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ABSTRACT: PURPOSE: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. MATERIALS AND METHODS: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m(2)) + cisplatin (60 mg/m(2)) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m(2)) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. RESULTS: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31) in groups A and B, respectively. During the intra-arterial chemotherapy cycle, although more than 50 % patients experienced some toxicities, most were minor and reversible [grade 1-2 (46.7 %) vs. grade 1-2 (6.9 %)]. CONCLUSION: These findings suggest that combining intra-arterial chemotherapy with intravesical chemotherapy could delay tumour recurrence and progression compared with intravesical chemotherapy alone and this type treatment is relatively safe.
CardioVascular and Interventional Radiology 03/2013; · 2.09 Impact Factor
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ABSTRACT: Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.
ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.
CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.
ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.
Journal of Translational Medicine 06/2012; 10:133. · 3.41 Impact Factor
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Fan Lian,
Yu Wang,
Wei Chen, Jiaping Li,
Zhongping Zhan,
Yujin Ye,
Yunxiao Zhu,
Jia Huang,
Hanshi Xu,
Xiuyan Yang,
Liuqin Liang,
Jianyong Yang
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ABSTRACT: This study was designed to compare the effectiveness of systemic methotrexate (MTX) with uterine artery embolization (UAE) combined with local MTX for the treatment of cesarean scar pregnancy (CSP) with different ultrasonographic pattern, and to indicate the preferable therapy in CSP patients.
The results of 21 CSP cases were reviewed. All subjects were initially administrated with systemic MTX (50 mg/m(2) body surface area). UAE combined with local MTX was added to the patients who had failed systemic MTX. The transvaginal ultrasonography data were retrospectively assessed, and two different ultrasonographic patterns were found: surface implantation and deep implantation of amniotic sac. The management and its effectiveness for patients with the two ultrasonographic patterns were studied retrospectively. Ultrasound scan and serum β-hCG were monitored during follow-up. Data were analyzed with the Student's t test.
Nine patients were successfully treated with systemic MTX. The remaining 12 cases were successfully treated with additional UAE combined with local MTX. According to the classification by Vial et al. of CSP on ultrasonography, most surface implanted CSPs (8/11, 72.7%) could be successfully treated with systemic MTX, whereas most deeply implanted CSPs (9/10, 90%) had failed systemic MTX but still could be successfully treated with additional UAE combined with local MTX. All patients recovered without severe side effects. Most patients with a future desire for reproduction achieved subsequent pregnancy.
For CSP patients suitable for nonsurgical treatment, UAE combined with local MTX would be the superior option compared with systemic MTX in the cases with deep implantation of amniotic sac.
CardioVascular and Interventional Radiology 01/2011; 35(2):286-91. · 2.09 Impact Factor
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ABSTRACT: Sixty percent of paragangliomas are located unilaterally at the carotid bifurcation. These are referred to as carotid body tumors (CBTs).
To present our 10-year experience in the management of patients with CBTs, and to evaluate the efficacy of angiography and preoperative embolization technique in this retrospective study.
Sixty-two patients with surgically removed CBTs (Shamblin class II and III), were divided into two groups. Group I, the preoperative embolization group, included 33 patients with 11 class II lesions and 25 class III lesions. Group II, the group that had surgery only, without preoperative embolization, included 29 patients with 9 class II lesions and 21 class III lesions. Comparisons were made between the groups in terms of mean intraoperative blood loss, mean operation time, mean postoperative hospital stay, and clinical complications.
In group I, post-embolization angiography demonstrated complete tumor devascularization in 25 (76%) lesions and partial devascularization in 11 (24%) lesions. All but 1 (2%) lesion were completely excised. Mean intraoperative blood loss, mean operation time, and mean hospital stay were 354.8 ± 334.4 mL, 170.3 ± 75.4 min, 8.0 ± 2.1 days in group I and 656.4 ± 497.4 mL, 224.6 ± 114.0 min, 9.5 ± 3.5 days in group II, respectively. In group II, 27 lesions (91%) were completely removed. The transient ischemic attack (TIA) and cranial nerve injury incidence rates were 10.3% and 13.8% in group II and only 3% for TIA in group I.
These results suggest angiography is highly valuable for the diagnosis of CBT. Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors.
