Survivin-siRNA抑制肺癌A549细胞的增殖并增强其对顺铂的敏感性

目的：构建靶向存活素（survivin）的干扰RNA（siRNA）质粒,观察其对A549细胞增殖、凋亡以及顺铂敏感性的影响。方法：应用pSilencerU6质粒构建survivinsiRNA干扰质粒,RTPCR和Western blotting检测survivin mRNA和蛋白的表达,DAPI染色法检测细胞的凋亡,MTT法检测细胞的增殖。结果：成功构建了survivinsiRNA干扰质粒。SurvivinsiRNA质粒转染可明显下调A549细胞中survivin mRNA和蛋白的表达、抑制A549细胞的增殖、促进细胞的凋亡、增强A549细胞对顺铂的敏感性。结论：SurvivinsiRNA沉默survivin在肺癌细胞中的表达能够抑制肿瘤细胞的增殖、促进细胞凋亡,并能增强肿瘤细胞对化疗药物顺铂的敏感性,survivin 可作为肺癌治疗的潜在靶点。     

pVAX-iNOS真核表达载体的构建及其抗肺癌作用研究

背景与目的 iNOS与NO介导的抗肿瘤效应有关.本研究旨在构建pVAX-iNOS载体并转染A549肺癌细胞,检测其基因的表达并初步探讨iNOS基因表达增高后对A549肺癌细胞的抗肿瘤作用.方法 应用RT-PCR方法扩增人iNOS编码序列的CDS片段,构建pVAX-iNOS载体后转染肺癌A549细胞,通过RT-PCR和Western blot方法检测目的基因的表达;采用MTT法、Hoechst 3235染色和划痕实验分别检测iNOS高表达在体外对肺癌A549细胞增殖、凋亡和迁移作用的影响.结果 真核表达质粒载体pVAX-iNOS构建成功,iNOS蛋白在转染后的A549细胞中表达升高.pVAX-iNOS转染A549肺癌细胞后能明显诱导细胞发生凋亡并抑制肿瘤细胞的生长和迁移.结论 本研究成功构建pVAX-iNOS真核表达质粒,高表达iNOS能明显抑制A549细胞的增殖、迁移并促进细胞发生凋亡.本研究有望为临床治疗肺癌提供一个新的有效策略.     

核苷酸切除修复基因XPB反义RNA表达质粒的构建及其功能的初步研究

背景与目的：核苷酸切除修复机制是细胞修复损伤DNA的重要途径,肿瘤细胞的耐药常伴随DNA损伤修复基因表达增强,采取反义策略降低细胞的DNA损伤修复能力可以增加肿瘤细胞的药物敏感性。本研究拟构建能在哺乳动物细胞中表达XPB反义RNA的表达质粒pcDNA-XPB/AS(XPB：着色性干皮病B基因),并初步探讨其对肺癌细胞DNA损伤修复能力及抗肿瘤药物耐药性的影响。方法：采用RT-PCR技术扩增的XPB cDNA5′端一段69--520bp的序列被反向插入表达质粒pcDNA3．1／His。将该重组质粒瞬时转染肺癌A549细胞。单细胞凝胶电泳(SCGE)比较阿霉素诱导的转染前后细胞DNA损伤修复情况。MTT法检测转染前后细胞对阿霉素的敏感性。结果：酶切图谱分析和基因测序证实反义表达质粒构建成功。RT-PCR显示转染细胞XPB mRNA表达水平下降。以4．Oμg／ml阿霉素诱导细胞DNA损伤,SCGE显示转染细胞修复DNA损伤能力受到抑制。MTT显示未转染细胞与转染细胞对阿霉素的敏感性存在差别,但无统计学意义。结论：构建的反义表达质粒能下调转染细胞XPB mRNA表达,抑制细胞DNA损伤修复能力,为进一步研究XPB基因功能奠定了基础。     

