血浆EBV DNA水平测定在监测鼻咽癌放疗后复发、转移中的临床意义

目的 探讨定量分析血浆EBV DNA水平在监测鼻咽癌复发、转移中的临床意义。方法 应用荧光定量PCR技术（real-time PCR）,检测360例根治放疗后鼻咽癌患者血浆EBV DNA水平,并与临床及影像学检查结果 比较。结果 360例患者中87例血浆EBV DNA检测阳性,273例阴性。在87例检出阳性者中,25例证实为临床复发,45例证实为远处转移,故其预测肿瘤进展阳性预测值为80%（70/87）。在273例血浆EBV DNA检测阴性患者中,共有17例复发和4例转移,故其阴性预测值为92%（252/273）。总计91例肿瘤进展患者中70例血浆EBV DNA阳性,其中复发42例,25例血浆EBV DNA阳性;转移49例,45例血浆EBVDNA阳性。269例临床缓解患者中17例血浆EBV DNA阳性,故其敏感性、特异性、假阳性率和假阴性率分别为77%（70/91）、94%（252/269）、6%（17/269）、23%（21/91）、90%（322/360）。复发患者、转移患者、肿瘤进展患者和临床缓解患者EBVDNA阳性率和中位拷贝数分别为：60%,4700 copies/ml;92%,425000 copies/ml;77%,38000 copies/ml;6%,〈500copies/ml。复发患者与转移患者比较、肿瘤进展患者与临床进展患者比较,血浆EBV DNA阳性率和中位拷贝数均有显著性差异。结论 血浆EBV DNA水平的检测是监测放疗后鼻咽癌患者转移、复发的有效指标。     

EBV DNA定量分析在监测鼻咽癌转移和复发中的临床意义

背景与目的:EB病毒(Epstein-Barrvirus,EBV)感染与鼻咽癌关系密切,近年来,有报道鼻咽癌患者血浆/血清中可检测到游离EBVDNA,但血浆EBVDNA水平对判断放疗后鼻咽癌患者转移、复发的临床意义尚缺少大宗研究报道。本研究定量检测鼻咽癌放疗后随诊患者血浆EBVDNA含量,探讨其在监测鼻咽癌转移、复发中的临床意义。方法:选择在中山大学肿瘤防治中心门诊随诊的放疗后鼻咽癌患者90例,用荧光定量PCR方法检测血浆EBVDNA含量,比较转移、复发与持续缓解患者血浆EBVDNA拷贝数。结果:放疗后转移或复发患者血浆EBVDNA的检出率为96.7%(29/30),中位拷贝数为2650copies/ml(0～5900000copies/ml);而持续缓解组患者血浆EBVDNA检出率12%(7/60),中位拷贝数为0copy/ml(0～71000copies/ml),差异均有统计学意义(P<0.01)。3例临床持续缓解但有血浆EBVDNA升高患者,在随后的3～4个月随访中,证实有肿瘤转移或复发。结论:血浆EBVDNA李宇红,等.EBVDNA定量分析在646定量检测可能成为监测放疗后鼻咽癌患者肿瘤转移、复发的敏感肿瘤标记物。     

鼻咽癌患者血浆EB病毒DNA水平与肿瘤复发的关系

目的 :探讨鼻咽癌患者放射治疗后血浆EB病毒 (EBV)DNA水平与肿瘤复发的关系。方法 :11例临床缓解期患者和 9例临床复发患者分别抽血 3ml。所有的标本均采用荧光定量PCR的方法 ,在PE770 0型检测仪上定量检测血浆标本中EB病毒DNA的含量。结果 :肿瘤复发组 89% ( 8/ 9)的患者血浆中可检测到高拷贝数的EB病毒DNA ,中位浓度为4 70 0 0 0 (copies/ml) ,在临床缓解组患者中 ,仅 9% ( 1/ 11)的患者血浆中可检测到较高拷贝数的EB病毒DNA ,中位浓度为 0(copies/ml)。两组阳性率及中位浓度的比较均有显著性差异 (P <0 0 0 1)。结论 :鼻咽癌患者血浆EBVDNA水平与肿瘤复发关系密切 ,值得进一步研究。     

