Developed new agents for lung cancer

Platinum-based chemotherapy is considered to be the standard chemotherapy of non-small cell lung cancer (NSCLC) at present. New agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, topotecan, and amurubicin were developed in the 1990s. Combination chemotherapy using new agents improved survival rates compared with the classic regimen. Irinotecan, paclitaxel, docetaxel, vinorelbine, and gemcitabine have been confirmed to be effective against NSCLC. However, chemotherapy for NSCLC is controversial because the differences in the efficacies of combination chemotherapies including new agents have not been recognized in randomized controlled trials. The Four-Arms Cooperative Study is an ongoing postmarketing clinical trial in Japan. The a ntitumor agents irinotecan, topotecan, paclitaxel, and amurubicin have been confirmed to be effective in small cell lung cancer (SCLC). The combination of etoposide and cisplatin (PE) is the standard regimen for SCLC in Western countries. However, the combination of irinotecan and cisplatin (CP) resulted in higher response rates and better median survival times than PE for extensive-disease SCLC in a JCOG trial. At present, CP is considered to be the standard chemotherapy regimen to treat SCLC in Japan. The development of new agents, particularly molecular target-based drugs and multimodality treatment, is necessary to improve the therapeutic results in lung cancer further.     

Effective transfection of a cis element "decoy" of the nuclear factor-kappaB binding site into the experimental choroidal neovascularization

PURPOSE: To evaluate the efficacy of the gene transfer of a double-stranded phosphorothioate oligonucleotides (ODNs), called a "decoy", against the NF-kappaB binding site into cells of an experimentally-induced choroidal neovascularization. METHODS: FITC-labeled decoy was injected into the subretinal space of rat eyes by the HVJ-liposome delivery system, and 3 days later, choroidal neovascularization was induced by laser photocoagulation. The eyes were removed and the transfected cells were detected by fluorescence microscopy and also detected by immunohistochemistry. The degree of neovascularization was evaluated by fluorescein angiography. RESULTS: The decoy was transfected into the retinal pigment epithelial (RPE) cells, inner and outer segment of the photoreceptors at 3 days after the injection. When choroidal neovascularization was induced, highly effective transfection of the decoy was observed 3 to 14 days after photocoagulation, after which the level decreased. Decoys were transfected into the RPE cells and macrophages in the choroidal neovascularization. The eyes transfected with NF-kappaB decoy showed a weaker leakage in fluorescein angiograms than that of the control eyes transfected with scrambled decoy. CONCLUSIONS: A decoy can be transfected into retinal cells and cells within a choroidal neovascularization by the HVJ-liposome method. The transferred NF-kappaB decoy reduced the degree of choroidal neovascularization. Decoy targeted against NF-kappaB may be considered as a potential therapy for neovascularization.     

Anesthetic factors that influence pH of neonatal umbilical artery from mothers in severe gestosis during cesarean section under sevoflurane anesthesia

Twenty-two patients complicated with severe gestosis underwent cesarean section. General anesthesia was induced with intravenous thiopental and suxamethonium and maintained with sevoflurane below 1.5% with 40-50% oxygen and 50-60% nitrous oxide. Mean artery pressure at and after the induction as well as at the delivery, expired maternal sevoflurane concentrations at the delivery and neonate birth weight were measured for statistical analyses in relation with neonates pH of umbilical artery. Mean artery pressure at the delivery and neonates birth weight influence neonates pH of umbilical artery.     

Bispectral index monitoring is useful to reduce total amount of propofol and to obtain immediate recovery after propofol anesthesia

Bispectral index (BIS) is a processed EEG parameter for assessment of hypnotic effects of anesthetics. We studied whether BIS monitoring can improve recovery from propofol anesthesia and decrease the total amount of propofol needed. Forty-six patients without hypertension and obesity were studied. In the BIS group (n = 20), propofol infusion rate was adjusted to achieve a target BIS value between 40-60, increasing to 65 during the final 10 min of the surgical procedure. In the control group (n = 19), propofol infusion rate was adjusted based only on standard clinical signs. Compared with the control group, patients in the BIS group required lower propofol infusion rates(4.3 +/- 1.1 vs 4.9 +/- 0.8 mg.kg-1.h-1; P < 0.05), and the total amount of propofol decreased significantly (709 +/- 210 vs 914 +/- 326 mg; P < 0.05). BIS monitoring led to immediate recovery after propofol anesthesia. There were no significant differences in the incidence of intraoperative responses between the two groups. BIS monitoring decreased the total amount of propofol and led to immediate recovery after propofol anesthesia. These findings indicate that the use of BIS monitoring may be useful in controlling the infusion rate of propofol during surgery.     

Mosaic development of the olfactory cortex with Pax6-dependent and -independent components

The olfactory cortex is the target area of olfactory bulb axons and is suggested to be derived from neuroepithelial progenitors of various ventricular domains during development. In the present study, we examined the development of the olfactory cortex, using the newly developed monoclonal antibody (mAb) 9-4c, which recognizes reticulon 1-A and -B. The mAb labeled neuroepithelial progenitors at the pallio-subpallial boundary (PSB) and their putative descendants in the deep layers of the olfactory cortex. In the Pax6 mutant embryo, labeling at the PSB was specifically lacking, and the number of immunopositive cells in the olfactory cortex was markedly reduced. In contrast, the guidepost neurons of olfactory bulb axons, lot cells, developed relatively normally in the superficial layer of the olfactory cortex in the mutant embryo. These guidepost neurons have been recently shown to originate in the pallium and eventually guide the initial projection of olfactory bulb axons. The olfactory bulb projection in the Pax6 mutant embryo also suggested the dualistic nature of the olfactory cortex development; the initial projection of olfactory bulb axons developed relatively normally, whereas the final projection of their collateral branches was severely defective.     

Bone and joint diseases in the elderly

As a current attention of the medical treatment has been paid to improve guality of the life rather than to save the life of the patient, so the treatment of bone and joint diseases, which are not ordinarily fatal and deteriorate quality of the life of the patient, would become important in the aged society of 21 century. In a strategy to improve the quality of life in the patient with osteoarthritis, disease modifying anti-osteothritis drugs are investigated for primary prevention and complete recovery of osteoarthritis. In osteoporosis, a characteristic bone disease of the aged, aims of the treatment have been changed from freeing of pain in the nineteen sixties, increase of bone mass in the nineteen eighties and reduction of the fracture rate in the nineteen nineties to improve of quality of the life through decrease of pain and fracture in 21 century. In conclusion, current management for bone and joint diseases in the elderly is finally designed to enjoy a healthy life of long span by medical intervention.     

Carboxyl-terminal Heparin-binding Fragments of Platelet Factor 4 Retain the Blocking Effect on the Receptor Binding of Basic Fibroblast Growth Factor

Platelet factor 4 (PF-4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor. In the present study, we constructed carboxyl-terminal fragments, which represent the heparin-binding region of the PF-4 molecule, and examined whether these synthetic peptides retain the blocking effects on the receptor binding of bFGF. Synthetic peptides inhibited the receptor binding of bFGF. Furthermore, they inhibited the migration and tube formation of bovine capillary endothelial cells in culture (these phenomena are dependent on endogenous bFGF).