外源性P73基因对WtP53型人肺腺癌细胞A549化疗敏感性的影响

目的 研究外源p73基因转染wtp53型人肺腺癌A549细胞对其化疗药物敏感性的影响。方法 用脂质体介导的转染技术。将含有全长人野生型p73α cDNA和野生型p53 cDNA的真核表达重组质粒分别导入A549细胞，观察基因转染前后肿瘤细胞对化疗药物顺铂和阿霉素敏感性的变化。结果 A549-p73α细胞可以稳定地表达P73α蛋白，其生长速度较未转染p73α和转染wtp53基因的A549细胞明显减慢，克隆形成数下降，凋亡细胞明显增多。与未转染组比较，在原本没有抑制和杀伤作用的化疗药物浓度作用下A549-p73α细胞生长明显受到抑制，顺铂和阿霉素的IC50值分别降低为约1／6和／70。结论 研究显示外源性p73基因的导人增加了wtp53型人肺腺癌A549细胞对顺铂和阿霉素等化疗药物的敏感性，为p73基因用于治疗wtp53不能发挥作用的恶性肿瘤提供实验依据。     

针对CD44V3的短发夹RNA抑制肺癌A549细胞体外增殖

目的研究针对CD44 V3的短发夹RNA(short hairpin RNA,shRNA)对体外培养的人肺腺癌A549细胞CD44 V3表达及增殖能力的影响.方法设计和构建带有U6启动子的、能产生针对CD44V3的shRNA的RNA干扰表达质粒,转染至A549细胞,以RT-PCR和Western blot检测A549细胞转染前后CD44 V3表达,以MTT实验和软琼脂细胞集落形成实验比较A549细胞转染前后增殖能力.结果和转染前相比,转染了RNA干扰表达质粒的A549细胞CD44V3 mRNA和蛋白表达、以及增殖能力皆明显降低.结论针对CD44V3的短发夹RNA能明显抑制人肺腺癌A549细胞体外增殖能力.     

针对CD44V3的短发夹RNA抑制肺癌A549细胞体外增殖

目的：研究针对CD44V3的短发夹RNA（short hairpin RNA，shRNA）对体外培养的人肺腺癌A549细胞CD44V3表达及增殖能力的影响。方法：设计和构建带有U6启动子的、能产生针对CD44V3的shRNA的RNA干扰表达质粒，转染至A549细胞，以RT—PCR和Western blot检测A549细胞转染前后CD44V3表达，以MTT实验和软球脂细胞集落形成实验比较A549细胞转染前后增殖能力。结果：和转染前相比，转染了RNA干扰表达质粒的A549细胞CD44V3 mRNA和蛋白表达、以及增殖能力皆明显降低。结论：针对CD44V3的短发夹RNA能明显抑制人肺腺癌A549细胞体外增殖能力。     

托瑞米芬与表阿霉素联用对A549、H1299细胞生长与凋亡的影响

目的：探讨托瑞米芬（TOR）与表阿霉素（EADM）联用对人肺癌细胞株A549、H1299细胞生长与凋亡的影响及其机制.方法：用MTT比色法检测TOR的化疗增敏作用,用流式细胞仪检测细胞周期的变化及p-gp在两种肺癌细胞中的表达.结果：TOR（≥20μmol/L）能直接抑制两种细胞的生长,低剂量的TOR（5、10μmol/L）与EADM联用后的抑制率均低于单用EADM组（P＜0.01）,并呈现浓度依赖性.两者联用可引起两种肿瘤细胞凋亡,呈现浓度依赖性.两种细胞周期均发生明显变化.13.1?49细胞有p-gp的存在,44.9%H1299细胞有p-gp的存在.结论：低浓度的托瑞米芬与表阿霉素联用对两种细胞有明显的协同作用.A549细胞的TOR对EADM的协同作用较H1299细胞强.其化疗增敏效应可能与增加肿瘤细胞凋亡、改变细胞周期分布有关.P53基因可能参与了TOR对两种细胞的化疗增敏及逆转耐药的调节.     

