Background Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this ...study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. Methods A sFlt-1–expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti–platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. Results The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1–expressing adenoviral vector–infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1–expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. Conclusion The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.
Background/Aims Complete operative resection is the only approach to cure for intrahepatic cholangiocellular carcinoma (ICC), but the disease’s prognosis is notably poor. A novel therapeutic approach ...is urgently required. CXC chemokine receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human cancers. In this study, we investigated the suppressive effect of ICC growth by blocking CXCR2. Material and methods The role of CXCR2 was estimated using the human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration assays, and invasion assays were performed to confirm the suppressive effect of blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice, and the mice were given SB225002. The expression of CXCR2 in ICC was determined by immunohistochemical staining of 34 ICC specimens. We investigated the relationship between CXCR2 expression and prognosis in ICC. Results The prognosis of patients who had higher CXCR2 expression in ICC was significantly poor ( P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression in both RBE and SSP25. Cell proliferation, migration, and invasion were significantly suppressed by both CXCR2 siRNA and SB225002 compared with the control group. SB225002 also suppressed the growth of transplanted subcutaneous tumors ( P = .02) Conclusion Our results demonstrated that blocking CXCR2 clearly suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic approach for ICC.
Edwardsiella tarda
is an anaerobe associated with freshwater and marine life. Necrotizing soft tissue infection caused by
E. tarda
is rare, but its mortality rate is extremely high (61.1%). We ...experienced a survival case of Fournier’s gangrene with
E. tarda
. A key clinical feature for the diagnosis was gas production; however, there have been no previous reports of such a phenomenon in relation to
E. tarda
. A 64-year-old man was admitted with a 3-day history of a high fever. His medical history, which included paraplegia from the Th6 level down, made the focus of inflammation at the perineum difficult to notice. Whole-body CT revealed subcutaneous gas from the posterior scrotum around the entire circumference of the anus. During emergency surgery, an incision at the posterior scrotum revealed extensive fascia necrosis, and
E. tarda
and
Streptococcus anginosus
were identified. We speculated the gas production in this case to be the product of a mixed infection of aerobes and anaerobes, which acted synergistically to induce bacterial growth. Timely surgical debridement and antibiotic therapy led to the patient’s survival.
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