Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

Experimental validation tests of fast Fourier transform convolution and multigrid superposition algorithms for dose calculation in low-density media.

BACKGROUND AND PURPOSE: Modern conformal radiotherapy treatments require accurate dose calculation in any relevant clinical situation. One of these situations is the treatment of lung tumors, where irradiation has to be planned under challenging conditions for dose calculation. In this study we assess the errors in dose values predicted by fast Fourier transform convolution (FFTC) and multigrid superposition (MGS) algorithms implemented in a commercial treatment planning system (TPS). MATERIALS AND METHODS: FFTC and MGS algorithms were used in a FOCUS 3.0.0 (Computerized Medical Systems, USA) to calculate doses in treatment plans using photon beams of 6 and 25 MV nominal energy from a Saturne 43 linac (GE Medical Systems, USA). A 10x10-cm beam irradiating a mediastinum-lung and a thoracic wall-lung-thoracic wall modeled geometry was assessed. The calculated data were compared with measurements performed with radiographic films and ionization chamber. RESULTS: FFTC algorithm leads to an average deviation from ionometric dose measurements of over 10%. Discrepancies between measured and calculated beam fringe values (distance between 50 and 90% isodose lines) of up to 8 mm were observed. For MGS algorithm, all the points assessed in both geometries fulfilled the 3%-3 mm accuracy criteria and the average deviation of absolute dose was about 1%. A maximum of 3 mm deviation in the beam fringe for any depth was found and was within 2 mm beyond the buildup region. Deviations between ionometric and film measurements were within 3%. CONCLUSIONS: MGS algorithm assesses with reasonable accuracy dose distributions and absolute dose in inhomogeneous regions like the lung region. Therefore, and respecting the inhomogeneity dose calculation, the system could be used in routine clinical practice and in dose-escalation programs. This is not true in the case of FFTC algorithm which leads to errors greater than 10% in the absolute dose calculation and underestimates the beam fringe by up to 8 mm.     

羊红膻根的化学成分研究

从羊红膻(Pimpinella thellungiana Wolff.)根中分得四个化合物,经理化常数测定和光谱数据解析证明为棕榈酸(Ⅰ)、4-丙烯基苯酚(Ⅱ)、松酯酚(Ⅲ)和新化合物2-甲基-2-羟基-5-甲氧基苯并[d]氢化呋喃-3-酮(Ⅳ)。     

Association of Helicobacter pylori Infection with Gastric Adenocarcinoma

Gastric adenocarcinoma is the most prevalent cancer in South Korea, and Helicobacter pylori (H. pylori) infection is also common. This study was performed to examine the association between H. pylori infection and gastric cancer, taking into account various other factors. To investigate the association between gastric adenocarcinoma and H. pylori infection, determined by urease-positive reaction in the CLO test, a total of 175 paired specimens (175 tumor and 175 tissues adjacent to tumor) of stomach cancer patients and a total of 113 control specimens were obtained. The positive H. pylori infection rates were 78.9% (138/175) among the patients in specimens of tumor or tissues adjacent to the tumor and 41.6% (47/113) among controls in the CLO test. A positive correlation between H. pylori infection and gastric cancer was observed (age-adjusted odds ratio, 7.0; MH χ²=34.5 with P <0.0005). These data suggest that stomach cancer patients in Korea have high infection rates of H. pylori regardless of site specificity, and this infection might be causally associated with stomach cancer.     

人急性早幼粒细胞性白血病细胞诱导分化生成树突状细胞的体外研究

树突状细胞(dendritic cells,DC)在激发机体抗白血病T细胞免疫应答中具有重要作用,有报道DC可以由单核细胞及粒细胞分化生成,本研究应用细胞因子在体外诱导了急性早幼粒细胞性白血病(APL)细胞向DC的分化.从M3型APL患者外周血分离白血病细胞,加入GM-CSF(100ng/ml)或GM-CSF(100ng/ml) rhIL-4(500U/ml)体外培养14天,并于培养结束前3天加人TN-α(100ng/ml).结果表明,GM-CSF可以促进白血病细胞体外增殖,并从幼稚状态逐渐分化成熟,表达高水平的CD45分子,其中部分为CD14~ 的单核细胞,部分为CDla~ 的DC(M3DC);培养后期加入TNF-α,可以促进DC生成,约占35%;以GM-CSF IL-4培养也诱导了幼稚细胞的成熟,2周后DC约占10%,但较少单核细胞生成,培养至3周时DC约占60%;而在培养后第11天加入TNF-α则可以加速DC生成,3天后生成的白血病型DC达90%.电镜观察到M3DC具有与单核细胞来源的DC相似的超微结构,但具有的突出特征是部分细胞存在少量胞浆颗粒;M3DC高表达HLA-DR、B7-2、CD40、CD54分子,体外可以强烈刺激同种T细胞增殖.此类由白血病细胞诱导生成的DC可被用于体内外诱导生成肿瘤特异性CTL,在APL的免疫治疗中具有一定的应用价值.     