miRNA-192对非小细胞肺癌A549／DDP细胞顺铂耐药性的影响

目的 探讨抑制microRNA-192（miR-192）在非小细胞肺癌A549／DDP细胞对顺铂（DDP）耐药性方面的影响及可能机制。方法 通过实时荧光定量PCR（qRT-PCR）法检测人肺腺癌耐DDP细胞株A549／DDP及其亲本细胞株A549细胞中miR-192的表达水平,A549／DDP细胞转染miR-192抑制剂（inhibitor）和miR-阴性对照（NC）48h后采用qRT-PCR检测转染效率,分别采用MTT法、克隆形成实验及流式细胞术检测转染48h后A549／DDP细胞对DDP的药物敏感性、细胞增殖能力及细胞凋亡变化,Western blotting检测转染48h后细胞中Bax和Bcl-2的表达变化。结果 miR-192在A549／DDP细胞中的表达水平高于A549细胞（P＜0.05）;转染miR-192 inhibitor 48h后的A549／DDP细胞miR-192水平低于转染miR-NC者（P＜0.05）;转染miR-192 inhibitor后,A549／DDP细胞的增殖能力减弱、凋亡细胞增多、DDP对其半数抑制浓度降低、Bax蛋白水平升高和Bcl-2蛋白水平下降,与转染miR-NC者比较,差异均有统计学意义（P＜0.05）。结论 抑制miR-192能够降低A549／DDP细胞对DDP的耐药性,其作用机制可能是通过增加细胞凋亡以及下调Bcl-2蛋白和上调Bax蛋白表达来实现的。     

shRNA干扰HERG钾通道治疗裸鼠皮下人成神经细胞移植瘤

目的：探讨发卡结构小片段RNA（small hairpin interfering RNA，shRNA）干扰人ERG（human ether-α—go-go—related gene，HERG）钾通道治疗裸鼠皮下人成神经细胞移植瘤的疗效和作用机制。方法：用真核转录载体mU6pro构建针对herg基因的发卡状RNA干扰质粒（shRNA-herg）。18只BALB／c裸小鼠皮下接种成神经细胞瘤SH—SY5Y细胞，建立裸鼠皮下人成神经细胞移植瘤模型，当瘤体积达到100mm^3时随机分成3组，分别为生理盐水组（Ⅰ）、对照质粒组（Ⅱ）、干扰质粒组（Ⅲ）。各组瘤内分别注射生理盐水、对照质粒、干扰质粒，以后每7d注射1次，连续15d。观察各组肿瘤生长情况，RT—PCR测定肿瘤组织herg基因mRNA含量变化，免疫组化检测肿瘤组织中HERG钾通道蛋白变化。结果：经治疗后，第Ⅲ组肿瘤生长受到明显抑制，Ⅱ、Ⅲ组抑瘤率分别为3．04％和29．78％（P〈0．05）。肿瘤组织内berg基因mRNA含量、HERG钾通道蛋白，Ⅲ组较Ⅰ、Ⅱ组表达减弱。结论：构建的shRNA干扰质粒可通过靶向性抑制herg基因及其编码的HERG钾通道蛋白的表达，有效地抑制人成神经细胞瘤的生长。     

氧化铁磁性纳米颗粒介导wt-p53基因对肺腺癌细胞增殖和凋亡的影响

目的：探讨氧化铁磁性纳米颗粒介导野生型p53基因（wild type p53,wt-p53）对耐顺铂人肺腺癌细胞A549/DDP增殖抑制和凋亡诱导的作用。方法：氧化铁磁性纳米颗粒介导wt-p53转染肺腺癌细胞A549/DDP作为实验组,以纳米颗粒介导空载体pcDNA3转染作为阴性对照组,脂质体介导wt-p53转染作阳性对照组。MTT法和绘制生长曲线观察基因转染对A549/DDP细胞增殖抑制作用,荧光显微镜、流式细胞术观察其对A549/DDP细胞诱导凋亡作用,RT-PCR检测其对A549/DDP细胞Bax mRNA表达的影响。结果：氧化铁磁性纳米颗粒介导wt-p53对人肺腺癌细胞A549/DDP增殖有持续的抑制作用,而以脂质体介导wt-p53对增殖抑制作用持续时间短暂;纳米颗粒介导wt-p53对人肺腺癌细胞A549/DDP诱导凋亡作用明显强于以脂质体载体;同时介导wt-p53上调Bax mRNA表达水平的作用也明显强于以脂质体载体。结论：氧化铁磁性纳米颗粒介导wt-p53转染对人肺腺癌细胞A549/DDP有持续的增殖抑制和诱导凋亡的作用。     

HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin

Purpose Previous studies have found that the HERG K⁺ channel is highly expressed in some cancers. In the study reported here, we investigated HERG expression in various cancer cell lines, its correlation with chemosensitivity to vincristine, paclitaxel, and hydroxy-camptothecin, and its biochemical modulation.Methods The MTT assay and clonogenic assay were used to detect the cytotoxicity of anticancer drugs in vitro. HERG expression was analyzed by Western blotting or immunocytochemistry. Gene transfection was used to examine the changes in HERG-related chemosensitivity. Cell cycle phase distribution was detected by flow cytometry and drug combinations were evaluated by the MTT assay.Results HERG expression levels differed widely between various human cancer cell lines and HT-29 cells expressing high levels of HERG were more sensitive than A549 cells expressing low levels of HERG to vincristine, paclitaxel, and hydroxy-camptothecin. In terms of IC₅₀, the chemosensitivities of herg-transfected A549 cells to vincristine, paclitaxel and hydroxy-camptothecin were significantly increased. However, for cisplatin and 5-fluorouracil, no significant difference between herg-transfected A549 cells and parent A549 cells was detected. Erythromycin, a HERG K⁺ channel blocker, suppressed the growth of various cancer cells and the potency was correlated with HERG expression levels. Combinations of erythromycin and vincristine, paclitaxel or hydroxy-camptothecin showed synergy in cytotoxicity to HT-29 cells. Erythromycin also enhanced the G₂/M arrest induced by vincristine in HT-29 cells. There were synergistic effects between erythromycin and vincristine, paclitaxel, and hydroxy-camptothecin, and chemosensitivity was correlated with HERG expression level.Conclusions HERG expression levels and chemosensitivity were positively correlated for vincristine, paclitaxel, and hydroxy-camptothecin. Erythromycin was active as a modulator. These results suggest that HERG may serve as a molecular marker and modulating target for individualized cancer therapy.     

Three-dimensional culture system as a model for studying cancer cell invasion capacity and anticancer drug sensitivity

BACKGROUND: Three-dimensional (3-D) culture systems that simulate the tumor extracellular microenvironment may be appropriate to test cancer cell potential for invasion and tumor cell sensitivity to anticancer drugs. MATERIALS AND METHODS: Human PC-3 prostate, A549 colon, HT-29 lung and MCF-7 and MDA-MB231 breast cancer cells were embedded and grown in collagen gel surrounded by a fibrin clot. Increasing concentrations of cisplatin, doxorubicin, paclitaxel and 5-fluorouracil were comparatively evaluated for their ability to inhibit tumor cell proliferation and colony formation in vitro. RESULTS: All cells, except MDA, formed colonies in collagen. PC-3, A549 and HT-29 cells massively invaded fibrin forming migratory fronts. Cell colonies were also formed in fibrin (secondary tumor-like structures) apart from migratory fronts; HT-29 cells were the most aggressive in this regard MDA cells were particularly sensitive to doxorubicin, while MCF-7 cells showed sensitivity to all anticancer regimens tested. A549 cells were the tumor cell type with greatest potential for invasion and were sensitive mostly to cisplatin. PC-3 cells were primarily sensitive to cisplatin and doxorubicin, while HT-29 cells were sensitive to fluorouracil and doxorubicin. CONCLUSION: 3-D collagen cell culture systems can be used to study cancer cell potential for invasion and their relative sensitivity/resistance to anticancer drugs.     