鼻咽癌患者血浆 EBV DNA 水平和 VCA-IgA 检测的临床意义

目的:探讨鼻咽癌患者血浆EBV DNA水平和VCA-IgA联合检测对鼻咽癌早期诊断的临床价值。方法:用荧光定量PCR方法检测血浆EBV DNA水平,常规免疫酶法检测VCA-IgA抗体滴度。结果:68例鼻咽癌患者中,EBV DNA阳性率95.59,中位拷贝数93×104copies/ml,VCA-IgA抗体阳性率92.65,抗体滴度≥1:20;其他头颈肿瘤36例中,EBV DVA阳性率5.56,中位拷贝数为0copies/ml,VCA-IgA抗体阳率36.11,阳性滴度均≤1:20;健康对照组EBV DNA阳性率为35.56,其滴度除3例≥1:40外,余均≤1:20。鼻咽癌患者中EBV DNA和VCA-IgA抗体阳性率显著高于对照组。结论:进一步证实EBV与鼻咽癌有密切关系;EBV DNA水平和VCA-IgA抗体滴度联合检测,有助于鼻咽癌的早期辅助诊断。     

定量分析鼻咽癌患者外周血游离EBV

目的:分析外周血游离Epstein-Barr病毒(EBV)是否特异地出现于鼻咽癌患者。方法:收集鼻咽癌患者和非鼻咽癌肿瘤患者血浆各50例,正常人血浆30例,提取DNA,荧光定量PCR检测EBV拷贝数,比较游离EBV在上述人群的差异。结果:在25例(50%)鼻咽癌患者血浆中检测到游离EBV,其拷贝数波动于1×103拷贝/ml血浆～2.6×106拷贝/ml血浆,中位数为5.3×105拷贝/ml血浆。在50例非鼻咽癌肿瘤患者和30例正常人血浆中均未检测到游离EBV。结论:游离EBV出现于鼻咽癌患者外周血,可能是一个较特异的鼻咽癌标志物。     

血浆EBV DNA定量分析在监测鼻咽癌患者复发和转移中的价值

目的 探讨血浆EB病毒DNA(EBV DNA)含量在监测鼻咽癌患者放疗后复发和转移中的临床价值.方法 采用荧光定量PCR方法 检测81例放疗后随诊的鼻咽癌患者血浆EBV DNA含量,比较缓解组与复发、转移组血浆EBV DNA差异.结果 放疗后缓解组患者血浆EBV DNA阳性率为15.7%,中位拷贝数为0 copy/ml;放疗后复发或转移组患者血浆EBV DNA阳性率93.3%,中位拷贝数6 432 copies/ml,差异均有显著性(P<0.001).结论 血浆EBV DNA定量检测有可能成为监测鼻咽癌患者放疗后复发、转移的肿瘤标记物.     

