FLIP在非小细胞肺癌中的表达及其与细胞凋亡的关系

目的 研究FLIP在非小细胞肺癌(NSCLC)中的表达并观察其与细胞凋亡的关系。方法 采用免疫组化技术检测FLIP在48例NSCLC和16例肺良性疾病组织中的表达，并应用TUNEL技术检测48例NSCLC的凋亡情况。结果 肺癌组织中FLIP的表达率为83．33％(40／48)，明显高于肺良性病变组织(25.00％)(P＜0．01)。FLIP的表达水平与TNM分期及淋巴结转移有密切关系，但与肿瘤组织学分型、分化程度无明显关系。FLIP在肺癌组织中的表达水平与癌细胞凋亡指数(AI)末见明显相关性(r＝-0.211，P＞0.05)。结论 FLIP的过量表达在NSCLC的发生发展中起重要作用，但与细胞凋亡无明显关系。     

Endoscopic aspects in diagnosis of gastroesophageal reflux disease and motility disorders: Bravo,capsule, and functional lumen imaging probe

Catheter-based testing remains the current standard of practice for the diagnosis of gastroesophageal reflux disease and esophageal motility abnormalities. Ambulatory pH testing and esophageal manometry have been in use for the past 40 years, but with the development of high-resolution manometry and multichannel intraluminal impedance testing, catheter-based testing has undergone significant recent technological improvement. Nonetheless, these tests continue to have limitations. In the case of ambulatory reflux testing, patient discomfort and limited activity remain significant problems. For esophageal manometry, methodological issues limit its ability to evaluate the function of the esophagogastric junction in normal and diseased states. In recent years, several new diagnostic tools have been developed to address the shortcomings of catheter-based testing. The wireless pH probe has been available for clinical use for more than 10 years, is better tolerated than catheter-based testing, and provides longer monitoring periods. Esophageal capsule endoscopy has undergone clinical evaluation for gastroesophageal reflux disease and Barrett esophagus with mixed results. Functional lumen imaging probe testing is a new technology that is still undergoing clinical evaluation but holds promise as a complimentary method for evaluating esophageal physiology, in particular esophagogastric junction function.     

Cellular‐FLIP,Raji isoform (c‐FLIPR) modulates cell death induction upon T‐cell activation and infection

Dysregulation of apoptosis caused by an imbalance of pro‐ and anti‐apoptotic protein expression can lead to cancer, neurodegenerative, and autoimmune diseases. Cellular‐FLIP (c‐FLIP) proteins inhibit apoptosis directly at the death‐inducing signaling complex of death receptors, such as CD95, and have been linked to apoptosis regulation during immune responses. While the isoforms c‐FLIP_L and c‐FLIP_S are well characterized, the function of c‐FLIP_R remains poorly understood. Here, we demonstrate the induction of endogenous murine c‐FLIP_R in activated lymphocytes for the first time. To analyze c‐FLIP_R function in vivo, we generated transgenic mice expressing murine c‐FLIP_R specifically in hematopoietic cells. As expected, lymphocytes from c‐FLIP_R transgenic mice were protected against CD95‐induced apoptosis in vitro. In the steady state, transgenic mice had normal cell numbers and unaltered frequencies of B cells and T‐cell subsets in lymphoid organs. However, when challenged with Listeria monocytogenes, c‐FLIP_R transgenic mice showed less liver necrosis and better bacterial clearance compared with infected wild‐type mice. We conclude that c‐FLIP_R expression in hematopoietic cells supports an efficient immune response against bacterial infections.     

