唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

MMP－9、E GF水平对子宫肌瘤诊断特异性及准确性作用分析

目的：探讨子宫肌瘤患者血清基质金属蛋白酶9（MMP－9）、表皮生长因子（EGF）水平变化及诊断子宫肌瘤的临床价值。方法：选取84例经病理学确诊的子宫肌瘤患者（病例组）、84例健康妇女作为对照组，分别对比两组血清MMP－9、E GF水平，并根据肌瘤生长位置、肌瘤大小对病例组进行亚组分析。结果：病例组患者的血清MMP－9、EGF水平均高于对照组，差异具有统计学意义（P＜0．05）；MMP－9鉴别诊断子宫肌瘤与健康人群的最佳临界值为1．40μg／ml，EGF鉴别诊断子宫肌瘤与健康人群的最佳临界值为288．5pg／ml，对应的ROC曲线下面积AUC值分别为0．816、0．739。黏膜下肌瘤患者的血清MMP－9、EGF水平均高于肌壁间肌瘤患者，差异具有统计学意义（P＜0．05）；肌瘤最大径＞5．0cm 和肌瘤最大径≤5．0cm患者的血清MMP－9、EGF水平差异不具有统计学意义（P＞0．05）。结论：检测血清MMP－9、EGF水平有利于鉴别诊断子宫肌瘤患者。     

肺癌患者血清CA242测定的临床意义

为探讨CA242在肺癌诊断、分期中的作用，采用免疫放射分析法测定50例肺癌患者血清CA242水平。结果显示：肺癌患者血清CA242水平显著增高（P＜0．025），其增高的程度与肺癌TNM分期直接相关，依次为IV期＞皿期＞II期＞I期，其中鳞癌、腺癌、小细胞未分化癌患者血清CA242水平差异无显著性（P＞0．05）。以10U／ml为临界值，血清CA242；诊断肺癌的敏感度54．6％，特异度90％，准确度70．8％。表明血清CA242测定对于肺癌的诊断和分期具有一定的实用价值。     

肺癌患者血清CA125检测的临床意义

目的：探讨血清CA125在肺癌诊断和疗效观察中的价值。方法：检测87例肺癌治疗前后血清CA125水平。结果：以CA125＞35U／mL为阳性界值，CA125对肺癌的诊断率为47．1％，其阳性检出率分别是：鳞癌41．7％，腺癌43．3％，未分化癌61．9％，未分化癌与鳞癌CA125水平比较，有显著差异（P＜0．05）。CA125水平还与临床分期有关，Ⅲb、Ⅳ期明显高于Ib、Ⅱa、Ⅱb、Ⅲa期（P＜0．05）。结论：血清CA125水平对肺癌诊断具有一定的价值，是临床分期、疗效观察及预后判断的重要参考指标。     

参一胶囊联合化疗治疗晚期非小细胞肺癌疗效观察与血清MMP－9及TIMP－1变化

目的：探讨参一胶囊联合一线化疗方案与单独化疗治疗不能手术的晚期IIIb／Ⅳ初治非小细胞肺癌（NSCLC）患者血清基质金属蛋白酶9（MMP－9）及组织蛋白酶抑制剂－1（TIMP－1）水平变化,并观察其近期疗效和治疗后不良反应。方法：采用酶联免疫吸附法（ELISA）检测89例肺癌患者化疗前后血浆MMP－9及TIMP－1水平。结果：两组有效率无显著性差异（P＞0．05）,两组疾控率比较差异有显著性（P＜0．05）。全部CR＋PR、SD、PD患者治疗前血清MMP－9、TIMP－1水平比较,无显著性差异（P＞0．05）,治疗后差异均具有有显著性（P＜0．05）,随疗效降低呈升高趋势。两组相比疗前与疗后两次血清MMP－9水平,参一联合化疗组下降更明显,差异有显著性（P＜0．05）,而血清TIMP－1水平差异无显著性（P＞0．05）。IV期患者比IIIb 期患者外周血清MMP－9水平明显增高,差异有显著性（P＜0．05）。但外周血清TIMP－1在IIIb 期和IV期无统计学差异。其他因素如年龄、性别、ECOG评分、病理与MMP－9、TIMP－1水平均未发现显著性差异。患者治疗后出现常见不良反应及生活质量（quality of life,QOL）观察：观察组（即参一胶囊联合化疗组）在胃肠道反应（如恶心、呕吐、腹胀等）,骨髓抑制（如白细胞减少、贫血、血小板下降等）方面均较单独化疗组减轻（P＜0．05）,参一联合组在改善QOL方面也明显高于对照组,且有统计学差异（P＜0．05）。结论：参一胶囊联合化疗组患者外周血清MMP－9水平下降更明显,且有统计学差异,而患者血清TIMP－1水平变化无统计学差异。血清MMP－9、TIMP－1水平治疗后随疗效降低呈升高趋势,因此,两者对患者疗效判定具有一定的参考价值。两组外周血清MMP－9、TIMP－1水平变化不受性别、年龄、ECOG评分影响。肺癌患者TNM分期对NSCLC患者外周血清MMP－9水平变化有影响,分期越晚,其外周血清MMP－9水平值越高。因此,MMP－9血清值越高,提示预后越差。外周血清TIMP－1水平与MMP－9水平在化疗前后NSCLC患者呈正相关。参一胶囊对非小细胞肺癌患者可以增加疗效,减少毒副反应,生活质量得到提高,不良反应如消化道症状及骨髓抑制均可以减轻。     