Neurosurgery 10/2010; 67(4):941-8; discussion 948. · 2.79 Impact Factor
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Jiaping Li,
Komal Ramani,
Zhanfeng Sun,
Chishing Zee,
Edward G Grant,
Heping Yang,
Meng Xia,
Pilsoo Oh,
Kwangsuk Ko,
José M Mato,
Shelly C Lu
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ABSTRACT: Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine, the principal methyl donor, and is encoded by MAT1A and MAT2A in mammals. Normal liver expresses MAT1A, which is silenced in hepatocellular carcinoma. We have shown that hepatoma cells overexpressing MAT1A grew slower, but whether this is also true in vivo remains unknown. To investigate the effect of overexpressing MAT1A on in vivo tumorigenesis, we generated stable transfectants of Huh7 cells overexpressing either MAT1A or empty vector. Real-time PCR and Western blotting were used to measure expression, and BALB/c nude mice were injected subcutaneously with untransfected or Huh7 cells transfected with empty or MAT1A expression vector to establish tumors. Tumor properties such as proliferation, angiogenesis, and apoptosis were compared, and microarray analysis was performed. Huh7 cells overexpressing MAT1A had higher S-adenosylmethionine levels but lower bromodeoxyuridine incorporation than control cells. Tumor growth rates and weights were lower in MAT1A transfected tumors. In addition, microvessel density and CD31 and Ki-67 staining were lower in MAT1A transfected tumors than control tumors, whereas the apoptosis index was higher in MAT1A-transfected tumors. Forced expression of MAT1A induced genes related to apoptosis and tumor suppression and lowered expression of cell growth and angiogenesis proteins. Our data demonstrate in vivo overexpression of MAT1A in liver cancer cells can suppress tumor growth. They also suggest inducing MAT1A expression might be a strategy to treat hepatocellular carcinoma.
American Journal Of Pathology 04/2010; 176(5):2456-66. · 4.89 Impact Factor
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ABSTRACT: We previously showed that hepatic expression of glutathione (GSH) synthetic enzymes and GSH levels fell 2 weeks after bile duct ligation (BDL) in mice. This correlated with a switch in nuclear anti-oxidant response element (ARE) binding activity from nuclear factor erythroid 2-related factor 2 (Nrf2) to c-avian musculoaponeurotic fibrosarcoma (c-Maf)/V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (MafG). Our current aims were to examine whether the switch in ARE binding activity from Nrf2 to Mafs is responsible for decreased expression of GSH synthetic enzymes and the outcome of blocking this switch. Huh7 cells treated with lithocholic acid (LCA) exhibited a similar pattern of change in GSH synthetic enzyme expression as BDL mice. Nuclear protein levels of Nrf2 fell at 20 hours after LCA treatment, whereas c-Maf and MafG remained persistently induced. These changes translated to ARE nuclear binding activity. Knockdown of c-Maf or MafG individually blunted the LCA-induced decrease in Nrf2 ARE binding and increased ARE-dependent promoter activity, whereas combined knockdown was more effective. Knockdown of c-Maf or MafG individually increased the expression of GSH synthetic enzymes and raised GSH levels, and combined knockdown exerted an additive effect. Ursodeoxycholic acid (UDCA) or S-adenosylmethionine (SAMe) prevented the LCA-induced decrease in expression of GSH synthetic enzymes and promoter activity and prevented the increase in MafG and c-Maf levels. In vivo knockdown of the Maf genes protected against the decrease in GSH enzyme expression, GSH level, and liver injury after BDL. Conclusion: Toxic bile acid induces a switch from Nrf2 to c-Maf/MafG ARE nuclear binding, which leads to decreased expression of GSH synthetic enzymes and GSH levels and contributes to liver injury during BDL. UDCA and SAMe treatment targets this switch.