血浆EB病毒DNA浓度预测鼻咽癌远处转移的研究

背景与目的：鼻咽癌治疗失败的主要原因之一是远处转移,近年多项放化疗综合治疗的临床研究未显示出明显的远处转移率的降低和远期生存的获益,综合治疗适宜个体及最佳模式尚未确立。血浆EB病毒DNA（EBV DNA）浓度是一项能反映鼻咽癌分期、治疗反应、预后的灵敏、特异的分子生物学指标。我们设计此前瞻性研究。探讨通过鼻咽癌患者血浆EBV DNA浓度预测远处转移的发生．为个体化的综合治疗模式的选择提供分子学指标。方法：69例初治鼻咽癌患者分别在治疗前和治疗结束时采用荧光定量PCR方法检测血浆EBV DNA浓度。所有患者按计划随访。进行远期疗效及生存的评价。Kaplan-Meier法计算无转移生存率及总生存率,多因素分析用Cox回归模型。结果：远处转移患者治疗前血浆EBV DNA中位浓度（27 000copies／m1）及治疗后EBVDNA检出率（55．56％）均高于持续缓解者（4 000 copies／ml,5．56％）及局部复发者（3 850 copies／ml,0％）（P值分别为0．039,0．001）。以治疗前20 000 copies／ml、治疗后0 copies／ml为界值点．EBV DNA低浓度患者的无复发生存率、无转移生存率及总生存率均高于高浓度患者,差异有显著性。Cox回归分析显示治疗前EBV DNA浓度（P=0．050,RR=3．95）、治疗后EBVDNA浓度（P=0．001,RR=11．74）均是影响无转移生存的危险因素。进一步将患者治疗前后EBVDNA浓度变化综合进行生存分析,结果表明治疗后EBV DNA浓度能否降到0是影响无转移生存最重要的预后因素（P=0．000）。结论：鼻咽癌患者治疗前、后血浆EBV DNA浓度,尤其是治疗后能否降到0．能预测远处转移的发生,有望为放化综合治疗筛选高危患者,指导放化结合模式的选择。     

鼻咽癌患者血浆EBVDNA水平和VCA—IgA检测的临床意义

目的：探讨鼻咽癌患者血浆EBVDNA水平和VCA—IgA联合检测对鼻咽癌早期诊断的临床价值。方法：用荧光定量PCR方法检测血浆EBVDNA水平，常规免疫酶法检测VCA—IgA抗体滴度。结果：68例鼻咽癌患者中，EBVDNA阳性率95．59％，中位拷贝数93× 10^4 copies／ml，VCA—IgA抗体阳性率92．65％，抗体滴度≥1：20；其他头颈肿瘤36例中，EBVDVA阳性率5．56％，中位拷贝数为0copies／ml，VCA—IgA抗体阳率36．11％，阳性滴度均≤1：20；健康对照组EBVDNA阳性率为35．56％，其滴度除3例≥1：40外，余均≤1：20。鼻咽癌患者中EBVDNA和VCA—IgA抗体阳性率显著高于对照组。结论：进-步证实EBV与鼻咽癌有密切关系；EBVDNA水平和VCA—IgA抗体滴度联合检测，有助于鼻咽癌的早期辅助诊断。     

血浆EBV DNA监测鼻咽癌治疗疗效意义

目的 探讨血浆EBV DNA监测鼻咽癌治疗疗效的临床意义。方法 回顾分析2016-2017年间本院初诊的799例鼻咽癌根治性调强放疗患者的临床资料。分析疗前血浆EBV DNA与临床分期、肿瘤进展的相关性,比较放疗结束及随访中EBV DNA与肿瘤进展的关系。结果 疗前DNA表达水平与临床分期、肿瘤进展呈正相关(P<0.001)。放疗结束后6~8周,19例(2.3%)血浆EBV DNA持续阳性者预后最差,14例发生了肿瘤进展。9例放疗结束后6~8周转为EBV DNA阴性,3例肿瘤进展。而放疗结束EBV DNA阴性患者肿瘤进展率仅8.3%(64/772),3个组无肿瘤进展生存率不同(P<0.05)。随访中持续性血浆EBV DNA阳性,诊断肿瘤进展的敏感性、特异性、准确性分别为77.6%、100%、98.1%。结论 鼻咽癌患者疗前EBV DNA表达水平与肿瘤负荷和肿瘤进展相关,放疗结束6~8周EBV DNA持续阳性者预后极差,应给予合适的辅助治疗。随访中持续性血浆EBV DNA阳性诊断肿瘤进展的正确性高,是鼻咽癌根治性治疗后可靠的疗效监测指标。     

