免疫检查点抑制剂联合同步放化疗在周围型非小细胞肺癌老年患者中的应用价值分析

目的 探究免疫检查点抑制剂联合同步放化疗在治疗周围型非小细胞肺癌老年患者中的应用价值.方法 将98例周围型非小细胞肺癌患者按不同的治疗方法分为同步放化疗组与联合治疗组,每组49例.同步放化疗组进行同步放化疗,联合治疗组在同步放化疗组基础上进行免疫检查点抑制剂治疗.比较两组患者治疗前后的T淋巴细胞亚群水平、脂肪酸合成酶(FAS)、肿瘤型M2丙酮酸激酶(TuM2-PK)、血管内皮生长因子(VEGF)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原(CEA)、糖类抗原125(CA125),观察两组患者的临床疗效及不良反应发生情况.结果 治疗后,联合治疗组患者CD4+、CD3+水平均明显高于同步放化疗组(P﹤0.01),CD8+水平明显低于同步放化疗组(P﹤0.01),联合治疗组患者FAS、TuM2-PK、VEGF、CYFRA21-1、CEA、CA125水平均明显低于同步放化疗组(P﹤0.01).联合治疗组患者总有效率高于同步放化疗组,不良反应总发生率低于同步放化疗组,差异均有统计学意义(P﹤0.05).结论 在周围型非小细胞肺癌老年患者中应用同步放化疗联合免疫检查点抑制剂,使患者病情进展得到有效控制,明显改善其免疫功能,抑制患者肿瘤生长及转移,并改善其预后.     

血清肿瘤标志物联合检测在非小细胞肺癌脑转移诊疗中的价值

目的 探讨血清肿瘤标志物联合检测对非小细肺癌脑转移诊疗的价值.方法 选取148例非小细胞肺癌患者,分为转移组47例、未转移组101例,选取48例健康体检者为对照组.比较3组血清CEA、CA199、CA125、CY21-1水平及在肺癌脑转移诊断中的ROC曲线.结果 转移组、未转移组CEA、CA199、CA125、CY21-1水平均高于对照组,差异有统计学意义(P＜0.05);转移组CEA水平高于未转移组,差异有统计学意义(P＜0.05).血清CEA敏感度、特异性均高于CA199、CA125、CY21-1,差异有统计学意义(P＜0.05).治疗后转移组治疗有效者各项指标水平均低于治疗前,进展者各项指标水平均高于治疗前,差异有统计学意义(P＜0.05);稳定者各项指标水平与治疗前比较,差异无统计学意义(P＞0.05).治疗后有效者各项指标水平低于稳定者和进展者,稳定者各项指标水平低于进展者,差异有统计学意义(P＜0.05).结论 血清CEA、CA199、CA125、CY21-1联合检测,特别是CEA检测水平,有助于肺癌脑转移的早期诊断、指导治疗和预后评估,CEA水平＞10.00 μg/ml可作为1种较为理想的分界点.     

CEA、CYFRA21-1和CA125联合检测对非小细胞肺癌患者预后水平的评估价值

目的 观察非小细胞肺癌患者癌胚抗原(CEA)、血清细胞角蛋白19片段(CYFRA21-1)、糖类抗原125(CA125)水平在治疗前后的变化,探讨3项肿瘤标志物在评价非小细胞肺癌患者近期疗效和预后中的应用价值.方法 选取80例晚期(Ⅲ期、Ⅳ期)非小细胞肺癌患者,均接受至少2个周期的顺铂+吉西他滨(GP)方案或紫杉醇+顺铂(PC)方案化疗.所有患者在化疗前后均检测其血清CEA、CYFRA21-1、CA125水平.结果 腺癌患者CEA及CA125水平比鳞癌更高,而鳞癌CYFRA21-1水平比腺癌更高(P＜0.05);Ⅳ期、外转移部位数量≥3的患者的CEA、CYFRA21-1、CA125水平均比Ⅲ期、外转移部位数量＜3的患者高(P＜0.05).PR患者治疗后血清CEA、CYFRA21-1、CA125水平均比治疗前显著降低(P＜0.05).SD患者治疗前后3项肿瘤标志物水平差异不明显(P＞0.05).PD患者治疗后血清CEA、CYFRA21-1、CA125水平均显著增加(P＜0.05).CEA＜ 15 ng/mL患者的平均PFS、OS均比CEA≥15 ng/mL的患者长(8.48±3.24 VS 5.04±2.03;17.11±5.13 VS 13.11±4.12);CYFRA21-1 ＜5 ng/mL患者的平均PFS、OS均比CY-FRA21-1 ≥5 ng/mL的患者长(8.92±3.47 VS4.88±2.31;18.01±5.80 VS 13.44 ±4.75);CA125 ＜30 U/mL患者的平均PFS、OS均比CA125 ≥30 U/mL的患者长(7.96±3.51 VS 5.91±2.75;16.47±6.52 VS 13.51±5.18),差异均有统计学意义(P＜0.05).结论 血清CEA、CYFRA21-1、CA125水平对肿瘤分期及病理分型具有一定的参考意义,在评价晚期非小细胞肺癌患者的近期疗效和预后水平中具有较好的应用价值.     