子宫内膜癌中E-cad PTEN蛋白表达及其临床意义

目的:探讨上皮型钙粘素(E-cad)和PTEN在子宫内膜癌中的蛋白表达及临床意义.方法:应用免疫组织化学SP法,检测37例正常子宫内膜(NE),40例非典型增生内膜(AHE)和72例癌性内膜(CE)中E-cad、PTEN的蛋白表达,并结合临床指标、预后进行分析.结果:在NE、AHE和CE中E-cad表达阳性率为100%(37/37)、70.00%(28/40)和47.22%(34/72);PTEN表达阳性率为100%(37/37)、77.50%(31/40)和48.61%(35/72).E-cad的表达与内膜癌患者临床分期、浸润深度和病理分级相关.临床Ⅰ Ⅱ期和浸润深度≤1/2的E-cad表达阳性率高(P＜0.05),病理分级G1、G2、G3表达逐渐下降(P＜0.05).E-cad高表达组5年生存率比低表达组高(P＜0.05).PTEN的表达与临床分期和病理分级相关,Ⅰ Ⅱ期组的PTEN表达阳性率低于Ⅲ Ⅳ期;随着肿瘤细胞的去分化,PTEN表达降低(P＜0.05);PTEN高表达组的5年生存率高于低表达组(P＜0.05).结论:PTEN和E-cad均在子宫内膜癌的发生、发展中起重要作用,与预后密切相关.     

头孢克肟片和胶囊在健康人体的生物等效性

目的 评价头孢克肟片剂、胶囊剂与参比制剂在健康人体内的药代动力 学及其生物等效性。方法用三交叉全排列组合设计,18名健康男性受试者 交叉单剂量口服试验药头孢克肟片、胶囊和对照药头孢克肟胶囊剂,用高效液 相色谱法测定其的血药浓度。结果受试制剂头孢克肟片、胶囊与对照药头孢 克肟胶囊的Cmax分别为:(1．64±0．45),(1．58±0．37)和(1．67±O．46)μg· mL-1;tmax分别为:(3．78±0．38),(3．75±0．34)和(3．86±0．28)h;AUC0-24分 别为:(13．58±3．78),(13．49±3．63)和(13．36±4．16)mg·h·L-1;AUC0-∞ 分别为:(14．49±3．94),(14．32±3．87)和(14．05±4．31)mg·h·L-1。经统 计学分析,3组间均无显著性差异(P>0．05)。结论3种制剂具有生物等效 性。     

Expression of a synapse-associated membrane protein, P84/SHPS-1, and its ligand, IAP/CD47, in mouse retina

P84 and integrin associated protein (IAP) are heterophilic binding partners that are expressed in the central nervous system in addition to a variety of other tissues. Both molecules are known to be involved in cell signaling in nonneural tissues. In the retina, both molecules are expressed prominently in plexiform layers, suggesting a possible association with synapses. Here, we examined the cellular expression and ultrastructural localization of the two molecules in the developing mouse retina. Both appeared to be expressed at one or both sides of synaptic sites, although the expression of IAP in the retina precedes that of P84. Examination of transgenic IAP-null retinae revealed a failure of P84 to become associated with synaptic sites, suggesting the interaction of P84 with IAP was necessary for P84's synaptic localization. These findings suggest that the signaling activities of P84 and IAP are localized to sites of synaptic contact in the retina. Thus this pair of synapse-associated molecules represents a bidirectional signaling system that could function to modify synaptic activity or possibly trophic interactions between central neurons.     

Effect of chronic alcohol consumption on plasma lipid, vitamins A, and E in Korean alcoholics

This human study was conducted to evaluate the effect of chronic alcohol consumption on plasma concentrations of lipid and the antioxidative system in 44 Korean alcoholics and 45 age-, sex-, and nationality-matched nonalcoholic subjects. Plasma triacylglycerols and atherogenic index were higher in alcoholics than in control subjects. Plasma total cholesterol was not different among groups, but plasma high-density lipoprotein cholesterol was lower in alcoholics. There were positive correlations between ethanol consumption and plasma lipid peroxide and atherogenic index in all subjects; there were negative correlations between ethanol consumption and plasma high-density lipoprotein cholesterol in all subjects. There were no significant differences between alcoholics and control subjects in plasma concentrations of α-tocopherol, although plasma α-tocopherol/lipid tended to be lower in alcoholics. Plasma retinol was lower in alcoholics. These results suggest that chronic ethanol consumption can contribute to increased risk for vascular diseases in Korean alcoholics.     

小儿高脂血症危险因素的临床抽样调查

目的通过临床抽样调查，探讨与小儿高脂血症发病有关的危险因素，为小儿高脂血症的早期检测提供客观指标。 方法北京大学第一医院儿科等于2004年9月，调查并分析了962名北京市景山学校在校学生(5~19岁)的血脂浓度，其中采用酶法测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL C)及低密度脂蛋白(LDL C)等4项指标。采用坐高、腰围、上臂围、体重指数来反映身体肥胖程度，进一步分析了这些指标与血脂浓度的关系。 结果在962名学生中，共检出高脂血症患儿122例，总检出率为12.7%。高脂血症组的坐高、腰围、上臂围、体重指数4项指标明显高于正常组，2组间差异有显著性(P<0.05)；坐高、腰围、上臂围、体重指数等4项指标与甘油三酯均呈高度显著正相关(P<0.01)，与高密度脂蛋白均呈高度显著负相关(P<0.01)。 结论正常组与高脂血症组的坐高、腰围、上臂围、体重指数4项指标差异均有显著性；坐高、腰围、上臂围、体重指数均是影响甘油三酯和高密度脂蛋白浓度的危险因素。