The role of nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species in the acquisition of metastatic ability of tumor cells.
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We examined the role of phagocyte-derived oxygen radicals in tumor cell acquisition of metastatic phenotype by comparing gp91(phox-/-) mice and C57BL/6J wild-type (WT) mice. The gp91(phox-/-) mouse is deficient in the gp91(phox) gene, an essential subunit of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase that generates superoxide anion. QR-32 fibrosarcoma cells are nonmetastatic but are converted into metastatic tumors once in contact with foreign body (gelatin sponge)-induced phagocytes in vivo. Compared to QR-32 cells co-implanted with the foreign body in WT mice, those in gp91(phox-/-) mice exhibited reduced metastasis. There was no difference in the incidence of primary tumors after injection of B16BL6 melanoma cells in WT and gp91(phox-/-) mice. However, after resection of the primary tumors, metastases were reduced in gp91(phox-/-) mice. Thymosin beta4 gene expression and cell motility/invasion were seen in the tumors from WT mice but not in those from gp91(phox-/-) mice. Adoptive transfer of phagocytes from WT mice, but not those from gp91(phox-/-) mice, restored the metastatic ability of tumors grown in gp91(phox-/-) mice. These findings show that tumor metastatic behavior can primarily be endowed by phagocyte-derived superoxide anion and its oxidative metabolites, which are generated through activation of nicotinamide adenine dinucleotide phosphate oxidase. (+info)
Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts.
(26/97)
BACKGROUND: Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. METHODS AND RESULTS: H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1 x 10(6) genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 microg/mL), or (5) GF/MG/FGF (10 microg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function. CONCLUSIONS: Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective. (+info)
Cell-based tissue engineering for lung regeneration.
(27/97)
Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed "alveolar-like structures" at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration. (+info)
Visceral artery aneurysm: risk factor analysis and therapeutic opinion.
(28/97)
OBJECTIVES: To identify independent risk factors for visceral artery aneurysms. METHODS: Retrospective medical record review over 10 years. RESULTS: There were 26 men and 15 women, median age of 54 (range 22 to 85), and median follow-up was 20.6 months (range 0 to 94 months). There were 11 splenic, 17 hepatic, 8 gastroduodenal, 6 pancreatoduodenal, 5 superior mesenteric, and two inferior mesenteric artery aneurysms. Thirteen patients (13/41, 31.7%) were treated surgically without adjuvant endovascular intervention. Nineteen patients (19/41, 46.3%) were treated exclusively using endovascular procedures. Five patients (5/41, 12.2%) received second endovascular or surgical treatment as salvage procedure after the first procedure failed. Concomitant malignancy was positive predictors for in-hospital death. Renal failure, chronic lung disease, liver cirrhosis, previous abdominal surgery and concomitant malignancy were positive predictors of 2-year mortality. With the intention to treat in the whole cohort, less than 10% (2/21) of the endovascular treatments failed, compared to 18.5% (3/16) in the surgical group. Patients treated by surgery without aid of endovascular intervention, have lower 2-year mortality. In hospital-death rate was 9.8%, while overall mortality rate was 21.9%. CONCLUSIONS: The endovascular intervention provides compatible, even better early postoperative outcomes for visceral artery aneurysms to surgery. Concomitant malignancy was the major determinant of visceral artery aneurysms, both in-hospital death and survival. (+info)
The implantation of non-cell-based materials to prevent the recurrent disc herniation: an in vivo porcine model using quantitative discomanometry examination.
(29/97)
Recurrent disc herniation is frequently observed due to leakage of nucleus pulposus through injured anulus fibrosus. There is no effective treatment to prevent recurrent disc herniation yet. In this study, we proposed to implant non-cell-based materials into the porcine disc to stimulate the growth of fibrous tissue and thereby increase the disc functional integrity. The disc herniation was simulated by anular punctures using the spinal needles. Four clinically used implantation materials, i.e., gelfoam, platinum coil, bone cement and tissue glue, were delivered into the discs via percutaneous spinal needles. Two months after the surgery, the swine were killed. The degree of disc integrity of intact, naturally healed and implanted discs, was examined by quantitative discomanometry apparatus. We found the disc injury could not recover after 2 months of healing, and the disc implantation affected the degree of disc integrity. The disc integrity of gelfoam-implanted discs was better than that of coil-, bone cement-, and glue-implanted discs. The implantation of non-cell-based material was proved to be a potentially clinically applicable method to recover the integrity of injured discs and to prevent recurrent disc herniation. (+info)
Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma.