血清CEA、CA125、CYFRA21-1、CT联检对肺癌诊断的意义

目的 探讨血清CEA、CA125、CYFRA21-1、CT联检与肺癌临床诊断的相关性.方法 采用放射免疫分析法与电化学发光法对58例肺癌患者和30例正常健康人进行血清标本测定.结果 肺癌组CEA、CA125、CYFRA21-1、CT均高于正常对照组(P<0.01),CEA腺癌组的阳性率明显高于鳞癌组和小细胞癌组(P<0.01),CA125腺癌组、小细胞癌组阳性率明显高于鳞癌组(P<0.01),CYFRA21-1在鳞癌中的阳性率高于腺癌组和小细胞癌组(P<0.01),CT在鳞癌、腺癌、小细胞癌的阳性率,无明显差异(P>0.05).肺癌患者血清CEA、CA125、CYFRA21-1、与CT水平成正相关.结论 CEA、CA125、CYFRA21-1、与CT联检可互补,提高肺癌诊断阳性率.     

序贯放化疗与同步放化疗对ⅢA-N2期非小细胞肺癌的疗效比较

目的比较序贯放化疗与同步放化疗对ⅢA-N2期非小细胞肺癌的治疗效果。方法将40例ⅢA-N2期非小细胞肺癌患者按照随机数字表法分为序贯组(接受化疗序贯纵隔淋巴结放疗)与同步组(接受化疗同步纵隔淋巴结放疗),每组20例。比较两组患者的临床疗效、治疗前后的血清肿瘤标志物[糖类抗原125(CA125)、鳞状上皮细胞癌抗原(SCC-Ag)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)]水平、治疗期间不良反应发生情况、无进展生存时间(PFS)和总生存时间(OS)。结果同步组患者的总有效率为75%(15/20),高于序贯组患者的35%(7/20),差异有统计学意义(P﹤0.05)。同步组患者的临床疗效优于序贯组患者,差异有统计学意义(P﹤0.05)。治疗后,同步组患者血清中的CEA、CYFRA21-1、SCC-Ag水平均低于序贯组患者,差异均有统计学意义(P﹤0.05)。两组患者的各不良反应发生率比较,差异均无统计学意义(P﹥0.05)。同步组患者的PFS、OS均长于序贯组患者,差异均有统计学意义(P﹤0.05)。结论与序贯放化疗相比,同步放化疗对于ⅢA-N2期非小细胞肺癌患者的临床疗效更优,能够有效延长患者的生存时间,且不会增加不良反应。     

血清CA125、CEA、IL-10水平检测对晚期非小细胞肺癌患者预后价值分析

目的 探讨晚期非小细胞肺癌患者血清CA125、CEA、IL-10水平在预后中的价值.方法 采用ELISA法检测不同分期NSCLC患者治疗前后CA125、CEA、IL-10的水平;观察对比化疗前后不同分期的NSCLC患者CA125、CEA、IL-10的表达水平;评价化疗后NSCLC患者的疗效及生存期.结果 化疗前Ⅳ期患者CA125、CEA、IL-10水平高于Ⅲ期患者;PR患者血清CA125、CEA、IL-10水平治疗后明显降低,SD患者CA125、CEA、IL-10水平治疗前后无显著变化,PD患者CA125、CEA、IL-10水平治疗后均显著升高;PR患者平均生存期显著长于SD患者,SD患者平均生存期显著长于PD患者.结论 血清CA125、CEA、IL-10是评估晚期非小细胞肺癌患者预后有价值的指标.     

