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排序方式: 共有313条查询结果,搜索用时 15 毫秒
41.
Leese MP Jourdan FL Gaukroger K Mahon MF Newman SP Foster PA Stengel C Regis-Lydi S Ferrandis E Di Fiore A De Simone G Supuran CT Purohit A Reed MJ Potter BV 《Journal of medicinal chemistry》2008,51(5):1295-1308
The synthesis, SAR, and preclinical evaluation of 17-cyanated 2-substituted estra-1,3,5(10)-trienes as anticancer agents are discussed. 2-Methoxy-17beta-cyanomethylestra-1,3,5(10)-trien-3-ol ( 14), but not the related 2-ethyl derivative 7, and the related 3- O-sulfamates 8 and 15 display potent antiproliferative effects (MCF-7 GI 50 300, 60 and 70 nM, respectively) against human cancer cells in vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also observed, and the interaction between 15 and hCAII was investigated by protein crystallography. The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDA-MB-231 human breast cancer xenograft model. 相似文献
42.
43.
Ioana Fodor Sorin Claudiu Man Dan L Dumitrascu 《World Journal of Clinical Cases》2019,7(18):2666-2674
Irritable bowel syndrome (IBS) is a lifelong condition with a high prevalence among children and adults. As the diet is a frequent factor that triggers the symptoms, it has been assumed that by avoiding the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP), the symptoms might be improved. Therefore, in the past decade, low FODMAP diet has been intensively investigated in the management of IBS. The capacity of FODMAPs to trigger the symptoms in patients with IBS was related to the stimulation of mechanoreceptors in the small and large intestine. This stimulation appears as a response to a combination of increased luminal water (the osmotic effect) and the release of gases (carbon dioxide and hydrogen) due to the fermentation of oligosaccharides and malabsorption of fructose, lactose and polyols. Numerous studies have been published regarding the efficacy of a low FODMAP diet compared to a traditional diet in releasing the IBS symptoms in adults, but there are only a few studies in the juvenile population. The aim of this review is to analyze the current data on both low FODMAP diet in children with IBS and the effects on their nutritional status and physiological development, given the fact that it is a restrictive diet. 相似文献
44.
Intravascular T‐cell lymphoma: A rare,poorly characterized entity with cytotoxic phenotype 下载免费PDF全文
Tara L. Sharma Gabrielle A. Yeaney Payam Soltanzadeh Yuebing Li Claudiu V. Cotta 《Neuropathology》2017,37(4):365-370
Intravascular T‐cell lymphomas are rare, poorly characterized lesions. We discuss the clinical, radiologic and especially the laboratory characteristics of a lesion which presented in a 62‐year‐old woman with a history of progressive CNS abnormalities. Throughout the course of the disease, radiologic findings consisted mainly of multifocal mixed areas of ischemia and vasogenic edema involving cortical and subcortical regions. A brain biopsy identified an abnormal T‐cell population confined to lumens of vessels. These T‐cells were abnormal cytotoxic cells, positive for CD3, CD8, and negative for CD2, CD4, CD5, CD7 and CD30. While flow cytometry and immunohistochemistry failed to identify a similar population in the blood or bone marrow, molecular studies showed a clonal T‐cell population in both the brain and the bone marrow. No other organs were involved. In spite of aggressive treatment, the patient's medical condition continued to progress and she passed away. In conclusion, this abnormal population of cytotoxic T‐cells with intravascular localization probably represents a specific type of T‐cell lymphoma with specific clinical, radiologic, molecular and immunophenotypic characteristics. 相似文献
45.
Roxana Buzas Vlad-Sabin Ivan Oana-Florentina Gheorghe-Fronea Adina Flavia Morgovan Melania Ardelean Nicolae Albulescu Maria Dorobantu Daniel Florin Lighezan 《Arquivos brasileiros de cardiologia》2021,117(2):378
Background:Hyperuricemia is a frequent finding in patients with arterial hypertension, and there is increasing evidence that this entity is also a risk factor for cardiovascular disease.Objective:In the context of an aging population, this study aims to evaluate serum uric acid levels and arterial hypertension prevalence and control in a subgroup of Romanian adults (>65 years), concerning the influence of age on these parameters.Method:The study sample consists of 1,920 adults included in SEPHAR III survey, of whom 447 were elderly patients (>65 years of age). During the two study visits, three blood pressure (BP) measurements were performed at 1-min intervals and serum uric acid levels, kidney function by estimated glomerular filtration rate, blood pressure, and intima media thickness measurements were conducted. Hypertension and controls were defined according to the current guidelines. Intima-media thickness evaluation was assessed by B-mode Doppler ultrasound evaluation. A significance level p < 0.05 was adopted for the statistical analysis.Results:Adult patients had a significant lower serum uric acid levels, compared to elderly patients, regardless of glomerular filtration rate levels. Adult patients showed a significantly lower intima-media thickness levels, when compared to elderly patients.Conclusion:Similar to previous studies, in the present study, age represented one of the factors contributing to the increased level of serum uric acid. An increasing prevalence of arterial hypertension with age, together with a poor control of blood pressure, was also obtained. 相似文献
46.
Gieling RG Babur M Mamnani L Burrows N Telfer BA Carta F Winum JY Scozzafava A Supuran CT Williams KJ 《Journal of medicinal chemistry》2012,55(11):5591-5600
A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms. Three of the specific CA IX/XII inhibitors showed a positive response in in vitro assays for tumor cell migration and spreading. One of them, 4-(3'-(3″,5″-dimethylphenyl)ureido)phenyl sulfamate (S4), was taken forward into the orthotopic MDA-MB-231 (breast carcinoma) model in mice. Treatment with a 10 mg/kg maintenance dosage of S4 given daily on a "5 days on, 2 days off" regimen reduced metastatic tumor burden in the lung while not affecting primary tumor growth or mouse condition. CA inhibitors of the sulfamate class specifically targeting the tumor-associated isoforms are potential candidates in antimetastatic therapy. 相似文献
47.
