Anticancer chemosensitivity profile of freshly separated human pancreatic cancer cells assessed by DNA synthesis inhibition assay

The chemosensitivity of 49 freshly separated human pancreatic cancers to seven kinds of anticancer agents were assessed by a DNA synthesis (³H-thymidine incorporation) inhibition assay. DNA synthesis is higher in involved lymph nodes (n=7), malignant effusion (n=15), liver metastasis (n=7), primary cancer (n=15), and skin metastasis (n=5). Chemosensitivity assay demonstrates that etoposide, 4-epirubicin, carboquone, and 5-fluorouracil are more effective than cisplatin, mitomycin-C, and Adriamycin. In general, metastatic lesions of pancreatic cancer tend to show higher chemosensitivity than primary lesions. Pathological analysis demonstrates that small primary pancreatic cancers tend to be more responsive than large primary cancers, and primary pancreatic cancers with no regional lymph node involvement also tend to be more responsive than those with nodal involvement. No significant differences are seen in terms of tumor spread, vascular involvement, sex of patient, and histological type. When chemosensitivity assay is not available, the results of the present study may be beneficial to choose the regimens. © 1994 Wiley-Liss, Inc.     

Association of dietary fatty acids with urinary oxalate excretion in calcium oxalate stone-formers in their fourth decade

OBJECTIVE: To examine the influence of the dietary intake of fatty acid on urinary oxalate excretion in calcium oxalate stone-formers in their fourth decade, as previous reports show that animal fat intake is associated with urinary oxalate excretion. PATIENTS AND METHODS: The dietary intake of 58 idiopathic stone-formers in their fourth decade was recorded using the dietary-record method. The patients collected 24-h urine samples at home and their urinary oxalate excretion was measured in a clinical biochemistry laboratory. The results were used to determine the relationship between the dietary intake of fatty acids and urinary oxalate excretion. Associations between urinary oxalate excretion and dietary contents of animal fat, animal protein and various fatty acids were assessed using Spearman's correlation coefficient and multiple regression. RESULTS: The dietary content of arachidonic acid was positively correlated with urinary oxalate excretion, as assessed by univariate and multivariate analysis. CONCLUSION: The association between arachidonic acid and oxalate excretion suggests that arachidonic acid increases the intestinal absorption of oxalate and increases the clearance of oxalate in the kidneys.     

Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time dispersion in acute myocardial infarction

lodine-123 metaiodobenzylguanidine (MIBG) uptake was reported to be reduced compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an area, degrees of both sympathetic neural function and ischemic myocardial cell damage are considered to be greatly dispersed. These kinds of damage were reported to effect reporalization time in myocardial cells, and we evaluated our hypothesis that extension of the discordant MIBG uptake area correlates with recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated in 9 segments of SPECT by using four-point scoring. The total score was the sum of scores in 9 SPECT segments. ATI-MIBG was calculated by subtracting the total MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal-averaged ECG. RTc dispersion was defined as the difference between maximal and minimal RTc. The patients were assigned to two groups (group A; < or = Lown 4a, group B; > or = Lown 4b) according to the results of 24-hour Holter monitoring. A positive correlation between RTc dispersion and ATI-MIBG was found. ATI-MIBG and RTc dispersion in group B were greater than those in group A. These results suggested that ATI-MIBG could be used to predict the development of malignant ventricular arrhythmias.     

Detection of a coronary arterial thrombus by indium-111-oxine-labeled platelet scintigraphy

Coronary arteriography revealed significant left anterior descending coronary artery stenosis in a 72-year-old man with a history of myocardial infarction. Stenting of the stenotic vessel was performed. Twelve hours after stenting the patient complained of chest pain but emergent coronary arteriography did not show sign of any coronary arterial stenosis. Under suspicion of coronary thrombus formation, indium-111-oxine-labeled platelet scintigraphy was performed 5 days after stenting, and revealed accumulation of indium-111-oxine in the area corresponding to the stent implantation site.     

