幽门螺旋杆菌感染对胃上皮细胞RECK基因的影响

目的研究幽门螺旋杆菌（helicobacter pylori,Hp）感染对胃上皮细胞（GES-1）RECK基因启动子区域的甲基化以及mRNA表达水平的影响,并探讨其可能的致癌机制。方法用培养的Hp感染GES-1细胞0～144h。采用甲基化特异性聚合酶链式反应法检测RECK基因启动子区域的甲基化情况;逆转录PCR检测RECK基因mRNA水平;Westernblot检测核转录因子（NF-κB）的激活情况,并观察用NF-κB特异性抑制剂PDTC处理后的RECK的mRNA水平。结果 Hp感染GES-1细胞0～72h不能诱导RECK基因甲基化,感染96h后GES-1细胞内出现了明显的RECK基因甲基化,同时能降低RECK基因mRNA水平。Hp感染24h后能激活其NF-κB,24～72hNF-κB活性水平无明显改变。感染96h后NF-κB的活性有所增强,NF-κB特异性抑制剂PDTC能上调RECK基因的表达。结论 Hp感染通过诱导RECK基因启动子区域的甲基化,促进NF-κB激活,降低RECK基因的表达,这可能是Hp致胃癌的可能机制之一。     

抗癌活性肽对人胃癌BGC-823细胞周期的调控

目的:探讨抗癌活性肽(anti-cancer bioactive peptide,ACBP)对人胃癌细胞BGC-823细胞周期的影响及其作用机制。方法:体外培养BGC-823细胞,将不同浓度的ACBP作用于细胞,MTT法测定不同浓度的ACBP对BGC-823细胞的生长抑制率;HE染色观察形态学变化;半定量RT-PCR检测细胞周期负性调控分子p27基因mRNA表达的变化。结果:不同浓度(10.0～25.0mg/L)ACBP均能抑制BGC-823细胞的生长,细胞出现明显的凋亡特征性改变,且具有浓度和时间依赖性,25.0mg/LACBP作用72h抑制率为(84.4±2)%,中效浓度(IC50)为7.86mg/L。RT-PCR发现经ACBP处理后,BGC-823细胞的p27mRNA表达明显增加。结论:ACBP对BGC-823细胞的生长有明显的抑制作用,并可诱导细胞凋亡,其抑癌机制可能与其调控细胞周期有关,使p27mRNA重获表达,从而发挥抗BGC-823细胞增殖的作用。     

Effects of hTERT on metal ion-induced genomic instability

There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The longer-term genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased beta-galactosidase staining and apoptosis. This instability was not present in telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERT- cells. The growth and survival of both metal-exposed hTERT+ and hTERT- cells differed if they were cultured at subconfluent levels or plated out as colonies. Genomic instability is considered to be a driving force towards cancer. This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.     

前列腺癌的磁共振弥散加权成像与病理对照研究

目的 评价磁共振弥散加权成像(DWI)在前列腺癌诊断及鉴别诊断中的应用价值。方法 53例前列腺特异性抗原(PSA)异常、直肠指检或超声异常的疑似前列腺癌患者,术前行DWI检查,对比术后病理结果,分析其表观弥散系数(ADC)值。结果 术后病理检查发现前列腺癌15例,前列腺增生37例,上皮内瘤变1例。在弥散敏感系数(b)...     

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.     

依赖NKG2D的肿瘤免疫逃避

活化性受体NKG2D(natural-killer group 2,member D)和其配基在NK、γδ+T和CD8+T细胞介导的肿瘤免疫应答中扮演了重要角色.NKG2D识别肿瘤细胞表面的配体激活效应细胞,产生有效的抗肿瘤免疫应答.但是在完全具有免疫能力的机体内,表达NKG2D配基的肿瘤仍能够生长发育,因此,在患肿瘤小鼠和肿瘤病人中一定存在着依赖NKG2D的免疫逃避机制.本文就依赖于NKG2D的免疫逃避作一详细综述,主要包括:干涉NKG2D受体的免疫逃避、干涉NKG2D配基的免疫逃避、细胞因子破坏NKG2D受体和配基的免疫逃避、抑制性细胞参与NKG2D介导的免疫逃避.这些研究为抗肿瘤治疗提供了新的途径.     

