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121.
Simone Boehrer Daniel Nowak Natasa Kukoc-Zivojnov Simone Hochmuth Soo-Zin Kim Dieter Hoelzer Paris S Mitrou Eckhart Weidmann Kai Uwe Chow 《Pharmacological research》2005,51(4):367-374
BACKGROUND: The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector. RESULTS: Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents. CONCLUSIONS: We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents. 相似文献
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Mitch Dowsett Steve R Ebbs J Michael Dixon Anthony Skene Clive Griffith Irene Boeddinghaus Janine Salter Simone Detre Margaret Hills Susan Ashley Stephen Francis Geraldine Walsh Ian E Smith 《Journal of clinical oncology》2005,23(11):2477-2492
PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer. 相似文献
124.
Luisa Di Marzio Alfredo Di Leo Benedetta Cinque Donatella Fanini Alessio Agnifili Pasquale Berloco Michele Linsalata Dionigi Lorusso Michele Barone Claudio De Simone Maria Grazia Cifone 《Cancer epidemiology, biomarkers & prevention》2005,14(4):856-862
OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms. 相似文献
125.
Simone Bagel Bernd Wiedemann 《European journal of pharmaceutics and biopharmaceutics》2004,57(2):353-358
Nasal drops and nasal sprays are commonly supplied in multi-dose containers that usually include suitable levels of an appropriate preservative in order to kill or prevent growth of any microorganisms which might enter the dispensing system. Preservatives should both protect the patient from infection and prevent spoilage of the product. Unfortunately, preservatives often cause unwanted side effects; in particular, the nasal mucosa is irritated frequently. Consequently, the use of preservatives in nasal preparations should be avoided. The technical design of the 3K system, a new multi-dose container, combines several microbiological safety features and therefore allows use without preservatives. Earlier tests have shown its safety for 6 weeks after the first opening. In order to test the microbiological safety of this multi-dose system over longer time periods, an in-use stability test was designed. The results revealed that the first dose as well as the contents complied with the requirements of the European Pharmacopoeia. Therefore, from a microbiological point of view for the tested nasalia in the 3K system, the stability after opening could be extended from 6 weeks up to several months without loss of microbiological quality. 相似文献
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128.
Simone Marnitz 《Der Onkologe》2016,22(10):773-779
Chemoradiotherapy is an integral component of cervical cancer treatment in cases where surgery alone is not sufficient to achieve an optimal oncological outcome. The present German interdisciplinary guidelines on treatment of cervical cancer recommend performing either radical hysterectomy or primary chemoradiotherapy. The frequently used practice of trimodal therapy (i.e. radical hysterectomy, radiation and chemotherapy) doubles the risk for treatment-related delayed toxicity and should be avoided whenever possible. If risk factors are known prior to therapy, e.?g. lymph node metastases, parametrial infiltration or a combination of tumor size >4 cm, grade 3, lymphovascular space invasion (LVSI) or deep stromal infiltration, primary chemoradiotherapy should be recommended. The purely clinical FIGO classification does not consider lymph node involvement. This leads to a high rate of adjuvant chemoradiotherapy after radical surgery due to lymph node involvement. This could have been avoided in 90?% of patients, if surgical (laparoscopic) lymph node staging would have been used routinely. Whether this can result in advantages for patients with respect to the prognosis, was one of the aims of the Uterus-11 study of the working group for gynecological oncology (AGO) and the working group on radiological oncology (ARO).Mature data are expected to be available in 2018. For chemoradiotherapy sophisticated irradiation techniques should be used, which are available in all German treatment facilities. This is the only way to reduce acute and delayed side effects. Although ovarian preservation by ovarian transposition and organ sparing can be provided to premenopausal patients, a pregnancy after full-dose chemoradiotherapy is unlikely because of the resulting atrophy of the endometrium and fibrosis of the myometrium. Oncological results depend on treatment quality, full-dose external beam radiation, the use of brachytherapy and the administration of concomittant chemotherapy. The experience of the treatment facility is a predictor for patient outcome. The value of neoadjuvant chemotherapy in locally advanced cervical cancer is unclear and still under discussion. 相似文献
129.
David E. Barroso Terezinha M.P.P. Casti?eiras Fernanda S. Freitas Jane W. Marsh Mary G. Krauland Mary M. Tulenko érica L. Fonseca Ana C.P. Vicente Maria C. Rebelo Elaine O. Cerqueira Adriano C. Xavier Ana P.C.M. Cardozo Simone E.M. da Silva Lee H. Harrison 《Emerging infectious diseases》2013,19(11):1847-1850
During 2003–2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates. 相似文献
130.
Francesca Galeffi Simone Degan Gavin Britz Dennis A Turner 《Journal of cerebral blood flow and metabolism》2016,36(4):696-701
We investigated microvascular reactivity to synaptic train stimulation after induction of subarachnoid hemorrhage in adult rats, analyzing tissue oxygen levels [pO2] in intact hippocampus. In control rats, hippocampal pO2 averaged 11.4 mm Hg whereas hemodynamic responses averaged 13.1 mm Hg (to a 25 s train). After subarachnoid hemorrhage (at 2 days), we recorded a dramatic elevation in baseline pO2 in the hippocampus (to 68.4 mm Hg) accompanied by inverted pO2 responses to synaptic train stimulation (−9.46 mm Hg). These significant changes in baseline hippocampal pO2 and inverted pO2 responses after subarachnoid hemorrhage indicate severe alterations of neurovascular coupling and neuronal viability. 相似文献