Early and Mid-Term Outcomes after Vascular Reconstruction for Patients with Lower-Extremity Soft-Tissue Malignant Tumors.

Objective: To evaluate limb-salvage surgery including vascular resection for lower-extremity soft-tissue sarcomas and carcinomas for adult patients. Materials and Methods: Eight consecutive patients (median age, 59 years) who underwent vascular replacement during surgery for malignant tumors in the lower limbs between November 2006 and March 2018 were evaluated. Patient data were retrospectively obtained in a computerized database. Arterial and venous reconstructions were performed for seven patients, with one additional patient receiving venous reconstruction only. Autologous-vein (n=6) and synthetic bypasses were used for arterial repairs, whereas only autologous veins were implanted for venous repairs. Results: Morbidity was 62.5%, and in-hospital mortality was 12.5%. At a median follow-up of 24 months, the primary patency rates of arterial and venous reconstructions were 85.7% and 62.5%, respectively. Limb salvage was achieved in all cases. Conclusion: Early and mid-term bypass patency rates, the high percentage of limb salvage, and the oncologic outcome underline the efficacy of en bloc resection of soft-tissue tumors involving major vessels of the lower limbs. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma and carcinoma resections. However, efforts to achieve better control over systemic spread are required for long-term survival.

Oral and integumental uptake of free exogenous glycine by the Japanese spiny lobster Panulirus japonicus phyllosoma larvae.

The possibility of direct integumental absorption of the amino acid glycine from a solution in seawater was investigated in 250-260 day old (16.9-50.0 mg wet mass) phyllosoma larvae of the Japanese spiny lobster Panulirus japonicus Von Siebold 1824. The uptake of the amino acid was assessed by autoradiography and liquid scintillation counting (LSC) of larvae incubated with [2-(3)H]glycine and the net uptake was estimated by a time course high-performance liquid chromatography (HPLC) analysis of the concentration of glycine in the incubation medium. Autoradiography revealed the presence of labelled glycine in the cuticle, epidermis and internal tissues (digestive system, muscle, haemocytes) within 30 min of the onset of incubation. Absorption through the integument was confirmed by autoradiography and LSC as glycine uptake was observed even in larvae whose mouths were artificially sealed with cyanoacrylate bond prior to incubation. Scanning electron microscopic examination of the body surface revealed no bacterial population that could have mediated the uptake. HPLC revealed a consistent net uptake (0.29-0.39 micromol g(-1) body mass h(-1)) of glycine in larvae incubated in 6 micromol l(-1) glycine and high individual variation (e.g. absorption or release) in larvae incubated at higher concentrations (30 and 60 micromol l(-1)). Thus, the results of this study provide clear confirmation that, in addition to the known mode of oral feeding on macroscopic food masses, P. japonicus phyllosoma larvae are also able to absorb nutrients directly from the surrounding medium.

Suppression of choroidal neovascularization in lectin-like oxidized low-density lipoprotein receptor type 1-deficient mice.

PURPOSE: To elucidate the role of the scavenger receptor, lectin-like oxidized low-density lipoprotein receptor type 1 (LOX-1), in the formation of choroidal neovascularization (CNV). METHODS: CNV was induced by laser photocoagulation of the ocular fundus in mice. The expression of LOX-1 mRNA and protein after laser injury was determined by real-time RT-PCR and Western blot analysis. Gelatin zymography was used to measure the activity of matrix metalloproteinase (MMP)-2 and pro-MMP-9, and ELISA was used to determine monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels. At 14 days after laser injury, the extent of CNV was evaluated by fluorescein angiography and lectin staining using confocal microscopy. RESULTS: In wild-type mice, the relative expression level of LOX-1 mRNA compared with the control increased significantly 6 hours after laser injury and peaked 12 hours after laser injury (P = 0.011 and P = 0.0006, respectively), and the expression of LOX-1 protein was also detected 1 and 3 days after laser injury. Increases in MMP-2, pro-MMP2, and pro-MMP-9 after laser injury were reduced in LOX-1-deficient mice compared with wild-type mice. At 3 days after laser injury, increases in MCP-1 and VEGF significantly decreased in LOX-1-deficient mice compared with wild-type mice (P = 0.014 and P = 0.001, respectively). Morphometric analyses revealed that the induction of CNV formation was significantly inhibited in LOX-1-deficient mice. CONCLUSIONS: These results suggest that LOX-1 plays an important role in the formation of CNV. This scavenging system might thus be a novel therapeutic target for CNV.

Expression and localization of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in murine and human placentas.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the scavenger receptors that recognizes oxidized low-density lipoprotein as a major ligand. The placenta is a major source of prooxidant during pregnancy, and the level of placental oxidative stress increases rapidly at the end of the first trimester and tapers off later in gestation. In our study, we evaluated placental expression of LOX-1 during different gestational stages in mice and humans. We used immunohistochemistry and ISH to identify LOX-1-expressing cells in murine and human placentas. In both species, higher expression of LOX-1 mRNA during early to midgestational stages compared with late gestation-corresponding to the increased oxidative stress in early pregnancy-was shown by real-time RT-PCR. In murine placenta, we showed that LOX-1-expressing cells were fibroblast-like stromal cells in metrial glands and decidua basalis and that they were glycogen trophoblast cells in the junctional and labyrinth zones. In the human, LOX-1 expression was detected in villous cytotrophoblasts in both first trimester and term placentas. These localization patterns of LOX-1 in murine and human placentas suggest the possible involvement of LOX-1 in high oxidative stress conditions of pregnancy.

Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet.

Atherosclerosis is associated with oxidative stress and inflammation, and upregulation of LOX-1, an endothelial receptor for oxidized LDL (oxLDL). Here, we describe generation of LOX-1 knockout (KO) mice in which binding of oxLDL to aortic endothelium was reduced and endothelium-dependent vasorelaxation preserved after treatment with oxLDL (P<0.01 versus wild-type mice). To address whether endothelial functional preservation might lead to reduction in atherogenesis, we crossed LOX-1 KO mice with LDLR KO mice and fed these mice 4% cholesterol/10% cocoa butter diet for 18 weeks. Atherosclerosis was found to cover 61+/-2% of aorta in the LDLR KO mice, but only 36+/-3% of aorta in the double KO mice. Luminal obstruction and intima thickness were significantly reduced in the double KO mice (versus LDLR KO mice). Expression of redox-sensitive NF-kappaB and the inflammatory marker CD68 in LDLR KO mice was increased (P<0.01 versus wild-type mice), but not in the double KO mice. On the other hand, antiinflammatory cytokine IL-10 expression and superoxide dismutase activity were low in the LDLR KO mice (P<0.01 versus wild-type mice), but not in the double KO mice. Endothelial nitric oxide synthase expression was also preserved in the double KO mice. The proinflammatory signal MAPK P38 was activated in the LDLR KO mice, and LOX-1 deletion reduced this signal. In conclusion, LOX-1 deletion sustains endothelial function leading to a reduction in atherogenesis in association with reduction in proinflammatory and prooxidant signals.