甲状腺微小癌的外科手术治疗研究

目的 比较甲状腺微小癌全切术与传统手术的疗效.方法 比较82例经甲状腺全切术治疗的甲状腺微小癌患者(观察组)与82例经传统手术治疗的甲状腺微小癌患者(对照组)的疗效、手术指标(手术时间、出血量、切口长度、住院时间)、术后并发症发生情况和术后1年复发率、颈部淋巴结转移率、远处转移率.结果观察组患者治疗的总有效率为95.12%(39/41),高于对照组的78.05%(32/41),差异有统计学意义(P﹤0.05).观察组患者的手术时间、出血量、切口长度和住院时间分别为(41.5±11.4)min、(42.5±12.8)ml、(5.2±1.0)cm、(4.4± 1.2)d,均低于对照组的(68.7±14.6)min、(83.6±10.6)ml、(6.2±1.4)cm、(6.3±1.4)d,差异均有统计学意义(P﹤0.05).治疗后观察组患者的并发症发生率为7.32%(3/41),低于对照组的29.27%(12/41),差异有统计学意义(P﹤0.05).术后1年观察组患者的复发率、颈部淋巴结转移率和远处转移率分别为4.88%(2/41)、4.88%(2/41)、7.32%(3/41),均低于对照组的19.51%(8/41)、21.95%(9/41)、26.83%(11/41),差异均有统计学意义(P﹤0.05).结论 甲状腺全切术治疗甲状腺微小癌的疗效明显,对患者造成的创伤较小;同时可以明显减少术后并发症、复发率和转移率,有利于患者早日康复,值得临床推广应用.     

人咽喉部肿瘤组织HPV免疫组化及DNA斑点杂交的检测

用免疫组化及ＤＮＡ斑点杂交技术检测人咽喉部乳头状瘤及鳞状细胞癌组织中ＨＰＶ壳蛋白抗原及ＨＰＶ６、１１、１６、１８型ＤＮＡ。结果显示，５例正常粘膜、１５例声带息肉ＨＰＶ抗原及ＤＮＡ检测均阴性。１１例乳头状瘤ＨＰＶ抗原与ＨＰＶＤＮＡ阳性率均为４５．５％。２２例鳞状细胞癌ＨＰＶ抗原阳性率为２２．７％，ＨＰＶＤＮＡ阳性率为２７．３％。乳头状瘤ＨＰＶ检出率与组织学检查的结果相符。结果提示咽喉部乳头状瘤及鳞状细胞癌的发生和发展与ＨＰＶ感染有关系。     

丙酮酸乙酯注射液的大鼠长期毒性试验

目的： 观察连续肌肉注射丙酮酸乙酯 (ethyl pyruvate,EP)注射液后大鼠产生的长期毒性反应。方法：按年龄、体质量、性别均衡的原则将60只SD大鼠随机分成EP注射液高 (2 400 mg/kg)、中 (1 600 mg/kg)、低 (50 mg/kg)剂量组和溶剂对照组,每组15只,3个给药组每天进行双后肢 (或臀部)肌肉注射给药,连续14 d,溶剂对照组则给予等容量大豆油,观测大鼠一般情况、血常规、血液生物化学等相关毒性反应指标的变化。结果：大鼠每次注射EP药物后5 min内高剂量组产生明显抽搐、俯卧、后肢僵直、呼吸急促等毒性反应但逐渐缓解,注射后30 min内即恢复正常,未见动物死亡;中剂量组上述毒性反应较轻;低剂量组与溶剂对照组无明显差别。血常规和血液生物化学相关指标除在第1次给药14 d后高剂量组的肺和脾系数,中剂量组脾系数明显增加外 (P<0.05),其余各剂量组与溶剂对照组比较差异均无统计学意义 (P>0.05),停药后各剂量组均未见迟缓性毒性发生。结论：高剂量 (2 400 mg/kg) EP注射液对大鼠中枢神经系统会产生较明显毒性作用,但为可逆性的。EP 注射液作为单次用药对大鼠无长期毒性作用。     

bcl-2抑制剂联合地西他滨治疗慢性粒-单核细胞白血病转化型急性髓系白血病一例并文献复习

目的 提高对转化型急性髓系白血病(AML)及其治疗方法的认识.方法 报道1例慢性粒-单核细胞白血病(CMML)转化为AML患者的诊断及治疗过程,并进行文献复习.结果 患者为老年男性,初步诊断为CMML,并快速转化为AML-M4.初始给予小剂量地西他滨(10 mg/周,皮下注射)诱导分化治疗,3周后联合bcl-2抑制剂(venetoclax)治疗,取得了较好的疗效.但患者年龄较大,合并脏器功能受损,最终因呼吸衰竭,进而多器官衰竭死亡.结论 转化型AML目前尚无标准的治疗方案,预后差,长期生存率低,需要探索新的治疗方法来提高患者生存率.