(30/97)
AIM: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS: A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrast-enhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m(2), infused over 30 min using a peristaltic pump, and followed by Lipiodol and Gelfoam embolization. RESULTS: Patients characteristics were: mean age, 62 years; male/female 117/45; Child-Pugh score 6.2 +/- 1.1; MELD 8.7 +/- 2.3; mean HCC size, 3.6 (range 1.0-12.0) cm. HCC size class was 6.0 cm, n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 +/- 1.7). Complete tumor necrosis was obtained in 94 patients (58%), massive (90%-99%) necrosis in 16 patients (10%), partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was: 69%, 69%, 52%, 68%, 50% and, 13% for lesions of 6.0 cm, respectively. Kaplan-Mayer survival at 24-mo was 88%, 68%, 59%, 59%, 45%, and 53% for lesions of 6.0 cm, respectively. CONCLUSION: Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm, TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads may improve the effect on tumor necrosis. (+info)
A model of human cytomegalovirus infection in severe combined immunodeficient mice.
(31/97)
Animal models for the evaluation of therapies against human cytomegalovirus (HCMV) are limited due to the species-specific replication of CMV. Models utilizing human fetal tissues implanted into SCID mice have been used but tend to be labor intensive and require human tissues. We therefore developed a model using HCMV-infected human foreskin fibroblasts (HFF) seeded onto a biodegradable gelatin matrix (Gelfoam). Infected HFFs are then implanted subcutaneously into SCID mice. We next evaluated two antivirals in this model. Treatment from days 0 to 5 with ganciclovir (GCV) produced a marginally significant reduction in viral titer while treatment from days 0 to 14 resulted in a more significant reduction in viral titers of 1.47 log(10)pfu/ml (P<0.0001). Viral titers were similarly reduced in a group receiving GCV treatment from days 7 to 14 post-implantation (1.50 log(10)pfu/ml, P<0.0001). Cidofovir therapy from days 7 to 14 reduced viral titers by almost 2 log(10)pfu/ml (from 3.51+/-0.31 log(10)pfu/ml in untreated animals to 1.56+/-0.40 log(10)pfu/ml in treated animals, P<0.0001). These results indicate that the Gelfoam-HCMV SCID mouse model is suitable for the in vivo evaluation of new antivirals against HCMV and is simpler and more convenient than previous models. (+info)
Effects of fibrin sealer and resorbable gelatin on the repair of osseous defects in rat tibia.
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Gelfoam - a biologically resorbable gelatin sponge - has the function of restricting hemorrhage, providing platelet rupture, and supporting fibrin threads. Beriplast - a fibrinogen-thrombin compound - is used to adhere tissues, to consolidate sutures and in hemostasis. The objective of this study was to perform a histological analysis of the effects of haemostatic agents on osseous repair. These materials were inserted into surgical sites in young rat right and left tibiae. After the observation periods of 7, 14, 30 and 45 days, according to the bioethic protocol, the animals were killed, the tibiae were removed and fixed in 10% formalin and decalcified in equal parts of formic acid and sodium citrate solutions. After routine processing, the specimens were embedded in paraffin for microtomy. Analysis of the results demonstrated that the haemostatic agents are effective in controlling hemorrhage; they stimulate osteogenesis, featuring a pattern of osseous tissue formation similar to the control pattern, although the amount of osseous trabeculae was superior, especially in the Gelfoam group in the periods of 7 and 14 days; 30 days after surgery, the delay in tissue healing in the control group in relation to the experimental groups started to decrease, and the control and experimental groups exhibited similar tissue repair after 45 days, when all the groups exhibited secondary osseous tissue. (+info)