血清CA19—9的酶免测定及临床应用

本文用生物素—链霉亲和素酶联免疫吸附试验（BSA）对203例血清CA19－9水平进行定量测定。结果显示，在32例胰腺癌组为826±411U／ml，40例肝癌组为107±46．5U／ml，与76例正常人对照组21．2±9．24U／ml比较均有明显差异（P＜0．05），以胰腺癌组升高最显著。在39例胃癌组为25．4±11．0U／ml，与正常对照组比较均无明显差异（P＞0．05）。27例胰腺癌病人术前为910±452U／ml，术后为187±89．0U／ml，血清CA19－9水平明显下降（P＜0．05）。血清CA19－9水平分析对胰腺癌的鉴别诊断、疗效观察及预后评估有较高价值。     

肺癌的化疗与多药耐药的研究

目的：检测各种类型肺癌化疗前及化疗后复发病例P－gp蛋白的表达情况,探讨其与肺癌多药耐药及患者预后的关系。方法：采用免疫组化染色方法对66例化疗后复发病例及131例未经化疗的肺癌病例进行耐药基因MDR1表达蛋白P－gp检测,结果：化疗后复发病例P－gp阳性表达率明显高于未经化疗的病例（P＜0．05）,其中,癌,小细胞癌化疗后P－gp阳性表达率均明显高于化疗前（P＜0．05）,而肺腺癌则无明显差异（P＞0．05）,未经化疗组不同病理类型的肺癌P-g[蛋白阳性表达有显著性差异,从高到低依次为腺癌,鳞癌和小细胞癌（P＜0．05）,化疗后复发组各病理类型肺癌中P－gp蛋白阳性表达率无显著性差异（P＞0．1）,P－gp表达阳性的患者3年生存率明显低于阴性者（P＞0．05）。结论;化疗可能诱导各种病理类型肺癌P-gp蛋白表达增加,肺鳞癌和小细胞肺癌可能为获得性MDR1耐药,肺腺癌是原发性MDR1耐药,肺癌患者P－gp表达程度可作为指导化疗用药及预测预后的指标。     

血浆 MAL 基因甲基化检测对于肺癌早期诊断的意义

目的：研究肺癌患者、肺结核患者及健康人群 T 淋巴细胞相关蛋白（T －lymphocyte maturation －asso-ciated protein,MAL）基因启动子区的甲基化状态,进一步探讨血浆 MAL 基因甲基化检测对于肺癌早期诊断及鉴别肺癌与肺结核疾病的意义。方法：采用甲基化特异性 PCR（methylation special PCR,MSP）方法,检测75例肺癌组织标本、癌旁组织标本和对应的血浆标本及58例肺结核组织标本及对应的血浆标本的 MAL 基因启动子区甲基化状态;同时检测30例正常人群的血浆标本 MAL 甲基化状态作为对照。结果：肺癌组织和癌旁组织中 MAL 基因甲基化发生率分别为78．7％（59／75）和2．7％（2／75）,差别具有统计学意义（P ＜0．001）;肺癌和肺结核组织中 MAL 基因甲基化发生率分别为78．7％（59／75）和3．4％（2／58）,差别具有统计学意义（P＜0．001）;肺癌患者与肺结核患者对应的血浆中 MAL 基因甲基化发生率分别73．3％（55／75）和1．7％（1／58）,差别也具有统计学意义（P ＜0．001）。正常健康人群的血浆标本中未发现 MAL 基因甲基化改变;肺癌组和肺结核组分别与健康人群组比较,肺癌组明显高于健康人群（P ＜0．001）,而肺结核组患者与健康人群比较无明显差异（P ＝0．47）。组织标本和血浆标本的检出率具有一致性（P ＞0．05）。根据病理类型、TNM分期、性别、吸烟史等对肺癌患者进行分组,各组之间均无明显差异（P ＞0．05）。结论：MSP 法检测血浆 MAL 基因甲基化状态,可以作为一种有潜力的肺癌早期诊断方法,对于鉴别肺癌和肺结核也有一定的帮助。     

