11C-acetate clearance in nasopharyngeal carcinoma

This study assessed 11C-acetate turnover (clearance) in nasopharyngeal carcinoma (NPC). Data were acquired by dynamic PET after the intravenous injection of 4.625 MBq.kg-1 body weight of 11C-acetate for 30 min. Tomograms were reconstructed and evaluated visually. A time-activity curve of the nasopharynx and neck was generated and the clearance rate of 11C-acetate from the nasopharynx in the slow phase and from NPC was calculated using 0.693/T1/2. Ten patients with nasopharyngeal carcinoma and nine normal subjects were studied. The clearance of 11C-acetate from the normal nasopharynx was rapid and biexponential, in contrast to the rapid uptake followed by extremely slow clearance in patients with NPC. The clearance rate (mean +/- S.D.) was 0.0074 +/- 0.0042 in NPC and 0.0263 +/- 0.0152 in controls in the slow phase, being significantly different between the two groups with no overlap. All nasopharyngeal carcinomas were clearly visualized, in contrast to no obvious retention in the normal nasopharynx. Our initial results indicate that 11C-acetate clearance can be used to differentiate nasopharyngeal carcinoma from a normal nasopharynx. This finding may lead to new applications of 11C-acetate in oncology.     

An in vivo model of femtosecond laser intrastromal refractive surgery

BACKGROUND AND OBJECTIVE: To develop an animal model for evaluation of femtosecond laser intrastromal refractive surgery. METHODS: Intrastromal photodisruption was performed in New Zealand Albino rabbits using a femtosecond laser system. This surgical pattern consisted of a 100 microm-tick pyramid of laser pulses starting 180 microm below the corneal surface. Animals underwent serial slit lamp examinations and corneal thickness measurements at 1,3,7,14, and 28 days, then monthly up to 1 year. RESULTS: Approximately 70 microm of central corneal thinning were seen at 1 week, remaining stable up to 7 months. CONCLUSIONS: Intrastromal photodisruption with femtosecond lasers produced consistent changes in corneal thickness without loss of corneal transparency. These changes were more stable than those produced with excimer laser procedures in a similar animal model.     

Different pH Dependency of Mitomycin C Activity in Monolayer and Three-Dimensional Cultures

Purpose. Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pH_e) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions. We evaluated (a) the effect of pH_e on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures of human bladder RT4 tumor cells. Methods. Patient bladder tumors were maintained as 3-dimensional histocultures. RT4 cells were harvested and maintained as monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The cell pellets were 300–450 cell layers and 4,000–5,000 µm in diameter. Tumors or cells were incubated for 2 hr with MMC-containing media at pH_eof 5, 6, and 7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine) incorporation. The stability of MMC as a function of pH_e was determined. About 24% of MMC was degraded following 2 hr exposure at pH_e 5 and 2% at pH_e 6 and 7.4. Results. The drug concentrations required to inhibit thymidine incorporation by 50% (IC₅₀) were corrected for the degraded MMC at acidic pH_e. The results showed no pH-dependent MMC activity in human patient bladder tumors nor in RT4 multilayer cultures; the IC₅₀ values were about 10 µg/ml at all three pH_e. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC cytotoxicity; the IC₅₀ were 0.1, 0.8 and 1.2 µg/ ml at pH_e 5,6 and 7.4, respectively (p < 0.05). Pre-incubation of multi-layered RT4 cultures in acidic pH medium for 8 hr enhanced the MMC activity; the IC₅₀ was reduced by about 5 fold at pH_e 5 and about 3 fold at pH_e 6. Similar pH-dependent MMC activity was found when multilayers were pre-treated for 1 hr with 0.5 µml nigericin, a proton ionophore known to cause the intracellular pH (pH_i) to equilibrate with pH_e. Conclusions. These data suggest that the difference in the pH dependency of MMC activity in the monolayer and multilayer systems was due to the different experimental conditions. The time lag for pH_i to equilibrate with pH_e in the multilayer systems and the instability of MMC at low pH_e imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution.     

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted. No significant difference was found between diabetic groups or when diabetic groups were compared with control subjects. Nocturnal hypoglycemia was common among diabetic women during pregnancy and post partum. Although these episodes were usually asymptomatic, the mean concomitant cortisol levels were increased over the corresponding cortisol levels of nonhypoglycemic diabetic and control subjects. We conclude that differences between control and type I and II diabetic subjects in carbohydrate tolerance or glycemic excursion are not explained by differences in cortisol levels or rhythm. The pregnancy-associated blunting of the excursion of cortisol is consistent with an autonomous source of adrenocorticotropin. Asymptomatic nocturnal hypoglycemia is common in insulin-requiring diabetic women and is associated with increased cortisol secretion.     

Role of pilocarpine use following laser peripheral iridotomy in eyes with refractory acute angle closure glaucoma: A case report and literature review

Rationale:Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG.Patient concerns:A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours.Diagnoses:The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination.Interventions:The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes.Outcomes:No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for >6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed.Conclusion:This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.     

Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers

Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO. Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.