Combination of irinotecan hydrochloride and etoposide for treatment of refractory or relapsed small-cell lung cancer

We used a combination of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor as a support therapy for refractory or relapsed small-cell lung cancer (SCLC). This combination regimen was active against refractory or relapsed SCLC as gauged by a response rate of 71% and a median survival time of 271 days. Further studies of this combination regimen in refractory or relapsed SCLC are warranted.     

Pharmacokinetic and pharmacodynamic analysis of bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) administered once a day for five consecutive days: a phase I study

BACKGROUND: Bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) is the first orally given platinum complex that shows in vitro cytotoxicity comparable to that of cisplatin and in vivo cytotoxicity superior to those of cisplatin and carboplatin. METHODS: We conducted an escalating-dose (50, 75, 100, 120 mg/m2) phase I study of JM216 administered orally once a day for five consecutive days in patients with solid tumors to establish the toxicity profile, maximum tolerated dose (MTD) and pharmacokinetic profile. Twenty-three patients were enrolled and all were assessable for toxicity. RESULTS: The MTD was 120 mg/m2/day and the dose-limiting toxicities were leukopenia, thrombocytopenia, anemia and diarrhea. Because of the delayed hematological toxicities, it was difficult to repeat cycles every 26 days in some patients. Tumor shrinkage was observed in two patients with breast cancer, both of whom were resistant to doxorubicin. A pharmacokinetic study showed that the areas under the concentration-time curve (AUC) and peak plasma concentrations (Cmax) for total platinum (Pt) on days 1 and 5 and ultrafiltered Pt (UF-Pt) on day 1 increased in proportion to the dose of JM216. The AUCs for both total and UF-Pt on day 5 were higher than the AUCs on day 1. The AUC for UF-Pt on day 5 showed the best correlation with percentage reduction in leukocyte count and in absolute neutrophil count. CONCLUSION: The recommended dose for phase II studies is 100 mg/m2/day every 4-6 weeks. The observation of tumor shrinkage in previously heavily treated breast cancer patients supports a phase II investigation.     

A case of cystic cavernous angioma accompanied by a fluid-fluid level on magnetic resonance imaging]

We describe the case of a patient with cavernous angioma (CA). A 44-year-old woman complained of numbness on the left side of the body as an initial symptom of the disease. The initial magnetic resonance (MR) imaging revealed a cystic mass with a fluid-fluid level without perifocal edema in the right thalamus on the T 2-weighted image (T 2WI) and T2*-weighted image (T2*WI). Her symptoms were self-controllable; therefore we decided to observe her natural course only with serial MR imaging. The cystic mass was not enhanced by gadolinium on T1-weighted images, although, we suspected the tumor was complicated by vascular malformation. Therefore, we performed cranial angiography to eliminate the possibility of bleeding from the vascular malformation. Angiography did not demonstrate tumor staining nor vascular malformation. Longitudinally, the tumor demonstrated mosaic signal intensities on each sequence with perifocal edema. Moreover, the tumor exhibited hypointensities on T2* WIs without perifocal edema. The natural history of the tumor on MR imaging exhibited a typical case of CA. Some previous reports described cystic CA with perifocal edema and vascular malformation. In our present case, we clinically diagnosed CA on the basis of the final MR imaging together with previous reports. An intra-axial fluid-fluid level is a very rare finding of MR imaging. Here, we report the case of a patient with cystic CA accompanied by a fluid-fluid level. This finding is not a pathognomonic sign of CA; although, we consider that it is very important to follow up carefully the natural history of such cases.     

The 56 kd platelet-derived growth factor (PDGF)-related protein is phosphorylated and the most stable form in human glioma cells

We report herein the presence of a 56 kd platelet derived growth factor (PDGF)-related protein as a phosphorylated form in human glioma cells. The phosphorylation of the 56 kd form was found to be the longest of all PDGF-related proteins. By Western blotting using a monoclonal anti-PDGF B-chain, the 80 kd, 56 kd, 40 kd, 28 kd and 17 kd PDGF-related proteins were detected, while after treatment among the nitrocellulose membrane transblotted cell extracts with alkaline phosphatase, 40 kd was the most densely observed while the 56 kd and 80 kd PDGF-related proteins were also detected. In a ³²P flush labeling study, it was revealed that PDGF-related proteins incorporated with ³²P were detected at 28, 32, 35, 40, 56 and 80 kd but the 17 kd monomer was not labeled. Among the labeled PDGF-related proteins, the 56 kd PDGF-related protein alone remained intracellularly for at least 16 hours. These results indicated that the PDGF-related proteins in human glioma cells are synthesized in a phosphorylated form and partly remain in a 56 kd phosphorylated form intracellularly. The 56 kd form may thus be the most stable form and likely has a substantial biological effect.     

Multiple basilar trunk aneurysms and bilateral internal carotid artery hypoplasia

We describe a case of a 32-year-old woman with bilateral hypoplastic internal carotid arteries who presented with subarachnoid haemorrhage and was found to have two basilar trunk aneurysms. Carotid angiography showed that both internal carotid arteries were narrowed at their origin and terminated at the cervical segment. Vertebral angiography demonstrated a dilated vertebrobasilar system which supplied sufficient blood flow for both cerebral hemispheres through the posterior communicating arteries. The patient was successfully treated by multiple operations.     

Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.     

Chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats

Numerous cellular and molecular perturbations have been studied to elucidate the pathogenic mechanisms underlying nephrotic-range proteinuria, which may in turn shed light on disease-specific mechanisms. We have analyzed the publicly available data from the PhysGen partial panel of consomic rats to determine whether there are quantitative trait loci that associate with nephrotic-range proteinuria. As of this writing, consomic rat strains subjected to the renal protocol have been bred by the Program for Genomic Applications for 15 of the 22 rat chromosomes for both genders, predominantly with the Brown–Norway (BN) and Dahl salt-sensitive (SS) strains as parents. We defined chromosomes of interest as consomic SS-xBN strains whose phenotype measurements differed significantly from SS but not BN strains, stratified by gender. We filtered and clustered differentially expressed genes by function in renal tissue from relevant strains. Proteinuria was significantly higher in male SS vs. male SS-18BN, and it was significantly higher in male SS vs. female SS. Functional clustering of differentially expressed genes yielded two specific functional clusters: apoptosis (p=0.022) and angiogenesis (p=0.046). Gene expression profiles demonstrated differential expression of apoptotic and angiogenic genes. However, TUNEL stains of renal tissue showed no significant difference in the number of apoptotic nuclei. We conclude that chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.