FLIP、FADD在喉癌中的表达及其临床意义

目的：分析凋亡信号蛋白FLIP、FADD在人喉鳞状细胞癌组织中的表达及其临床意义。方法：应用免疫组织化学链霉素抗生物素蛋白-过氧化酶连接法（S-P法）,检测56例喉癌患者手术切除的病理组织标本中FLIP、FADD的表达情况,并且用PCNA检测喉鳞状细胞癌细胞增殖情况。结果：FLIP的表达与喉鳞状细胞癌细胞增殖正相关（P〈0．05）;FADD的表达与喉鳞状细胞癌细胞增殖负相关（P〈0．05）;FLIP表达与FADD表达无相关性（P〉0．05）;FLIP、FADD的表达与喉鳞状细胞癌临床分期,病理分级有关,而与患者的年龄、性别、淋巴结转移无关（P〉0．05）。结论：FLIP,FADD的异常表达在喉鳞状细胞癌的发生发展中起重要作用。     

c—FLIP、bcl—xS和caspase-3在乳腺癌中的表达及其临床意义

目的：探讨c—FLIP、bcl—xS和caspase-3在乳腺癌发生发展中的意义。方法：采用RT—PCR技术检测57例浸润性乳腺癌组织和癌周组织中c—FLIP、bcl—xS和caspase-3表达及其与肿瘤临床特征之间的关系。结果：与癌周组织相比，乳腺癌组织中c—FLIP呈过表达，其阳性率及半定量测定均明显高于癌周组织；c—FLIP表达与肿瘤的组织分级之间有显著相关性，随组织分级增高表达升高。而bcl—xS和caspase-3低表达，其阳性率及半定量测定均明显低于癌周组织。随分级增高，bcl—xS表达下降，同时临床Ⅰ期乳腺癌bcl—xS的表达阳性率明显高于Ⅱ期、Ⅲ期乳腺癌。结论：c—FLIP过表达、bcl—xS和caspase-3低表达是促进乳腺癌发生发展的因素之一，有望作为判断和监测乳腺癌预后的指标。     

Survivin和FLIP在骨巨细胞瘤组织中的表达及其临床意义

目的研究Survivin和FLIP（FLICE—inhibitory proteins即Fas相关死亡域样白介素1-β转化酶抑制蛋白）在骨巨细胞瘤（GCT）中的表达及其临床意义。方法采用免疫组化技术检测Survivin和FLIP在22例骨巨细胞瘤、13例骨肉瘤和8例正常骨组织中的表达，并分析其与Iaffe病理分级、x线分型、临床分型、综合分期之间的相关性。结果Survivin和FLIP在骨巨细胞瘤中的表达均明显高于正常骨组织（P〈0．01）。而与骨肉瘤组无显著性差异（P〉0．05）；骨巨细胞瘤Jaffe病理分级中Survivin和FLIP的表达在I级和Ⅱ级之间无显著性差异（P〉0．05），但均显著低于Ⅲ级（P〈0．05）。在x线分型、临床分型、综合分期之间无显著性差异（P〉0．05）。结论Survivin和FLIP在骨巨细胞瘤的发生发展中可能起重要的作用，其检测为判断骨巨细胞瘤的生物学行为、复发、预后，决定治疗方案，开拓新的治疗方法提供了理论依据。     

Immunohistochemical analysis of Fas and FLIP in prostate cancers

Fas‐mediated apoptosis is considered a principal pathway for apoptosis induction in normal and cancer cells. Expression of Fas has been reported in prostate tissues several times, but the data were not consistent. Expression of FLICE‐like inhibitory protein (FLIP), an inhibitor of Fas‐mediated apoptosis, has not been studied by immunohistochemistry in prostate tissues. The aim of this study is to explore whether alterations of Fas and FLIP expression occur in prostate cancer tissues. We analyzed the expression of Fas and FLIP in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray approach. Normal glandular cells of the prostates strongly expressed both Fas and FLIP proteins. Prostate intraepithelial neoplasm also showed a strong Fas immunoreacitity. Fas expression was strongly positive in 60 cancers (56.1%), but the remaining 47 cancers showed no (6.5%) or markedly decreased (37.4%) Fas immunostaining compared with the normal glandular cells of the same patients. By contrast, FLIP expression was strong in most (103/107; 96.3%) of the cancers, and only four cancers (3.7%) showed decreased immunoreactivities compared with the normal cells. The decreased expression of Fas was not associated with pathologic characteristics, including FLIP expression, size of the cancers, age, Gleason score and stage. The decreased expression of Fas in a large fraction of prostate cancers compared with their normal cells suggested that loss of Fas expression might play a role in tumorigenesis in some prostate cancers possibly by inhibiting apoptosis mediated by Fas.