血清CEA、CA125及Cyfra21-1水平对中晚期非小细胞肺癌患者预后的影响

目的 探讨晚期非小细胞肺癌（NSCLC） 患者血清癌胚抗原（CEA） 、糖类抗原（CA125）、非小细胞肺癌相关抗原（Cyfra21-1）水平与无疾病进展生存期的相关性。方法 选取2012年6月至2014年5月于宜昌市第二人民医院确诊的非小细胞肺癌患者120例,对其临床资料进行回顾性分析,了解CEA、CA125、Cyfra21-1水平与无疾病进展生存期的相关性。结果 与鳞癌患者相比,血清CEA水平在肺腺癌患者中明显升高（P＜0.05）;血清CA125水平在Ⅳ期肺腺癌患者中明显升高（P＜0.05）;血清Cyfra21-1在患者疾病一般特征中差异未见统计学意义（P＞0.05）。血清CEA、CA125、Cyfra21-1水平升高的患者中位无疾病进展生存期分别为4.2、4.5、4.3月,与正常组相比差异均有统计学意义（P＜0.05）。结论 晚期非小细胞肺癌患者CEA、CA125、Cyfra21-1升高与无疾病进展生存期存在明显的相关性,临床医师可通过检测患者血清CEA、CA125、Cyfra21-1水平判断预后。     

血清CEA、CYFAR21-1、SCC、CA125水平对晚期非小细胞肺癌放疗疗效的评估价值

目的探讨血清肿瘤标志物水平对晚期非小细胞肺癌患者放疗疗效的评估价值。方法将晚期非小细胞肺癌患者共176例,分为观察组(近期放疗有效)和对照组(近期放疗无效),采用电化学发光法检测放疗前、后血清肿瘤CEA、CYFAR21-1、SCC、CA125水平。结果 176例患者放疗有效率为58.0%,观察组放疗前血清CEA、CYFAR21-1、SCC、CA125水平分别为(33.65±5.41)ng/ml、(19.44±3.14)ng/ml、(16.87±2.74)ng/ml、(46.81±5.49)U/ml,放疗后各项标志物水平分别为(25.13±4.65)ng/ml、(12.35±4.18)ng/ml、(11.77±3.04)ng/ml、(39.67±4.63)U/ml,均明显低于放疗前,差异均有统计学意义(P<0.05);对照组放疗前血清肿瘤标志物CEA、CYFAR21-1、SCC、CA125水平分别为(46.87±5.93)ng/ml、(28.63±10.82)ng/ml、(26.46±8.68)ng/ml、(68.16±7.38)U/ml,放疗后各项标志物水平分别为(52.17±5.49)ng/ml、(46.72±11.75)ng/ml、(38.74±63.48)ng/ml、(87.34±8.16)U/ml,均明显高于放疗前,差异均有统计学意义(P<0.05);观察组放疗前各项标志物水平均低于对照组,差异显著(P<0.05);对照组放疗后标志物水平降低患者的近期疗效明显好于放疗后血清肿瘤标志物水平升高者,差异有统计学意义(χ2=76.45,P<0.05)。结论肿瘤血清肿瘤标志物CEA、CYFAR21-1、SCC、CA125的水平对晚期非小细胞肺癌患者放疗疗效具有评估价值。     

同步放化疗与序贯放化疗治疗Ⅲ期非小细胞肺癌的临床疗效比较

目的 探讨Ⅲ期非小细胞肺癌同步放化疗与序贯放化疗的临床疗效.方法 回顾性分析84例Ⅲ期非小细胞肺癌患者的临床资料,根据放疗方法不同分为同步放疗组和序贯放化疗组,对治疗前和治疗后1周2组患者的相关实验指标[血管内皮生长因子(VEGF)、癌胚抗原(CEA)、细胞角蛋白19的可溶性片段(CYFRA21-i)、缺氧诱导因子(HiF-1a)、Monototal、DKK-1]、治疗有效率、不良反应发生率和相关功能进行比较.结果 治疗后1周,同步放疗组相关实验指标(VEGF、DKK-1)、治疗的总有效率、生理评分和生活质量评分均优于序贯放化疗组(P＜0.05),白细胞下降的发生率低于序贯放化疗组(P =0.008),其他不良反应在2组之间无统计学差异(P＞0.05).结论 与序贯放化疗相比,同步放化疗治疗Ⅲ期非小细胞肺癌可提高临床疗效,提高患者的VEGF和DKK-1水平,改善患者的生理功能及生活质量.     