CT Supuran 《Expert opinion on therapeutic patents》2012,22(10):1251-1255
A series of sulfonamide derivatives incorporating an aromatic scaffold based on 1,4-phenylene diamine was prepared by a succession of five reactions. The lead molecule of these compounds was nimesulide (4-nitro-2-phenoxymethane-sulfoanilide), a cyclooxygenase (COX) inhibitor acting on both COX-1 and 2 isoforms, with some selectivity for COX-2. The new compounds from the patent are claimed to act as efficient antitumor agents, against a multitude of tumor types, such as leukemia, non-small cell lung cancer, colon cancer, brain cancer, melanoma, ovarian cancer, etc., although no COX inhibition data or other rationale to explain their biological effects are provided. As these compounds incorporate a methanesulfonamide moiety it is not unexpected that they may also appreciably inhibit tumor-associated carbonic anhydrases (CAs), such as isoforms CA IX and XII. 相似文献
48.
Supuran CT 《Expert opinion on emerging drugs》2012,17(1):11-15
Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes in mammals, being involved in numerous biosynthetic processes, including gluconeogenesis, lipogenesis and ureagenesis. It has recently emerged that CA inhibitors (CAIs) targeting the mitochondrial isoforms CA VA and VB have potential as novel antiobesity drugs. This Editorial discusses the biochemical and biological rationale for the use of CAIs in the management of obesity. 相似文献
49.
Claudiu Mărgăritescu Daniel Pirici Alin Stîngă Cristiana Simionescu Marius Raica Laurentiu Mogoantă Alex Stepan Domenico Ribatti 《Clinical and experimental medicine》2010,10(4):209-214
Angiogenesis is involved in tumor progression of oral squamous cell carcinoma (OSCC). In this study, we have investigated
by immunohistochemistry vascular endothelial growth factor (VEGF) expression in tumor cells and we have correlated VEGF expression
to microvessel area, evaluated by using CD105 as a marker of endothelial cells, in bioptic specimens of 54 human OSCC. Results
demonstrated that VEGF is highly expressed in OSCC tumor specimens when compared to pre-neoplastic and normal tissues, without
differences between the edge and inside the tumor. Moreover, VEGF expression is reduced in poor differentiated OSCC tumors
when compared to moderate and good differentiated forms, and tumor microvessel area is higher in tumors when compared to pre-neoplastic
lesions and normal tissues. Finally, VEGF and CD105 may be considered as reliable markers of tumor angiogenesis and progression
in OSCC, even if we did not demonstrate any correlation between VEGF expression, tumor microvascular area, clinical stage,
and lymph node status. 相似文献
50.
Cushing SL Daly MJ Treaba CG Chan H Irish JC Blaser S Gordon KA Papsin BC 《Acta oto-laryngologica》2012,132(4):361-368
Conclusion: In this study the outcomes from several indices (Category of Auditory Performance, CAP; Peabody Picture Vocabulary Test (Revised), PPVT-R; Test of Reception of Grammar, TROG; and Speech Intellegibility Rating, SIR) in three groups of children with different ages at implantation (from 4 to 36 months) with a follow-up time from 4 to 9 years demonstrate that very early cochlear implantation (<11 months) provides normalization of audio-phonologic parameters with no complications. Objectives: The aim of the present study was to investigate the efficacy of cochlear implants (CIs) in infants who were implanted at < 11 months of age versus children operated at later age (i.e. 12–36 months) and to document whether children who receive a CI below 11 months of age are able to achieve age-appropriate expected spoken language skills, at a follow-up time from 4 to 9 years. Subjects and methods: From November 1998 to November 2007, 185 children received CIs and 34 received auditory brainstem implants in our department. The present study focuses on 13 children implanted at ages younger than 12 months (4–11 months; mean, 8.2; SD = 2.4) and fitted with CIs between November 1998 and March 2004. To avoid bias these children were selected from a larger longitudinal cohort of pediatric CI recipients fitted with CIs because they all were implanted with the same cochlear device (Nucleus CI 24 M) during the same period. Postoperatively auditory abilities were evaluated at the latest follow-up, from 4 to 9 years after surgery, with CAP, PPVT-R, TROG, and SIR. The results obtained in this group of 13 children were compared with those obtained in two groups of children implanted at later ages (12–23 and 24–36 months, respectively). Results: No complication has been observed so far. The highest score of CAP function was achieved in all the three groups but at different intervals from CI activation as function of age at CI implantation. The rate of receptive language growth (PPVT-R) provides distinctive evidence that only the scores of the first group overlap the line of normal-hearing children, whereas the second and third group never reached the values of normal peers even after 9 years of CI use. TROG outcomes clearly indicate that only children from the first group (77%) are in the 76–100 percentile at 5 years follow-up. At 9 years follow-up, 100% of children in the first group, 38% in the second group, and 20% in the third group are in the 76–100 percentile. The SIR outcomes at the 5 years follow-up indicate that none of children was identified within the first two categories, only children from the third group (18%) were identified in category 3, all infants of the first group, 80% of group 2, and 63% of the third group were identified in category 5. At the 9 years follow-up, the number of children from the third group identified in category 3 was reduced to 10%, the second and third groups displayed a slightly higher percentage of children in category 5, but the difference from the values observed at the 5-year follow-up is not significant. 相似文献