Selective retention of rhodamine-123 by malignant glioma in the rat

Levels of rhodamine 123 (Rh-123), a new antineoplastic drug, were measured using high performance liquid chromatography in normal brain, malignant glioma and brain adjacent to tumor after a single intravenous injection of drug into rats with intracerebral tumors. Consistently higher levels of Rh-123 were seen in tumor compared to normal brain at all times. Tumor levels of Rh-123 increased up to a maximum level of 9.35 nm/mg at 5 hours after intravenous injection (10 mg/kg), afterwhich Rh-123 levels slowly decreased. Rh-123 concentration in serum reached a maximum level immediately after intravenous injection and Rh-123 was eliminated from the serum according to first order kinetics. The delayed (5 hours after injection) increase in tumor concentration of Rh-123 may reflect tumor hypoperfusion and/or the time required for the compound to diffuse from the blood to the cells within the tumor due to the blood brain barrier. These findings have directed us to study low dose continuous infusion and direct intratumoral injection of Rh-123 as ways of achieving higher Rh-123 levels in tumor with less risk of systemic toxicity due to elevated serum Rh-123 levels.     

Photosensitization of human glioma cells by chalcogenapyrylium dyes

Chalcogenapyrylium (CP) dyes which are specifically activated by red and near infrared light (600–900 nm) were examined as potential photosensitizers for photochemotherapy of malignant gliomas. Eleven CP dyes of varying chemical structure and redox potential were evaluated for selective toxicity against glioma and normal skin fibroblast cell cultures both before and after light activation. Eight of eleven CP dyes exhibited differential toxicity to tumor over fibroblast cells at dye concentrations of 1.0 µM. Dose dependent toxicity was seen both in the dark and after laser light activation. The toxicity of two of the CP dyes was significantly enhanced by photoactivation with 800 nm light.The CP dyes that absorb light maximally between 775 and 850 nm, in the range of excellent light penetration through brain, appear to be promising candidates as photosensitizers for treating malignant brain tumors.     

中药局部光化学疗法治疗银屑病27例报告

从７种中药中，经光敏试验筛试出光敏作用最强的二种中药白芷、大黄，将其各自配成３０％酊剂，涂于皮损后照射长波紫外线及中波紫外线。治疗２７例寻常型银屑病患者，总有效率９２．６％，可与口服中药光化疗法相比，并可避免口服光敏性药物引起的全身副作用及致癌、白内障等危险。     

光化学疗法对银屑病患者的遗传毒性影响及其预防的研究

本文研究33例银屑病患者内服8—甲氧基补骨脂素(8-MOP)或中药白芷加长波紫外线(UVA)照射对外周血淋巴细胞SCE率(姐妹染色单体互换率)和微核出现率的影响。光疗后淋巴细胞的SCE率和微核率均明显高于光疗前,提示本疗法对DNA有损伤作用,有潜在的致癌危险。治愈病例停治一年后复查,8-MOP组的微核率明显低于光疗后,接近光疗前的水平;8—MOP组和白芷组的SCE率比光疗后亦有降低,均提示细胞内DNA修复酶系统对DNA的损伤有修复作用。适当控制光化学疗法(PUVA)剂量,且治愈后不进行巩固治疗,其致癌可能性可以避免。     

Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood

BACKGROUND: Extracorporeal photochemotherapy (EPC) has recently been proposed for the treatment of adults with either acute or chronic GVHD. However, data on children given this therapy are scarce. A Phase I-II study was carried out on EPC in children experiencing GVHD after allogeneic transplantation of HPCs. STUDY DESIGN AND METHODS: Nine patients with steroid-resistant, grade II-IV acute GVHD and 14 with chronic GVHD, all of whom had been refractory to at least one line of treatment, were enrolled in this study and analyzed. The median age was 10.3 years (range, 5.4-18.1), and the median body weight was 35 kg (range, 17-89). RESULTS: Seven of the nine patients with acute GVHD showed a response to EPC, whereas the disease progressed in the remaining two children (both with skin, gastrointestinal, and liver GVHD), and they died of grade IV acute GVHD. Among the seven children who responded to EPC, it was possible to completely discontinue immunosuppressive treatment in three. In the 14 children with chronic GVHD, 4 and 5 patients experienced complete and partial response to EPC, respectively, whereas the remaining 5 patients, all with extensive chronic GVHD, had stable disease or disease that progressed during EPC. Among these latter 5 patients, 3 died. In 6 of the 9 patients with chronic GVHD responding to EPC, immunosuppressive therapy was discontinued. CONCLUSION: EPC is safe, feasible, and effective in children with either acute or chronic GVHD occurring after an allograft.     

Treatment of persistent severe atopic dermatitis in 113 Japanese patients with oral psoralen photo-chemotherapy

Oral administration of psoralen and whole body exposure to UVA (oral PUVA) has been used for the treatment of 113 patients with severe atopic dermatitis (AD). 8-Methoxypsoralen (8-MOP) was given at a dose of 0.5-0.6 mg/kg two hours prior to UVA (3-8 J/cm2) irradiation. Patients were treated three times a week while hospitalized. Other medications which had been given before PUVA therapy were permitted. At four and eight weeks after PUVA therapy, the severity score of AD had decreased by 51% and 80%, and the cumulative doses of UVA were 51.2 J/cm2 and 115.3 J/cm2, respectively. The amounts and strength of topical cortico-steroids were decreased during PUVA therapy. No adverse effects that required discontinuation of the PUVA therapy were observed. After discharge, maintenance therapy with UVB phototherapy and/or conventional treatment of AD kept the patients in remission in the outpatient clinic. The QOL of patients was greatly improved. Photochemotherapy with oral 8-MOP can be indicated in patients with severe, widespread AD, especially if standard therapy fails. This is the first report of oral PUVA therapy in a large series of Japanese patients with AD.     

ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF- production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.F.L.P. and M.F. contributed equally to this work.     

Treatment of polymorphous light eruption

Summary This study was designed in order to prove on a large-scale basis the efficacy of oral photochemotherapy (PUVA) in the prevention of polymorphous light eruption (PLE), to work out indication criteria for PUVA treatment of this disease, and to establish a simple method based on anamnestic data to differentiate UVA from UVB induced PLE. The results obtained in 106 PLE patients (85 UVA-, 21 UVB-induced) demonstrate that: 1) time consuming phototesting for determination of the disease's action spectrum is unnecessary for practical purposes; 2) PUVA-induced tanning under routine conditions represents a potent prophylaxis even in severe cases of PLE; and 3) topical sunscreens (sunblockers) in the majority of cases are sufficient to protect UVB-promoted PLE, but fail in UVA-induced disease. PUVA thus seems the treatment of choice only in UVA-mediated PLE, the action spectrum of the disease at least in most cases being easily discovered from certain anamnestic data.