血浆EBV DNA监测鼻咽癌治疗疗效意义

目的 探讨血浆EBV DNA监测鼻咽癌治疗疗效的临床意义。方法 回顾分析2016-2017年间本院初诊的799例鼻咽癌根治性调强放疗患者的临床资料。分析疗前血浆EBV DNA与临床分期、肿瘤进展的相关性,比较放疗结束及随访中EBV DNA与肿瘤进展的关系。结果 疗前DNA表达水平与临床分期、肿瘤进展呈正相关(P<0.001)。放疗结束后6~8周,19例(2.3%)血浆EBV DNA持续阳性者预后最差,14例发生了肿瘤进展。9例放疗结束后6~8周转为EBV DNA阴性,3例肿瘤进展。而放疗结束EBV DNA阴性患者肿瘤进展率仅8.3%(64/772),3个组无肿瘤进展生存率不同(P<0.05)。随访中持续性血浆EBV DNA阳性,诊断肿瘤进展的敏感性、特异性、准确性分别为77.6%、100%、98.1%。结论 鼻咽癌患者疗前EBV DNA表达水平与肿瘤负荷和肿瘤进展相关,放疗结束6~8周EBV DNA持续阳性者预后极差,应给予合适的辅助治疗。随访中持续性血浆EBV DNA阳性诊断肿瘤进展的正确性高,是鼻咽癌根治性治疗后可靠的疗效监测指标。     

Mouse models to interrogate the implications of the differentiation status in the ontogeny of gliomas

Glioblastoma multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors, with a median survival of 14-16 months despite optimal surgery, radiation and chemotherapy. A reason for this dismal prognosis is insufficient understanding of the ontogeny of GBMs, which are highly heterogeneous at a pathological level. This pathological diversity, between and within GBMs as well as varying grades of gliomas, has not been fully explained solely on the grounds of oncogenic stimulus. Interaction with the tumor microenvironment is likely a source of this pathological heterogeneity, as well as the inherent characteristics of the tumor cell of origin. Currently, controversy exists on whether the initial transformed cell is a differentiated astrocyte, progenitor or neural stem cell. Putative cancer stem cells (CSCs), which have features of normal stem cell plus the ability to recapitulate the tumor phenotype in vivo in small numbers, have been identified from a variety of solid human cancers, including GBMs. Evidence suggesting that regions harboring normal stem cells in the adult CNS, such as the subventricular zone and the dentate gyrus, are more prone to viral and chemical oncogenesis, is supportive of the hypothesis that brain tumors arise from stem cells. However, it is still to be determined whether the appearance of brain tumor stem cells (BTSC) is the cause or consequence of tumor initiation and progression. This review discusses emerging evidence highlighting the relevance of the state of differentiation and regional heterogeneity in the ontogeny of GBM. This is an area of high interest in cancer in general, with potential significant therapeutic and prognostic implications.     

肿瘤相关中性粒细胞的研究进展

肿瘤生长依赖肿瘤微环境,肿瘤相关中性粒细胞(TANs)是肿瘤微环境中的一种重要炎症细胞.TANs分为具有抗肿瘤效应的"N1"型和促肿瘤效应的"N2"型.因此,TANs具有对机体有利和有害的两面性.大量研究表明,TANs通过分泌细胞因子和化学因子等,影响肿瘤的生成、转移、血管生成与免疫调节.本文将从TANs的生物学特性和TANs与肿瘤发生发展、预后及治疗等方面,综述TANs和肿瘤关系的研究进展.     

Inadvertent tumor violation during musculoskeletal sarcoma surgery and risk of recurrence.