EGF、IL-6、TNF-α的含量与肺癌及其预后的关系

目的：探讨表皮生长因子（EGF）、白细胞介素－6（IL－6），肿瘤坏死因子－α（TNF－α）等3种细胞因子的含量与肺癌及其预后的关系。方法：取明确诊断为肺癌的患者术前和术后血清以及手术中肺癌及肺周围组织标本进行细胞因子的检测，同时进行该组患者肺癌复发和转移的观察。结果：TNF－α在肺癌组织与肺周边组织中含量无明显变化，EGF在癌组织中存活组与死亡组比较春含量差异有显著性（P＜0．05），IL－6在肺组织中存活组与死亡组比较其含量差异有显著性（P＜0．05）。结论：EGF、IL－6的变化与肺癌患者的生存期有一定关系，而TNF－α与本组患者的生存期似无明显关系。     

脂联素与肺癌合并 COPD 患者肺功能、年龄、性别的相关性分析

目的：探讨脂联素和肺癌合并COPD患者肺功能、年龄、性别的相关性。方法选取肺癌合并COPD患者90例，分为重症组和稳定组。45例健康者作为健康组。测量3组研究对象的肺功能指标（ FEV1／FVC以及FEV1％）以及血清中脂联素的含量，并确定脂联素与COPD患者肺功能、年龄、性别的相关性。结果3组被研究对象组内性别间的脂联素含量的差异均具有统计学意义（P＜0．05），女性高于男性，且组间的男性和女性脂联素含量的差异具有统计学意义（P＜0．05）；FEV1／FVC比值比较，3组被研究对象间男性和女性的差异具有统计学意义（P＜0．05）；FEV％预计值比较，3组被研究对象间男性和女性的差异具有统计学意义（ P＜0．05）。 COPD患者的血清中脂联素水平与FEV1／FVC （γ男＝－0．642，γ女＝－0．657）和FEV％预计值（γ男＝－0．819，γ女＝－0．751）均呈负相关性。在3组被研究对象中，只有健康组患者男性中脂联素含量水平与年龄呈正相关性，其他的均无明显的相关性。结论肺癌合并COPD患者中血清脂联素与肺功能和性别存在明显的关系，而与患者的年龄分布的关系不明显。     

血清唾液酸检测对癌症诊断的临床价值

作者测定了５７７例正常人和２４１例恶性肿瘤患者血清总唾液酸（ＴＳＡ）和血清脂质结合唾液酸（ＬＳＡ）的含量。结果表明：ＴＳＡ和ＬＳＡ的含量变化与疗效一致，治疗有效者ＴＳＡ和ＬＳＡ与正常人相比，均无显著性差异（Ｐ＞０．０５）；治疗无效（包括未经治疗）者与正常人相比除原发性肝癌、乳腺癌外均有显著性差异（Ｐ＜０．０１）。血清ＴＳＡ和ＬＳＡ测定对肺癌、胃癌、大肠癌等有临床诊断价值（Ｐ＜０．０１），对鼻咽癌诊断效果更好（Ｐ＜０．００１）。对肝癌、乳腺癌的诊断价值有限（Ｐ＞０．０５）。恶性肿瘤患者ＴＳＡ与ＬＳＡ含量间无相关关系（ｒ＝０．０９；Ｐ＞０．０５；ｎ＝１１７）。ＬＳＡ检测不能代替ＴＳＡ检测，两者应该联合检测以提高其阳性率。     

SERUM LIPID-BOUND SIALIC ACID IN LUNG CANCER PATIENTS

ＳＥＲＵＭＬＩＰＩＤ－ＢＯＵＮＤＳＩＡＬＩＣＡＣＩＤＩＮＬＵＮＧＣＡＮＣＥＲＰＡＴＩＥＮＴＳＬｉｎｇＸｉａｏｐｉｎｇ；林小萍；ＺｈａｎｇＸｉｚｅｎｇ；张熙曾；ＷａｎｇＱｉｎｇｓｈｅｎｇ；王庆生（ＤｅｐａｒｔｍｅｎｔｏｆＳｉｎｏ－ＪａｐｅｎＥｓｏｐｈａ...     

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.     

Serum sialic acid (TSA/LSA) and carcinoembryonic antigen (CEA) levels in cancer patients undergoing radiotherapy.

