Primary tumors of the spine. Initial oncologic aspects: epidemiology, anatomo-prognostic and therapeutic classification

Primary tumors of the vertebral column are rare: 20 per cent of all primary tumors of the spinal column. The distribution by type of tumor shows that the three most frequent primary tumors considered to be "radio and/or chemo resistant lesions" are the chordoma (15.5 to 24.5%), the chondrosarcoma (20%) and the giant cell tumor (10%). A second group with "chemo and/or radiosensitive lesions" include the Ewing sarcoma, primary lymphoma and plasmocytoma (5%). We consider a third group with the benign tumor: osteochondroma, chondroma, osteoid osteoma, osteoblastoma, aneurysmal bone cyst, hemangioma and eosinophilic granuloma (2 to 3%). The last tumoral group agrees with sarcomatous tumors: osteogenic sarcoma, fibrosarcoma, malignant fibro-histiocytoma, angiosarcoma and hemangio-pericytoma (1 to 3% of primary tumors of the vertebral column); they are most frequently secondary to Paget's disease, giant cell tumor or to radiation therapy and their prognosis is poor.     

Cross-sectional and 4-year longitudinal associations between brachial pulse pressure and common carotid intima-media thickness in a general population. The EVA study

BACKGROUND AND PURPOSE: The cross-sectional and 4-year longitudinal associations between brachial pulse pressure (PP) and ultrasound measurements of common carotid intima-media thickness (CCA-IMT) were assessed. METHODS: A population of 957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France) and reexamined 4 years later. Longitudinal changes in PP and CCA-IMT were computed as the difference between 4-year follow-up and baseline values. RESULTS: Baseline CCA-IMT and PP were positively associated in both age- and sex-adjusted analysis (partial correlation coefficient=0.20, P<0.001) and in multivariate analysis adjusted for traditional cardiovascular risk factors and mean blood pressure (partial correlation coefficient=0.18, P<0.001). In longitudinal analysis, baseline PP was associated with the change in 4-year CCA-IMT (partial correlation coefficient=0.11, P<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP (partial correlation coefficient=0.10, 0.001相似文献   

Effect of the new imidazoline derivative S-22068 (PMS 847) on insulin secretion in vitro and glucose turnover in vivo in rats.

We have investigated the possible mechanisms underlying the antihyperglycaemic effect of the imidazoline derivative S-22068. In vitro, in the presence of 5 mmol/l glucose, S-22068 (100 micromol/l) induced a significant and sustained increase in insulin secretion from isolated, perifused, rat islets and a marked sensitization to a subsequent glucose challenge (10 mmol/l). S-22068 (100 micromol/l was able to antagonize the stimulatory effect of diazoxide on 86Rb efflux from preloaded islets incubated in the presence of 20 mmol/l glucose. Experiments were also performed to investigate whether S-22068 can alter glucose turnover and peripheral insulin sensitivity in vivo in mildly diabetic rats and obese, insulin resistant, Zucker rats. Neither glucose production nor individual tissue glucose utilization was modified by S-22068 in either group of rats. Similar results were obtained whether the studies were performed under basal conditions or during euglycaemic/hyperinsulinemic clamps. The results suggest that S-22068 exerts part of its antihyperglycaemic effect by promoting insulin secretion without alteration of peripheral insulin sensitivity.     

Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline

Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2', 4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of alpha2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4', 5'-dihydro-1'H-imidazol-2'-yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 micromol/kg) as after ip administration and appears as a good candidate for clinical investigations.     

Preoperative radiation therapy and surgery in the treatment of "bulky" squamous cell carcinoma of the uterine cervix (stage Ib, IIa, and IIb operable tumors).

Forty-two women with "bulky" squamous cell carcinoma of the uterine cervix, larger than 5 cm, were treated between 1982 and 1988. The median follow-up was 5 years (from 37 to 106 months). The age range was from 25 to 77 years (mean: 49). There were 14 stage Ib, 5 stage IIa, and 23 stage IIb operable patients. Forty grays were delivered at mid-plane of the pelvis (23 fractions in 31 days) using the four-field technique (6-18 MV). External beam radiation therapy was followed by 20 Gy of intracavitary radiation therapy. Forty-eight days later total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and bilateral pelvic lymphadenectomy were performed. The 3- and 5-year disease-free survival was 83 and 81%, respectively. The 5-year locoregional control rate was 83%. Thirteen patients suffered from mild to severe complications (31%) but there were only two long-term (5%) complications.     

Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.

PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.