New treatment strategies for malignant gliomas

Malignant gliomas are the most prevalent type of primary brain tumor in adults. Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. The median survival of patients with glioblastoma muhiforme, the most common grade of malignant glioma, is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Essentially, tumor recurrence is inevitable. Salvage treatments upon recurrence are palliative at best and rarely provide significant survival benefit. Therapies targeting the underlying molecular pathogenesis of brain tumors are urgently required. Common genetic abnormalities in malignant glioma specimens are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy.     

Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P相似文献   

Neutrophil alkaline phosphatase (NAP) score in the diagnosis of hypophosphatasia

Hypophosphatasia is an inherited disease characterised by low tissue non-specific alkaline phosphatase (TNSALP) levels and skeletal defects. Diagnosis is usually made by measurement of serum total alkaline phosphatase (TALP, reference range 40-130 iu/l) and pyridoxal-5'-phosphate (PLP), and urine phosphoethanolamine (PEA). Neutrophil alkaline phosphatase (NAP) scores (reference range 20-150) have been reported to be low in isolated cases, but no comparison has been made of the diagnostic value of NAP, TALP, PEA and PLP in hypophosphatasia. We undertook such a comparison in six families with hypophosphatasia. In four families (Families 1, 2, 5, 6) with the adult type of hypophosphatasia, inherited as autosomal dominant, the NAP score and TALP (<40 iu/l), were low, <20 and <40 iu/l respectively, in all affected subjects, though the PEA and PLP were not consistently abnormal. In one of the two families (Family 3) with the autosomal recessive type of hypophosphatasia an affected subject had low NAP as well as low TALP, PLP and PEA. In another family (Family 4) one of the heterozygotes had a low NAP while the other had a normal NAP score (45). A child in this family had a normal TALP level. Her low NAP score (15) supported her to be a possible heterozygote. NAP score is readily available from most laboratories and may be diagnostically helpful in hypophosphatasia.     

Variations in hyperacuity performance with age

The term hyperacuity has been applied to a group of stimuli which produce spatial thresholds smaller than those expected given the relatively large receptor spacing and the retinal image quality of the human eye. It is not yet firmly established whether hyperacuity performance declines with increasing age in the same way as most other measures of visual ability. This is perhaps due to the use of varying task configurations and criterion-dependent psychophysical techniques. The present study examines age-related performance in three different hyperacuity tasks using a criterion independent forced-choice method. Both displacement and bisection thresholds were found to increase with age, but there was no significant change in vernier acuity. This indicates that age has a differential effect on thresholds for various hyperacuities depending upon the task requirements. No significant age-related trend was observed in hyperacuity bias, which represents the difference between subjective and true physical alignment.     

THE DILEMMA OF STAGE III BREAST CANCER: A STUDY OF PREOPERATIVE RADIOTHERAPY

The results of treatment of 68 patients with Stage III breast cancer treated by preoperative radiotherapy and subsequent mastectomy have been compared with those in 68 patients treated by more conventional methods, matched individually for age, stage, and year of treatment. Preoperative radiotherapy delayed the time of the first local recurrence, but did not improve overall survival. It is concluded that preoperative radiotherapy may be justified in patients with Stage III breast cancer in an attempt to control local disease, but is unlikely to improve control of systemic recurrence.