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1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
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Circumscribed low grade astrocytomas in the dominant opercular and insular region: A pilot study 总被引:4,自引:0,他引:4
Summary Intraoperative mapping techniques allow a reliable identification or exclusion of eloquent brain areas and are well tolerated by the patients. In dominant opercular tumours radical surgery can only be achieved without lasting deficits with intraoperative histological examination of the resection line and mapping. If an early post-operative MRI shows residual opercular tumour in non-eloquent areas re-operation is recommended.In large dominant insular or opercular-insular tumours only biopsy is recommended, because only an incomplete removal can be accomplished, because the trial of radical removal carries a high risk of postoperative deficits due to possible vascular damage of the lenticulo-striate arteries or internal capsule. Because subtotal removal of low grade gliomas does not increase the progression free interval, we would not recommend surgery in these cases, as they carry a significant risk of a further deficit. 相似文献
4.
一个进行性肌营养不良症家系的研究 总被引:1,自引:0,他引:1
目的寻找由DNA损伤(如突变)引起的人类表型缺陷,为人类遗传资源的收集与保藏以及人类基因结构与功能的研究打下基础。方法通过实地调查得到表型缺陷家系,然后进行系谱分析。结果得到一进行性肌营养不良家系,4代41位成员中有12例患者。结论进行性肌营养不良是由DNA损伤引起的人类表型缺陷;该病症符合常染色体显性遗传;该病的发生具有一定的外显率和表现度。 相似文献
5.
Leo Sher Juan J Carballo Michael F Grunebaum Ainsley K Burke Gil Zalsman Yung-yu Huang J John Mann Maria A Oquendo 《Bipolar disorders》2006,8(5P2):543-550
Objectives: Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods: Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results: Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions: Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides. 相似文献
Methods: Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results: Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions: Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides. 相似文献
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目的:探讨HBcAg显性失活突变体质粒pCDNA4-C-GFP的构建及体外表达。方法:选择编码乙肝核心抗原C基因片段及绿色荧光蛋白(green fluorescent protein,GFP)基因片段,利用基因重组技术构建成DNA质粒pCDNA4-C-GFP,并将该质粒转染肝癌细胞株HepG2。结果:通过RT-PCR检测到其RNA的表达,Confocal观察到GFP绿色荧光。结论:HBcAg显性失活突变体质粒pCDNA4-C-GFP的构建成功可以进行对HBV作用的研究。 相似文献
8.
Intraductal papillary mucinous tumor of the pancreas associated with autosomal dominant polycystic kidney disease 总被引:1,自引:0,他引:1
Hiroshi Naitoh M.D. Hisanori Shoji M.D. Isao Ishikawa M.D. Reina Watanabe M.D. Yuichi Furuta M.D. Shigeru Tomozawa M.D. Hiroaki Igarashi M.D. Sachiko Shinozaki M.D. Hideyuki Katsura M.D. Ryoichi Onozato M.D. Masayoshi Kudoh M.D. 《Journal of gastrointestinal surgery》2005,9(6):843-845
A 43-year-old male with a history of autosomal dominant polycystic kidney disease (ADPKD) was admitted to our center with severe abdominal pain and was diagnosed with acute pancreatitis. CT showed multiple cysts in the liver and both kidneys along with ADPKD and a cystic mass, 4 cm in diameter, in the pancreatic head. The main pancreatic duct was dilated to 1 cm in diameter. The patient was diagnosed with acute pancreatitis due to intraductal papillary mucinous tumor (IPMT), and pancreatoduodenectomy was performed. Histologic examination revealed a multiloculated cystic tumor filled with mucin in the head of the pancreas. Microscopically, the tumor was diagnosed as adenocarcinoma and was found to have invaded the main pancreatic duct. Although, in addition to our case, only seven cases with association between ADPKD and malignant neoplasms have been reported, five of these cases had neoplasms arising from the pancreas. Therefore, we suggest that some genetic interactions may exist between ADPKD and pancreatic carcinogenesis. 相似文献
9.
Observations on two members of the Swedish family with congenital dyserythropoietic anaemia,type III
S. N. Wickramasinghe A. Wahlin D. Anstee S. F. Parsons G. Stopps I. Bergstrom M. Eriksson H. Sandstrom S. Shiels 《European journal of haematology》1993,50(4):213-221
Abstract: Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28c (1c = haploid DNA content) and 48c respectively, and some DNA synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with 3H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins Dolichos biflorus and Ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents. 相似文献
10.
Farida Daïkha-Dahmane Françoise Narcy Marc Dommergues Mireille Lacoste Agnes Beziau Marie-Claire Gubler 《Pediatric nephrology (Berlin, Germany)》1997,11(3):267-273
An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney
diseases. Most of these interactions are mediated by β1-integrins, a subfamily of integrin receptors, formed by the association
of the β1-chain with different α-subunits. To date, no study on α-integrin subunit distribution during the early stages of
cyst development has been reported. Using immunofluorescence, we analyzed the distribution of α-integrin subunits (α1, α2,
α3, α5, and α6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive
polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys,
and in fetal cystic dysplasia and Meckel syndrome. Marked increase in α1-integrin staining was observed in normal and cystic
collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin
subunits α2, α3, and α6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the
α1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD.
In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of α2,
α3, and α6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may
participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases.
Received May 28, 1996; received in revised form October 2, 1996; accepted October 25, 1996 相似文献