Serum carcinoembryonic antigen level in non-small-cell lung cancer patients with preoperative normal serum level

Objective  The prognostic significance of serum carcinoembryonic antigen (CEA) levels in non-small-cell lung cancer (NSCLC) patients with a normal serum CEA level (<5.0 ng/ml) was examined. Methods  A total of 220 consecutive NSCLC patients with preoperative normal serum CEA levels were included. Patients were subdivided into two groups: preoperative serum CEA level ≥2.5 and <2.5 ng/ml. Results  The 5-year survival of patients with preoperative serum CEA level less and more than 2.5 ng/ml were 79.62% and 62.0%, respectively (P = 0.0036). Multivariate analysis indicated that a preoperative serum CEA level of ≥2.5 ng/ml was an independent prognostic factor. Similar results were found in patients with adenocarcinoma but not found in others. Conclusion  NSCLC patients with a high serum CEA level, especially adenocarcinoma patients, had poorer prognosis even if their serum CEA levels were within the normal upper limit.     

High oxygen tension prolongs the survival of osteoclast precursors via macrophage colony-stimulating factor

The oxygen tension affects the function, differentiation, and transformation of various cells, including bone cells. In pathological conditions such as rheumatoid arthritis (RA), rapidly destructive arthropathy, and primary or metastatic tumors, severe bone destruction or osteolysis occurs. Abundant blood vessels are often observed around these destructive lesions. At such sites, we have confirmed the increased production of reactive oxygen species (ROS) induced by a high oxygen tension and/or oxidative stress, as well as numerous osteoclasts detectable by immunohistochemistry. These findings suggest that osteoclasts are influenced by the high oxygen tension in pathological bone lesions because the zone around blood vessels has a relatively high oxygen tension. In this study, we investigated the effects of oxygen tension on osteoclastogenesis by culturing human CD14-positive cells (osteoclast precursors) with or without osteoblast-like supporting cells (Saos-4/3 cells) under a normal oxygen tension (20% O(2)) or a high oxygen tension (40% O(2)). A high oxygen tension markedly prolonged the duration of osteoclast precursor formation in the presence of supporting cells, and also markedly and persistently increased the production of macrophage colony stimulating factor (M-CSF) by supporting cells. Furthermore, we found an increase of cells expressing M-CSF and cells positive for tartrate-resistant acid phosphatase (TRAP) in hypervascular destructive bone lesions of RA patients where ROS were also abundant.     

Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-beta-galactosidase (ABase) for ABO-incompatible transplantation

BACKGROUND: ABO incompatibility in organ transplantation is still a high risk factor for antibody-mediated rejection, despite the progress in effective treatments. We have explored the possibility of using the enzyme to remove the blood type A/B antigen in organs. METHODS: Recombinant endo-beta-galactosidase (ABase), which releases A/B antigen, was produced in E. coli BL-21. Human A/B red blood cells (RBC) were digested with ABase, and subjected to flow cytometric analysis after incubation with human sera. Purified recombinant ABase was intravenously administered to a baboon. Biopsies were taken from kidney and liver before and 1, 4 and 24 h after in vivo administration. Excised baboon kidneys were perfused with cold UW solution+/-purified recombinant ABase and preserved at 4 degrees C. Biopsies were taken before and 1 and 4 h after ex vivo perfusion. The change in A/B antigen expression was analyzed by immunohistochemical study. RESULTS: ABase removed 82% of A antigen and 95% of B antigen in human A/B red blood cells, and suppressed anti-A/B antibody binding and complement activation effectively. ABase was also found to remain active at 4 degrees C. In vivo infusion of ABase into a blood type A baboon demonstrated a marked reduction of A antigen expression in the glomeruli of kidney (85% at 1 h, 9% at 4 h and 13% at 24 h) and the sinusoids of liver (47% at 1 h, 1% at 4 h and 3% at 24 h) without serious adverse effects. After ex vivo perfusion and cold storage of excised baboon kidney (blood type B) with ABase, the expression levels of B antigen in glomeruli were reduced to 49% at 1 h and 6% at 4 h. CONCLUSIONS: This alternative approach might be useful for minimizing antibody removal and anti-B cell immunosuppression as an adjuvant therapy in ABO-incompatible kidney, liver and possibly heart transplantation.     

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR),lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT),it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI,firstly reported in our department,and IVR (PELI and IVR,lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment,the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus,this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.