Transverse-sigmoid sinus dural arteriovenous fistula presenting with parkinsonism.

Dural arteriovenous fistula (DAVF) is rarely associated with parkinsonism. A 52-year-old woman presented with a rare case of DAVF manifesting as parkinsonism and subsequently akinetic mutism. She showed dramatic recovery after endovascular treatment. We also review 10 published reports of DAVF presenting with parkinsonism. The clinical features of these cases at presentation was more closely compatible with lower body parkinsonism or vascular parkinsonism rather than Parkinson's disease. Most lesions are located at the transverse-sigmoid sinus (TSS) with venous reflux into the straight sinus with probable venous congestion of the basal ganglia. Most importantly, parkinsonism due to TSS DAVF is reversible if embolization is achieved successfully.

Tenascin-C-coated platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model.

OBJECT: Detachable platinum coils are widely used in the endovascular treatment of intracranial aneurysms. The use of coil placement produces a higher incidence of aneurysm recurrence compared with surgical clipping. To reduce the incidence of recurrence by promoting clot organization, the authors designed a platinum coil coated with tenascin-C (TNC), an extracellular matrix glycoprotein, and then histologically examined tissue responses. METHODS: Platinum coils were prepared by successive coatings with cationic polyethyleneimine and anionic heparin and then TNC or basic fibroblast growth factor (bFGF) was immobilized by affinity binding to the heparin. Six unmodified, six heparin-coated, six bFGF-coated, or eight TNC-coated platinum coils were inserted into ligated common carotid arteries (CCAs) of adult male rats, and CCA segments were harvested after 14 or 28 days. The percentages of organized areas occupying the luminal cavity in unmodified, heparin-coated, bFGF-coated, and TNC-coated groups were 4.8 +/- 4.6, 1.6 +/- 1.1, 17.9 +/- 10.7, and 93.4 +/- 6.9%, respectively. In addition, the mean lumen size in the TNC-coated group (0.35 +/- 0.23 mm2) was reduced to less than half that of the unmodified group (0.72 +/- 0.21 mm2). Immunohistochemical analysis revealed that alpha-smooth muscle actin-positive cells were a major cellular component of the organized tissue within the TNC-coated coils but not in the bFGF group. Collagen fibrils in the organized areas were also much thicker and denser with TNC-coated coils than with bFGF-coated coils. CONCLUSIONS: Placement of TNC-coated coils can remarkably accelerate organization of luminal cavities and reduce their volume, providing improved efficacy of these coils for endovascular embolization.

The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer.

PURPOSE: RECK, a membrane-anchored regulator of matrix metalloproteinases (MMPs), is widely expressed in healthy tissue, whereas it is expressed at lower levels in many tumor-derived cell lines. Studies in mice and cultured cells have shown that restoration of RECK expression inhibits tumor invasion, metastasis, and angiogenesis. However, the clinical relevance of these findings remains to be fully documented. Here we examined the expression of RECK and one of its targets, MMP-9, in colorectal cancer tissue. EXPERIMENTAL DESIGN: The RECK and MMP-9 expression levels in colorectal cancer samples from 53 patients were determined by immunohistochemical techniques. The expression level of each protein was scored, and the patients were divided into two groups based on these scores. In 33 cases, we performed gelatin zymography to estimate the degree of MMP-2 and MMP-9 activation. Microvessel density and vascular endothelial growth factor (VEGF) expression were also evaluated histologically. RESULTS: RECK protein was detected in 30 of 53 (56.6%) specimens. Importantly, patients with tumors expressing relatively high levels of RECK (high-RECK group) had a significantly lower risk of recurrence than did patients with tumors expressing relatively low levels of RECK (low-RECK group; P = 0.011). Moreover, RECK-dominant (RECK score > or = MMP-9 score) patients showed a significantly lower incidence of recurrence than did MMP-9-dominant patients (P = 0.0003). Multivariate analysis revealed that the RECK/MMP-9 balance was an independent prognostic factor (P = 0.0122). The expression of VEGF and microvessel density were inversely correlated with the level of RECK expression. CONCLUSIONS: RECK/MMP-9-balance is an informative prognostic indicator for colorectal cancer. Our data also suggest that RECK suppresses tumor angiogenesis, probably by limiting the availability of VEGF in tumor tissues.

Adenovirus-mediated gene transduction of truncated I kappa B alpha enhances radiosensitivity in human colon cancer cells.

Nuclear factor kappa B (NF-kappa B) is a transcription factor that is known to regulate apoptosis when cells are exposed to DNA-damaging agents such as ionizing radiation and cytotoxic drugs. We sought to determine if inhibition of NF-kappa B could enhance radiosensitivity in human colon cancer cells in vitro and in vivo. To inhibit NF-kappa B activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein I kappa B alpha (I kappa B alpha Delta N) that lacks the phosphorylation sites essential for activation of NF-kappa B, and transfected two human colon cancer cell lines (HT29 and HCT15) with this vector. In vitro colony-forming assays revealed that the overexpression of the stable I kappa B alpha by AxI kappa B alpha Delta N infection significantly suppressed cell growth after irradiation in both cell lines as compared to infection with a control vector, AxLacZ. Treatment with AxI kappa B alpha Delta N and irradiation successfully inhibited the growth of HT29 xenografted subcutaneous tumors in nude mice with an 83.8% volume reduction on day 38 as compared to the untreated tumors. Furthermore, it was demonstrated that apoptosis was increased by adenovirus-mediated gene transduction of I kappa B alpha Delta N in vitro and in vivo. These results indicated that inhibition of NF-kappa B could enhance radiosensitivity through an increase in radiation-induced apoptosis. We believe that radio-gene therapy using adenovirus-mediated gene transduction of I kappa B alpha Delta N could be an attractive candidate as a treatment strategy for colorectal cancer.

Chemo-radio-gene therapy for colorectal cancer cells using Escherichia coli uracil phosphoribosyltransferase gene.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents, and is known to be a radiosensitizer. Previously, we reported that adenoviral transduction of the Escherichia coli (E. coli) uracil phosphoribosyltransferase (UPRT) gene induced marked sensitivity in human colon cancer cells to 5-FU. The aim of the current study was to investigate the efficacy of virally-directed UPRT and 5-FU to enhance the radiosensitivity of HT29 human colon cancer cells. Cytotoxicity as a result of radiation treatment following AdCA-UPRT infection and 5-FU exposure was confirmed by radiation dose-response analysis with colony formation assay. In vivo chemoradio-gene therapy using the UPRT/5-FU/radiation system showed tumor regressive effects even against large HT29-established subcutaneous tumors in nude mice. Our results suggested that adenovirus-mediated UPRT gene transduction combined with 5-FU administration and radiation may be an effective new chemo-radio-gene therapy for colorectal cancer.