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991.
Badia E Duchesne MJ Semlali A Fuentes M Giamarchi C Richard-Foy H Nicolas JC Pons M 《Cancer research》2000,60(15):4130-4138
Antiestrogen resistance is frequently observed in patients after longterm treatment with tamoxifen, a nonsteroidal antiestrogen widely used for endocrine therapy of breast cancer. In vitro studies in resistant cells showed that the expression of natural estrogen-responsive genes is frequently altered. Using MVLN cells, an MCF-7-derived cell model, we previously demonstrated that 4-hydroxytamoxifen (OHT) treatment irreversibly inactivated an estrogen-regulated chimeric luciferase response by a direct effect of the drug and not through a cell selection process (E. Badia et al., Cancer Res., 54: 5860-5866, 1994). In the present study, we present tamoxifen-resistant but still estrogen-dependent clones isolated after long-term treatment of MVLN cells with OHT and show that progesterone receptor (PR) expression was irreversibly decreased in some of these clones, whereas the PRA:PRB ratio of residual PR remained unchanged. The irreversible inactivation of both chimeric luciferase gene and PR gene expression was associated with the disappearance of DNase 1-hypersensitive sites. In the case of the chimeric gene, at least one of these sites was close to the estrogen responsive element. Genomic sequencing analysis of a clone with very low PR content did not reveal any methylation on CpG dinucleotides or any mutation in the PR gene promoter region. In all of the resistant clones tested and independently of their PR content, estrogen receptor expression was only lowered by half and remained functional, whereas pS2 expression was not modified. We also observed that the residual luciferase activity level (1-2%) of the MVLN clones, the luciferase expression of which had been irreversibly inactivated, was raised 4-fold by trichostatin A treatment. We conclude that long-term OHT treatment may modify the chromatin structure and thus could contribute to differentially silencing natural target genes. 相似文献
992.
Patrick Balaguer Hélène Fenet Virginie Georget Franck Comunale Béatrice Térouanne Rodolphe Gilbin Elena Gomez Anne-Marie Boussioux Charles Sultan Michel Pons Jean-Claude Nicolas Claude Casellas 《Ecotoxicology (London, England)》2000,9(1-2):105-114
In order to monitor the (anti)steroid activity of environmental samples, we established stable cell lines expressing luciferase under the control of estrogens, androgens, progestives and glucocorticoids. The breast cancer MCF-7 cells which express the estrogen receptor (ER), the glucocorticoid receptor (GR) and the progesterone receptor (PR) were transfected by an estrogen (ERE-Glob-Luc) or a glucocorticoid/progestin/androgen (MMTV-Luc) regulated luciferase plasmid in order to enable the detection of compounds which bind both ER, PR and GR (MELN and MMLN cells). Human prostatic cells PC3 were stably transfected by both an androgen receptor gene and the MMTV-luciferase plasmid (PALM cells). These three cellular models were validated as tools to check the estrogenic, progestive, glucocorticoid and androgenic activities using several potential xenohormones and environmental samples. As these environmental samples were fractionated after solid phase extraction to isolate active compounds, we used these cellular models to monitor the different fractions. In the estrogenic model mid-polar fractions of environmental samples were found active while in the androgenic model, the same fractions had antagonist activity. 相似文献
993.
