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71.
Seilicovich A Pisera D Sciascia SA Candolfi M Puntel M Xiong W Jaita G Castro MG 《Current gene therapy》2005,5(6):559-572
Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. 相似文献
72.
73.
Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas 总被引:3,自引:0,他引:3
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Bastian BC Xiong J Frieden IJ Williams ML Chou P Busam K Pinkel D LeBoit PE 《The American journal of pathology》2002,161(4):1163-1169
Large congenital melanocytic nevi (CMN) are at an increased risk of developing melanoma. Several forms of secondary proliferations can arise in congenital nevi on rare occasions. Although some of these closely resemble melanoma both clinically and histologically, metastasis is rare. We used comparative genomic hybridization to analyze chromosomal aberrations in different types of proliferations arising in CMN and compared them to typical congenital nevi, clear-cut melanomas arising in congenital nevi, as well as primary cutaneous melanomas that were not associated with a CMN. Cases of CMN and CMN with secondary proliferations were assigned to six groups according to the predominant histological pattern: group I, bland congenital nevi (n = 6); group II, congenital nevi with foci of increased cellularity (n = 4); group III, CMN with a proliferation simulating superficial spreading melanoma in situ (n = 3); group IV, CMN with a proliferation simulating nodular melanoma (n = 9); group V, proliferating neurocristic hamartoma (n = 1); and group VI, melanoma arising in congenital nevus (n = 6). No aberrations were found in groups I to III, whereas seven of nine cases of group IV, and one of one case of group V, showed aberrations. In group IV six of seven cases with aberrations (86%) showed numerical aberrations of whole chromosomes exclusively. This pattern differed significantly from the findings in melanoma that arose within CMN (n = 6), group VI, or independent of CMN (n = 122) in which only 5% showed numerical changes only. The single case in group V showed aberrations similar to melanoma. The finding of frequent numerical chromosomal aberrations in atypical nodular proliferations arising in CMN identifies these as clonal neoplasms with a genomic instability consistent with a mitotic spindle checkpoint defect. This difference compared to the aberration pattern found in melanoma might explain their more benign clinical behavior and may be of diagnostic value in ambiguous cases. 相似文献
74.
API0134对大鼠血浆和血小板血栓素B2生成与血小板聚集的影响 总被引:2,自引:0,他引:2
用放射免疫分析法和比浊法测定PAI0134对大鼠血浆血栓素B2浓度,血小板TXB2生成血小板聚集的影响。静脉注射API013470mg或100mg.kg显著降低血浆TXB2浓度,其降低2率分别为38.8%和51.6%,API0134明显抑制ADP诱导的大鼠血小板聚集和TXB2生成,抑制率分别为27.8%,39.5%,和41.4%,53.6%,两抑制率间呈显著正相关。 相似文献
75.
APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).
Sarju G Mehta Giles D J Watts Jennifer L Adamson Mike Hutton Geanie Umberger Shuling Xiong Sheena Ramdeen Mark A Lovell Virginia E Kimonis Charles D Smith 《Genetics in medicine》2007,9(1):9-13
PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype. 相似文献
76.
Amyloid-beta peptide (Abeta), the major component of amyloid plaques, can activate brain mononuclear phagocytes (MP; macrophages and microglia), leading to their secretion of neurotoxins. Recent studies strongly suggest that MP-mediated neurotoxicity plays an important role in the pathogenesis of Alzheimer's disease (AD). To further explore this notion, human monocyte-derived macrophages (MDM) were stimulated with naturally secreted alpha-processing soluble amyloid precursor protein/p3 (alphaAPPs/p3) or beta-processing APP/Abeta (betaAPPs/Abeta). MDM conditioned media (MCM) was recovered and tested for its ability to activate recombinant N-methyl-d-aspartate (NMDA) receptor subtype NR1a/NR2B expressed in Xenopus oocytes. Pressure ejection of alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM produced inward currents of 59.5 +/- 8.9 nA (mean +/- S.E.M., n = 31) and 111.1 +/- 21.0 nA (n = 42) in NR1a/NR2B-expressing oocytes, respectively. The MCM-induced currents were concentration dependent and blocked by 50 microM of the NMDA receptor antagonist 2-amino-5-phosphnovalerate, but not by a non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). The alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM placed in non-injected oocytes failed to generate inward current. These results demonstrate that APPs/Abeta-stimulated MCM directly activate NMDA receptor subtypes relevant in the pathogenesis of AD. 相似文献
77.
