Biochemical Modulation of 5-Fluorouracil with Murine Interferon-α/β Against Murine Renal Cell Carcinoma

Department of Urology, School of Medicine, Keio University, Tokyo, Japan
Background Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate the mechanisms of interaction between the 2 agents in mice.
Methods Antitumor effects and biochemical modulation of murine IFN-α/β and 5-FU were determined against the murine renal cell carcinoma cell line, Renca, in vivo. The activity of thymidylate synthetase and thymidine kinase was measured using cytosolic extracts of the tumors.
Results Combination treatment with IFN-α/β and 5-FU produced a significant enhancement of growth inhibition against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the total amount of thymidylate synthetase and an 11.6-fold increase in the thymidylate synthetase inhibition rate, while the administration of IFN-α/β did not significantly reduce the 5-FU-induced increase in thymidylate synthetase. The administration of IFN-α/β decreased thymidine kinase activity to 65.5% maximally, compared with that in the control mice or the mice treated with 5-FU.
Conclusions The reduction of thymidine kinase caused by treating the mice with IFN-α/β changes the utilization of exogenous thymidine for DNA synthesis, and may represent the mechanism of the additive antitumor effect of the 2 agents, through the suppression of the salvage pathway for deoxythymidine monophosphate induction.     

Application of magnetic resonance imaging to evaluation of femoral neck structure in growing girls.

Conventional density measures by dual-energy X-ray absorptiometry (DXA) are confounded by increases in bone size and do not assess bone geometry. We assessed precision of magnetic resonance imaging (MRI) and used MRI, DXA, and hip structure analysis (HSA) to assess 7-mo changes in bone structure at the femoral neck in 18 prepubertal girls. At baseline, girls were 10.4 (0.5) yr, 144.0 (8.2) cm, and 35.2 (7.0) kg, on average. Total bone and cortical cross-sectional area (ToA and CoA) were calculated from high-resolution T1-weighted MRI oblique axial images of the femoral neck. We used proximal femur DXA scans (Hologic QDR-4500) and the HSA program to estimate bone cross-sectional area (CSA), and calculate section modulus. MRI precision was determined by scanning 10 volunteers (13-46 yr old) three times with and without repositioning. Precision (CVrms) was 2% for ToA and 7% for CoA. Significant correlations were observed between FN area and MRI-derived ToA (r = 0.57, p = 0.013) and CoA (r = 0.47, p = 0.050). There were significant positive changes over 7 mo by both methods. In conclusion, MRI provides useful information on femoral neck bone area in children. The reproducibility of cortical dimensions at the femoral neck needs improvement through technical modifications and appropriate analysis software.     

Papillo-Choledochectomy in the Operative Management of Mucosal Neoplasms of the Periampullary Region

Two patients with mucosal cancer of the periampullary region were treated with papillocholedochectomy, which entails removal of the papilla of Vater and the whole length of the common bile duct. The neoplasm is dissected out through the plane between the duodenal circular and longitudinal muscles, deep to the sphincter of Oddi and the fibromuscular layer of the bile duct. Pathological examination showed that cancer was confined to the mucosal layer without stromal invasion, and that the operation achieved radical cure. For mucosal cancer, papillo-choledochectomy is an alternative to pancreatoduodenectomy, provided that repeated frozen-section studies confirm the completeness of excision.     

Synchronous pulmonary atypical adenomatous hyperplasia and metastatic osteosarcoma in a young female

A 17-year-old female underwent metastasectomy of three synchronous lesions in the bilateral lungs under the diagnosis of metastatic osteosarcoma, however, one of them was found to be atypical adenomatous hyperplasia (AAH). Since AAH is very rare among young people, a careful evaluation of high-resolution computed tomographic image is important in determining the operative indications and procedures in patients with multiple metastatic tumors.     

Alleviation of gallbladder complications by treatment of hepatic arterial embolization with caerulein

Transcatheter arterial embolization (TAE) with the concurrent use of caerulein was assessed for the purpose of preventing gallbladder complications often seen after TAE of hepatic carcinoma. Ninety-six cases with primary hepatic carcinoma, who had undergone TAE in the right hepatic arterial region over the past 4 years, were divided into three groups: 22 cases for which embolization was possible on a selective basis by passing the catheter to the peripheral side beyond the bifurcated region of the cystic artery; 40 cases who had undergone TAE in which caerulein was not administered, from the central side of the bifurcated region of the cystic artery; and 34 cases given 20 g caerulein 15–30 min before TAE. A comparison was made using the abdominal pain, pyrexia, rate of leukocytosis and the US findings of the gallbladder as the indices of the gallbladder complications. As a result, it become evident that it was possible to prevent or alleviate gallbladder complications if caerulein were administered before TAE in cases where the embolizing substances were infused in the right hepatic artery from the central side of the bifurcated region of the cystic artery. It was conclusively shown that the gallbladder blood flow decreases if the organ is contracted by caerulein, which in turn causes a decrease in the inflow of the embolizing substances whereby complications are alleviated.     

Evaluation of dengue IgM detection tests using sera from patients with autoimmune diseases

Three commercial dengue IgM test kits and 'in-house' IgM-capture enzyme-linked immunosorbent assay (ELISA) were examined for false positive reactions, using 49 serum samples from patients with autoimmune diseases. All the samples were found to be negative by the 'in-house' IgM-capture ELISA. Five samples were determined to be positive by the immunochromatographic test and three of the five samples were also found positive by one commercial IgM-capture ELISA kit. These results suggest that a possibility of false positive reaction should be considered when serum samples from autoimmune disease patients are tested for dengue IgM by some commercial dengue IgM test kits.     

Switching from a restricted to an effective CD4 T cell response by activating CD8+ murine dendritic cells with a Toll-like receptor 9 ligand

Freshly isolated quiescent splenic dendritic cell (DC) subtypes differ in their capacity to activate naive CD4 T cells in culture. The CD8+ DC showed a reduced capacity to stimulate T cell proliferation compared to either of the CD8- DC subsets, regardless of antigen and DC dose. In contrast to CD8- DC, the quiescent CD8+ DC did not induce IFN-gamma production from CD4 T cells. The difference between the DC subtypes appeared to be at the level of initial surface molecule interactions, but could not be attributed to differences in expression of MHC class II or B7 family molecules, or to the expression of Fas ligand on DC. However, when activated by inclusion of the Toll-like receptor 9 ligand CpG in culture, CD8+ DC became potent stimulators of both CD4 T cell proliferation and IFN-gamma production. In contrast, similar activation of CD8- DC produced a more modest increase in capacity to stimulate CD4 T cell proliferation and no increase in capacity to stimulate IFN-gamma production. The difference between a quiescent and an activated state is therefore more extreme for CD8+ than for CD8- DC. The especially tight regulation of the activity of CD8+ DC may be essential for the maintenance of self tolerance.