During the limb preserving procedure for musculoskeletal sarcoma, the course of action that should be taken when a tumor or tumor-cell-contaminated adjacent tissue is violated remains controversial. From January, 1973, to July, 1989, 120 patients with musculoskeletal sarcoma were treated by limb salvage surgery and, in 40 of them, such violations inadvertently occurred during surgery. Follow-up studies on the patients have been conducted for at least one year after the violation. Soft tissue sarcoma was noted in 24 cases (low grade, 4; high grade, 20) and bone sarcoma in 16 (low grade, 6; high grade, 10). To treat the violation, re-excision with a clean margin and copious lavage was generally conducted after careful closure of the violated site. Sixteen cases in the soft tissue sarcoma group and eight in the bone sarcoma group were treated in this way. Local recurrences were found in 13 of the 40 cases (33%), but the percentage was reduced to 13 in cases treated by re-excision with a clean margin. In the present study, there was no significant effect of adjuvant therapy after violation. The survival rate in cases of local recurrence was very low, and not at all improved by adjuvant therapy.     

肿瘤血管生长因子在原发性肝癌血清中的表达及其意义

目的：探讨肿瘤血管生长因子（ＴＡＦ）在原发性肝癌血清中的表达及其意义。方法：对１８４例临床确诊的原发性肝癌（肝癌）病人行ＦＡＭ方案肝动脉化疗栓塞术。应用生化比色定量法分别检测术前、术后血清ＴＡＦ的表达水平,并且与血清中甲胎蛋白（ＡＦＰ）表达、肿瘤大小、碘化油栓塞剂肿物充填量及其形态分布进行比较分析。结果：全部病例ＴＡＦ术前、术后水平均高于正常水平,肝癌病人中仍有３０．４％ＡＦＰ,其术前、术后ＴＡＦ     

大肠杆菌内毒素体外诱生肿瘤坏死因子及影响因素的分析

本实验应用细胞培养及细胞毒生物测定法分别观察了各因素（单独或组合后）对培养上清中肿瘤坏死因子（ＴＮＦ）细胞毒性的诱生作用。结果表明：经不同浓度ＬＰＳ刺激后小鼠腹腔巨噬细胞培养上清对Ｌ９２９靶细胞具有强烈的细胞毒性（Ｐ＜０．０１）。不同浓度的庆大霉素也表现出一定的ＴＮＦ诱生作用（Ｐ＜０．０５）。当各因素分别与ＬＰＳ配伍后发现，低浓度的氢化考的松便可对ＬＰＳ诱生ＴＮＦ产生抑制（Ｐ＜０．０５），随着浓度增高抑制性加强（Ｐ＜０．０１）。关于激活或抑制效应产生的机理尚有待于深入研究。     

泰素帝对胰腺癌细胞侵袭能力的影响

目的 研究泰素帝（TXT）在体外对肿瘤细胞的运动，黏附及侵袭能力的影响。探讨TXT治疗胰腺癌的作用。方法 用Transwell小室重建基底膜侵袭模型。趋化运动模型及采用细胞黏附分子方法检测TXT对胰腺癌细胞株SUIT-2及其药细胞株S2/TXT的侵袭，运动及黏附能力的影响。结果 TXT可明显抑制SUIT-2细胞的侵袭及运动能力，但对其黏附能力无明显影响。与SUIT-2细胞相比，TXT对S2/TXT细胞的侵袭，运动及黏附能力均无明显作用。结论 TXT可降低胰腺癌细胞的体外侵袭能力。但对胰腺癌耐药细胞株的侵袭能力无明显作用。     

DDC提高纳米级阿霉素碘油乳剂抗肿瘤作用的实验研究

目的　探讨二乙基二硫代氨基甲酸酯 (DDC )对提高纳米级阿霉素碘油乳剂在体内外的抗肿瘤作用。方法　用MTT试验评价纳米级阿霉素碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用 ,用SD大鼠建立Walk -2 5 6肝癌模型 ,通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂 ,DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂 ,分别测定各组的肿瘤生长率和小鼠生命延长率。结果　经过DDC预处理后 ,阿霉素对阿霉素耐药肿瘤细胞SGC 790 1/CVR和SGC 790 /WT的IC5 0 (μg/ml)分别从原来的 18.40降至 0 .74和 4.0 0降至 0 .3 2。未经DDC处理过的各组平均肿瘤生长率远高于预先用DDC处理过的各组 (P <0 .0 1)。而小鼠生命延长率则明显低于预先用DDC处理过的各组 (P <0 .0 5 )。结论　用DDC预先处理抑制肿瘤细胞中的超氧化物歧化酶 (SOD)可提高阿霉素的抗肿瘤作用。     

