Effect of naturally derived surgical hemostatic materials on the proliferation of A549 human lung adenocarcinoma cells.

Hemostatic materials are generally applied in surgical operations for cancer, but their effects on the growth and recurrence of tumors are unclear. Herein, three commonly used naturally derived hemostatic materials, gelatin sponge, Surgicel (oxidized regenerated cellulose), and biopaper (mixture of sodium hyaluronate and carboxymethyl chitosan), were cocultured with A549 human lung adenocarcinoma cells in vitro. Furthermore, the performance of hemostatic materials and the tumorigenicity of the materials with A549 â€‹cells were observed after subcutaneous implantation into BALB/c mice. The in vitro results showed that biopaper was dissolved quickly, with the highest cell numbers at 2 and 4 days of culture. Gelatin sponges retained their structure and elicited the least cell infiltration during the 2- to 10-day culture. Surgicel partially dissolved and supported cell growth over time. The in vivo results showed that biopaper degraded rapidly and elicited an acute Th1 lymphocyte reaction at 3 days after implantation, which was decreased at 7 days after implantation. The gelatin sponge resisted degradation and evoked a hybrid M1/M2 macrophage reaction at 7-21 days after implantation, and a protumor M2d subset was confirmed. Surgicel resisted early degradation and caused obvious antitumor M2a macrophage reactions. Mice subjected to subcutaneous implantation of A549 â€‹cells and hemostatic materials in the gelatin sponge group had the largest tumor volumes and the shortest overall survival (OS), while the Surgicel and the biopaper group had the smallest volumes and the longest OS. Therefore, although gelatin sponges exhibited cytotoxicity to A549 â€‹cells in vitro, they promoted the growth of A549 â€‹cells in vivo, which was related to chronic M2d macrophage reaction. Surgicel and biopaper inhibited A549 â€‹cell growth in vivo, which is associated with chronic M2a macrophage reaction or acute Th1 lymphocyte reaction.

Long Noncoding RNA H19 Participates in the Regulation of Adipose-Derived Stem Cells Cartilage Differentiation.

Adipose-derived stem cells (ADSCs) are multipotent and have received increasing attention for their applications in medicine. Cell-based therapies are optimal for diseases with loss or damage to tissues or organs. ADSCs and bone marrow mesenchymal stem cells (BMSCs) can differentiate into many cell lineages. Because of their advantages in accessibility and volume, ADSCs are regarded as a desirable alternative to BMSCs. In this study, we focused on the chondrocytic differentiation potential of ADSCs and the underlying mechanism. We found that the long noncoding RNA H19 plays an important role in this process. Overexpression of H19 in ADSCs induced differentiation towards chondrocytes. H19 is abundantly expressed during embryonic development and downregulated after birth, implying its regulatory role in determining cell fate. However, in our experiments, H19 exerted its regulatory function during cartilage differentiation of ADSCs through competing miRNA regulation of STAT2.

[Celecoxib induces apoptosis and inhibits angiogenesis in gastric cancer].

OBJECTIVE: The aim of this study was to explore the effect of celecoxib, a cyclooxygenase-2 inhibitor, on induction of apoptosis and inhibition of angiogenesis in gastric cancer. METHODS: Fifty nine gastric cancer patients were randomly divided into 2 groups: celecoxib group (n = 37) and control group (n = 22). The patients in the celecoxib group were treated orally with celecoxib 200 mg twice daily for 7 days before resection. The patients in the control group received surgical resection alone. Another group of 20 healthy subjects were recruited as normal control. The number of apoptotic tumor cells was measured by terminal deoxynucleotidyl transferse-mediated dUTP nick end labeling (TUNEL). The expression of COX-2, VEGF and the microvessel density (MVD) were evaluated by immunohistochemistry. RESULTS: The TUNEL results showed an increase of apoptosis in the tumor cells after celecoxib treatment in comparison with that in the control group (7.1% +/- 1.0% vs. 6.2% +/- 0.9%, P < 0.05). The expression level of COX-2 and VEGF in the gastric cancer tissues was significantly decreased in the celecoxib group compared with those in the control group (P < 0.05). Furthermore, MVD was also significantly lower in the celecoxib group when compared with that in the control group (30.48 +/- 5.02 vs. 38.98 +/- 4.58, P < 0.05). CONCLUSION: Oral intake of celecoxib can induce apoptosis and suppress angiogenesis in gastric cancer. It may become an effective agent in the treatment of gastric cancer.

[The role of hepatic stellate cells SSeCKS expression in liver fibrosis].

OBJECTIVE: To investigate the change and effect of SSeCKS (src suppressed c kinase substrates) in the activation of hepatic stellate cells (HSCs). METHODS: HSCs were isolated from normal rats, the change of SSeCKS mRNA expression on HSCs culture in vitro was determined using real-time PCR, protein level was determined by Western blot and immunofluorescence methods. A rat model of liver fibrosis was established. The expression and location of SSeCKS and alpha-SMA (alpha-smooth muscle actin) in liver tissues were detected by immunofluorescence methods. RESULTS: SSeCKS mRNA expression was low in freshly isolated HSCs cell and the expression increased in activated HSCs in vitro. In liver fibrosis tissue, the number of SSeCKS-positive cells was increased and these cells were distributed along the sinusoids which also contained alpha-SMA positive cells. CONCLUSION: The expression of SSeCKS was increased in activated HSCs in vitro. Therefore, SSeCKS may be involved in the liver inflammation and fibrosis.

The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis.