Arcangelo Barbonetti Settimio D’Andrea Francesca Cavallo Alessio Martorella Sandro Francavilla Felice Francavilla 《The journal of sexual medicine》2019,16(5):624-632
Introduction
Comparative studies on differences in sexual function outcomes between homosexual and heterosexual men are sparse and inconclusive.Aim
To systematically evaluate whether, and to what extent, a statistically significant difference exists in the odds of erectile dysfunction (ED) and premature ejaculation (PE) between homosexual and heterosexual men.Methods
A thorough search of Medline, SCOPUS, CINAHL, and Web of Science databases was carried out to identify case-control studies comparing the prevalence of ED and PE in homosexual and heterosexual men. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Odds ratios (ORs) of reporting ED and PE were combined using random effect models. The Cochrane Q and I2 tests were carried out to analyze the between-studies heterogeneity. Funnel plots and trim-and-fill analysis were used to assess publication bias.Main Outcome Measures
The relationship between sexual orientation and odds of ED and PE was assessed by calculating pooled ORs with a 95% CI.Results
4 studies included in the quantitative analysis collectively provided information on 1,807 homosexual and 4,055 heterosexual men. The pooled ORs indicated that homosexual orientation was associated with 1.5-fold higher odds of reporting ED (OR = 1.49, 95% CI = 1.03–2.16; P = .04) and 28.0% lower odds of reporting PE in comparison to the heterosexual orientation (OR = 0.72, 95% CI = 0.52–1.00; P = .05). However, a significant heterogeneity among the studies was observed. Funnel plots revealed a possible publication bias only for the ED analysis, where the trim-and-fill test detected a putative missing study. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a significantly higher risk of ED in the homosexual group (adjusted OR = 1.60, 95% CI = 1.10–2.30; P = .01).Clinical Implications
These findings can drive future studies on sexual needs and concerns of homosexual men, which might not exactly match those of heterosexual individuals.Strength & Limitations
This is the first meta-analysis exploring the differences in the prevalence of ED and PE between homosexual and heterosexual men. However, the results should be interpreted with caution, because their generalization could be hindered by the non-probabilistic nature of the samples, and a measurement bias could result from the use of different non-standardized indicators of sexual dysfunctions.Conclusion
Homosexual orientation is associated with higher odds of ED and lower odds of PE compared with heterosexual orientation. Further studies are warranted to elucidate the clinical significance of these findings and whether they reflect differences in patterns of sexual lifestyle.Barbonetti A, D’Andrea S, Cavallo F, et al. Erectile Dysfunction and Premature Ejaculation in Homosexual and Heterosexual Men: A Systematic Review and Meta-Analysis of Comparative Studies. J Sex Med 2019;16:624–632. 相似文献994.
Francesco Paolo Mangino Federico Romano Giovanni Di Lorenzo Francesca Buonomo Davide De Santo Federica Scrimin Giuseppe Ricci 《Journal of minimally invasive gynecology》2019,26(6):1011-1012
Study ObjectiveTo evaluate the efficacy of total surgical treatment of ectopic cervical pregnancy [1] with a minimally invasive approach performed by hysteroscopy [2].DesignStep-by-step video demonstration of the surgical technique using 5 mm hysteroscopy followed by 10 mm resectoscopy.SettingA research and university hospital (IRCCS Burlo Garofolo, Trieste, Italy).PatientsA 41-year-old woman with an ultrasound diagnosis of ectopic cervical pregnancy at 6 + 6 weeks of gestation with a beta human chorionic gonadotropin serum level of 55.951 mUI/mL.InterventionsWe performed a 2-step technique using 5- and 10-mm hysteroscopy (Video 1). During the first step, a 5-mm Bettocchi hysteroscope (Karl Storz, Tuttlingen, Germany) with a 5F bipolar electrode Versapoint Twizzle (Gynecare, Menlo Park, CA) was used. In this phase, the gestational sac was identified in order to confirm the diagnosis and its site of implantation. Later, the gestational sac was opened, and the pregnancy was terminated by cord section under an embryoscopic view (Fig. 1). Finally, a partial vessel coagulation was performed. Afterward, the cervix was dilated, and a resectoscopy was performed. During the second step, a 10-mm Gynecare resectoscope with the bipolar Gynecare Versapoint was used and the gestational sac with the embryo was removed; subsequently, a complete chorial villi resection was achieved. At last, a coagulation of bleeding vessels on the implantation site in order to control the hemostasis was performed (Fig. 2).Measurements and Main ResultsThe study was approved by the institutional review board. The patient was discharged 24 hours after the procedure with an uneventful postoperative course, and the beta human chorionic gonadotropin serum level became negative in 20 days. After 40 days, the ultrasound cervical findings were regular, whereas office hysteroscopy showed the implantation site scar. After 5 months, the patient was pregnant with regular intrauterine implantation (Fig. 3).ConclusionThe total hysteroscopic approach with a 2-step technique offers an effective, safe, and minimally invasive surgical treatment to ectopic cervical pregnancy. Considering that our method, in contrast with the recent literature 3, 4, 5, is performed without any medical treatment, we reported for the first time an approach, that deserve more clinical data to confirm its effectiveness. 相似文献
995.