NGX6基因联用5-Fu对人结肠癌细胞凋亡的影响

目的:探讨候选抑瘤基因NGX6联用5-Fu对结肠癌细胞凋亡的影响.方法:以稳定转染并表达NGX6基因的HT-29细胞与5-Fu联用作为实验组.以PDTC与5-Fu联用的HT-29细胞作为对照组.通过EMSA检测各组结肠癌HT-29细胞核转录因子-κB(NF-κB)的激活情况,利用MTT比色法检测各组细胞增殖的情况.吖啶橙(AO)/溴化乙啶(EB)双染法显微镜观测以及PI/Annexin-V双染流式细胞仪检测各组细胞凋亡情况.结果:稳定转染并表达NGX6基因的HT-29细胞以及应用了PDTC的HT-29细胞NF-κB的激活均明显受到抑制;与5-Fu作用的HT-29细胞组比较,5-Fu联合PDTC作用于HT-29细胞后,HT-29细胞增殖受到明显抑制,5-Fu诱导HT-29细胞凋亡作用增强;与5-Fu联合PDTC作用于HT-29细胞的对照组比较,在诱导细胞凋亡以及抑制细胞增殖方面,稳定转染并表达NGX6基因的HT-29细胞与5-Fu联用组和对照组所取得一致的效果,NGX6基因增强5-Fu对HT-29细胞增殖抑制的能力及诱导HT-29细胞凋亡的能力.结论:NGX6基因抑制了肿瘤细胞NF-κB的激活,具有增强5-Fu诱导结肠癌细胞凋亡的能力,其机制可能是抑制肿瘤细胞NF-κB的激活,NGX6基因对肿瘤的治疗及预后起积极作用.     

Elevated expression of DNA topoisomerase II in camptothecin-resistant human tumor cell lines

In a previous study, we established camptothecin (CPT)-resistant cell lines, A549/CPT and HT-29/CPT, from human lung cancer A549 and human colon cancer HT-29. A549/CPT was shown to express similar amounts of DNA topoisomerase I (topo I) as the parental line, and HT-29/CPT was shown to express lower amounts of topo I than its parental line. DNA topoisomerases I and II are known to be functionally related. In the present study, the possible alterations in topo II expression were examined in these human CPT-resistant lines. In A549/CPT and HT-29/CPT, the cellular contents of topo II and its mRNA were elevated over that seen in each parental line. Nuclear extracts from A549/CPT and HT-29/CPT showed higher topo II activity than those from the corresponding parental lines when the same amounts of nuclear protein were used. Topo II was partially purified from HT-29 and HT-29/CPT by hydroxylapatite column chromatography, and the enzyme activities were compared. HT-29/CPT showed higher topo II activity in the hydroxylapatite column-eluted fractions than HT-29. These results indicate the possible activation of topo II expression in the CPT-resistant cell lines.     

Effects of BTG2 on proliferation inhibition and anti-invasion in human lung cancer cells

The objective of the study was to investigate the impact of the B cell translocation gene 2 (BTG2) on lung cancer cell growth, proliferation, metastasis, and other biological characteristics and to provide experimental evidence for the biological treatment of human lung cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the human lung cancer cell line A549. The biological changes in the BTG2-expressing cells were analyzed using growth curves, the MTT (tetrazolium) assay, propidium iodide (PI) staining, and the Transwell invasion chamber. Additionally, Western blotting was used to determine the impact of BTG2 on the protein expression of cyclin D1, MMP-1, and MMP-2. Compared to the empty vector-transfected A549 cells or the mock-transfected A549 cells, the pcDNA3.1-BTG2-transfected A549 cells grew significantly slower. No significant differences were detected between the empty vector-transfected group and the mock-transfected A549 cells. The growth curve analysis and the PI staining showed that the pcDNA3.1-BTG2-transfected cells grew significantly slower than the empty vector-transfected A549 cells (P < 0.05). The cell invasion assay results suggested that the invasion rate of the pcDNA3.1-BTG2-transfected A549 cells was significantly slower than the invasion rate of the empty vector-transfected group and the mock-transfected group (P < 0.05). The overexpression of BTG2 may inhibit the protein expression of cyclin D1, MMP-1, and MMP-2 in A549 cells. The overexpression of BTG2 may inhibit the growth, proliferation, and invasiveness of the A549 human lung cancer cell line.     

herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells

The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy. We report in this article that K(+) ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells. Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.     

