Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial.

BACKGROUND AND PURPOSE: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. PATIENTS AND METHODS: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. RESULTS: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P = 0.28). Significantly lower use of antibiotics (P = 0.002) and antispasmodics (P < 0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P = 0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P = 0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. CONCLUSIONS: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up.     

The effect of divalent cations on neuronal nitric oxide synthase activity.

Neuronal nitric oxide synthase (NOS I) is a Ca(2+)/calmodulin-binding enzyme that generates nitric oxide (NO*) and L-citrulline from the oxidation of L-arginine, and superoxide (O(2)*(-)) from the one-electron reduction of oxygen (O(2)). Nitric oxide in particular has been implicated in many physiological processes, including vasodilator tone, hypertension, and the development and properties of neuronal function. Unlike Ca(2+), which is tightly regulated in the cell, many other divalent cations are unfettered and can compete for the four Ca(2+) binding sites on calmodulin. The results presented in this article survey the effects of various divalent metal ions on NOS I-mediated catalysis. As in the case of Ca(2+), we demonstrate that Ni(2+), Ba(2+), and Mn(2+) can activate NOS I to metabolize L-arginine to L-citrulline and NO*, and afford O(2)*(-) in the absence of L-arginine. In contrast, Cd(2+) did not activate NOS I to produce either NO* or O(2)*(-), and the combination of Ca(2+) and either Cd(2+), Ni(2+), or Mn(2+) inhibited enzyme activity. These interactions may initiate cellular toxicity by negatively affecting NOS I activity through production of NO*, O(2)*(-) and products derived from these free radicals.     

A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results

OBJECTIVE: Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. This study was a preliminary result of a randomized two arms, prospective, open-label phase III trial comparing the activity and safety of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin alone in locally advanced cervical cancer. MATERIALS AND METHODS: The stage IIB-IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225 mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min, weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin alone concurrent with standard radiotherapy (Group B). RESULTS: Four hundred and sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The tumor response at 3-month follow-up time showed no significant difference. The only prognostic factor to improve the complete response rate was the hemoglobin level. The patients in Group A, who had Hb <10 gm/dL had the relatively better change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI 1.07, 2.04). No severe toxicity or adverse event had been reported. The median follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively. There was no statistical difference in PFS and OS. CONCLUSION: Concurrent chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor response rate or treatment toxicity compared to carboplatin alone. The combination drugs might have benefit in poor prognostic patients such as the baseline Hb <10 gm/dL.     

Prenatal sonographic diagnosis of Majewski syndrome

Majewski syndrome is an autosomal recessive disorder characterized by short ribs, polydactyly, short limbs, and a cleft lip. A 26-year-old woman with no family history of genetic diseases presented at 31 weeks' menstrual age with preterm labor and underwent prenatal sonography to screen for fetal anomalies. Sonography revealed a small thorax, markedly short ribs, micromelia, polydactyly, a cleft lip, dolichocephaly, and severe oligohydramnios. The other structures appeared normal. The most likely diagnosis was Majewski syndrome. Vaginal breech delivery was allowed to proceed. The 1,850-g male newborn died of respiratory failure shortly after birth. The postnatal appearance and radiographs confirmed the prenatal diagnosis.     

Prenatal sonographic diagnosis of diastrophic dwarfism

A healthy 27-year-old pregnant woman underwent sonographic examination because her uterine size was large for 20 weeks' menstrual age. Sonograms showed short fetal limbs with hitchhiker thumbs and toes, thoracic scoliosis, clubbed feet, and polyhydramnios. The ossification of all bony structures appeared normal, and there was no evidence of fractures. On the basis of these sonographic findings, we diagnosed skeletal dysplasia and short-limbed dwarfism, most likely diastrophic dwarfism. We counseled the parents, and the pregnancy was continued. At 37 weeks menstrual age, the patient vaginally delivered a male infant that weighed 2,560 g. The infant survived with respiratory support during his first few days of life. Postnatal physical and radiologic examinations confirmed the prenatal diagnosis of diastrophic dwarfism. Sonography is the modality of choice for prenatal detection of diastrophic dwarfism.     

Comparative proteomic analysis of juvenile and adult liver fluke, Opisthorchis viverrini

We used comparative two-dimensional gel electrophoresis to highlight proteins that are differentially expressed in the maturation stage of the parasite Opisthorchis viverrini (OV). The proteins differentially expressed in the juvenile/adult forms of the parasite are thought to be important for survival and pathogenesis. We used a nonlinear gradient pH ranged 3-10 strips for isoelectric focusing to resolve soluble proteins from four different maturation periods of OV from 1 week juvenile to 4 week adult. Approximately 210-240 protein spots were resolved by 2-DE in two ranges of pI (4.5-5.8 and 6.0-8.0). At least 35 protein spots were differentially expressed in 4 week adult compared to 1 week juvenile fluke. These proteins may involve in sex organ development and egg production. Comparative analysis of the OV proteome of different aged parasites during maturation may help to better understand parasite biology, pathogenesis/carcinogenesis related to this parasite and lead to the identification of new targets of vaccines and drugs.