骨髓间充质干细胞在子宫内膜异位症局部微环境作用的实验研究

目的:探讨骨髓间充质干细胞(BMSCs)在内异症中的局部微环境作用。方法:60只雌性大鼠采用皮下移植法内异症造模,术后6h随机分为3组,每组20只。A组:尾静脉注射1×107PKH26标记的BMSCs,用DMEM-F12培养基悬浮成单细胞悬液1ml;B组:尾静脉注射DMEM-F12培养基1ml;C组:尾静脉注射生理盐水1ml。饲养2周和6周时,检测内异症病灶体积,荧光显微镜检测PKH26标记细胞在内异症的迁移情况,免疫组化法检测VEGF、CD34、Bcl-2及Bax的表达,TUNEL法检测细胞凋亡情况。结果:移植后2周和6周时,A组内异症病灶均可见PKH26标记的BMSCs散在分布。移植后2周和6周时,3组间的异位病灶体积、微血管密度(MVD)、细胞凋亡率均有显著差异。A组的异位病灶体积和MVD均大于B组和C组,细胞凋亡率均低于B组和C组;3组间VEGF、Bcl-2表达均有显著差异,A组均高表达VEGF和Bcl-2;3组间Bax表达均无统计学差异。结论:BMSCs可经血循环迁移至内异症病灶,调节局部微环境,可能对内异症的发生发展发挥一定作用。     

Selective elimination of leukemia stem cells: Hitting a moving target

Despite the widespread use of chemotherapeutic cytotoxic agents that eradicate proliferating cell populations, patients suffering from a wide variety of malignancies continue to relapse as a consequence of resistance to standard therapies. In hematologic malignancies, leukemia stem cells (LSCs) represent a malignant reservoir of disease that is believed to drive relapse and resistance to chemotherapy and tyrosine kinase inhibitor (TKIs). Major research efforts in recent years have been aimed at identifying and characterizing the LSC population in leukemias, such as chronic myeloid leukemia (CML), which represents an important paradigm for understanding the molecular evolution of cancer. However, the precise molecular mechanisms that promote LSC-mediated therapeutic recalcitrance have remained elusive. It has become clear that the LSC population evolves during disease progression, thus presenting a serious challenge for development of effective therapeutic strategies. Multiple reports have demonstrated that LSC initiation and propagation occurs as a result of aberrant activation of pro-survival and self-renewal pathways regulated by stem-cell related signaling molecules including β-catenin and Sonic Hedgehog (Shh). Enhanced survival in LSC protective microenvironments, such as the bone marrow niche, as well as acquired dormancy of cells in these niches, also contributes to LSC persistence. Key components of these cell-intrinsic and cell-extrinsic pathways provide novel potential targets for therapies aimed at eradicating this dynamic and therapeutically recalcitrant LSC population. Furthermore, combination strategies that exploit LSC have the potential to dramatically improve the quality and quantity of life for patients that are resistant to current therapies.     

Inflammation and cancer stem cells

Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial–mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.     

应用微流控芯片技术探讨膀胱癌细胞Warburg效应及其分子机制

目的:探讨膀胱癌细胞Warburg效应的发生发展及其分子机制。方法:常规培养膀胱癌细胞系T24细胞,利用微流控芯片技术平台,体外模拟肿瘤细胞生长微环境,分光光度法测定细胞有氧糖酵解的代谢产物尼克酰胺腺嘌呤二核苷酸磷酸(NADPH)的含量变化。结果:成功设计并制作了本研究所用微流控芯片。T24细胞内NADPH含量在一定时间范围内随着细胞培养时间的增加呈下降趋势,提示NADPH在T24细胞合成代谢中以还原形式被消耗,经磷酸戊糖代谢途径的生成来源一定程度上受到抑制。结论:T24细胞的代谢形式主要是以有氧糖酵解的形式进行,部分参与磷酸戊糖代谢通路。     

Dasatinib in combination with fludarabine in patients with refractory chronic lymphocytic leukemia: A multicenter phase 2 study

Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL.     

Mesenchymal stem cell-like cells derived from human gastric cancer tissues

Mesenchymal stem cells (MSCs) have been identified in and isolated from numerous human tissues. The characteristics of mesenchymal stem cells, including their plasticity, the secretion of cytokines, and their low immunogenicity, contribute to their therapeutic potential. It has recently been reported that MSCs are also involved in tumorigenesis and its prognosis. Here, we present the first report of MSC-like cells isolated from human gastric cancer tissues. In our study, gastric cancer-derived MSC-like cells (hGC-MSCs) were isolated from 13 out of 20 cancer tissue samples. Their characteristics, including their morphology, surface antigens, specific gene expression, and differentiation potential, were similar to those of MSCs derived from human bone marrow (hBM-MSCs) but different from gastric cancer cells. The existence of MSC-like cells in gastric cancer tissues suggests that they may be potential targets for cancer therapy and provides an experimental foundation for investigating their role in the initiation and progression of gastric cancers.     

Aromatase and aromatase inhibitors

Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.     

上皮间质转化与肝癌微环境变化的关系

通过对上皮间质转化理论基础的回顾,探讨上皮间质转化、间质上皮转化与肝脏纤维化及肝癌干细胞转化的关系,从而寻找肝癌干细胞的相关基因、抗体标记物及关键通路,这不仅有利于肝细胞癌分期的诊断,提示预后,更为寻找医治肝癌的方法提供更多的研究方向。     

外环境湿度和换气次数对独立通风笼盒微环境湿度和氨浓度的影响

目的：评估在独立通风笼盒（IVC）所处环境不同湿度条件下,IVC 不同换气次数时,大、小鼠 IVC 微环境湿度和氨浓度的变化。方法屏障环境内,以7 d 为换笼周期,分别设定室内环境低湿（40％）、中湿（50％）、高湿（60％）,IVC 换气次数为40次/h、60次/h 时,对3个品牌大、小鼠 IVC 微环境进行测定,观察笼盒内湿度和氨浓度的变化。结果当室内环境为低湿条件,小鼠和大鼠 IVC 换气次数设置为40次/h 时;当室内环境为中湿条件,小鼠换气次数设置为40次/h、大鼠换气次数设置为60次/h 时;当室内环境为高湿条件,小鼠换气次数设置为60次/h 时,笼盒内微环境均基本能够满足 GB14925-2010对湿度和氨浓度的要求。而在高湿情况下,即使大鼠 IVC换气次数置为60次/h 也不能满足要求。结论室内环境湿度和 IVC 换气次数是影响 IVC 微环境的关键指标,只有依据室内环境条件合理设置 IVC 换气次数才能较好地维护 IVC 微环境和达到有效管理的目的。     

肿瘤发生发展过程中相关微环境的动态改变研究进展

在肿瘤干细胞(TSC)的自我更新及分化过程中,肿瘤微环境(TME)发挥着重要作用。在癌变过程中,微环境顺应肿瘤的发展而变化,促使肿瘤细胞获得更多的侵袭性。对肿瘤发展过程中微环境改变的深入研究,将有可能为肿瘤治疗带来新的思路和方法。