Hepatology 11/2009; 51(4):1291-301. · 11.66 Impact Factor
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ABSTRACT: Glutathione (GSH) provides important antioxidant defense and regulates multiple critical processes including fibrogenesis. There are conflicting literature studies regarding changes in GSH during cholestasis. Here we examined changes in the GSH synthetic enzymes during bile duct ligation (BDL) in mice and how treatment with ursodeoxycholic acid (UDCA) and/or S-adenosylmethionine (SAMe) affects the expression of these enzymes and liver injury. The hepatic expression of glutamate-cysteine ligase (GCL) subunits and GSH synthase (GS) increased transiently after BDL but fell to 50% of baseline by 2 weeks. Nuclear factor-erythroid 2-related factor 2 (Nrf2) trans-activates gene expression by way of the antioxidant response element (ARE), which controls the expression of all three genes. Despite increased Nrf2 nuclear levels, Nrf2 nuclear binding to ARE fell 2 weeks after BDL. Nuclear levels of c-Maf and MafG, which can negatively regulate ARE, were persistently induced during BDL and the dominant proteins bound to ARE on day 14. UDCA and SAMe induced the expression of GCL subunits and raised GSH levels. They increased nuclear Nrf2 levels, prevented c-Maf and MafG induction, and prevented the fall in Nrf2 nuclear binding to ARE. Combined treatment had additive effects, reduced liver cell death, and prevented fibrosis. CONCLUSION: GSH synthesis falls during later stages of BDL due to lower expression of GSH synthetic enzymes. UDCA and SAMe treatment prevented this fall and combined therapy was more effective on preserving GSH levels and preventing liver injury.
Hepatology 03/2009; 49(6):1982-91. · 11.66 Impact Factor
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ABSTRACT: To analyze at one institution the endovascular treatment for aortic arch and proximal thoracic aortic lesions, categorize open arch reconstruction, and make preliminary recommendations based on pathology (dissection vs aneurysm), and anatomical extent of disease.
A retrospective review of aortic arch and descending thoracic aortic lesions managed with endovascular treatment between June 2002 and June 2007.
Thirty-four patients received endovascular repair for aortic dissection (n = 28) and aneurysm (n = 6). Open supra-aortic transposition or debranching of the great vessels was performed in 14 cases of dissection (50%) and six cases (100%) of aneurysm. In 14 dissections, the entry tear was located in the distal aortic arch, enabling the left subclavian artery to be sealed without reconstruction. The procedures were successful in 33 patients (97.1%); one intraoperative death occurred. Type I endoleaks were found intraoperatively in eight cases. After management with balloon angioplasty and by extending the stent implantation, the endoleaks resolved in four cases and decreased in four cases. One patient with Stanford type A dissection died from an unknown cause 3 months after treatment. The overall survival rate was 94.1% (32/34), and all bypass grafts remained patent during the follow-up period.
Endovascular stent grafting is a safe and effective method for the treatment of aortic arch lesions. Transposition of the supra-aortic great vessels can be effectively combined with endovascular stent grafting to ensure both cerebral blood supply and enough landing area for the stent graft.
Journal of Vascular Surgery 08/2008; 48(1):64-8. · 3.21 Impact Factor
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ABSTRACT: In this study, porous 3D fiber deposition titanium (3DFT) and 3DFT combined with porous biphasic calcium phosphate ceramic (3DFT+BCP) implants, both bare and 1 week cultured with autologous bone marrow stromal cells (BMSCs), were implanted intramuscularly and orthotopically in 10 goats. To assess the dynamics of bone formation over time, fluorochrome markers were administered at 3, 6 and 9 weeks and the animals were sacrificed at 12 weeks after implantation. New bone in the implants was investigated by histology and histomorphometry of non-decalcified sections. Intramuscularly, no bone formation was found in any of the 3DFT implants, while a very limited amount of bone was observed in 2 BMSC 3DFT implants. 3DFT+BCP and BMSC 3DFT+BCP implants showed ectopic bone formation, in 8 and 10 animals, respectively. The amount of formed bone was significantly higher in BMSC 3DFT+BCP as compared to 3DFT+BCP implants. Implantation on transverse processes resulted in significantly more bone formation in composite structure as compared to titanium alloy alone, both with and without cells. Unlike intramuscularly, the presence of BMSC did not have a significant effect on the amount of new bone either in metallic or in composite structure. Although the 3DFT is inferior to BCP for bone growth, the reinforcement of the brittle BCP with a 3DFT cage did not negatively influence osteogenesis, osteoinduction and osteoconduction as previously shown for the BCP alone. The positive effect of BMSCs was observed ectopically, while it was not significant orthotopically.