BACKGROUND: Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis. METHODS: Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 - 1.75, p< 0.00001, I2=26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 - 1.92, p< 0.00001, I2=66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 - 0.68, p< 0.00001, I2=44%), CSS (pooled HR = 0.54, 95% CI: 0.40 - 0.72, p< 0.00001, I2=11%) and DFS (pooled HR = 0.82, 95% CI: 0.71- 0.94,p=0.005, I2=29%). CONCLUSIONS: Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.

Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction.

The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.

Continuous low-dose-rate radiation of radionuclide phosphorus-32 for hemangiomas.

The study goal was to clarify the therapeutic effect and the absorbed dose of radionuclide phosphorus-32 for skin hemangiomas and the consequent risk of side effects in these patients. Phosphorus-32 is an ß emitter and is used for skin hemangioma treatment. In comparison with the few Gy per minute of the linear accelerators, the dose rate of phosphorus-32 for hemangiomas is much <1 Gy/hour; so, the latter is called low-dose-rate radiation. To achieve the therapeutic dose, continuous hours or days of radiation is necessary. For strawberry hemangiomas, the phosphorus-32 applicator was tightly placed on the lesion site for several hours until reaching therapeutic dose. The absorbed dose was estimated by radiochromic films. The absorbed dose of phosphorus-32 irradiation declined exponentially with a depth from 0 to 2.5 mm. Of the 316 patients with strawberry hemangiomas, the lesion disappeared completely within 3 months after one-time treatment in 259 cases (82%). For cavernous hemangiomas, 370KBq phosphorus-32 colloid was injected into the hemangioma each square centimeter, and the absorbed radiation was estimated by theoretical calculation. Forty-two of the 58 patients with cavernous hemangiomas (72%) had lesions that completely disappeared within 3 months after receiving one to six treatments. Thus, the phosphorus-32 for strawberry hemangiomas and the chromium phosphate-32 colloid for cavernous hemangiomas were clearly efficacious.

Blood concentration of pantoprazole sodium is significantly high in hepatogenic peptic ulcer patients, especially those with a poor CYP2C19 metabolism.

OBJECTIVE: To determine the plasma concentration of pantoprazole sodium by high performance liquid chromatography and its distribution in patients with different CYP2C19 genotypes in an attempt to provide experimental data for the clinical dosage adjustment of the drug. METHODS: Patients with liver disease and associated peptic ulcer were genotyped according to their CYP2C19 wild-type sequences and mutations in CYP2C19m1 and CYP2C19m2 by the principles of the American Surgical Association using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma concentration of pantoprazole sodium was detected after oral administration of the enteric-coated capsules in all patients. Included in the present study were 21 patients with primary liver cancer complicated by pathogenic peptic ulcers (confirmed by endoscopy), 22 patients with fatty liver and 25 healthy volunteers between January 2006 and October 2007. The subjects were administered orally with pantoprazole sodium at 40 mg/day for 1 week consecutively. The drug concentration was detected at 24 h and 1 week after drug administration by drawing 3.0 mL blood from the cubital vein. RESULTS: The plasma concentration of pantoprazole sodium was related to the CYP2C19 enzyme type. The plasma concentration of extensive metabolizers (EM) was lower than that of poor metabolizers (PM) in the healthy control group at day 7 of drug administration. Regardless of PM or EM, the plasma concentration of pantoprazole sodium in primary liver cancer patients was higher than that in fatty liver patients, and even higher than that in healthy controls (P < 0.05). CONCLUSION: These results suggest that CYP2C19 activity is inversely correlated with the severity of liver disease, especially in PM patients.

[Effects of short-term treatment of somatostatin on angiogenesis of gastric carcinoma].

BACKGROUND & OBJECTIVE: It is a hot spot in tumor therapies to inhibit the angiogenesis of carcinoma. Our current study was designed to investigate the inhibitory effect of somatostatin analogue on the angiogenesis of gastric carcinoma by hypodermic injection. METHODS: Twenty-five patients who have positive expression of vascular endothelial growth factor(VEGF) and somatostatin receptor 2(SSTR2)were selected by gastroscopic biopsy and immunohistochemical staining before surgical operation. After 7 days of Sandostatin administration (10 microg/kg, hypodermic injection, twice a day), the tumor extirpations were made. During the Sandostatin treatment, the serum levels of VEGF and the basic fibroblast growth factor(bFGF)were measured by enzyme-linked immunosorbant assay (ELISA) (d1,d3,d7, separately). Before and after operation,the expression levels of VEGF and bFGF were examined by Western blot analysis and the density of micro-vessels was determined by immunohistochemical staining. RESULTS: After a week of Sandostatin therapy,the concentration of VEGF and bFGF in serum was drastically diminished (VEGF:1.02+/-0.41 microg /L vs 1.88+/-0.87 microg/L, P< 0.05;bFGF:0.88+/-0.32 ng/L vs 2.12+/-1.06 ng/L,P< 0.05). The expression levels of VEGF(absorbance:1.306 vs 488,P< 0.01) and bFGF(absorbance:1.287 vs 512,P< 0.01) were obviously decreased after the remedy. The density of micro-vessels turn to the less, but there was no statistical difference before and after operation(P >0.05). CONCLUSION: By the short-term therapy of sandostatin, the expression of VEGF and bFGF can be inhibited. There is a tendency that the serum levels of VEGF and bFGF decrease with the increase of therapy time.

Control of facial muscle development by MyoR and capsulin.

Members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors control the formation of all skeletal muscles in vertebrates, but little is known of the molecules or mechanisms that confer unique identities to different types of skeletal muscles. MyoR and capsulin are related bHLH transcription factors expressed in specific facial muscle precursors. We show that specific facial muscles are missing in mice lacking both MyoR and capsulin, reflecting the absence of MyoD family gene expression and ablation of the corresponding myogenic lineages. These findings identify MyoR and capsulin as unique transcription factors for the development of specific head muscles.