Skin cancer is the most common cancer worldwide. Its incidence is doubling every 15–20 years likely because of an aging population,
changes in behaviour towards sun exposure, and increased UV light fluency at the earth surface due to ozone depletion. In
this review, we summarize the most important genetic changes contributing to the development of malignant melanoma, basal
cell carcinoma and squamous cell carcinoma, the main tumor entities arising in the skin. While our understanding of the oncogenes
and tumor suppressor genes involved in the development and progression of skin tumors is still fragmentary, recent advances
have shown alterations affecting conserved signalling pathways that control cellular proliferation and viability. These pathways
includeINK4a/Rb,ARF/p53, RAS/MAPKs, and sonic hedgehog/Gli.
Supported by an unrestricted educational grant by Bristol-Myers Squibb. 相似文献
996.
Mila Roceri Francesca Cirulli Cassandra Pessina Paolo Peretto Giorgio Racagni Marco A Riva 《Neuropsychopharmacology》2004,55(7):708-714
BACKGROUND: Adverse life events occurring early in development may alter the correct program of brain maturation and render the organism more vulnerable to psychiatric disorders. Identification of persistent changes associated with these events is crucial for the development of novel therapeutic strategies. METHODS: We used postnatal repeated maternal deprivation (MD) from postnatal day (PND) 2-14 to investigate changes in brain-derived neurotrophic factor (BDNF) levels. RNase protection assay and enzyme linked immunosorbent assay were employed to determine the anatomic profile of neurotrophin expression at different ages following MD. RESULTS: We found that MD produces a short-term up-regulation of neurotrophin expression in hippocampus and prefrontal cortex, as measured on PND 17, whereas at adulthood, a selective reduction of BDNF expression was observed in prefrontal cortex. When adult animals were challenged with a chronic swim stress paradigm, both a reduced expression of BDNF in prefrontal cortex and a significant reduction in striatal protein levels were found only in control subjects, whereas levels in the MD group were not further decreased. CONCLUSIONS: Our data suggest that MD produces a significant reduction of BDNF expression within prefrontal cortex and striatum, which may render these structures less plastic and more vulnerable under challenging conditions. 相似文献
997.
A Muxí M Solá P Bassa F Pons A García M Moragas F Lome?a R Herranz R Fernández M Trias 《Nuclear medicine communications》1992,13(4):261-270
Radioimmunoscintigraphy (RIS) with BW 431/26 monoclonal antibody (MoAb) labelled with 99Tcm (962 MBq) has been performed in 64 patients with colorectal carcinoma, one of them with two independent tumours. The group consisted of 46 primary lesions, 15 pelvic recurrences and four suspected recurrences which were shown to be liver metastases. Imaging of liver was obtained in all patients, but surgical liver examination was performed in only 56 of them. Planar scans were obtained at 4 and 24 h postinjection. Tomographic images were also performed in five patients. The final diagnosis was confirmed in all patients by their clinical course and by findings at surgery and pathology. A comparative study between the RIS results and the final diagnosis gave a global sensitivity in primary tumours and pelvic recurrences of 59.7% with an accuracy of 59.0%. When rectal tumours were excluded, the results were 81.1 and 84.9%, respectively. In liver metastases the sensitivity was 50%, with an accuracy of 85.7% and a specificity of 100%. No correlation has been found between CEA serum levels and lesion detection. In conclusion, RIS is a useful technique for the study and localization of colorectal tumours, being also indicated in patients with normal carcinoembryonic antigen (CEA) serum levels and clinical suspicion of illness. 相似文献
998.
