STAT3和ZEB1在食管鳞癌中的表达及其与放疗敏感性的关系

[目的]研究STAT3和ZEB1在食管鳞癌组织中的表达及其与放疗敏感性的关系。[方法 ]采用免疫组化法分别检测100例食管癌组织中STAT3和ZEB1的表达情况,并分析其与放疗敏感性的关系。[结果]STAT3和ZEB1的阳性表达率分别为66.0%(66/100)和64.0%(64/100)。低分化以及临床分期为T_3+T_4的组织STAT3表达阳性率分别为85.7%(30/35)、82.9%(42/51),均显著高于中、高分化以及临床分期为T_1+T_2组织中的55.4%(36/65)、49.0%(24/49);低分化以及临床分期为T_3+T_4的组织ZEB1表达阳性率分别为85.7%(30/35)、76.5%(39/51),均显著高于中、高分化以及临床分期为T_1+T_2组织中的52.3%(34/65)、51.0%(25/49),差异均有统计学意义(P<0.05)。放疗有效组的STAT3、ZEB1阳性率均显著低于放疗无效组,差异均有统计学意义(59.2%vs 87.5%,P=0.011;55.3%vs 91.7%,P=0.001)。多因素Logistic回归分析结果显示T分期是影响放疗疗效的独立因素(P=0.001)。食管癌组织中STAT3与ZEB1的表达呈正相关(r=0.341,P=0.001)。[结论 ]STAT3和ZEB1蛋白表达与食管癌放疗的敏感性呈负相关,二者可能可作为预测食管癌患者的放射敏感性的分子标志物。

右美托咪定对小鼠内毒素性急性肺损伤时JAK2/STAT3信号通路的影响

目的 评价右美托咪定对小鼠内毒索性急性肺损伤时蛋白酪氨酸激酶2（JAK2）/信号转导和转录激活因子3（STAT3）信号通路的影响.方法 清洁级健康雄性成年C57BL/6小鼠24只,体重20～25 g.采用随机数字表法分为3组（n=8）：对照组（C组）、内毒素性急性肺损伤组（ALI组）和右美托咪定组（Dex组）.采用腹腔注射脂多糖（LPS）5 mg/kg的方法制备小鼠内毒素性急性肺损伤模型.Dex组于注射LPS后1h时腹腔注射右美托咪定40 μg/kg,C组和ALI组给予等容量生理盐水.腹腔注射LPS后6h,采集颈动脉血样测定PaO2,随后处死动物,收集支气管肺泡灌洗液（BALF）,测定BALF总蛋白、IL-1β、IL-6及TNF-α的浓度;取肺组织称重,计算肺湿重/干重（W/D）比值,检测磷酸化JAK2（p-JAK2）及磷酸化STAT3（p-STAT3）、IL-1β mRNA、IL-6 mRNA和TNF-α mRNA的表达,观察病理学结果并进行肺损伤评分.结果 与C组比较,ALI组和Dex组PaO2降低、肺W/D比值、肺损伤评分、BALF总蛋白、IL-1β、IL-6及TNF-α、肺组织IL-1β、IL-6和TNF-α的mRNA、p-JAK2和p-STAT3表达水平升高（P＜0.05）;与ALI组比较,Dex组PaO2升高、肺W/D比值、肺损伤评分、BALF总蛋白、IL-1β、IL-6及TNF-α、肺组织IL-1β、IL-6和TNF-α的mRNA、p-JAK2和p-STAT3表达水平降低（P＜0.05）.结论 右美托咪定减轻小鼠内毒素性急性肺损伤的机制可能与抑制JAK2/STAT3信号通路激活有关.

STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats

Willed-movement training has been demonstrated to be a promising approach to increase motor per- formance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are in- volved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups： middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction （PCR） and im- munofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 （STAT3） mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor （BDNF）, synaptophysin, and protein in- teracting with C kinase 1 （PICK1）. In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.

Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer

The protein tyrosine phosphatase 1B（PTP1B）is an important regulator of metabolism.The relationship between PTP1B and tumors is quite complex.The purpose of this study is to explore the expression pattern and role of PTP1B in breast cancer.The expression of PTP1B was detected in 67 samples of breast cancer tissue by Western blot.Cell growth assay,Transwell migration assay,and Scratch motility assay were used to examine the proliferation and migration of MCF-7 with and without PTP1B.The total levels and phosphorylated levels of signal transduction and activator of transcription 3（STAT3）and the expression of C-C motif chemokine ligand 5（CCL5）were also examined by Western blot.PTP1B was overexpressed in over 70%of breast cancer tissues,correlating with patients with estrogen receptor（ER）-negative,progesterone receptor（PR）-negative,and human epidermal growth factor receptor 2（HER2）-positive tumors.The data also showed that both tumor size and lymph node metastasis were significantly higher in patients with a higher level of PTP1B.The proliferation and migration of MCF-7 cells were found to be inhibited after knocking down the gene of PTP1B.Our data also showed that PTP1B could up-regulate the dephosphorylated level of STAT3,which could increase the expression of CCL5.These phenomena indicated that PTP1B may play a crucial role in the development of breast cancer.