Use of electroporation to accelerate the skin permeability enhancing action of oleic acid

Rat skin permeability after treatment by electroporation (newly developed frog type electrode, 100V, 10 pulses), oleic acid/propylene glycol (PG) and a combination of both were investigated using Fourier transformed infrared attenuated total reflectance (FT-IR/ATR) analysis. Electroporation immediately disordered the stratum corneum lipid structure up to a certain threshold level. This action lasted throughout the experiment. This may be attributed to the formation of long lifetime of metastable lipid structures, which may allow molecules to pass to the inside of the stratum corneum due to the electroporation-induced fluidized lipid membranes. Electroporation also altered the protein structure of the stratum corneum. When electroporation was combined with 0.05 M oleic acid/PG, uptake of oleic acid and PG into the stratum corneum was remarkably accelerated compared to the application of only 0.05 M oleic acid/PG to the skin. This indicates that electroporation enables oleic acid and PG to penetrate the stratum corneum easily by disrupting the structure of the latter. PG transfer into the dermis from the epidermis was accelerated, not because of the direct action of electroporation on the dermis, but because electroporation induced the rapidly disordering action of oleic acid on the stratum corneum. Lipid-soluble indomethacin permeated the skin more rapidly when the skin was treated with electroporation plus oleic acid/PG than with 0.05 M oleic acid/PG in vitro.     

Serum carotenoids and other antioxidative substances associated with urothelial cancer risk in a nested case-control study in Japanese men

PURPOSE: We assayed whether high serum carotenoids and antioxidative substances decrease the risk of urothelial cancer in a case-control study nested in a community based cohort in Japan, that is the Japan Collaborative Cohort Study. MATERIALS AND METHODS: Information on subject life-styles and serum were collected in 1988 to 1990 and subjects were followed as late as 1999. Individuals who had or died of urothelial cancer and controls were matched for study area, sex and age. Serum was stored at -80C and analyzed in 2003. Of 14,097 male and 25,662 female subjects 40 to 79 years old there were 42 cases, which were matched to 124 controls. RESULTS: The OR for the highest to lowest tertile of serum concentration was 0.28 (95% CI 0.07 to 1.15, trend p = 0.08) for beta-carotene, 0.36 (95% CI 0.10 to 1.27, trend p = 0.10) for total carotenes and 0.31 (95% CI 0.09 to -1.09, trend p = 0.09) for total carotenoids after adjustment for smoking in addition to matching variables. High concentrations of tocopherols and xanthophylls slightly tended to decrease the risk of urothelial cancer. In contrast, serum retinol, oxidized low density lipoprotein and Cu/Zn-superoxide dismutase were not associated with urothelial cancer risk. CONCLUSIONS: Our results suggest that high serum carotenoids may decrease the risk of urothelial cancer with carotenes more effective than xanthophylls.     

Functional interaction between tumor suppressor menin and activator of S-phase kinase

Multiple endocrine neoplasia type I (MEN1), a hereditary tumor syndrome, is characterized by the development of tumors in multiple endocrine organs. The gene mutated in MEN1 patients, Men1, encodes a tumor suppressor, menin. Overexpression of menin leads to inhibition of Ras-transformed cells. However, it is unclear whether menin is essential for repression of cell proliferation, and if it is, how it inhibits cell proliferation. Here, we show that targeted disruption of the Men1 gene leads to enhanced cell proliferation, whereas complementation of menin-null cells with menin reduces cell proliferation. Moreover, menin interacts with activator of S-phase kinase (ASK), a component of the Cdc7/ASK kinase complex that is crucial for cell proliferation, but does not appear to alter Cdc7 kinase activity in in vitro kinase assays. We identify the COOH terminus of menin as the domain that mediates the specific interaction with ASK. Notably, wild-type menin completely represses ASK-induced cell proliferation, although it does not obviously affect the steady-state cell cycle profile of ASK-infected cells. Interestingly, disease-related COOH-terminal menin mutants that do not interact with ASK completely fail to repress ASK-induced cell proliferation. Together, these findings demonstrate a functional link between menin and ASK in the regulation of cell proliferation.     

mRNA expression of chemokine receptors in hepatic and pancreatic tumor cell lines

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, and directional migration. Recent observations have indicated that the expression of chemokine receptors on cancer cells may play a role in tumor progression and metastasis. In this study, the expression of mRNA for chemokine receptors in various human tumor cell lines was analyzed by multiplex-polymerase chain reaction (M-PCR). Strong expression of CCR6 mRNA in 3 of 3 hepatoma cell lines was observed. In the 3 pancreatic cancer cell lines, no specific expression of chemokine receptors was observed. Raji (lymphoma cell line) strongly expressed CCR7 and CXCR4. We further investigated CCR6 mRNA expression in these cell lines by real-time quantitative-PCR. Similar results were obtained by both the PCR methods. Because human liver constitutively express liver and activation-regulated chemokine (specific ligand for CCR6), hepatoma cells may selectively root and spread in the liver. Strong CCR7 and CXCR4 expressions in the lymphoma cell may explain the organ specificity of lymphoma for lymphoid organs as well. These findings probably indicate that some cancer cells have organ specificity via expression of chemokine receptors.