Biomaterials 11/2007; 28(29):4209-18. · 7.40 Impact Factor
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ABSTRACT: The in vivo behavior of a porous Ti6Al4V material that was produced by a positive replica technique, with and without an octacalcium phosphate (OCP) coating, has been studied both in the back muscle and femur of goats. Macro- and microporous biphasic calcium phosphate (BCP) ceramic, known to be both osteoconductive and able to induce ectopic bone formation, was used for comparison purpose. The three groups of materials (Ti6Al4V, OCP Ti6Al4V and BCP) were implanted transcortically and intramuscularly for 6 and 12 weeks in 10 adult Dutch milk goats in order to study their osteointegration and osteoinductive potential. In femoral defects, both OCP Ti6Al4V and BCP were performing better than the uncoated Ti6Al4V, at both time points. BCP showed a higher bone amount than OCP Ti6Al4V after 6 weeks of implantation, while after 12 weeks, this difference was no longer significant. Ectopic bone formation was found in both OCP Ti6Al4V and BCP implants after 6 and 12 weeks. The quantity of ectopically formed bone was limited as was the amount of animals in which the bone was observed. Ectopic bone formation was not found in uncoated titanium alloy implants, suggesting that the presence of calcium phosphate (CaP) is important for bone induction. This study showed that CaPs in the form of coating on metal implants or in the form of bulk ceramic have a significantly positive effect on the bone healing process.
Biomaterials 02/2005; 26(1):23-36. · 7.40 Impact Factor
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ABSTRACT: Macroporous biphasic calcium phosphate (BCP) with channel-shaped pores was produced by a novel dual-phase mixing method. The processing route includes mixing water-based BCP slurry and polymethylmethacrylate resin; shaping in a mold; and polymerization, drying, pyrolyzing, and sintering. After comparison with two other commercial macroporous BCP materials, which were produced along different routes, it was found that conventional parameters such as porosity and pore size cannot describe a macroporous structure precisely enough for the application as tissue-engineering scaffold. Instead, permeability can be seen as an intrinsic and quantitative parameter to describe the macroporous structure of various scaffolds, because it is independent of sample size and fluid used in the test. Another parameter, the permeability/porosity ratio, provides an indication of the percolative efficiency per unit porous volume of a scaffold. Structural characterizations and permeability studies of other macroporous scaffold materials were also performed, and it was found that permeability could reflect a combination of five important parameters for scaffold: (1) porosity, (2) pore size and distribution, (3) interconnectivity, (4) fenestration size and distribution, and (5) orientation of pores. Finally, the implications of relating permeability with biological performances are also discussed.
Tissue Engineering 07/2003; 9(3):535-48. · 4.02 Impact Factor
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ABSTRACT: The objective of our study was to evaluate the changes in quantitative diffusion tensor (DT) metrics and normalized T2-signal intensity (nT2-SI) values of normal-appearing cortical gray matter (CGM) and deep gray matter (DGM) in patients with multiple sclerosis (MS).
Fifty patients with MS and 25 patients with no MS matched on sex/age were selected as controls. Conventional magnetic resonance imaging and DT imaging were performed. Fractional anisotropy (FA)/mean diffusivity (MD) and nT2-SI values of CGM and DGM were measured. Analyses of variance between the 2 groups were analyzed; Pearson correlations between DT metrics and nT2-SI values and brain parenchymal fraction (BPF) and T2 lesion volumes (LVs) were used.
Patients with MS showed larger MD/smaller FA values in the CGM region compared with controls (P < 0.05). However, MD/FA values were not statistically significant in the DGM between MS and healthy control group. In DGM of MS patients, a significant decrease of nT2-SI values were observed when compared with controls (P < 0.05), but nT2-SI values in the CGM of MS patients showed no significant decrease. In CGM, only MD values of frontal lobes in MS patients were significantly (negatively) correlated with BPF(right: P = 0.009, left: P = 0.036) or T2 LVs (right: P = 0.002, left: P = 0.047). Normalized T2-SI values in all DGM regions of MS patients were significantly correlated with BPF (r = 0.282-0.504, P < 0.05) except for the left thalamus and bilateral red nucleus. There was no correlation between nT2-SI in all DGM regions and T2 LVs of MS patients.
In CGM, the change in quantitative DT metrics of MS patients and the association with BPF and T2 LVs suggest the existence of microstructural destruction corresponding to inflammation, demyelination, or wallerian degeneration, but the changes in CGM were independent of the concomitant changes in BPF and T2 lesion. In DGM, a decrease of nT2-SI in MS patients and the correlation of nT2-SI values with BPF (brain atrophy) suggest excessive iron deposition related to chronic destruction. Our investigation indicates the possibility of different mechanism of pathological change in CGM and DGM.
Journal of computer assisted tomography 34(3):431-6. · 1.38 Impact Factor