血清TK1检测在非小细胞肺癌诊断中的临床意义

目的 探讨肿瘤标志物胸苷激酶1(thymidine kinase 1,TK1)在非小细胞肺癌患者血清中的水平及对非小细胞肺癌诊断的意义.方法 采用免疫印迹增强化学发光法检测96例非小细胞肺癌患者及108例健康对照者血清中的CEA、CA125及TK1水平.结果 肺癌组血清TK1、CA125、CEA水平分别为(30.87±14.62) pmol/L、(123.66±43.79)μg/L、(30.52±10.68) U/mL,显著高于健康对照组(P＜0.01、P＜0.01、P＜0.05).肿瘤标志物单项检测的阳性率依次为TK1 (79.2％)＞CA125 (67.7％)＞CEA(55.2％),其中血清TK1的阳性检出率最高.TK1+ CA125联合检测,其阳性率进一步提高至87.5％.结论 血清TK1检测对非小细胞肺癌临床诊断有重要参考价值.     

Diagnostic Significance of Cancer Antigen 125, Pancreatic Oncofetal Antigen, and Carcinoembryonic Antigen in Malignant and Tuberculous Pleural Effusions

Pleural fluid levels of cancer antigen 125 (CA 125), pancreaticoncofetal antigen (POA), and carcinoembryonic antigen (CEA)were determined in 56 patients with malignant pleural effusionand in 35 patients with tuberculous effusion. Malignant effusionshad significantly higher pleural fluid CA 125 and CEA levelsthan those of tuberculous origin (p < 0.005). No significantdifference in POA titers was found between the two kinds ofeffusion. Assays of CA 125 and CEA in pleural fluid may be usefulin separating malignant from tuberculous effusions. Concurrentmeasurement of CA 125 and CEA proved superior to determinationof CEA alone in discriminating between the two groups.     

Cancer Testis Antigen,NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.     

D-二聚体、癌胚抗原、糖类抗原199联合检测在胰腺癌诊断中的应用价值

目的探讨D-二聚体（D-D）、癌胚抗原（CEA）、糖类抗原199（CA199）联合检测在胰腺癌诊断中的临床价值。方法随机选取胰腺癌患者58例、胰腺良性疾病患者27例和健康成人40例,血清D-D以免疫比浊法检测,血清CEA、CA199采用电化学发光法检测,并对3组检测值进行分析。结果胰腺癌组与胰腺良性疾病组和健康成人组对比,血清D-D、CEA、CA199检测值均升高（P〈0.05）。在敏感性和特异性的单项指标分析中,CA199的敏感性最高,而D-D的特异性最高,分别为77.6%、82.5%。三者联合检测的特异性最高,达到97.5%。结论 D-D、CEA、CA199联合检测在胰腺癌诊断中具有较高应用价值。     

Tumor Markers in Colorectal Carcinoma An Evaluation of Carcinoembryonic Antigen, Tissue Polypeptide Antigen, Placental Alkaline Phosphatase and Pseudouridine

The biologic markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), placental alkaline phosphatase (PLAP) and pseudouridine were analysed in 37 patients with colorectal carcinoma. CEA, TPA and PLAP were derived from the serum and pseudouridine from the urine. The incidence of all four markers increased with advancing stages of the disease. Patients with distant metastases had elevated levels of CEA, TPA, PLAP and pseudouridine in 85, 27, 18 and 33 per cent of the total cases, respectively. When survival was compared, patients with 2 to 4 elevated markers had shorter survival than those with none or only one elevated marker.     

Preoperative Serum Carcinoembryonic Antigen,Carbohydrate Antigen19-9 and Carbohydrate Antigen 125 as Prognostic Factors for Recurrence-free Survival in Colorectal Cancer