Survivin反义核酸对大肠癌HT-29细胞侵袭力的影响

目的观察反义Survivin寡核苷酸对人大肠癌HT-29细胞侵袭力的影响。方法 应用针对Survivin模板序列的反义寡核苷酸链处理大肠癌HT-29细胞, 观察细胞培养生长增殖状况, 半定量RT-PCR检测不同组别Survivin基因表达的水平, 应用Transwell小室检测体外侵袭力变化。结果 反义组细胞数量少, 生长稀疏, 细胞贴壁缓慢;大肠癌细胞的集落形成能力受到抑制, 经过RT-PCR扩增后半定量分析结果显示, 反义核酸治疗组的表达量低于对照组和正义组。侵过小室滤膜细胞数减小。结论 Survivin反义寡核苷酸作用后的大肠癌HT-29细胞株生长受到抑制, 细胞株侵袭力降低。     

DNA 甲基化抑制剂对肿瘤细胞中核糖核酸酶抑制因子表达下调的影响

背景与目的:人核糖核酸酶抑制因子 (ribonucleasE-inhibitor, RI) RI能有效抑制血管生成因子诱导的血管形成及某些可移植性实体瘤在动物体内的生长.然而, RI抗肿瘤的分子机制还未完全阐明.许多抑癌基因通过启动子区域异常的甲基化而使表达缺失,去甲基化抑制能使其表达恢复.为了进一步了解 RI的功能以及探讨 RI与肿瘤发生的关系,本实验拟研究甲基化抑制剂 5-aza-2′-deoxycytidinE-(5-Aza-CdR)对肿瘤细胞中 RI表达的影响.方法:用 5-Aza-CdR作用人乳腺癌细胞系 MCF-7、人胃癌细胞系 BGC-823、人的前列腺癌细胞系 DU-145和人结肠癌细胞系 HT-29.通过 RT PCR,蛋白免疫印迹法( Western blot) ,免疫荧光( immunofluorescence)和免疫细胞化学( immunocytochemistry)技术分析 RI基因的表达.结果:与对照组比较, 5-Aza-CdR能显著提高 RI基因在 MCF-7、 BGC-823和 DU 145细胞中的表达, RT PCR检测结果分别为 37.2%、 46.0%和 32.4%, Western blot检测结果分别为 26.4%、 20.9%和 24.4%( P< 0.01);但对 HT-29细胞没有明显的影响.结论: RI基因可能与胃癌、前列腺癌和乳腺癌的发生有关.     

Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

PURPOSE: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. METHODS AND MATERIALS: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 degrees C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. RESULTS: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 degrees C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 degrees C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 degrees C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. CONCLUSION: The present data suggest that a significant radiosensitization of prostatic cancer cells could be obtained by the combined treatment of radiation and mild hyperthermia. Future clinical trials should be aimed at achieving mild heating and fractionated radiation therapy.     

HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium

HERG K(+)channels, besides contributing to regulate cardiac and neuronal excitability, are preferentially expressed in tumour cell lines of different histogenesis, where their role in the development and maintenance of the neoplastic phenotype is under study. We show here that both herg gene and HERG protein are expressed with high frequency in primary human endometrial cancers, as compared to normal and hyperplastic endometrium. RT-PCR and immunohistochemistry, using specific anti-HERG antibodies developed in our laboratory, were applied to tissue specimens obtained from 18 endometrial cancers and 11 non-cancerous endometrial tissues. herg RNA and HERG protein are expressed in 67% and 82%, respectively, of cancerous, while in only 18% of non-cancerous tissues. In particular, no expression was found in endometrial hyperplasia. Moreover, electrophysiological experiments confirmed the presence of functioning HERG channels on the plasma membrane of tumour cells. On the whole, these data are the first demonstration of the presence of HERG channels in primary human neoplasias, and could candidate HERG as a potential tool capable of marking cancerous versus hyperplastic endometrial growth.