目的探讨含银介孔二氧化硅-壳聚糖复合材料(Ag/MSN-Chi)的制备方法及其微观表征、细胞毒性、吸水性能、抗菌性能及止血性能。
方法以正硅酸乙酯为前驱体,十六烷基三甲基溴化铵为致孔剂,采用离子交换法在介孔二氧化硅纳米粒子(MSN)中引入银离子,制备出具有抗菌作用的新型有序的含银介孔二氧化硅纳米粒子(Ag/MSN)材料。再利用烷基化壳聚糖负载Ag/MSN,制备出Ag/MSN-Chi。根据所用材料不同将实验分为实验组和空白对照组,实验组又分为3个亚组:MSN组、Ag/MSN组、Ag/MSN-Chi组,空白组为不加任何材料的阳性对照。计算MSN和Ag/MSN的比表面积、孔容、孔径和Ag/MSN与Ag/MSN-Chi的电荷。并通过吸水实验、体外凝血实验、抗菌实验对MSN、Ag/MSN和Ag/MSN-Chi的细胞毒性、吸水性能、止血性能及抗菌性能进行评价,计算细胞相对存活率、吸水率、凝血酶原时间(PT)、凝血活酶时间(APTT)及抑菌率。取健康成年新西兰大白兔18只,随机分成3组:对照组(采用医用纱布处理)、Ag/MSN组(采用Ag/MSN处理)、Ag/MSN-Chi组(采用Ag/MSN-Chi处理),每组6只,建立肝创伤出血模型,计算止血时间。数据比较采用方差分析和t检验。
结果MSN的比表面积为(523.8±12.4) m2/g、孔容为(1.2±0.4) m3/g、孔径为(3.5±0.9) nm;Ag/MSN的比表面积为(521.6±11.7) m2/g、孔容为(1.15±0.5) m3/g、孔径为(3.6±0.7) nm,2种材料的比表面积、孔容、孔径比较差异均无统计学意义(t=0.224、0.135、0.015,P值均大于0.05)。经测量,Ag/MSN的Zeta电位为-19.7 mV,Ag/MSN-Chi的Zeta电位为10.27 mV,表明Ag/MSN表面电荷从负值变为正值。Ag/MSN-Chi组、Ag/MSN组和MSN组与小鼠成肌细胞共培养1、4、7 d的细胞相对存活率比较,差异均无统计学意义(F=2.61、4.72、3.52, P值均大于0.05)。Ag/MSN组吸水率分别与MSN组和Ag/MSN-Chi组比较,差异均无统计学意义(t=0.482、1.159,P值均大于0.05)。经检测,Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组的PT比较,差异无统计学意义(F=10.28,P>0.05);Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组APTT分别为(20.9±2.1)、(28.5±3.4)、(31.4±2.6)、(38.7±2.5) s,4组比较差异有统计学意义(F=8.70,P<0.05);Ag/MSN-Chi组、Ag/MSN组、MSN组APTT分别与空白对照组比较,差异均有统计学意义(t=9.443、4.186、3.506,P值均小于0.05);Ag/MSN-Chi组APTT与Ag/MSN组比较,差异有统计学意义(t=3.294,P<0.05)。MSN组在培养0.5、2、4、6、24 h 5个时间点抑菌率比较差异无统计学意义(F=5.437,P>0.05);培养0.5 h,Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(99.7±5.2)%、(97.1±5.4)%,与培养0.5 h MSN组抑菌率(11.2±5.8)%比较,差异均有统计学意义(t=19.678、18.775, P值均小于0.05);培养24 h,Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(73.2±5.1)%和(72.9±6.9)%,与MSN组(11.8±5.7)%比较,差异均有统计学意义(t=13.904、11.825, P值均小于0.05)。Ag/MSN-Chi组、Ag/MSN组和对照组止血时间分别为(12.3±1.5)、(17.2±3.4)、(28.1±3.8) s,3组比较差异有统计学意义(F=5.892,P<0.05);Ag/MSN-Chi组和Ag/MSN组止血时间分别与对照组比较,差异均有统计学意义(t=9.473、5.236, P值均小于0.05);且Ag/MSN-Chi组与Ag/MSN组止血时间比较,差异有统计学意义(t=3.230,P<0.05)。
结论Ag/MSN-Chi在不增加细胞毒性的基础上具有有较好的吸水性能、止血性能及抗菌性能。 相似文献
78.
Palmer SL Gajjar A Reddick WE Glass JO Kun LE Wu S Xiong X Mulhern RK 《Neuropsychology》2003,17(4):548-555
Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline. 相似文献
79.
Under conditions of low [Ca(2+)](o) and high [K(+)](o), the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the slices were exposed to different extracellular pH environments in vitro. The field bursts were highly sensitive to extracellular pH over the range 7.0-7.6 and were suppressed at low pH and enhanced at high pH. Granule cell resting membrane potential, action potentials, and postsynaptic potentials were not significantly altered by pH changes within the range that suppressed the bursts. The pH sensitivity of the bursts was not altered by pharmacologic blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and GABA(A) receptors at concentrations of these agents sufficient to eliminate both spontaneous and evoked synaptic potentials. Gap junction patency is known to be sensitive to pH, and agents that block gap junctions, including octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a manner similar to low pH. Perfusion with gap junction blockers or acidic pH suppressed field bursts but did not block spontaneous firing of single and multiple units, including burst firing. These data suggest that the pH sensitivity of seizures and epileptiform phenomena in vivo may be mediated in large part through mechanisms other than suppression of NMDA-mediated or other excitatory synaptic transmission. Alterations in electrotonic coupling via gap junctions, affecting field synchronization, may be one such process. 相似文献
80.
Xiong W Li J Chen L Price RA Freedman G Ding M Qin L Yang J Ma CM 《Physics in medicine and biology》2004,49(10):1973-1989
Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field. 相似文献