surgically-resected OSCC and 34 epithelial dysplasia samples. We analyzed associations between aberrant expression of EZH2 and BMI1, and clinicopathological findings and patient outcome. P53 expression was also examined and analyzed in relation to EZH2 and BMI1 expression. RESULTS: EZH2 and BMI1 protein were up-regulated in OSCC tissues compared with epithelial dysplasia and normal epithelium. Aberrant EZH2 and BMI1 protein expression was observed in 32 and 59 of the 99 OSCC samples, respectively. Aberrant EZH2 and BMI1 expression was significantly associated with mode of invasion, but not with lymph node metastasis or survival rate. Aberrant EZH2 expression was associated with P53 alteration in OSCC tissue. Expression of EZH2 mRNA in SAS/neo cells, which have wild-type P53, was significantly lower than in SAS/mp53 cells that have a mutant P53 gene. CONCLUSION: P53 alteration may be involved in dysregulated EZH2 expression, and aberrant expression of EZH2 may play a role in carcinogenesis of OSCC.

microRNA expression profiles in oral squamous cell carcinoma.

microRNAs (miRNAs) are involved in cancer pathogenesis, apoptosis and cell growth, thereby functioning as both tumor suppressors and oncogenes. However, the expression patterns and roles of miRNAs in oral squamous cell carcinoma (OSCC) remain largely unknown. We hypothesized that oral cancer may have a unique miRNA profile, which in turn may play a critical role in oral cancer development, progression, diagnosis and prognosis. We, therefore, investigated the expression profiles of 29 OSCC tumors and 7 normal oral mucosal samples. The miRNA expression patterns in OSCC were examined by TaqMan-based microRNA assays. We were subsequently able to identify the candidates of cancer-related miRNAs through analysis of the miRNA expression profiles. In conclusion, OSCC tissues were shown to have a unique miRNA profile pattern when compared with that in normal tissues. The present study may provide useful information for further investigation of the functional roles of miRNAs in OSCC development, progression, diagnosis and prognosis.