Tumor necrosis factor-α alters protein metabolism and cell-cycle kinetics in malignant tumor

The effects of tumor necrosis factor-α (TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma, were injected intraperitoneally with recombinant human TNF at a dose of 4.75×10⁶ U/kg for 3 consecutive days. Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control. TNF resulted in significant decrease in tumor protein fractional synthesis rate, protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and G1 phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.     

Clinical Application of Serum Tumor Abnormal Protein from Patients with Gastric Cancer

Background: To verify whether serum tumor abnormal protein (TAP) would correlate with the responsivenessof palliative chemotherapy in patients with advanced gastric cancer, and the variation of conventional serumtumor markers e.g., carcinoembryonic antigen (CEA), antigen 125 (CA125),carbohydrate antigen19-9 (CA19-9) ofadjuvant chemotherapy in patients with early gastric cancer. Materials and Methods: Patients with histologicallyconfirmed gastric cancer and treated with chemotherapy were enrolled into this study. TAP values of thesepatients were determined by detecting abnormal sugar chain glycoprotein in serum, combined with the area ofagglomerated particles. For patients with advanced gastric cancer, responsiveness of palliative chemotherapywas compared with variation of TAP and the relation between variation of TAP and tumor markers in patientswith early gastric cancer was analyzed. Results: Totally 82 gastric cancer patients were enrolled into this study.The value of TAP is more closely related to responsiveness of palliative chemotherapy for patients with advancedgastric cancer. The correlation between TAP and responsiveness to palliative chemotherapy is stronger thanthe correlation between several conventional serum tumor markers (CEA, CA125 and CA199) .The variationof TAP was also positively correlated with the trend of CA125 in adjuvant chemotherapy. Conclusions: TAP issensitive in monitoring the responsiveness to palliative chemotherapy in patients with advanced gastric cancer.But this result should be confirmed by randomized clinical trials for patients with gastric cancer.     

鼻咽癌患者血清中肿瘤相关物质群水平变化的临床意义

目的　探讨血清中肿瘤相关物质群 (TSGF)水平与鼻咽癌 (NPC)临床病理因素的关系。方法　采用比色法测定 3 2 2例NPC患者 (治疗前 179例 ,复发 5 9例 ,治疗后 84例 )和 13 4例健康人血清TSGF水平。结果　治疗前、复发和健康对照组TSGF水平 ( x±s)分别为 ( 65 .2± 12 .1)、( 72 .9± 12 .4)和 ( 5 4.5± 5 .2 )U /ml,相互比较有非常显著性差异 (P <0 .0 1) ;TSGF水平随着NPC病情进展 (P <0 .0 1)而显著升高 ,远处转移者TSGF水平显著高于无远处转移者 (P <0 .0 1) ;以健康对照组的TSGF均值 ( 5 5U /ml)来判断NPC的灵敏度、特异度、阳性预测值和阴性预测值 ,分别为 81.0 %、5 6.7%、71.4%和 80 .5 % ;以无远处转移患者的TSGF均值 ( 62U /ml)作为临界值检测远处转移的灵敏度、特异度和阴性预测值分别为 93 .9%、48.4%和 96.1% ;放疗和化疗后NPC完全缓解或部分缓解组TSGF水平显著低于未缓解者 (P <0 .0 1)。结论　TSGF水平与NPC病情进展、疗效有关 ,尤其与远处转移与否有关。