The role of a regional trauma system in the management of a mass disaster: an analysis of the Keystone, Colorado, chairlift accident 总被引:1,自引:0,他引:1
M A Ammons E E Moore P T Pons F A Moore B L McCroskey H C Cleveland 《The Journal of trauma》1988,28(10):1468-1471
On December 14, 1985, the Teller chairlift at the Keystone, Colorado, ski area collapsed, throwing 60 of the 372 people aboard to the ground from heights up to 50 feet. Initial triage and management of the victims was carried out by the local ski patrol, the on-duty physician at the area's Snake River Health Services Clinic, and by volunteer physicians and nurses present at the scene. Thirty-three people required immediate evacuation to hospitals, most of them being transported 75 miles by helicopter air ambulance to level I and II trauma centers in the Denver metropolitan area. Eighteen of these air-evacuated patients were in serious or critical condition. Less seriously injured victims were treated at local medical facilities. The scene evacuation was carried out by helicopter and ground vehicles in accordance with an existing disaster plan coordinated by the Colorado Trauma Institute (CTI). The unique problems posed by a mass casualty incident in a remote mountain location are emphasized by this tragedy. Patient salvage due to the efficacy of a regionally organized trauma system is clearly demonstrated. 相似文献
999.
Late neuropsychological and behavioural outcome of children surgically treated for craniopharyngioma
D. Riva Chiara Pantaleoni Monica Devoti Veronica Saletti Francesca Nichelli Cesare Giorgi 《Child's nervous system》1998,14(4-5):179-184
Late outcome in 12 children treated by radical surgery for craniopharyngioma is presented. None of the patients presented
underwent fractionated traditional or stereotactic radiotherapy. The results show no neurological (except visual dysfunction
in 6 subjects), cognitive or short-term memory deficits. Three children were found to have a minor attention deficit. In 5
cases “frontal lobe” malfunctioning was disclosed, and in 5 there were bursts of unpredictable anger. Three children showed
worsening of functioning at school: a combination of various causes is suggested to explain the worsening of academic performances.
The size of the sample calls for a careful evaluation of results, with due consideration for the influence of various factors
on outcome. Multicentre studies are required to increase the sample size and achieve more general conclusions.
Received: 25 November 1997 相似文献
1000.
H. P. Killackey H. J. Gould C. G. Cusick T. P. Pons J. H. Kaas 《The Journal of comparative neurology》1983,219(4):384-419
Corpus callosum connections of parietal and motor cortex were studied in New World owl monkeys (Aotus trivirgatus)and Old World macaque monkeys (Macaca fascicnlaris) after multiple injections of 3H-proline and horseradish peroxidase, HRP, into one cerebral hemisphere, and extensive microelectrode mapping of architectonic Areas 3b, 1, and 2 of the other hemisphere. Results were obtained both from parasagittal brain sections cut orthogonal to the brain surface and from sections from flattened brains cut parallel to the brain surface. Cortical fields varied in density of callosal connections, and the density of connections varied according to body part within sensory representations. Thus, Area 3b had few, Area 1 had more, and Area 2 had relatively dense callosal connections. Within each of these fields, connections were much less dense for the representations of the glabrous hand and foot and much more dense for the representations of the face and trunk. For the representation of the hand, retrogradely labeled cells were extremely sparse in Area 3b, moderately sparse in Area 1, and moderate in Area 2. There were less dense callosal connections in the hand representations of Areas 3b, 1, and 2 in macaque as compared to owl monkeys. Label in posterior parietal cortex was uneven with zones of extremely dense connections. A large region of very dense callosal connections was noted in motor cortex just medial to the probable location of the hand representation. In all regions, callosally projecting cells appeared to be more broadly distributed than callosal terminations. In no region was the discontinuous arrangement of callosal connections obviously organized into an extensive pattern of mediolateral or rostrocaudal bands or strips. 相似文献