Nek2 siRNA therapy using a portal venous port-catheter system for liver metastasis in pancreatic cancer.

Nek2 (NIMA-related kinase 2) is a serine-threonine kinase and human homolog of the mitotic regulator NIMA of Aspergillus nidulan. We reported the efficiency of Nek2 siRNA in several cancer xenograft models using cholangiocarcinoma, breast cancer and colorectal cancer. Pancreatic cancer is difficult to treat due to its rapid progression and resistance to chemotherapy. Novel treatments are urgently required to improve survival in pancreatic cancer, and siRNA are a promising therapeutic option. However, finding an in vivo drug delivery system of siRNA remains a major problem for clinical application. In this study, the overexpression of Nek2 was identified in pancreatic cancer cell lines. Nek2 siRNA inhibited tumor growth in a subcutaneous xenograft mouse model of pancreatic cancer, prolonged the survival time in an intraperitoneal xenograft mouse model and efficiently prevented the progression of liver metastasis using a portal venous port-catheter system. Taken together, Nek2 is an effective therapeutic target in pancreatic cancer. An adequate delivery system is considered important in treating advanced pancreatic cancer, such as peritoneal dissemination and liver metastasis. Further investigations are required on the safety and side effects of the portal venous port-catheter system. We hope that Nek2 siRNA will be a novel therapeutic strategy for pancreatic cancer with liver metastasis and peritoneal dissemination.

Interfacial shear strength of bioactive-coated carbon fiber reinforced polyetheretherketone after in vivo implantation.

Despite the excellent osseointegration of carbon-fiber-reinforced polyetheretherketone (CFR/PEEK) with a surface hydroxyapatite (HA) coating, the bone-implant interfacial shear strength of HA-coated CFR/PEEK after osseointegration is unclear. We examined the interfacial shear strength of HA-coated CFR/PEEK implants after in vivo implantation in a rabbit femur-implant pull-out test model. HA coating was performed by a newly developed method. Uncoated CFR/PEEK, HA-coated blasted titanium alloy, and uncoated blasted titanium alloy were used as control implants. The implants were inserted into drilled femoral cortex, and pull-out tests were conducted after 6 and 12 weeks of implantation to determine maximum interfacial shear strength. The HA-coated CFR/PEEK (15.7 ± 4.5 MPa) and HA-coated titanium alloy (14.1 ± 6.0 MPa) exhibited significantly larger interfacial shear strengths than the uncoated CFR/PEEK (7.7 ± 1.8 MPa) and the uncoated titanium alloy (7.8 ± 2.1 MPa) at 6 weeks. At 12 weeks, only the uncoated CFR/PEEK (8.3 ± 3.0 MPa) exhibited a significantly smaller interfacial shear strength, as compared to the HA-coated CFR/PEEK (17.4 ± 3.6 MPa), HA-coated titanium alloy (14.2 ± 4.8 MPa), and uncoated titanium alloy (15.0 ± 2.6 MPa). Surface analysis of the removed implants revealed detachment of the HA layer in both the HA-coated CFR/PEEK and titanium alloy implants. The proposed novel HA coating method of CFR/PEEK significantly increased interfacial shear strength between bone and CFR/PEEK. The achieved interfacial shear strength of the HA-coated CFR/PEEK implant is of the same level as that of grit-blasted titanium alloy with HA.

Multiarterial phase dynamic MRI of small early enhancing hepatic lesions in cirrhosis or chronic hepatitis: differentiating between hypervascular hepatocellular carcinomas and pseudolesions.

OBJECTIVE: The purpose of this study was to assess the value of multiarterial phase contrast-enhanced dynamic MRI of the whole liver obtained during a single breath-hold for small early enhancing hepatic lesions in patients with cirrhosis or chronic hepatitis, emphasizing the distinction between hypervascular hepatocellular carcinomas and pseudolesions. MATERIALS AND METHODS: The study population included 40 patients with cirrhosis or chronic hepatitis who had small early enhancing hepatic lesions (a total of 70 lesions: 40 hepatocellular carcinomas, 30 pseudolesions). All patients underwent multiarterial phase contrast-enhanced dynamic MRI (six phases) of the whole liver during a single breath-hold. RESULTS: Twenty-one (53%) of 40 hypervascular hepatocellular carcinomas showed rapid central washout after early enhancement of the lesion as well as peritumoral coronal enhancement, but these findings were not observed in any hypervascular pseudolesions (p < 0.001). In 19 hepatocellular carcinomas without rapid central washout, early enhancement of the lesion appeared at the second, third, or fourth phase (mean, 2.5 phases). In eight of these 19 hepatocellular carcinomas, lesion enhancement disappeared by the sixth phase. Conversely, in 30 hypervascular pseudolesions, early enhancement of the lesion appeared at the second, third, fourth, or fifth phase (mean, 3.0 phases). In 28 of these 30 pseudolesions, lesion enhancement continued until the sixth phase. CONCLUSION: Rapid central washout after the early enhancement of the lesion and coronal enhancement surrounding the lesion are highly specific and diagnostic findings of small hypervascular hepatocellular carcinomas if present at multiarterial phase contrast-enhanced dynamic MRI. Hypervascular pseudolesions tend to show prolonged enhancement during the arterial phase compared with hypervascular hepatocellular carcinomas.