The main aim of this study was to evaluate the response of total Sialic Acid (TSA) and "Lipid-bound" Sialic Acid (LSA) compared to Carcinoembryonic Antigen (CEA), in 284 patients undergoing radiotherapy. Serial measurements of TSA by the enzymatic method (Boehringer-Mannheim Kit), LSA by the resorcinol-HC1 (Katopodis and Stock) and CEA by EIA (Abbott Kit) were performed in a total of 1017 blood sera. We statistically estimated the four greater groups of cancer patients [bladder (69), lung (58), uterus (31) and breast (29)]. Diagnostic marker sensitivities (% true positives) estimated from the 0-time-values--before initiation of radiotherapy--in relation to the established cut-off levels were in decreasing order: TSA 89.3% (80 mg/dL). LSA 88.8% (20 mg/dL) and CEA 26.75% (5 ng/mL). The overall tumor marker response to treatment, after its completion, estimated as % of patients with final blood serum levels of these markers, was in decreasing order: LSA 85.6%, TSA 81.3%, and CEA 65.8%. These data show that a) the diagnostic sensitivity of Sialic Acid (LSA/TSA) is more than 3 times higher than that of CEA and b) the response of Sialic Acid (LSA/TSA) to treatment is about 15% higher than that of CEA. In conclusion, this study confirms the high diagnostic sensitivity of Sialic Acid as a tumor marker and suggests that, with marginal superiority of Sialic Acid, all three markers are sufficiently responsive to be employed as adjunctive means in monitoring cancer patients underdoing radiotherapy.     

肺癌患者血清脂质结合唾液酸含量动态变化

血清脂质结合唾液酸(Lipid Bound sialic Acid LSA)是肺癌诊断及鉴别诊断的一项有用的标志物,其与肿瘤恶性行为关系密切,因之肺癌患者血清LSA含量的动态变化,可作为对其治疗后病情或疗效的监测指标。此研究证实肺癌患者治疗前后血清LSA含量变化有显著性差异(P＜0.0001)。肺癌的治疗手术切除后阴转率为54.17%,化疗组为42.11%,放疗组为50.00%。     

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.     

Total and lipid-bound plasma sialic acid as diagnostic markers in colorectal cancer patients: correlation with cathepsin B expression in progression to Dukes stage

PURPOSE: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease. METHODS: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis. RESULTS: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed. CONCLUSION: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.     

血清总唾液酸在食管癌早诊中的研究

 目的：探讨血清总唾液酸对食管癌早诊的作用。方法：采用化学比色法对我国食管癌高发区之一—磁县1510例普查人群的血清总唾液酸(TSA)分析研究。结果：高发人群血清TSA含量随食管上皮细胞增生加重逐渐增加。方差分析显示食管癌、近癌、重增Ⅱ与重增Ⅰ、轻增、正常人群血清TSA含量具有显著性差异(P<0.01),食管各级病变血清TSA含量两两比较的q检验结果表明：在食管上皮细胞重增Ⅱ时TSA含量与正常人群就有显著性差异(P<0.01),而重增Ⅰ、轻增和正常人群TSA无显著性差异(P>0.05)。结论：提示血清TSA含量可作为一种食管癌早诊指标用于人群筛查工作。     

Levels of soluble intercellular adhesion molecule-1 and total sialic acid in serum of patients with colorectal cancer

BACKGROUND AND OBJECTIVES: Serum soluble intercellular adhesion molecule-1 (sICAM-1) and total sialic acid (TSA) are related to the metastatic potential of cancer cells. The purpose of the present investigation was to determine sICAM-1 and TSA levels in colorectal carcinoma and correlate their levels with the cancer stage. METHODS: The sera from 65 patients with colorectal cancer (18 at Dukes' B, 24 at Dukes' C, 23 at Dukes' D) were extracted before treatment. The concentrations of sICAM-1 and TSA were measured by enzyme-linked immunoassay and the thiobarbituric acid method, respectively, and compared with those from a healthy control group (n = 42). RESULTS: Mean serum sICAM-1 and TSA levels were found to be higher in the total patient group than in the control group (P < 0.0001). The concentrations of sICAM-1 and TSA were significantly higher in patients with Dukes' C and Dukes' D. The correlations between sICAM-1 and TSA became more significant as the stage of the disease increased (r = 0.58, P < 0.05 in Dukes' B, r = 0.88, P < 0.01 in Dukes' C and r = 0.81, P < 0.01 in Dukes' D). CONCLUSIONS: The results of this investigation indicate that sICAM-1 and TSA are the best of the tested markers. These markers should prove useful for monitoring malignant disease stage and for evaluating the effectiveness of various therapeutic approaches for colorectal carcinomas.