Objective: Colorectal cancer (CRC) is among the most common malignancies worldwide. Understanding CRCprognosis at the initial diagnosis is very important for therapeutic strategy selection. This study was conductedto evaluate the prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonicantigen (CEA) and carbohydrate antigen 125 (CA125) for predicting 5-year recurrence-free survival (RFS) inCRC patients. Methods: Preoperative serum CA19-9, CEA and CA125 levels were detected by C12 proteinchip diagnostic system in 103 patients with CRC, and their correlations with the 5-year RFS were analyzed.Results: Patients with positive preoperative serum CA19-9, CEA and CA125 had higher 5-year recurrent rates(75.0% vs 41.0%, 65.6% vs 39.4%, and 87.5% vs 44.2% respectively, all p<0.05), and reduced median RFS (14vs 35 months, 20 vs 36 months, and 4 vs 35 months respectively, all p<0.05) compared with patients negative forcorresponding tumor marker (TM). The median RFS was 59 months (95% CI 28.9-89.1 months) with negativeTMs, 14 months (95% CI 4.5-23.5) for 1~2 positive TMs, and 4 months (95% CI 2.4-5.6) for all 3 positive TMs.Patients with simultaneously positive serum CA19-9, CEA and CA125 had the highest recurrence rate (100%)and the shortest RFS (median 4 months). Univariate analysis showed that stage and the preoperative singleTM or combined TMs correlated with RFS, whereas multivariate Cox regression model analysis revealed onlystage and preoperative serum status of CEA+CA19-9+CA125 to be independent prognostic factors. Conclusion:Preoperative serum CA19-9+CEA+CA125 can be used an independent prognostic factor for CRC 5-year RFS.     

Development, Characterization, and Immunotherapeutic Use of Peptide Mimics of the Thomsen-Friedenreich Carbohydrate Antigen

The tumor-associated carbohydrate Thomsen-Friedenreich antigen (TF-Ag; Galβ1-3GalNAcα-O-Ser/Thr) is overexpressed on the cell surface of several types of tumor cells, contributing to cancer cell adhesion and metastasis to sites containing TF-Ag-binding lectins. A highly specific immunoglobulin G₃ monoclonal antibody (Ab) developed to TF-Ag (JAA-F11) impedes TF-Ag binding to vascular endothelium, blocking a primary metastatic step and providing a survival advantage. In addition, in patients, even low levels of antibodies to TF-Ag seem to improve prognosis; thus, it is expected that vaccines generating antibodies toward TF-Ag would be clinically valuable. Unfortunately, vaccinations with protein conjugates of carbohydrate tumor-associated Ags have induced clinically inadequate immune responses. However, immunization using peptides that mimic carbohydrate Ags such as Lewis has resulted in both Ab and T-cell responses. Here, we tested the hypothesis that vaccinations with unique TF-Ag peptide mimics may generate immune responses to TF-Ag epitopes on tumor cells, useful for active immunotherapy against relevant cancers. Peptide mimics of TF-Ag were selected by phage display biopanning using JAA-F11 and rabbit anti-TF-Ag Ab and were analyzed in vitro to confirm TF-Ag peptide mimicry. In vitro, TF-Ag peptide mimics bound to TF-Ag-specific peanut agglutinin and blocked TF-Ag-mediated rolling and stable adhesion of cancer cells to vascular endothelium. In vivo, the immunization with TF-Ag-mimicking multiple antigenic peptides induced TF-Ag-reactive Ab production. We propose that this novel active immunotherapy approach could decrease tumor burden in cancer patients by specifically targeting TF-Ag-positive cancer cells and blocking metastasis.     

A Common Tumour Specific Antigen: II. Further Characterization of the Whole Antigen and of a Cross-Reacting Antigen of Normal Tissues

Experimental evidence supporting the postulated analogy between myelin basic protein and a previously described common tumour specific antigen is summarized under antigenic cross-reactivity, subcellular localization, molecular size, basicity and proteolipid nature. A third protein antigen, present in all tissues, also shows strong similarities in all these respects.     

Carcinoembryonic Antigen in the Management of Gastric Cancer Patients

The usefulness and limitations of the determination of carcinoembryonicantigen (CEA) levels were investigated in 226 cases of gastriccancer. Pre-operatively, elevated CEA levels were found in 23.9%.As the stage of cancer progressed, CEA elevation was found inhigher percentages. In particular, in patients with liver metastasisan incidence as high as 68.8% was obtained. Elevated CEA levelswere also observed more frequently in patients with unresectabletumors than in those with resectable ones and in those undergoingnoncurative surgery more frequently than in those undergoingcurative surgery. In most patients with preoperative elevated CEA levels, thelevels returned to normal by one month after curative resection,while the levels rarely returned to normal after noncurativeresection, showing the usefulness of CEA determination for evaluatingthe effect of surgery. CEA levels were determined serially before and after surgeryin patients with unresectable tumors, liver metastasis or peritonealdissemination. In most patients with preoperative elevated CEAlevels, the levels increased with postoperative tumor enlargement.Postoperative CEA levels increased to above the normal rangein some of the patients with normal preoperative CEA levels. Serial measurement of CEA levels was useful for observing thecourse of the disease even in patients with normal preoperativelevels.